title: Successful treatment of gestational trophoblastic neoplasia in the uterine cornus with laparoscopic cornuostomy and postoperative methotrexate injection.

text: OBJECTIVE Management of cornual gestational trophoblastic neoplasia (GTN) has never been reported. Here, we describe the first case of cornual GTN. CASE REPORT A 32-year-old woman was diagnosed with left cornual GTN after evacuation of a complete mole. Laparoscopic cornuostomy was performed with intramural vasopression injection and barbed sutures. Histopathology revealed hydropic chorionic villi. Complete hydatidiform mole was diagnosed, and treated with adjuvant methotrexate, to address the poor decline of β-human chorionic gonadotropin levels during follow-up. The β- human chorionic gonadotropin levels declined to < 1 mIU/mL 9 months after cornuostomy. She successfully conceived 16 months after cornuostomy, and underwent cesarean section at 37 gestational weeks due to concomitant severe preeclampsia. CONCLUSION Cornual GTN can be successfully managed with laparoscopic cornuostomy and adjuvant methotrexate.


title: Single-port access (SPA) laparoscopic surgery in gynecology: a surgeon's experience with an initial 200 cases.

text: OBJECTIVE To report our initial two hundred single-port access (SPA) gynecologic surgeries and present the perioperative outcomes. STUDY DESIGN This is a prospective single-center study (Canadian Task Force classification II-2). Two hundred selected patients with gynecological disease were recruited for the study from May 2008 through December 2009 at Samsung Medical Center. RESULTS Two hundred patients underwent SPA gynecological surgery (105 a total hysterectomy; 11 a subtotal hysterectomy; 43 an oophorectomy; 31 an ovarian cystectomy; 5 a salpingectomy; 2 a myomectomy; 3 adhesiolysis only). The median age and body mass index were 45.5 and 22.9 kg/m(2), respectively. SPA surgery was successfully completed in 187 patients, without the need for ancillary ports (93.5%). Two cases required a conventional multiport, and nine cases needed one additional port. Two patients were converted to a laparotomy. One intra- and five post-operative complications occurred. The complication rate was 3.2% (6/187). The median operative time was 120 min (54-250) for a total hysterectomy, 180 (150-345) for a subtotal hysterectomy, 60 (27-245) for an oophorectomy, 105 (50-185) for a cystectomy, and 60 (30-115) for a salpingectomy. CONCLUSION Single-port surgery was safe and feasible for gynecological indications. Further study of single-port surgery is required to determine whether it has significant benefits compared to conventional techniques.


docid: utqkmvxn

title: Reduction of postoperative pain after lumbar microdiscectomy with DuraSeal Xact Adhesion Barrier and Sealant System.

text: BACKGROUND CONTEXT An excessive amount of scar tissue after lumbar microdiscectomy may increase postoperative pain. Several fibrosis inhibitors have been used in the past in an endeavor for better functional outcome. PURPOSE The goal of this study was to evaluate DuraSeal Xact Adhesion Barrier and Sealant System (DSX), a polyethylene glycol-based synthetic fibrosis inhibitor, for its ability to reduce postoperative pain after lumbar microdiscectomy. STUDY DESIGN This is a prospective randomized controlled study. PATIENT SAMPLE Twenty patients between 19 and 71 years of age about to undergo elective lumbar single-level discectomy were randomized into two groups of 10. OUTCOME MEASURES Assessments included the visual analog scale (VAS) pain score, the short form (SF)-36 questionnaire, and the Oswestry low back pain scale, preoperatively and at discharge, and 30, 90, and 180 days after surgery. METHODS One group was treated with DSX, and the control group received the local standard of care. DSX was applied as a thin layer on the nerve root and surrounding area after microdiscectomy. RESULTS The VAS pain scale was lower at all time points in the DSX treatment group than in the control group. The reductions at 30, 90, and 180 days for DSX and control groups, respectively, were 43.9% versus 35.6%, 64.3% versus 44.8%, and 75.4% versus 59.6%. The SF-36 scores in the DSX treatment group showed more improvement than in the control group as soon as 30 days for physical functioning, general health, vitality, social functioning, mental health, and emotional patterns, and by 90 days for bodily pain and general health. The Oswestry pain score was lower at all time points in the DSX treatment group than in the control group. The reductions at 30, 90, and 180 days for DSX and control groups, respectively, were 41.5% versus 34.3%, 68.2% versus 42.4%, and 73.3% versus 55.4%. Wound healing was normal in the DSX treatment group, there were no complications related to DSX use, and no patient in either group required reoperation. CONCLUSIONS Although this study is too small to have conclusions of efficacy and will need confirmation by larger trials, treatment of a microdiscectomy site with DSX for fibrosis prevention shows promising results in terms of safety, reduction of postoperative pain and functional results when compared to control with the additional advantage of being suitable for use in the presence of a dural tear.


docid: zoaqljte

title: Pernicious anaemia: switch to oral B12 supplementation to reduce risk of covid-19 transmission.


title: Prevalence of pre-stroke depression and its association with post-stroke depression: a systematic review and meta-analysis.

text: BACKGROUND Depression is a common post-stroke complication. Pre-stroke depression may be an important contributor, however the epidemiology of pre-stroke depression is poorly understood. Using systematic review and meta-analysis, we described the prevalence of pre-stroke depression and its association with post-stroke depression. METHODS We searched multiple cross-disciplinary databases from inception to July 2017 and extracted data on the prevalence of pre-stroke depression and its association with post-stroke depression. We assessed the risk of bias (RoB) using validated tools. We described summary estimates of prevalence and summary odds ratio (OR) for association with post-stroke depression, using random-effects models. We performed subgroup analysis describing the effect of depression assessment method. We used a funnel plot to describe potential publication bias. The strength of evidence presented in this review was summarised via 'GRADE'. RESULTS Of 11 884 studies identified, 29 were included (total participants n = 164 993). Pre-stroke depression pooled prevalence was 11.6% [95% confidence interval (CI) 9.2-14.7]; range: 0.4-24% (I2 95.8). Prevalence of pre-stroke depression varied by assessment method (p = 0.02) with clinical interview suggesting greater pre-stroke depression prevalence (~17%) than case-note review (9%) or self-report (11%). Pre-stroke depression was associated with increased odds of post-stroke depression; summary OR 3.0 (95% CI 2.3-4.0). All studies were judged to be at RoB: 59% of included studies had an uncertain RoB in stroke assessment; 83% had high or uncertain RoB for pre-stroke depression assessment. Funnel plot indicated no risk of publication bias. The strength of evidence based on GRADE was 'very low'. CONCLUSIONS One in six stroke patients have had pre-stroke depression. Reported rates may be routinely underestimated due to limitations around assessment. Pre-stroke depression significantly increases odds of post-stroke depression.Protocol identifierPROSPERO identifier: CRD42017065544.


docid: ufldsbxf

title: Dermatopathic lymphadenitis associated with human papilloma virus infection and verruca vulgaris.

text: Here we present a pediatric case of human papilloma virus associated with dermatopathic lymphadenitis (DL). A 5-year-old boy presented to the pediatric oncology clinic with swelling of the neck and warts on his lower jaw. His blood chemistry and complete blood count were normal, as was chest x-ray. HIV, EBV, CMV, and parvovirus serologies were negative. The patient was investigated for malignancy and lymphoma but no association was found. Histopathologic examination of the lymph node and the lesion revealed DL and verruca vulgaris, respectively. DL represents a benign form of reactive lymph node hyperplasia and described in patients with HIV and EBV infections. It is a rare entity described in patients with human papilloma virus infection. To our knowledge, this is the first report of DL in a patient with human papilloma virus infection.


title: The Syrian conflict and infectious diseases.

text: The conflict in Syria is a big humanitarian emergency. More than 200,000 Syrians have been killed, with more than half of the population either having been displaced or having immigrated. Healthcare has been interrupted due to the destruction of facilities, a lack of medical staff, and a critical shortage of life-saving medications. It produced suitable conditions leading to the re-emergence of tuberculosis, cutaneous leishmaniasis, polio, and measles. Lebanon and Jordan reported increased rates of tuberculosis among Syrian refugees. Cutaneous leishmaniasis outbreaks were noted not only in Syria but also in Turkey, Jordan, and Lebanon. After a polio-free 15 years, Syria reported a polio outbreak. Ongoing measles outbreaks in the region was accelerated by the conflict. Iraq declared a cholera outbreak among the Syrian refugees. The healthcare facilities of the countries hosting immigrants, mainly Turkey, Lebanon, Jordan, Iraq, and Egypt, are overburdened. The majority of the immigrants live in crowded and unsanitary conditions. Infectious diseases are big challenges for Syria and for the countries hosting immigrants. More structured support from international organizations is needed for the prevention, control, diagnosis, and treatment of infectious diseases.


title: One does not fit all: new adjuvants are needed and vaccine formulation is critical.

text: In recent years, adjuvant research has moved from empirical trial and error to a more rational approach engaging the multidisciplinary fields of immunology, biochemistry, pharmacy and physical chemistry. At the Modern Vaccines/Adjuvants Formulation meeting held in Cannes, France in October 2010, scientists from this broad field met to discuss recent progress in adjuvant research and development. The focus of the meeting was on formulation and as a result clinically and pharmaceutically relevant aspects of how to design and optimize vaccines and adjuvants were also addressed.


