title: Feasibility of incremental laparoscopic inguinal hernia repair development in China: an 11-year experience.

text: BACKGROUND Our objective was to investigate the feasibility of laparoscopic inguinal hernia repair during its developmental phases in China. STUDY DESIGN The clinical data of 2,056 patients (2,473 hernias) who underwent laparoscopic inguinal hernia repair at Shanghai Minimally Invasive Surgery Center between January 2001 and December 2011 were analyzed retrospectively. The operation priority was used to divide the patients into 7 groups for analysis of the learning curve. RESULTS There were 1,005 transabdominal preperitoneal patch plastic repairs (TAPP), 1,458 total extraperitoneal repairs (TEP), and 10 intraperitoneal onlay mesh repairs performed on 874, 1,175, and 7 patients, respectively. Median follow-up period was 60 months. The operation time and postoperative hospital stay for TEP were considerably shorter than those for TAPP. The complication rate for TEP, especially seroma, was considerably lower. Transabdominal preperitoneal patch plastic repair was performed in 81.4% of the recurrent inguinal hernias. Seven patients underwent unilateral intraperitoneal onlay mesh repair and 3 others underwent unilateral intraperitoneal onlay mesh repair and TAPP on the opposite. Most of patients with grade I and II hernias underwent TEP. The learning curve has demonstrated that more obstacles occurred in the earlier phase of the laparoscopic inguinal hernia repair training, supported by findings such as fewer cases performed annually, longer operation time, and higher incidence of complications and recurrence. These findings have improved as experience is accumulated through more operations. In addition, the ratios of TEP to TAPP and mesh nonfixation to fixation also evolved throughout the course of the study. CONCLUSIONS Laparoscopic inguinal hernia repair is a feasible technique that can be popularized in China.


Reply to Wachholz et al.


Patient-Driven Discontinuation of Dupilumab During the COVID-19 Pandemic in Two Academic Hospital Clinics at the University of Toronto.


Understanding the enemy.


Scientists put survivors' blood plasma to the test.


title: Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter.

text: BACKGROUND AND PURPOSE Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials. METHODS A total of 121 volunteers aged ≥35 years with cardiovascular risk factors and MRI-confirmed WMLs were randomized to receive 200 mg mixed tocotrienols or placebo twice a day for 2 years. The WML volumes were measured from MRI images taken at baseline, 1 year, and 2 years using a validated software and were compared. Fasting blood samples were collected for full blood chemistry investigation. RESULTS According to per-protocol (88 volunteers) and intention-to-treat (121 volunteers) analyses, the mean WML volume of the placebo group increased after 2 years, whereas that of the tocotrienol-supplemented group remained essentially unchanged. The mean WML volume change between the 2 groups was not significantly different (P=0.150) at the end of 1 year but was significant at the end of 2 years for both per-protocol and intention-to-treat analyses (P=0.019 and P=0.018). No significant difference was observed in the blood chemistry parameters between the 2 groups. CONCLUSIONS Mixed tocotrienols were found to attenuate the progression of WMLs. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00753532.


title: Comparison of liver SUV using unenhanced CT versus contrast-enhanced CT for attenuation correction in (18)F-FDG PET/CT.

text: AIM The aim of the study was to compare standardized uptake values (SUVs) in liver tissue obtained using whole-body unenhanced low-dose computed tomography (CT) with those obtained using contrast-enhanced high-dose CT for PET attenuation correction in PET/CT scanning. MATERIALS AND METHODS Ten patients scheduled for (18)F-FDG PET and contrast-enhanced CT of the abdomen were included in this study. PET data were corrected for attenuation using both unenhanced low-dose CT images and contrast-enhanced high-dose CT images. Differences in SUV(mean) and SUV(max) were compared in three liver regions. RESULTS The average SUV(mean) and SUV(max) of all regions were 2.43 and 2.91 g/cm in the unenhanced data set and 2.53 and 3.17 g/cm in the enhanced data set, respectively. CONCLUSION SUV(mean) and SUV(max) were significantly elevated in liver tissue when using PET images corrected for attenuation with contrast-enhanced high-dose CT compared with PET images corrected with unenhanced low-dose CT. Although the differences may not be relevant in daily clinical practice, unenhanced and contrast-enhanced CT should not be selected randomly for attenuation correction if exact quantitative results are required.


title: Angioarchitectural Risk Factors for Hemorrhage and Clinical Long-Term Outcome in Pediatric Patients with Cerebral Arteriovenous Malformations.

text: BACKGROUND Intracranial arteriovenous malformation (AVM) in children is a rare diagnosis. Little is known about factors determining AVM rupture and appropriate treatment strategies to prevent hemorrhage and associated disability. Available data suggest that children are subject to an increased risk for AVM rupture compared with adults. METHODS In 46 pediatric patients with AVM, demographic factors, clinical presentation, angioarchitectural features, and treatment regimens as well as clinical and radiologic outcomes were retrospectively analyzed. First-line treatment option was microsurgical resection of the disease, with or without preoperative embolization. RESULTS Twenty-four boys (52.2%) and 22 girls (47.8%) with a mean age on admission of 12.4 years (4-18 years) were included. Mean follow-up was 4 years (median, 1.5; range, 0.1-16.4). Thirty-one children presented with intracerebral hemorrhage (67.4%). Small AVMs (<3 cm) ruptured in 83.3% (n = 25) and were shown to be more prone to hemorrhage than larger ones (P < 0.01). Small AVM size (P < 0.01; odds ratio [OR], 0.12; 95% confidence interval [CI] 0.02-0.59) and exclusive deep venous drainage (P < 0.01; OR, 29.74; 95% CI, 2.45-4445.34) were independent risk factors for hemorrhage in the presented cohort. Good long-term outcome was associated with a high score on the Glasgow Coma Scale on admittance (P < 0.05; OR, 0.148; 95% CI, 0.03-0.73). CONCLUSIONS Two-thirds of children with AVM are admitted with intracerebral hemorrhage. Microsurgical resection was successful as confirmed by radiologic studies in 95%, and 79.5% of patients presented in a good clinical condition on follow-up (modified Rankin Scale 0 or 1). Microsurgical treatment is recommended if the lesion is accessible and angioarchitectural risk factors favor definitive treatment.


title: Rescue strategies for refractory hypoxemia: a critical appraisal.

text: Mechanical ventilation is the most important aspect of supportive care of patients with severe acute respiratory failure. Most research directed to improving the prognosis of these patients has focused on improving support of the injured lung. In this report, current knowledge on innovative ways to manage refractory hypoxemia and ventilation without further damaging the injured lung is briefly discussed.


title: Reasons and outcomes of laparoscopic revisional surgery after laparoscopic adjustable gastric banding for morbid obesity.

text: BACKGROUND Laparoscopic adjustable gastric banding (LAGB) is a purely restrictive procedure that has been proved to be an effective tool in achieving weight loss. The low operative morbidity and reversibility are often seen as advantages of this procedure compared with other bariatric approaches. We have attempted to define the reasons for revisional surgery after LAGB and the outcomes. METHODS A retrospective review of a prospectively maintained database was performed from February 2001 to October 2008 at a center of excellence after institutional review board approval. The patients who had undergone revisional surgery after primary LAGB were evaluated. RESULTS Of 343 patients who had undergone primary LAGB, 60 subsequently underwent a revisional procedure. In addition, 28 revisional procedures were performed on patients who had undergone primary LAGB at an outside institution. These procedures included 39 (44.3%) band removals alone, 12 (13.6%) band removals with conversion to sleeve gastrectomy, 13 (14.8%) band removals with conversion to Roux-en-Y gastric bypass, 9 (10.2%) band repositioning, and 2 (2.3%) band replacements. In addition, 13 (14.8%) port-related procedures (3 relocations, 6 reconnections, and 4 replacements/removals) were performed. CONCLUSION Although reversible and efficacious, LAGB appears to have a high incidence of complications requiring revisional surgery and/or band removal. The results of our study have shown that laparoscopic revisional surgery after primary LAGB is safe and can be performed with minimal morbidity.


title: Single-incision laparoscopic-assisted right colon resection for cancer.

text: INTRODUCTION We present an approach to laparoscopic right colon resection utilizing a single port placed through the umbilicus. The technique described is performed through a single small umbilical incision with a virtually scar-free result. METHODS A 77-year-old woman with a tubulovillous adenoma in her cecum underwent a laparoscopic right colectomy using a single port placed through the umbilicus. Straight and reticulating laparoscopic instruments were utilized. RESULTS The total operative time was 112 minutes. No intraoperative or postoperative complications occurred. The patient was discharged home on day 5 postoperatively with normal bowel function and tolerance of a solid diet. CONCLUSIONS Laparoscopic right colectomy can be safely performed through a single incision through the umbilicus with an excellent cosmetic result.


title: Endovascular aortic repair reduces gluteal oxygenation.

