title: Reflux control is important in the management of Barrett's Esophagus: results from a retrospective 1,830 patient cohort.

text: BACKGROUND It is unknown whether acid/reflux control prevents progression in Barrett's esophagus. In this study, we investigate whether medical or surgical control of reflux is associated with a decreased risk of progression to dysplasia/esophageal adenocarcinoma. METHODS We retrospectively collected and analyzed data from a cohort of Barrett's esophagus patients participating in this single-center study comprised of all patients diagnosed with Barrett's esophagus at NorthShore University Health System hospitals and clinics over a 10-year period. Patients were followed in order to identify those progressing from Barrett's esophagus to low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. We collected information from the patient's electronic medical records regarding demographic, endoscopic findings, histological findings, smoking/alcohol history, medication use including proton-pump inhibitors, and history of bariatric and antireflux surgery. Risk-adjusted modeling was performed using multivariable logistic regression. RESULTS This study included 1,830 total Barrett's esophagus patients, 102 of which had their Barrett's esophagus progress to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma (confirmed by biopsy) with an annual incidence rate of 1.1%. Mean follow-up period was 5.51 years (10,083 patient-years). Compared to the group that did not progress, the group that progressed was older (69.3 ± 13.7 vs. 63.9 ± 13.4 years. p < 0.001) and likely to be male (75 vs. 61%, p < 0.01). In the multivariable analysis, patients who had a history of antireflux surgery (n = 44) or proton-pump inhibitor use without surgery (n = 1,641) were found to progress at significantly lower rates than patients who did not have antireflux surgery or were not taking PPI's (OR 0.18, 95% CI 0.09-0.36). CONCLUSIONS Reflux control was associated with decreased risk of progression to low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. These results support the use of reflux control strategies such as proton-pump inhibitor therapy or surgery in patients with non-dysplastic Barrett's esophagus for the prevention of progression to dysplasia/adenocarcinoma.


title: Risk factors for endovenous heat-induced thrombosis after endovenous radiofrequency ablation performed in Thailand.

text: OBJECTIVE We aimed to determine the incidence of and associated risk factors for endovenous heat-induced thrombosis (EHIT) after endovenous radiofrequency ablation (RFA). METHODS We retrospectively reviewed the medical records of 82 patients with 97 great saphenous veins undergoing RFA from 2012 to 2014. RESULTS The incidence of EHIT was 10.3%. Class 1, 2, and 3 EHIT was found in 50%, 30%, and 20% of legs, respectively. No class 4 EHIT, deep vein thrombosis, or pulmonary emboli occurred. Univariate analysis revealed that the associated risk factors for EHIT were a vein diameter of >10 mm, operative time of >40 min, and Caprini score of >6. Multivariate analysis revealed that the independent risk factors associated with EHIT were a vein diameter of >10 mm and operative time of >40 min. CONCLUSIONS A vein diameter of >10 mm and operative time of >40 min might be predictive factors for EHIT following RFA.


title: Laparoscopic reduced port surgery for schwannoma of the sigmoid colon: a case report.

text: A 74-year-old woman who developed schwannoma of the sigmoid colon was referred to our hospital for colonography to determine the cause of her stool occult blood. Colonoscopy revealed a submucosal tumor, which measured 3 cm in diameter, in the sigmoid colon. Endoscopic ultrasonography revealed a low echoic, homogeneous and demarcated submucosal tumor that continued into the fourth layer of the colonic wall. Gastrointestinal stromal, myogenic or neurogenic tumor was suspected, and thus, laparoscopic sigmoidectomy was carried out. We used two ports during the operation, a SILS Port in the umbilical region and a 12-mm port in the right lower abdominal wall, and performed sigmoidectomy with D2 lymph node dissection. Histological findings revealed spindle-like tumor cells with multiform nuclei. The tumor was diagnosed by immunostaining as benign schwannoma of the sigmoid colon. The conventional surgical treatment for schwannoma of the digestive tract is partial resection, but if preoperative diagnosis is unknown, radical resection with lymphadenectomy is acceptable for submucosal tumors in the digestive tract. In this case, laparoscopic reduced port surgery using only one or two ports may be more feasible and beneficial with regard to cosmesis and reduced postoperative pain than conventional laparoscopic colectomy.


Covid-19: retired doctors could be asked to return to work, says Hancock.


title: Does the number of veins ligated during microsurgical subinguinal varicocelectomy impact improvement in pain post-surgery?

text: BACKGROUND We examined the impact of the number of veins ligated during varicocelectomy on post-surgical improvement of pain in a group of men presenting with clinical varicocele and pain as an indication for surgery. METHODS This is a retrospective study of patients presenting with clinical left varicocele to the male infertility unit at a teaching hospital in Qatar. Files of all patients who underwent sub-inguinal microsurgical varicocelectomy were retrieved and categorized into three groups indicating the number of spermatic veins ligated during varicocelectomy. The presence of pain was assessed during pre- and post-operation (at 3 and 6 months). Statistical analysis was performed using Kruskal-Wallis test (K) and Chi-square test (C). RESULTS Out of 675 records, 207 (30.7%) patients did left varicocelectomy for pain. Their mean age was 35.3±9.2 years. Pain was assessed in 106/207 (51.2%) patients post operatively, of whom 89 (84%) reported complete resolution of symptoms. This improvement was maintained irrespective of the number of veins ligated during surgery (<5 veins: 90.0%, 5-10 veins: 81.5%, and >10 veins: 85.7%). CONCLUSIONS Microsurgical subinguinal varicocelectomy is a valid treatment method for patients with a symptomatic clinical varicocele. While a significant post-surgical (at 6 months) reduction of pain was detected, the number of veins ligated intraoperatively was not predictive of post-operative improvement of pain in this study population.


title: Coronaviruses fusion with the membrane and entry to the host cell.

text: Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.


title: A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

text: Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 μM BDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. IMPORTANCE Yellow fever is an acute viral hemorrhagic disease which threatens approximately 1 billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than 7 decades, the low vaccination rate fails to prevent outbreaks in at-risk regions. It has been estimated that up to 1.7 million YFV infections occur in Africa each year, resulting in 29,000 to 60,000 deaths. Thus far, there is no specific antiviral treatment for yellow fever. To cope with this medical challenge, we identified a benzodiazepine compound that selectively inhibits YFV by targeting the viral NS4B protein. To our knowledge, this is the first report demonstrating in vivo safety and antiviral efficacy of a YFV NS4B inhibitor in an animal model. We have thus reached a critical milestone toward the development of specific antiviral therapeutics for clinical management of yellow fever.


title: Differential sensitivity of well-differentiated avian respiratory epithelial cells to infection by different strains of infectious bronchitis virus.

text: Infectious bronchitis virus (IBV) is an avian coronavirus affecting the respiratory tract of chickens. To analyze IBV infection of the lower respiratory tract, we applied a technique that uses precision-cut lung slices (PCLSs). This method allows infection of bronchial cells within their natural tissue composition under in vitro conditions. We demonstrate that IBV strains 4/91, Italy02, and QX infect ciliated and mucus-producing cells of the bronchial epithelium, whereas cells of the parabronchial tissue are resistant to infection. This is the first study, using PCLSs of chicken origin, to analyze virus infection. PCLSs should also be a valuable tool for investigation of other respiratory pathogens, such as avian influenza viruses.


title: Venous thromboembolic events in critically ill traumatic brain injury patients.

text: PURPOSE To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit. METHODS A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death. RESULTS Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65). CONCLUSIONS Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.


title: Relationships between hydration biomarkers and total fluid intake in pregnant and lactating women.

text: INTRODUCTION Previous research established significant relationships between total fluid intake (TFI) and urinary biomarkers of the hydration process in free-living males and females; however, the nature of this relationship is not known for pregnant (PREG) and lactating (LACT) women. PURPOSE To determine the relationship between urinary and hematological hydration biomarkers with TFI in PREG and LACT. METHODS Eighteen PREG/LACT (age: 31 ± 3 years, pre-pregnancy BMI: 24.26 ± 5.85 kg m-2) collected 24-h urine samples, recorded TFI, and provided a blood sample at 5 time points (15 ± 2, 26 ± 1, 37 ± 1 weeks gestation, 3 ± 1 and 9 ± 1 weeks postpartum during lactation); 18 pair-matched non-pregnant (NP), non-lactating (NL) women (age: 29 ± 4 years, BMI: 24.1 ± 3.7 kg m-2) provided samples at similar time intervals. Twenty-four-hour urine volume (U VOL), osmolality (U OSM), specific gravity (U SG), and color (U COL) were measured. Hematocrit, serum osmolality (S OSM), and serum total protein (S TP) were measured in blood. RESULTS Significant relationships were present between TFI and urinary biomarkers in all women (P < 0.004); these relationships were not different between PREG and NP, and LACT and NL, except U VOL in PREG (P = 0.0017). No significant relationships between TFI and hematological biomarkers existed (P > 0.05). CONCLUSION Urinary biomarkers of hydration, but not hematological biomarkers, have a strong relationship with TFI in PREG, LACT, NP, and NL women. These data suggest that urinary biomarkers of hydration reflect TFI during pregnancy and breast-feeding.