title: Meta-analysis of randomized trials comparing the effectiveness of different strategies for the treatment of drug-eluting stent restenosis.

text: The investigators performed a network meta-analysis of randomized trials comparing the effectiveness of currently available strategies for the treatment of drug-eluting stent (DES) restenosis. Despite the widespread use of DES in patients who undergo percutaneous coronary intervention, the optimal treatment for DES restenosis remains poorly defined. A systematic search of electronic resources was performed. The primary end point was diameter stenosis at follow-up angiography. Seven trials were included, enrolling a total of 1,586 patients with 1,728 restenotic lesions. The following treatment options were found: balloon angioplasty (BA) in 343 patients (19.3%), iopromide-based paclitaxel-eluting balloons (PEB) in 343 (21.6%), sirolimus-eluting stents in 441 (27.8%), paclitaxel-eluting stents in 462 (29.1%), and everolimus-eluting stents in 34 (2.2%). Compared with BA, PEB (-17.74%, 95% credible interval [CI] -25.17% to -11.31%), everolimus-eluting stents (-14.93%, 95% CI -33.47% to 1.16%), paclitaxel-eluting stents (-15.3%, 95% CI -22.96% to -8.35%), and sirolimus-eluting stents (-11.08%, 95% CI -17.89% to -3.4%) had similar reductions in diameter stenosis at follow-up angiography. PEB (85%) and everolimus-eluting stents (68%) had the greatest probabilities for being the best treatment option. Furthermore, PEB were the best treatment in terms of late luminal loss (85%) and binary restenosis (85%). BA had the lowest efficacy with respect to all study end points. In conclusion, in patients with DES restenosis, repeat DES implantation and iopromide-based PEB are valid alternatives. However, PEB had greater angiographic efficacy and therefore should be considered the new benchmark comparator in the treatment of DES restenosis. The use of BA should be discouraged in patients with DES restenosis.


docid: urofdyxb

title: Rapid detection of ermB gene in Clostridium difficile by loop-mediated isothermal amplification.

text: Macrolide-lincosamide-streptogramin B resistance in Clostridium difficile is mostly due to the ermB resistance determinant. Here, we describe a sensitive and rapid molecular method to detect ermB in C. difficile to contribute to the wider epidemiological study. Five sets of loop-mediated isothermal amplification (LAMP) primers were designed and optimized for rapid detection of ermB. The specificity and sensitivity of the primers for ermB were detected, and the ermB LAMP assay was compared to conventional PCR with 80 clinical isolates of C. difficile. Real-time monitoring of turbidity and chromogenic reaction were used to determine negative and positive results. A total of 26 pathogenic bacterial strains of different species were found to be negative for ermB, which indicated the high specificity of the primers. ermB was detected in 78.8 % (63/80) of the clinical isolates by both LAMP and conventional PCR. The detection limit of LAMP was 36.1 pg DNA μl- 1 and its sensitivity was 10-fold greater than that of conventional PCR. This study is the first report regarding the development and application of the LAMP assay for detection of the ermB gene in C. difficile strains. The developed LAMP method is sensitive, specific and provides a user-friendly visual approach for the rapid detection of ermB-bearing C. difficile.


title: Fluorescence-enhanced europium-diethylenetriaminepentaacetic (DTPA)-monoamide complexes for the assessment of renal function.

text: Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca. 2700-fold) Eu(3+) fluorescence enhancement. Indeed, complex 18b exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance property was assessed using the corresponding radioactive (111)In complex 18a, and the data suggest that this complex clears via a complex mechanism that includes glomerular filtration.


title: Haemodynamic changes with the use of neuromuscular electrical stimulation compared to intermittent pneumatic compression.

text: INTRODUCTION Enhancement of peripheral circulation has been shown to be of benefit in many vascular disorders, and the clinical effectiveness of intermittent pneumatic compression is well established in peripheral vascular disease. This study compares the haemodynamic efficacy of a novel neuromuscular electrical stimulation device with intermittent pneumatic compression in healthy subjects. METHODS Ten healthy volunteers (mean age 27.1 ± 3.8 years, body mass index 24.8 ± 3.6 kg/m(2)) were randomised into two groups, in an interventional crossover trial. Devices used were the SCD Express™ Compression System, (Covidien, Ireland) and the geko™, (Firstkind Ltd, UK). Devices were applied bilaterally, and haemodynamic measurements taken from the left leg. Changes to haemodynamic parameters (superficial femory artery and femoral vein) and laser Doppler measurements from the hand and foot were compared. RESULTS Intermittent pneumatic compression caused 51% (p = 0.002), 5% (ns) and 3% (ns) median increases in venous peak velocity, time-averaged maximum velocity and volume flow, respectively; neuromuscular electrical stimulator stimulation caused a 103%, 101% and 101% median increases in the same parameters (all p = 0.002). The benefit was lost upon deactivation. Intermittent pneumatic compression did not improve arterial haemodynamics. Neuromuscular electrical stimulator caused 11%, 84% and 75% increase in arterial parameters (p < 0.01). Laser Doppler readings taken from the leg were increased by neuromuscular electrical stimulator (p < 0.001), dropping after deactivation. For intermittent pneumatic compression, the readings decreased during use but increased after cessation. Hand flux signal dropped during activation of both devices, rising after cessation. DISCUSSION The neuromuscular electrical stimulator device used in this study enhances venous flow and peak velocity in the legs of healthy subjects and is equal or superior to intermittent pneumatic compression. This warrants further clinical and economic evaluation for deep venous thrombosis prophylaxis and exploration of the haemodynamic effect in venous pathology. It also enhances arterial time-averaged maximum velocity and flow rate, which may prove to be of clinical use in the management of peripheral arterial disease. The effect on the microcirculation as evidenced by laser Doppler fluximetry may reflect a clinically beneficial target in microvascular disease, such as in the diabetic foot.


title: A novel technique for tumor localization and targeted lymphatic mapping in early-stage lung cancer.

text: OBJECTIVE To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). METHODS Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR+ SLNs and adverse events were recorded. RESULTS Twelve patients underwent NB-guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR+ "tattoo" was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false-negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB-labeling or indocyanine green dye itself. CONCLUSIONS NB-guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image-guided technique may permit the accurate localization and nodal staging of early stage lung cancers.


title: Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome.

text: Few studies have been performed on noninvasive ventilation (NIV) to treat hypoxic acute respiratory failure in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The outcomes of these patients, for whom endotracheal intubation is not mandatory, depend on the degree of hypoxia, the presence of comorbidities and complications, and their illness severity. The use of NIV as an alternative to invasive ventilation in severely hypoxemic patients with ARDS (ie, P(aO(2))/F(IO(2)) < 200) is not generally advisable and should be limited to hemodynamically stable patients who can be closely monitored in an intensive care unit by highly skilled staff. Early NIV application may be extremely helpful in immunocompromised patients with pulmonary infiltrates, in whom intubation dramatically increases the risk of infection, pneumonia, and death. The use of NIV in patients with severe acute respiratory syndrome and other airborne diseases has generated debate, despite encouraging clinical results, mainly because of safety issues. Overall, the high rate of NIV failure suggests a cautious approach to NIV use in patients with ALI/ARDS, including early initiation, intensive monitoring, and prompt intubation if signs of NIV failure emerge.


title: Evaluation of airway management associated hands-off time during cardiopulmonary resuscitation: a randomised manikin follow-up study.

text: INTRODUCTION Airway management is an important component of cardiopulmonary resuscitation (CPR). Recent guidelines recommend keeping any interruptions of chest compressions as short as possible and not lasting more than 10 seconds. Endotracheal intubation seems to be the ideal method for establishing a secure airway by experienced providers, but emergency medical technicians (EMT) often lack training and practice. For the EMTs supraglottic devices might serve as alternatives. METHODS 40 EMTs were trained in a 1-hour standardised audio-visual lesson to handle six different airway devices including endotracheal intubation, Combitube, EasyTube, I-Gel, Laryngeal Mask Airway and Laryngeal tube. EMTs performances were evaluated immediately after a brief practical demonstration, as well as after 1 and 3 months without any practice in between, in a randomised order. Hands-off time was pair-wise compared between airway devices using a repeated-measures mixed-effects model. RESULTS Overall mean hands-off time was significantly (p<0.01) lower for Laryngeal tube (6.1s; confidence interval 5.2-6.9s), Combitube (7.9s; 95% CI 6.9-9.0s), EasyTube (8.8s; CI 7.3-10.3s), LMA (10.2s; CI 8.6-11.7s), and I-Gel (11.9s; CI 10.2-13.7s) compared to endotracheal intubation (39.4s; CI 34.0-44.9s). Hands-off time was within the recommended limit of 10s for Combitube, EasyTube and Laryngeal tube after 1 month and for all supraglottic devices after 3 months without any training, but far beyond recommended limits in all three evaluations for endotracheal intubation. CONCLUSION Using supraglottic airway devices, EMTs achieved a hands-off time within the recommended time limit of 10s, even after three months without any training or practice. Supraglottic airway devices are recommended tools for EMTs with lack of experience in advanced airway management.


title: Emerging infectious disease risk: shared drivers with environmental change.