text: Background Provoked gluteal claudication is a known risk after endovascular aortic repair (EVAR). Lowered gluteal muscle oxygenation (SgmO2) may be demonstrated by near-infrared spectroscopy (NIRS). Purpose To evaluate NIRS-determined SgmO2 in EVAR patients. Material and Methods NIRS-determined SgmO2 was used in an observational study design (n = 17). From the ambulatory setting, seven EVAR patients were included with reported gluteal claudication from medical records. In 10 patients scheduled for EVAR, SgmO2 was measured before and after the procedure. NIRS sensors were applied bilaterally on the gluteal region. Treadmill walking (12% incline, 2.4 km/h) was introduced to stress gluteal muscles. Results A reduced SgmO2 with regional side difference (P < 0.05) was noted in all 10 patients following EVAR and four reported gluteal claudication. In patients with gluteal claudication (n = 7), treadmill decreased SgmO2. The time to recover the SgmO2 was prolonged for tissue exposed to occluded hypogastric artery (median = 512 s, range = 73-1207 s vs. median = 137, range = 0-643 s; P = 0.046). Conclusions EVAR affects gluteal muscle oxygenation. NIRS could be used to assess whether gluteal claudication is related to lowered SgmO2.


title: Vexing, Veiled, and Inequitable: Social Distancing and the "Rights" Divide in the Age of COVID-19.

text: Although unprecedented in scope and beyond all our life experiences, sweeping social distancing measures are not without historical precedent. Historically, racism, stigma, and discrimination resulted in grossly inequitable application of disease containment measures. But history also provides examples in which broad measures enjoyed remarkable public support. When it comes to COVID-19, blame and division continue to shape containment responses. But the COVID-19 pandemic also resonates with moments in which there was broad social support for containment precisely because lockdowns or stay at home orders are, on the surface, remarkably equitable. Yet even in a context in which a majority of Americans support social distancing, small but coordinated conservative groups are challenging social distancing as a matter of individual rights. In sharp contrast, vulnerable populations, who bear the heaviest burden of disease, have claimed a right to social distancing as a matter of protection.


Combination prevention for COVID-19.


title: Under the COVID-19 lockdown: Rapid review about the unique case of North Cyprus.

text: COVID-19 has been causing tragic outcomes all over the world. On one island nation, North Cyprus, that has been politically isolated from the rest of the world due to a very complicated history and political stance, the rapid enforcement of lockdown measures, despite having negative psychological effects, helped interfere with the spread of COVID-19 and flatten the curve. We propose that the traumas of the past may have caused resilient factors when faced with the psychological impact of COVID-19, and lack of trust toward the capacities of governing bodies may have caused people take strict precautions to help contain the spread of the virus. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Autoinflammatory grey matter lesions in humans: cortical encephalitis, clinical disorders, experimental models.

text: PURPOSE OF REVIEW In recent years, evidence has accumulated that grey matter abnormalities are common in many inflammatory central nervous system (CNS) disorders, such as multiple sclerosis (MS), which is by far the most frequent autoimmune-mediated CNS disease. RECENT FINDINGS A recent study described comprehensively the pathology of grey matter lesions in early MS. In this study, cortical demyelination together with inflammation was frequently observed in early MS cases. This study and others serve as a basis for a model of the development of cortical MS lesions in which several consecutive events may be involved. After the activation of T cells, which may open the blood-brain barrier, the humoral immune system may mediate the inflammatory process. The inflammation may become chronic through the involvement of activated glial cells and the persistence of immune cells in the meninges.Apart from MS, other grey matter CNS disorders exist in which antibodies against neuronal structures contribute to pathophysiological events such as in limbic encephalitis. Humoral and adaptive immunity mediates the pathophysiology of Rasmussen encephalitis. SUMMARY This review focuses on the difference between inflammatory grey matter and white matter lesions. New insights into inflammatory grey matter lesions in MS and other CNS inflammatory processes such as limbic encephalitis are discussed.


title: Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

text: In the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10-4; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10-3; hazard ratio: 1.74:95%CI: 1.16-2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10-5) and C allele of CFH rs1329428 (P = 3.0 × 10-3) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.


title: Transumbilical endoscopic cholecystectomy with the trichannel trocar technique: a porcine feasibility study.

text: The aim of this study is to verify the feasibility of another option: transumbilical endoscopic cholecystectomy by using the trichannel trocar technique. Eight domestic pigs were submitted to transumbilical endoscopic cholecystectomy by using the trichannel trocar technique. A fine grasper of 2 mm in diameter was inserted through a small skin incision on the right upper abdomen for grasping the gallbladders. The natural scar of the umbilicus was restored after extract of the specimen. All the gallbladders were removed successfully without severe bleeding during dissection, intraoperative, and postoperative complications. Postmortem examination revealed that the gallbladder fossa was clean, the clips on the cystic duct and artery were secure, and neither bile nor blood leakage was found at the operative field. The feasibility and safety of transumbilical endoscopic cholecystectomy are demonstrated by this study. It is possible to use this approach in patients with gallbladder diseases.


[COVID-19: what does epidemiology tell to decisionmakers?]


title: The p4-p2' amino acids surrounding human norovirus polyprotein cleavage sites define the core sequence regulating self-processing order.

text: UNLABELLED Noroviruses (NoV) are members of the family Caliciviridae. The human NoV open reading frame 1 (ORF1) encodes a 200-kDa polyprotein which is cleaved by the viral 20-kDa 3C-like protease (Pro, NS6) into 6 nonstructural proteins that are necessary for viral replication. The NoV ORF1 polyprotein is processed in a specific order, with "early" sites (NS1/2-3 and NS3-4) being cleaved rapidly and three "late" sites (NS4-5, NS5-6, and NS6-7) processed subsequently and less efficiently. Previously, we demonstrated that the NoV polyprotein processing order is directly correlated with the efficiency of the enzyme, which is regulated by the primary amino acid sequences surrounding ORF1 cleavage sites. Using fluorescence resonance energy transfer (FRET) peptides representing the NS2-3 and NS6-7 ORF1 cleavage sites, we now demonstrate that the amino acids spanning positions P4 to P2' (P4-P2') surrounding each site comprise the core sequence controlling NoV protease enzyme efficiency. Furthermore, the NoV polyprotein self-processing order can be altered by interchanging this core sequence between NS2-3 and any of the three late sites in in vitro transcription-translation assays. We also demonstrate that the nature of the side chain at the P3 position for the NS1/2-3 (Nterm/NTPase) site confers significant influence on enzyme catalysis (kcat and kcat/Km), a feature overlooked in previous structural studies. Molecular modeling provides possible explanations for the P3 interactions with NoV protease. IMPORTANCE Noroviruses (NoV) are the prevailing cause of nonbacterial acute gastroenteritis worldwide and pose a significant financial burden on health care systems. Proteolytic processing of the viral nonstructural polyprotein is required for norovirus replication. Previously, the core sequence of amino acids surrounding the scissile bonds responsible for governing the relative processing order had not been determined. Using both FRET-based peptides and full-length NoV polyprotein, we have successfully demonstrated that the core sequences spanning positions P4-P2' surrounding the NS2-3, NS4-5, NS5-6, and NS6-7 cleavage sites contain all of the structural information necessary to control processing order. We also provide insight into a previously overlooked role for the NS2-3 P3 residue in enzyme efficiency. This article builds upon our previous studies on NoV protease enzymatic activities and polyprotein processing order. Our work provides significant additional insight into understanding viral polyprotein processing and has important implications for improving the design of inhibitors targeting the NoV protease.


title: Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity.

text: Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in nonclassical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). Compared with classical secondary lymphoid organs such as lymph nodes and Peyer's patches, FALCs develop along distinct differentiation trajectories and display a reduced structural complexity. Although it is well established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of classical secondary lymphoid organs, the role of FRCs in FALC-dependent peritoneal immunity remains unclear. Using FRC-specific gene targeting, we found that FRCs play an essential role in FALC-driven immune responses. Specifically, we report that initiation of peritoneal immunity was governed through FRC activation in a myeloid differentiation primary response 88 (MYD88)-dependent manner. FRC-specific ablation of MYD88 blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation and IgG class switching. Moreover, containment of Salmonella infection was compromised in mice lacking MYD88 expression in FRCs, indicating that FRCs in FALCs function as an initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.


title: Active humidification with Boussignac CPAP: in vitro study of a new method.

text: OBJECTIVE To carry out an in vitro study of Boussignac CPAP valve performance with a new humidification method, using a heated humidifier. METHODS Two heated humidifiers were evaluated: Fisher & Paykel MR850, and Covidien Kendall Aerodyne 2000. Baseline measurements were taken in all experimental conditions without humidification. The Boussignac valve was adapted to the input of the humidification chamber. The system was connected to a test lung to assess the degree of pressurization. Hygrometric and pressure measurements were performed with the following gas flows: 10, 20, 30 and 40 L/min. RESULTS The mean values of pressure generated by the Boussignac valve were 1.99 ± 0.02, 6.97 ± 0.05, 16.61 ± 0.08 and 21.24 ± 0.08 cm H2O, 10, 20, 30 and 40 L/min, respectively, no differences being detected between study groups. Overall absolute humidity was significantly greater with a heated humidifier than without humidification (range 40.01 ± 0.57-25.46 ± 0.49 compared to 0.16 ± 0.13 mgH2O/L, P < .001). Absolute humidity was significantly higher in Kendall Aerodyne 2000 compared to MR850, regardless of the selected temperature and flow (P < .001). CONCLUSIONS This new method of Boussignac CPAP humidification yielded humidity values above 25 mg H2O/L regardless of the heated humidifier and flow used. Pressurization values remained constant in each experimental situation and were not influenced by adding humidification. These data open up the possibility of using Boussignac CPAP on different types of patients, with different interfaces and for long periods of time.


title: Clinical Features Deserve Consideration for a Urologist in COVID-19.

