title: Comparison of hand-assisted laparoscopic surgery using tissue fusion devices and open resection for treatment of rectosigmoid carcinoma.

text: Modern tissue fusion devices used in hand-assisted laparoscopic surgery (HALS), a method of combining endoscopic surgery with tactile sensation, can minimize surgical trauma and hospitalization times beyond both conventional laparoscopy and open surgery. The outcomes of HALS using tissue fusion devices and conventional open surgery for curative resection of rectosigmoid carcinoma were compared. A total of 78 (45 males, 33 females; mean age, 57.2±11.7 y) rectosigmoid carcinoma patients underwent HALS surgery (HALS group) and 78 age-matched, sex-matched, and tumor status-matched rectosigmoid carcinoma patients (control group) underwent open resection between June 2008 and June 2010. In the HALS and control groups, abdominal incision length, intraoperative blood loss, procedure time, postoperative abdominal drainage, time to first flatus (bowel function return), length of hospital stay, morbidity, mortality, and pathology were assessed. Procedure times were similar in both groups (142.37±42.09 vs. 137.56±36.24 min). However, length of abdominal incision (5.14±0.47 vs. 13.17±2.41 cm), intraoperative blood loss (125.96±75.58 vs. 142.56±65.37 mL), need for postoperative analgesia, bowel function return (68.01±22.64 vs. 79.77±19.94 h), and postoperative hospital stay (6.47±1.73 vs. 7.73±1.71 d) were all significantly improved in the HALS group. At a median follow-up of 26 months, no significant differences in anastomotic recurrence were observed between groups (1 case/each group). Thus, the HALS approach for curative resection of rectosigmoid carcinoma was found to be similarly safe and effective compared with open resection. Furthermore, HALS may improve postoperative recovery and reduce hospitalization times.


title: Endoscopic intraoperative anastomotic testing may avoid early gastrointestinal anastomotic complications. A prospective study.

text: BACKGROUND Gastrointestinal anastomotic complications represent serious events; methods to evaluate anastomotic integrity seem to be suboptimal. Since endoscopic intraoperative anastomotic testing allows direct visualization of anastomosis, complication rates may be theoretically reduced by the use of this technique. METHODS A prospective study involving 118 consecutive oncologic patients undergoing endoscopically tested gastrointestinal stapled anastomoses was carried out. As controls, 148 historical patients without anastomotic testing were used for comparisons. RESULTS In the study group, anastomotic testing revealed 16 defects: 11 (9.3%) air leaks and five (4.3%) bleeding anastomoses. All leaks were oversewn and secured. Bleeding anastomoses were managed under direct visualization, and one non-patent anastomosis was redone. Forty-one (15.4%) postoperative anastomotic complications were observed: eight (3%) bleeding anastomoses, seven (2.6%) stenoses, and 26 (9.8%) clinical leaks. No early dehiscence or bleeding occurred if anastomoses were intraoperatively checked, while these complications were significantly more frequent in non-checked anastomoses (6.1% and 5.4%, respectively). Conversely, late leak and stenosis rates were similar between the two groups. CONCLUSION Endoscopic anastomotic testing was a safe and reliable method to assess integrity of gastrointestinal anastomoses, to correct any defect under direct visualization, and to avoid early complications. However, this method seemed inadequate to predict late anastomotic complications.


title: Antigenic relationships among porcine epidemic diarrhea virus and transmissible gastroenteritis virus strains.

text: UNLABELLED Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are economically important swine enteropathogenic coronaviruses. These two viruses belong to two distinct species of the Alphacoronavirus genus within Coronaviridae and induce similar clinical signs and pathological lesions in newborn piglets, but they are presumed to be antigenically distinct. In the present study, two-way antigenic cross-reactivity examinations between the prototype PEDV CV777 strain, three distinct U.S. PEDV strains (the original highly virulent PC22A, S indel Iowa106, and S 197del PC177), and two representative U.S. TGEV strains (Miller and Purdue) were conducted by cell culture immunofluorescent (CCIF) and viral neutralization (VN) assays. None of the pig TGEV antisera neutralized PEDV and vice versa. One-way cross-reactions were observed by CCIF between TGEV Miller hyperimmune pig antisera and all PEDV strains. Enzyme-linked immunosorbent assays, immunoblotting using monoclonal antibodies and Escherichia coli-expressed recombinant PEDV and TGEV nucleocapsid (N) proteins, and sequence analysis suggested at least one epitope on the N-terminal region of PEDV/TGEV N protein that contributed to this cross-reactivity. Biologically, PEDV strain CV777 induced greater cell fusion in Vero cells than did U.S. PEDV strains. Consistent with the reported genetic differences, the results of CCIF and VN assays also revealed higher antigenic variation between PEDV CV777 and U.S. strains. IMPORTANCE Evidence of antigenic cross-reactivity between porcine enteric coronaviruses, PEDV and TGEV, in CCIF assays supports the idea that these two species are evolutionarily related, but they are distinct species defined by VN assays. Identification of PEDV- or TGEV-specific antigenic regions allows the development of more specific immunoassays for each virus. Antigenic and biologic variations between the prototype and current PEDV strains could explain, at least partially, the recurrence of PEDV epidemics. Information on the conserved antigenicity among PEDV strains is important for the development of PEDV vaccines to protect swine from current highly virulent PEDV infections.


title: Construction of recombinant lactobacilli expressing the core neutralizing epitope (COE) of porcine epidemic diarrhea virus and a fusion protein consisting of COE and Escherichia coli heat-labile enterotoxin B, and comparison of the immune responses by orogastric immunization.

text: The core neutralizing epitope (COE) region of porcine epidemic diarrhea virus (PEDV) plays an important role in the development of the subunit vaccine against PEDV infection. To enhance the vaccine's immunogenicity, Escherichia coli heat-labile enterotoxin B (LTB) has usually been adopted as a molecular adjuvant. In this study, the COE and LTB-COE genes were engineered into the Lactobacillus -Escherichia coli shuttle vectors pSAPG1 (surface-displaying) and pSAPG2 (secreting) followed by electrotransformation into Lactobacillus casei (Lc) to yield the following recombinant strains: Lc:PG1-LTB-COE, Lc:PG2-LTB-COE, Lc:PG1-COE, and Lc:PG2-COE. Our results showed that mice immunized orogastrically with L. casei expressing COE or LTB-COE produced secretory immunoglobulin A and immunoglobulin G with the ability to neutralize PEDV in sera and mucus. Moreover, higher levels of interleukin-4 and gamma interferon were also exhibited compared with negative control. These data displayed the tendency of Lc:PG2-LTB-COE > Lc:PG1-LTB-COE > Lc:PG2-COE > Lc:PG1-COE at the same time point. Taken together, LTB-COE is more suitable for Lactobacillus expressing system to engineer mucosal vaccine against PEDV infection.


title: Letter to the Editor: Radiological approaches to COVID-19 pneumonia.

text: Dear editor, We read with great interest the article titled ?Radiological approaches to COVID-19 pneumonia? by Akcay S. et al. in the latest issue of Turk J Med Sci [1]. The authors provided a review of the radiological findings of novel coronavirus disease (COVID-19) pneumonia. We would like to highlight some missing radiological findings in this article, and we want to contribute to some critical radiological findings.


docid: vvjunosm

title: Incidental benign metastasizing leiomyoma in a patient with bone sarcoma: a case report.

text: Background. The benign metastasizing leiomyoma is an exceptionally rare entity; it presents with ectopic leiomyoma nodules with a benign pattern. Symptoms vary according to the anatomic location. The diagnosis is histopathological, usually in patients with history of hysterectomy. Case Presentation. A 36-year-old female with 2-month history of left knee pain was diagnosed with bone fibrosarcoma. A CT scan showed pulmonary nodules. The patient started neoadjuvant chemotherapy. Conservative surgery of pelvic limb was achieved. A new CT scan reported pulmonary nodules that remained in relation to the previous CT. A nodule resection by thoracotomy and TOB (transoperative biopsy) was performed. The final pathology report described benign proliferative lesions consistent with benign metastatic leiomyoma. Conclusions. Benign metastatic leiomyoma is a rare condition presenting with uterine and extrauterine nodules most commonly in the lung. The diagnosis is histopathological. The surgical procedure must be reserved for selected patients.


docid: vaswxlch

title: Risk factors in patients with COVID-19 developing severe liver injury during hospitalisation.


title: Spontaneous Thrombolysis of Multiple Thrombi at Distal Region of Hypoplastic Vertebral Artery After Stent-assisted Angioplasty on Vertebral Artery Origin Stenosis: Angiographic Follow-up.

text: Vertebral artery hypoplasia (VAH) can be easily overlooked if the contralateral side vertebral artery is intact, because of compensation by the contralateral artery or cerebral collateral network. The clinical relevance and hemodynamic impact of VAH is still controversial. However, VAH has recently been considered a risk factor for posterior circulation ischemia. Ischemic stroke is seldom caused by free floating thrombi (FFT) in the artery. Pathophysiology of FFT has not yet been clarified. The state of reduced blood flow such as a vertebral artery origin stenosis may cause FFT. Their instability may make them sources of recurrent artery to artery embolism. Patients with FFT will require appropriate medical and endovascular treatment. The current case illustrates a short-term angiographic change of spontaneous thrombolysis of VAH and multiple thrombi at the distal region of the stenosed lesion after stent-assisted angioplasty for a vertebral artery origin stenosis.