text: Outbreaks of emerging infectious diseases (EIDs) seemingly appear without warning, severely exacerbating public and animal health burdens and spreading across borders. Since 1940, the rate of infectious disease emergence events has risen. Given the considerable economic and other societal costs associated with EIDs, understanding the specific drivers of these diseases and developing concrete measures to prevent and mitigate their spread is urgently needed in both health security and sustainable development discussions. Human modification of the environment serves as an underlying driver in EID risk: environmental change thus warrants consideration in surveillance and outbreak investigations to identify the origin of the disease and contribute to the development of effective actions to prevent, prepare for or reduce the risk of future events. Coordinated approaches to address the underlying and, in some cases, overlapping causes of both disease emergence and global environmental change may yield benefits for sustainable and healthy solutions to meet or reshape the demands of a growing global population and contribute to global health security.


title: Initial Experience with p64: A Novel Mechanically Detachable Flow Diverter for the Treatment of Intracranial Saccular Sidewall Aneurysms.

text: BACKGROUND AND PURPOSE Flow diverters are important tools for the treatment of intracranial aneurysms. We report a retrospective evaluation of the safety and efficacy of p64, a fully resheathable, detachable flow diverter, in the endovascular treatment of intracranial sidewall aneurysms. MATERIALS AND METHODS Results of 121 patients with 130 aneurysms (median neck size, 3 mm; median fundus size, 4 mm), treated from April 2012 through October 2014, were analyzed. Aneurysms were unruptured or beyond the acute SAH phase. Thirteen aneurysms were located in the posterior circulation. Twenty-three aneurysms had previous saccular treatment but no previous parent vessel stent placement. In 19 aneurysms, a combination of coiling and flow diversion was performed. RESULTS Successful p64 deployment was achieved in 127/130 aneurysms. The average number of p64s used was 1.1 per aneurysm. The rates of transient and permanent morbidity and mortality were 5%, 1.7%, and 0.8%, respectively. Three-month DSA follow-up in 123/130 aneurysms showed complete occlusion in 58.5%. Nine-month DSA follow-up in 93/106 (87.7%) eligible aneurysms showed complete occlusion in 79.6%. Late follow-up (median, 496 days) has already been performed in 35 aneurysms, showing complete occlusion in 30 (85.7%). CONCLUSIONS p64 offers an efficacious treatment option for intracranial sidewall aneurysms with a high aneurysm occlusion and an acceptable complication rate. The possibility of repositioning or removing the device was an advantage. The higher attenuation may lead to fewer devices per case and early aneurysm occlusion. Long-term follow-up data are pending.


title: The use of prosthetic mesh for abdominal wall repairs: A semi-systematic-literature review.

text: Following abdominal wall surgery, incisions are commonly sutured, stapled, or glued together by primary intention. Developments within the field of tissue engineering have led to the use of prosthetic meshes, with over 20 million meshes implanted each year worldwide. The function of the mesh is to hold together abdominal wall incisions and repair abdominal hernias. This has been demonstrated to be highly effective in some individuals; however, some patients have experienced postoperative complications, including dehiscence with further abdominal herniation (viscera protruding through the abdominal wall). Little is currently known about why these complications occur in a subset of patients who have had prosthetic mesh implants in abdominal wall repairs; therefore, this literature review examined existing studies identified via six electronic databases. A total of 463 studies were identified, of which 13 were included in this review. The results identified that the prosthetic mesh is highly successful in a large proportion of patients who have had a had a hernia repair in a range of locations; however, the prosthetic mesh has long-term complications, with rejection being observed in a subset of patients. The reason why the prosthetic is being rejected is still largely unknown, and therefore, further investigation needs to be carried out.


title: Communicable diseases in the South-East Asia Region of the World Health Organization: towards a more effective response.

text: This article looks at the current burden of communicable diseases in the South-East Asia Region of the World Health Organization and analyses whether the current levels and trends in funding are adequate to meet the needs of control, prevention and treatment. Our analysis considers the Millennium Development Goals (MDGs) for health and indicators of economic progress in each country, as well as the impact of the global financial crisis on progress towards MDGs for communicable diseases in the region. The analysis indicates that the current focus of funding may need to be expanded to include less-discussed but high-burden diseases often related to inadequacies in the health sector and the particular development paths that countries pursue. Scarce funding during times of global economic recession could be used more effectively if informed by a careful analysis of the complex set of factors, including behavioural, environmental and health systems factors, that determine the burden of communicable diseases. Significant gaps in funding as well as varying regional needs warrant a more diverse set of national and international aid measures. Although regional and global collaboration is critical, the effectiveness of future policies to deal with the burden of communicable diseases in the region will only be assured if these policies are based on evidence and developed by policy-makers familiar with each country's needs and priorities.


title: Dose-response and transmission: the nexus between reservoir hosts, environment and recipient hosts.

text: Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose-response could determine the likelihood of transmission. There is a need to explore dose-response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose-response literature and discuss the unique role dose-response models have to play in understanding and predicting spillover events. We present a re-analysis of dose-response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose-response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.


Response to: 'Antimalarial use and arrhythmias in COVID-19 and rheumatic patients: a matter of dose and inflammation?' by Erre et al.


title: Thoracic cancer surgery during the COVID-19 pandemic: A consensus statement from the Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery.

text: OBJECTIVES Healthcare resources have been mobilized to combat the COVID-19 pandemic of 2020. The Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery reports a consensus statement on the provision of thoracic cancer surgery during this pandemic. METHODS A Thoracic Experts Panel was convened by the Society. A consensus on the provision, safety, and setting of thoracic cancer surgery during the pandemic was obtained through a Delphi process. RESULTS Responses were received from 26 panel members (96% response rate) from 10 regions across Asia. The Society recommended that elective thoracic cancer surgery services may need to be reduced or postponed if medical resources were needed for COVID-19 patients, especially intensive care unit beds and ventilators. However, thoracic cancer surgery should proceed as normal for all solid tumors, without restrictions based on disease stage, availability of non-surgical treatment options, or patient condition (unless there is a high likelihood of postoperative intensive care unit stay). Aerosol-forming procedures should be avoided intra- and perioperatively. The surgical approach does not make a difference in terms of safety. Services for thoracic cancer patients should be offered only in hospitals that maintain isolation wards for patients with confirmed or suspected COVID-19. CONCLUSIONS Services for patients with thoracic cancer should be maintained during the COVID-19 pandemic. The position of the Society is that thoracic surgeons have a responsibility to perform good surgical management of thoracic cancer during the pandemic, to advocate for patients' rights to receive it, and to safeguard patients and staff from infection.


title: Incursions of Candida auris into Australia, 2018.

text: Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization. Phylogenetic analysis revealed putative transmission between 2 patients and suspected overseas acquisition in the others. Vigilant screening of at-risk patients is required.


title: Evaluation of a multi-epitope subunit vaccine against avian leukosis virus subgroup J in chickens.

text: The intricate sequence and antigenic variability of avian leukosis virus subgroup J (ALV-J) have led to unprecedented difficulties in the development of vaccines. Much experimental evidence demonstrates that ALV-J mutants have caused immune evasion and pose a challenge for traditional efforts to develop effective vaccines. To investigate the potential of a multi-epitope vaccination strategy to prevent chickens against ALV-J infections, a recombinant chimeric multi-epitope protein X (rCMEPX) containing both immunodominant B and T epitope concentrated domains selected from the major structural protein of ALV-J using bioinformatics approach was expressed in Escherichia coli Rosetta (DE3). Its immunogenicity and protective efficacy was studied in chickens. The results showed that rCMEPX could elicit neutralizing antibodies and cellular responses, and antibodies induced by rCMEPX could specifically recognize host cell naturally expressed ALV-J proteins, which indicated that the rCMEPX is a good immunogen. Challenge experiments showed 80% chickens that received rCMEPX were well protected against ALV-J challenge. This is the first report of a chimeric multi-epitope protein as a potential immunogen against ALV-J.


title: Fighting Liver Fibrosis with Naturally Occurring Antioxidants.

text: Liver fibrosis is a wound-healing response characterized by the accumulation of extracellular matrix following various liver injuries, which results in the deformation of the normal liver architecture and the development of liver cirrhosis and even hepatocellular carcinoma. Numerous in vitro and in vivo studies indicated that oxidative stress mediates the initiation and progression of liver fibrosis. Overaccumulation of reactive oxygen species disrupts macromolecules, induces necrosis and apoptosis of hepatocytes, stimulates the production of pro-fibrogenic mediators, and directly activates hepatic stellate cells, thereby resulting in liver damage and initiating liver fibrosis. Ameliorating oxidative stress is a potential therapeutic strategy for the treatment of liver fibrosis. Natural antioxidants have attracted increasing attention in treating liver fibrosis due to their safety and efficacy. In this review, the pathogenesis of liver fibrosis and the role of oxidative stress in liver fibrosis were discussed. Naturally occurring antioxidants that can treat and prevent liver fibrosis were summarized. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of oxidative stress in liver fibrosis to representative antioxidants for treating liver fibrosis. Naturally occurring antioxidants show a potential for further investigations as lead compounds in fighting liver fibrosis.


title: Synthesis and biological evaluation of tylophorine-derived dibenzoquinolines as orally active agents: exploration of the role of tylophorine e ring on biological activity.