text: We have studied up-to-date knowledge about the clinical feature of the Novel coronavirus pandemic worth consideration by the urologist. PubMed database, the United States centers for disease control and prevention (CDC), and the World Health Organization (WHO) websites were also accessed. A staging system introduced by Siddiqi et al. for the COVID-19 is acknowledged. Hemodialysis centers are high-risk zones in the outbreak of a COVID-19 epidemic. Symptoms and signs, clinical features, and laboratory findings of the renal transplant patients are almost similar to non-transplanted patients.


title: Simultaneous noninvasive recording of electrocardiogram and skin sympathetic nerve activity (neuECG).

text: neuECG, the simultaneous noninvasive recording of ECG and skin sympathetic nerve activity (SKNA), directly records sympathetic nerve activity over a long period of time. It can be used to measure sympathetic tone in healthy subjects and in subjects with non-cardiovascular diseases. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the SKNA. neuECG is voltage calibrated and does not require invasive procedures to impale electrodes in nerves and thus has advantages over microneurography. Here, we present a protocol that takes <10 min to set up. The neuECG can be continuously recorded over a 24-h period or longer. We also describe methods to efficiently analyze neuECG from humans using commercially available hardware and software to facilitate adoption of this technology in clinical research.


title: Treatment of cancer pain.

text: In patients with active cancer, the management of chronic pain is an essential element in a comprehensive strategy for palliative care. This strategy emphasises multidimensional assessment and the coordinated use of treatments that together mitigate suffering and provide support to the patient and family. This review describes this framework, an approach to pain assessment, and widely accepted techniques to optimise the safety and effectiveness of opioid drugs and other treatments. The advances of recent decades suggest a future that includes increased evidence-based targeting of specific analgesic interventions within an individualised plan of care that is appropriate throughout the course of illness.


title: Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks.

text: BACKGROUND Coxsackievirus A16 (Cox A16) and enterovirus 71 (EV71) are common pathogens causing hand, foot, and mouth disease (HFMD) in pediatric population. Little is known about the basic reproductive number (R0) for these enteroviruses. METHODS We estimated the R0 of EV71 and of Cox A16 from laboratory-confirmed HFMD outbreaks reported to the Department of Health, from 2004 to 2009. We derived a mathematical model and calculated R₀ based on the cumulative number of cases at the initial growth phase of the outbreaks, as determined by the epidemic curves. We tested the association of R₀ with settings and sizes of the institution and total number of persons affected. RESULTS We analyzed 34 outbreaks, 27 caused by Cox A16 and 7 caused by EV71. Assuming the incubation period to be 5 days, the median R₀ of EV71 was 5.48 with an interquartile range of 4.20 to 6.51, whereas the median R₀ of Cox A16 was 2.50 with an interquartile range of 1.96 to 3.67. The R₀ of EV71 was significantly higher than that of CoxA16, P = 0.002; and sensitivity analysis showed the same results. The R₀ was not associated with outbreak settings, sizes of the institutions, or number of persons affected. CONCLUSIONS The R₀ for EV71 and for Cox A16 was determined using a model which showed that the R₀ for EV71 was higher than that of Cox A16. This finding helps better understand the transmission dynamics of HFMD outbreaks and formulate public health measures for controlling the disease.


title: Who and when should we screen for prostate cancer? Interviews with key opinion leaders.

text: Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening.


title: A HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues.

text: Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are generated and sensed in biological tissues. However, testing these mechanical hypotheses on proteins in their natural environment remains inaccesible to conventional tools. To address this limitation, here we demonstrate a mouse model carrying a HaloTag-TEV insertion in the protein titin, the main determinant of myocyte stiffness. Using our system, we specifically sever titin by digestion with TEV protease, and find that the response of muscle fibers to length changes requires mechanical transduction through titin's intact polypeptide chain. In addition, HaloTag-based covalent tethering enables examination of titin dynamics under force using magnetic tweezers. At pulling forces < 10 pN, titin domains are recruited to the unfolded state, and produce 41.5 zJ mechanical work during refolding. Insertion of the HaloTag-TEV cassette in mechanical proteins opens opportunities to explore the molecular basis of cellular force generation, mechanosensing and mechanotransduction.


title: Single-port laparoscopy in colorectal surgery.

text: PURPOSE Laparoscopy is the approach of choice for the majority of colorectal disorders that require a minimally invasive abdominal operation. As the emphasis on minimizing the technique continues, natural orifice surgery is quickly evolving. The authors utilized an embryologic natural orifice, the umbilicus, as sole access to the abdomen to perform a colorectal procedure. Herein, we present our initial experience of single-port laparoscopic colorectal surgery using a Uni-X Single-Port Access Laparoscopic System (Pnavel Systems, Morganville, New Jersey, USA) with a multi-channel cannula and specially designed curved laparoscopic instrumentation. METHOD The abdomen was approached through a 3.5 cm incision via the umbilicus and a single-port access device was utilized to perform a right hemicolectomy on a patient with an unresectable caecal polyp and a body mass index of 35. Ligation of the ileocolic artery was done with a LigaSure Device (Covidien Ltd, Norwalk, Connecticut, USA), and was followed by colonic mobilization, extraction and extracorporeal ileocolic anastomosis. RESULTS The total operative time was 115 min with minimal blood loss. Hospital stay was 4 days with no undue sequelae. CONCLUSION Single-port laparoscopic surgery may allow common colorectal laparoscopic operations to be performed entirely through the patient's umbilicus and enable an essentially scarless procedure. Additional experience and continued investigation are warranted.


title: The effects of operative indication and urgency of intervention on patient outcomes after thoracic aortic endografting.

text: BACKGROUND Endovascular repair for complex thoracic aortic pathology has emerged over the past decade as an alternative to open surgical repair. Reports suggest lower morbidity and mortality rates associated with endovascular interventions. The purpose of this report was to analyze a large single institution experience in endovascular thoracic aortic repair based on clinical presentation as well as within and outside specific instructions for use. METHODS Records of all patients undergoing thoracic aortic endografting at our institution were retrospectively reviewed for demographics, interventional indications and acuity, operative details, and clinical outcomes. Study outcomes were analyzed by clinical presentation (urgent/emergent vs elective) and aneurysm morphology that was within and outside specific instructions for use as recommended by the manufacturer. RESULTS Between March 2006 and October 2009, 96 patients underwent thoracic endografting for aneurysm (n = 43), transection (n = 7), penetrating ulcer (n = 11), dissection (n = 19; acute = 9, chronic = 10), pseudoaneurysm (n = 11), or miscellaneous indications (n = 5). Endografting was performed with various endografts (Gore TAG: 59; Medtrontic Talent: 26; Zenith-TX2: 7; Combination: 4.Involvement of the arch (n = 42, 43.75%) was treated with subclavian artery coverage without revascularization in 13 (13.5%), debranching in 20 (20.8%), and fenestration/stenting in 9 (9.38%). Involvement of the visceral vessels (n = 24, 25%) was treated with debranching in 15 (15.6%) or fenestration/stenting in 9 (9.4%). Patients had a mean follow-up of 11.5 ± 10.96 (range: 0-38) months. Overall mortality was 6.25% (n = 6). Mean intensive care unit stay was 6.26 ± 8.55 (range: 1-63, median: 4) days, and hospital stay was 9.97 ± 10.31 (range: 1-65, median: 65) days. Major complications were infrequent and included: spinal cord ischemia (n = 6, 6.25%), stroke (n = 6, 6.25%), myocardial infarction (n = 3, 3.15%), renal failure (n = 6, 6.25%), and wound complications (n = 9, 9.38%). Reoperation was required in 13 (13.54%), with early intervention in 2 (2.1%). The vast majority of patients were discharged directly to home (n = 66, 68.8%). There were no significant differences between death (1/49 [2%] vs 5/47 [10.6%], P = .07), stroke (3/49 [6%] vs 3/47 [6%], P = 1.0), or spinal cord ischemia (3/49 [6%] vs 3/47 [6%], P = 1.0) when comparing urgent/emergent presentation to elective cases, respectively. However, there were significant differences in death (6/58 [10.5%] vs 0/38 [0%], P = .04) and spinal cord ischemia (6/58 [10.5%] vs 0/38 [0%], P = .04) but not stroke (5/58 [8.8%] vs 1/38 [2.5%], P = .24] when procedures were performed outside the specific instructions for use. CONCLUSIONS Results of this single-institution report suggest that endovascular thoracic aortic repair is a safe and effective treatment option for a variety of thoracic pathology including both elective and emergent cases. However, off-label usage of the devices is associated with a significantly higher risk of mortality and spinal cord ischemia, but the risk still appears acceptable given the majority of cases were emergent.


title: Embryonic genotype and inbreeding affect preimplantation development in cattle.

text: Infertility in cattle herds is a growing problem with multifactorial causes. Embryonic genotype and level of inbreeding are among the many factors that can play a role on reproductive efficiency. To investigate this issue, we produced purebred and crossbred bovine embryos by in vitro techniques from Holstein oocytes and Holstein or Brown Swiss semen and analyzed several cellular and molecular features. In the first experiment, purebred and crossbred embryos, obtained from abattoir oocytes, were analyzed for cleavage, development to morula/blastocyst stages, amino acid metabolism and gene expression of developmentally important genes. The results indicated significant differences in the percentage of compacted morulae, in the expression of three genes at the blastocyst stage (MNSOD, GP130 and FGF4) and in the utilization of serine, asparagine, methionine and tryptophan in day 6 embryos. In the second experiment, bovine oocytes were collected by ovum pick up from ten Holstein donors and fertilized with the semen of the respective Holstein sires or with Brown Swiss semen. The derived embryos were grown in vitro up to day 7, and were then transferred to synchronized recipients and recovered on day 12. We found that purebred/inbred embryos had lower blastocyst rate on days 7-8, were smaller on day 12 and had lower expression of the trophoblast gene PLAC8. Overall, these results indicate reduced and delayed development of purebred embryos compared with crossbred embryos. In conclusion, this study provides evidence that embryo genotype and high inbreeding can affect amino acid metabolism, gene expression, preimplantation development and therefore fertility in cattle.


