title: Practical considerations in prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19.

text: DISCLAIMER In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE There are increasing reports in the literature of high rates of coagulopathy and venous thromboembolism (VTE) among hospitalized patients with coronavirus disease 2019 (COVID-19). Understanding of these abnormalities is continually evolving, but these conditions may pose a risk to COVID-19 patients beyond the risk typically seen in critically ill patients. SUMMARY There are currently no widely accepted evidence-based guidelines regarding specifics related to treatment and prevention of COVID-19-related coagulopathies. Areas of management requiring clinical equipoise include agent selection and dosing, continuation vs interruption of home oral anticoagulant therapy during hospital admission, and postdischarge VTE prophylaxis. Clinicians may wish to consider use of a stratified, 3-tiered approach of low-intensity anticoagulation, intermediate-intensity anticoagulation, and therapeutic-dose anticoagulation. Patients can be categorized by tier depending on their risk factors for VTE, acuity of illness, and laboratory values such as D-dimer level. CONCLUSION Practical guidance on anticoagulation considerations and dosing suggestions are provided to assist clinicians faced with challenging anticoagulation-related situations in caring for hospitalized COVID patients until formal evidence-based guidelines become available.


MANAGEMENT OF OLDER PEOPLE DURING THE COVID-19 OUTBREAK: RECOMMENDATIONS FROM AN ITALIAN EXPERIENCE.


title: Preserved right ventricular function but increased right atrial contractile demand in altitude-induced pulmonary hypertension.

text: PURPOSE Ascent to high altitude increases right ventricular (RV) afterload and decreases myocardial energy supply. This study evaluates physiologic variables and comprehensive echocardiographic indices of RV and right atrial (RA) function following rapid ascent to high altitude. METHODS Fifty healthy volunteers actively ascended from 1130 to 4559 m in < 22 h. All participants underwent 2D echocardiography during baseline examination at low altitude (424 m) and at three study time-points (7, 20 and 44 h) after arrival at high altitude. In addition to systolic pulmonary artery pressure (sPAP), comprehensive 2D planimetric-, tissue Doppler- and speckle-tracking-derived strain indices of RA and RV function were obtained. RESULTS sPAP increased from baseline (24 ± 4 mmHg) to the first altitude examination (39 ± 8 mmHg, p < 0.001) and remained elevated during the following 44 h. Global RV function did not change. RA reservoir strain showed a trend towards increase from baseline (50.2 ± 12.1%) to the first altitude examination (53.8 ± 11.0%, p = 0.07) secondary to a significant increase of RA contraction strain (19.2 ± 6.4 vs. 25.4 ± 9.6%, p < 0.001). Volumetric RA data largely paralleled RA strain results and RA active emptying volume was increased throughout the 44 h stay at high altitude. CONCLUSION Active and rapid ascent of healthy individuals to 4559 m is associated with an increased contractile performance of the RA that compensates for the increased workload of the RV.


title: Adverse intraoperative events during surgical repair of ruptured cerebral aneurysms: a systematic review.

text: Compared with endovascular techniques, clipping of ruptured cerebral aneurysms has been shown to associate with increased morbidity in several studies. Despite this, clipping remains the preferred option for many aneurysms. The objective of this study is to describe the reported adverse events of open repair of ruptured cerebral aneurysms and their impact on patient outcome. The PubMed, Embase and Cochrane databases were searched between June 1999 and June 2019 to identify original studies of at least 100 patients undergoing surgical repair of ruptured cerebral aneurysms and in which adverse event rates were reported. Thirty-six studies reporting adverse events in a total of 12,410 operations for repair of ruptured cerebral aneurysms were included. Surgical adverse events were common with 36 event types reported including intraoperative rupture (median rate of 16.6%), arterial injury (median rate of 3.8%) and brain swelling (median rate 5.6%). Only 6 surgical events were statistically shown to associate with poor outcomes by any author and for intraoperative rupture (the most frequently analysed), there was an even split between authors finding a statistical association with poor outcome and those finding no association. Even with modern surgical techniques, the technical demands of surgical aneurysm repair continue to lead to a high rate of intraoperative adverse events. Despite this, it is not known which of these intraoperative events are the most important contributors to the poor outcomes often seen in these patients. More research directed towards identifying the events that most drive operative morbidity has the potential to improve outcomes for these patients.


docid: zqwkyqbj

title: Paper-based microfluidic point-of-care diagnostic devices.

text: Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.


Esophageal detection method may be a good choice to confirm endotracheal tube placement for patients with COVID-19 infection.


title: Single-incision laparoscopic surgery as a teaching procedure: a single-center experience of more than 2100 procedures.

text: PURPOSE To confirm the safety and feasibility of single-incision laparoscopic surgery (SILS) and to compare the patient outcomes of single-incision laparoscopic surgery for laparoscopic appendectomy (SILS-LA) performed by resident doctors vs. staff surgeons. METHODS We performed a retrospective analysis of patients who underwent SILS between May, 2009 and May, 2015 at Osaka Police Hospital. RESULTS We analyzed 2172 patients. The operations performed consisted of cholecystectomy (n = 598), appendectomy (n = 202), inguinal hernia repair (n = 301), colorectal surgery (n = 673), and gastrectomy (n = 398). SILS was performed safely for a wide range of procedures with acceptable conversion and perioperative complication rates. The resident doctors in our department operated safely on 77 % (156/202) of patients undergoing SILS-LA. The staff surgeons operated on more elderly patients and patients with complicated appendicitis than did the resident doctors. The operative outcomes of the resident-performed SILS-LAs were better than those of the staff surgeons, although there was a patient selection bias. CONCLUSIONS SILS seems safe and feasible for a wide range of procedures. Based on our findings, we believe that SILS-LA could be a useful teaching procedure for resident doctors to perform on selected patients, under the guidance of an experienced staff surgeon.


title: Associations between group sizes, serum protein levels, calf morbidity and growth in dairy-beef calves in a Finnish calf rearing unit.

text: Efficient dairy-beef production relies on good quality of purchased calves, defined by breed, health, and growth characteristics. Several management factors, such as commingling of calves and large group size, predispose calves to diseases. Acute phase proteins are sensitive detectors of calf diseases. We studied the associations between group size, serum acute phase proteins, immunoglobulin G (IgG), calf morbidity and growth of dairy-beef calves in a random field trial in a calf-rearing unit in Finland. The randomized trial was carried out at a calf rearing unit, where approximately 80 dairy or crossbred calves were allocated either into a single group of 40 calves or into four groups of 10 on arrival at the calf-rearing unit (at age 24.1 SD ± 9.2 days). The study was carried out on 6 arrival batches: 476 calves. Calves were clinically examined and blood sampled on arrival (day 0), and haptoglobin (Hp), serum amyloid A (SAA), albumin and IgG were determined. Calves were weighed on arrival (day 0, average age 24.1 days), at the end of the milk feed period (day 49), at approximately 200 days of age and at slaughter (carcass weight) at 15-18 months of age. During the rearing calves were observed by the farm workers and treated, if necessary, according to predetermined instructions of the veterinary surgeon. All NSAID and antimicrobial treatments were recorded and used as morbidity indicators in statistical analysis. There were no differences in the numbers of antimicrobial treatments or growth among the groups. The majority (84.1%) of antimicrobial treatments were used against respiratory tract infections. Higher concentrations of albumin and IgG on arrival extended the time before the first and the second antimicrobial treatments. Complex relationships between group size, morbidity, concentrations of serum acute phase proteins and IgG at arrival, and growth of calves were explored. Group size of 10 calves did not protect calves from respiratory tract infections, when the small groups were sharing the air space with a large group. An increased SAA concentration on arrival was associated with poorer average daily gain at two rearing periods and with lower carcass weight at slaughter. Serum proteins could be valuable health indicators for purchased calves because they have numerous and variable associations with health and growth. The mechanisms that connect increased SAA concentration and poorer average daily gain over the long term remain unclear.


title: Masses and malformations of the third ventricle: normal anatomic relationships and differential diagnoses.