text: A series of novel tylophorine-derived dibenzoquinolines has been synthesized and their biological activity evaluated. Three assays were conducted: inhibition of cancer cell proliferation, inhibition of TGEV replication for anticoronavirus activity, and suppression of nitric oxide production in RAW264.7 cells (a measure of anti-inflammation). The most potent compound from these assays, dibenzoquinoline 33b, showed improved solubility compared to tylophorine 9a, in vivo efficacies in a lung A549 xenografted tumor mouse model and a murine paw edema model, good bioavailability, and no significant neurotoxicity (as tested by a rota-rod test for motor coordination). This is the first study to explore in detail the role of the tylophorine E ring on biological activity and very strongly suggests that tylophorine-derived dibenzoquinolines merit further development into orally active agents.


title: Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia.

text: Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP.


title: Slow versus fast rewarming after hypothermic circulatory arrest: effects on neuroinflammation and cerebral oedema.

text: OBJECTIVES Among the factors that could determine neurological outcome after hypothermic circulatory arrest (HCA) rewarming is rarely considered. The optimal rewarming rate is still unknown. The goal of this study was to investigate the effects of 2 different protocols for rewarming after HCA on neurological outcome in an experimental animal model. METHODS Forty-four Sprague Dawley rats were cooled to 19 ± 1°C body core temperature by cardiopulmonary bypass (CPB). HCA was maintained for 60 min. Animals were randomized to receive slow (90 min) or fast (45 min) assisted rewarming with CPB to a target temperature of 35°C. After a total of 90 min of reperfusion in both groups, brain samples were collected and analysed immunohistochemically and with immunofluorescence. In 10 rats, magnetic resonance imaging was performed after 2 and after 24 h to investigate cerebral perfusion and cerebral oedema. RESULTS Interleukin 6, chemokine (C-C motif) ligand 5, intercellular adhesion molecule 1 and tumour necrosis factor α in the hippocampus are significantly less expressed in the slow rewarming group, and microglia cells are significantly less activated in the slow rewarming group. Magnetic resonance imaging analysis demonstrated better cerebral perfusion and less water content in brains that underwent slow rewarming at 2 and 24 h. CONCLUSIONS Slow rewarming after HCA might be superior to fast rewarming in neurological outcome. The present experimental study demonstrated reduction in the inflammatory response, reduction of inflammatory cell activation in the brain, enhancement of cerebral blood flow and reduction of cerebral oedema when slow rewarming was applied.


title: Middle cerebral artery aneurysm endovascular and surgical therapies: comprehensive literature review and local experience.

text: The middle cerebral artery is a common location for cerebral aneurysms and is associated with a lower risk of rupture than aneurysms located in the anterior or posterior communicating arteries. No evidence supports the superiority of clipping over coiling to treat middle cerebral artery aneurysm (MCAA) or vice versa. The feasibility of treating the MCAA with endovascular therapy as the first choice of treatment in cohorts of nonselected aneurysms exceeds 90%. A randomized clinical trial comparing the 2 approaches in nonselected cases with long-term follow-up will shed light on which patients may benefit from one approach over another.


title: COMMENT ON: Hospital care in Departments defined as COVID-free: A proposal for a safe hospitalization protecting healthcare professionals and patients not affected by COVID-19.

text: The COVID-19 outbreak dramatically changed hospital everyday life, impairing the course of previous routine activity, also in urology. In the next months, together with keeping the focus on the prevention of contagion recrudescence, the health care system will face another stringent issue, i.e. to restore all the services not COVID-related. Leonardi et al. in their paper report an equilibrate overview on the incoming "Phase 2", in order to set up so-called COVID-free hospitals and departments. The authors offer an insight from a practical point of view, detailing protocols for any of the steps of the path of care, from the outpatient visit to surgery.


docid: tlnfmipn

title: Distinction between contrast staining and hemorrhage after endovascular stroke treatment: one CT is not enough.

text: BACKGROUND Postinterventional cerebral hyperdensities (PCHDs) are a common finding after endovascular stroke treatment. There is uncertainty about the extent to which PCHDs correspond to hemorrhage or contrast staining. Our aim was to evaluate the use of PCHD density on immediate postinterventional CT, and PCHD evolution on follow-up CT for differentiating contrast staining from hemorrhage after endovascular treatment. METHODS We retrospectively reviewed the imaging data of 84 patients who underwent endovascular treatment for acute arterial ischemic stroke in the anterior circulation and who received an immediate postinterventional CT, a follow-up CT within 36 h, and a follow-up MRI within 10 days. RESULTS PCHDs were seen in 62 of 84 patients in a total of 130 Alberta Stroke Program Early CT Score (ASPECTS) areas. A specificity of 100% to predict hemorrhage was only seen for PCHDs with densities <40 HU (for ruling hemorrhage out) and ≥140 HU (for ruling hemorrhage in), at the cost of a low sensitivity of 1.1% and 2.4%, respectively. Persisting PCHDs correlated with hemorrhage with a specificity of 93.3% and a sensitivity of 62.5%. When follow-up CT was performed at least 19 h after the first CT, persisting PCHDs correlated with hemorrhage with a specificity of 100% and a sensitivity of 62.5%. CONCLUSIONS There are no density thresholds for PCHDs that allow predicting the absence or presence of hemorrhage with 100% specificity and acceptable sensitivity. A CT scan performed at least 19-24 h after endovascular therapy is the only reliable method to differentiate contrast staining from hemorrhage.


title: Protocol for a scoping review of post-trial extensions of randomised controlled trials using individually linked administrative and registry data.

text: INTRODUCTION Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects. There have been recent important examples, including 20+ years follow-up studies of trials of pravastatin and mammography. Despite the potential value of post-trial extension, there has been no systematic study of this literature. This scoping review aims to characterise published post-trial extension studies, assess their value, and identify any potential challenges associated with this approach. METHODS AND ANALYSIS This review will use the recommended methods for scoping reviews. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A draft search strategy is included in this protocol. Review of titles and abstracts, full texts of potentially eligible studies and data/information extraction will be conducted independently by pairs of investigators. Eligible studies will be RCTs that investigated healthcare interventions that were extended by individual linkage to administrative/registry/electronic medical records data after the completion of the planned follow-up period. Information concerning the original trial, characteristics of the extension study, any clinical, policy or ethical implications and methodological or practical challenges will be collected using standardised forms. ETHICS AND DISSEMINATION As this study uses secondary data, and does not include person-level data, ethics approval is not required. We aim to disseminate these findings through journals and conferences targeting triallists and researchers involved in health data linkage. We aim to produce guidance for investigators on the conduct of post-trial extensions using routinely collected data.


title: A retrospective analysis of delays in the diagnosis of lung cancer and associated costs.

text: PURPOSE Diagnosis of lung cancer at advanced stages can result in missed treatment opportunities, worse outcomes, and higher health care costs. This study evaluated the wait time to diagnose non-small-cell lung cancer (NSCLC) and the cost of diagnosis and treatment based on the stage at diagnosis. PATIENTS AND METHODS Adult patients diagnosed with NSCLC between January 2007 and September 2011 were identified from a proprietary oncology registry and linked to health insurance claims from a large US health insurance company. Continuous enrollment in the health plan was required for at least 12 months prediagnosis (baseline) and at least 3 months postdiagnosis (follow-up). Use of diagnostic tests and time to diagnosis were examined. The rates of health care utilization and per-patient per-month (PPPM) health care costs were calculated. RESULTS A total of 1,210 patients with NSCLC were included in the analysis. Most patients (93.6%) had evidence of diagnostic tests beginning 5 to 6 months prior to diagnosis, and most were diagnosed at an advanced stage (23% Stage IIIb and 46% Stage IV). The PPPM total health care costs in USD pre- and postdiagnosis were $2,407±$3,364 (mean±standard deviation) and $16,577±$33,550, respectively. PPPM total health care costs and utilization after lung cancer diagnosis were significantly higher among patients diagnosed at Stage IV disease and lowest among patients diagnosed at Stage I disease ($7,239 Stage I, $9,484 Stage II, $11,193 Stage IIIa, $17,415 Stage IIIb, and $21,441 Stage IV). CONCLUSION This study showed that most patients experienced long periods of delay between their first diagnostic test for lung cancer and a definitive diagnosis, and the majority were diagnosed at advanced stages of disease. Costs associated with the management of lung cancer increased substantially with higher stages at diagnosis. Procedures that diagnose lung cancer at earlier stages may allow for less resource use and costs among patients with lung cancer.


