title: Influenza Virus and Chromatin: Role of the CHD1 Chromatin Remodeler in the Virus Life Cycle.

text: UNLABELLED Influenza A virus requires ongoing cellular transcription to carry out the cap-snatching process. Chromatin remodelers modify chromatin structure to produce an active or inactive conformation, which enables or prevents the recruitment of transcriptional complexes to specific genes; viral transcription thus depends on chromatin dynamics. Influenza virus polymerase associates with chromatin components of the infected cell, such as RNA polymerase II (RNAP II) or the CHD6 chromatin remodeler. Here we show that another CHD family member, CHD1 protein, also interacts with the influenza virus polymerase complex. CHD1 recognizes the H3K4me3 (histone 3 with a trimethyl group in lysine 4) histone modification, a hallmark of active chromatin. Downregulation of CHD1 causes a reduction in viral polymerase activity, viral RNA transcription, and the production of infectious particles. Despite the dependence of influenza virus on cellular transcription, RNAP II is degraded when viral transcription is complete, and recombinant viruses unable to degrade RNAP II show decreased pathogenicity in the murine model. We describe the CHD1-RNAP II association, as well as the parallel degradation of both proteins during infection with viruses showing full or reduced induction of degradation. The H3K4me3 histone mark also decreased during influenza virus infection, whereas a histone mark of inactive chromatin, H3K27me3, remained unchanged. Our results indicate that CHD1 is a positive regulator of influenza virus multiplication and suggest a role for chromatin remodeling in the control of the influenza virus life cycle. IMPORTANCE Although influenza virus is not integrated into the genome of the infected cell, it needs continuous cellular transcription to synthesize viral mRNA. This mechanism implies functional association with host genome expression and thus depends on chromatin dynamics. Influenza virus polymerase associates with transcription-related factors, such as RNA polymerase II, and with chromatin remodelers, such as CHD6. We identified the association of viral polymerase with another chromatin remodeler, the CHD1 protein, which positively modulated viral polymerase activity, viral RNA transcription, and virus multiplication. Once viral transcription is complete, RNAP II is degraded in infected cells, probably as a virus-induced mechanism to reduce the antiviral response. CHD1 associated with RNAP II and paralleled its degradation during infection with viruses that induce full or reduced degradation. These findings suggest that RNAP II degradation and CHD1 degradation cooperate to reduce the antiviral response.


title: [Analysis of adenovirus infection in acute respiratory tract infection cases in Shanghai from 2015 to 2019].

text: Objective: To study the epidemiological characteristics and mixed infection of adenovirus in acute respiratory tract infections in Shanghai from 2015 to 2019, and to provide scientific basis for the prevention and control of adenovirus. Methods: Acute respiratory tract infections were collected from 3 hospitals in Shanghai from 2015 to 2019. Relevant information was registered and respiratory specimens were sampled for detection of respiratory pathogens by multiplex PCR. Results: A total of 1 543 cases of acute respiratory tract infection were included. The positive rate of adenovirus was 2.92%(45/1 543), the positive rates of influenza like illness (ILI) and severe acute respiratory illness (SARI) were 2.74%(29/1 058) and 3.30%(16/485), respectively. The positive rate of ILI during January-May 2019 was 5.43%(7/129), higher than that in the same period of 2015- 2018 (0.52%-4.48%) (Fisher's exact test value=8.92, P=0.036). The incidence of adenovirus-positive cases was mainly distributed in the first and second quarters, accounting for 62.22% (28/45). The difference of the incidence of adenovirus-positive cases in each quarter was significant (χ(2)= 12.52, P=0.006). The positive rate in the second quarter was highest (6.03%), which was higher than that in other quarters (1.89%-2.93%). There were significant differences among different age groups (χ(2)=16.94, P=0.001), and the positive rate decreased with age (χ(2)=10.16, P=0.001). The positive rate of 13-19 years old group (9.43%) was higher than that of other age groups (1.48%-4.81%). The positive rate of student group (12.07%) was higher than that of other occupations (2.61%). The difference was systematic (χ(2)=11.53, P=0.001). Mixed infection accounted for 31.11% (14/45) of 45 adenovirus positive cases. The mixed infection rates of ILI and SARI were 34.48% (10/29) and 25.00% (4/16), respectively. Among 14 cases of mixed infection, the main mixed infection pathogens of adenovirus were influenza A virus and coronavirus. Conclusion: Adenovirus surveillance should be further strengthened in adolescents with a focus on students and other key groups in the second quarter.


title: Magnetic resonance visualization of iron-loaded meshes in patients with pain after inguinal hernia repair.

text: PURPOSE Chronic post-operative inguinal pain (CPIP) is defined as pain lasting more than 3 months and the incidence is less than 4% after laparoscopic hernia repair. CPIP can have several causes. In this study, we aimed to show that 3D-iron loaded mesh preparations are useful in radiological evaluation of post-operative complications, especially patients with chronic pain and the mesh status of operated inguinal hernia cases. METHODS A total of 450 cases who had been operated for inguinal hernia with 3D-iron loaded mesh and who had ongoing pain at the post-operative period were included in this study. MRI (Magnetic Resonance Imaging) was performed at the post-operative 90th day of the seven symptomatic (groin pain, limitation of movement) cases which were operated using a 3D-iron loaded mesh, 10 × 15 cm in size, (DynaMeshEndolap visible with 25% MRI-visible filaments, FEG TextiltechnikmbH, Aachen, Germany) for inguinal hernia repair to evaluate mesh status, localization, and local complications. Gradient echo sequences in the sagittal, axial, and coronal sections on MRI were discussed by two radiologists. Mesh localizations, their relationship with surrounding structures and their complications related with mesh were evaluated by two radiologists (D.Y, D.E.T.Ş). RESULTS No significant radiological findings related to defined anatomical structures were found in the MRI images of the study group. The dimensions measured on the sagittal, axial and coronal images were correlated with original mesh sizes and no significant shrinkage was detected. CONCLUSION Mesh position and deformation as shrinkage can be the mesh-related cause of pain. The incidence of CPIP in our patients is less than 2%. 3D-iron loaded meshes were monitored with MRI in CPIP patients and there was no mesh-related changes found in our study. The use of MRI-visible meshes will most likely help us to monitor mesh preparations and show potential time-dependent changes in mesh characteristics and consequent complications. In case of doubtful clinical postoperative hernia recurrence or chronic groin pain, mesh position can be identified by MRI and unnecessary surgical intervention can be avoided.


title: Standardized transportation of human islets: an islet cell resource center study of more than 2,000 shipments.

text: Preservation of cell quality during shipment of human pancreatic islets for use in laboratory research is a crucial, but neglected, topic. Mammalian cells, including islets, have been shown to be adversely affected by temperature changes in vitro and in vivo, yet protocols that control for thermal fluctuations during cell transport are lacking. To evaluate an optimal method of shipping human islets, an initial assessment of transportation conditions was conducted using standardized materials and operating procedures in 48 shipments sent to a central location by eight pancreas-processing laboratories using a single commercial airline transporter. Optimization of preliminary conditions was conducted, and human islet quality was then evaluated in 2,338 shipments pre- and postimplementation of a finalized transportation container and standard operating procedures. The initial assessment revealed that the outside temperature ranged from a mean of -4.6 ± 10.3°C to 20.9 ± 4.8°C. Within-container temperature drops to or below 15°C occurred in 16 shipments (36%), while the temperature was found to be stabilized between 15°C and 29°C in 29 shipments (64%). Implementation of an optimized transportation container and operating procedure reduced the number of within-container temperature drops (≤ 15°C) to 13% (n = 37 of 289 winter shipments), improved the number desirably maintained between 15°C and 29°C to 86% (n = 250), but also increased the number reaching or exceeding 29°C to 1% (n = 2; overall p < 0.0001). Additionally, postreceipt quality ratings of excellent to good improved pre- versus postimplantation of the standardized protocol, adjusting for preshipment purity/viability levels (p < 0.0001). Our results show that extreme temperature fluctuations during transport of human islets, occurring when using a commercial airline transporter for long distance shipping, can be controlled using standardized containers, materials, and operating procedures. This cost-effective and pragmatic standardized protocol for the transportation of human islets can potentially be adapted for use with other mammalian cell systems and is available online at http://iidp.coh.org/sops.aspx.


title: E-health in China: challenges, initial directions, and experience.

text: China started to pay more attention to the construction of a regional and national health information network after the outbreak of the severe acute respiratory syndrome (SARS) epidemic in 2003. The construction of a public health system is considered the most important part of national medical reform, with information and computer technology serving as the key to deploying regional collaborative medical service, also known as e-health. In this paper, we analyze the difficulties in carrying out e-health projects in China, a discussion of ongoing projects, and a case presentation representing current progress.