text: The third ventricle lies in the center of the brain. It is surrounded by critical nuclear structures (the hypothalamus and thalami) and important glandular structures (the pituitary and pineal glands). Although a wide array of pathologic processes may involve the third ventricle, most are extrinsic masses. By understanding the anatomic boundaries of the third ventricle and its relationship to adjacent structures, it is possible to create short lists of differential diagnoses. Third ventricle masses can be classified as arising in or immediately adjacent to one of five locations: anterior, posterior, inferior, foramen of Monro, and intraventricular. Anterior masses involve the optic and infundibular recesses, posterior masses affect or arise in the posterior commissure and pineal gland, and inferior masses involve or affect the ventricle floor. Masses may also arise at or adjacent to the foramen of Monro or entirely within the third ventricle. Of the intraventricular masses, chordoid glioma-a rare low-grade primary neoplasm-is unique to the third ventricle. Congenital malformations of the third ventricle are uncommon and are most often noted during childhood. Most commonly, these anomalies represent malformations of the neurohypophysis, which may manifest as hormonal abnormalities, or stenosis of the aqueduct of Sylvius, which manifests as dilatation of the third and lateral ventricles (hydrocephalus).


title: Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

text: BACKGROUND AND PURPOSE Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.


title: Infectious disease surveillance and modelling across geographic frontiers and scientific specialties.

text: Infectious disease surveillance for mass gatherings (MGs) can be directed locally and globally; however, epidemic intelligence from these two levels is not well integrated. Modelling activities related to MGs have historically focused on crowd behaviours around MG focal points and their relation to the safety of attendees. The integration of developments in internet-based global infectious disease surveillance, transportation modelling of populations travelling to and from MGs, mobile phone technology for surveillance during MGs, metapopulation epidemic modelling, and crowd behaviour modelling is important for progress in MG health. Integration of surveillance across geographic frontiers and modelling across scientific specialties could produce the first real-time risk monitoring and assessment platform that could strengthen awareness of global infectious disease threats before, during, and immediately after MGs. An integrated platform of this kind could help identify infectious disease threats of international concern at the earliest stages possible; provide insights into which diseases are most likely to spread into the MG; help with anticipatory surveillance at the MG; enable mathematical modelling to predict the spread of infectious diseases to and from MGs; simulate the effect of public health interventions aimed at different local and global levels; serve as a foundation for scientific research and innovation in MG health; and strengthen engagement between the scientific community and stakeholders at local, national, and global levels.


Building Local Health Department COVID-19 Emergency and Risk Communications Capacity.


title: Gastrojejunal stoma diameter predicts weight regain after Roux-en-Y gastric bypass.

text: BACKGROUND & AIMS Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with reductions in health status and quality of life. We evaluated whether gastrojejunal stoma diameter is a risk factor for weight regain after RYGB. METHODS We examined data collected over 4 years from consecutive patients referred to a tertiary care bariatric center for upper endoscopy after RYGB. We used linear regression analysis to determine the association between the gastrojejunal stoma diameter and weight regain. We applied a logistic regression model using clinical and endoscopic parameters to develop a prediction rule for weight gain after RYGB. RESULTS Among 165 patients included in our study, 59% had significant weight regain (≥ 20% of maximum weight lost after the RYGB) and 41% did not. The mean percentage of maximal weight lost after RYGB that was regained in the entire cohort was 30% ± 22%. Gastrojejunal stoma diameter was associated significantly with weight regain after RYGB surgery in univariate analysis (β = .31, P < .0001). This association remained significant after adjusting for several known or purported risk factors for weight regain (β = .19, P = .003). We developed a simple prediction rule for weight regain after RYGB using a 7-point scoring system that includes the gastrojejunal stoma diameter, race, and percentage of maximal body weight lost after RYGB; a cut-off score of 4 or more points had an area under receiver operating characteristic curve of 0.76 and a positive predictive value of 75%. CONCLUSIONS Increased gastrojejunal stoma diameter is a risk factor for weight regain after RYGB and can be incorporated in a novel prediction rule.


Postanesthesia persistent amnesia in a patient with a prior history of dissociative fugue state: the case for the two-hit hypothesis.


title: Oxygen-ozone therapy as adjuvant in the current emergency in SARS-COV-2 infection: a clinical study.

text: The aim of the multicentre study promoted by Nuova FIO is to evaluate the beneficial effects of the systemic Oxygen-Ozone (O2O3) therapy in patients suffering from SARS COV-2 disease in the early phases of the disease, before worsening, up to the need of tracheal intubation. The study is based on the rationale on that the systemic oxygen-ozone treatment could be effective, positively influencing the disease evolution and/or being able to mitigate the onset of the cytokine storm syndrome at least partially.


title: A review of palivizumab and emerging therapies for respiratory syncytial virus.

text: INTRODUCTION Respiratory syncytial virus (RSV) is an important pathogen in children and adults; however, current treatment options are primarily supportive. Palivizumab, the only approved specific monoclonal antibody for RSV is used prophylactically to reduce morbidity in a select population of high-risk children. AREAS COVERED The development and current use of palivizumab; the potential role of palivizumab as preventive therapy in patients with cystic fibrosis, asthma and compromised immune systems; and explores the limited research in which palivizumab has been used for treatment of RSV. The modified recommendations for the use of palivizumab espoused by the American Academy of Pediatrics and research on the cost-effectiveness of this product are presented. In addition, the authors discuss the development of enhanced monoclonal antibodies including motavizumab, which was recently denied FDA approval for preventative therapy. The authors explore the historical and current efforts to develop a vaccine targeting RSV. The current status of antiviral drug development is also reviewed. The literature search included RSV-Ig, palivizumab, and emerging drugs and vaccines for the treatment of RSV as keywords and titles from 1997 to 2011. EXPERT OPINION Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.


docid: djlrtuvy

title: SARS-CoV-2 serology: Test, test, test, but interpret with caution!

text: SARS-CoV-2 serological tests are a subject of intense interest and have the potential to significantly enhance the diagnostic capability of healthcare services in the current pandemic. However, as with all novel assays, significant validation is required to understand the clinical relevance of results.We present the first study to assess clinician interpretation of SARS-CoV-2 serology scenarios. We identify common key assumptions regarding patient infectivity and protection that are not currently supported by the SARS-CoV-2 evidence base. In this rapidly developing field, we therefore strongly recommend serological assay results are accompanied by clear interpretive support from laboratory and infectious diseases specialists.


title: Antibacterial Potential and Apoptosis Induction by Pigments from the Endophyte Burkholderia sp. WYAT7.

text: Pigment from the endophyte Burkholderia sp. WYAT7 isolated from the medicinal plant Artemisia nilagirica (Clarke) Pamp. was extracted. The antibacterial efficacy of the crude pigment Y was assessed as a source of antibiotic against both Gram-positive and Gram-negative bacterial pathogens. The pigment Y exhibited a significant level of antibacterial activity against the tested pathogens Salmonella typhi (MTCC 733), Staphylococcus aureus (MTCC 1430), Pseudomonas aeruginosa (MTCC 2453), Klebsiella pneumoniae (MTCC 432), Escherichia coli (MTCC 1610), Salmonella paratyphi (3220), Bacillus subtilis (441) and Acinetobacter baumannii (12,889). The minimum inhibitory concentration of crude pigment extract Y for most of the bacterial pathogens tested was below or equal to 0.25 µg/mL and the minimum bactericidal concentration was below or equal to 0.5 µg/mL. In the cytotoxicity evaluation, crude pigment Y exhibited less toxicity toward normal cells lines (L929). Crude pigment extract Y also showed powerful anticancer activity toward melanoma cancer cells (A375). The IC50 value obtained was 68.08 µg/mL. Acridine orange (AO) and ethidium bromide (EB) double staining of cells treated with the pigment helped in the morphological assessment of nuclear condensation, apoptotic bodies and live cells. The DNA fragmentation analysis and caspase-9 quantification in the pigment-treated A375 cells determined the apoptosis activity mediated by the crude pigment extract Y. The compounds in the crude pigment extract Y was identified by HR-LCMS analysis. Further studies on the active compounds can lead to a rise in new drugs for cancer treatment and also against rising antibacterial resistant pathogens.


title: A rodent model of metabolic surgery for study of type 2 diabetes and positron emission tomography scanning of beta cell mass.