Video-assisted thoracoscopic surgery (VATS) for locally advanced lung cancer.


title: Laser Angiography with Indocyanine Green to Assess Vaginal Cuff Perfusion during Total Laparoscopic Hysterectomy: A Pilot Study.

text: STUDY OBJECTIVE To determine feasibility of using laser angiography with indocyanine green (ICG) to assess vaginal cuff vascular perfusion during total laparoscopic hysterectomy (TLH). DESIGN Pilot feasibility trial (Canadian Task Force classification II-2). SETTING Academic-affiliated hospital. PATIENTS Twenty women undergoing TLH for benign disease. INTERVENTIONS Participants underwent 1:1 randomization of energy method used for colpotomy (ultrasonic vs monopolar) and vaginal cuff closure suture (barbed vs nonbarbed). After intravenous administration of ICG, laser angiography was used to capture images of the vaginal cuff before and after closure. Three reviewers analyzed fluorescent images of vaginal cuffs to determine percent of cuff perimeter with adequate perfusion when open and length of vaginal cuff adequately perfused when closed. MEASUREMENTS AND MAIN RESULTS ICG fluorescence was visible at the vaginal cuff in all participants. Mean time to appearance of ICG in the pelvis after administration was 19.8 ± 6.8 seconds (mean ± SD) preclosure, and 26.0 ± 22.2 seconds postclosure. With ultrasonic energy 67.5% ± 17.4% of open cuff perimeter and 74.4% ± 20.5% of closed cuff length were adequately perfused, whereas with monopolar energy use 59.1% ± 17.4% of the open cuff perimeter and 66.3% ± 15.4% of closed cuff length were adequately perfused. Cuffs closed with barbed suture showed adequate perfusion along 71.5% ± 15.1% of the length, whereas those closed with nonbarbed suture showed 68.9% ± 20.9% adequate perfusion. When normalized to cervical cup circumference, ultrasonic energy required 1.0 ± .2 s/mm, whereas monopolar energy required .8 ± .3 s/mm (p = .162). Linear regression showed no association of normalized time of energy activation to percentage of perimeter of open cuff (R2 = .007) or length of closed cuff (R2 = .005) with adequate perfusion. No complications related to intravenous ICG administration occurred. CONCLUSION Laser angiography with ICG allows evaluation of vascular perfusion at the vaginal cuff during TLH. This technique may facilitate future prospective studies examining causes for vaginal cuff dehiscence, a complication with potential for severe morbidity.


title: Rapid Degradation of Host mRNAs by Stimulation of RNase E Activity by Srd of Bacteriophage T4.

text: Escherichia coli messenger RNAs (mRNAs) are rapidly degraded immediately after bacteriophage T4 infection, and the host RNase E contributes to this process. Here, we found that a previously uncharacterized factor of T4 phage, Srd ( S: imilarity with R: po D: ), was involved in T4-induced host mRNA degradation. The rapid decay of ompA and lpp mRNAs was partially alleviated and a decay intermediate of lpp mRNA rapidly accumulated in cells infected with T4 phage lacking srd. Exogenous expression of Srd in uninfected cells significantly accelerated the decay of these mRNAs. In addition, lpp(T) RNA, with a sequence identical to the decay intermediate of lpp mRNA and a triphosphate at 5'-end, was also destabilized by Srd. The destabilization of these RNAs by Srd was not observed in RNase E-defective cells. The initial cleavage of a primary transcript by RNase E can be either direct or dependent on the 5'-end of transcript. In the latter case, host RppH is required to convert the triphosphate at 5'-end to a monophosphate. lpp(T) RNA, but not lpp and ompA mRNAs, required RppH for Srd-stimulated degradation, indicating that Srd stimulates both 5'-end-dependent and -independent cleavage activities of RNase E. Furthermore, pull-down and immunoprecipitation analyses strongly suggested that Srd physically associates with the N-terminal half of RNase E containing the catalytic moiety and the membrane target sequence. Finally, the growth of T4 phage was significantly decreased by the disruption of srd. These results strongly suggest that the stimulation of RNase E activity by T4 Srd is required for efficient phage growth.


title: Detection of viruses by counting single fluorescent genetically biotinylated reporter immunophage using a lateral flow assay.

text: We demonstrated a lateral flow immunoassay (LFA) for detection of viruses using fluorescently labeled M13 bacteriophage as reporters and single-reporter counting as the readout. AviTag-biotinylated M13 phage were functionalized with antibodies using avidin-biotin conjugation and fluorescently labeled with AlexaFluor 555. Individual phage bound to target viruses (here MS2 as a model) captured on an LFA membrane strip were imaged using epi-fluorescence microscopy. Using automated image processing, we counted the number of bound phage in micrographs as a function of target concentration. The resultant assay was more sensitive than enzyme-linked immunosorbent assays and traditional colloidal-gold nanoparticle LFAs for direct detection of viruses.


title: Sternal tumor resection and reconstruction with titanium mesh: a preliminary study.

text: OBJECTIVE To explore the clinical efficacy and complications of treating sternal tumors by resection and titanium mesh thoracic reconstruction. METHODS This retrospective analysis of eight patients with sternal tumors treated in the Department of Orthopedic Surgery at the First Affiliated Hospital of Zhengzhou University from January 2008 to June 2012 included five men and three women aged 37-66 years (mean, 50.4 years). The histological diagnoses were chondrosarcoma (two cases), osteosarcoma (one), malignant fibrous histiocytoma (two), eosinophilic granuloma (one) and sternal metastasis from breast cancer (two). The tumors were invading the manubrium sterni (three cases), manubrium sterni and body (three) and sternal body (two). All patients underwent needle or incisional biopsy prior to sternal tumor resection and titanium mesh thoracic reconstruction. RESULTS All patients were followed for 9 months to 4 years. There were no intraoperative complications or operative or postoperative deaths. One patient developed a deep wound hematoma 1 week postoperatively; incisional drainage and debridement resulting in healing within 2 weeks. There was no loosening or exsertion of the titanium mesh and no patients developed respiratory complications or thoracic deformity. One patient with malignant fibrous histiocytoma died of lung metastases 9 months postoperatively, another with malignant fibrous histiocytoma died of liver metastases 14 months postoperatively; the remaining patients survived without tumor recurrence. CONCLUSION Titanium mesh chest reconstruction after sternal tumor resection has the advantages of simplifying the procedure, achieving a good shape and having few complications. Titanium mesh is an ideal material for reconstruction of the sternum.


title: [Interpretation of "Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)"].

text: the National Health Commission of the People's Republic of China publish the guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 5) .With the awareness and understanding of the disease, the guidelines have been revised for recognize, treat, and prevent diseases. Then, what are the contents of the fifth edition of the guide issued updated compared to the fourth edition, now, learn together.


title: Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

text: BACKGROUND AND PURPOSE Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.


title: Motives and considerations regarding PGT in couples carrying a structural chromosomal abnormality: a qualitative exploration.

text: PURPOSE This study aims to describe the motives and considerations of couples carrying a structural chromosomal abnormality deciding on preimplantation genetic testing (PGT). METHODS A qualitative exploratory study was conducted using semi-structured dyadic interviews with 13 couples (N = 26) carrying a structural chromosomal abnormality. All couples had an informative consultation in our PGT centre in the Netherlands. RESULTS Almost all couples considered PGT or natural conception combined with prenatal diagnosis (PND) as the only two reproductive options. Among several considerations mentioned, the majority indicated that the wish to increase the chance of a successful pregnancy was the most important motive to opt for PGT. All couples who opted for PGT had first tried to conceive spontaneously and entered the PGT programme because of their adverse experiences during these attempts (infertility, recurrent miscarriage, termination of pregnancy, birth of an affected child). Couples that refrained from PGT were of advanced maternal age and expressed the long trajectory of PGT as the main reason to refrain. If conceiving spontaneously would not lead to an ongoing pregnancy, these couples also indicated that they would use PGT. CONCLUSION This study shows that couples carrying a structural chromosomal abnormality consider PGT and spontaneous conception with PND as relevant reproductive options. They are looking for the option that is in their opinion the fastest way to establish a successful pregnancy. Information on the perceived pros and cons of PGT or spontaneous conception in these couples can help to optimize counselling and psychological support during the decision-making process.


title: Treatment of Brain AVMs (TOBAS): study protocol for a pragmatic randomized controlled trial.

text: BACKGROUND The management of unruptured brain arteriovenous malformation (AVM) patients remains controversial. Furthermore, curative attempts to treat ruptured AVM patients have not been questioned so far, and there is a lack of prospective data on clinical results according to treatment modality. Endovascular treatment is often used aiming to improve the safety or efficacy of surgery or radiation therapy, but benefits have never been documented in a trial. A care trial context is needed to evaluate interventions at the same time they are practised. METHODS/TRIAL DESIGN TOBAS is a pragmatic, prospective, multicenter, randomized, controlled trial and registry which offers a care trial context for brain AVM patients, including surgical resection, radiosurgery or endovascular embolization, alone or combined. The study includes two RCTs and a multimodality prospective registry. The objectives of the proposed study are to assess whether preventive interventions (surgery, embolization, radiation therapy, alone or combined), selected by the local treatment team and performed as locally practiced, randomly allocated and compared with conservative management, in unruptured brain AVM patients eligible for active or conservative management, can improve the proportion of patients having an independent outcome (modified Rankin Scale (mRS) < 3, as assessed by a standardized questionnaire administered by non-masked care personnel) at 10 years. All patients judged ineligible for randomized allocation are to be entered in a multimodal registry. The objective of a nested trial in patients with ruptured or unruptured AVMs to be treated by surgery or radiation therapy, is to assess whether pre-surgical or pre-radiation embolization, randomly allocated and compared with no embolization, can improve the proportion of patients with complete eradication of the AVM, as locally adjudicated, combined with a good clinical outcome (mRS < 3). The study will require up to 2000 patients in approximately 30 centers or more, followed for 10 years. TOBAS is registered at clinicaltrials.gov: NCT02098252 as of 25 March 2014.