title: Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?

text: Purpose Increase in FLAIR signal of the fluid within the resection cavity is described as a highly specific and early sign for tumor recurrence in gliomas. The aim of this study was to assess the prognostic value of FLAIR signal increase in partially or completely resected brain metastases. Materials and Methods 209 cases of surgery for brain metastases were assessed. 41 cases with at least two follow-up MRIs were retrospectively included in this study. Quantitative and qualitative assessment of the FLAIR signal intensity of the fluid within the resection cavity was performed in the MRI examination at recurrent disease/last contact and in the previous MRI examination. Results 3 of 6 cases with local tumor recurrence showed a FLAIR signal increase (sensitivity 50.0 %, specificity 100.0 %). In one case, this sign was observed even about 3 months before tumor recurrence. The specificity of FLAIR signal increase for overall tumor recurrence (local and distant) was also 100.0 %, but with a lower sensitivity of 13.0 %. Quantitative analysis showed significant differences for signal intensity of the resection cavity as well as for the change of signal intensity of the resection cavity in cases with or without local tumor recurrence. Conclusion An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases. Key points: · An increase in FLAIR signal intensity of the fluid within the resection cavity is also observed in previously resected brain metastases.. · The pathophysiology of this sign might be due to a cell-proliferative process.. Citation Format · Bette S, Gempt J, Wiestler B et al. Increase of the FLAIR Signal of the Fluid within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?. Fortschr Röntgenstr 2017; 189: 63 - 70.


title: Measuring the success of interventions for caregivers: a focussed systematic review.

text: PURPOSE OF REVIEW The selection and application of outcome measures are fundamental steps in the research process because they inform decisions around intervention efficacy. We aimed to describe the outcomes used in trials of supportive interventions for adult caregivers of people with three exemplar life-limiting conditions: heart failure, dementia or stroke. RECENT FINDINGS We performed a focussed review of 134 published trials that included interventions designed to improve caregivers' health and wellbeing and/or ability to function in their caring role. We extracted and categorized all caregiver outcomes described in the studies. We identified inconsistency in the outcomes measured; frequent use of bespoke and adapted tools (29% of outcomes were bespoke), and a lack of clarity in outcome priorities (the mean number of outcomes per trial was four [range: 1-11]). Outcome scales that purport to measure the psychological impact of the caring role were the most popular tools in all three caregiver groups. SUMMARY Outcomes used in trials related to adult caregivers are characterized by inconsistencies in outcome measure selection and assessment. This heterogeneity complicates comparisons of treatments and attempts to pool data.


title: Percutaneous radiofrequency ablation for pulmonary metastases from esophageal cancer: retrospective evaluation of 21 patients.

text: PURPOSE To evaluate retrospectively outcomes after radiofrequency (RF) ablation for pulmonary metastases from esophageal cancer. MATERIALS AND METHODS This study included 21 consecutive patients who met inclusion criteria (all men; mean age, 66.0 y) and had pulmonary metastases from esophageal cancer. There were 31 tumors (mean size, 1.7 cm) that were treated with 27 planned ablation sessions. At the initial RF ablation sessions, 3 patients had viable extrapulmonary recurrences, and 18 patients had viable recurrences confined to the lung. Primary study endpoints included patient survival and the determination of prognostic factors. Secondary endpoints included local efficacy and safety of the treatment. The log-rank test was used to identify prognostic factors. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. RESULTS Median follow-up duration after the initial RF ablation was 22.4 months (range, 6.2-76.1 mo). Estimated overall survival rates were 85.7% at 1 year, 54.8% at 2 years, and 38.4% at 3 years after the initial RF ablation session. The presence of viable extrapulmonary recurrences at the initial RF ablation session was an unfavorable prognostic factor (P < .001). Local tumor progression was observed in 25.8% (8 of 31) of tumors and occurred 2.6-10.0 months (median, 4.8 mo) after RF ablation. Grade 3 adverse events occurred in 7.4% (2 of 27) of sessions, including pleural effusion requiring chest tube placement and pneumoderma requiring surgical intervention. No grade 4 or greater adverse events occurred. CONCLUSIONS RF ablation is a promising treatment option for patients with pulmonary metastases from esophageal cancer.


title: Holder pasteurization of donated human milk is effective in inactivating SARS-CoV-2.

text: BACKGROUND Provision of pasteurized donor human milk, as a bridge to mother's own milk, is the standard of care for very low-birth-weight infants in hospital. The aim of this research was to confirm that Holder pasteurization (62.5°C for 30 min) would be sufficient to inactivate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in donated human milk samples. METHODS We spiked frozen milk samples from 10 donors to the Rogers Hixon Ontario Human Milk Bank with SARSCoV-2 to achieve a final concentration of 1 × 107 TCID50/mL (50% of the tissue culture infectivity dose per mL). We pasteurized samples using the Holder method or held them at room temperature for 30 minutes and plated serial dilutions on Vero E6 cells for 5 days. We included comparative controls in the study using milk samples from the same donors without addition of virus (pasteurized and unpasteurized) as well as replicates of Vero E6 cells directly inoculated with SARS-CoV-2. We reported cytopathic effects as TCID50/mL. RESULTS We detected no cytopathic activity in any of the SARS-CoV-2-spiked milk samples that had been pasteurized using the Holder method. In the SARSCoV-2-spiked milk samples that were not pasteurized but were kept at room temperature for 30 minutes, we observed a reduction in infectious viral titre of about 1 log. INTERPRETATION Pasteurization of human milk by the Holder method (62.5°C for 30 min) inactivates SARS-CoV-2. Thus, in the event that donated human milk contains SARS-CoV-2 by transmission through the mammary gland or by contamination, this method of pasteurization renders milk safe for consumption and handling by care providers.


title: Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

text: Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis.


title: The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence.

text: BACKGROUND Participation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e., the psychological, physical, and financial burdens) experienced by patients through their participation in a RCT. METHODS We conducted a systematic review of qualitative studies exploring adult patients' experiences with RCT participation. We searched MEDLINE (PubMed), CINAHL, PSYCHINFO, and Embase (search date March 2018) for eligible reports. Qualitative data coding and indexing were assisted by NVivo. The quality of reports was assessed by using the Critical Appraisal Skills Program (CASP) tool. RESULTS We included 45 qualitative studies that involved 1732 RCT participants. Important psychological burdens were identified at every stage of the trial process. Participants reported feeling anxiety and being afraid of "being a 'guinea pig'" and described undergoing randomization and allocation to a placebo as particularly difficult resulting in disappointment, anger, and depression. Patients' follow-up and trial closure were also responsible for a wide range of psychological, physical, and financial burdens. Furthermore, factors related to burdensome impacts and consequences were discerned. These factors involved trial information, poorly organized and too-demanding follow-up, and lack of appropriate management when the patient's participation ended. Trial participation was also associated with beneficial effects such as the satisfaction of feeling "useful," gaining "a sense of control," and receiving special attention. CONCLUSIONS Our finding provides a detailed description of research burden across the whole RCT process. Many of the burdens described could be anticipated, and some avoided in a movement toward minimally disruptive clinical research. Such an approach could improve trial recruitment and retention. REVIEW REGISTRATION PROSPERO CRD42018098994.


title: Exploring the potential of next-generation sequencing in detection of respiratory viruses.