title: COVID-19 and viral hepatitis elimination programs: Are we stepping backward?

text: As Mendlowitz and colleagues mentioned in a recent commentary, the World Health Organization set a goal for the elimination of viral hepatitis until 2030. This means that the number of newly infected persons and related mortality should be decreased by 90% and 65%, respectively. The elimination programs focus on different parts such as testing, treatment, immunization against hepatitis B virus (HBV), preventing mother to child transmission, blood safety, and harm reduction. Now, COVID-19 is spreading fast throughout the world and more than one million people have been affected by this virus so far. While all attentions are now on providing effective medicines and vaccines for COVID-19, we should not forget other viruses and diseases.


title: Successful surgical and medical treatment of rhizopus osteomyelitis following hematopoietic cell transplantation.

text: Mucormycosis has been reported in otherwise healthy individuals; however, it is primarily seen in immunocompromised patients, such as those with diabetes mellitus, malignancy, or chronic graft-versus-host disease, and has a high mortality rate. Because most cases of mucormycosis are associated with contiguous rhinocerebral infection, only 5 cases of isolated musculoskeletal Rhizopus infection have been reported in the literature. One patient underwent hematopoietic cell transplant, which resulted in a fatal outcome.This article describes the successful treatment of isolated Rhizopus osteomyelitis in a patient who underwent hematopoietic cell transplant using a combined surgical and medical approach. A 33-year-old woman with pre-B cell acute lymphoblastic leukemia underwent hematopoietic cell transplant with few complications but developed chronic graft-versus-host disease 8 months posttransplant. She was treated with high-dose steroids for 6 weeks before she was admitted for severe right tibial pain in the absence of trauma. Early detection, aggressive therapies, and a multidisciplinary surgical and medical team allowed for the microbiologically confirmed resolution of the infection. Treatment included multiagent antimicrobial therapy with amphotericin B, daptomycin, and ertapenem. Several surgical irrigation and debridement procedures were also performed, with the eventual placement of amphotericin-impregnated polymethylmethacrylate cement beads and small fragment titanium screws. The patient continued taking postoperative antifungal treatment for 7 months after discharge. Six months following the discontinuation of antifungal therapy, the team's multidisciplinary approach achieved a continued resolution of the patient's infection and a return to a fully ambulatory and radiographically proven recovery without limb loss.


title: The role of BST2/tetherin in feline retrovirus infection.

text: Pathogenic retroviral infections of mammals have induced the evolution of cellular anti-viral restriction factors and have shaped their biological activities. This intrinsic immunity plays an important role in controlling viral replication and imposes a barrier to viral cross-species transmission. Well-studied examples of such host restriction factors are TRIM5α, an E3 ubiquitin ligase that binds incoming retroviral capsids in the cytoplasm via its C-terminal PRY/SPRY (B30.2) domain and targets them for proteasomal degradation, and APOBEC3 proteins, cytidine deaminases that induce hypermutation and impair viral reverse transcription. Tetherin (BST-2, CD317) is an interferon-inducible transmembrane protein that potently inhibits the release of nascent retrovirus particles in single-cycle replication assays. However, whether the primary biological activity of tetherin in vivo is that of a restriction factor remains uncertain as recent studies on human tetherin suggest that it is unable to prevent spreading infection of human immunodeficiency virus type 1 (HIV-1). The feline tetherin homologue resembles human tetherin in amino acid sequence, protein topology and anti-viral activity. Transiently expressed feline tetherin displays potent inhibition of feline immunodeficiency virus (FIV) and HIV-1 particle release. However, stable ectopic expression of feline tetherin in a range of feline cell lines has no inhibitory effect on the growth of either primary or cell culture-adapted strains of FIV. By comparing and contrasting the activities of the felid and primate tetherins against their respective immunodeficiency-causing lentiviruses we may gain insight into the contribution of tetherins to the control of lentiviral replication and the evolution of lentiviral virulence.


title: Macrolide treatment for COVID-19: Will this be the way forward?

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that has developed in late 2019 and 2020 is a serious threat to human health. With no vaccines or drugs approved for prevention and treatment until now, all efforts at drug design and/or clinical trials of already approved drugs are worthy and creditable. Using structure-based drug selection for identification of SARS-CoV-2 protease inhibitors, old drugs such as macrolides (MAC) were predicted to be effective for COVID-19. Lately, the anti-viral effects of macrolides have attracted considerable attention. Very recently, hydroxychloroquine in combination with azithromycin treatment was reported to be effective for COVID-19. We believe that treatments with macrolides alone or in combination with other drugs are promising and open the possibility of an international strategy to fight this emerging viral infection.


Delaying COP26 is not a reason to delay climate action.


title: African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates.

text: Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. Importance: Ferrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we observed significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a nonhuman primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza virus vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.


Covid-19: four fifths of cases are asymptomatic, China figures indicate.


title: Comparative analysis of different transection techniques in minor and major hepatic resections: a prospective cohort study.

text: BACKGROUND In liver surgery different transection techniques are available without clear evidence regarding indication and advantage for each technique. The aim of this study was to identify the most superior liver transection technique between the different techniques (stapler, water-jet and electrocautery). Comparative analyses were performed for minor and major hepatectomies. METHODS In a single-center study, all liver resections performed between July 2007 and July 2012 were prospectively recorded and analysed. RESULTS 366 liver resections were included according to predefined eligibility criteria. No clear benefit for one particular technique in minor or major hepatectomy could be shown. Cost-effectiveness analysis revealed disadvantages for stapler-hepatectomies. However, minor hepatectomies were performed with significantly lower morbidity (p < 0.001), lower operating time (p = 0.001), fewer need of transfusion (p < 0.0001) and shorter ICU stay (p = 0.001) than major hepatectomies. CONCLUSIONS If possible, minor hepatectomies should be chosen. Competing techniques, selected according to surgeon's preference, revealed no significant differences in primary outcome measures.


title: Population Bottlenecks and Pathogen Extinction: "Make This Everyone's Mission to Mars, Including Yours".

text: Kapusinszky et al. (J Virol 89:8152-8161, 2015, http://dx.doi.org/10.1128/JVI.00671-15) report that host population bottlenecks may result in pathogen extinction, which provides a compelling argument for an alternative approach to vaccination for the control of virus spread. By comparing the prevalence levels of three viral pathogens in two populations of African green monkeys (AGMs) (Chlorocebus sabaeus) from Africa and two Caribbean Islands, they convincingly show that a major host bottleneck resulted in the eradication of select pathogens from a given host.


Women are most affected by pandemics - lessons from past outbreaks.


docid: exeaxvqs

title: MUC1 in mesenchymal-to-epithelial transition during human nephrogenesis: changing the fate of renal progenitor/stem cells?

text: BACKGROUND The development of the human kidney is a complex process requiring interactions between epithelial and mesenchymal cells. The condensed cap mesenchyme is hypothesized to generate a population of stem/progenitor cells that undergo mesenchymal-epithelial transition (MET) originating nephrons. Few immunohistochemical markers are available for detecting cap mesenchymal cells in the early phases of MET. METHODS The expression of MUC1 was evaluated in the kidneys, of 4 human foetuses and 2 newborns. RESULTS MUC1 immunoreactivity was detected in all the examined kidneys in the cap mesenchyme and in the renal vesicles. Immunostaining for MUC1 in cap mesenchymal cells changed from one nodule to the next: some mesenchymal nodules were negative, some showed MUC1 reactivity in scattered cells, whereas in others, positive cells revealed the presence of a roundish developing epithelial structure. CONCLUSIONS Our data clearly indicates, for the first time to the best of our knowledge, immunohistochemical evidence of MUC1 expression during human kidney development. We focused on MUC1 reactivity in the cap mesenchyme. On the basis of these preliminary data, we speculate that MUC1 may be involved in human nephrogenesis and may play a relevant role in MET from the cap mesenchyme to the renal vesicle, changing the fate of renal stem/progenitor cells.


title: Uterine retroversion for vaginoperineal reconstruction following resection of distal rectal tumors.

text: PURPOSE Vaginal and perineal reconstruction following wide resection of locally invasive rectal cancer can be challenging. Various techniques have been reported, all of which contribute the additional morbidity inherent in tissue procurement. We present a technique applicable to nonhysterectomized patients who undergo posterior vaginal wall reconstruction with retroversion of the in situ uterus. METHODS Four nonhysterectomized patients with recurrent rectal carcinoma and abdominoperineal resection with en bloc resection of the posterior vagina leaving a large defect necessitating reconstruction of the vagina, perineum, or both, have undergone posterior vaginal wall and perineal reconstruction with uterine retroversion into the posterior pelvis and fixation to the perineum. RESULTS Satisfactory vaginoperineal reconstruction was achieved in all our patients at 3 months. In addition, patients are able to resume sexual activity after tissue re-epithelialization. CONCLUSION Uterine retroversion is a viable option for vaginal and perineal reconstruction.