The perianesthesia nurse's role in the prevention of opioid-related sentinel events.


title: Gastritis might be considered as a technical factor affecting laparoscopic sleeve gastrectomy.

text: There is a paucity of data regarding gastritis as a technical factor affecting the surgical technique. Antritis and gastritis usually cause stomach wall thickness which can interrupt stapler function or even can cause serosal tear during the dissection. We report a video presentation of laparoscopic sleeve gastrectomy in a morbidly obese patient with antritis. Choosing black cartridge for patients with Helicobacter pylori gastritis might be the optimal technique for division of the antrum in laparoscopic sleeve gastrectomy. Further studies are required to clarify this parameter.


docid: tcdbkffj

title: Patients with uncontrolled components of metabolic syndrome have increased risk of complications following total joint arthroplasty.

text: Metabolic syndrome (MetS)-a diagnostic grouping of diabetes, dyslipidemia, hypertension, and obesity-has been indicated as a risk factor for perioperative complications following total joint arthroplasty (TJA). This study investigates the impact of MetS on perioperative complications, specifically the importance of controlling MetS components. One hundred thirty-three patients undergoing TJA with all four components of MetS were identified. They were matched one-to-one with patients without MetS. Control of diabetes, dyslipidemia, and hypertension was assessed. Thirty-five patients with MetS were found to have at least a single uncontrolled component. The complication rates were 49%, 8%, and 8% for uncontrolled MetS, controlled MetS, and no MetS, respectively. Multivariate analysis confirmed independent associations between control of MetS components and both perioperative complications and length of stay. Both surgeons and patients should be aware of the substantial risk of dangerous complications following TJA in patients with uncontrolled metabolic syndrome.


title: Randomized clinical trial of laparoscopic gastric bypass versus laparoscopic duodenal switch for superobesity.

text: BACKGROUND Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic biliopancreatic diversion with duodenal switch (LDS) are surgical options for superobesity. A randomized trial was conducted to evaluate perioperative (30-day) safety and 1-year results. METHODS Sixty patients with a body mass index (BMI) of 50-60 kg/m(2) were randomized to LRYGB or LDS. BMI, percentage of excess BMI lost, complications and readmissions were compared between groups. RESULTS Patient characteristics were similar in the two groups. Mean operating time was 91 min for LRYGB and 206 min for LDS (P < 0.001). One LDS was converted to open surgery. Early complications occurred in four patients undergoing LRYGB and seven having LDS (P = 0.327), with no deaths. Median stay was 2 days after LRYGB and 4 days after LDS (P < 0.001). Four and nine patients respectively had late complications (P = 0.121). Mean BMI at 1 year decreased from 54.8 to 38.5 kg/m(2) after LRYGB and from 55.2 to 32.5 kg/m(2) after LDS; percentage of excess BMI lost was greater after LDS (74.8 versus 54.4 per cent; P < 0.001). CONCLUSION LRYGB and LDS can be performed with comparable perioperative safety in superobese patients. LDS provides greater weight loss in the first year.


docid: cviayiqh

title: Blueprint for a pop-up SARS-CoV-2 testing lab.


What the Diamond Princess taught the world about covid-19.


title: Whole-Body 18F-FDG PET/CT Is Superior to CT as First-Line Diagnostic Imaging in Patients Referred with Serious Nonspecific Symptoms or Signs of Cancer: A Randomized Prospective Study of 200 Patients.

text: A fast-track pathway has been established in Denmark to investigate patients with serious nonspecific symptoms and signs of cancer (NSSC), who are not eligible to enter an organ-specific cancer program. The prevalence of cancer in this cohort is approximately 20%. The optimal screening strategy in patients with NSSC remains unknown. The aim of the study was to investigate whether 18F-FDG PET/CT was superior to CT as an initial imaging modality in patients with NSSC. In a randomized prospective trial, the imaging modalities were compared with regard to diagnostic performance. Methods: Two hundred patients were randomized 1:1 to whole-body 18F-FDG PET/CT or CT of the thorax and abdomen as the imaging modality. A tentative diagnosis was established after first-line imaging. The final referral diagnosis was adjudicated by the physician, when sufficient data were available. Results: One hundred ninety-seven patients were available for analysis because 3 patients withdrew consent before scanning. Thirty-nine (20%) patients were diagnosed with cancer, 10 (5%) with an infection, 15 (8%) with an autoimmune disease, and 76 (39%) with other diseases. In the remaining 57 patients (28%), no specific disease was found. 18F-FDG PET/CT had a higher specificity (96% vs. 85%; P = 0.028) and a higher accuracy (94% vs. 82%; P = 0.017) than CT. However, there were no statistically significant differences in sensitivity (83% vs. 70%) or negative predictive values (96% vs. 92%). No difference in days to final referral diagnosis according to randomization group could be shown (7.2 vs. 7.6 d). However, for the subgroups in which the imaging modality showed a suggestion of malignancy, there was a significant delay to final diagnosis in the CT group compared with the 18F-FDG PET/CT group (11.6 vs. 5.7 d; P = 0.02). Conclusion: Compared with CT, we found a higher diagnostic specificity and accuracy of 18F-FDG PET/CT for detecting cancer in patients with NSSC. 18F-FDG PET/CT should therefore be considered as first-line imaging in this group of patients.


title: Traditional techniques of esophagectomy.

text: Several well described and accepted traditional techniques exist for the performance of an open esophagectomy. The rationale for selecting one of these techniques is determined by the location and histology of the disease being treated and surgeon and institutional preferences. Large retrospective studies and a limited number of prospective studies have comparatively evaluated the operative and long-term oncologic outcomes of transthoracic versus transhiatal surgical approaches, which indicate trends toward higher perioperative complications but improved long-term outcomes among patients treated with a transthoracic approach. Other retrospective studies investigated the extent of a thoracic lympadenectomy that is necessary at the time of an esophagectomy to optimize survival.


title: Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge.

text: Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.


title: Comparing glomerular filtration rate equations and the impact of different creatinine assays on the assessment of renal function in cancer patients.

text: BACKGROUND Equations to estimate glomerular filtration rate based on serum creatinine are commonly used in cancer patients to assess renal function. However, there is uncertainty regarding which equation is most appropriate for this population and the impact of different creatinine assays. METHODS Measured isotopic glomerular filtration rate results from 120 oncology patients were used to evaluate and compare all four versions of the Wright equation, Cockcroft and Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration and the Janowitz and Williams formula; using eight different creatinine assays (five Jaffe, three enzymatic). RESULTS The enzymatic version of the Wright equation without creatine kinase performed better than the other versions for all eight creatinine assays. However, MDRD and Janowitz and Williams gave the best overall performance in this patient population. Performance was highly dependent on the creatinine assay used, for example, the percentage of results within 30% of the isotopic glomerular filtration rate (P30) ranged from 90.8% to 60.8% for MDRD. CONCLUSION The performance of any equation to estimate glomerular filtration rate is highly dependent on the creatinine assay used. Oncology units should assess the performance of glomerular filtration rate equations using their laboratory creatinine assay to determine whether they can be used safely and effectively in cancer patients.


title: Temporal Trends in Sex Differences With Regard to Stroke Incidence: The Dijon Stroke Registry (1987-2012).