text: Efficient detection of human respiratory viral pathogens is crucial in the management of patients with acute respiratory tract infection. Sequence-independent amplification of nucleic acids combined with next-generation sequencing technology and bioinformatics analyses is a promising strategy for identifying pathogens in clinical and public health settings. It allows the characterization of hundreds of different known pathogens simultaneously and of novel pathogens that elude conventional testing. However, major hurdles for its routine use exist, including cost, turnaround time, and especially sensitivity of the assay, as the detection limit is dependent on viral load, host genetic material, and sequencing depth. To obtain insights into these aspects, we analyzed nasopharyngeal aspirates from a cohort of 81 Thai children with respiratory disease for the presence of respiratory viruses using a sequence-independent next-generation sequencing approach and routinely used diagnostic real-time reverse transcriptase PCR (real-time RT-PCR) assays. With respect to the detection of rhinovirus and human metapneumovirus, the next-generation sequencing approach was at least as sensitive as diagnostic real-time RT-PCR in this small cohort, whereas for bocavirus and enterovirus, next-generation sequencing was less sensitive than real-time RT-PCR. The advantage of the sequencing approach over real-time RT-PCR was the immediate availability of virus-typing information. Considering the development of platforms capable of generating more output data at declining costs, next-generation sequencing remains of interest for future virus diagnosis in clinical and public health settings and certainly as an additional tool when screening results from real-time RT-PCR are negative.


title: Laparoendoscopic single-site surgery for management of ovarian endometriomas.

text: BACKGROUND AND OBJECTIVES To compare our initial experience in laparoscopic surgery for ovarian endometriomas performed through an umbilical incision using a single 3-channel port and flexible laparoscopic instrumentation versus traditional laparoscopy. METHODS This study was conducted in 3 tertiary care referral centers. Since September 2009, we have performed laparoendoscopic single-site surgery in 24 patients diagnosed with ovarian endometriomas. A control group of patients with similar diagnoses who underwent traditional operative laparoscopy during the same period was included (n = 28). In the laparoendoscopic single-site surgery group, a multichannel port was inserted into the peritoneum through a 1.5- to 2.0-cm umbilical incision. RESULTS Patients in the laparoendoscopic single-site surgery group were significantly older (P = .04) and had a higher body mass index (P = .005). Both groups were comparable regarding history of abdominal surgery, lateral pelvic side wall involvement, and cul-de-sac involvement. After we controlled for age and body mass index, the size of the resected endometriomas, duration of surgery, and amount of operative blood loss were comparable in both groups. When required, an additional 5-mm port was inserted in the right or left lower quadrant in the laparoendoscopic single-site surgery group to allow the use of a third instrument for additional tissue retraction or manipulation (10 of 24 patients, 41.6%). However, adhesiolysis was performed more frequently in the conventional laparoscopy group. The duration of hospital stay was <24 hours in both groups. No intraoperative complications were encountered. All incisions healed and were cosmetically satisfactory. CONCLUSION The laparoendoscopic single-site surgery technique is a reasonable initial approach for the treatment of endometriomas. In our experience, an additional side port is usually needed to treat pelvic side wall and cul-de-sac endometriosis that often accompanies endometriomas.


title: Oral chlorhexidine and microbial contamination during endoscopy: possible implications for transgastric surgery. A randomized, clinical trial.

text: BACKGROUND One of the biggest concerns associated with transgastric surgery is contamination and risk of intra-abdominal infection with microbes introduced from the access route. The purpose of this study was to evaluate the effect of oral decontamination with chlorhexidine on microbial contamination of the endoscope. METHODS In a prospective, randomized, single-blinded, clinical trial the effect of chlorhexidine mouth rinse was evaluated. As a surrogate for the risk of intra-abdominal contamination during transgastric surgery, microbial contamination of the endoscope during upper endoscopy was examined. Patients referred to upper endoscopy were assessed for eligibility and randomized to either chlorhexidine or no mouth rinse. Culture samples were collected from gastric aspirates and endoscopes. The primary outcome measure was colony forming units (CFU) in the endoscope samples. Secondary outcome measures were species specific effect of chlorhexidine on micro-organisms with abscess forming capabilities and the effect of proton pump inhibitor (PPI) treatment on CFU. RESULTS Chlorhexidine mouth rinse resulted in a significant reduction of CFU in the endoscope samples (p = 0.001). There was no species specific effect and micro-organisms with abscess forming capabilities were equally present. PPI treatment was associated with significantly higher CFU counts in both the gastric (p = 0.004) and endoscope samples (p = 0.049). CONCLUSIONS Chlorhexidine mouth rinse was effective in reducing microbial contamination of the endoscope, but micro-organisms with abscess forming capabilities were still present. PPI treatment significantly increased CFU and should be discontinued before transgastric surgery.


title: The core content of emergency medical services medicine.

text: On September 23, 2010, the American Board of Medical Specialties (ABMS) approved emergency medical services (EMS) as a subspecialty of emergency medicine. As a result, the American Board of Emergency Medicine (ABEM) is planning to award the first certificates in EMS medicine in the fall of 2013. The purpose of subspecialty certification in EMS, as defined by ABEM, is to standardize physician training and qualifications for EMS practice, to improve patient safety and enhance the quality of emergency medical care provided to patients in the prehospital environment, and to facilitate integration of prehospital patient treatment into the continuum of patient care. In February 2011, ABEM established the EMS Examination Task Force to develop the Core Content of EMS Medicine (Core Content) that would be used to define the subspecialty and from which questions would be written for the examinations, to develop a blueprint for the examinations, and to develop a bank of test questions for use on the examinations. The Core Content defines the training parameters, resources, and knowledge of the treatment of prehospital patients necessary to practice EMS medicine. Additionally, it is intended to inform fellowship directors and candidates for certification of the full range of content that might appear on the examinations. This article describes the development of the Core Content and presents the Core Content in its entirety.


title: Reliability of real-time reverse-transcription PCR in clinical diagnostics: gold standard or substandard?

text: Molecular diagnostics is one of the major growth areas of modern medicine, with real-time PCR established as a qualitative and quantitative technology that is rapid, accurate and sensitive. The sequencing of the human genome, comprehensive genomic, mRNA and miRNA expression profiling of numerous cancer types, the ongoing identification of disease-associated polymorphisms and the expanding availability of genomic sequence information for human pathogens has opened the door to a wide range of translational applications for this technology. Consequently, novel real-time PCR assays have been developed for diagnosis and prognosis, treatment monitoring, transplant biology and pathogen detection, as well as more controversial uses such as lifestyle genotyping. However, this technology is still troubled by significant technical deficiencies. Hence its often-improper use as a clinical tool has important public health implications, most recently demonstrated through its association with the measles, mumps and rubella vaccine/autism controversy. This serves as a timely reminder of the indispensable requirement for careful experimental design, validation and analysis.


title: HELP-VDL: study protocol for a multicentre, open, randomised, controlled clinical trial comparing the use of the head-elevated laryngoscopy position and the use of a videolaryngoscope to facilitate orotracheal intubation in a patient population without predictable difficulty of intubation.

text: INTRODUCTION Tracheal intubation remains an everyday challenge for anaesthesiologists, even in patients without suspected difficult airways. The ideal positioning of the patient's head (flat, raised a few centimetres on a cushion in the sniffing position (SP), or raised to achieve horizontal alignment between the external acoustic meatus and the sternal angle) and the use of videolaryngoscopy remain controversial. This trial aims to compare the efficacy for orotracheal intubation of the SP or the head-elevated laryngoscopy position (HELP), which has been shown to improve laryngeal visualization and the intubation condition particularly in obese patients, in combination with a McGrath Mac videolaryngoscope whose video screen is either on or off (Video or NoVideo). METHODS AND ANALYSIS The HELP-VDL factorial trial is a prospective, randomised, parallel, multicentre, open study of 240 adult patients undergoing tracheal intubation under general anaesthesia. Patients will be allocated into four groups: SP-NoVideo, HELP-NoVideo, SP-Video and HELP-Video. The primary outcome is the proportion of orotracheal intubations that requires the assistance of a nurse anaesthetist. The secondary outcomes include the intubation duration, the first intubation success rate, the quality of visualisation of the glottis, the glottis visualisation score, adjunctive manoeuvres and alternative techniques used, the occurrence of oesophageal intubation, failure of tracheal intubation, the incidence of arterial oxygen desaturation, the perception of a difficult intubation, the score on the Intubation Difficulty Scale, cooperation among the members of the anaesthesia team, the evolution of vital signs and the frequency and severity of intubation complications. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION Ethics approval was obtained from the Ethical Committee Ile de France V (Paris, France). Participant recruitment began on 3 July 2019. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03987009; Pre-results.


title: Human Norovirus Replication in Human Intestinal Enteroids as Model to Evaluate Virus Inactivation.