text: BACKGROUND Type 2 diabetes mellitus is a worldwide healthcare problem with major socioeconomic implications. Metabolic surgical procedures have been shown to improve diabetes, but the mechanism of action is poorly understood. The Goto-Kakizaki (GK) rodent is a type 2 diabetic animal model that is ideally situated for studying the effect of surgery on diabetes; however, the operative mortality is high. The aim of this study was to describe the operative technique, improvements in perioperative management, and the technique of micro-positron emission tomography (PET) scanning of the beta-cell mass in GK rodents. METHODS A total of 53 GK rats were divided into 1 of 3 operative groups: sham, sleeve gastrectomy, and duodenojejunal bypass. A subset of animals underwent micro-PET scanning with [11C]-dihydrotetrabenazine to determine the vesicular monoamine transporter 2 binding index, an indicator of beta-cell mass. RESULTS The 30-day mortality in the sham and sleeve gastrectomy rodents was 0; however, 2 sleeve gastrectomy rodents developed enterocutaneous fistula and 1 developed an abscess. In the duodenojejunal bypass group, the initial mortality rate was close to 90%; however, refinements in the surgical technique and perioperative management (fluids, antibiotics, pain control) lowered the mortality rate to 60%. The surgical technique is discussed in detail. [11C]-Dihydrotetrabenazine uptake in the pancreas was demonstrated on micro-PET scanning in the sham and duodenojejunal bypass rodents. CONCLUSION Intensive medical management in the perioperative period and attention to the operative technique lowered the mortality. [11C]-Dihydrotetrabenazine micro-PET scanning is a feasible method for assessing the beta-cell mass in GK rodents and could prove to be an important modality for evaluating beta-cell performance in type 2 diabetes.


docid: mvzhksze

title: Comparison of the reliability and efficacy of LigaSure hemorrhoidectomy and a conventional Milligan-Morgan hemorrhoidectomy in the surgical treatment of grade 3 and 4 hemorrhoids.

text: Objective The aim of this study was to compare the clinical results of LigaSure-assisted hemorrhoidectomy and Milligan-Morgan hemorrhoidectomy as a conventional method in our clinic. Materials and Methods Patients who underwent LigaSure-assisted hemorrhoidectomy or conventional hemorrhoidectomy for grade 3 and 4 hemorrhoids in our clinic between 2009 and 2014 were included in this study. The patient data were reviewed by screening records. Gender, age, preoperative hemoglobin and hematocrit levels, operation time, presence of thrombosis, number of packages, hospitalization time, early and late postoperative complications, prolonged pain presence, and follow-up period were recorded. Results In this period, surgical interventions were performed on 365 patients diagnosed with hemorrhoids. Among these, 159 underwent LigaSure-assisted operations, while 206 were operated on by conventional methods. One hundred forty-four (39.5%) cases were female, while 221 (60.5%) cases were male. The median age of the patients was 40 (19-82) years in the LigaSure group and 41 (16-78) years in the conventional method group. The operation time was 15 (4-60) min in the LigaSure group and 20 (6-40) min in the conventional method group. Postoperative analgesics were given to the 182 (88.3%) cases in the conventional group and 107 (67.3%) cases in the LigaSure group. The time required for returning to normal daily activity was 6 (1-15) days in the LigaSure group and 7 (1-30) days in the conventional method group. Conclusion In this study, LigaSure was determined to be superior to a conventional method in terms of operation time, hospitalization period, postoperative analgesic requirements, time required for returning to normal daily activity, and postoperative bleeding.


title: Use of a novel epidermal harvesting system in resource-poor countries.

text: The 2010 earthquake in Port-au-Prince, Haiti, highlighted the need for wound care in resource-poor countries. Subsequently, the University of Miami in Florida established one of the first interprofessional wound care centers located at Bernard Mevs Hospital in the central portion of Port-au-Prince, caring for patients with acute and chronic wounds. In 2012, the authors used a novel epidermal harvesting system (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) to harvest epithelium to be grafted on 7 patients at the Mevs Hospital with longstanding wounds. Epidermal microblisters were obtained from each patient's thigh using the CelluTome Epidermal Harvesting System. After 35 minutes, microblisters were raised using the device harvester, and an adhesive dressing was inserted into the harvester for transfer to the wound site. In patients with lower-extremity wounds, a 2-layer compression dressing was placed over epidermal grafts. Six of the 7 wounds improved or achieved complete closure in 4 weeks. One of the patients with a 2-year-old thigh wound failed to demonstrate improvement; this may have been secondary to an inability to adequately secure the graft. All donor sites healed without any visible scarring. The authors were able to conclude that epidermal grafting may represent a viable reconstructive option for patients in resource-poor countries.


Life after ICU: five minutes with . . . Ron Daniels.


title: Total laparoscopic pancreaticoduodenectomy.

text: INTRODUCTION Total laparoscopic pancreaticoduodenectomy (TLPD) remains one of the most advanced laparoscopic procedures. Owing to the evolution in laparoscopic technology and instrumentation within the past decade, laparoscopic pancreaticoduodenectomy is beginning to gain wider acceptance. METHODS Data were collected for all patients who underwent a TLPD at our institution. Preoperative evaluation consisted of computed tomography scan with pancreatic protocol and selective use of magnetic resonance imaging and/or endoscopic ultrasonography. The TLPD was done with 6 ports on 3 patients and 5 ports in 2 patients and included a celiac, periportal, peripancreatic, and periduodenal lymphadenectomy. Pancreatic stents were used in all 5 cases, and intestinal continuity was re-established by intracorporeal anastomoses. RESULTS Five patients underwent a TLPD for suspicion of a periampullary tumor. There were 3 women and 2 men with a mean age of 60 years and a mean body mass index of 32.8. Intraoperatively, the mean operative time was 9 hours 48 minutes, with a mean blood loss of 136 mL. Postoperatively, there were no complications and a mean length of stay of 6.6 days. There was no lymph node involvement in 4 out of 5 specimens. The pathological results included intraductal papillary mucinous neoplasm in 2 patients, pancreatic adenocarcinoma in 1 patient (R0 resection), benign 4-cm periampullary adenoma in 1 patient, and a somatostatin neuroendocrine carcinoma in 1 patient (R0, N1). CONCLUSION TLPD is a viable alternative to the standard Whipple procedure. Our early experience suggests decreased length of stay, quicker recovery, and improved quality of life. Complication rates appear to be improved or equivalent.


title: Release of severe acute respiratory syndrome coronavirus nuclear import block enhances host transcription in human lung cells.

text: The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo.


title: The passage of time during the UK Covid-19 lockdown.

text: In March 2020, in response to the Covid-19 pandemic, the UK Government imposed social and physical distancing measures on the population. These lockdown measures caused significant changes to all aspects of daily life. The current study examined how the passage of time was distorted during the lockdown period. Using an online questionnaire, day and week passage of time judgments were collected. In addition, measures of affect, task load and satisfaction with current levels of social interaction were taken. The results show that over 80% of participants experienced distortion to the passage of time during lockdown in comparison with normal. The passage of time during the day was predicted by age, stress, task load and satisfaction with current levels of social interaction. A slowing of the passage of time was associated with increasing age, increasing stress, reduced task load and reduced satisfaction with current levels of social interaction. Only age and satisfaction with current levels of social interaction predicted passage of time across a week. Again, increasing age and reduced satisfaction with levels of social interaction were associated with a slowing of the passage of time. These findings demonstrate that significant changes to daily life have a significant impact on our experience of time, with younger, more socially satisfied people more likely to experience time as passing more quickly during the lockdown.


title: Management of Large Cecal Polyps: When Can the Ileocecal Valve Be Spared?