text: BACKGROUND AND PURPOSE We evaluated temporal trends in stroke incidence between men and women to determine whether changes in the distribution of vascular risk factors have influenced sex differences in stroke epidemiology. METHODS Patients with first-ever stroke including ischemic stroke, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, and undetermined stroke between 1987 and 2012 were identified through the population-based registry of Dijon, France. Incidence rates were calculated for age groups, sex, and stroke subtypes. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating incidence rate ratios (IRRs) with Poisson regression. RESULTS Four thousand six hundred and fourteen patients with a first-ever stroke (53.1% women) were recorded. Incidence was lower in women than in men (112 versus 166 per 100 000/y; IRR, 0.68; P<0.001), especially in age group 45 to 84 years, and for both ischemic stroke and intracerebral hemorrhage. From 1987 to 2012, the lower incidence of overall stroke in women was stable (IRR ranging between 0.63 and 0.72 according to study periods). When considering stroke subtype, a slight increase in the incidence of ischemic stroke was observed in both men (IRR, 1.011; 95% confidence interval, 1.005-1.016; P=0.001) and women (IRR, 1.013; 95% confidence interval, 1.007-1.018; P=0.001). The sex gap in incidence remained unchanged in ischemic stroke and intracerebral hemorrhage. Conversely, the lower subarachnoid hemorrhage incidence in women vanished with time because of an increasing incidence. CONCLUSIONS The sex gap in stroke incidence did not change with time except for subarachnoid hemorrhage. Despite lower rates, more women than men experience an incident stroke each year because of a longer life expectancy.


docid: gkysknzn

title: COVID-19 platform trial delivers.


title: Interrogation of safety and efficacy of home-use light-based devices.

text: We read with interest the short paper describing, and commend the authors on sharing their experience the continued use of phototherapy in COVID-19 affected Italy. Phototherapy is undoubtedly a long-established, relatively safe means of reducing the burden of inflammatory skin disease avoiding large doses of immunosuppression. Home phototherapy devices and services have a long-established use in many countries throughout the world, as described in previous issues of this journal.


title: C6orf106 is a novel inhibitor of the interferon-regulatory factor 3-dependent innate antiviral response.

text: Host recognition of intracellular viral RNA and subsequent induction of cytokine signaling are tightly regulated at the cellular level and are a target for manipulation by viruses and therapeutics alike. Here, we characterize chromosome 6 ORF 106 (C6orf106) as an evolutionarily conserved inhibitor of the innate antiviral response. C6orf106 suppresses the synthesis of interferon (IFN)-α/β and proinflammatory tumor necrosis factor (TNF) α in response to the dsRNA mimic poly(I:C) and to Sendai virus infection. Unlike canonical inhibitors of antiviral signaling, C6orf106 blocks interferon-regulatory factor 3 (IRF3) and, to a lesser extent, NF-κB activity without modulating their activation, nuclear translocation, cellular expression, or degradation. Instead, C6orf106 interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing the nuclear levels of the coactivator proteins p300 and CREB-binding protein (CBP). In summary, we have defined C6orf106 as a negative regulator of antiviral immunity that blocks IRF3-dependent cytokine production via a noncanonical and poorly defined mechanism. This work presents intriguing implications for antiviral immunity, autoimmune disorders, and cancer.


title: Transanal endoscopic operation for rectal lesions using two-dimensional visualization and standard endoscopic instruments: a prospective cohort study and comparison with the literature.

text: BACKGROUND The transanal endoscopic operation (TEO) has proved to be an effective alternative to conventional surgery for the treatment of rectal lesions. The TEO procedure offers reduced morbidity, faster recovery and equivalent oncologic outcome. Currently, two instrument sets are available: one with three-dimensional (Wolf) and one with two-dimensional (Storz) optic capacities. The three-dimensional (3D) instrument set is considered the golden standard. Although the advantages of TEO are imposing, the procedure with the 3D armamentarium has certain technical and financial drawbacks. This study therefore aimed to compare results for the TEO 2D alternative with recently published results for 3D TEO. METHODS All consecutive patients with benign or malignant pT1 or pT2 rectal lesions undergoing TEO were prospectively followed. All procedures were performed with the 2D armamentarium using standard endoscopic instruments, a rectoscope (diameter, 4 cm; working length, 7.5-15 cm), and 5-mm Ligasure and Ultracision. Operating times, complications, hospital stay, and oncologic outcome were gathered and compared with published data. RESULTS Between 2004 and 2006, 31 patients with a median age of 75 years (range, 33-87 years) underwent 31 TEOs for a total of 36 rectal lesions (29 tubulovillous adenomas and 7 adenocarcinomas). The median distance of the lesion from the anal verge was 7.5 cm (range, 5-15 cm). The median lesion diameter was 2.3 cm (range, 0.5-5.0 cm). The locations of the lesions were as follows: 18 on the dorsal, 5 on the ventral, and 5 on the lateral rectal wall. The median operating time was 55 min (range, 25-165 min), compared with 105 min reported in the literature. All the lesions except one could be radically excised. No intraoperative complications occurred. Postoperative complications occurred for three patients, all due to hemorrhage. The median hospital stay was 3 days (range, 1-21 days). During a median follow-up period of 15 months (range, 1-35 months), two recurrences took place. CONCLUSION The study findings showed that for rectal tumors located up to 15 cm from the anal verge with a maximal diameter of 5 cm, TEO using standard laparoscopic instruments with a 2D view is feasible and provides results comparable with those associated with a 3D view and dedicated instruments. Furthermore, the 2D procedure can be performed with improved ergonomics due to movable monitors and is considerably less expensive.


title: Tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes and Diabetic Nephropathy: A Pilot Phase II Clinical Trial.

text: Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate diabetes through its superior antioxidant, antihyperglycemic, and anti-inflammatory properties in diabetic rats. This study aimed to investigate the effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes. Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C were assessed for possible correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded, placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg twice a day while the control group (n = 23) received placebo twice a day for 8 weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and renal parameters such as UACR, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) were compared between the two groups. It was found that serum Nε-CML significantly correlated to the severity of microalbuminuria. For every 1 ng/mL increase in serum Nε-CML, the odds of diabetic nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum biomarkers. In conclusion, serum Nε-CML is a potential biomarker for diabetic nephropathy. Treatment with Tocovid significantly reduced serum creatinine; therefore Tocovid may be a useful addition to the current treatment for diabetic nephropathy.


title: A comprehensive analysis of bio-inspired design of femoral stem on primary and secondary stabilities using mechanoregulatory algorithm.

text: The coated porous section of stem surface is initially filled with callus that undergoes osseointegration process, which develops a bond between stem and bone, lessens the micromotions and transfers stresses to the bone, proximally. This phenomenon attributes to primary and secondary stabilities of the stems that exhibit trade-off the stem stiffness. This study attempts to ascertain the influence of stem stiffness on peri-prosthetic bone formation and stress shielding when in silico models of solid CoCr alloy and Ti alloy stems, and porous Ti stems (53.8 GPa and 31.5 GPa Young's moduli) were implanted. A tissue differentiation predictive mechanoregulation algorithm was employed to estimate the evolutionary bond between bone and stem interfaces with 0.5-mm- and 1-mm-thick calluses. The results revealed that the high stiffness stems yielded higher stress shielding and lower micromotions than that of low stiffness stems. Contrarily, bone formation around solid Ti alloy stem and porous Ti 53.8 GPa stem was augmented in 0.5-mm- and 1-mm-thick calluses, respectively. All designs of stems exhibited different rates of bone formation, diverse initial micromotions and stress shielding; however, long-term bone formation was coherent with different stress shielding. Therefore, contemplating the secondary stability of the stems, low stiffness stem (Ti 53.8 GPa) gave superior biomechanical performance than that of high stiffness stems.


title: Exogenous fluorescent tracer agents based on pegylated pyrazine dyes for real-time point-of-care measurement of glomerular filtration rate.