title: Patterns of pleural pressure amplitude and respiratory rate changes during therapeutic thoracentesis.

text: BACKGROUND Although the impact of therapeutic thoracentesis on lung function and blood gases has been evaluated in several studies, some physiological aspects of pleural fluid withdrawal remain unknown. The aim of the study was to assess the changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS The study included 23 patients with symptomatic pleural effusion. Baseline pleural pressure curves were registered with a digital electronic manometer. Then, the registrations were repeated after the withdrawal of consecutive portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all patients the pleural pressure curves were analyzed in five points, at 0, 25%, 50%, 75% and 100% of the relative volume of pleural effusion withdrawn in particular patients. RESULTS There were 11 and 12 patients with right sided and left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85 years). The most common cause of pleural effusion were malignancies (20 pts., 87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400) ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23 patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9) cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes were identified. Although the patterns of RR changes were more diversified, a significant increase between RR at baseline and the last measurement point was found (p = 0.0097). CONCLUSIONS In conclusion, therapeutic thoracentesis is associated with significant changes in Pplampl during the respiratory cycle. In the vast majority of patients Pplampl increased steadily during pleural fluid withdrawal. There was also an increase in RR. The significance of these changes should be elucidated in further studies. TRIAL REGISTRATION ClinicalTrial.gov, registration number: NCT02192138 , registration date: July 1st, 2014.


title: Laparoscopic sigmoid resection with transrectal specimen extraction has a good short-term outcome.

text: BACKGROUND Transrectal specimen extraction in laparoscopic sigmoid resection avoids a muscle-split incision for specimen retrieval. A technique for transrectal specimen extraction is described, and the results of a pilot study concerning feasibility are presented. METHODS All consecutive patients undergoing laparoscopic sigmoid resection with transrectal specimen extraction were included in this observational study. A specimen retrieval pouch was used to facilitate specimen extraction. All preoperative and operative data, postoperative morbidity, and short-term outcome were gathered in a database. RESULTS The described technique was used to treat 21 patients. The median age of the patients was 41 years (interquartile range [IQR], 34-66 years). The median body mass index (BMI) was 23 kg/m2 (IQR, 22-26 kg/m2), and 90% of the patients were women. Of the 21 patients, 13 (62%) underwent a resection for endometriosis, 5 (24%) had resection for diverticular disease, and 3 (14%) underwent a tumor resection. The median operating time was 105 min (IQR, 90-110 min), and the median intraoperative blood loss was 10 ml (IQR, 0-20 ml). All the procedures except one (95%) were performed within 2 h. The median length of the extracted specimen was 20 cm (IQR, 13-25 cm). There was one anastomotic leak (5%), treated by emergency laparotomy and creation of a new colorectal anastomosis. None of the patients required a temporary diverting stoma, and no postoperative mortality occurred. The median hospital stay was 6 days (IQR, 5-7 days). All the patients did well during a median follow-up period of 3.6 months, and none reported any anal dysfunction. CONCLUSIONS Laparoscopic sigmoid resection with transrectal specimen extraction is feasible and has a good short-term outcome.


title: Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2)-infected pneumonia (COVID-19).

text: Objectives In December 2019, a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, China. Laboratory-based diagnostic tests utilized real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat samples. This study evaluated the diagnostic value to analyzing throat and sputum samples in order to improve accuracy and detection efficiency. Methods Paired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by the RT-PCR assay. Results The positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using the RT-PCR assay (p = 0.001). Conclusions The detection rates of 2019-nCoV from sputum specimens were significantly higher than those from throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.


title: Insights into aphid prey consumption by ladybirds: Optimising field sampling methods and primer design for high throughput sequencing.

text: Elucidating the diets of insect predators is important in basic and applied ecology, such as for improving the effectiveness of conservation biological control measures to promote natural enemies of crop pests. Here, we investigated the aphid diet of two common aphid predators in Central European agroecosystems, the native Coccinella septempunctata (Linnaeus) and the invasive Harmonia axyridis (Pallas; Coleoptera: Coccinellidae) by means of high throughput sequencing (HTS). For acquiring insights into diets of mobile flying insects at landscape scale minimizing trapping bias is important, which imposes methodological challenges for HTS. We therefore assessed the suitability of three field sampling methods (sticky traps, pan traps and hand-collection) as well as new aphid primers for identifying aphid prey consumption by coccinellids through HTS. The new aphid primers facilitate identification to species level in 75% of the European aphid genera investigated. Aphid primer specificity was high in silico and in vitro but low in environmental samples with the methods used, although this could be improved in future studies. For insect trapping we conclude that sticky traps are a suitable method in terms of minimizing sampling bias, contamination risk and trapping success, but compromise on DNA-recovery rate. The aphid diets of both field-captured ladybird species were dominated by Microlophium carnosum, the common nettle aphid. Another common prey was Sitobion avenae (cereal aphid), which got more often detected in C. septempunctata compared to H. axyridis. Around one third of the recovered aphid taxa were common crop pests. We conclude that sampling methodologies need constant revision but that our improved aphid primers offer currently one of the best solutions for broad screenings of coccinellid predation on aphids.


title: The comparison between stroke volume variation and filling pressure as an estimate of right ventricular preload in patients undergoing renal transplantation.

text: PURPOSE The purpose of this prospective, observational study was to respiratory variation of stroke volume (stroke volume variation, SVV) against central venous pressure (CVP) and pulmonary artery diastolic pressure (PADP) as an estimate of right and left ventricular preload. METHODS With IRB approval and informed consent, 31 patients undergoing living related renal transplantation were analyzed. Under general anesthesia with positive pressure ventilation, stroke volume index and SVV were continuously monitored with FloTrac/Vigileo monitor. Right ventricular end-diastolic volume index (RVEDVI) as well as CVP and PADP were continuously monitored with volumetric pulmonary artery catheter. Data of every 30 min interval were used for analysis. The relationship between RVEDVI and CVP, PADP, SVV was analyzed with non-linear regression and the goodness-of-fit was assessed with coefficient of determination (R(2)) of each regression curve. The ability of CVP, PADP and SVV to correctly differentiate RVEDVI <100, <120 or >138 ml/m(2), which were used to guide fluid administration, was also assessed with ROC analysis. RESULTS Three hundred forty-eight data sets were obtained and analyzed. The goodness of fit between RVEDVI and SVV (R(2)) = 0.48) was better than that between RVEDVI and CVP or PADP (R(2)) = 0.19 and 0.33, respectively). The area under the ROC curve of SVV was significantly high compared to CVP or PADP. CONCLUSIONS This study confirmed the theoretical framework of right ventricular preload and ventricular filling pressure and respiratory variation of stroke volume. The result also suggests that SVV can correctly predict preload status compared to pressure-based indices.


title: Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks.

text: OBJECTIVES This study sought to derive and validate outcome-driven thresholds of central blood pressure (CBP) for diagnosing hypertension. BACKGROUND Current guidelines for managing patients with hypertension mainly rely on blood pressure (BP) measured at brachial arteries (cuff BP). However, BP measured at the central aorta (central BP [CBP]) may be a better prognostic factor for predicting future cardiovascular events than cuff BP. METHODS In a derivation cohort (1,272 individuals and a median follow-up of 15 years), we determined diagnostic thresholds for CBP by using current guideline-endorsed cutoffs for cuff BP with a bootstrapping (resampling by drawing randomly with replacement) and an approximation method. To evaluate the discriminatory power in predicting cardiovascular outcomes, the derived thresholds were tested in a validation cohort (2,501 individuals with median follow-up of 10 years). RESULTS The 2 analyses yielded similar diagnostic thresholds for CBP. After rounding, systolic/diastolic threshold was 110/80 mm Hg for optimal BP and 130/90 mm Hg for hypertension. Compared with optimal BP, the risk of cardiovascular mortality increased significantly in subjects with hypertension (hazard ratio: 3.08, 95% confidence interval: 1.05 to 9.05). Of the multivariate Cox proportional hazards model, incorporation of a dichotomous variable by defining hypertension as CBP ≥ 130/90 mm Hg was associated with the largest contribution to the predictive power. CONCLUSIONS CBP of 130/90 mm Hg was determined to be the cutoff limit for normality and was characterized by a greater discriminatory power for long-term events in our validation cohort. This report represents an important step toward the application of the CBP concept in clinical practice.