text: Human noroviruses are a leading cause of epidemic and endemic acute gastroenteritis worldwide and a leading cause of foodborne illness in the United States. Recently, human intestinal enteroids (HIEs) derived from human small intestinal tissue have been shown to support human norovirus replication. We implemented the HIE system in our laboratory and tested the effect of chlorine and alcohols on human norovirus infectivity. Successful replication was observed for 6 norovirus GII genotypes and was dependent on viral load and genotype of the inoculum. GII.4 viruses had higher replication levels than other genotypes. Regardless of concentration or exposure time, alcohols slightly reduced, but did not completely inactivate, human norovirus. In contrast, complete inactivation of the 3 GII.4 viruses occurred at concentrations as low as 50 ppm of chlorine. Taken together, our data confirm the successful replication of human noroviruses in HIEs and their utility as tools to study norovirus inactivation strategies.


title: In vitro blood-perfused bovine liver model: a physiologic model for evaluation of the performance of radiofrequency ablation devices.

text: PURPOSE To describe an in vitro blood-perfused bovine liver model for the testing of radiofrequency (RF) ablation devices and compare the performance of a specific RF ablation device in the model relative to three other biologic models. MATERIALS AND METHODS Fresh bovine livers were used to create three in vitro models: blood-perfused, Krebs-Henseleit (KH) solution-perfused, and nonperfused. The perfused models were connected to a heart-lung machine via the portal vein and perfused with heparinized autologous blood or KH solution under physiologic conditions. Six swine were used as in vivo liver models. A cluster electrode and RF ablation system was operated in impedance mode for 12 minutes in all models. Ablated livers were sectioned, with long- and short-axis measurements of the ablations obtained, and statistical analysis was performed. RESULTS A total of 39, 23, 17, and 12 ablations were performed in 14, 6, 5, and 6 blood-perfused bovine livers, KH solution-perfused bovine livers, nonperfused bovine livers, and in vivo porcine livers, respectively. On cut specimens, the average diameters of ablation zones were 4.00 cm (95% CI, 3.88-4.13) in blood-perfused livers, 4.34 cm (95% CI, 4.14-4.50) in KH solution-perfused livers, 4.67 cm (95% CI, 4.50-4.83) in nonperfused livers, and 3.56 cm (95% CI, 3.26-3.83) in in vivo porcine livers. In all models, the ablation zone diameters were normally distributed. CONCLUSIONS In the in vitro blood-perfused bovine liver model, the size of ablations produced by an RF ablation device are closer in size to those seen in porcine liver in vivo compared with the lesions produced in KH solution-perfused or nonperfused bovine liver.


Covid-19 could widen mental health inequalities for a generation, warns charity.


title: Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial).

text: BACKGROUND For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. METHODS/DESIGN This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥ 18 and ≤ 80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. DISCUSSION This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. TRIAL REGISTRATION Dutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790.


title: Processed electroencephalogram response of patients undergoing carotid endarterectomy: a pilot study.

text: BACKGROUND A risk during carotid endarterectomy (CEA) is cerebral ischemia as a result of clamping of the carotid artery. The Cerebral State Monitor is one of several electroencephalogram monitors that reflects level of consciousness of patients during anesthesia. The monitor reports level of consciousness with the empirical parameter Cerebral State Index (CSI) on a 0-100 scale. In this patient-controlled prospective pilot study, we compared the CSI measured from the surgical and control hemispheres of patients undergoing CEA surgery to determine whether the parameter is affected by presumed changes in cerebral blood flow. METHODS Fifteen consenting CEA patients entered this institutionally approved study. We connected a separate Cerebral State Monitor to the left and right sides of the patient's head and recorded CSI intraoperatively. We compared the control-side data with the surgical-side data. RESULTS Clamping caused the surgical-side CSI to drop below the control-side CSI. Shunt activation caused the CSI to rise above the control. The greatest difference between the surgical-side CSI and control-side CSI occurred at the completion of the CEA procedure. These observed trends were not statistically significant in this pilot project. CONCLUSION Our preliminary results suggest that the CSI, and perhaps other similar indexes, may indicate changes in cerebral blood flow acutely during CEA. Our findings lend promise to a new use for these types of electroencephalogram monitors, which are prevalent in operating rooms today.


title: Hispanic participants in the National Institute on Drug Abuse's Clinical Trials Network: A scoping review of two decades of research.

text: Introduction Hispanics significantly underutilize substance abuse treatment and are at greater risk for poor treatment outcomes and dropout. Two decades of research from the National Drug Abuse Treatment Clinical Trials Network (CTN) offers an opportunity to increase our understanding in how to address the disparities experienced by Hispanics in substance abuse treatment. Methods A scoping review was utilized to determine what has been learned from the CTN about Hispanic populations with substance use disorder. A systematic search was conducted within the CTN Dissemination Library and nine databases. Potentially relevant studies were independently assessed by two reviewers for inclusion. Results Twenty-four studies were included in the review. Results identified issues in measurement, characteristics of Hispanic substance use, effective interventions, and gaps for future research. Characteristics that interfere with treatment participation were also identified including low employment rates, less likelihood of having insurance, lower rates of internet access, and increased travel time to services, as were treatment issues such as high rates of alcohol and tobacco use. Effective interventions were identified; however, the effectiveness of these interventions may be limited to specific factors. Conclusions Despite efforts to improve inclusion of minority populations, Hispanics remain underrepresented in clinical trials. Future research including Hispanic populations should examine measurement equivalence and consider how cultural and historical experiences, as well as patient characteristics, influence utilization of services. Finally, more studies are needed that examine the impact of structural factors that act as barriers to treatment access and engagement and result in significant disparities in treatment outcomes.


Body composition estimated by bioelectrical impedance analyses is diminished by prenatal stress in neonatal lambs and by heat stress in feedlot wethers.


COVID 19 vaccination lessons from Japanese anti-HPV vaccination lobby.


Double lumen endotracheal tube for percutaneous tracheostomy–reply.


Have We Passed the Peak? The COVID-19 Plastic Surgery Webinar Pandemic.


title: Safety model for chest drainage in pandemic by COVID-19.

text: Over one million cases of the SARS-CoV-2 virus have been confirmed worldwide, with the death toll exceeding 50,000 people. An important issue to be addressed concerns the exposure of health professionals to this new virus. The first reports from Wuhan province, China, described infection rates of up to 29% among healthcare professionals before the use of personal protective equipment (PPE) was fully regulated. There are several protocols on the correct use of PPE during aerosol-generating procedures. However, there is no specific guidance on how to proceed in cases of need for chest tubes in patients with positive COVID-19 active air leak. The objective of this work is to assist surgeons of the most diverse specialties during the chest drainage of a patient with COVID-19 and to avoid a risk of contamination to the professional and the environment.


title: Rhinologic Practice Special Considerations During COVID-19: Visit Planning, Personal Protective Equipment, Testing, and Environmental Controls.

text: As rhinologists return to practice amid SARS-CoV-2, special considerations are warranted given the unique features of their subspecialty. Rhinologist manipulation of nasal tissue, proximity, and frequent aerosol-generating procedures (AGPs) create high risk for infection transmission. There are 4 areas of special consideration to mitigate risk: (1) previsit planning for risk stratification/mitigation, (2) appropriate personal protective equipment, (3) preprocedural testing, and (4) environmental controls. During previsit planning, risk factors of the patient and procedures are considered. High-risk AGPs are identified by duration, proximity, manipulation of high-viral load tissue, and use of powered instrumentation. Appropriate personal protective equipment includes selection of respiratory and eye protection. COVID-19 testing can screen for asymptomatic carriers prior to high-risk procedures; however, alternative testing methods are required in rhinologic patients not eligible for nasopharyngeal testing due to nasal obstruction or skull base defects. Last, AGPs in rhinologic practices require considerations of room air handling and environmental controls.


title: Evaluation of pediatric near-infrared cerebral oximeter for cardiac disease.

text: BACKGROUND Cerebral hypoxia-ischemia remains a complication in children with congenital heart disease. Near-infrared spectroscopy can be utilized at the bedside to detect cerebral hypoxia-ischemia. This study aimed to calibrate and validate an advanced technology near-infrared cerebral oximeter for use in children with congenital heart disease. METHODS After institutional review board approval and parental consent, 100 children less than 12 years and less than 40 kg were enrolled. Phase I (calibration) measured arterial and jugular venous saturation (SaO(2), SjO(2)) by co-oximetry simultaneously with device signals to calibrate an algorithm to determine regional cerebral saturation against a weighted average cerebral saturation (0.7 SjO(2) + 0.3 SaO(2)). Phase II (validation) evaluated regional cerebral saturation from the algorithm against the weighted average cerebral saturation by correlation, bias, precision, and A(Root Mean Square) assessed by linear regression and Bland-Altman analysis. RESULTS Of 100 patients, 86 were evaluable consisting of 7 neonates, 44 infants, and 35 children of whom 55% were female, 79% Caucasian, and 41% with cyanotic disease. The SaO(2) and regional cerebral saturation ranged from 34% to 100% and 34% to 91%, respectively. There were no significant differences in subject characteristics between phases. For the entire cohort, A(RMS), bias, precision, and correlation coefficient were 5.4%, 0.5%, 5.39%, and 0.88, respectively. Age, skin color, and hematocrit did not affect these values. CONCLUSIONS This cerebral oximeter accurately measures the absolute value of cerebral saturation in children over a wide range of oxygenation and subject characteristics, offering advantages in assessment of cerebral hypoxia-ischemia in congenital heart disease.