text: Novel pyrazine carboxamides bearing hydrophilic poly(ethylene glycol) (PEG) moieties were designed, synthesized, and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, compounds 4d and 5c that contain about 48 ethylene oxide units in the PEG chain exhibited the most favorable physicochemical and renal clearance properties. In vitro studies show that these two compounds have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that 4d and 5c have a higher urine recovery of the injected dose than iothalamate (a commonly considered gold standard GFR agent). Pharmacokinetic studies show that these two compounds exhibit a plasma clearance equivalent to iothalamate, but with a faster (i.e. lower) terminal half-life than iothalamate (possibly from restricted distribution into the extracellular space due to large molecular size and hydrodynamic volume). Furthermore, the plasma clearance of 4d and 5c remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration exclusively. Finally, noninvasive real-time monitoring of this class of compounds was demonstrated by pharmacokinetic clearance of 5c by optical measurements in rat model, which correlates strongly with plasma concentration of the tracer. Hence, 4d and 5c are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.


title: Fusion imaging with contrast-enhanced ultrasonography for evaluating the early therapeutic efficacy of radiofrequency ablation for small hypervascular hepatocellular carcinomas with iso-echoic or unclear margins on conventional ultrasonography.

text: PURPOSE We evaluated the efficacy of fusion imaging combining contrast-enhanced ultrasonography (CEUS) images and arterial phase contrast-enhanced CT (CECT) or hepatobiliary phase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) images for the early evaluation of the effectiveness of radiofrequency ablation (RFA) for small hypervascular hepatocellular carcinoma (HCC) with iso-echoic or unclear margins on conventional US. METHODS Forty HCCs (22 iso-echoic and 18 unclear margin lesions) with mean diameters of 13.7 mm were treated using RFA under the guidance of fusion imaging with CEUS. The adequacy of RFA was evaluated using fusion imaging with CEUS 1 day after RFA. CECT or EOB-MRI was performed 1 month after RFA. We reviewed the images obtained using both modalities. RESULTS When the 1-month CECT or EOB-MRI scans were used as the reference standard, the sensitivity, specificity, and accuracy of the 1-day fusion imaging for the diagnosis of the adequate ablation of these HCCs were 97, 100, and 98%, respectively; the kappa value for the agreement between the findings using the two modalities was 0.655. CONCLUSION Fusion imaging with CEUS appears to be a useful method for the early evaluation of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear margins on conventional US.


Covid-19: GP surgeries close for two weeks after staff test positive.


Why do nice people get bad pneumonia? "Be quick or be dead" (Iron Maiden).


title: Transanal colorectal resection using natural orifice translumenal endoscopic surgery (NOTES).

text: The surgical management of rectal cancer has evolved over the past century, with total mesorectal excision (TME) emerging as standard of care. As a result of the morbidity associated with open TME, minimally invasive techniques have become popular. Natural orifice translumenal endoscopic surgery (NOTES) has been held as the next revolution in surgical techniques, offering the possibility of 'incisionless' TME. Early clinical series of transanal TME with laparoscopic assistance (n = 72) are promising, with overall intraoperative and postoperative complication rates of 8.3% and 27.8%, respectively, similar to laparoscopic TME. The mesorectal specimen was intact in all patients, and 94.4% had negative margins. There was no oncological recurrence in average-risk patients at short-term follow up, and 2-year survival rates in high-risk patients were comparable to that after laparoscopic TME. These preliminary studies demonstrate transanal NOTES TME with laparoscopic assistance to be clinically feasible and safe given careful patient selection, surgical expertise, and appropriate procedural training. We are hopeful that with optimization of transanal instruments and surgical techniques, pure transanal NOTES TME will become a viable alternative to open and laparoscopic TME in the future.


title: A probable atypical skin manifestation of COVID-19 infection.

text: The manifestations of COVID-19 are diverse. We report a 56-year-old man with confirmed COVID-19 infection who presented with a probable atypical skin manifestation of this disease mimicking arthropod bite reaction. Early identification may expedite proper management and control of the disease.


title: Addressing trauma and stress in the COVID-19 pandemic: Challenges and the promise of integrated primary care.

text: Integrated primary care settings are ideal locations for treatment of posttraumatic stress concerns as primary care is the principal access point for mental health treatment in the United States. The COVID-19 global pandemic will increase the necessity of posttraumatic stress-related psychological care for vulnerable populations and frontline providers through traditional and virtual methods; integrated primary care settings are rapidly adapting to meet this need. Integrating more behavioral health clinicians into primary care clinics will provide better access to whole-person care when it is needed most. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Mourning our dead in the covid-19 pandemic.


Physician mothers of children with complex needs: untapped wisdom, resilience, and a hidden workforce.


title: Cytokine release syndrome in severe COVID-19.

text: Lessons from arthritis and cell therapy in cancer patients point to therapy for severe disease.


title: Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients.

text: OBJECTIVE The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange. DESIGN Prospective, crossover, nonrandomized interventional study. SETTING Medical and surgical ICUs at Massachusetts General Hospital. PATIENTS Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m(2)) patients (n = 14). INTERVENTIONS This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial. MEASUREMENTS AND MAIN RESULTS The average body mass index was 50.7 ± 16.0 kg/m(2). The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 ± 4.0 vs 21.3 ± 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (Δ11 ± 7 mL/kg; p < 0.01) and oxygenation (Δ86 ± 50 torr; p < 0.01) and decreased lung elastance (Δ5 ± 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 ± 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation. CONCLUSIONS Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation.


Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China.


title: Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19.

text: Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.


title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report.

text: Background The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were■ cancer prognosis and anticipated benefit from treatment,■ risk of treatment toxicity during scarce health care access, and■ patient risk of contracting covid-19. Conclusions This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.


title: Retrospective Analysis of Delayed Intraparenchymal Hemorrhage after Flow-Diverter Treatment: Presentation of a Retrospective Multicenter Trial.

text: BACKGROUND AND PURPOSE Intracranial aneurysm treatment with flow diverters has shown satisfying results in terms of aneurysm occlusion, and while some cases of delayed intraparenchymal hemorrhage have been described, no systematic analysis of the risk factors affecting its occurrence has been conducted in a large series of patients. This retrospective analysis of delayed intraparenchymal hemorrhage after flow-diverter treatment is a multicenter, retrospective study using a large series of treated patients to analyze factors affecting the occurrence of delayed intraparenchymal hemorrhage. MATERIALS AND METHODS Patients treated with flow diverters and presenting with delayed intraparenchymal hemorrhage were included from December 2007 to December 2014 in 7 participating centers in France. Patient and aneurysm characteristics were recorded as were characteristics of bleeding (size, lateralization, and time to bleed), treatment, and clinical outcome after 1, 3, and 6 months. RESULTS Delayed intraparenchymal hemorrhage occurred in 11 patients between 1 and 21 days after the procedure. In 10 of these patients, hemorrhages were ipsilateral to the treated aneurysms. Five of the 11 underwent surgery, and 9 of the 11 had good clinical outcomes at 6 months (mRS ≤2). CONCLUSIONS The pathogenesis of delayed intraparenchymal hemorrhage occurring after flow-diverter treatment remains unclear. The multidisciplinary management of delayed intraparenchymal hemorrhage yields a relatively low morbidity-mortality rate compared with the initial clinical presentation.


title: A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection.

text: Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42-0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82-0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23-43.26] for a 400 mg/μg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/μg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/μg cutoff, 2.26-13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.


title: Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations.

text: BACKGROUND Enhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus. METHODS A systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations. RESULTS A total of 157 full texts were screened. Thirty-seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal-directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia. CONCLUSIONS The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.


title: Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

text: Importance Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration ClinicalTrials.gov Identifier: NCT02241655.


title: Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.