COVID-19 and Hypercoagulable State: A New Therapeutic Perspective.


title: A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

text: BACKGROUND Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). METHOD Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. RESULTS Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). CONCLUSION In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl.


title: Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics.

text: Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (μECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics. Further applications, such as transparent penetrating electrode arrays, multi-electrode electroretinography, and electromyography, are also viable with this technology. The procedures described herein, from the material characterization methods to the optogenetic experiments, can be completed within 3-4 weeks by an experienced graduate student. These protocols should help to expand the boundaries of neurophysiological experimentation, enabling analytical methods that were previously unachievable using opaque metal-based electrode arrays.


title: Hybrid notes cholecystectomy in an experimental model of laparoscopic acute cholecystitis.

text: The purpose of this study was to evaluate the feasibility of hybrid natural orifice translumenal endoscopic surgery (NOTES) transvaginal cholecystectomy in a porcine model of acute cholecystitis. We have developed an experimental model of acute cholecystitis in 8 female pigs (33.37±3.11 kg) through the surgical occlusion of the common bile duct. After 4 days, hybrid NOTES cholecystectomy was performed in all animals with the assistance of only one 5 mm trocar. The transvaginal approach and the abdomen exploration were performed without any complication. The hybrid NOTES cholecystectomy was successfully completed in all animals. The mean operative time was 76.50±10 minutes. Gallbladder rupture appeared in 2 cases, and there was no bleeding or laceration of adjacent organs. Our experiments showed the feasibility of hybrid NOTES cholecystectomy in an experimental model of acute cholecystitis. Additional research and training on experimental models of pathology will be necessary to validate NOTES surgery.


Outbreak column 14: Staphylococcus aureus - new outbreaks of old infections.


title: Emerging Viral Infections in Pakistan: Issues, Concerns, and Future Prospects.

text: Emerging infectious diseases pose a serious threat to public health security; this is especially true in the underdeveloped world because of limited resources to combat them. These emerging pathogens are characterized by a novel mode of pathogenesis and, in some cases, a broad host range. Over the past few decades, Pakistan has suffered a great deal from infectious diseases such as dengue, Crimean-Congo fever, hepatitis, measles, and polio. Changing climate conditions, environmental degradation, global warming, loss of biodiversity, and other ecological determinants have a direct effect on these diseases and result in the emergence and reemergence of infectious entities. The causes of such disease outbreaks are complex and often not well understood. Dealing with an outbreak requires an integrated and coordinated approach, with decision making by various state departments. Stringent biosecurity and biosafety protocols can help to reduce the chances of infection dissemination. In order to mitigate the risks associated with emerging pathogens, there is a greater need to understand the interactions of pathogen-host-environment, to monitor molecular evolution and genomic surveillance, and to facilitate the gearing up of scientists across the globe to control these emerging diseases. This article reviews recent outbreaks in Pakistan and challenges for the development of an agile healthcare setup in the country.


title: Early effect of intra-arterial treatment in ischemic stroke on aphasia recovery in MR CLEAN.

text: OBJECTIVE To investigate the effect of intra-arterial treatment (IAT) on early recovery from aphasia in acute ischemic stroke. We hypothesized that the early effect of IAT on aphasia is smaller than the effect on motor deficits. METHODS We included patients with aphasia from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), in which 500 patients with a proximal anterior circulation stroke were randomized to usual care plus IAT (<6 hours after stroke, mainly stent retrievers) or usual care alone. We estimated the effect of IAT on the shift on the NIH Stroke Scale (NIHSS) item language and the NIHSS item motor arm at 24 hours and 1 week after stroke with multivariable ordinal logistic regression as a common odds ratio, adjusted for prognostic variables (acOR). Differences between the effect of IAT on aphasia and on motor deficits were tested in a multilevel model with a multiplicative interaction term. RESULTS Of the 288 patients with aphasia, 126 were assigned to IAT and 162 to usual care alone. The acOR for improvement of language score at 24 hours was 1.65 (95% confidence interval [CI] 1.05-2.60), and at 1 week 1.86 (95% CI 1.18-2.94). The acOR for improvement of motor deficit at 24 hours was 2.44 (95% CI 1.54-3.88), and at 1 week 2.32 (95% CI 1.43-3.77). The effect of IAT on language deficits was significantly different from the effect on motor deficits at 24 hours and 1 week (p = 0.005 and p = 0.011). CONCLUSIONS IAT results in better early recovery from aphasia than usual care alone. The early effect of IAT on aphasia is smaller than the effect on motor deficits. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with acute ischemic stroke IAT increases early recovery from aphasia and that the early effect on aphasia, as measured by the NIHSS, is smaller than the effect on motor deficits.


title: Disability Rights as a Necessary Framework for Crisis Standards of Care and the Future of Health Care.

text: In this essay, we suggest practical ways to shift the framing of crisis standards of care toward disability justice. We elaborate on the vision statement provided in the 2010 Institute of Medicine (National Academy of Medicine) "Summary of Guidance for Establishing Crisis Standards of Care for Use in Disaster Situations," which emphasizes fairness; equitable processes; community and provider engagement, education, and communication; and the rule of law. We argue that interpreting these elements through disability justice entails a commitment to both distributive and recognitive justice. The disability rights movement's demand "Nothing about us, without us" requires substantive inclusion of disabled people in decision-making related to their interests, including in crisis planning before, during, and after a pandemic like Covid-19.


title: Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment.

text: OBJECTIVE To evaluate the effects of two bariatric procedures versus intensive medical therapy (IMT) on β-cell function and body composition. RESEARCH DESIGN AND METHODS This was a prospective, randomized, controlled trial of 60 subjects with uncontrolled type 2 diabetes (HbA1c 9.7 ± 1%) and moderate obesity (BMI 36 ± 2 kg/m(2)) randomized to IMT alone, IMT plus Roux-en-Y gastric bypass, or IMT plus sleeve gastrectomy. Assessment of β-cell function (mixed-meal tolerance testing) and body composition was performed at baseline and 12 and 24 months. RESULTS Glycemic control improved in all three groups at 24 months (N = 54), with a mean HbA1c of 6.7 ± 1.2% for gastric bypass, 7.1 ± 0.8% for sleeve gastrectomy, and 8.4 ± 2.3% for IMT (P < 0.05 for each surgical group versus IMT). Reduction in body fat was similar for both surgery groups, with greater absolute reduction in truncal fat in gastric bypass versus sleeve gastrectomy (-16 vs. -10%; P = 0.04). Insulin sensitivity increased significantly from baseline in gastric bypass (2.7-fold; P = 0.004) and did not change in sleeve gastrectomy or IMT. β-Cell function (oral disposition index) increased 5.8-fold in gastric bypass from baseline, was markedly greater than IMT (P = 0.001), and was not different between sleeve gastrectomy versus IMT (P = 0.30). At 24 months, β-cell function inversely correlated with truncal fat and prandial free fatty acid levels. CONCLUSIONS Bariatric surgery provides durable glycemic control compared with intensive medical therapy at 2 years. Despite similar weight loss as sleeve gastrectomy, gastric bypass uniquely restores pancreatic β-cell function and reduces truncal fat, thus reversing the core defects in diabetes.


title: Exposure to influenza virus aerosols during routine patient care.

text: BACKGROUND Defining dispersal of influenza virus via aerosol is essential for the development of prevention measures. METHODS During the 2010-2011 influenza season, subjects with influenza-like illness were enrolled in an emergency department and throughout a tertiary care hospital, nasopharyngeal swab specimens were obtained, and symptom severity, treatment, and medical history were recorded. Quantitative impaction air samples were taken not ≤0.305 m (1 foot), 0.914 m (3 feet), and 1.829 m (6 feet) from the patient's head during routine care. Influenza virus was detected by rapid test and polymerase chain reaction. RESULTS Sixty-one of 94 subjects (65%) tested positive for influenza virus. Twenty-six patients (43%) released influenza virus into room air, with 5 (19%) emitting up to 32 times more virus than others. Emitters surpassed the airborne 50% human infectious dose of influenza virus at all sample locations. Healthcare professionals (HCPs) were exposed to mainly small influenza virus particles (diameter, <4.7 µm), with concentrations decreasing with increasing distance from the patient's head (P < .05). Influenza virus release was associated with high viral loads in nasopharyngeal samples (shedding), coughing, and sneezing (P < .05). Patients who reported severe illness and major interference with daily life also emitted more influenza virus (P < .05). CONCLUSIONS HCPs within 1.829 m of patients with influenza could be exposed to infectious doses of influenza virus, primarily in small-particle aerosols. This finding questions the current paradigm of localized droplet transmission during non-aerosol-generating procedures.


title: COVID-19, hypertension and cardiovascular diseases: Should we change the therapy?

text: The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.


title: Activation of unfolded protein response pathway during infectious salmon anemia virus (ISAV) infection in vitro an in vivo.

text: Infectious salmon anemia virus (ISAV) is a salmon pathogen causing serious outbreaks in fish farms world-wide. There is currently no effective commercially available vaccine and there is a need for better understanding of host pathogen interactions with this virus. Various strains can cause both acute and persistent infections and therefore establish a balance with the host immune responses. We have studied host responses to this infection by analyzing the main branches of the unfolded protein response (UPR) in salmon cells in vitro and in tissues from infected fish to gain a better understanding of virus-host interactions. ISAV induce the main symptoms and signaling pathways of UPR (ATF6, PERK and IRE1) without inducing translational attenuation. This may be due to concomitant induction of an important negative feedback loop via the phosphatase regulator GADD34. The host cells can therefore respond with translation of cytokine and antiviral proteins to curb or control infection.


title: Tackle the free radicals damage in COVID-19.

text: COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.


title: Biodiversity and Phylogenetic Relationships of Novel Bacteriocinogenic Strains Isolated from Animal's Droppings at the Zoological Garden of Lille, France.