text: BACKGROUND Endoscopic mucosal resection comprises the first-line treatment for large cecal polyps. With up to 14% of unresectable colonic polyps harboring malignancy, the management of endoscopically unresectable cecal polyps remains an oncologic right hemicolectomy, which can be associated with substantial postoperative morbidity. OBJECTIVE This study compares the outcomes of patients with cecal polyps who underwent either endoscopic mucosal resection, a cecectomy, or a right hemicolectomy. DATA SOURCES Patients undergoing either endoscopic mucosal resection, partial cecectomy, or right hemicolectomy from 2008 to 2017 at a single tertiary care institution were selected. STUDY SELECTION This was a retrospective cohort study. MAIN OUTCOME MEASURES The primary outcomes measured were the rate of malignancy, complication rate, estimated blood loss, and hospital length of stay between surgical cohorts. RESULTS One hundred twenty-nine patients with cecal polyps were identified, of which 52 were referred for surgery. Nineteen underwent partial cecectomy and 33 (27.3%) underwent right hemicolectomy. Two patients undergoing cecectomy required conversion to hemicolectomy because the resected specimen did not contain the polyp. The 2 surgical cohorts did not differ significantly regarding age, sex, or ASA classification. Procedural complication rates were higher among those undergoing hemicolectomy compared with those undergoing cecectomy (37.1% versus 5.9%, p = 0.02). Estimated blood loss (50 vs 10 mL, p = 0.02), operative duration (98 vs 76 minutes, p = 0.009), and length of stay (4 vs 2 days, p < 0.001) were higher in patients undergoing hemicolectomy than in those undergoing cecectomy. No invasive malignancies were identified on final pathology within the cecectomy cohort. LIMITATIONS Single-institution data and retrospective design were limitations of this study. CONCLUSIONS In tertiary centers, the majority of large cecal polyps are benign and can be addressed by using endoscopic mucosal resection. When involvement of the appendiceal orifice or ileocecal valve precludes endoscopic treatment, surgical resection is the standard of care. In the subset of cases not involving the ileocecal valve and without preoperative evidence of malignancy, partial cecectomy spares the ileocecal valve and can offer reduced postoperative morbidity compared with a formal right hemicolectomy. See Video Abstract at http://links.lww.com/DCR/A674.


title: Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans.

text: PURPOSE Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. METHODS Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. RESULTS Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 h in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). CONCLUSION This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases.


title: Early diffuse recurrence of hepatocellular carcinoma after percutaneous radiofrequency ablation: analysis of risk factors.

text: OBJECTIVE To evaluate the risk factors affecting early diffuse recurrence within 1 year of percutaneous ultrasound-guided radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS Out of 146 patients who received transcatheter arterial chemoembolisation (TACE) for treatment of recurrent HCC after percutaneous ultrasound-guided RFA, we selected 23 patients with early diffuse recurrence. Early diffuse recurrence was defined as three or more new recurrent HCCs within 1 year of initial RFA. As a control group, we selected 23 patients, matched exactly for age and sex, in which there was no local tumour progression or new recurrence after RFA. To analyse the risk factors, we examined patient factors and tumour factors. RESULTS Recurrent tumours occurred from 30 to 365 days after RFA (median time, 203 days). Univariate analysis indicated that larger tumour size and poorly defined margin were significant risk factors (P < 0.05). Multivariate analysis indicated that poorly defined margin was a significant risk factor (P < 0.05). CONCLUSION Larger tumour size and poorly defined margin may be risk factors for early diffuse recurrence of HCC within 1 year of RFA. Tumours with such risk factors should be treated with a combination of TACE to minimise the potential for therapeutic failure.


title: Muscarinic receptors modulate Nerve Growth Factor production in rat Schwann-like adipose-derived stem cells and in Schwann cells.

text: Regenerative capability of the peripheral nervous system after injury is enhanced by Schwann cells (SCs) producing several growth factors. The clinical use of SCs in nerve regeneration strategies is hindered by the necessity of removing a healthy nerve to obtain the therapeutic cells. Adipose-derived stem cells (ASCs) can be chemically differentiated towards a SC-like phenotype (dASCs), and represent a promising alternative to SCs. Their physiology can be further modulated pharmacologically by targeting receptors for neurotransmitters such as acetylcholine (ACh). In this study, we compare the ability of rat dASCs and native SCs to produce NGF in vitro. We also evaluate the ability of muscarinic receptors, in particular the M2 subtype, to modulate NGF production and maturation from the precursor (proNGF) to the mature (mNGF) form. For the first time, we demonstrate that dASCs produce higher basal levels of proNGF and mature NGF compared to SCs. Moreover, muscarinic receptor activation, and in particular M2 subtype stimulation, modulates NGF production and maturation in both SCs and dASCs. Indeed, both cell types express both proNGF A and B isoforms, as well as mNGF. After M2 receptor stimulation, proNGF-B (25 kDa), which is involved in apoptotic processes, is strongly reduced at transcript and protein level. Thus, we demonstrate that dASCs possess a stronger neurotrophic potential compared to SCs. ACh, via M2 muscarinic receptors, contributes to the modulation and maturation of NGF, improving the regenerative properties of dASCs.


title: N-butyl cyanoacrylate embolization using a detachable tip microcatheter: initial experience.

text: INTRODUCTION Endovascular embolization of intracranial vascular malformations with N-butyl cyanoacrylate (nBCA) using a detachable tip microcatheter allows prolonged injection and decreases the risk of catheter retention. METHODS Between March and December 2013, the Apollo 1.5 cm detachable tip microcatheter was used in five patients after being approved by both the Food and Drug Administration and the institutional review board as a compassionate use device. Nine pedicles were embolized and the follow-up ranged from 1 to 3 months. RESULTS Five of the nine catheter tips detached. The length of reflux was not directly associated with the detachment of the distal tip. There were no cases of premature microcatheter detachment during navigation, manipulation with multiple microguidewire reintroduction and guidance. There was no leak of embolic agent at the detachment zone. Follow-up showed the detached tip to be stable without migration. CONCLUSIONS A detachable tip microcatheter offers an advance in the safety and effectiveness of nBCA embolization. Catheter retrieval becomes more controlled and less traumatic. Our initial experience is encouraging, and more experience is needed to categorically ascertain its safety and efficacy.


title: Angiotensin converting enzyme 2 and the kidney.

text: PURPOSE OF REVIEW Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes angiotensin II (AngII). AngII levels can be modulated by ACE2 in tissues where the enzyme is highly expressed, such as the kidney. In the kidney, ACE2 has the potential to regulate the intrarenal renin-angiotensin system (RAS), which can impact blood pressure and renal injury. Thus, in disease states where the RAS is often upregulated, the function of ACE2 plays a particularly important role. This review highlights the results of recent studies that demonstrate the interplay between ACE2 and the kidney under normal and pathological conditions. RECENT FINDINGS ACE2 has been reported to play a key role in renal and cardiovascular function. Recent studies have implicated shedding of the membrane-bound ectodomain of ACE2 as one way in which the enzyme can be regulated and enzymatic activity altered. This posttranslational modification releases a fragment which retains enzymatic activity, and thus provides a novel mechanism by which the RAS can be altered in response to physiological stimuli. Decreased ACE2 activity is associated with increased blood pressure, diabetes, and oxidative stress, whereas, increased levels of ACE2 appear to be renoprotective. SUMMARY A growing body of evidence, involving both experimental and human studies, points out the crucial role that ACE2 plays on the modulation of renal injury. Thus, therapeutic targets aiming to increase ACE2 activity and the ACE2-Ang(1-7)-MasR axis could potentially become clinically relevant, especially in disease states where the renal RAS is upregulated.


title: Application of Enhanced Recovery After Surgery in Single-incision Laparoscopic Distal Gastrectomy.

text: BACKGROUND Recently, enhanced recovery after surgery (ERAS) was widely used in the perioperative management of gastric cancer. The study aimed to evaluate the safety and effectiveness of ERAS in single-incision laparoscopic distal gastrectomy (SIDG). MATERIALS AND METHODS A total of 90 patients who received laparoscopic gastric cancer resection were divided into 3 groups: group A (n=30), underwent traditional multiport laparoscopic distal gastrectomy with conventional perioperative management; group B (n=30) underwent traditional multiport laparoscopic distal gastrectomy with ERAS concept; and group C (n=30), underwent SIDG with ERAS concept. Clinical data and gut function were assessed in 3 groups. RESULTS There were no significant differences in terms of postoperative complication, number of resected lymph nodes and blood loss among 3 groups. However, operation time was longer (P=0.003) and treatment cost was higher (P<0.001) in group C than that in group A and B. Group C had faster recovery of bowel function (P<0.001), shorter postoperative hospital stay (P=0.002), and less postoperative complication (P=0.044) than those in group A. There were no significant differences in terms of recovery of bowel function and postoperative hospital stay between group C and B (all P>0.05). The white blood cell counts were lower than group A and B (all P<0.05) and C-reactive protein in group C were lower than group A (P<0.05) and B (P>0.05). CONCLUSIONS The findings suggest that SIDG with ERAS may be a feasible and safe procedure for early gastric cancer because it provides a favorable cosmetic result while not compromising postoperative complications, number of resected lymph nodes, and blood loss.