title: A population-based analysis of emergent versus elective paraesophageal hernia repair using the Nationwide Inpatient Sample.

text: BACKGROUND As the life expectancy in the United States continues to increase, more elderly, sometimes frail patients present with sub-acute surgical conditions such as a symptomatic paraesophageal hernia (PEH). While the outcomes of PEH repair have improved largely due to the proliferation of laparoscopic surgery, there is still a defined rate of morbidity and mortality. We sought to characterize the outcomes of both elective and emergent PEH repair using a large population-based data set. METHODS The Nationwide Inpatient Sample was queried for primary ICD-9 codes associated with PEH repair (years 2006-2008). Outcomes were in-hospital mortality and the occurrence of a pre-identified complication. Multivariate analysis was performed to determine the risk factors for complications and mortality following both elective and emergent PEH repair. RESULTS A total of 8,462 records in the data, representing 41,723 patients in the US undergoing PEH repair in the study interval, were identified. Of these procedures, 74.2% was elective and 42.4% was laparoscopic. The overall complication and mortality rates were 20.8 and 1.1%, respectively. Emergent repair was associated with a higher rate of morbidity (33.4 vs. 16.5%, p < 0.001) and mortality (3.2 vs. 0.37%, p < 0.001) than elective repair. Emergent repair patients were more likely to be male, were older, and more likely to be minority. Logistic modeling revealed that younger age, elective case status, and a laparoscopic approach were independently associated with a lower probability of complications and mortality. CONCLUSIONS Patients undergoing emergent PEH repair in the United States tend to be older, more likely a racial minority, and less likely to undergo laparoscopic repair. Elective repair, younger age, and a laparoscopic approach are associated with improved outcomes. Considering all of the above, we recommend that patients consider elective repair with a surgeon experienced in the laparoscopic approach, especially when symptoms related to the hernia are present.


title: Asymptomatic Lymphogranuloma Venereum in Men who Have Sex with Men, United Kingdom.

text: We investigated prevalence of lymphogranuloma venereum (LGV) among men who have sex with men who were tested for chlamydia at 12 clinics in the United Kingdom during 10 weeks in 2012. Of 713 men positive for Chlamydia trachomatis, 66 (9%) had LGV serovars; 15 (27%) of 55 for whom data were available were asymptomatic.


title: Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses.

text: The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas.


El impacto que ha originado la enfermedad por coronavirus 2019 (COVID-19) en diferentes partes del mundo, alcanza en la actualidad 597, 072 personas contagiadas y 27,364 fallecidas según los últimos reportes. En ese contexto, en nuestro país, una zona de relevancia epidemiológica es la amazonia peruana, debido a la distribución de enfermedades endémicas como las enfermedades metaxénicas (Dengue, Malaria entre otras), en donde el problema se incrementa debido a que la infección por COVID-19 puede llevar a falsos positivos en las pruebas de cribado para Dengue. Conllevando de esa forma a un retraso en el diagnóstico de la infección por COVID-19 y una mayor diseminación del virus, debido a que en la mayor parte de los casos de Dengue no se presentan signos de alarma y el tratamiento es ambulatorio. Este artículo busca emitir una opinión sobre la necesidad del abordaje de casos de coinfección entre Dengue y Covid-19 en zonas endémicas.


title: A systematic evaluation of dual functionality of sodium lauryl sulfate as a tablet lubricant and wetting enhancer.

text: Appropriate lubrication is important in tablet manufacturing as it lowers punch sticking propensity and protects tooling by reducing friction between die wall and tablet during tablet manufacturing. Most commercial lubricants negatively impact tabletability and dissolution. A delicate balance is usually attained by trial and error to identify the optimal level of lubricant in a tablet formulation. In this work, we have evaluated the effectiveness of sodium lauryl sulfate (SLS), a surfactant, as a tableting lubricant. If adequate lubrication efficiency is achieved, the use of SLS may be suitable to mitigate problems associated with hydrophobic lubricants. Results show that SLS, when applied in the proper amount to typical pharmaceutical powder mixtures, achieved lubrication efficiency comparable to a grade of magnesium stearate (MgSt) without deteriorating tabletability. Moreover, SLS-containing tablets of celecoxib also exhibited improved in vitro dissolution compared to MgSt-containing tablets. The enhancement in dissolution properties was attributed to the improved wetting by the dissolution medium due to the presence of SLS.


Covid-19: Health needs of sex workers are being sidelined, warn agencies.


Resistance of children to Covid-19. How?


title: Robot-Assisted Thoracoscopic Surgery versus Video-Assisted Thoracoscopic Surgery for Lung Lobectomy: Can a Robotic Approach Improve Short-Term Outcomes and Operative Safety?

text: Background Minimally invasive surgery has been recently recommended for treatment of early-stage non-small cell lung cancer. Despite the recent increase of robotic surgery, the place and potential advantages of the robot in thoracic surgery has not been well defined until now. Methods We reviewed our prospective database for retrospective comparison of our first 28 video-assisted thoracoscopic surgery lobectomies (V group) and our first 28 robotic lobectomies (R group). Results No significant difference was shown in median operative time between the two groups (185 vs. 190 minutes, p = 0.56). Median preincision time was significantly longer in the R group (80 vs. 60 minutes, P < 0.0001). The rate of emergency conversion for uncontrolled bleeding was lower in the R group (one vs. four). Median length of stay was comparable (6 days in the R group vs. 7 days in the V group, p = 0.4) with no significant difference in the rate of postoperative complications (eight Grade I in both groups, four Grade III or IV in the V group vs. six in the R group, according to the Clavien-Dindo classification, p = 0.93). No postoperative cardiac morbidity was observed in the R group. Median drainage time was similar (5 days, p = 0.78), with a rate of prolonged air leak slightly higher in the R group (25 vs. 17.8%, p = 0.74). Conclusion Perioperative outcomes are similar even in the learning period but robotic approach seems to offer more operative safety with fewer conversions for uncontrolled bleeding.


title: Protective effect of sevoflurane preconditioning on ischemia-reperfusion injury in patients undergoing reconstructive plastic surgery with microsurgical flap, a randomized controlled trial.

text: BACKGROUND In many clinical conditions that involve free flaps and tissue transplantations the possibility of minimizing ischemia-reperfusion injury can be a determinant factor for the success of the surgery itself. We hypothesize that preconditioning with sevoflurane is a protective factor against ischemia-reperfusion injury. METHODS In this randomized controlled trial, patients ASA I-II undergoing breast reconstruction with deep inferior epigastric perforator flaps were allocated into two groups and analyzed: group BAL included patients who received balanced anesthesia with sevoflurane for 30 min before removal of the flap and throughout the surgery. The TCI group included patients who received a total intravenous anesthesia with propofol and remifentanil. We evaluated regional tissue oximetry at the end of the surgery and at 4, 12 and 20 h after surgery. Other assessed parameters were: blood lactate clearance, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, creatine phosphokinase. RESULTS In total 54 patients, twenty-seven per group, were analyzed. There was a significant increase of the average value of regional tissue oximetry measured 4 h after surgery in the BAL group compared to the TCI group: BAL: 84.05 % (8.96 SD); TCI : 76.17 % (12.92 SD) (P = 0.03), but not at the other time frames. The creatine phosphokinase value was significantly lower in the BAL group at the end of surgery, but not at the other time-frames. There were no significant differences in blood levels of other markers. CONCLUSIONS From our results, the positive preconditioning impact of sevoflurane on ischemia-reperfusion injury in patients undergoing free flap surgery is expressed in the early postoperative hours, but it does not persist in the long-term. TRIAL REGISTRATION ClinicalTrial.gov identifier: NCT01905501 . Registered July 18, 2013.


title: Quantitating T cell cross-reactivity for unrelated peptide antigens.

text: Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides ( approximately 1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.


title: High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

text: We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.


title: Adjuvant 17-hydroxyprogesterone caproate in women with history-indicated cerclage: A systematic review and meta-analysis.