text: This study aimed at exploring droppings of animals living in captivity in the zoological garden (Zoo) of Lille (France), as novel sources of bacteriocinogenic strains. A collection of 295 bacterial isolates was constituted from droppings of capybara, alpaca, muntjac, zebra, tapir, rhinoceros, binturong, armadillo, saki monkey and cockatoo. Of 295 isolates, 51 exhibited antagonism against a panel of pathogenic target bacteria like Escherichia coli MC4100, Clostridium perfringens DSM 756 and Salmonella enterica subsp. enterica Newport ATCC6962. Remarkably, within this collection, only 2 Gram-negative bacilli exhibited activity against E. coli MC4100 strain used as target organism. Then, the 16S rDNA sequencing revealed these thereafter cited species, Pediococcus pentosaceus, Weissella cibaria, E. coli, Lactobacillus reuteri, Enterococcus hirae and Enterococcus faecalis. Characterization of this antagonism has revealed 11 strains able producing extracellular protease-sensitive inhibitory compounds. These strains included E. coli ICVB442 and ICVB443, Ent. faecalis ICVB472, ICVB474, ICVB477 ICVB479, ICVB481, ICVB497 and ICVB501 and Ped. pentosaceus ICVB491 and ICVB492. The genomes of the 5 most promising bacteriocinogenic strains were sequenced and analysed with Bagel4 software. Afterwards, this bioinformatics analysis permitted to locate genes encoding bacteriocins like colicin Y (E. coli), enterocin 1071A, enterocin 107 B (Ent. faecalis) and penocin A (Ped. pentosaceus), associating the above-mentioned antibacterial activity of proteinaceous nature to possible production of bacteriocins. All these results enabled us to select different bacteriocinogenic strains for a further characterization in terms of beneficial traits.


title: The COVID-19 Pandemic Confronts the Motivation Fallacy within Pulmonary Rehabilitation Programs.

text: Social distancing and quarantines have been implemented worldwide to reduce the spread of Coronavirus Disease (COVID-19). However, social distancing has had far-reaching health consequences, considering that the COVID-19 pandemic has exposed people to the hazard of physical inactivity and sedentary behavior. For patients with Chronic Obstructive Pulmonary Disease (COPD), which is one of the main diseases at risk for COVID-19, the impact is even greater since outpatient pulmonary rehabilitation (PR) programs are temporarily closed. More than ever, patients' behavior change to exercise calls for urgent debate. We propose a theoretical discussion in light of Self-Determination Theory, aiming to make PR a setting that supports autonomous forms of motivation. The scenario will not be changed in the short-term; but if other conditions hinder the development of PR in its most traditional form, the PR community will be better prepared to overcome the barriers to maintain physical exercise.


A Bold Response to the COVID-19 Pandemic: Medical Students, National Service, and Public Health.


title: Reiterative Radiofrequency Ablation in the Management of Pediatric Patients with Hepatoblastoma Metastases to the Lung, Liver, or Bone.

text: BACKGROUND AND PURPOSE Conventional treatments of systemic chemotherapy and surgical resection for recurrent or metastatic hepatoblastoma (HB) may be inhibitive for the pediatric patient and family who have already been through extensive therapies. This single-institution case series evaluates the safety and efficacy of percutaneous radiofrequency ablation (RFA) in the management of metastatic HB. MATERIALS AND METHODS Between March 2008 and February 2015, RFA was used as part of multidisciplinary management for HB recurrence or metastasis in 5 children (median 5.0 years old) in an attempt to provide locoregional control and preclude additional surgery. Combined local treatments of 38 metachronous metastases included surgical metastasectomy (14 lesions: 7 lung, 7 liver), percutaneous RFA (23 lesions: 21 lung, 1 liver, 1 bone), and stereotactic radiotherapy (1 liver lesion). RESULTS For lesions treated with RFA (median diameter 6 mm, range 3-15 mm), local control was achieved in 22/23 metastases (95.6%) with median follow-up of 30.1 months after RFA (range 18.9-65.7). Median hospitalization was 3 days (2-7), with major complications limited to 1 pneumothorax requiring temporary small-caliber chest tube. Four children remain in complete remission with median follow-up of 67 months (range 41.2-88.8) after primary tumor resection, with mean disease-free survival of 31.7 months after last local treatment. One child succumbed to rapidly progressive disease 12 months after RFA (23.9 months after primary tumor resection). CONCLUSION RFA provides a safe and effective reiterative treatment option in the multidisciplinary management of children with metastatic HB.


title: Direct extubation onto high-flow nasal cannulae post-cardiac surgery versus standard treatment in patients with a BMI ≥30: a randomised controlled trial.

text: PURPOSE Patients with a body mass index (BMI) ≥30 kg/m(2) experience more severe atelectasis following cardiac surgery than those with normal BMI and its resolution is slower. This study aimed to compare extubation of patients post-cardiac surgery with a BMI ≥30 kg/m(2) onto high-flow nasal cannulae (HFNC) with standard care to determine whether HFNC could assist in minimising post-operative atelectasis and improve respiratory function. METHODS In this randomised controlled trial, patients received HFNC or standard oxygen therapy post-extubation. The primary outcome was atelectasis on chest X-ray. Secondary outcomes included oxygenation, respiratory rate (RR), subjective dyspnoea, and failure of allocated treatment. RESULTS One hundred and fifty-five patients were randomised, 74 to control, 81 to HFNC. No difference was seen between groups in atelectasis scores on Days 1 or 5 (median scores = 2, p = 0.70 and p = 0.15, respectively). In the 24-h post-extubation, there was no difference in mean PaO2/FiO2 ratio (HFNC 227.9, control 253.3, p = 0.08), or RR (HFNC 17.2, control 16.7, p = 0.17). However, low dyspnoea levels were observed in each group at 8 h post-extubation, median (IQR) scores were 0 (0-1) for control and 1 (0-3) for HFNC (p = 0.008). Five patients failed allocated treatment in the control group compared with three in the treatment group [Odds ratio 0.53, (95 % CI 0.11, 2.24), p = 0.40]. CONCLUSIONS In this study, prophylactic extubation onto HFNC post-cardiac surgery in patients with a BMI ≥30 kg/m(2) did not lead to improvements in respiratory function. Larger studies assessing the role of HFNC in preventing worsening of respiratory function and intubation are required.


title: Asymptomatic SARS-CoV-2 Infection in Household Contacts of a Healthcare Provider, Wuhan, China.

text: We found that all 5 asymptomatic household contacts of a Wuhan, China, physician with coronavirus disease had severe acute respiratory syndrome coronavirus 2 detected by PCR. The index patient and 2 contacts also had abnormal chest computed tomography scans. Asymptomatic infected household contacts of healthcare workers with coronavirus disease might be underrecognized.


Classic Spotlight, 2014 and 2015: Articles of Significant Interest Selected from the Journal of Virology Archives by the Editors.


title: Viral metagenomics analysis demonstrates the diversity of viral flora in piglet diarrhoeic faeces in China.

text: To investigate the diversity of viral flora, we used metagenomics to study the viral communities in a pooled faecal sample of 27 diarrhoeic piglets from intensive commercial farms in China. The 15 distinct mammalian viruses identified in the pooled diarrhoeic sample were, in order of abundance of nucleic acid sequence, Porcine epidemic diarrhea virus (PEDV), sapovirus, porcine bocavirus-4 (PBoV-4), sapelovirus, torovirus, coronavirus, PBoV-2, stool-associated single-stranded DNA virus (poSCV), astrovirus (AstV), kobuvirus, posavirus-1, porcine enterovirus-9 (PEV-9), porcine circovirus-like (po-circo-like) virus, picobirnavirus (PBV) and Torque teno sus virus 2 (TTSuV-2). The prevalence rate of each virus was verified from diarrhoeic and healthy piglets by PCR assay. A mean of 5.5 different viruses were shed in diarrhoeic piglets, and one piglet was in fact co-infected with 11 different viruses. By contrast, healthy piglets shed a mean of 3.2 different viruses. Compared with samples from healthy piglets, the co-infection of PEDV and PBoV had a high prevalence rate in diarrhoea samples, suggesting a correlation with the appearance of diarrhoea in piglets. Furthermore, we report here for the first time the presence of several recently described viruses in China, and the identification of novel genotypes. Therefore, our investigation results provide an unbiased survey of viral communities and prevalence in faecal samples of piglets.


title: Transrectal rigid-hybrid NOTES cholecystectomy can be performed without peritoneal contamination: a controlled porcine survival study.