text: BACKGROUND Xpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)-recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review. OBJECTIVES To determine diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for tuberculosis in adults with presumptive pulmonary tuberculosis (PTB) and for rifampicin resistance in adults with presumptive rifampicin-resistant tuberculosis. SEARCH METHODS We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, to 11 October 2018, without language restriction. SELECTION CRITERIA Randomized trials, cross-sectional, and cohort studies using respiratory specimens that evaluated Xpert MTB/RIF, Xpert Ultra, or both against the reference standard, culture for tuberculosis and culture-based drug susceptibility testing or MTBDRplus for rifampicin resistance. DATA COLLECTION AND ANALYSIS Four review authors independently extracted data using a standardized form. When possible, we also extracted data by smear and HIV status. We assessed study quality using QUADAS-2 and performed meta-analyses to estimate pooled sensitivity and specificity separately for tuberculosis and rifampicin resistance. We investigated potential sources of heterogeneity. Most analyses used a bivariate random-effects model. For tuberculosis detection, we first estimated accuracy using all included studies and then only the subset of studies where participants were unselected, i.e. not selected based on prior microscopy testing. MAIN RESULTS We identified in total 95 studies (77 new studies since the previous review): 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF and Xpert Ultra on the same participant specimen.Tuberculosis detectionOf the total 86 studies, 45 took place in high tuberculosis burden and 50 in high TB/HIV burden countries. Most studies had low risk of bias.Xpert MTB/RIF pooled sensitivity and specificity (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants; high-certainty evidence). We found similar accuracy when we included all studies.For a population of 1000 people where 100 have tuberculosis on culture, 103 would be Xpert MTB/RIF-positive and 18 (17%) would not have tuberculosis (false-positives); 897 would be Xpert MTB/RIF-negative and 15 (2%) would have tuberculosis (false-negatives).Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%); Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%), (1 study, 1439 participants; moderate-certainty evidence).Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear-positive and 67% (62% to 72%) in smear-negative, culture-positive participants, (45 studies). Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV-negative and 81% (75% to 86%) in HIV-positive participants; specificities were similar 98% (97% to 99%), (14 studies).Rifampicin resistance detectionXpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants; high-certainty evidence).For a population of 1000 people where 100 have rifampicin-resistant tuberculosis, 114 would be positive for rifampicin-resistant tuberculosis and 18 (16%) would not have rifampicin resistance (false-positives); 886 would be would be negative for rifampicin-resistant tuberculosis and four (0.4%) would have rifampicin resistance (false-negatives).Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%), (1 study, 551 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found Xpert MTB/RIF to be sensitive and specific for diagnosing PTB and rifampicin resistance, consistent with findings reported previously. Xpert MTB/RIF was more sensitive for tuberculosis in smear-positive than smear-negative participants and HIV-negative than HIV-positive participants. Compared with Xpert MTB/RIF, Xpert Ultra had higher sensitivity and lower specificity for tuberculosis and similar sensitivity and specificity for rifampicin resistance (1 study). Xpert MTB/RIF and Xpert Ultra provide accurate results and can allow rapid initiation of treatment for multidrug-resistant tuberculosis.


title: Pure Laparoscopic Versus Open Right Hepatectomy for Hepatocellular Carcinoma in Patients With Cirrhosis: A Propensity Score Matched Analysis.

text: OBJECTIVE We aimed to describe our experience with pure laparoscopic right hepatectomy (LRH) and to compare its outcomes with those of open right hepatectomy (ORH) in hepatocellular carcinoma (HCC) patients with liver cirrhosis. BACKGROUND Laparoscopic liver resection has been reported as a safe and effective approach for the management of liver cancer; however, its outcomes have not been evaluated in a large cohort of HCC patients with liver cirrhosis. METHODS We retrospectively reviewed the medical records of 152 patients who underwent pure LRH (n = 37) or ORH (n = 115) between June 2008 and July 2015 at the Asan Medical Center in Seoul, Korea. We performed 1:1 propensity score matching between the LRH and ORH groups. Subsequently, 33 patients were included in each group. RESULTS There was no statistically significant difference between the LRH and ORH groups regarding the rate of complications (P = 0.053). However, the mean comprehensive complication index, which accounts for the severity of complications, was significantly lower in the LRH group (0.63 vs 4.42; P = 0.025). There were no significant differences between the LRH and ORH groups regarding 2-year disease-free survival rate or 2-year overall survival rate (P = 0.645 and P = 0.090, respectively). CONCLUSIONS Even in patients with cirrhosis, pure LRH is not less safe than the traditional open approach. The oncological outcomes of HCC were also comparable between the two groups. In selected patients, pure LRH for HCC appears to represent a viable alternative to ORH.


title: Early Outcomes with Single-antenna High-powered Percutaneous Microwave Ablation for Primary and Secondary Hepatic Malignancies: Safety, Effectiveness, and Predictors of Ablative Failure.

text: Objective Microwave ablation (MWA) of liver malignancies has gained much traction over the past 5 years. However, MWA carries relatively higher rates of residual disease compared to resection. Likelihood of MWA success is multifactorial and newer devices with more reliable ablation zones are being developed to overcome these drawbacks. This manuscript is a review of our first 100 liver ablations with the newer single antenna high powered MWA system. Materials and Methods Retrospective chart review of patients that underwent MWA for either primary or secondary hepatic malignancies between March 2015 and July 2016 was conducted. The complete ablation rates, rate of new lesions, complications, and short-term survival were analyzed. Multiple statistical tests, including multivariate regression, were used to assess risk factors for local residual and recurrent disease. Results Fifty-three patients (median age 61 ± 9 years, 39 males) underwent 100 MWAs. Of the 100 lesions ablated, 76 were hepatocellular cancers (HCCs) and 24 were metastases. Median lesion size was 16 ± 9 mm. Seventy- five of these patients had multifocal disease targeted in the same session. Seventy patients had cirrhosis (median model for end-stage liver disease score 9 ± 3; Child-Pugh B and C in 42%). An 83% complete lesion ablation rate was seen on follow-up imaging with liver protocol magnetic resonance imaging/computed tomography (median follow-up of 1 year). The minor complication rate was 9.4% with no major complications or 30-day mortality. Despite this, evidence of new foci of hepatic disease was found in 47% of patients, the majority (80%) of which were in HCC patients (P < 0.01) and most of these new lesions were in a different hepatic segment (64%). Degree of cirrhosis (P < 0.01), presence of non-alcoholic steatohepatitis (NASH) (P = 0.01) and lesion's subcapsular location (P = 0.03) was significant predictors of residual disease. With the subset analysis of only HCC lesions larger than 1 cm, only the presence of NASH remained significant. Conclusion The single probe high power MWA of malignant hepatic lesions is safe and effective with minimal morbidity. Degree of cirrhosis, NASH, and subcapsular location was associated with an increased rate of residual disease on short-term follow-up.


title: Ablation of skeletal metastases: current status.

text: Image-guided percutaneous ablation of bone metastases is an effective, minimally invasive alternative to conventional therapies in the palliation of pain from metastatic disease. Ablative technologies applied in the treatment of skeletal metastases include radiofrequency ablation, cryoablation, microwave ablation, laser ablation, ethanol ablation, and, most recently, focused ultrasound. These ablative methods may be performed in combination with percutaneous cementoplasty to provide support and stabilization for metastases in weight-bearing bones at risk for pathologic fracture.


title: The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.

text: The serine proteases of the trypsin-like (S1) family play critical roles in many key biological processes including digestion, blood coagulation, and immunity. Members of this family contain N- or C-terminal domains that serve to tether the serine protease catalytic domain directly to the plasma membrane. These membrane-anchored serine proteases are proving to be key components of the cell machinery for activation of precursor molecules in the pericellular microenvironment, playing vital functions in the maintenance of homoeostasis. Substrates activated by membrane-anchored serine proteases include peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules and viral coat proteins. In addition, new insights into our understanding of the physiological functions of these proteases and their involvement in human pathology have come from animal models and patient studies. The present review discusses emerging evidence for the diversity of this fascinating group of membrane serine proteases as potent modifiers of the pericellular microenvironment through proteolytic processing of diverse substrates. We also discuss the functional consequences of the activities of these proteases on mammalian physiology and disease.


title: Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits.