Therapy: Immunotherapy for T1DM--targeting innate immunity.


title: Effects of renal denervation on atrial arrhythmogenesis.

text: Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity and mortality. In addition to mechanisms such as atrial stretch and atrial remodeling, the activity of the autonomic nervous system has also been suggested to contribute to the progression from paroxysmal to persistent atrial fibrillation. Catheter-based renal denervation was introduced as a minimally invasive approach to reduce renal and whole body sympathetic activation with accompanying blood pressure reduction and left-ventricular morphological and functional improvement in drug-resistant hypertension. This review focuses on the potential effects of renal denervation on different arrhythmogenic mechanisms in the atrium and discusses potential anti-remodeling effects in atrial fibrillation patients with hypertension, heart failure and sleep apnea.


Vasopressin guidelines in surviving sepsis campaign: 2012.


title: Is there a difference in clinical outcomes, inflammation, and hypermetabolism between scald and flame burn?

text: OBJECTIVE Severe thermal injury induces inflammatory and hypermetabolic responses that are associated with morbidity and mortality. However, it is not well-documented whether the causes of burns affect inflammation, hypermetabolism, and morbidity. The aim of the present study was to determine whether there is a difference in degree of inflammation, hypermetabolism, endocrine and acute-phase response, and clinical outcome between pediatric patients with scald and flame burns. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Children with burns requiring surgical intervention were enrolled in this cohort study and divided into two groups, scald or flame burn. In a second assignment, we analyzed the study populations in representative subgroups containing individuals with third-degree burns of 40% to 60% total body surface area. We determined clinical outcomes, resting energy expenditures, cytokine profiles, acute-phase proteins, constitutive proteins, and hormone panels. Statistical analysis was evaluated by analysis of variance, Student's t test corrected with the Bonferroni post hoc test, and the propensity score. Statistical significance was set at p < .05. A total of 912 patients were identified. Six hundred seventy-four had a flame burn and 238 had a scald burn. There was a significant difference (p < .05) in burn size (flame, 48% ± 23%; scald, 40% ± 21%), third-degree burn (flame, 39% ± 27%; scald 22% ± 25%), age (flame, 8 ± 5 yrs; scald, 3 ± 3 yrs), and mortality between groups. Propensity analysis confirmed the type of burn as a significant risk factor for morbidity and mortality. Subanalysis conducted in a representative patient group suffering from 40% to 60% burn total body surface area revealed that flame burns lead to significantly increased hypermetabolic, inflammatory, and acute-phase responses when compared to scald burns (p < .05). The frequency of sepsis was 3% in the scald burn group, while it was 14% in the flame group (p < .001). Multiorgan failure occurred in 14% of the scald patients, while it occurred in 17% of flame patients. The mortality in patients suffering from a scald burn was 3% compared to 6% in the flame-burned group (p < .05). CONCLUSION The type of burn affects hypermetabolism, inflammation, acute-phase responses, and mortality postburn.


docid: ymlcyxng

title: Safely performing neurosurgical procedures during COVID-19 pandemic.

text: INTRODUCTION The novel coronavirus disease (COVID-19) pandemic poses a substantial threat to the health of healthcare personnel on the front line of caring for COVID-19 patients. The Centers for Medicare and Medicaid Services previously announced that all non-essential planned surgeries and procedures should be postponed until further notice and only urgent procedures should proceed. METHODS We share our experiences with safely performing neurosurgical procedures on confirmed and suspected COVID-19 patients, to aide other neurosurgical teams in preparing for these high-risk cases, especially for neurosurgical interventions which are essential at saving a life or preserving functioning of the central nervous system that cannot be delayed. Perioperative and intraoperative strategies, considerations, as well as challenges arisen under the specific circumstance have been discussed: the hospital should be equipped with negative pressure areas and multiple areas to quarantine positive patients; the operating rooms should be negative pressure or have HEPA-filtration systems in place; all healthcare personnel who immediately participate in neurosurgical interventions for confirmed and suspected COVID-19 patients should take airborne precautions and wear enhanced personal protective equipment. RESULTS Successful management of neurosurgical emergencies without healthcare personnel infection has been achieved during this pandemic crisis. CONCLUSION Following the proposed guidance, urgent neurosurgical surgeries and procedures can be safely performed for the benefit of critical patients with or suspected for COVID-19.


title: Respiratory viruses in exacerbations of non-cystic fibrosis bronchiectasis in children.

text: BACKGROUND Respiratory viral infections precipitate exacerbations of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease though similar data in non-cystic fibrosis (CF) bronchiectasis are missing. Our study aimed to determine the point prevalence of viruses associated with exacerbations and evaluate clinical and investigational differences between virus-positive and -negative exacerbations in children with bronchiectasis. METHODS A cohort of 69 children (median age 7 years) with non-CF bronchiectasis was prospectively followed for 900 child-months. PCR for 16 respiratory viruses was performed on nasopharyngeal aspirates collected during 77 paediatric pulmonologist-defined exacerbations. Clinical data, systemic (C reactive protein (CRP), IL-6, procalcitonin, amyloid-A, fibrinogen) and lung function parameters were also collected. FINDINGS Respiratory viruses were detected during 37 (48%) exacerbations: human rhinovirus (HRV) in 20; an enterovirus or bocavirus in four each; adenoviruses, metapneumovirus, influenza A virus, respiratory syncytial virus, parainfluenza virus 3 or 4 in two each; coronavirus or parainfluenza virus 1 and 2 in one each. Viral codetections occurred in 6 (8%) exacerbations. HRV-As (n=9) were more likely to be present than HRV-Cs (n=2). Children with virus-positive exacerbations were more likely to require hospitalisation (59% vs 32.5% (p=0.02)) and have fever (OR 3.1, 95% CI 1.2 to 11.1), hypoxia (OR 25.5, 95% CI 2.0 to 322.6), chest signs (OR 3.3, 95% CI 1.1 to 10.2) and raised CRP (OR 4.7, 95% CI 1.7 to 13.1) when compared with virus-negative exacerbations. INTERPRETATION Respiratory viruses are commonly detected during pulmonary exacerbations of children with bronchiectasis. HRV-As were the most frequently detected viruses with viral codetection being rare. Time-sequenced cohort studies are needed to determine the role of viral-bacterial interactions in exacerbations of bronchiectasis.


title: Laparoscopic sleeve gastrectomy: efficacy of fibrin sealant in reducing postoperative bleeding. A randomized controlled trial.

text: Staple line leakage and bleeding are worrisome complications of laparoscopic sleeve gastrectomy (LSG). Solutions such as buttressing, oversewing or roofing the staple line with gelatin matrix have been proposed with controversial results. Because the use of fibrin sealant has shown a possible benefit in reducing the reoperation rate due to early complication in patients (pts) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP), this solution has been tested in 100 consecutive pts undergoing LSG. A clinical trial has been performed on 100 consecutive pts. Exclusion criteria from the study were considered ASA IV pts, treated or untreated malignancies at any stage, steroids or FANS assumption, previous sovramesocolic surgery and conversion to open surgery. All pts were randomized to receive (group A, 50 pts) or to not receive (group B, 50 pts) 4 ml of human fibrin sealant (Tisseel™, Baxter(®) Deerfield, IL, USA) sprayed along the suture line. Primary endpoint was the incidence of postoperative complications: leaks, bleeding of the staple line or stenosis of the gastric remnant. Significance was assigned at a p level <0.05. By considering pts in group A vs. pts in group B our results shown no significant difference in fistulas or strictures occurrence (p = 0.2). Bleeding was significantly higher in patients not sprayed with sealant (group A vs. group B, 1/7, p = 0.03). This randomized trial has so far shown the use of fibrin sealant in LSG to significantly reduce postoperative bleeding. Although a trend in reducing leak occurrence emerges, it does not reach statistical significance.


title: T-fastener migration after percutaneous gastropexy for transgastric enteral tube insertion.

text: BACKGROUND/AIMS To determine the prevalence and time-course of t-fastener migration after gastropexy deployment. METHODS We reviewed our procedural database for all percutaneous gastrostomy and gastrojejunostomy tube insertions performed over a 14-month period using a widely accepted t-fastener kit for gastropexy (Kimberly-Clark). Of 201 patients, 71 (41 males, 30 females; mean age, 56 years) underwent subsequent abdominal computed tomography (CT) imaging. The location and associated findings of each t-fastener were retrospectively recorded for each CT scan performed after the tube insertion. RESULTS A total of 153 t-fasteners were deployed during 71 procedures with subsequent CT follow-up. In the short term (within 4 weeks after deployment), 5.1% of the t-fasteners had detached and were no longer present; 59.5% were intraluminal or within the gastric wall; and 35.5% were within the anterior abdominal wall musculature or subcutaneous. In the long term (>3 months), 48.6% of the t-fasteners had detached and were no longer present, 25.0% were intraluminal or within the gastric wall, and 26.4% were within the anterior abdominal wall musculature or subcutaneous. No t-fastener-related complications, such as abscesses, fluid collections, or fistulae, were identified. CONCLUSIONS Following gastropexy for percutaneous transgastric feeding tube placement, t-fastener migration into the abdominal wall frequently occurred soon after the tube insertion. Therefore, recent t-fastener deployment does not guarantee an intact gastropexy.