The GP workforce: no room for complacency.


title: Sorafenib induces autophagy in human myeloid dendritic cells and prolongs survival of skin allografts.

text: BACKGROUND Sorafenib, a multikinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, has been reported inhibitory on the function of dendritic cells. This study was aimed to determine the effects of sorafenib on inducing autophagy and immunomodulatory activity and its implication on graft rejection. METHODS Cell viability and surface antigens were examined by 7-amino-actinomycin D and flow cytometric analysis. Autophagy was characterized using light microscopy and transmission electron microscopy for morphology, Western blotting for LC3B-I lipidation and mammalian target of rapamycin signaling molecules, and immunofluorescence staining for endogenous LC3B, GFP-LC3 transfection, and acidic component vacuoles. Skin allograft in mice was used as an experimental transplantation rejection model. Soluble factors contained in culture medium and serum were measured by enzyme-linked immunosorbent assay. RESULTS We found that sorafenib inhibited the viability of dendritic cells accompanied by morphologic changes characteristic of autophagy and immature differentiation. This autophagic effect induced by sorafenib was validated by LC3B-I lipidation and autophagosome accumulation. Sorafenib treatment was associated with the down-regulation of phosphorylated mammalian target of rapamycin and its downstream substrate p70S6K. We next performed skin graft model to testify the role of sorafenib-induced immature and autophagic dendritic cells. Intriguingly, sorafenib prolonged the survival of skin allograft without major toxicity. Blockade of autophagic flux by chloroquine partially diminished the protective effect of sorafenib, indicating an autophagy-related mechanism in vivo. CONCLUSION This study suggests that sorafenib, in addition to being an anticancer agent, may have potential to be developed as a new category of immunosuppressant drugs acting via autophagy induction of dendritic cells.


title: Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0),Tyr(3)]octreotate.

text: PURPOSE Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called "remainder of the body" to the bone marrow. METHODS Bone marrow aspirates were drawn in 15 patients after treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. RESULTS A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. CONCLUSION (1) After PRRT with [(177)Lu-DOTA(0),Tyr(3)]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary.


title: Feedback to the central dogma: cytoplasmic mRNA decay and transcription are interdependent processes.

text: Transcription and RNA decay are key determinants of gene expression; these processes are typically considered as the uncoupled beginning and end of the messenger RNA (mRNA) lifecycle. Here we describe the growing number of studies demonstrating interplay between these spatially disparate processes in eukaryotes. Specifically, cells can maintain mRNA levels by buffering against changes in mRNA stability or transcription, and can also respond to virally induced accelerated decay by reducing RNA polymerase II gene expression. In addition to these global responses, there is also evidence that mRNAs containing a premature stop codon can cause transcriptional upregulation of homologous genes in a targeted fashion. In each of these systems, RNA binding proteins (RBPs), particularly those involved in mRNA degradation, are critical for cytoplasmic to nuclear communication. Although their specific mechanistic contributions are yet to be fully elucidated, differential trafficking of RBPs between subcellular compartments are likely to play a central role in regulating this gene expression feedback pathway.


title: Intraoperative endoscopic assessment of the pouch and anastomosis during laparoscopic Roux-en-Y gastric bypass.

text: As an advanced surgical procedure, laparoscopic Roux-en-Y gastric bypass (LRYGB) is associated with considerable morbidity, especially in the learning curve period. The aim of this study was to evaluate the role of endoscopy during LRYGB surgery in assessing the gastric pouch and anastomosis for air leak, bleeding, and structure at the beginning of a bariatric surgery program. Patients who underwent LRYGB for morbid obesity between May 2008 and May 2009 were included in this study. After the completion of the anastomosis, an endoscopic examination was carried out. The transection line and anastomosis site were examined for bleeding and patency and inspected for air leak under laparoscopic vision. Thirteen morbidly obese patients (mean body mass index, 48.0 ± 6.8 kg/m(2)) were evaluated by endoscopic examination during the LRYGB operation. None of the cases had bleeding at the transection line or anastomosis site. In two patients, air leak test was positive and the anastomosis was reinforced with additional sutures. All the patients, including those with positive air leak test, were discharged from the hospital with no leak complications. After a mean follow-up of 9.1 ± 5.5 months, except for the patient who underwent balloon dilatation, no other patient had anastomotic stricture. Intraoperative endoscopy is invaluable in the assessment of bleeding, anastomotic patency, and air leak during LRYGB, and it might be a helpful auxiliary tool to decrease morbidity during the learning curve period. Also, it helps solve intraoperative problems during the surgery so that postoperative complications might be prevented.


title: Effect of hygiene interventions on acute respiratory infections in childcare, school and domestic settings in low- and middle-income countries: a systematic review.

text: OBJECTIVES Acute respiratory infections (ARIs) disproportionately affect those living in low- and middle-income countries (LMICs). We aimed to determine whether hygiene interventions delivered in childcare, school or domestic settings in LMICs effectively prevent or reduce ARIs. METHODS We registered our systematic review with PROSPERO (CRD42017058239) and searched MEDLINE, EMBASE, CENTRAL, and Scopus from inception to 17 October 2017 for randomised controlled trials (RCTs) examining the impact of hygiene interventions on ARI morbidity in adults and children in community-based settings in LMICs. We stratified data into childcare, school and domestic settings and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess evidence quality. RESULTS We identified 14 cluster RCTs evaluating hand-hygiene interventions in LMICs with considerable heterogeneity in setting, size, intervention delivery and duration. We found reduced ARI-related absenteeism and illness in childcare settings (low- to moderate-quality evidence). In school settings, we found reduced ARI-related absenteeism and laboratory-confirmed influenza (moderate- to high-quality evidence), but no reduction in ARI illness (low-quality evidence). In domestic settings, we found reduced ARI illness and pneumonia amongst children in urban settlements (high-quality evidence) but not in rural settlements (low-quality evidence), and no effect on secondary transmission of influenza in households (moderate-quality evidence). CONCLUSIONS Evidence suggests that hand-hygiene interventions delivered in childcare, school and domestic settings can reduce ARI morbidity, but effectiveness varies according to setting, intervention target and intervention compliance. Further studies are needed to develop, deliver and evaluate targeted and sustainable hygiene interventions in LMICs.


Should We Monitor Pulsus Paradoxus via Pulse Oximetry in COVID-19 Patients with Acute Respiratory Failure?


title: Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network.

text: The North American Clinical Trials Network (NACTN) includes 9 clinical centers funded by the US Department of Defense and the Christopher Reeve Paralysis Foundation. Its purpose is to accelerate clinical testing of promising therapeutics in spinal cord injury (SCI) through the development of a robust interactive infrastructure. This structure includes key committees that serve to provide longitudinal guidance to the Network. These committees include the Executive, Data Management, and Neurological Outcome Assessments Committees, and the Therapeutic Selection Committee (TSC), which is the subject of this manuscript. The NACTN brings unique elements to the SCI field. The Network's stability is not restricted to a single clinical trial. Network members have diverse expertise and include experts in clinical care, clinical trial design and methodology, pharmacology, preclinical and clinical research, and advanced rehabilitation techniques. Frequent systematic communication is assigned a high value, as is democratic process, fairness and efficiency of decision making, and resource allocation. This article focuses on how decision making occurs within the TSC to rank alternative therapeutics according to 2 main variables: quality of the preclinical data set, and fit with the Network's aims and capabilities. This selection process is important because if the Network's resources are committed to a therapeutic, alternatives cannot be pursued. A proposed methodology includes a multicriteria decision analysis that uses a Multi-Attribute Global Inference of Quality matrix to quantify the process. To rank therapeutics, the TSC uses a series of consensus steps designed to reduce individual and group bias and limit subjectivity. Given the difficulties encountered by industry in completing clinical trials in SCI, stable collaborative not-for-profit consortia, such as the NACTN, may be essential to clinical progress in SCI. The evolution of the NACTN also offers substantial opportunity to refine decision making and group dynamics. Making the best possible decisions concerning therapeutics selection for trial testing is a cornerstone of the Network's function.


title: Development of a rapid, simple, and specific real-time PCR assay for detection of pseudorabies viral DNA in domestic swine herds.

text: Despite successful eradication of pseudorabies virus (PRV) from the commercial pig industry in the United States in 2004, large populations of feral swine in certain regions act as wildlife reservoirs for the virus. Given the threat of reintroduction of the virus into domestic herds, a rapid, reliable, easily implemented assay is needed for detection of PRV. Although a real-time PCR (rtPCR) assay exists, improvements in rtPCR technology and a greater understanding of the diversity of PRV strains worldwide require an assay that would be easier to implement, more cost effective, and more specific. We developed a single-tube, rapid rtPCR that is capable of detecting 10 copies of PRV glycoprotein B ( gB) DNA per 20-µL total volume reaction. The assay did not produce a false-positive in samples known to be negative for the virus. The assay was negative for genetically similar herpesviruses and other porcine viruses. Our assay is a highly specific and sensitive assay that is also highly repeatable and reproducible. The assay should be a useful tool for early detection of PRV in pigs in the case of a suspected introduction or outbreak situation.