text: Elevated intraocular pressure is the only treatable risk factor for glaucoma, an eye disease that is the leading cause of irreversible blindness worldwide. We have identified cromakalim prodrug 1 (CKLP1), a novel water-soluble ATP-sensitive potassium channel opener, as a new ocular hypotensive agent. To evaluate the pharmacokinetic and safety profile of CKLP1 and its parent compound levcromakalim, Dutch-belted pigmented rabbits were treated intravenously (0.25 mg/kg) or topically (10 mM; 4.1 mg/ml) with CKLP1. Body fluids (blood, aqueous and vitreous humor) were collected at multiple time points and evaluated for the presence of CKLP1 and levcromakalim using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based assay. Histology of tissues isolated from Dutch-belted pigmented rabbits treated once daily for 90 days was evaluated in a masked manner by a certified veterinary pathologist. The estimated plasma parameters following intravenous administration of 0.25 mg/kg of CKLP1 showed CKLP1 had a terminal half-life of 61.8 ± 55.2 min, Tmax of 19.8 ± 23.0 min and Cmax of 1968.5 ± 831.0 ng/ml. Levcromakalim had a plasma terminal half-life of 85.0 ± 37.0 min, Tmax of 61.0 ± 32.0 min and Cmax of 10.6 ± 1.2 ng/ml. Topical CKLP1 treatment in the eye showed low levels (<0.3 ng/mL) of levcromakalim in aqueous and vitreous humor, and trace amounts of CKLP1 and levcromakalim in the plasma. No observable histological changes were noted in selected tissues that were examined following topical application of CKLP1 for 90 consecutive days. These results suggest that CKPL1 is converted to levcromakalim in the eye and likely to some extent in the systemic circulation.


title: Preliminary experience with the percutaneous embolization of juvenile angiofibromas using only ethylene-vinyl alcohol copolymer (Onyx) for preoperative devascularization prior to surgical resection.

text: BACKGROUND AND PURPOSE Juvenile angiofibromas are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss by using only Onyx for percutaneous juvenile angiofibroma tumor embolization. MATERIALS AND METHODS We reviewed the clinical records and preoperative and postoperative imaging studies of a consecutive series of 9 patients with juvenile angiofibromas who were treated with preoperative embolization with direct percutaneous injection of Onyx followed by resection from a standard open surgical or endoscopic approach. RESULTS Two Fisch type I, 1 Fisch type II, 5 Fisch type IIIa, and 1 Fisch type IVa tumor were treated. Complete devascularization was achieved in all cases percutaneously with only Onyx. There were no complications. The average intraoperative blood loss was 567.7 mL (range, 10-1700 mL). An average of 2.2 needles (range, 1-5 needles) was placed into the tumor. An average of 14.6 mL of Onyx (range, 2-25 mL) was injected into each tumor. Four Fisch type IIIa tumors were removed completely from only an ENE approach. CONCLUSIONS Presurgical direct percutaneous embolization of a juvenile angiofibroma with only EVOH before surgical resection is safe and feasible. Our preliminary experience suggests that Onyx may offer a higher degree of devascularization compared with other embolic agents. This may facilitate an easier surgical resection with lower blood loss.


title: Validation of a radioimmunoassay of serum trypsin-like immunoreactivity in ferrets.

text: Measurement of serum trypsin-like immunoreactivity (TLI) is used to assess exocrine pancreatic function in dogs and cats. Ferrets ( Mustela putorius furo) serve as valuable animal models for human diseases such as cystic fibrosis and other pulmonary diseases, and may be a useful model of other diseases including pancreatitis. We developed and analytically validated a competitive radioimmunoassay (RIA) for measurement of TLI in ferret serum by determination of analytical sensitivity, assay linearity, accuracy of spiking recovery, precision, and reproducibility. Analytical sensitivity of the assay was 0.55 μg/L. Observed-to-expected (O/E) ratio for dilutional parallelism was 90.2-127.9% (mean: 108.1 ± 11.9%). The O/E ratio for spiking recovery was 94.5-113.0% (mean: 103.9 ± 7.2%). The intra- and inter-assay coefficients of variation (CVs) were 2.7-5.7% and 3.5-8.2%, respectively. The reference interval (RI) for serum TLI derived from 31 healthy ferrets was 28-115 μg/L; the 90% confidence interval for the lower and upper limits of the RI were 10.0-32.1 μg/L and 103-126 μg/L, respectively. This TLI RIA is analytically sensitive, sufficiently linear, accurate, precise, and reproducible for the measurement of TLI in ferret serum samples.


This scientist hopes to test coronavirus drugs on animals in locked-down Wuhan.


title: Performance of blow-by methods in delivering oxygen to pediatric patients during transport: A laboratory study.

text: BACKGROUND Providing supplemental oxygen with a blow-by method is used to provide additional oxygen to patients who will not tolerate an oxygen delivery device in direct contact with their face. Blow-by methods are often improvised from parts of standard equipment. The performance is very dependent on the distance to the face and the direction of the gas flow. Blow-by methods are used by anesthetists during transport but their performance in delivering supplemental oxygen has only been tested in static situations. The aim of this nonclinical study was to determine the performance of different blow-by methods in the delivery of additional oxygen to pediatric patients during transport. METHODS A manikin of a child with a facemask of appropriate size was transported along a 60 m corridor from the operating theater to the PACU. Oxygen delivery to the face of the manikin was measured during transport. Six blow-by methods were tested with oxygen flows of 3, 6, and 10 L/min and with the facemask at 0 cm from the face and at 5 cm from the face. The outcome parameter was: blow-by method reaching and maintaining an FiO2 >50% during transport from the pediatric operating theater to the PACU. RESULTS At 0 cm from the face, five out of six blow-by methods maintained a FiO2 >50% with all three flow rates. At 5 cm only two of the blow-by methods were able to maintain an FiO2 >50% and this only at flow rates of 10 L/min. All other blow-by methods provided lower FiO2 s; in three, the FiO2 decreased to values only marginally above 21%. The decrease in FiO2 typically started within 6-12 m from the start of the transport. CONCLUSION It is concluded that the ability of blow-by methods to deliver a FiO2 >50% depends on the method used and distance from the face.


title: Predictors of malignant brain edema after mechanical thrombectomy for acute ischemic stroke.

text: BACKGROUND Malignant brain edema (MBE) is a devastating complication in ischemic stroke. Data on MBE in patients who have had mechanical thrombectomy (MT) are relatively scarce. OBJECTIVE To investigate the incidence, predictors, and clinical outcomes of MBE in patients after MT. METHODS We included 130 consecutive patients after MT caused by anterior circulation large vessel occlusion stroke, treated with MT. MBE was defined as a midline shift of ≥5 mm on the follow-up imaging within 72 hours after MT. Characteristics of patients at admission and details of treatment were collected. The 90-day modified Rankin scale score was used as a measure of functional outcomes. RESULTS Of the 130 patients (age, 68.6±10.9 years; male, 50%), 35 (26.9%) patients developed MBE. The patients with MBE had a lower rate of functional independence (OR=7.831; 95% CI 1.731 to 35.427; p=0.008) and significantly higher mortality at 90 days (OR=7.958; 95% CI 2.274 to 27.848; p=0.001) than patients without MBE. In 104 (80%) patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3), 24 (23.1%) patients exhibited MBE. After adjustment for confounding, ICA occlusion (OR=3.746; 95% CI 1.169 to 12.006; p=0.026) and worse collateral score (grade 1 vs grade 0: OR=0.727; 95% CI 0.192 to 2.753; p=0.638; grade 2 vs grade 0: OR=0.130; 95% CI 0.021 to 0.819; p=0.030) were significantly associated with the development of MBE, despite successful recanalization. CONCLUSIONS MBE after MT is not uncommon and was related to poor functional outcomes. Localization of a vessel occlusion and collateral status may play a role in the development of MBE.


title: Pure transanal total mesorectal excision for rectal cancer: experience with 55 cases.