title: Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy.

text: Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.


title: Single-incision laparoscopic colectomy versus conventional multiport laparoscopic colectomy: a meta-analysis of comparative studies.

text: OBJECTIVE This study aimed to compare single-incision laparoscopic colectomy (SILC) to conventional multiport laparoscopic colectomy (MLC). BACKGROUND Single-incision laparoscopic surgery (SILS) is a minimally invasive technique being recently applied to colorectal surgery. A number of studies comparing SILC to conventional MLC have recently been published. METHODS A literature search of PubMed and MEDLINE databases for studies comparing SILC to conventional MLC was conducted. The primary outcome measures for meta-analysis were postoperative complications, length of stay, and operative time. Secondary outcome measures were incision length, estimated blood loss, and number of lymph nodes harvested. RESULTS Fifteen studies comparing 467 patients undergoing SILC to 539 patients undergoing conventional MLC were reviewed and the data pooled for analysis. Patients undergoing SILC had a shorter length of stay (pooled weighted mean difference (WMD) = -0.68; 95 % CI = -1.20 to -0.16; p = 0.0099), shorter incision length (pooled WMD = -1.37; 95 % CI = -2.74 to 0.000199; p = 0.05), less estimated blood loss (pooled WMD = -20.25; 95 % CI = -39.25 to -1.24; p = 0.037), and more lymph nodes harvested (pooled WMD = 1.75; 95 % CI = 0.12 to 3.38; p = 0.035), while there was no significant difference in the number of postoperative complications (pooled odds ratio = 0.83; 95 % CI = 0.57 to 1.20; p = 0.33) or operative time (pooled WMD = 5.06; 95 % CI = -2.91 to 13.03; p = 0.21). CONCLUSION SILC appears to have comparable results to conventional MLC in the hands of experienced surgeons. Prospective randomized trials are necessary to define the relative benefits of one procedure over the other.


title: Aneurysm Recurrence Volumetry Is More Sensitive than Visual Evaluation of Aneurysm Recurrences.

text: PURPOSE Considerable inter-observer variability in the visual assessment of aneurysm recurrences limits its use as an outcome parameter evaluating new coil generations. The purpose of this study was to compare visual assessment of aneurysm recurrences and aneurysm recurrence volumetry with an example dataset of HydroSoft coils (HSC) versus bare platinum coils (BPC). METHODS For this retrospective study, 3-dimensional time-of-flight magnetic resonance angiography datasets acquired 6 and 12 months after endovascular therapy using BPC only or mainly HSC were analyzed. Aneurysm recurrence volumes were visually rated by two observersas well as quantified by subtraction of the datasets after intensity-based rigid registration. RESULTS A total of 297 aneurysms were analyzed (BPC: 169, HSC: 128). Recurrences were detected by aneurysm recurrence volumetry in 9 of 128 (7.0 %) treated with HSC and in 24 of 169 (14.2 %) treated with BPC (odds ratio: 2.39, 95 % confidence interval: 1.05-5.48; P = 0.039). Aneurysm recurrence volumetry revealed an excellent correlation between observers (Cronbach's alpha = 0.93). In contrast, no significant difference in aneurysm recurrence was found for visual assessment (3.9 % in HSC cases and 4.7 % in BPC cases). Recurrences were observed in aneurysms smaller than the sample median in 10 of 33 (30.3 %) by aneurysm recurrence volumetry and in 1 of 13 (7.7 %) by visual assessment. CONCLUSIONS Aneurysm recurrences were detected more frequently by aneurysm recurrence volumetry when compared with visual assessment. By using aneurysm recurrence volumetry, differences between treatment groups were detected with higher sensitivity and inter-observer validity probably because of the higher detection rate of recurrences in small aneurysms.


title: Worthy or not? Six-year experience of revisional bariatric surgery from an Asian center of excellence.

text: BACKGROUND Revisional bariatric surgery (RBS) is increasing. The various primary operations with their distinctive complications make this group of patients quite heterogeneous, and treatment has to be individualized. There are concerns regarding the safety profile and efficacy of these procedures. The objective of the present study was to analyze the indications, safety, and efficacy of RBS at a high-volume Asian center and provide insight into the different treatment options. METHODS Of a total of 1578 bariatric surgeries from July 2006 to June 2012, 52 patients underwent revisional bariatric procedures. The primary operations included 6 different procedures. The indications for surgery were grouped into weight loss failure (n = 21) or complications related to the primary operation (n = 31). The revisional operations performed were conversion to another procedure (n = 22), revision of existing anatomy (n = 29), or reversal to normal anatomy (n = 1). RESULTS 96% of revisional surgeries were performed laparoscopically. The median operating time was 72 minutes (25-240 min), and the median duration of hospital stay was 4 days (3-25 d). The mean body mass index for weight loss failure decreased significantly from 36.3 to 29.6 kg/m(2) after 1 year of revisional surgery (P<.01). However, revision of RYGB was only associated with a body mass index loss of 3.2 kg/m(2) and percentage of excess weight loss of 31.8%. More than 90% of the patients with complications had complete resolution of their preoperative symptoms. There were 3 major complications with an overall morbidity rate of 5.8%. There was no mortality. CONCLUSIONS RBS is well-tolerated, with satisfactory early outcomes, in high-volume centers. However, larger studies with longer follow-up periods are needed to determine the long-term efficacy of these procedures.


Reply: Endobronchial Ultrasound-guided Transbronchial Needle Aspiration under General Anesthesia.


title: Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.

text: Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.


title: Impact of norovirus/sapovirus-related diarrhea in renal transplant recipients hospitalized for diarrhea.

text: BACKGROUND Diarrhea of unspecified cause frequently occurs after renal transplantation and is usually ascribed to mycophenolic acid toxicity. Norovirus (NoV) and sapovirus (SaV) have been sporadically reported to cause chronic diarrhea in immunocompromised patients. METHODS We undertook a retrospective study (2008-2009) to examine the clinical and epidemiologic significance of NoV and SaV infections in adult renal transplant recipients hospitalized for acute or chronic diarrhea. RESULTS Ninety-six renal transplant recipients were hospitalized for diarrhea at our institution during a 16-month period, 87 of whom were included in the study, including 46 patients with chronic diarrhea. Among 41 patients with unexplained diarrhea, 20 patients were screened for NoV/SaV, 16 of whom were positive. Fifteen of them (94%) had chronic diarrhea. When compared with bacterial and parasitic infections, NoV/SaV infections were associated with a greater weight loss at the time of admission, a 8.7-fold longer duration of symptoms and a more frequent need for mycophenolic acid dosage reduction. Eighty-one percent of patients hospitalized for NoV/SaV-associated diarrhea experienced acute renal failure. Five and one patients subsequently had biopsy-diagnosed active graft rejection and oxalate nephropathy, respectively. Ten of the 14 patients who underwent a longitudinal study of NoV/SaV stool's clearance exhibited a prolonged viral shedding period with a median time of 289 days (107-581 days). CONCLUSIONS Our study indicates that NoV/SaV infection causes posttransplant chronic diarrhea potentially complicated by severe kidney graft impairment.


title: Intracranial and Extracranial Neurovascular Manifestations of Takayasu Arteritis.

text: BACKGROUND AND PURPOSE Takayasu arteritis is a rare, large-vessel vasculitis that presents with symptoms related to end-organ ischemia. While the extracranial neurovascular manifestations of Takayasu arteritis are well-established, little is known regarding the intracranial manifestations. In this study, we characterize the intracranial and cervical neurovascular radiologic findings in patients with Takayasu arteritis. MATERIALS AND METHODS Patients with Takayasu arteritis who presented to our institution between 2001 and 2016 with intracranial and/or cervical vascular imaging were included in this study. Images were evaluated for the presence of vascular abnormalities, including intracranial or extracranial stenosis, vessel-wall thickening, dissection, subclavian steal, aneurysms, infarcts, and hemorrhages. Descriptive analyses are reported. RESULTS Seventy-nine patients with Takayasu arteritis met the criteria for inclusion in this study. The most common presenting neurologic symptoms were headache (32.9%) and dizziness (15.2%). Intracranial and extracranial vascular imaging was performed in 84.8% and 89.9% of patients, respectively. Among patients with intracranial vascular imaging, 3 (3.9%) had intracranial aneurysms, 3 (3.9%) had acute large-vessel occlusion, 6 (7.6%) had intracranial vasculitis, and 1 (1.3%) had reversible cerebrovascular constriction syndrome. Among patients with cervical vascular imaging, 42 (53.1%) had some degree of narrowing of the common carotid artery and 18 (22.8%) had narrowing of the ICAs. Seventeen patients (23.6%) had subclavian steal. CONCLUSIONS Intracranial vascular abnormalities in patients with Takayasu arteritis presenting with neurologic symptoms are not rare, with cerebral vasculitis seen in 7.8% of patients, and stroke secondary to large-vessel occlusion, in 3.9% of patients. Cervical vascular manifestations of Takayasu arteritis were present in most patients in our study.