text: INTRODUCTION The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent spontaneous preterm birth in women with a prophylactic cerclage. MATERIAL AND METHODS Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before June 2018. Keywords included "preterm birth", "prophylactic cerclage", "history-indicated cerclage", "pregnancy" and "17-hydroxyprogesterone caproate". Studies comparing history-indicated cerclage alone with cerclage+17-OHPC were included. The primary outcome measure was preterm birth at <24 weeks of gestation. Secondary outcome measures include preterm birth at <28 weeks, <32 weeks and <37 weeks of gestation, respiratory distress syndrome, necrotizing enterocolitis, fetal birthweight, neonatal intensive care unit stay, mean gestational age at delivery, fetal/neonatal death, neurological morbidity (intraventricular hemorrhage plus periventricular leukomalacia), neonatal sepsis and a composite of severe neonatal morbidity. Severe neonatal morbidity was defined as a composite measure of periventricular leukomalacia, intraventricular hemorrhage (grades III and IV), necrotizing enterocolitis or respiratory distress syndrome. Meta-analysis was performed using the random-effects model of DerSimonian and Laird. Risk of bias and quality assessment were performed using the ROBINS-I and GRADE tools, respectively. PROSPERO Registration Number: CRD42018094559. RESULTS Five studies met the inclusion criteria and were included in the final analysis. Of the 546 women, 357 (75%) received history-indicated cerclage alone and 189 (35%) received adjuvant 17-OHPC. The composite endpoint, severe neonatal morbidity, was present in 84 of 1515 neonates. Though there was a trend toward a reduced risk of preterm birth, the summary estimate of effect was not statistically significant when comparing cerclage alone with cerclage+17-OHPC at <24 weeks (relative risk [RR] .86, 95% confidence interval [CI] .45-1.65). Similarly, we found no differences in preterm birth at <37 weeks (RR .90, 95% CI .70-1.17) and <28 weeks (RR .85, 95% CI .54-1.32) when comparing cerclage alone with cerclage+17-OHPC. There were no differences in fetal birthweight, respiratory distress syndrome or necrotizing enterocolitis comparing cerclage alone with cerclage+17-OHPC. CONCLUSIONS Intramuscular 17-OHPC in combination with prophylactic cerclage in women with prior preterm birth had no synergistic effect in reducing spontaneous recurrent preterm birth or improving perinatal outcomes.


title: The murine coronavirus nucleocapsid gene is a determinant of virulence.

text: The murine coronavirus, mouse hepatitis virus (MHV) strain A59, causes acute encephalitis and chronic demyelinating disease as well as hepatitis in mice. The JHM strain (also called MHV-4 or JHM.SD) causes fatal encephalitis and only minimal hepatitis. Previous analysis of chimeric recombinant MHVs in which the spike gene, encoding the protein that mediates viral entry and cell-to-cell fusion, was exchanged between JHM and A59 showed that the spike plays a major role in determining organ tropism and neurovirulence but that other genes also play important roles in pathogenic outcome. Here, we have investigated the role of the nucleocapsid protein in MHV-induced disease. The multifunctional nucleocapsid protein is complexed with the genomic RNA, interacts with the viral membrane protein during virion assembly, and plays an import role in enhancing the efficiency of transcription. A pair of chimeric recombinant viruses in which the nucleocapsid gene was exchanged between JHM and A59 was selected and compared to wild-type parental strains in terms of virulence. Importantly, expression of the JHM nucleocapsid in the context of the A59 genome conferred increased mortality and spread of viral antigen in the mouse central nervous system compared to the parental A59 strain, while having little effect on the induction of hepatitis. While the JHM nucleocapsid did not appear to enhance neuron-to-neuron spread in primary neuronal cultures, the increased neurovirulence it conferred may be due in part to the induction of a less robust T-cell response than that induced by strain A59.


title: Sodium intake and blood pressure in children and adolescents: protocol for a systematic review and meta-analysis.

text: INTRODUCTION Hypertension is a major risk factor for cardiovascular diseases. In adults, high sodium intake is associated with elevated blood pressure. In children, experimental studies have shown that reducing sodium intake can reduce blood pressure. However, their external validity is limited, notably because the sodium reduction was substantial and not applicable in a real-life setting. Observational studies, on the other hand, allow assess the association between blood pressure and sodium intake across usual levels of consumption. There is also evidence that the association differs between subgroups of children according to age and body weight. Our objective is to conduct a systematic review and meta-analysis of experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents and to assess whether the association differs according to age and body weight. METHODS AND ANALYSIS A systematic search of the MEDLINE, EMBASE, CINAHL and CENTRAL databases will be conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age will be included. The exposure will be dietary sodium intake, estimated using different methods including urinary sodium excretion. The outcomes will be systolic and diastolic blood pressure, elevated blood pressure and hypertension. If appropriate, meta-analyses will be performed by pooling data across all studies together and separately for experimental and observational studies. Subgroup meta-analyses by age and body weight will be also conducted. Moreover, separate meta-analyses for different sodium intake levels will be conducted to investigate the dose-response relationship. ETHICS AND DISSEMINATION This systematic review and meta-analysis will be published in a peer-reviewed journal. A report will be prepared for national authorities and other stakeholders in the domains of nutrition, public health, and child health in Switzerland. TRIAL REGISTRATION NUMBER CRD42016038245.


SLE patients are not immune to covid-19: importance of sending the right message across.


House Calls for Stem Cell Transplants During the COVID-19 Pandemic.


title: Changes in causes of acute gastroenteritis in the United Kingdom over 15 years: microbiologic findings from 2 prospective, population-based studies of infectious intestinal disease.

text: BACKGROUND Large-scale, prospective studies of infectious intestinal disease (IID) in developed countries are uncommon. Two studies of IID incidence and etiology have been conducted in the United Kingdom: the Infectious Intestinal Disease Study in England (IID1) in 1993-1996 and the Second Study of Infectious Intestinal Disease in the Community (IID2) in 2008-2009. We examined changes in etiology and diagnostic yield of IID cases over 15 years. METHODS Fecal samples submitted by IID cases were examined for a range of bacterial, viral, and protozoal pathogens using traditional and molecular microbiological methods. We calculated the percentage of specimens positive for each organism based on traditional methods and on traditional and molecular methods combined. We compared the distributions of organisms in the 2 studies. RESULTS For pathogens investigated in both studies, 40% of fecal samples submitted by cases in IID2 were positive compared with 28% in IID1. Viruses were most frequent among community cases in IID2. Campylobacter was the most common bacterial pathogen among cases presenting to healthcare. Major differences between the 2 studies were increases in the detection of norovirus and sapovirus and a decline Salmonella. CONCLUSIONS Most fecal specimens were negative for the pathogens tested in both studies, so new strategies are needed to close the diagnostic gap. Among known pathogens, effective control of norovirus, rotavirus, and Campylobacter remain high priorities. The reduction in nontyphoidal salmonellosis demonstrates the success of Europe-wide control strategies, notably an industry-led Salmonella control program in poultry in the United Kingdom.


title: Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

text: BACKGROUND Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.


title: Technology-driven diagnostics: From smart doctor to smartphone.

text: This review explores recent innovations in four seemingly unrelated areas of medical diagnostics, which, when used concurrently, promise to revolutionize the future of medicine. Novel microfluidics and microelectronics, combined with smartphones, allow individuals to test themselves at anytime and anywhere, thus providing instant health information. An emerging development is the availability of genomic testing directly to consumers for assessing disease predisposition. Some organizations have opened diagnostic laboratories in pharmacies and other public outlets, are encouraging consumers to test themselves, and claim that by doing so consumers will be empowered to diagnose the early disease that could be effectively treated or prevented. Another recent development is the initiation of large studies that aim to better understand wellness and disease processes, through the frequent and sometimes continuous monitoring of hundreds or thousands of parameters. These are then analyzed by health coaches who advise participants on follow-up steps to correct the abnormalities and return to wellness. A number of these approaches have now entered the health market and the services can be purchased. It is highly likely that further technological innovations will contribute to the popularity of these approaches among millions of health-conscious consumers. However, the evidence for the effectiveness of these strategies to prevent or detect early disease, or to promote wellness, does not yet exist. We here analyze the perceived benefits and (neglected) harms of these approaches, in an effort to balance the optimism about their utility, until the evidence for their benefit is clearly demonstrated.


title: Clinical review: Goal-directed therapy-what is the evidence in surgical patients? The effect on different risk groups.