text: Background Although the anatomic difficulties of laparoscopic surgery for rectal cancer have been resolved by hybrid transanal total mesorectal excision (h-taTME), a completely incisionless surgical procedure has not yet been developed. This study was performed to explore the efficacy of pure taTME (p-taTME) without laparoscopic assistance as a completely non-invasive surgical procedure for rectal cancer. Methods We retrospectively evaluated all patients with rectal cancer who underwent p-taTME between December 2015 and April 2018. Relevant patient characteristics and clinical information including the surgical procedure, specimens, pathological characteristics, and patients' post-operative state were analysed and the feasibility of p-taTME in patients with rectal cancer was assessed. Results Fifty-five patients who had undergone p-taTME were included in this study. They comprised 32 (58.2%) men and 23 (41.8%) women with a mean age of 65.6 ± 10.6 years and mean body mass index of 23.4 ± 3.3 kg/m2. The median surgical time was 180.0 (range, 130-360) min and estimated blood loss was 25.0 (range, 15-80) mL. The commonest post-operative complication was varying degrees of faecal incontinence (56.4%). However, such incontinence greatly improved after pelvic-floor-function-rehabilitation exercises and did not seriously affect the patients' quality of life. Conclusions p-taTME is a relatively safe and incisionless procedure for patients with middle and low rectal cancer, especially in those with obesity or a narrow pelvis. However, further studies of the indications and long-term efficacy are needed to verify the suitability of this procedure.


title: Exercise for reducing falls in people living with and beyond cancer.

text: BACKGROUND Current treatment modalities for cancer have been successful in achieving improved survivorship; however, they come with a number of long-term adverse effects. Accidental falls are a common and clinically significant adverse event in people living with and beyond cancer and rates are higher than in the rest of the population. OBJECTIVES To assess the effects of prescribed or provided exercise for reducing accidental falls, and falls risk factors of strength, flexibility and balance, in people living with and beyond cancer. SEARCH METHODS We searched the following electronic databases from inception to 10 July 2018, with no restrictions: CENTRAL, MEDLINE, Embase, and seven other databases. We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) for ongoing trials, and reference lists of reviews and retrieved articles for additional studies. SELECTION CRITERIA We included all randomised controlled trials investigating exercise interventions versus no treatment, usual care or non-exercise interventions on falls incidence or falls risk factors in adults living with and beyond cancer (18 years of age or older at diagnosis). We excluded cross-over studies and studies in acute or inpatient hospice care. DATA COLLECTION AND ANALYSIS At least two review authors independently completed data extraction for included papers. We used Covidence software to manage screening, data collection and extraction. We assessed evidence using GRADE and presented results in a 'Summary of findings' table. MAIN RESULTS Eleven studies (835 participants) compared exercise to usual care. No studies compared exercise with no treatment or non-exercise interventions. The quality of the evidence was very low for the primary outcome rates of falls, and very low to low for the secondary outcomes. We downgraded the evidence due to study limitations (risk of bias), and issues of imprecision due to small sample sizes, inconsistency and indirectness. All studies were at high risk of bias for blinding of participants and personnel due to inability to blind participants to an exercise intervention. Risk of bias was generally low or unclear for other categories.There was generally little information on the important outcomes comparing exercise to usual care.Rates of falls and number of fallers: one study (223 participants) measured accidental falls, but reported neither the rate of falls or the number of fallers; there was no difference in the number of falls between exercise and usual care (very low-quality evidence).Strength: 10 studies (813 participants) reported on strength outcomes. Two analyses favoured exercise over usual care: quadriceps strength (2 studies, 72 participants; mean difference (MD) 8.99 kg, 95% confidence interval (CI) 1.29 to 16.70; low-quality evidence), and leg press (4 studies, 388 participants; MD 21.1 kg, 95% CI 8.47 to 33.74; low-quality evidence). In one analysis of the Sit-to-Stand Test, there was no difference between exercise and usual care (4 studies, 214 participants; standardised mean difference (SMD) -0.45, 95% CI -1.05 to 0.14; very low-quality evidence).Flexibility: one study (21 participants) reported on flexibility for Sit-and-Reach Distance (MD 2.05 cm, 95% CI 0.59 to 3.51; very low-quality evidence).Balance: five studies (350 participants) measured three different balance outcomes. Two analyses favoured exercise over usual care: postural balance (4 studies, 127 participants; standardised mean difference (SMD) 0.44, 95% CI 0.08 to 0.79; very low-quality evidence), and Backward Walk Test (2 studies, 280 participants; SMD -0.24, 95% CI -0.48 to -0.01; low-quality evidence). There was no difference between exercise and usual care for the Timed Up-and-Go Test (1 study, 15 participants; MD -0.35 seconds, 95% CI -1.47 to 0.77; low-quality evidence).Number of people sustaining a fall-related fracture: the quality of the evidence for exercise reducing fall-related fractures was very low.Adverse events: a single study (223 participants) noted some temporary muscle soreness on initiation of exercise or when there was an increase in the weight lifted. As no occurrence data were reported, we could not assess this variable further. No studies reported musculoskeletal injury. Analysis indicated that there was very low-quality evidence that exercise did not increase fatigue. AUTHORS' CONCLUSIONS There is a paucity of evidence for exercise training to reduce fall rates in people living with and beyond cancer. Exercise training may improve strength, flexibility and balance for people in this population, but the evidence is very low quality.


[Management of Patients with COVID-19 - Recommendations from a Palliative Care Perspective].


title: Management of gynecomastia-changes in psychological aspects after surgery-a systematic review.

text: Gynecomastia affects up to two-thirds of the male population. For many patients the psychological impact of the disease is substantial. Surgical treatment is indicated when medical treatments fail. Until now, most published research on the subject has focused on how effective surgical treatment is on correcting the cosmetic appearance of the breast. Little is known about the effect of surgical treatment on the psychological aspects of the disease. The aim of this review was to identify the psychological domains affected by the disease and the effect of surgical treatment on these. A systematic search of the published literature was performed. All studies on the subject were evaluated for inclusion and six studies were included in the review. Several of the included studies reported improvement in quality of life and several psychological domains after surgical treatment for gynecomastia. Among these domains, are; vitality, emotional discomfort, limitations due to physical aspects and limitations due to pain. Impact of surgical treatment for gynecomastia seems to be beneficial for several psychological domains. The current level of evidence on this subject is very low and future studies, examining the impact of the surgical intervention for gynecomastia on psychological domains, are greatly needed. More data on this subject could improve the pre-operative evaluation of these patients and help identify the patients that will benefit from treatment.


Viewpoint: The COVID-19 and climate crises.


title: The covariation of acoustic features of infant cries and autonomic state.

text: The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of physiological systems in promoting social behavior and responding to social challenges. This phylogenetic shift in neural regulation of the autonomic nervous system in mammals has produced a neuroanatomically integrated social engagement system, including neural mechanisms that regulate both cardiac vagal tone and muscles involved in vocalization. Mammalian vocalizations are part of a conspecific social communication system, with several mammalian species modulating acoustic features of vocalizations to signal affective state. Prosody, defined by variations in rhythm and pitch, is a feature of mammalian vocalizations that communicate emotion and affective state. While the covariation between physiological state and the acoustic frequencies of vocalizations is neurophysiologically based, few studies have investigated the covariation between vocal prosody and autonomic state. In response to this paucity of scientific evidence, the current study explored the utility of vocal prosody as a sensitive index of autonomic activity in human infants during the Still Face challenge. Overall, significant correlations were observed between several acoustic features of the infant vocalizations and autonomic state, demonstrating an association between shorter heart period and reductions in heart period and respiratory sinus arrhythmia following the challenge with the dampening of the modulation of acoustic features (fundamental frequency, variance, 50% bandwidth, and duration) that are perceived as prosody.


title: A novel approach in retrieving retained pulmonary bullet injury.

text: Video-assisted thoracoscopic surgery can be a useful tool in selected penetrating chest trauma patients for diagnostic and therapeutic purposes. It is currently a safe and feasible alternative to thoracotomy in the management of chest trauma especially for hemodynamically stable patients. Penetrating chest trauma with retained bullet was removed successfully in a 25 years old patient using double-port VATS technique in combination with fluoroscopy, he made full recovery, hospital stay was very short.


docid: tpwzwfkv

title: The many uncertainties of COVID-19.


title: Impact of System-Wide King LT Airway Implementation on Orotracheal Intubation.