Ebola: a game changer for vaccines, or a scare that will soon be forgotten?


title: Clinical Impact of Intrathoracic Herniation of Gastric Tube Pull-Up via the Retrosternal Route following Esophagectomy.

text: BACKGROUND Intrathoracic herniation of gastric tube (IHGT) pull-up via the retrosternal route is a rare complication following esophagectomy, which is caused due to an injury in the parietal pleura during a blunt dissection of the retrosternal space. However, little is known regarding the clinical impact of IHGT pull-up via the retrosternal route. PATIENTS AND METHODS Clinical data of 231 patients receiving gastric tube reconstruction via the retrosternal route following esophagectomy were collected from medical charts. RESULTS Of the 231 patients, 19 (8%) developed IHGT. Vocal cord palsy, particularly with delayed onset, developed at a significantly high frequency in the group of patients with IHGT. There were no significant differences in the frequency of other surgical complications. CONCLUSION This is the first report to examine the clinical impact of IHGT pull-up via the retrosternal route. Vocal cord palsy, particularly with delayed onset, developed in the group of patients with IHGT. Therefore, when reconstruction is performed via the retrosternal route, it is very important that blunt and blind dissection of the retrosternal space be performed with extreme care to prevent pleural injury.


title: China's growing biomedical industry.

text: The biomedical industry in China is developing rapidly, and new biological drugs are increasing their share of the pharmaceutical market based on people's needs. China is the largest producer and user of vaccines in the world, but the existing production of vaccines is far from enough to meet the needs of the market. The entire market of biological drugs in China is still smaller than that for traditional medicines and chemicals. Therefore, the biopharmaceutical industry has the potential to be the rising star in the pharmaceutical market in the future.


Management strategies for patients with autoimmune diseases during the COVID-19 pandemic: A perspective from China.


title: Carotid angioplasty and stenting is safe and effective for treatment of recurrent stenosis after eversion endarterectomy.

text: OBJECTIVE This study was conducted to determine the efficiency and long-term durability of percutaneous transluminal angioplasty and carotid artery stenting in carotid restenosis (CR) treatment after eversion endarterectomy, with emphasis on variables that could influence the outcome. METHODS We analyzed 319 patients (220 asymptomatic and 99 symptomatic) who underwent carotid angioplasty from 2002 until 2012 for CR that occurred after eversion endarterectomy. During this period, 7993 eversion endarterectomies were done for significant carotid artery stenosis. Significant CR was detected by ultrasound examination and confirmed by digital subtraction angiography or multidetector computed tomography angiography. After angioplasty (with or without stenting), color duplex ultrasound imaging was done after 1 month, 6 months, 1 year, and annually thereafter. End points encompassed myocardial infarction, stroke, and cardiovascular death (fatal myocardial infarction, fatal cardiac failure, fatal stroke), and also puncture site hematoma and recurrent restenosis. Primary end points were analyzed as early results (≤30 days after the procedure), and secondary end points were long-term results (>30 days). Variables and risk factors influencing the early-term and long-term results were also analyzed. Median follow-up was 49.8 ± 22.8 months (range, 17-121 months). RESULTS All but one procedure ended with a technical success (99.7%). In the early postoperative period, transient ischemic attack occurred in 2.8% of the patients and stroke in 1.6%, followed by one lethal outcome (0.3%). Stent thrombosis occurred in one patient (0.3%) several hours after the angioplasty, followed by urgent surgery and graft interposition. In the long-term follow-up, there were no transient ischemic attacks or strokes, non-neurologic mortality was 3.13%, and the recurrent restenosis rate was 4.4%. The rate of non-neurologic outcomes during the follow-up was significantly higher in asymptomatic patients than in symptomatic patients (4.54% vs 0%; P = .034). The statically highest rate of transient ischemic attack was verified in patients in whom Precise (Cordis Corporation, New Brunswick, NJ) stents was used (12.2%) and a Spider Fx (Covidien, Dublin, Ireland) cerebral protection device (12.5%) was used. Female gender, coronary artery disease, plaque calcifications, and smoking history were associated with an adverse outcome after angioplasty. CONCLUSIONS Carotid artery stenting is safe and reliable procedure for CR after eversion endarterectomy treatment, with low rate of postprocedural complications. Type of stent and cerebral embolic protection device may influence the rate of postprocedural neurologic ischemic events.


title: The laparoscopic modified Sugarbaker technique is safe and has a low recurrence rate: a multicenter cohort study.

text: BACKGROUND Parastomal hernia is a frequent complication of intestinal stomata. Mesh repair gives the best results, with the mesh inserted via laparotomy or laparoscopically. It was the aim of this retrospective multicenter study to determine the early and late results of the laparoscopically performed, modified Sugarbaker technique with ePTFE mesh. METHODS From 2005 to 2010, a total of 61 consecutive patients (mean age = 61 years), with a symptomatic parastomal hernia, underwent laparoscopic repair using the modified Sugarbaker technique with ePTFE mesh. Fifty-five patients had a colostomy, 4 patients an ileostomy, and 2 a urostomy according to Bricker. The records of the patients were reviewed with respect to patient characteristics, postoperative morbidity, and mortality. All patients underwent physical examination after a follow-up of at least 1 year to detect a recurrent hernia. Morbidity rate was 19 % and included wound infection (n = 1), ileus (n = 2), trocar site bleeding (n = 2), reintervention (n = 2), and pneumonia (n = 1). One patient died in the postoperative period due to metastasis of lung carcinoma that caused bowel obstruction. Concomitant incisional hernias were detected in 25 of 61 patients (41 %) and could be repaired at the same time in all cases. A recurrent hernia was found in three patients at physical examination, and in one patient an asymptomatic recurrence was found on a CT scan. The overall recurrence rate was 6.6 % after a mean follow-up of 26 months. CONCLUSION The laparoscopic Sugarbaker technique is a safe procedure for repairing parastomal hernias. In our study, the overall morbidity was 19 % and the recurrence rate was 6.6 % after a mean follow-up of 26 months. Moreover, the laparoscopic approach revealed concomitant hernias in 41 % of the patients, which could be repaired successfully at the same time.


title: The impact of a modified electronic probe tip design on patient perception of discomfort during periodontal probing using standardised probing force. A randomised controlled trial.

text: AIMS This study evaluated pain associated with electronic probing comparing two commercially available probe tip designs using standardised force. MATERIAL & METHODS Twenty adult patients with slight-moderate chronic periodontitis received periodontal probing using controlled-force electronic probe at 2 visits. In visit 1, a random arch was probed with either a ball-end (0.6mm diameter, 408 kPa; Test) or straight (0.45mm diameter, 726 kPa; Control) probe tip. The opposing arch was then probed using the other probe tip. Discomfort associated with each probing episode was recorded using visual analogue scale (VAS). 7 days later, tip assignments were alternated from visit 1 and VAS re-scored. VAS scores were compared by probe tip, arches and visits. RESULTS Both tips provided similar VAS scores (median 13.5 for ball-end and 14 for straight, p=0.3713). However, the straight tip was associated with decreased VAS scores in the maxilla (p=0.01). Overall, VAS values did not differ by arch or study visit. Individual VAS scores showed high levels of correlation between study visits and between tips used (R2 =0.86 and 0.64, respectively, P<0.0001). CONCLUSIONS Both probing approaches were associated with low levels of pain on probing. The straight tip, it may be perceived as more comfortable in the maxilla.


title: Thioredoxin-1 and protein disulfide isomerase catalyze the reduction of similar disulfides in HIV gp120.

text: HIV-1 enters cells via interaction of the viral glycoprotein gp120, the host cell surface receptor CD4 and the co-receptors CCR5 or CXCR4. For entry, gp120 undergoes conformational changes that depend on the reduction of one or more disulfides. Previous studies indicate that protein disulfide isomerase (PDI), thioredoxin-1 (Trx1), and glutaredoxin-1 (Grx1) catalyze gp120 reduction, but their specific disulfide targets are not known. Here, it was demonstrated that PDI and Trx1 have similar gp120 disulfide targets as determined by labeling after reduction, but with some pattern differences, including overall stronger labeling with Trx1 than with PDI. Furthermore, uneven labeling of the residues of a disulfide may reflect altered accessibility by conformational changes upon the reduction process. Since both PDI and Trx1 may be involved in viral entry, compounds that target the host redox system or the viral gp120 were tested in vitro to investigate whether redox regulation is a target for anti-HIV therapy. Carbohydrate binding agents (CBAs), previously shown to bind gp120 and inhibit HIV entry, were now demonstrated to inhibit gp120 disulfide reduction. Auranofin, an inhibitor of thioredoxin reductase 1 (TrxR1), also showed inhibitory activity towards HIV infection, although close to its cytotoxic concentration. Our results demonstrate that both the host redox system and the viral surface glycoproteins are of interest for the development of new generations of anti-HIV therapeutics.


title: Total laparoscopic Roux-en-Y cholangiojejunostomy for the treatment of biliary disease.