text: Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery. By augmenting oxygen delivery index (DO2I) with a combination of intravenous fluids and inotropes (goal directed therapy (GDT)), postoperative mortality and morbidity of high-risk patients may be reduced. However, although most studies suggest that GDT may improve outcome in high-risk surgical patients, it is still not widely practiced. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct. We performed a systematic search of Medline, Embase and CENTRAL databases for randomized controlled trials (RCTs) and reviews of GDT in surgical patients. To minimize heterogeneity we excluded studies involving cardiac, trauma, and paediatric surgery. Extremely high risk, high risk and intermediate risks of mortality were defined as >20%, 5 to 20% and <5% mortality rates in the control arms of the trials, respectively. Meta analyses were performed and Forest plots drawn using RevMan software. Data are presented as odd ratios (OR; 95% confidence intervals (CI), and P-values). A total of 32 RCTs including 2,808 patients were reviewed. All studies reported mortality. Five studies (including 300 patients) were excluded from assessment of complication rates as the number of patients with complications was not reported. The mortality benefit of GDT was confined to the extremely high-risk group (OR = 0.20, 95% CI 0.09 to 0.41; P < 0.0001). Complication rates were reduced in all subgroups (OR = 0.45, 95% CI 0.34 to 0.60; P < 0.00001). The morbidity benefit was greatest amongst patients in the extremely high-risk subgroup (OR = 0.27, 95% CI 0.15 to 0.51; P < 0.0001), followed by the intermediate risk subgroup (OR = 0.43, 95% CI 0.27 to 0.67; P = 0.0002), and the high-risk subgroup (OR 0.56, 95% CI 0.36 to 0.89; P = 0.01). Despite heterogeneity in trial quality and design, we found GDT to be beneficial in all high-risk patients undergoing major surgery. The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death. The reduction of complication rates was seen across all subgroups of GDT patients.


title: The safety and effectiveness of the Woven EndoBridge (WEB) system for the treatment of wide-necked bifurcation aneurysms: final 12-month results of the pivotal WEB Intrasaccular Therapy (WEB-IT) Study.

text: INTRODUCTION The Woven EndoBridge Intrasaccular Therapy (WEB-IT) Study is a pivotal, prospective, single-arm, investigational device exemption study designed to evaluate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. METHODS One-hundred and fifty patients with wide-neck bifurcation aneurysms were enrolled at 21 US and six international centers. Angiograms from the index procedure, and 6-month and 1-year follow-up visits were all reviewed by a core laboratory. All adverse events were reviewed and adjudicated by a clinical events adjudicator. A data monitoring committee provided oversight during the trial to ensure subject safety. RESULTS One-hundred and forty-eight patients received the WEB implant. One (0.7%) primary safety event occurred during the study-a delayed ipsilateral parenchymal hemorrhage-on postoperative day 22. No primary safety events occurred after 30 days through 1 year. At the 12-month angiographic follow-up, 77/143 patients (53.8%) had complete aneurysm occlusion. Adequate occlusion was achieved in 121/143 (84.6%) subjects. CONCLUSIONS The prespecified safety and effectiveness endpoints for the aneurysms studied in the WEB-IT trial were met. The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer. TRIAL REGISTRATION NUMBER NCT02191618.


title: Single incision versus conventional laparoscopic resection in gastrointestinal stromal tumors: a retrospective cohort analysis at a single tertiary care center.

text: BACKGROUND Single-incision laparoscopic surgery (SILS), an advanced form of minimally invasive surgery, has recently been used for surgical management of gastrointestinal stromal tumors (GIST). The literature comparing SILS to conventional laparoscopic surgery for treatment of this disease is limited. This study aimed to evaluate the feasibility and effectiveness of SILS compared with conventional laparoscopic resection for GIST. METHODS A retrospective case-cohort study compared the benefits and outcomes of SILS and conventional laparoscopic partial gastrectomy for GIST. Between April 2008 and December 2012, 39 patients underwent laparoscopic gastrectomy for gastric stromal tumors in our department. All operations were performed by a single experienced surgeon. The medical records of these patients were reviewed retrospectively with regard to tumor size, operating time, and other clinical features. RESULTS SILS resection was performed on 19 patients, whereas 20 patients had conventional laparoscopic resection. Compared with the conventional laparoscopic group, the operative time for the SILS group was shorter, but the time for recovery of gastrointestinal function and postoperative hospital stay for the SILS group was similar to that of the conventional laparoscopic group. No intraoperative or postoperative complications were recorded in either group. CONCLUSION Compared with the conventional laparoscopic procedure, SILS in gastric stromal tumors is as feasible and safe when performed by experienced surgeons.


title: Outcome analysis of laparoscopic incisional hernia repair and risk factors for hernia recurrence in liver transplant patients.

text: INTRODUCTION Incisional hernia is a common complication after liver transplantation (LT). Immunosuppression, obesity, and use of steroids are known risk factors. The purpose of the retrospective study was to summarize and evaluate experiences and results of laparoscopic intraperitoneal onlay mesh (IPOM) hernia repair. METHODS We reviewed our liver transplant patients over a seven-yr period with laparoscopic incisional hernia repair (LIHR) to direct our attention on risk factors for hernia recurrence after hernia repair. RESULTS Fifty-four patients after LT with incisional hernia were treated with laparoscopic repair, 42 male and 12 female patients of overall mean age of 58 ± 9 yr and body mass index (BMI) of 25 ± 4 kg/m(2) . A total of 755 LTs were performed at our institution in this time period, resulting in 7.15% of patients undergoing laparoscopic hernia repair. The mean postoperative hospital stay after was nine d. During the follow-up, nine recurrent hernias were noted (17%). BMI (p = 0.001) and sirolimus as immunosuppressive therapy were significantly associated with hernia recurrence (p = 0.014). CONCLUSION LIHR is a safe and feasible method to treat hernias after LT. BMI and sirolimus as immunosuppressive therapy are risk factors for recurrence of hernia after laparoscopic hernia repair.


title: Intravenous thrombolysis and platelet count.

text: OBJECTIVE To study the effect of platelet count (PC) on bleeding risk and outcome in stroke patients treated with IV thrombolysis (IVT) and to explore whether withholding IVT in PC < 100 × 109/L is supported. METHODS In this prospective multicenter, IVT register-based study, we compared PC with symptomatic intracranial hemorrhage (sICH; Second European-Australasian Acute Stroke Study [ECASS II] criteria), poor outcome (modified Rankin Scale score 3-6), and mortality at 3 months. PC was used as a continuous and categorical variable distinguishing thrombocytopenia (<150 × 109/L), thrombocytosis (>450 × 109/L), and normal PC (150-450 × 109/L [reference group]). Moreover, PC < 100 × 109/L was compared to PC ≥ 100 × 109/L. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from the logistic regression models were calculated. RESULTS Among 7,533 IVT-treated stroke patients, 6,830 (90.7%) had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had thrombocytosis. Decreasing PC (every 10 × 109/L) was associated with increasing risk of sICH (ORadjusted 1.03, 95% CI 1.02-1.05) but decreasing risk of poor outcome (ORadjusted 0.99, 95% CI 0.98-0.99) and mortality (ORadjusted 0.98, 95% CI 0.98-0.99). The risk of sICH was higher in patients with thrombocytopenic than in patients with normal PC (ORadjusted 1.73, 95% CI 1.24-2.43). However, the risk of poor outcome (ORadjusted 0.89, 95% CI 0.39-1.97) and mortality (ORadjusted 1.09, 95% CI 0.83-1.44) did not differ significantly. Thrombocytosis was associated with mortality (ORadjusted 2.02, 95% CI 1.21-3.37). Forty-four (0.3%) patients had PC < 100 × 109/L. Their risks of sICH (ORunadjusted 1.56, 95% CI 0.48-5.07), poor outcome (ORadjusted 1.63, 95% CI 0.82-3.24), and mortality (ORadjusted 1.38, 95% CI 0.64-2.98) did not differ significantly from those of patients with PC ≥ 100 × 109/L. CONCLUSION Lower PC was associated with increased risk of sICH, while higher PC indicated increased mortality. Our data suggest that PC modifies outcome and complications in individual patients, while withholding IVT in all patients with PC < 100 × 109/L is challenged.


title: Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots.