title: Fighting pandemics: Inspiration from Islam.

text: Infectious disease has killed more people than any other cause throughout history. The current pandemic of coronavirus disease (COVID-19) has again revealed how vulnerable we remain. Muslims constitute the world's second-largest religious group, making up about a quarter of the world population. They have distinctive faith and culture, pertaining to their religious beliefs and practices that need special attention, in situations such as current COVID-19 pandemic. Congregational prayers are an indispensable part of Islamic culture. Performance of obligatory prayers in congregation is compulsory and mandatory for every Muslim adult male who has no excuse for not doing so. But, doing so during a pandemic can help in the spread of the COVID-19. Muslims look up to the Holy Qur'an and teachings of Prophet (PBUH) (Hadiths) for guidance under all the circumstances. In this review we will cover how Islamic teaching can guide us to manage pandemics like COVID-19.


What I learnt from studying doctors' mental health over 20 years-an essay by Jenny Firth-Cozens.


title: Effect of diclofenac on cyclooxygenase-2 levels and early breaking strength of experimental colonic anastomoses and skin incisions.

text: BACKGROUND Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs on the anastomotic leakage rate after colorectal surgery. METHODS An experimental, randomized, placebo-controlled prospective study on 32 male Wistar rats was carried out. We examined the effect of diclofenac 4 mg/kg/day on the cyclooxygenase-2 (COX-2) enzyme in the anastomotic tissue and on the breaking strength of anastomotic and incisional wounds. The operation was performed with colonic resection and hand-sewn anastomosis. After 3 days, the rats were sacrificed and the breaking strength and the COX-2 content of the anastomosis were measured. RESULTS There was a significantly reduced level of COX-2 in the rats treated with diclofenac (p = 0.001); no significant differences in any of the breaking strength measurements and no significant correlation between COX-2 levels and breaking strength of the anastomotic or incisional wounds could be found (p = 0.073 and p = 0.727). CONCLUSION This study for the first time showed that a diclofenac dose of 4 mg/kg/24 h was sufficient to reduce the level of COX-2 enzymes in the anastomotic tissue in rats. This inhibition of the inflammatory response did not lead to reduced breaking strength of either anastomotic or incisional wounds. Whether there is a detrimental effect of COX inhibition on colorectal anastomoses in the clinical setting remains controversial.


title: Single-incision totally extraperitoneal inguinal hernia repair: our initial 100 cases and comparison with conventional three-port laparoscopic totally extraperitoneal inguinal hernia repair.

text: PURPOSE To compare the outcomes of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) and conventional three-port totally extraperitoneal (TEP) repair. METHODS We performed a retrospective analysis of 137 patients (SILS-TEP, 100; conventional TEP, 37) scheduled to undergo elective inguinal hernia from January 2011 to July 2013 at Osaka Police Hospital. RESULTS There were no significant differences in the patient demographics. There were no significant differences in the length of the operation between the two groups (SILS-TEP group, 93 min vs. conventional TEP group, 92 min for unilateral hernias, p = 0.8; SILS-TEP group, 142 min vs. conventional TEP, 128 min for bilateral hernias, p = 0.4). The postoperative hospital stay, total medical charge for the hospital stay and the numerical rating scale before and 3 months after surgery were comparable in both groups. Two cases treated by SILS-TEP repair were converted to conventional three-port TEP repair (one case) and mesh-plug method (one case). The postoperative complications were comparable in both groups, and these were managed conservatively. One recurrence (2 %, 1/37) developed in the conventional TEP group, compared with 0 recurrences (0/100) in the SILS-TEP group. CONCLUSIONS SILS-TEP repair seems to be safe and feasible, with no significant differences in the total medical charges for the hospital stay or the postoperative pain score 3 months after surgery compared with conventional three-port TEP repair.


title: White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies.

text: Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.


title: Keeping the Family in Family Medicine.

text: In this personal reflection, as a Family Medicine resident at an Academic Center in Northeast Florida, as well as being a chronic illness patient myself, I explore the notion of dying alone and away from family. Although COVID-19 has changed the practice of medicine in many ways, prior to that, and before the instillation of hospital no-visitor policies and stay at home orders, I experienced a case of a patient dying alone in the hospital. These chronicles that case and the impact it had on me afterward in regard to my own family and how I hope the future of medicine can address this.


title: From SARS coronavirus to novel animal and human coronaviruses.

text: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic.


title: Assessing sinus aerosol deposition: benefits of SPECT-CT imaging.

text: PURPOSE Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders. This paper proposes a comparative study of the nasal deposition patterns of micron and submicron particles using planar gamma-scintigraphy imaging vs. a new 3-dimensional (3D) imaging approach based on SPECT-CT measurements. METHODS Radiolabelled nebulizations have been performed on a plastinated model of human nasal cast coupled with a respiratory pump. First, the benefits provided by SPECT-CT imaging were compared with 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage as reference for the sonic 2.8 μm aerosol sinusal deposition. Then, the impact on nasal deposition of various airborne particle sizes was assessed. RESULTS The 2D methodology overestimates aerosol deposition in the maxillary sinuses by a factor 9 whereas the 3D methodology is in agreement with the maxillary sinus lavage reference methodology. Then with the SPECT-CT approach we highlighted that the higher particle size was mainly deposited in the central nasal cavity contrary to the submicron aerosol particles (33.8 ± 0.6% of total deposition for the 2.8 μm particles vs. 1 ± 0.3% for the 230 nm particles). CONCLUSION Benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially used for scintigraphic imaging of sinusal deposition in Human.


title: Comparative clinical study of Bactigras and Telfa AMD for skin graft donor-site dressing.

text: The Bactigras(®) paraffin tulle coated with chlorhexidine is normally used for the treatment of donor-site wounds in burn patients who received split-thickness skin grafts in several centers. It has some disadvantages, such as adhesion to wound surfaces and pain from the irritation caused by this dressing. The Telfa AMD(®), a non-adherent wound dressing which consists of absorbent cotton fibers impregnated with polyhexamethylene biguanide enclosed in a sleeve of thermoplastic polymers, is a new option for donor-site wound care which causes less adherence to the wound. The purpose of this study was to compare clinical efficacy of these two dressings for the management of donor-site wounds. Thirty-two patients who received split-thickness skin grafts by donor site harvesting from the thigh were enrolled in this study and randomized into two groups receiving either the Bactigras(®) or the Telfa AMD(®) wound treatment. Re-epithelialization, pain, infection and cost-effectiveness analyses were compared between both groups. The results showed that there was no significant difference in age, area of donor sites or length of hospital stays between the groups (p > 0.05). However, the day of re-epithelialization (≥90%) was significantly shorter in patients treated with the Telfa AMD(®) compared to the Bactigras(®) group (14.00 ± 3.05 vs. 9.25 ± 1.88 days for Bactigras(®) and Telfa AMD(®) groups, respectively, p < 0.001). The average pain score was also significantly lower in the Telfa AMD(®) group (1.57 ± 0.55 vs. 4.70 ± 1.16, p < 0.001). There was no difference in the cost of treatment between the groups (4.64 ± 1.97 vs. 5.72 ± 2.54 USD, p = 0.19). This study indicated that the Telfa AMD(®) was an effective dressing for the treatment of donor-site wounds.


title: Late-onset bronchopleural fistula after lobectomy and adjuvant chemotherapy for lung cancer: A case report and review of the literature.

text: RATIONALE Late-onset bronchopleural fistula (BPF) induced by chemotherapy after lobectomy for lung cancer is rarely reported, lacking reliable preventive approaches. A timely identification and individualized treatment is essential for prognosis. PATIENT CONCERNS A 52-year-old female patient complained of fever, productive cough, and fatigue 1 week after adjuvant chemotherapy following right lower lobectomy and systemic mediastinal lymph node dissection. Chest computed tomography (CT) indicated pneumothorax and thick-walled empyema cavity within her right-sided thorax. DIAGNOSES The patient was diagnosed as late-onset BPF based on clinical manifestation and chest radiography. INTERVENTIONS In addition to antibiotics, a chest tube was reinserted under CT guidance, and vacuum suction was utilized for continuous drainage. Next cycle of adjuvant chemotherapy was terminated. OUTCOMES The empyema cavity was gradually closed in 1 month after conservative treatment, and the patient survived with good condition up to now. LESSONS Late-onset BPF should be kept in mind when the patient suffered from productive cough and chills during postoperative chemotherapy. And a prompt conservative management might be effective.


title: Effects of anti-VEGF on predicted antibody biodistribution: roles of vascular volume, interstitial volume, and blood flow.

text: BACKGROUND The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. METHODOLOGY/PRINCIPAL FINDINGS Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. CONCLUSIONS/SIGNIFICANCE These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF.