Working in isolation to find a cure for COVID-19.


title: Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals.

text: The ongoing COVID-19 outbreak has spread rapidly on a global scale. While the transmission of SARS-CoV-2 via human respiratory droplets and direct contact is clear, the potential for aerosol transmission is poorly understood1-3. This study investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the COVID-19 outbreak in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients' toilet areas. Levels of airborne SARS-CoV-2 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions showing peaks in submicrometre and/or supermicrometre regions, but these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted via aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.


title: Application of real time RT-PCR for the genetic homogeneity and stability tests of the seed candidates for live attenuated influenza vaccine production.

text: Development and improvement of quality control tests for live attenuated vaccines are a high priority because of safety concerns. Live attenuated influenza vaccine (LAIV) viruses are 6:2 reassortants containing the hemagglutinin (HA) and neuraminidase (NA) gene segments from circulating influenza viruses to induce protective immune responses, and the six internal gene segments from a cold-adapted Master Donor Virus (MDV). LAIV candidate viruses for the 2012-2013 seasons, A/Victoria/361/2011-CDC-LV1 (LV1) and B/Texas/06/2011-CDC-LV2B (LV2B), were created by classical reassortment of A/Victoria/361/2011 and MDV-A A/Leningrad/134/17/57 (H2N2) or B/Texas/06/2011 and MDV-B B/USSR/60/69. In an attempt to provide better identity and stability testing for quality control of LV1 and LV2B, sensitive real-time RT-PCR assays (rRT-PCR) were developed to detect the presence of undesired gene segments (HA and NA from MDV and the six internal genes from the seasonal influenza viruses). The sensitivity of rRT-PCR assays designed for each gene segment ranged from 0.08 to 0.8EID50 (50% of Egg Infectious Dose) per reaction for the detection of undesired genes in LV1 and from 0.1 to 1EID50 per reaction for the detection of undesired genes in LV2B. No undesired genes were detected either before or after five passages of LV1 or LV2B in eggs. The complete genome sequencing of LV1 and LV2B confirmed the results of rRT-PCR, demonstrating the utility of the new rRT-PCR assays to provide the evidence for the homogeneity of the prepared vaccine candidate.


title: Video-Assisted Thoracoscopic Surgery Is a Safe and Effective Alternative to Thoracotomy for Anatomical Segmentectomy in Patients With Clinical Stage I Non-Small Cell Lung Cancer.

text: BACKGROUND There is rising interest among thoracic surgeons in anatomical segmental resection for early-stage non-small cell lung cancer (NSCLC). In the current study we compared video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches for segmentectomy to explore the safety and oncologic efficacy of VATS for stage I NSCLC. METHODS We retrospectively analyzed all patients who underwent segmentectomy for clinical stage I NSCLC from 2000 to 2013. Perioperative and oncologic outcomes were evaluated. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and multivariate Cox regression analysis. RESULTS We identified 193 segmentectomies, including 91 (47%) performed by VATS and 102 (53%) performed by thoracotomy. Patients who underwent VATS, although older (median age 72 versus 68 years; p = 0.016), had similar sex distribution (63% versus 61% women; p = 0.792) and similar clinical stages as the thoracotomy group (stage IA: VATS, 93.4% versus thoracotomy 87.3%; p = 0.152). No significant differences were found in the final pathologic stages (p = 0.439), total number of lymph nodes (LNs) sampled (7 versus 8; p = 0.104), or median number of mediastinal LN stations sampled (2 versus 2; p = 0.234). VATS was associated with decreased length of stay (4 versus 5 days; p = 0.001) and decreased pulmonary complications (13.2% versus 26.5%; p = 0.022). Five-year DFS and OS favored VATS over thoracotomy (58% versus 47%; p = 0.013 and 75% versus 62%; p = 0.017, respectively). By multivariable analysis, the only predictor of poor DFS or OS was larger tumor size. CONCLUSIONS VATS segmentectomy is a safe and oncologically effective technique for the treatment of stage I NSCLC. Patients who underwent VATS had a shorter length of stay, fewer pulmonary complications, equivalent lymphadenectomy results, and similar oncologic outcomes compared with patients undergoing thoracotomy.


title: India's contribution on "Guillain-Barre syndrome": mapping of 40 years research.

text: OBJECTIVE Guillain-Barre Syndrome (GBS) is an acute inflammatory polyradiculoneuropathy causing limb weaknesses. The mortality is around 8%, with about 20% of patients remaining disabled. The purpose of this study is to examine the performance of Indian Medical Scientists in the area of GBS over a period of 40 years. India's contribution to GBS has been examined based on the global publication output and share, growth rate, citation impact, publication share in various field, highly cited papers and their impact, most productive authors and their citation impact and collaboration of research on GBS with the international community. MATERIALS AND METHODS The data for this study has been taken from Scopus, a multidisciplinary database using keywords GBS and Miller Fisher Syndrome. The contribution of India on GBS has been compared with different countries for its publication and citation count during a period of 40 years (1973-2012). RESULTS It is found that there were 10,633 publications available from global medical research covering the various aspects of GBS. India's share is 2.92% of global output and holds 10 th rank in overall publication output on GBS, whereas United States topped the rank with the highest number of publications. Sanjay Gandhi Post-graduate Institute of Medical Research, Lucknow is the most productive institutions while Tally AB from the National Institute of Mental Health and Neurosciences, Bangalore is the most productive author who has contributed the highest number of papers on GBS. CONCLUSION India is far behind in GBS research as compared to other countries like USA, as there might be a low case report of GBS in Indian population. Still the research focusing this disease is quite prominent and needs a careful medical attention through research capacity building in order to look for better treatment of the disease in Indian cases. This study shall be helpful in enhancing the awareness of the GBS by Indian scientists.


title: Biological Scaffolds for Abdominal Wall Repair: Future in Clinical Application?

text: Millions of abdominal wall repair procedures are performed each year for primary and incisional hernias both in the European Union and in the United States with extremely high costs. Synthetic meshes approved for augmenting abdominal wall repair provide adequate mechanical support but have significant drawbacks (seroma formation, adhesion to viscera, stiffness of abdominal wall, and infection). Biologic scaffolds (i.e., derived from naturally occurring materials) represent an alternative to synthetic surgical meshes and are less sensitive to infection. Among biologic scaffolds, extracellular matrix scaffolds promote stem/progenitor cell recruitment in models of tissue remodeling and, in the specific application of abdominal wall repair, have enough mechanical strength to support the repair. However, many concerns remain about the use of these scaffolds in the clinic due to their higher cost of production compared with synthetic meshes, despite having the same recurrence rate. The present review aims to highlight the pros and cons of using biologic scaffolds as surgical devices for abdominal wall repair and present possible improvements to widen their use in clinical practice.


title: The effect of exposure to long working hours on ischaemic heart disease: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

text: BACKGROUND The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may cause ischaemic heart disease (IHD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from IHD that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (three outcomes: prevalence, incidence and mortality). DATA SOURCES We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies which contained an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effect meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS Thirty-seven studies (26 prospective cohort studies and 11 case-control studies) met the inclusion criteria, comprising a total of 768,751 participants (310,954 females) in 13 countries in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (30 studies) or self-reported physician diagnosis (7 studies). The outcome was defined as incident non-fatal IHD event in 19 studies (8 cohort studies, 11 case-control studies), incident fatal IHD event in two studies (both cohort studies), and incident non-fatal or fatal ("mixed") event in 16 studies (all cohort studies). Because we judged cohort studies to have a relatively lower risk of bias, we prioritized evidence from these studies and treated evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. IHD incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). No eligible study was found on the effect of long working hours on IHD prevalence. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) IHD of working 41-48 h/week (relative risk (RR) 0.98, 95% confidence interval (CI) 0.91 to 1.07, 20 studies, 312,209 participants, I2 0%, low quality of evidence) and 49-54 h/week (RR 1.05, 95% CI 0.94 to 1.17, 18 studies, 308,405 participants, I2 0%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderately, clinically meaningful increase in the risk of acquiring IHD, when followed up between one year and 20 years (RR 1.13, 95% CI 1.02 to 1.26, 22 studies, 339,680 participants, I2 5%, moderate quality of evidence). Compared with working 35-40 h/week, we are very uncertain about the effect on dying (mortality) from IHD of working 41-48 h/week (RR 0.99, 95% CI 0.88 to 1.12, 13 studies, 288,278 participants, I2 8%, low quality of evidence) and 49-54 h/week (RR 1.01, 95% CI 0.82 to 1.25, 11 studies, 284,474 participants, I2 13%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of dying from IHD when followed up between eight and 30 years (RR 1.17, 95% CI 1.05 to 1.31, 16 studies, 726,803 participants, I2 0%, moderate quality of evidence). Subgroup analyses found no evidence for differences by WHO region and sex, but RRs were higher among persons with lower SES. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed"), outcome measurement (health records versus self-reports) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for the exposure categories 41-48 and 49-54 h/week for IHD prevalence, incidence and mortality, and for the exposure category ≥55 h/week for IHD prevalence. Evidence on exposure to working ≥55 h/week was judged as "sufficient evidence of harmfulness" for IHD incidence and mortality. Producing estimates for the burden of IHD attributable to exposure to working ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates.