text: BACKGROUND AND STUDY AIMS The risk of infectious complications due to peritoneal contamination is a major concern and inhibits the widespread use of transrectal NOTES. A standardized rectal washout with a reversible colon occlusion device in situ has previously shown potential in reducing peritoneal contamination. The aim of this study was to compare the peritoneal contamination rate and inflammatory reaction for transrectal cholecystectomy after ideal rectal preparation (trCCE) and standard laparoscopic cholecystectomy (lapCCE) in a porcine survival experiment. METHODS Twenty pigs were randomized to trCCE (n = 10) or lapCCE (n = 10). Before trCCE, rectal washout was performed with saline solution. A colon occlusion device was then inserted and a second washout with povidone-iodine was performed. The perioperative course and the inflammatory reaction (leukocytes, C-reactive protein) were compared. At necropsy, 14 days after surgery the abdominal cavity was screened for infectious complications and peritoneal swabs were obtained for comparison of peritoneal contamination. RESULTS Peritoneal contamination was lower after trCCE than after lapCCE (0/10 vs. 6/10; p = 0.003). No infectious complications were found at necropsy in either group and postoperative complications did not differ (p = 1.0). Immediately after the procedure, leukocytes were higher after lapCCE (17.0 ± 2.7 vs. 14.6 ± 2.3; p = 0.047). Leukocytes and C-reactive protein showed no difference in the further postoperative course. Intraoperative complications and total operation time (trCCE 114 ± 32 vs. 111 ± 27 min; p = 0.921) did not differ, but wound closure took longer for trCCE (31.5 ± 19 vs. 13 ± 5 min; p = 0.002). CONCLUSIONS After standardized rectal washout with a colon occlusion device in situ, trCCE was associated without peritoneal contamination and without access-related infectious complications. Based on the findings of this study, a randomized controlled clinical study comparing clinical outcomes of trCCE with lapCCE should be conducted.


title: Assessment of molecular and genetic evolution, antigenicity and virulence properties during the persistence of the infectious bronchitis virus in broiler breeders.

text: The infectious bronchitis virus (IBV) causes a highly contagious disease [infectious bronchitis (IB)] that results in substantial economic losses to the poultry industry worldwide. We conducted a molecular and phylogenetic analysis of the S1 gene of Brazilian (BR) IBV isolates from a routinely vaccinated commercial flock of broiler breeders, obtained from clinical IB episodes that occurred in 24-, 46- and 62-week-old chickens. We also characterized the antigenicity, pathogenesis, tissue tropism and spreading of three IBV isolates by experimental infection of specific pathogen-free (SPF) chickens and contact sentinel birds. The results reveal that the three IBV isolates mainly exhibited mutations in the hypervariable regions (HVRs) of the S1 gene and protein, but were phylogenetically and serologically closely related, belonging to lineage 11 of the GI genotype, the former BR genotype I. All three isolates caused persistent infection in broiler breeders reared in the field, despite high systemic anti-IBV antibody titres, and exhibited tropism and pathogenicity for the trachea and kidney after experimental infection in SPF chickens and contact birds. In conclusion, BR genotype I isolates of IBV evolve continuously during the productive cycle of persistently infected broiler breeders, causing outbreaks that are not impaired by the current vaccination programme with Massachusetts vaccine strains. In addition, the genetic alterations in the S1 gene of these isolates were not able to change their tissue tropism and pathogenicity, but did seem to negatively influence the effectiveness of the host immune responses against these viruses, and favour viral persistence.


Predictive Mathematical Models of the COVID-19 Pandemic: Underlying Principles and Value of Projections.


title: A novel assessment tool for evaluating competence in video-assisted thoracoscopic surgery lobectomy.

text: BACKGROUND Specific assessment tools can accelerate trainees' learning through structured feedback and ensure that trainees attain the knowledge and skills required to practice as competent, independent surgeons (competency-based surgical education). The objective was to develop an assessment tool for video-assisted thoracoscopic surgery (VATS) lobectomy by achieving consensus within an international group of VATS experts. METHOD The Delphi method was used as a structured process for collecting and distilling knowledge from a group of internationally recognized VATS experts. Opinions were obtained in an iterative process involving answering repeated rounds of questionnaires. Responses to one round were summarized and integrated into the next round of questionnaires until consensus was reached. RESULTS Thirty-one VATS experts were included and four Delphi rounds were conducted. The response rate for each round were 68.9% (31/45), 100% (31/31), 96.8% (30/31), and 93.3% (28/30) for the final round where consensus was reached. The first Delphi round contained 44 items and the final VATS lobectomy Assessment Tool (VATSAT) comprised eight items with rating anchors: (1) localization of tumor and other pathological tissue, (2) dissection of the hilum and veins, (3) dissection of the arteries, (4) dissection of the bronchus, (5) dissection of lymph nodes, (6) retrieval of lobe in bag, (7) respect for tissue and structures, and (8) technical skills in general. CONCLUSION A novel and dedicated assessment tool for VATS lobectomy was developed based on VATS experts' consensus. The VATSAT can support the learning of VATS lobectomy by providing structured feedback and help supervisors make the important decision of when trainees have acquired VATS lobectomy competencies for independent performance.


title: The impact of the novel coronavirus on trauma and orthopaedics in the UK.

text: At first glance, the novel coronavirus pandemic and orthopaedic surgery appear separate entities. Orthopaedic surgeons are not generally considered front-line staff in terms of the treatment of the disease that the novel coronavirus causes compared with anaesthetic and medical colleagues. However, the impact that the novel coronavirus is likely to have on the musculoskeletal injury burden and the morbidity associated with chronic musculoskeletal disease is significant. This article summarises the strategies currently being developed for the remodelling of orthopaedic services in the UK and the emergency British Orthopaedic Association Standards for Trauma and Orthopaedic guidelines released on 24 March 2020 in managing urgent orthopaedic patients during the novel coronavirus pandemic.


title: CIRSE standards of practice guidelines on iliocaval stenting.

text: Chronic venous insufficiency (CVI) as an advanced stage of chronic venous disease is a common problem that occurs in approximately 1-5 % of the adult population. CVI has either a nonthrombotic (primary) or postthrombotic (secondary) cause involving reflux, obstruction, or a combination of both. The role of venous obstruction is increasingly recognized as a major cause of CVI, with obstructive lesions in the iliocaval segment being markedly more relevant than lesions at the levels of the crural and femoral veins. Approximately 70-80 % of iliac veins develop a variable degree of obstruction following an episode of acute deep venous thrombosis. Nonthrombotic iliac vein obstruction also known as May-Thurner or Cockett's syndrome is the most common cause of nonthrombotic iliac vein occlusion. While compression therapy is the basis of therapy in CVI, in many cases, venous recanalization or correction of obstructive iliac vein lesions may result in resolution of symptoms. This document reviews the current evidence on iliocaval vein recanalization and provides standards of practice for iliocaval stenting in primary and secondary causes of chronic venous disease.


title: Nutritional considerations for head and neck cancer patients: a review of the literature.

text: PURPOSE Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer. MATERIALS AND METHODS A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer. RESULTS Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented. CONCLUSION Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect.


title: Laparoscopic single-port colectomy for sigmoid cancer.

text: BACKGROUND Single-port laparoscopic surgery can be performed via one incision hidden in the umbilicus. Herein, we report a patient with a sigmoid colon cancer undergoing single-port laparoscopic sigmoid colectomy. METHODS Laparoscopic single-port sigmoid colectomy through a 3-cm umbilical incision was performed on a patient with a diagnosis of sigmoid cancer. Patient was 54-year-old female with a body mass index of 25.8 kg/m(2). Preoperatively, a CAT scan in the metastasis evaluation did not show any lesion. RESULTS The total operative time was 198 min. Estimated blood loss was 300 ml. Length of hospital stay was 3 days. Patient had no intraoperative or postoperative complications. Examination of pathological specimen showed a specimen containing a circumferential lesion measuring 5 cm x 2.5 cm x 2.5 cm with adequate surgical margins (10 and 5.5 cm), and no regional lymph node metastases in 14 lymph nodes collected. Patient did not receive adjuvant chemotherapy after surgery. Colonoscopy performed 1 year after surgery showed no neoplasm or polyp identified. Abdomen and pelvis CT also found no evidence of recurrence or metastatic disease. CONCLUSION Single-port laparoscopic surgery may allow common benign procedures via an incision in the umbilicus. It can also be performed with good surgical and oncologic results in selected patients with a colorectal cancer.


Topic: Inguinal Hernia - Tailored surgery.


title: Novel fork-tip needles versus standard needles for EUS-guided tissue acquisition from solid masses of the upper GI tract: a matched cohort study.

text: BACKGROUND There are very few available data on the novel SharkCore™ needles for EUS-FNB. AIM Comparison of the performance of the SharkCore™ needles with the standard EUS-FNA needles for the diagnosis of solid upper GI masses. PATIENTS AND METHODS Single-center, retrospective cohort study in an academic tertiary referral hospital. Patients were matched 1:1 for the site of the lesion and the presence or absence of rapid on-site evaluation (ROSE). RESULTS A total of 102 patients were included. There was no statistically significant difference in the mean number of passes (3.3 ± 1.3 versus 3.4 ± 1.5; p = .89). Similar results were observed at the subgroup with ROSE (4.3 ± 1.3 versus 3.7 ± 1.5; p = .26). More histological specimens were obtained with the SharkCore™ needles compared to standard needles (59 versus 5%; p < .001). Diagnostic test characteristics were not significantly different (sensitivity: 91.5 versus 85.7; specificity: 100 versus 100%; accuracy: 92.2 versus 85.4% for SharkCore™ versus standard needles, p > .05 in all cases). At multivariable analysis, there was no statistically significant difference in the mean number of passes in all patients (p = .23) and in the ROSE subgroup (p = .66). However, the SharkCore™ needle obtained significantly more histological material than the standard needle (odds ratio 66; 95% confidence interval: 11.8, 375.8, p < .001). There was no significant difference in complication rates (p = .5). LIMITATIONS Retrospective study, single-center. CONCLUSION The SharkCore needles were similar to standard FNA needles in terms of the number of passes to reach diagnosis, but obtained significantly more histological specimen.