Immune biomarker-based enrichment in sepsis trials.


title: Programmed -1 frameshifting efficiency correlates with RNA pseudoknot conformational plasticity, not resistance to mechanical unfolding.

text: Programmed -1 frameshifting, whereby the reading frame of a ribosome on messenger RNA is shifted in order to generate an alternate gene product, is often triggered by a pseudoknot structure in the mRNA in combination with an upstream slippery sequence. The efficiency of frameshifting varies widely for different sites, but the factors that determine frameshifting efficiency are not yet fully understood. Previous work has suggested that frameshifting efficiency is related to the resistance of the pseudoknot against mechanical unfolding. We tested this hypothesis by studying the mechanical properties of a panel of pseudoknots with frameshifting efficiencies ranging from 2% to 30%: four pseudoknots from retroviruses, two from luteoviruses, one from a coronavirus, and a nonframeshifting bacteriophage pseudoknot. Using optical tweezers to apply tension across the RNA, we measured the distribution of forces required to unfold each pseudoknot. We found that neither the average unfolding force, nor the unfolding kinetics, nor the parameters describing the energy landscape for mechanical unfolding of the pseudoknot (energy barrier height and distance to the transition state) could be correlated to frameshifting efficiency. These results indicate that the resistance of pseudoknots to mechanical unfolding is not a primary determinant of frameshifting efficiency. However, increased frameshifting efficiency was correlated with an increased tendency to form alternate, incompletely folded structures, suggesting a more complex picture of the role of the pseudoknot involving the conformational dynamics.


title: Anti-IL-5 in Mild Asthma Alters Rhinovirus-induced Macrophage, B-Cell, and Neutrophil Responses (MATERIAL). A Placebo-controlled, Double-Blind Study.

text: RATIONALE Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. OBJECTIVES To study the effect of mepolizumab on virus-induced immune responses in mild asthma. METHODS Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV1, FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. MEASUREMENTS AND MAIN RESULTS Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV1, FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. CONCLUSIONS Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils. Clinical trial registered with www.clinicaltrials.gov (NCT 01520051).


title: Are you suffering from a large arterial occlusion? Please raise your arm!

text: Background and purpose Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke. Methods Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined. Results The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively. Conclusions Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions.


docid: wqgbtbbo

title: Difficult tracheal tube passage and subglottic airway injury during intubation with the GlideScope® videolaryngoscope: a randomised, controlled comparison of three tracheal tubes.

text: Difficulty during placement of the tracheal tube is a known problem when intubating with the GlideScope® , which may lead to subglottic airway injury. This randomised, controlled clinical trial was designed to compare the resistance to passage of PVC (polyvinyl chloride), reinforced or BlockBuster tracheal tubes during intubation with the GlideScope. Secondary outcomes included the time taken to intubate and assessment of subglottic airway injury. One-hundred and seventy-seven patients were included in the data analysis. There was difficult tracheal tube passage (moderate or severe resistance) in 15 (21.4%) patients using the PVC tube compared with 4 (7.4%) and 1 (1.9%) using the reinforced and BlockBuster tubes, respectively (p = 0.003 for PVC vs. BlockBuster). The median (IQR [range]) time taken to intubate was 35 (27-45 [15-115]) s, 25 (20-27 [15-110]) s and 25 (22-30 [16-90]) s, respectively, (p < 0.001 for PVC vs. reinforced as well as PVC vs. BlockBuster). Subglottic airway injury, assessed using a fibreoptic bronchoscope after extubation, was higher with the PVC tube (p < 0.001) and the reinforced tube (p = 0.012) compared with the BlockBuster tube. We conclude that the BlockBuster tracheal tube is a better choice for orotracheal intubation with the GlideScope than PVC or reinforced tubes.


docid: gjephmag

title: Single-portal access laparoscopic radical nephrectomy for renal cell carcinoma in transplant patients: the first experience.

text: We present the details of the first three single-portal access laparoscopic radical nephrectomies (S-Portal-RN) performed in patients with a malignant renal tumour that developed after a renal transplant. The mean operative time was 171.6 ± 37.5 min, with a mean blood loss of 126.6 ± 25.1 ml. A single small skin incision (5 cm) was performed to remove the kidney. No significant difference in glomerular filtration rate was observed postoperatively. The postoperative recovery was uneventful with favourable short-term outcomes and high patient satisfaction at the 2-mo follow-up. We believe that S-Portal-RN for renal cancer after a renal transplant can be performed without increased risks for the patients or for the transplanted kidney.


title: The link between anemia and adverse outcomes in patients with acute coronary syndrome.

text: INTRODUCTION Anemia is one of the most frequent comorbidities in acute coronary syndrome (ACS) patients and is associated with a significant impact on clinical outcomes. This review summarizes the knowledge and updated management of anemia in the setting of ACS. Areas covered: We provide a review on the prevalence, pathophysiology, prognosis, impact, and updated management of anemia. Expert opinion: Patients with anemia represent a therapeutic challenge in the setting of acute coronary syndrome and require specific acute and chronic management. Despite the high prevalence of anemia and the large amount of data confirming its strong impact on short- and long-term outcomes, a commonly used and accurate definition in the context of patients undergoing percutaneous coronary intervention and stent implantation for ACS is still lacking. Furthermore, therapeutic options to address anemia remain limited. The combined use of risk scores to identify high-risk characteristics for adverse bleeding or thrombotic events may guide individualized treatment of anemic patients, for example, by selecting an antiplatelet regimen aimed at minimizing bleeding or thrombotic risk. The optimal strategy for blood transfusion is currently being evaluated by an ongoing randomized trial.


title: Laparoscopic colpotomy using monopolar electrocautery: does power really matter?

text: OBJECTIVE The purpose of this study was to assess the extent and rate of vaginal tissue injury associated with the utilization of various monopolar electrosurgical power settings when laparoscopically transecting vaginal tissue. METHODS This is an Institutional Animal Care and Use Committee-approved prospective, paired, single-blinded study. Externalized porcine vagina was transected using monopolar energy at 30, 50, and 80 W in the cut mode with laparoscopic Endo Shears. The slides were prepared and stained with both hematoxylin-eosin and Masson trichrome and were examined by board-certified veterinary pathologists blinded to the study. RESULTS There were 18 swine; each animal was tested on all 3 power settings (n = 54). Tissue injury was measured to a mean (SD) of 767 (519) μm at 30 W, 690 (600) μm at 50 W, and 556 (470) μm at 80 W. When comparing the monopolar settings, the results were as follows: 30 versus 50 W (P = 0.33), 30 versus 80 W (P = 0.067), and 50 versus 80 W (P = 0.17). The mean (SD) time for complete transection was measured at each power setting (n = 18), with 35.8 (5.4) seconds for 30 W, 13.5 (5.5) seconds for 50 W, and 8.4 (5.1) seconds for 80 W (P < 0.001). There was a statistically significant difference in the mean (SD) rates of injury, with 20.8 (8.8) μm/s at 30 W, 39.8 (11.8) μm/s at 50 W, and 50.1 (19.2) μm/s at 80 W (P = 0.01). CONCLUSIONS Using various power settings of monopolar energy may not make a significant difference in swine vaginal tissue damage at the time of colpotomy. However, there was a significant difference in the times and rates at which tissue was transected when using higher powers. We recommend using the 50- or 80-W setting, as this will likely decrease surgical times without altering vaginal tissue damage.


Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems.


title: Vortioxetine for attention deficit hyperactivity disorder in adults: A randomized, double-blind, placebo-controlled, proof-of-concept study.

text: BACKGROUND: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances. AIMS: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design. METHODS: Patients aged 18-55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59). RESULTS: Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale. CONCLUSION: Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated.


title: Barriers and enablers to patient recruitment for randomised controlled trials on treatment of chronic wounds: A systematic review.

text: Randomised controlled trials represent the gold standard in intervention efficacy evaluation. However, suboptimal recruitment affects completion and the power of a therapeutic trial in detecting treatment differences. We conducted a systematic review to examine the barriers and enablers to patient recruitment for randomised controlled trials on chronic wound treatment. Review registration was under PROSPERO 2017:CRD42017062438. We conducted a systematic search of Ovid MEDLINE, EBSCOhost CINAHL, Ovid Cochrane Library, Ovid EMBASE, and Ovid PsycINFO databases in June 2017 for chronic wound treatment randomised controlled trials. Twenty-seven randomised controlled trials or qualitative studies met the inclusion criteria. Among the 24 randomised controlled trials, 21 were assessed as low quality in relation to recruitment, and 3 were assessed as high quality. All 27 studies reported barriers to recruitment in chronic wound randomised controlled trials. The reported barriers to recruitment were: study-related, patient-related, clinician-related, health system-related, and/or operational-related. No study reported recruitment enablers. To enhance randomised controlled trial recruitment, we propose the need for improved integration of research and clinical practice. To alleviate the problems arising from inadequate reporting of randomised controlled trials, the Consolidated Standards of Reporting Trials Statement could include an additional item on recruitment barriers. This approach will allow for increased awareness of the potential barriers to recruitment for Randomised controlled trials (RCTs) in both wound management and other health care research.


title: Development of bilateral tension pneumothorax under anesthesia in a Boerhaave's syndrome patient: a case report.

text: A 33-year-old male visited the emergency room with abdominal pain which developed after a vomiting episode. Based on the pneumomediastinum findings from a chest radiograph and a contrast-enhanced chest and abdominal computed tomography scan, the patient was diagnosed with Boerhaave's syndrome. Preoperative radiologic findings showed no pneumothorax or pleural effusion. Once anesthesia was administered, the patient developed near complete cardiopulmonary collapse due to a bilateral tension pneumothorax, which was treated by bilateral thoracentesis, followed by chest tube insertion. Despite a left side rupture, the damaged right lung was unable to overcome single right ventilation, so the surgery was completed via right thoracotomy. The ruptured site was treated, and the patient was transferred to the intensive care unit. We discuss the anesthetic implications of this disease and how to prevent fatal complications.


docid: indagivd

title: How Flow Reduction Influences the Intracranial Aneurysm Occlusion: A Prospective 4D Phase-Contrast MRI Study.

text: BACKGROUND AND PURPOSE Flow-diverter stents are widely used for the treatment of wide-neck intracranial aneurysms. Various parameters may influence intracranial aneurysm thrombosis, including the flow reduction induced by flow-diverter stent implantation, which is assumed to play a leading role. However, its actual impact remains unclear due to the lack of detailed intra-aneurysmal flow measurements. This study aimed to clarify this relationship by quantitatively measuring the intra-aneurysmal flow using 4D phase-contrast MR imaging. MATERIALS AND METHODS We acquired prospective pre- and post-stent implantation 4D phase-contrast MR imaging data of a consecutive series of 23 patients treated with flow-diverter stents. Velocity field data were combined with the intraprocedural 3D angiogram vessel geometries for precise intracranial aneurysm extraction and partial volume correction. Intra-aneurysmal hemodynamic modifications were compared with occlusion outcomes at 6 and 12 months. RESULTS The averaged velocities at systole were lower after flow-diverter stent implantation for all patients and ranged from 21.7 ± 7.1 cm/s before to 7.2 ± 2.9 cm/s after stent placement. The velocity reduction was more important for the group of patients with aneurysm thrombosis at 6 months (68.8%) and decreased gradually from 66.2% to 55% for 12-month thrombosis and no thrombosis, respectively (P = .08). CONCLUSIONS We propose an innovative approach to measure intracranial flow changes after flow-diverter stent implantation. We identified a trend between flow reduction and thrombosis outcome that brings a new insight into current understanding of the flow-diversion treatment response.


title: Hunting with lead: association between blood lead levels and wild game consumption.

text: BACKGROUND Wild game hunting is a popular activity in many regions of the United States. Recently, the presence of lead fragments in wild game meat, presumably from the bullets or shot used for hunting, has raised concerns about health risks from meat consumption. OBJECTIVE This study examined the association between blood lead levels (PbB) and wild game consumption. METHODS We recruited 742 participants, aged 2-92 years, from six North Dakota cities. Blood lead samples were collected from 736 persons. Information on socio-demographic background, housing, lead exposure source, and types of wild game consumption (i.e., venison, other game such as moose, birds) was also collected. Generalized estimating equations (GEE) were used to determine the association between PbB and wild game consumption. RESULTS Most participants reported consuming wild game (80.8%) obtained from hunting (98.8%). The geometric mean PbB were 1.27 and 0.84 microg/dl among persons who did and did not consume wild game, respectively. After adjusting for potential confounders, persons who consumed wild game had 0.30 microg/dl (95% confidence interval: 0.16-0.44 microg/dl) higher PbB than persons who did not. For all game types, recent (<1 month) wild game consumption was associated with higher PbB. PbB was also higher among those who consumed a larger serving size (> or = 2 oz vs. <2 oz); however, this association was significant for 'other game' consumption only. CONCLUSIONS Participants who consumed wild game had higher PbB than those who did not consume wild game. Careful review of butchering practices and monitoring of meat-packing processes may decrease lead exposure from wild game consumption.


title: The roles of chemokines in rabies virus infection: overexpression may not always be beneficial.

text: It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1alpha further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.


title: Increases in electroencephalogram and electromyogram variability are associated with an increased incidence of intraoperative somatic response.

text: BACKGROUND sBIS, the variability of the Bispectral Index (BIS), sEMG, the variability of facial electromyogram power (EMG), and the Composite Variability Index (CVI) are 3 new measures of electroencephalogram and EMG variability. CVI is a single measure of the combined variability in BIS and EMG. We investigated whether increases in these variables are associated with intraoperative somatic responses. METHODS This multicenter study included 120 patients undergoing elective, noncardiac surgery from 4 different sites. General anesthesia was maintained using propofol and remifentanil at 2 of the sites and sevoflurane and remifentanil at the 2 other sites. Propofol or sevoflurane was adjusted to maintain BIS between 45 and 60. Clinicians were blinded to CVI (v2.0) at all times, and remifentanil infusions were adjusted at the discretion of the clinician. The times of all intraoperative somatic events, defined as movement, grimacing, or eye opening, were recorded. Offline, the maintenance phase of each case was divided into consecutive, nonoverlapping, 10-minute segments. Segments were identified as containing a somatic event or containing no events. For each segment, mean sBIS, sEMG, and CVI and the heart rate (HR) range and mean arterial blood pressure range were calculated. To quantify how effectively each variable discriminated between somatic event segments and nonevent segments, we computed the area under the receiver operating characteristic (ROC) curve for each variable. Finally, we observed the time course of sBIS, sEMG, CVI, and the HR range before each somatic event and characterized the earliest time before the somatic event at which each variable was able to discriminate between the somatic events and a specified set of nonevents. RESULTS The analysis included 33 somatic event segments and 829 nonevent segments from 105 surgical cases. The areas under the ROC curve (±SE) for sBIS, sEMG, and CVI were 0.83 ± 0.04, 0.92 ± 0.02, and 0.89 ± 0.03, respectively. The areas under the ROC curve for HR range and mean arterial blood pressure range were 0.77 ± 0.03 and 0.68 ± 0.05, respectively. CVI, sBIS, and sEMG all demonstrated higher average values before upcoming somatic events when compared with nonevents. HR range only showed a difference within a few seconds before the somatic event. CONCLUSION sBIS, sEMG, and CVI, measures of electroencephalogram and EMG variability, increased when intraoperative somatic events occurred. sBIS, sEMG, and CVI discriminated between 10-minute segments that contained a somatic event and those segments that did not contain an event better than changes in HR and mean arterial blood pressure. Furthermore, CVI increases before somatic events began earlier than HR changes and may provide caregivers with an early warning of potentially inadequate antinociception.