title: Hypoxia enhances glucocorticoid-induced apoptosis and cell cycle arrest via the PI3K/Akt signaling pathway in osteoblastic cells.

text: Although osteonecrosis of the femoral head is a known primary limitation of long-term or high-dose clinical administration of glucocorticoids, the mechanisms underlying this side effect remain unclear. Hypoxia is an important biological state under numerous pathological conditions. In this study, we investigated glucocorticoid-induced osteonecrosis under hypoxic conditions in the MC3T3-E1 osteoblast cell line using a cell cytotoxicity assay, flow cytometry, and western blotting. 6α-Methylprednisolone sodium succinate (MPSL) more effectively induced apoptosis and G0/G1 arrest of MC3T3-E1 osteoblasts under hypoxic conditions than under normoxic conditions. Correspondingly, MPSL more effectively upregulated cellular levels of cleaved caspase 3, p53, and its target p21, and downregulated cyclin D1 levels in hypoxia. Moreover, overexpression of Akt abrogated the MPSL activation of p53, p21, and cleaved caspase 3 and the attenuation of cyclin D1 expression and rescued osteoblasts from MPSL-induced cell cycle arrest and apoptosis, indicating that phosphatidylinositol 3-kinase (PI3K)/Akt signaling might play an essential role in MPSL-induced inhibition of osteoblasts. Furthermore, the suppression of PI3K/Akt signaling and upregualtion of cellular p85α monomer levels by MPSL were more pronounced under hypoxic conditions than under normoxic conditions. Finally, we found that the enhancement of the effects of MPSL under hypoxic conditions was attributed to hypoxia-upregulated glucocorticoid receptor activity. In conclusion, our results demonstrate that MPSL, a synthetic glucocorticoid receptor agonist, promotes the level of p85α and inhibits PI3K/Akt signaling to induce apoptosis and cell cycle arrest in osteoblasts, and that this effect is enhanced under hypoxic conditions.


title: The search for the missing 50-year-old gold.

text: Intramuscular and subcutaneous injections of foreign bodies have been used for a number of years for a variety of reasons, including medical and cosmetic purposes. The author describes a case of chronic wound complications secondary to intramuscular gold injections for the treatment of rheumatoid arthritis. The lesions were completely excised, the defect first treated with negative-pressure wound therapy, and, ultimately, split-thickness skin grafting with excellent functional result.


title: Chylothorax secondary to venous outflow obstruction treated with transcervical retrograde thoracic duct cannulation with embolization and venous reconstruction.

text: A chylothorax may be due to either direct trauma or occlusion of the thoracic duct. Treatments include antegrade or retrograde glue and coil embolization as well as thoracic duct stent graft placement. This report describes a patient with chylothorax secondary to venous outflow occlusion. Left upper extremity venography demonstrated multifocal left brachiocephalic and axillary vein occlusions with retrograde filling of an engorged and disrupted thoracic duct. Retrograde thoracic duct lymphangiography with embolization and left upper extremity venous reconstruction were performed with complete resolution of chylothorax.


No posee por ser editorial.


title: Incidence of salivary side effects after radioiodine treatment using a new specifically-designed questionnaire.

text: Sialadenitis is one of the common complications of radioiodine treatment for thyroid malignancy. The aim of this study was to evaluate the prevalence of radioiodine-induced sialadenitis and other side effects by using a self-administered questionnaire. From 1 January 2011 to 31 December 2012 all consecutive patients with a newly-established diagnosis of thyroid cancer who were treated with adjuvant radioiodine at La Timone University Hospital were sent a self-administered questionnaire on salivary complaints that had been specifically designed for this study. A total of 413 patients sent the questionnaire back, of whom 100 (24%) had experienced pain, 116 (28%) discomfort or swelling, and 147 (36%) dry mouth or xerostomia. This survey has highlighted the number of side effects of radioiodine treatment in a large group of patients and corroborates previous observations. Our new self-administered questionnaire may be useful to others for follow-up and research.


Severe Hypoxemia in Early COVID-19 Pneumonia.


title: Evaluation of serum levels of C-reactive protein after total knee arthroplasty.

text: OBJECTIVE To evaluate the behavior of C-reactive protein (CRP) levels in the first three weeks after total knee arthroplasty (TKA) and define the factors related to its variation. METHODS We evaluated the CRP values in 103 patients undergoing primary TKA. Serum CRP was measured on the day before surgery, and on the third and twenty-first days after the procedure. RESULTS PCR showed sudden increase on the third day after surgery, reaching the mean value of 111.9 mg/L, median 75.9 mg/L. Only one-third of the patients returned to normal levels in the third week. In the immediate postoperative period, CRP was not correlated with body mass index (BMI), age, gender, blood transfusion, or complications. CONCLUSION Serum CRP remains high in the third week after TKA in most patients, and this change is primarily related to surgical trauma.


title: MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4.

text: MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P<0.05). MiR-29b level negatively associated with NIHSS scores (r=-0.349, P<0.01) and brain infarct volume (r=-0.321, P<0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r=0.723, P<0.05). MiR-29b overexpression reduced infarct volume (49.50±6.55 versus 35.48±2.28 mm(3), P<0.05), edema (164±4% versus 108±4%, P<0.05), and blood-brain barrier (BBB) disruption compared with controls (15±9% versus 7±3%, P<0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11±3%, P<0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P<0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.


docid: yyhalbqy

title: Making the Case for "COVID-19 Prophylaxis" With Lifestyle Medicine.


title: Pulmonary drug delivery system: newer patents.

text: Inhalational route for drug delivery and desired effects has been known since centuries. This lung-targeted therapy has benefited asthmatics and those with chronic respiratory problems. The technique has evolved greatly from crude pots and pipes to modern sophisticated drug-dispensing devices. This mode is effective, rapid and safe. Its outcome, however, is majorly determined by drug formulation, device structure and patient's coordinating skill. In spite of great advances in this field, more efforts are required to meet the unmet needs. This noninvasive mode is being increasingly studied for transfer of drugs for systemic action with promising results. The present article is an attempt to capture the recent development and progress in this field and review relevant newer patents.


Sequence analysis of feline coronaviruses and the circulating virulent/avirulent theory.


Psychogeriatrics in a World with COVID-19.


title: Endovascular management of pancreatitis-related pseudoaneurysms: A review of techniques.

text: OBJECTIVES To present the various techniques used in the management of pancreatitis-related pseudoaneurysms of visceral vessels. METHODS The retrospective clinical study was carried out at the Department of Diagnostic and Interventional Radiology at Poznan University of Medical Sciences from 2011 to 2016. The fifteen patients included in the study were diagnosed with pseudoaneurysms of visceral arteries, as a complication of chronic pancreatitis. The diagnosis was made using contrast-enhanced computed tomography, followed by angiography. On admission, all patients were symptomatic, with varying degrees of abdominal pain. One patient was haemodynamically unstable. Treatments with endovascular techniques were analysed, along with their efficacy and outcomes. Coil embolisation was performed in 5 patients. Stent graft was used in 1 patient. Liquid embolic agents were used in 7 cases, of which 5 patients were treated with thrombin injection and 2 with Squid. A combination of techniques was used in 2 patients. RESULTS The most common artery affected by pseudoaneurysm formation was the splenic artery (7/15; 46.7%), and the size of the pseudoaneurysms ranged from 27 mm to 85 mm. Primary technical success was achieved in 14 out of 15 patients (93.3%). One patient required reintervention. Two patients required splenectomy after embolisation due to splenic ischemia. No recanalisation was present at the follow-up computed tomography performed after 1 to 3 weeks, and no mortality was observed within 30 days. CONCLUSION Vascular complications of pancreatitis require accurate diagnosis and immediate treatment. Endovascular intervention is highly effective and is the preferred treatment option. The technique used is determined based on vascular anatomy and the patient's haemodynamic status.