text: A pseudoknot forms in an RNA when nucleotides in a loop pair with a region outside the helices that close the loop. Pseudoknots occur relatively rarely in RNA but are highly overrepresented in functionally critical motifs in large catalytic RNAs, in riboswitches, and in regulatory elements of viruses. Pseudoknots are usually excluded from RNA structure prediction algorithms. When included, these pairings are difficult to model accurately, especially in large RNAs, because allowing this structure dramatically increases the number of possible incorrect folds and because it is difficult to search the fold space for an optimal structure. We have developed a concise secondary structure modeling approach that combines SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) experimental chemical probing information and a simple, but robust, energy model for the entropic cost of single pseudoknot formation. Structures are predicted with iterative refinement, using a dynamic programming algorithm. This melded experimental and thermodynamic energy function predicted the secondary structures and the pseudoknots for a set of 21 challenging RNAs of known structure ranging in size from 34 to 530 nt. On average, 93% of known base pairs were predicted, and all pseudoknots in well-folded RNAs were identified.


title: Onyx Embolization for Tentorial Dural Arteriovenous Fistula with Pial Arterial Supply: Case Series and Analysis of Complications.

text: OBJECTIVE We describe treatment with Onyx embolization in a series of cases of tentorial dural arteriovenous fistula (DAVF) with pial arterial supply. The aim of this study was to analyze the cause of intraoperative hemorrhage and to explore therapeutic strategies. METHODS Retrospective review was performed of 53 consecutive patients with DAVF treated by Onyx embolization between February 2009 and December 2014. Tentorial DAVF with pial arterial supply was diagnosed in 6 patients (2 women and 4 men; mean age, 47.3 years ± 10.2), and transarterial Onyx embolization was performed in these patients. Fisher exact test was used to analyze differences of incidence of procedure-related complications. RESULTS Intraoperative hemorrhage occurred in 2 of 6 patients with pial arterial supply. One patient died as a result of hemorrhage, and the other patient survived after craniotomy. The incidence of complications for these 6 patients (2 of 6; 33.3%) was significantly higher (P = 0.0309) compared with patients with DAVF without pial arterial supply (1 of 47; 2.1%). CONCLUSIONS Pial arterial supply may be a risk factor for intraoperative hemorrhage during transarterial embolization of DAVF through dural feeders. Identification of pial feeders and early superselective occlusion of such feeders are important for safe management.


title: Robot-assisted laparoscopic hepaticojejunostomy for advanced malignant biliary obstruction.

text: INTRODUCTION To report our experience in palliative hepaticojejunostomy for advanced malignant biliary obstruction by means of robotic approach METHODS Robot-assisted laparoscopic hepaticojejunostomy for advanced malignant biliary obstruction was performed in nine patients from May 2009 to April 2014. RESULTS During the study period, robotic hepaticojejunostomy for advanced malignant biliary obstruction was completed successfully in nine patients. Roux-en-Y hepaticojejunostomy and double (hepaticojejunostomy, and gastrojejunostomy) bypass were performed in five and four patients, respectively. The mean operating time was 212.8 minutes. The mean blood loss was 38.7 mL. The overall complication rate was 22.2%. Bile leak complication occurred in one patient only. There was no procedure-related mortality. The mean postoperative hospital stay was 13.3 days. Five patients received palliative systemic chemotherapy after bypass surgery. The mean survival time was 11.1 months. During follow up, only three patients with cholangiocarcinoma had recurrent biliary obstruction after end-to-side hepaticojejunostomy due to tumor progression, and needed percutaneous transhepatic biliary drainage. Among these nine patients, there were a total of eight episodes of readmission in four patients due to tumor-related symptoms or complications. CONCLUSIONS Robot-assisted laparoscopic hepaticojejunostomy for advanced malignant biliary obstruction had a low complication rate and was associated with an improved quality of life.


title: Evaluation of the Angiographic Grading Scale in Aneurysms Treated with the WEB Device in 80 Rabbits: Correlation with Histologic Evaluation.

text: BACKGROUND AND PURPOSE The WEB Occlusion Score has been proposed to assess angiographic outcomes for intracranial aneurysms treated with the Woven EndoBridge (WEB) device. Using a large series of experimental aneurysms treated with the WEB, we had the following objectives: 1) to compare angiographic outcomes as measured by the WEB Occlusion Scale with histologic results, and 2) to assess interobserver and intraobserver agreement of the WEB Occlusion Scale. MATERIALS AND METHODS Intracranial aneurysms were created in 80 rabbits and treated with WEB devices. Animals were sacrificed at last follow-up for histologic evaluation. DSA was performed just after the deployment of the device and at follow-up. Four investigators independently and retrospectively graded the DSA twice according to the WEB Occlusion Scale. One histopathologist blinded to the angiographic results graded the occlusion according to a 4-point scale patterned on the WEB Occlusion Scale. Intra- and interobserver agreement were evaluated for DSA. Follow-up angiographic grading and histologic reference were compared to determine the WEB Occlusion Scale accuracy for complete (with or without recess filling) versus incomplete occlusion and adequate (complete occlusion or neck remnant) versus inadequate occlusion. RESULTS Inter- and intraobserver weighted κ for the angiographic WEB Occlusion Scale were, respectively, 0.76 and 0.76, indicating substantial agreement. The sensitivity and specificity of the WEB Occlusion Scale for complete occlusion at follow-up compared with the histologic reference standard were, respectively, 75% and 83.3%, with an overall accuracy of 80%. Similarly, for adequate occlusion at follow-up, sensitivity was 97.7%, specificity was 64.9%, and overall accuracy was 82.5%. CONCLUSIONS The WEB Occlusion Scale appears to be consistent, reliable, and accurate compared with a histologic reference standard.


title: Meeting report VLPNPV: Sessions 1 and 2: Plenary.

text: Following the highly successful inaugural meeting in 2012, the second installment of Virus-Like Particles and Nano-Particle Vaccines (VLPNPV), proved to be a worthy follow-up in an outstanding conference series. VLPNPV is a forum for academics and industry to address one of the major areas of need in biomedical sciences, the development of novel prophylactic and therapeutic vaccines. The conference was opened by Professor Marianne Manchester of the University of California, San Diego who pointed to the significance of the site chosen for the conference, the Salk Institute. Founded by Jonas Salk, the Salk Institute for Biological Studies is a non-profit, independent research institute with focuses in molecular biology and genetics, neurosciences, and plant biology. This diversity in research themes reflects the wishes of the institute's founder who saw value in using interdisciplinary approaches to understanding the basic principles in life, aimed at generating new therapies and treatments for human disease. Likewise, interdisciplinarity was reflected in the main themes of the meeting, which also highlight some of the potential advantages of virus-like particle (VLP) and nanoparticle vaccines, including novel formulations/adjuvanting effects, structurally accurate/designed antigens, production systems and capacity, and tailoring the immune response. These themes were covered by the 2 plenary sessions that opened the conference and are described in this report.


title: Economic modeling of new stent platforms to evaluate cost effectiveness: analysis of the TAXUS Liberté versus TAXUS express stents.

text: BACKGROUND With the changing health care environment, cost effectiveness is an important adjunct to clinical investigation when assessing new medical devices. This study presents an economic model to evaluate cost effectiveness of coronary stents. METHODS Markov modeling was developed comparing total costs (Medicare payer perspective) between TAXUS Liberté and TAXUS Express based on 3-year clinical outcomes from the TAXUS ATLAS Small Vessel and Long Lesion trials. RESULTS The TAXUS Liberté 2.25-mm stent provided cost savings relative to TAXUS Express from a payer perspective ($17,605 vs. $20,281), driven by reduced target vessel revascularization (0.16 events/patient vs. 0.33 events/patient). In probabilistic sensitivity analyses, TAXUS Liberté was less costly with fewer major adverse cardiac events in over 99% of parameter sets. The TAXUS Liberté Long (38 mm) stent was cost neutral relative to TAXUS Express from a payer perspective ($18,545 vs. $18,551) with fewer myocardial infarctions and cardiac deaths. Accounting for angiography-driven revascularizations, TAXUS Liberté 2.25 mm still provided cost savings relative to TAXUS Express ($16,822 vs. $19,139), although TAXUS Liberté Long was more expensive than TAXUS Express ($17,886 vs. $17,652). From a hospital perspective, TAXUS Liberté Long provided cost savings up to a price premium of $671/stent, driven by fewer stents employed per patient. CONCLUSIONS This analysis confirms the utility of economic modeling in assessing new stent platforms. TAXUS Liberté 2.25 mm is economically dominant relative to TAXUS Express when treating small vessels. TAXUS Liberté Long is cost neutral to modestly more costly than TAXUS Express 2.25 mm from a payer perspective.


title: Standard versus hypofractionated intensity-modulated radiotherapy for prostate cancer: assessing the impact on dose modulation and normal tissue effects when using patient-specific cancer biology.

text: Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 16.3% (p-value:0.01) and 16.0% (p-value:0.04) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 37.4% (p-value:<0.01) and 46.8% (p-value:0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.