title: Visual Aids for Patient, Family, and Physician Decision Making About Endovascular Thrombectomy for Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Rapid decision making optimizes outcomes from endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate swift review of potential outcomes and can accelerate decision processes. METHODS From patient-level, pooled randomized trial data, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification. RESULTS For the full 7-category modified Rankin Scale, thrombectomy added to IV tPA (intravenous tissue-type plasminogen activator) alone had number needed to treat to benefit 2.9 (95% confidence interval, 2.6-3.3) and number needed to harm 68.9 (95% confidence interval, 40-250); thrombectomy for patients ineligible for IV tPA had number needed to treat to benefit 2.3 (95% confidence interval, 2.1-2.5) and number needed to harm 100 (95% confidence interval, 62.5-250). Visual displays of treatment effects on 100 patients showed: with thrombectomy added to IV tPA alone, 34 patients have better disability outcome, including 14 more normal or near normal (modified Rankin Scale, 0-1); with thrombectomy for patients ineligible for IV tPA, 44 patients have a better disability outcome, including 16 more normal or nearly normal. Displays also showed that harm (increased modified Rankin Scale final disability) occurred in 1 of 100 patients in both populations, mediated by increased new territory infarcts. The person-icon figures integrated these outcomes, and early side-effects, in a single display. CONCLUSIONS Visual decision aids are now available to rapidly educate healthcare providers, patients, and families about benefits and risks of endovascular thrombectomy, both when added to IV tPA in tPA-eligible patients and as the sole reperfusion treatment in tPA-ineligible patients.


title: Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains.

text: Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods.


title: Laparoscopic management for non-traumatic colon perforation in children.

text: PURPOSE Although recent reports have seen an increase in acceptance of laparoscopic surgery as treatment for traumatic colon injury, its role in the management of non-traumatic colon perforation in children has not been reported. In this study, we review our experience in laparoscopic non-resectional management for children who presented with non-traumatic colonic perforation. METHODS Between October 2003 and May 2011, 15 children who had been diagnosed with colonic perforation and underwent laparoscopic surgery were included in the study. Their medical records were reviewed for analysis. RESULTS The clinical manifestation of non-traumatic colon perforation in children was non-specific. The most likely aetiology was infective colitis. Solitary perforation at the caecum was the most common finding. The exact perforation site could not be identified in 3 patients. Nine patients had primary closure while 3 patients underwent wedge resection. The single trocar laparoscopic surgery was successful in 12 patients. The mean postoperative hospital stay was 7.3 days. CONCLUSION For children presenting with suspected non-traumatic colon perforation, laparoscopic management is the desirable approach. The peritoneal lavage, wedge excision and primary repair can be performed with single trocar techniques and is associated with minimal morbidity. Future prospective studies are needed to compare this minimally invasive approach with conventional open surgery.


title: Deep sequencing identifies viral and wasp genes with potential roles in replication of Microplitis demolitor Bracovirus.

text: Viruses in the genus Bracovirus (BV) (Polydnaviridae) are symbionts of parasitoid wasps that specifically replicate in the ovaries of females. Recent analysis of expressed sequence tags from two wasp species, Cotesia congregata and Chelonus inanitus, identified transcripts related to 24 different nudivirus genes. These results together with other data strongly indicate that BVs evolved from a nudivirus ancestor. However, it remains unclear whether BV-carrying wasps contain other nudivirus-like genes and what types of wasp genes may also be required for BV replication. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV). Here we characterized MdBV replication and performed massively parallel sequencing of M. demolitor ovary transcripts. Our results indicated that MdBV replication begins in stage 2 pupae and continues in adults. Analysis of prereplication- and active-replication-stage ovary RNAs yielded 22 Gb of sequence that assembled into 66,425 transcripts. This breadth of sampling indicated that a large percentage of genes in the M. demolitor genome were sequenced. A total of 41 nudivirus-like transcripts were identified, of which a majority were highly expressed during MdBV replication. Our results also identified a suite of wasp genes that were highly expressed during MdBV replication. Among these products were several transcripts with conserved roles in regulating locus-specific DNA amplification by eukaryotes. Overall, our data set together with prior results likely identify the majority of nudivirus-related genes that are transcriptionally functional during BV replication. Our results also suggest that amplification of proviral DNAs for packaging into BV virions may depend upon the replication machinery of wasps.


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title: Transumbilical single port laparoscopic surgery for the treatment of concomitant disease.

text: BACKGROUND We report our experience of transumbilical single port laparoscopic surgery (TUSPLS) for multiple concomitant intraabdominal pathologies, and assess the feasibility of this technique with several technical tips. METHODS Various combined procedures using TUSPLS were performed since April, 2008. All records of concomitant laparoscopic procedures using TUSPLS were searched at three hospitals. RESULTS Forty-one patients underwent 82 combined procedures using TUSPLS in a single session. The perioperative outcomes of simultaneously performed cholecystectomy and ovarian cystectomy using TUSPLS (n = 14) are compared with those of using CLS (n = 11). The operating time was significantly longer with the TUSPLS method than with the CLS method. However, postoperative convalescent outcomes such as postoperative hospital stay, VAS pain score, and required analgesics showed no differences between the two methods. Also, there were no significant operative complications associated with the two methods. Fewer trocars were used with the TUSPLS method. CONCLUSIONS Combined laparoscopic procedures for various concomitant pathologies in the abdomen can be performed using transumbilical single port laparoscopic surgery without increasing morbidity or hospital stay in patients with acceptable risk.


title: Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases.

text: BACKGROUND AND PURPOSE Percutaneous cryoablation has emerged as a minimally invasive technique for the management of osseous metastases. The purpose of this study was to assess the safety and effectiveness of percutaneous imaging-guided spine cryoablation for pain palliation and local tumor control for vertebral metastases. MATERIALS AND METHODS Imaging-guided spine cryoablation was performed in 14 patients (31 tumors) with vertebral metastases refractory to conventional chemoradiation therapy or analgesics, to achieve pain palliation and local tumor control in this retrospective study. Spinal nerve and soft-tissue thermal protection techniques were implemented in all ablations. Patient response was evaluated by a pain numeric rating scale administered before the procedure and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural analgesic requirements (expressed as morphine-equivalent dosages) were also analyzed at the same time points. Pre- and postprocedural cross-sectional imaging was evaluated in all patients to assess local control (no radiographic evidence of disease at the treated sites). Complications were monitored. Analysis of the primary end points was undertaken via paired-comparison procedures by using the Wilcoxon signed rank test. RESULTS Thirty-one tumors were ablated in 14 patients (9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine (n = 1, 3%). There were statistically significant decreases in the median numeric rating scale score and analgesic usage at 1-week, 1-month, and 3-month time points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of tumors (median follow-up, 10 months). Two patients had transient postprocedural unilateral lower extremity radiculopathy and weakness. CONCLUSIONS Percutaneous imaging-guided spine cryoablation is a safe and effective treatment for pain palliation and local tumor control for vertebral metastases.


title: Diagnosis and management of rare inferior vena cava leiomyosarcoma guided by a novel minimally invasive vascular biopsy technique.

text: Primary vascular tumors such as vascular leiomyosarcomas are rare, but exhibit markedly different characteristics than tumors that invade the vasculature from a secondary source. Establishing a diagnosis is essential in determining the appropriate treatment plan, but obtaining a histologic specimen may prove challenging and carry significant risks. Minimally invasive endovascular biopsy techniques can be pivotal in the diagnosis-and thus in the management-of vascular tumors. We present a case of a primary inferior vena cava leiomyosarcoma, not able to be adequately assessed by noninvasive imaging and deemed too risky to be approached with traditional percutaneous biopsy techniques. Accurate diagnosis of such tumors is critical, as the success of surgical resection, although high risk, depends greatly upon the type, location, and extent of malignancy.