Continuous high-dose ivermectin appears to be safe in patients with acute myelogenous leukemia and could inform clinical repurposing for COVID-19 infection.


title: European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage.

text: The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.


title: Design and implementation of the Americas Hernia Society Quality Collaborative (AHSQC): improving value in hernia care.

text: PURPOSE Wide variation in care and costs exists regarding the management of abdominal wall hernias, with unproven benefit for many therapies. This work establishes a specialty society-based solution to improve the quality and value of care delivered to hernia patients during routine clinical management on a national scale. METHODS The Americas Hernia Society Quality Task Force was charged by the Americas Hernia Society leadership to develop an initiative that utilizes the concepts of continuous quality improvement (CQI). A disease-based registry was created to collect information for CQI incorporating real-time outcome reporting, patient reported outcomes, stakeholder engagement, and collaborative learning methods to form a comprehensive quality improvement effort. RESULTS The Americas Hernia Society Quality Collaborative (AHSQC) was formed with the mission to provide health care professionals real-time information for maximizing value in hernia care. The initial disease areas selected for CQI were incisional and parastomal hernias with ten priorities encompassing the spectrum of care. A prospective registry was created with real-time analytic feedback to surgeons. A data assurance process was implemented to ensure maximal data quality and completeness. Four collaborative meetings per year were established to meet the goals of the AHSQC. As of the fourth quarter 2014, the AHSQC includes nearly 2377 patients at 38 institutions with 82 participating surgeons. CONCLUSIONS The AHSQC has been established as a quality improvement initiative utilizing concepts of CQI. This ongoing effort will continually refine its scope and goals based on stakeholder input to improve care delivered to hernia patients.


title: Graphene-Enabled Electrodes for Electrocardiogram Monitoring.

text: The unique parameters of graphene (GN)-notably its considerable electron mobility, high surface area, and electrical conductivity-are bringing extensive attention into the wearable technologies. This work presents a novel graphene-based electrode for acquisition of electrocardiogram (ECG). The proposed electrode was fabricated by coating GN on top of a metallic layer of a Ag/AgCl electrode using a chemical vapour deposition (CVD) technique. To investigate the performance of the fabricated GN-based electrode, two types of electrodes were fabricated with different sizes to conduct the signal qualities and the skin-electrode contact impedance measurements. Performances of the GN-enabled electrodes were compared to the conventional Ag/AgCl electrodes in terms of ECG signal quality, skin-electrode contact impedance, signal-to-noise ratio (SNR), and response time. Experimental results showed the proposed GN-based electrodes produced better ECG signals, higher SNR (improved by 8%), and lower contact impedance (improved by 78%) values than conventional ECG electrodes.


title: Determination of EC95 of remifentanil for smooth emergence from propofol anesthesia in patients undergoing transsphenoidal surgery.

text: BACKGROUND In patients undergoing pituitary surgery using a transsphenoidal approach, anesthesia emergence should be smooth with minimal coughing. Recent studies demonstrated that a target-controlled infusion of remifentanil effectively suppresses coughing induced by the endotracheal tube. We investigated the EC95 of remifentanil for smooth emergence without coughing from propofol anesthesia in patients undergoing transsphenoidal hypophysectomy. MATERIALS AND METHODS A total of 41 patients undergoing transsphenoidal hypophysectomy, aged 20 to 65 years, with an ASA physical status of I or II, were enrolled. For all participants, anesthesia was induced and maintained with a target-controlled infusion of remifentanil and propofol using predicted effect-site concentration (Ce). A biased coin design up-and-down sequential allocation and isotonic regression method were used to determine the remifentanil EC95 to prevent emergence coughing. In addition, we observed recovery profiles after anesthesia. RESULTS According to the study design, 19 patients received remifentanil 2.6 ng/mL Ce and 22 patients received a lower Ce, ranging from 1.0 to 2.2 ng/mL. The EC95 of remifentanil to prevent coughing was estimated as 2.51 ng/mL (95% confidence interval, 2.28-2.57 ng/mL). Despite the exclusion of 1 case because of delayed emergence, 17 of 18 patients receiving 2.6 ng/mL of remifentanil had bradypnea (<10 breaths/min) until 3 minutes after extubation. However, end-tidal carbon dioxide was maintained below 55 mm Hg during anesthetic emergence and respiratory rate recovered within 20 minutes of admission to the postanesthetic care unit. CONCLUSIONS The EC95 of remifentanil for smooth emergence from anesthesia was 2.51 ng/mL after transsphenoidal hypophysectomy.


title: Biochip system for rapid and accurate identification of mycobacterial species from isolates and sputum.

text: The accurate detection of mycobacterial species from isolates and clinical samples is important for pathogenic diagnosis and treatment and for disease control. There is an urgent need for the development of a rapid, simple, and accurate detection method. We established a biochip assay system, including a biochip, sample preparation apparatus, hybridization instrument, chip washing machine, and laser confocal scanner equipped with interpretation software for automatic diagnosis. The biochip simultaneously identified 17 common mycobacterial species by targeting the differences in the 16S rRNA. The system was assessed with 64 reference strains and 296 Mycobacterium tuberculosis and 243 nontuberculous mycobacterial isolates, as well as 138 other bacteria and 195 sputum samples, and then compared to DNA sequencing. The entire biochip assay took 6 h. The concordance rate between the biochip assay and the DNA sequencing results was 100%. In conclusion, the biochip system provides a simple, rapid, reliable, and highly accurate clinical assay for determination of mycobacterial species in a 6-h procedure, from either culture isolates or sputum samples, allowing earlier pathogen-adapted antimicrobial therapy in patients.


title: Improving Quality of Patient Data for Treatment of Multidrug- or Rifampin-Resistant Tuberculosis.

text: International policy for treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR TB) relies largely on individual patient data (IPD) from observational studies of patients treated under routine conditions. We prepared guidance on which data to collect and what measures could improve consistency and utility for future evidence-based recommendations. We highlight critical stages in data collection at which improvements to uniformity, accuracy, and completeness could add value to IPD quality. Through a repetitive development process, we suggest essential patient- and treatment-related characteristics that should be collected by prospective contributors of observational IPD in MDR/RR TB.


title: Cardiac Care of Patients with Cardiac Amyloidosis.

text: Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the importance of multidisciplinary care.


title: The usability of ventilators: a comparative evaluation of use safety and user experience.

text: BACKGROUND The design complexity of critical care ventilators (CCVs) can lead to use errors and patient harm. In this study, we present the results of a comparison of four CCVs from market leaders, using a rigorous methodology for the evaluation of use safety and user experience of medical devices. METHODS We carried out a comparative usability study of four CCVs: Hamilton G5, Puritan Bennett 980, Maquet SERVO-U, and Dräger Evita V500. Forty-eight critical care respiratory therapists participated in this fully counterbalanced, repeated measures study. Participants completed seven clinical scenarios composed of 16 tasks on each ventilator. Use safety was measured by percentage of tasks with use errors or close calls (UE/CCs). User experience was measured by system usability and workload metrics, using the Post-Study System Usability Questionnaire (PSSUQ) and the National Aeronautics and Space Administration Task Load Index (NASA-TLX). RESULTS Nine of 18 post hoc contrasts between pairs of ventilators were significant after Bonferroni correction, with effect sizes between 0.4 and 1.09 (Cohen's d). There were significantly fewer UE/CCs with SERVO-U when compared to G5 (p = 0.044) and V500 (p = 0.020). Participants reported higher system usability for G5 when compared to PB980 (p = 0.035) and higher system usability for SERVO-U when compared to G5 (p < 0.001), PB980 (p < 0.001), and V500 (p < 0.001). Participants reported lower workload for G5 when compared to PB980 (p < 0.001) and lower workload for SERVO-U when compared to PB980 (p < 0.001) and V500 (p < 0.001). G5 scored better on two of nine possible comparisons; SERVO-U scored better on seven of nine possible comparisons. Aspects influencing participants' performance and perception include the low sensitivity of G5's touchscreen and the positive effect from the quality of SERVO-U's user interface design. CONCLUSIONS This study provides empirical evidence of how four ventilators from market leaders compare and highlights the importance of medical technology design. Within the boundaries of this study, we can infer that SERVO-U demonstrated the highest levels of use safety and user experience, followed by G5. Based on qualitative data, differences in outcomes could be explained by interaction design, quality of hardware components used in manufacturing, and influence of consumer product technology on users' expectations.


title: Clinical Relevance of Targeting the Gastrin-Releasing Peptide Receptor, Somatostatin Receptor 2, or Chemokine C-X-C Motif Receptor 4 in Breast Cancer for Imaging and Therapy.

text: UNLABELLED Imaging and therapy using radioligands targeting receptors overexpressed on tumor cells is successfully applied in neuroendocrine tumor patients. Because expression of the gastrin-releasing peptide receptor (GRPR), somatostatin receptor 2 (SSTR2), and chemokine C-X-C motif receptor 4 (CXCR4) has been demonstrated in breast cancer, targeting these receptors using radioligands might offer new imaging and therapeutic opportunities for breast cancer patients. The aim of this study was to correlate messenger RNA (mRNA) expression of GRPR, SSTR2, and CXCR4 with clinicopathologic and biologic factors, and with prognosis and prediction to therapy response, in order to identify specific breast cancer patient groups suited for the application of radioligands targeting these receptors. METHODS First, we studied GRPR and SSTR2 expression in 13 clinical breast cancer specimens by in vitro autoradiography and correlated this with corresponding mRNA levels to investigate whether mRNA levels reliably represent cell surface expression. Next, GRPR, SSTR2, and CXCR4 mRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction in 915 primary breast cancer tissues and correlated with known clinicopathologic and biologic factors, disease-free survival, distant metastasis-free survival, and overall survival (DFS, MFS, and OS, respectively). In 224 adjuvant hormonal treatment-naïve estrogen receptor (ER, ESR1)-positive patients who received tamoxifen as first-line therapy for recurrent or metastatic disease, the expression levels of the receptors were correlated with progression-free survival. RESULTS Our results showed a significant positive correlation between GRPR and SSTR2 expression analyzed by in vitro autoradiography and by quantitative reverse transcriptase polymerase chain reaction (Spearman's rank correlation coefficient [Rs]=0.94, P<0.001, and Rs=0.73, P=0.0042, respectively). Furthermore, high GRPR and SSTR2 mRNA levels were observed more frequently in ESR1-positive specimens, whereas high CXCR4 expression was associated with ESR1-negative specimens. Also, high mRNA expression of CXCR4 was associated with a prolonged DFS, MFS, and OS (multivariate hazard ratio MFS=0.76 [95% confidence interval, 0.64-0.90], P=0.001), whereas high mRNA levels of GRPR were associated with a prolonged progression-free survival after the start of first-line tamoxifen treatment (multivariate hazard ratio=0.68 [95% confidence interval, 0.48-0.97], P=0.031). CONCLUSION Our data indicate that imaging and therapy using GRPR or SSTR2 radioligands might especially be beneficial for ESR1-positive breast cancer and CXCR4 radioligands for ESR1-negative breast cancer.