text: BACKGROUND AND OBJECTIVES Roux-en-Y cholangiojejunostomy (RCJS) has been widely used in biliary bypass surgeries, but in most reported literature, an assisted miniincision was needed, and studies reporting total laparoscopic Roux-en-Y cholangiojejunostomy (TLRCJS) are rare. The goal of this study was to investigate how to treat hepatic portal bile duct diseases and perform jejunojejunostomy and cholangiojejunostomy totally laparoscopically. We evaluated the feasibility of TLRCJS in treating biliary tract diseases. METHODS TLRCJS were performed in 103 patients from January 2000 to August 2011. There were 28 cases of recurrent choledocholithiasis combined with stricture of the common bile duct (CBD) after several stone extractions, 3 patients with iatrogenic bile duct injury, 24 patients with choledochal cyst, 36 patients with hepatic portal cholangiocarcinoma, and 12 patients with cancer of the pancreatic head and periampullary cancer. All surgeries were performed through 5 trocars. First, laparoscopic surgery on the CBD was performed according to the original disease. The CBD was opened and stones were extracted in choledocholithiasis patients. In iatrogenic injury patients, strictured CBD was resected and repaired. Dilated CBD or choledochal cyst with tumor was transected. In patients with malignant jaundice, the CBD was opened longitudinally. At the same time, the bile duct was prepared for cholangiojejunostomy. Second, the positions of the laparoscope and surgeons were altered. The jejunal mesentery and jejunum were transected, and side-to-side jejunojejunostomy (JJS) was performed. The laparoscope and surgeon positions were exchanged again; the Rouxen-Y biliary limb was lifted close to the residual bile duct; and side-to-side or end-to-side choledochojejunostomy (CJS) was performed. Finally, an abdominal drainage tube was placed. RESULTS All the surgeries were performed successfully. The diameter of the residual bile duct ranged from 0.4 to 3.2 cm (average, 0.9 cm). Three patients had postoperative bile leakage and were treated from 1 week to approximately 1 month with abdominal drainage. Postoperative intraperitoneal hemorrhage and stress ulcer of the stomach occurred in 2 patients with biliary tract injury combined with obstructive jaundice. One with intraperitoneal hemorrhage was cured by another laparoscopic surgery. The other patient was cured after 2 days of abdominal drainage, antacids, and hemostatic drug therapy. The follow-up duration of 95 patients was 4 to 93 months (average, 48.3 months). The follow-up rate was 92.2% (95/103). Patients with cancer died of metastasis or cachexia during 14-month follow-up with no postoperative complication. Reflux cholangitis occurred in 3 patients 2, 3, and 5 years after the operation, respectively. No anastomotic stricture or other complication was found in other patients during the follow-up. CONCLUSIONS TLRCJS is the best and first choice for patients with biliary tract diseases that need biliary-jejunal anastomosis. But it is essential that the surgeon has proficiency in laparoscopic surgeries.


title: Evaluation of total laparoscopic hysterectomy with and without the use of barbed suture.

text: OBJECTIVE To evaluate the outcome of total laparoscopic hysterectomy with and without the use of barbed suture. METHODS We conducted a retrospective study among patients who underwent total laparoscopic hysterectomy between February 2008 and August 2012. The parameters evaluated were age, BMI, operative time, hospital stay, pre- and postoperative hemoglobin levels, uterine weight, intraoperative blood loss, and postoperative complications. RESULTS A total of 202 women underwent total laparoscopic hysterectomy; barbed suture (V-Loc) was used in 63 women, and polydioxanone (PDS) in 139. Estimated blood loss, difference in hemoglobin level before and after surgery, operative time, and the duration of hospital stay were comparable between the two groups of patients. The incidence of postoperative fever was higher in the V-Loc group than in the PDS group (P = 0.003). Multiple linear regression analysis showed that the incidence of postoperative fever was related to BMI (P = 0.02, r = 0.22) and estimated blood loss (P = 0.004, r = 0.28) and not to age, operative time, or uterine weight. CONCLUSION The use of barbed suture to close the vaginal vault after laparoscopic hysterectomy, compared with standard suture, results in similar operative time, blood loss, and duration of hospital stay. The use of barbed suture is technically less demanding than the use of regular sutures.


title: Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction.

text: INTRODUCTION The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction. METHODS PSV, NAVA, and PAV were set to obtain a tidal volume (VT) of 6 to 8 ml/kg (PSV₁₀₀, NAVA₁₀₀, and PAV₁₀₀) in 16 intubated patients. Assistance was further decreased by 50% (PSV₅₀, NAVA₅₀, and PAV₅₀) and then increased by 50% (PSV₁₅₀, NAVA₁₅₀, and PAV₁₅₀) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. VT, peak EAdi, coefficient of variation of VT and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated. RESULTS PAV and NAVA prevented the increase of VT with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV₁₅₀ and NAVA₁₅₀ versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV₁₅₀, P <0.05). EAdi was higher with PAV than with PSV at level₁₀₀ and level₁₅₀. The coefficient of variation of VT was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA₁₀₀ and PAV₁₀₀ versus 13 (IQR 11 to 18)% with PSV₁₀₀, P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV (P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV (P <0.05). CONCLUSIONS PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes. TRIAL REGISTRATION Clinicaltrials.gov NCT02056093 . Registered 18 December 2013.


title: Fluorescent Tissue Assessment of Colorectal Cancer Liver Metastases Ablation Zone: A Potential Real-Time Biomarker of Complete Tumor Ablation.

text: BACKGROUND This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments. METHODS This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30 min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (H&E). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the H&E and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus H&E and IHC assessments were calculated. RESULTS A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent H&E and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45). CONCLUSIONS The study showed a high concordance rate between the immediate fluorescent assessment and the standard H&E and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.


title: IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers.

text: Healthcare workers (HCW) are a risk group for TB. Even in countries with low TB incidence, the risk of TB in HCW is elevated for a wide range of tasks in healthcare, and the prevention of nosocomial infection of HCW remains as a challenge. IFN-γ release assays (IGRA) facilitate the screening of HCW for latent TB infection. In comparison with the tuberculin skin test, the IGRA reduces the number of x-rays and the amount of chemoprevention needed. However, a borderline zone should be introduced for the interpretation of IGRA results in the serial testing of HCW. More data on disease progression depending on conversion and reversion in IGRA is needed and a better test, which is able to distinguish recent from remote latent TB infection, would be desirable in the future.


title: Histopathologic evaluation of arterial wall response to 5 neurovascular mechanical thrombectomy devices in a swine model.

text: BACKGROUND AND PURPOSE Five commercial devices are available for mechanical thrombectomy in acute ischemic stroke. This study evaluated and compared the resultant arterial damage from these devices. MATERIALS AND METHODS Wall damage after 4 wall-contact devices (the Merci retriever, Catch thromboembolectomy system, and Solitaire FR revascularization devices of 4 and 6 mm) and 1 aspiration device (the Penumbra System) was evaluated in the superficial femoral arteries of 20 male swine. Each device was tested with and without intraluminal clot. Twenty control vessels were not subjected to any intervention. Acute histopathologic changes were evaluated. RESULTS In the device samples, endothelial denudation (72.8 ± 29.4% versus 0.9 ± 1.9%, P < .0001), medial layer edema (52 ± 35.9% versus 18.1 ± 27.8%, P = .004), and mural thrombus (5.3 ± 14.2% versus 0%, P = .05) were found to a greater extent compared with the control samples. The aspiration device provoked more intimal layer (100 ± 79.1% versus 58.8 ± 48.9%, P = .27) and medial layer (75 ± 35.4% versus 46.3 ± 34.8%, P = .13) edema than the wall-contact devices. CONCLUSIONS All devices caused vascular injuries extending into the medial layer. The aspiration device was associated with more intimal and medial layer edema, compared with the wall-contact devices except for the Catch thromboembolectomy system.


title: Solo Single-Incision Laparoscopic Resectional Roux-en-Y Gastric Bypass for Morbid Obesity with Metabolic Syndrome.

text: With the advancement of laparoscopic devices and surgical technology, the era of minimal invasive surgery has progressed to reduced-port surgery, and finally to single-incision laparoscopic surgery (SILS). Several reports show successful application of SILS to various types of bariatric surgery. Oftentimes, this requires a skilled and experienced scopist to perform the procedure. To overcome the technical difficulties of single-incision Roux-en-Y gastric bypass, a manual scope holder was used instead of an assistant scopist, greatly stabilizing the field of view. This allows the surgery to be performed at any time without being influenced by the need of a highly experienced scopist. In this report, we describe in detail the world's first solo single-incision laparoscopic resectional Roux-en-Y gastric bypass.


title: Feasibility of Catheter Placement Under Ultrasound Guidance for Progressive Preoperative Pneumoperitoneum for Large Incisional Hernia with Loss of Domain.

text: INTRODUCTION Large incisional hernias with loss of domain (LIHLD) of the abdominal wall remain a therapeutic challenge due to the difficulty of replacing the contents of the hernia sac into the peritoneal cavity. Preoperative progressive pneumoperitoneum (PPP) is a valuable option. The purpose of this study was to evaluate the feasibility of peritoneal catheter insertion under ultrasound guidance for PPP and to compare the morbidity and mortality of this new technique to previously used techniques in our department. METHODS Medical records were reviewed retrospectively from February 1989 to April 2013 in a single institution. Three different techniques of PPP were evaluated: surgical subcutaneous implantable port (SIP), surgical peritoneal dialysis catheter (PDC), and radiologic multipurpose drainage catheter (MDC). Collected data included patients' age, sex, body mass index, medical and surgical history, hernia location, PPP technique, length of hospitalization, volume of air injected, morbidity and mortality linked to PPP, and the procedure of hernia repair. RESULTS Thirty-seven patients with a mean age of 63.1 years were evaluated. Progressive preoperative pneumoperitoneum was performed using SIP, PDC, and MDC for 14, 11, and 12 patients, respectively. Overall morbidity related to the technique was seen in 36 % of SIP, 27 % of PDC, and 0 % of MDC. One patient from the SIP group died on the 3rd postoperative day due to septic shock following aspiration pneumonia. No postoperative mortality in the other groups was observed. CONCLUSION The MDC is an interesting modification of the original technique and is a safe procedure. It is a minimally invasive technique with a very low risk of perforation of the viscera. Therefore, the use of a non-absorbable prosthesis with MDC technique can be offered for all patients undergoing PPP without increasing the risk of infection.