A Canadian survey of self-infusion practices in persons with haemophilia A.


title: Endoscopic Transoral Hybrid Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy.

text: OBJECTIVES The hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP, that is, open partial horizontal laryngectomies OPHL Type IIa) has been described using a flexible next generation robotic surgical platform for manipulation. We sought to evaluate the feasibility of performing this procedure using endoscopic transoral (EndoT) surgical techniques without robotics. METHODS Preclinical cadaveric study using two human cadavers. Hybrid SCPL-CHEP was performed with a flexible endoscope for visualization and hand-held instruments for manipulation (SILS Hook monopolar and Dissect, HAVAS LaryngoFIT malleable straight jaw instruments, and Stratafix 4-0 spiral knotless barbed suture). RESULTS EndoT hybrid SCPL-CHEP was successfully performed. The hand-manipulated rigid instruments allowed for transoral incisions and mucosal suturing. We provide the procedural steps of EndoT hybrid techniques. CONCLUSIONS EndoT hybrid SCPL-CHEP was technically feasible in the preclinical cadaveric laboratory setting and appeared comparable to the hybrid SCPL-CHEP via transoral robotic surgery (TORS). Selected handheld instruments and flexible endoscopy appear to facilitate minimally invasive surgery of the larynx. This novel procedure and technique warrant further clinical study for consideration of feasibility, applicability, and patient benefit.


title: Periprocedural complications associated with endovascular treatment of intracranial aneurysms in 1764 cases.

text: BACKGROUND Intracranial aneurysms are increasingly treated with endovascular treatment. Based on our observation that cerebral complications are associated with this treatment, we predict that the number of intraprocedural complications will rise as a result of this trend. METHODS Between January 2007 and December 2013, 1739 patients underwent 1764 detachable coil embolizations to treat intracranial aneurysms (637 ruptured and 1127 unruptured). We reviewed their records and images to evaluate the periprocedural complications and related morbidity and mortality. RESULTS 61 complications occurred during coil embolization and 33 periprocedural complications occurred within 1 week. These complications were observed in 8.6% of ruptured aneurysm embolization procedures (55/637) and in 3.5% of unruptured aneurysm embolization procedures (39/1127). There were 17 (0.96%) cerebral thromboembolisms, 34 (1.93%) intraprocedural aneurysm ruptures, 8 (0.45%) coil migrations, 13 (0.74%) postprocedural aneurysmal ruptures, and 22 (1.24%) neurologic deficits or transient neurologic deficits related to embolization. 63 complications had no neurologic consequences, 3 were associated with transient neurologic morbidity, 15 resulted in persistent neurologic morbidity on discharge, and 12 resulted in death. The procedure-related neurologic morbidity and mortality rates for all 1764 procedures were 0.85% in ruptured aneurysms and 0.68% in unruptured aneurysms. CONCLUSIONS The periprocedural complication rate was higher in ruptured aneurysms than in unruptured aneurysms. The main causes of morbidity and mortality were thromboembolisms, intraprocedural aneurysm perforations, and postprocedural aneurysmal ruptures. While some periprocedural complications are inevitable, we can minimize the occurrence of such complications by advancing our skill and experience, thereby improving patient prognosis.


10th Annual Australian Health Outcomes Conference 2004: 10 years on and going strong.


title: Influenza A infection of primary human airway epithelial cells up-regulates proteins related to purine metabolism and ubiquitin-related signaling.

text: Virus-host interactions are important determinants of virus replication and immune responses, but they are not well-defined. In this study we analyzed quantitative host protein alterations in nuclei-enriched fractions from multiple primary human bronchial airway epithelial (HBAE) cells infected by an H1N1 influenza A virus (A/PR/8/34). We first developed an effective detergent-free nuclear lysis method that was coupled with in-solution digestion and LC-MS/MS. Using SILAC, we identified 837 HBAE nuclear proteins in three different donors and compared their responses to infection at 24 h. Some proteins were altered in all three donors, of which 94 were up-regulated and 13 were down-regulated by at least 1.5-fold. Many of these up-regulated proteins clustered into purine biosynthesis, carbohydrate metabolism, and protein modification. Down-regulated proteins were not associated with any specific pathways or processes. These findings further our understanding of cellular processes that are altered in response to influenza in primary epithelial cells and may be beneficial in the search for host proteins that may be targeted for antiviral therapy.


title: A Tale of (Glycogen Synthase Kinase) Three: Lithium, The Kidney and Coronavirus Disease 19.

text: The long-term use of lithium salts has long been associated with tubular damage and chronic kidney disease development. Nevertheless, there is some interest in the potential role of these drugs in inflammatory pathways regulation including those pathways in the setting of acute kidney injury (AKI).


title: Selective and specific regulation of ectodomain shedding of angiotensin-converting enzyme 2 by tumor necrosis factor alpha-converting enzyme.

text: Angiotensin-converting enzyme 2 (ACE2) is a newly identified regulator of the renin-angiotensin system. This type I membrane-anchored protein has a catalytically active ectodomain that undergoes shedding. Tumor necrosis factor alpha-converting enzyme (TACE) has been shown to be involved in ACE2 shedding. Although pathophysiological significance of ACE2 shedding has been suggested, regulation of this process by TACE is not clearly defined. We characterized TACE-mediated constitutive ectodomain shedding of ACE2 using wild-type Chinese Hamster Ovary (WT-CHO), the TACE-mutant M2 (M2-CHO) cells, and EC-4 and EC-2 cells that are fibroblasts from wild-type and TACE-null mice, respectively. ACE2 was constitutively cleaved to release two distinct major soluble forms. The deglycosylated molecular masses of the larger (LSF) and smaller soluble form (SSF) were approximately 80 and 70 kDa, respectively. These forms had equivalent enzyme activities. Reduced shedding for the LSF from M2-CHO and EC-2 cells when compared with WT-CHO and EC-4 cells, respectively, was noted. TACE reconstitution in EC-2 cells expressing ACE2 resulted in increase in LSF but not SSF release, demonstrating a main role of TACE in LSF release and distinct regulations of release of the two soluble forms. Deletions of the juxtamembrane region of ACE2 reduced LSF release in CHO cell lines, whereas it abolished TACE-induced shedding in EC-2 cells. Analysis of TACE structural domains confirmed that the active site in the catalytic domain is essential for ACE2 shedding but that noncatalytic domains also play additional roles. These results demonstrate selective and specific regulation of constitutive shedding of ACE2 by TACE.


title: Perfusion Index in Preterm Infants during the First 3 Days of Life: Reference Values and Relation with Clinical Variables.

text: BACKGROUND The perfusion index (PI) derived from pulse oximetry readings represents the ratio of pulsatile (arterial blood) and nonpulsatile contributors to infrared light absorption. PI has been shown to correlate with cardiac performance. In theory, PI is readily available on every pulse oximeter; therefore, no additional sensors or infant handling are required. Currently, reference values are lacking in (preterm) neonates and the association with common clinical conditions is unclear. OBJECTIVES To establish reference values for the PI in premature infants and at the same time determine the influence of common clinical conditions. METHODS PI was prospectively monitored on the lower limb for 72 h in 311 neonates born with a gestational age <32 weeks between January 2011 and December 2013. Longitudinal mixed-effects modeling was used. Linear, quadratic, and cubic models were explored. Main effects and interactions were investigated. RESULTS A squared model (0-24 h) followed by a linear model (24-72 h) provided the best fit of the data. PI was lowest around 12-18 h after birth and showed a steady increase thereafter. PI was positively related with female gender, gestational age, and pulse pressure. Negative associations were found with SIMV/HFOV ventilation, dopamine administration, mean arterial blood pressure, and arterial oxygen saturation. Although more complex, the general association with a patent ductus arteriosus was positive. CONCLUSION PI varied according to several clinical conditions. The association with common clinical factors suggests that PI might be used for monitoring neonatal hemodynamics and possibly as an additional guidance for interventions.


Anaesthesiology and perioperative medicine around the world: different names, same goals.


title: Comparison of equine platelet function and survival in whole blood collected in acid-citrate-dextrose solution or citrate-phosphate-dextrose-adenine solution.

text: BACKGROUND Equine whole blood collection and storage methods have been evaluated to assess red blood cell viability; however, platelet (PLT) viability has not been comprehensively assessed. OBJECTIVES The purpose of the study was to compare viability of PLTs collected in whole blood into 2 different anticoagulants. METHODS Whole blood from 6 healthy adult Thoroughbred horses was collected into citrate-phosphate-dextrose-adenine (CPDA) or acid-citrate-dextrose (ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured within 10 minutes of collection and then again one hour later at which time PLT aggregometry was performed to assess PLT function. RESULTS Aggregometry mean amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH, bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA compared to ACD. Lactate concentration was higher following one hour in either anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were significantly higher in ACD compared to CPDA at collection. CONCLUSIONS Platelet aggregometry results suggest that CPDA is superior to ACD for maintaining PLT viability following whole blood collection. This may be associated with the higher, more neutral pH as well as an increase in glucose available for metabolism. Although lactate was increased in the CPDA samples it was not high enough to decrease pH and therefore may not have been high enough to cause morphologic lesions and loss of PLT viability.


title: Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors.

text: Found throughout biology, polyvalent interactions are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another (top part of the illustration) and have a number of characteristics that monovalent interactions do not (bottom). In particular, polyvalent interactions can be collectively much stronger than corresponding monovalent interactions, and they can provide the basis for mechanisms of both agonizing and antagonizing biological interactions that are fundamentally different from those available in monovalent systems.