title: Diagnostic Imaging in Disasters: A Bibliometric Analysis.

text: OBJECTIVE To investigate the role of diagnostic imaging in the clinical diagnosis, treatment, and follow-up management of patients in response to disasters. METHODS A MEDLINE (OVID) search of original research articles identified 177 articles on this topic published since 2000. A bibliometric analysis was conducted on the top 100 articles ranked by average yearly citation. RESULTS The most frequently studied disaster categories were disease outbreak (55 articles), armed conflict (23 articles), terrorist incident (10 articles), and earthquake (7 articles). The most studied disasters were the H1N1 influenza outbreak in 2009 (28 articles), Severe Acute Respiratory Syndrome outbreak in 2003 (24 articles), War in Afghanistan, 2001-2014 (8 articles), Iraq War, 2003-2011 (6 articles), and the Sichuan earthquake (China) in 2008 (6 articles). Among the first authors, 59 were primarily affiliated with Radiology. The United States of America produced the most articles (25 articles), followed by the People's Republic of China (24 articles). Eighty-one studies were retrospective, with 19 studies being prospective. Computed tomography was the most investigated modality (52.8%), followed by conventional radiography (33.3%) and ultrasound (9.7%). CONCLUSIONS Our study identifies intellectual milestones in the utility of diagnostic imaging in response to various disasters, and could help guide future research in developing disaster management plans. (Disaster Med Public Health Preparedness. 2018;12:265-277).


title: Similar cytokine profiles in response to infection with respiratory syncytial virus type a and type B in the upper respiratory tract in infants.

text: Human respiratory syncytial virus (RSV) is the leading viral cause of severe respiratory illness in infants and young children worldwide. RSV isolates can be divided into 2 subgroups, type A and type B. Here, we compare for the first time the nasal profiles of 27 immune mediators in response to both viral subtypes in 14 children infected with RSV/A, 8 children infected with RSV/B, 11 children coinfected with RSV/A plus other respiratory viruses, and finally, 27 control children, all <2 years old. Our results evidence that children's infection with both RSV subtypes induces very similar profiles of immune mediators in the upper respiratory tract, characterized by the elevation of Th1 and Th2 cytokines, chemokines and growth factors. Interestingly, no major differences in the profiles of the immune mediators were found between the children infected exclusively with RSV/A and those infected with RSV/A plus other respiratory viruses.


Ethics Rounds: Benefits and Risks of Visitor Restrictions for Hospitalized Children During the COVID Pandemic.


Tocilizumab: From the Rheumatology Practice to the Fight Against COVID-19, a virus infection with multiple faces.


title: [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

text: Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95%CI 1.51-16.48, P=0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.


title: Frequency, risk factors and survival associated with an intrasubsegmental recurrence after radiofrequency ablation for hepatocellular carcinoma.

text: BACKGROUND In the treatment of hepatocellular carcinoma (HCC), hepatic resection has the advantage over radiofrequency ablation (RFA) in terms of systematic removal of a hepatic segment. METHODS We enrolled 303 consecutive patients of a single naïve HCC that had been treated by RFA at The University of Tokyo Hospital from 1999 to 2004. Recurrence was categorized as either intra- or extra-subsegmental as according to the Couinaud's segment of the original nodule. To assess the relationship between the subsegments of the original and recurrent nodules, we calculated the kappa coefficient. We assessed the risk factors for intra- and extra-subsegmental recurrence independently using univariate and multivariate Cox proportional hazard regression. We also assessed the impact of the mode of recurrence on the survival outcome. RESULTS During the follow-up period, 201 patients in our cohort showed tumor recurrence distributed in a total of 340 subsegments. Recurrence was categorized as exclusively intra-subsegmental, exclusively extra-subsegmental, and simultaneously intra- and extra-subsegmental in 40 (20%), 110 (55%), and 51 (25%) patients, respectively. The kappa coefficient was measured at 0.135 (95% CI, 0.079-0.190; P<0.001). Multivariate analysis revealed that of the tumor size, AFP value and platelet count were all risk factors for both intra- and extra-subsegmental recurrence. Of the patients in whom recurrent HCC was found to be exclusively intra-subsegmental, extra-subsegmental, and simultaneously intra- and extra-subsegmental, 37 (92.5%), 99 (90.8%) and 42 (82.3%), respectively, were treated using RFA. The survival outcomes after recurrence were similar between patients with an exclusively intra- or extra-subsegmental recurrence. CONCLUSIONS The effectiveness of systematic subsegmentectomy may be limited in the patients with both HCC and chronic liver disease who frequently undergo multi-focal tumor recurrence.


title: Comparison of two minimal invasive techniques of splenectomy: Standard laparoscopy versus transumbilical multiport single-site laparoscopy with conventional instruments.

text: BACKGROUND Laparoendoscopic single-site (LESS) splenectomy which is performed on small number of patients, has been introduced with better cosmetic outcome, less postoperative pain, greater patient satisfaction and faster recovery compared to standard laparoscopy. MATERIALS AND METHODS Thirty six patients were included in the study comparing standard laparoscopic splenectomy (LS, 17 patients) transumbilical multiport splenectomy performed with conventional laparoscopic instruments (TUMP-LS, 19 patients). Two groups of patients were compared retrospectively by means of operation time, intra- and postoperative blood loss, perioperative complications, packed red cell and platelet requirements, lenght of hospitalization, pain scores and patient satisfaction. RESULTS There was no mortality in any of the groups, and no significant differences determined in operative time (P = 0,069), intraoperative blood loss (P = 0,641), patient satisfaction (P = 0,506), pain scores (P = 0,173) and the average length of hospital stay (P = 0,257). Umbilical incisions healed uneventfully and no hernia formation or wound infection was observed during follow-up period (2-34 months). There were no conversions to open surgery. CONCLUSIONS Transumbilical multiport splenectomy performed with the conventional laparoscopic instruments is feasible and could be a logical alternative to classical laparoscopic splenectomy by combining the advantages of single access techniques and standard laparoscopy.


COVID-19: fail to prepare, prepare to fail.


title: Anxiety Symptoms Questionnaire (ASQ): development and validation.

text: Background The Anxiety Symptoms Questionnaire (ASQ) is a brief self-report questionnaire which measures frequency and intensity of symptoms and was developed to improve assessment of anxiety symptoms in a clinical setting. We examined the reliability and validity of the ASQ in patients with anxiety disorders and/or depression, non-clinical control subjects and college students. Methods 240 outpatients with generalised anxiety disorder, social anxiety disorder, panic disorder or major depressive disorder were administered the ASQ and additional questionnaires measuring depression and anxiety, as were 111 non-clinical control subjects and 487 college students. Factor analysis, Pearson's correlation coefficients and logistic regression were used to assess reliability and validity. Test-retest reliability of the ASQ was measured using a subset who were re-administered the ASQ after 4 weeks. Results Factor analysis revealed measurement of a single dimension by the ASQ. Internal consistency and test-retest reliability were strong. The ASQ total score also significantly distinguished patients with an anxiety disorder from the clinical controls above and beyond the clinician-rated Hamilton Anxiety Scale. Conclusions The ASQ is a valid, reliable and effective self-rated measure of anxiety and may be a useful tool for screening and assessing anxiety symptoms in psychiatric as well as college settings.


title: Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation.

text: Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr(3)]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar cycloaddition ("click" reaction) between peptidic azides and dendrimer-derived alkynes and a subsequent metal-free introduction of DOTA via the thio acid/sulfonyl azide amidation ("sulfo-click" reaction). In a competitive binding assay using rat pancreatic AR42J tumor cells, the monomeric [Tyr(3)]octreotide conjugate displayed the highest binding affinity (IC(50) = 1.32 nM) followed by dimeric [Tyr(3)]octreotide (2.45 nM), [DOTA(0),Tyr(3)]octreotide (2.45 nM), and tetrameric [Tyr(3)]octreotide (14.0 nM). Biodistribution studies with BALB/c nude mice with subcutaneous AR42J tumors showed that the (111)In-labeled monomeric [Tyr(3)]octreotide conjugate had the highest tumor uptake (42.3 +/- 2.8 %ID/g) at 2 h p.i., which was better than [(111)In-DOTA(0),Tyr(3)]octreotide (19.5 +/- 4.8 %ID/g). The (111)In-labeled dimeric [Tyr(3)]octreotide conjugate showed a long tumor retention (25.3 +/- 5.9 %ID/g at 2 h p.i. and 12.1 +/- 1.3 %ID/g at 24 h p.i.). These promising results can be exploited for therapeutic applications.