text: OBJECTIVES Orotracheal intubation is a key component of prehospital airway management and success rates are dependent on procedural experience. Supraglottic airway devices are increasingly being used in the prehospital setting. As a result, paramedics may have fewer opportunities for performing intubation, limiting their proficiency in the procedure. We aimed to determine the trends in intubation versus supraglottic airway use over an 8 year period. We also aimed to determine the association between system-wide introduction of King LT guidelines and ETI success rates. METHODS We performed a retrospective observational study of 37 Emergency Medical Services (EMS) agencies in a 10 county region of Southwestern Pennsylvania. Cases between January 1, 2005 and December 31, 2012 were included if an advanced airway procedure was performed. We determined trends in advanced airway placement and compared the proportion of cases with first pass intubation success before and after the King LT was introduced and promoted by statewide protocol starting in 2007. Use of airway devices before and after King LT implementation were presented using descriptive statistics and compared using Pearson's Chi-square or Fishers Exact test as appropriate. We compared first pass success rate of orotracheal intubation between study periods using multivariable logistic regression, controlling for other factors that may impact success of orotracheal intubation (year, EMS agency, age category, traumatic injury, and cardiac arrest). RESULTS There were 712 cases of orotracheal intubation before and 2,835 cases after introduction of the King LT. The proportion of cases ultimately managed with orotracheal intubation before and after 2007 decreased from 72.3% (95% CI 68.9-75.6%) to 67.1% (95% CI 65.3-68.8%) (p = 0.007). In the multivariable analysis, success of orotracheal intubation was not associated with implementation of the King LT airway (OR 1.02, 95% CI 0.74-1.41). CONCLUSION Fewer patients with advanced airway management received orotracheal intubation since introduction of the King LT. In spite of this modest change in airway management, there has not been a change in orotracheal intubation success rate since introduction of this supraglottic device as a primary or rescue airway in this regional EMS setting.


title: Glucose and Insulin Response of Horses Grazing Alfalfa, Perennial Cool-Season Grass, and Teff Across Seasons.

text: Elevated nonstructural carbohydrate (NSC) values in pasture forages can cause adverse health effects in some horses (Equus caballus L.). The objectives of this study were to determine the impact of different forage species on blood glucose and insulin concentrations of horses throughout the grazing season. Research was conducted in July (summer) and September (fall) in St. Paul, MN. Alfalfa (Medicago sativa L.), mixed perennial cool-season grasses (CSG), and teff (Eragrostis tef [Zucc.] Trotter) pastures were grazed by six horses (24 ± 2 years) that were randomly assigned to one of three forage types in a replicated Latin-square design. Jugular catheters were inserted 1 hour before the start of grazing and horses had access to pasture each day from 08:00 to 16:00 hours. Jugular venous blood samples were collected from each horse before being turned out (0 hours) and then at 2-hour intervals following turnout. Plasma and serum samples were collected and analyzed for glucose and insulin, respectively. Corresponding forage samples were taken by hand harvest. Seasons were analyzed separately and data were analyzed using the MIXED procedure in SAS with P ≤ .05. Teff generally had lower (P ≤ .05) equine digestible energy, crude protein, and NSC compared to the other forages. Differences in peak insulin were observed between horses grazing CSG and teff during the fall grazing (P ≤ .05). These results suggest grazing teff could lower the glucose and insulin response of some horses.


title: Preparing emergency personnel in dialysis: a just-in-time training program for additional staffing during disasters.

text: BACKGROUND There are 341 000 patients in the United States who are dependent on routine dialysis for survival. Recent large-scale disasters have emphasized the importance of disaster preparedness, including supporting dialysis units, for people with chronic disease. Contingency plans for staffing are important for providing continuity of care for a technically challenging procedure such as dialysis. PReparing Emergency Personnel in Dialysis (PREP-D) is a just-in-time training program designed to train individuals having minimum familiarity with the basic steps of dialysis to support routine dialysis staff during a disaster. METHODS A 5-module educational program was developed through a collaborative, multidisciplinary effort. A pilot study testing the program was performed using 20 nontechnician dialysis facility employees and 20 clinical-year medical students as subjects. RESULTS When comparing pretest and posttest scores, the entire study population showed a mean improvement of 28.9%, with dialysis facility employees and medical students showing improvements of 21.8% and 36.4%, respectively (P < .05 for all comparisons). CONCLUSIONS PREP-D participants were able to demonstrate improved tests scores when taught in a just-in-time training format. The knowledge gained by using the PREP-D program during a staffing shortage may allow for continuity of care for critical services such as dialysis during a disaster.


title: The establishment of a bank of stored clinical bone marrow stromal cell products.

text: BACKGROUND Bone marrow stromal cells (BMSCs) are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. METHODS The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP) used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. RESULTS Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. CONCLUSIONS The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria.


title: Peptides as protein binding site mimetics.

text: The rational/structure-based design and/or combinatorial development of molecules capable of structurally and functionally mimicking the binding sites of proteins represents a promising strategy for the exploration and understanding of protein structure and function. The ultimate goal of using such molecules is the modulation of protein function through controlled interference with the underlying binding events. In addition to their basic significance, such proteinmimetics are also useful tools for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. Owing to their chemical and structural relation to proteins, as well as the relative simplicity of their chemical or recombinant synthesis, peptides have emerged as adequate molecules for the mimicry of protein binding sites, as well as the inhibition of protein-protein interactions.


docid: tywsbowc

title: Completely intracorporeal robotic-assisted laparoscopic ileovesicostomy.

text: We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100 mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively.


title: A monoclonal antibody against transmissible gastroenteritis virus generated via immunization of a DNA plasmid bearing TGEV S1 gene.

text: Transmissible gastroenteritis virus (TGEV) is a member of the coronaviruses. The viral spike (S) protein of TGEV mediates interaction between TGEV and its susceptible cells. Herein, DNA plasmid bearing TGEV S1 gene (the N terminal half of TGEV S gene) was used to immunize BALB/c mice followed by generation of a monoclonal antibody (MAb) using the hybridoma technique. The generated MAb (1H4) was identified by ELISA. Immunofluorescence assays showed that MAb 1H4 was able to detect infection of cells with TGEV. The MAb 1H4 distinguished TGEV from other control viruses. Additionally, although the type of MAb 1H4 was IgM, it could reduce cell infection by TGEV in a dose-dependent manner.


title: Tensile strength and adhesion formation of mesh fixation systems used in laparoscopic incisional hernia repair.

text: BACKGROUND Mesh tearoff from the tissue is the most common reason for hernia recurrence after hernia surgery involving the use of a synthetic mesh. Various fixation systems were critically compared in terms of their retention strength and the formation of adhesions. METHODS In a prospective study with 25 Sprague-Dawley rats, two pieces of Parietex composite meshes measuring 2 x 3 cm were fixed intraperitoneally in a paramedian location. The randomized mesh fixation groups included transfascial fixed suture, ProTack, AbsorbaTack, and I-Clip. Of the 25 rats, 12 were killed and analyzed 1 week after implantation, with the remaining 13 rats killed and analyzed after 2 months. Adhesions observed at the time of mesh removal were measured according to an adhesion scoring system, and the fixation strengths of the individual fixation systems were tested. Additionally, the foreign body reaction to the mesh and fixation systems was measured as well as their potential degradation. RESULTS After 1 week, the retention strength of transfascial fixed suture was significantly higher (8.7 N/cm(2)) than that of ProTack (5.6 N/cm(2)) or AbsorbaTack (5.7 N/cm(2)). After 2 months, the retention strength had increased to 13.2 N/cm(2) in the transfascial fixed suture group, which was significantly higher than in the ProTack (9.7 N/cm(2)) or AbsorbaTack (8.7 N/cm(2)) groups. In contrast, the mesh could be fixed with the I-Clip only in 56% of the cases, and then achieved rather poor retention strength. Adhesion was significantly greater in the ProTack group than in any of the other groups (p < 0.001). At 2 months, scanning electron microscopy showed only marginal degradation of the absorbable elements. CONCLUSIONS Suture fixation led to satisfactory attachment of the prosthesis. Additional widespread anchorage of the mesh was achieved with ProTack or AbsorbaTack. The feasibility and retention strength of the I-Clip were poor.


title: Modern technical approaches in resectional hepatic surgery.

text: Techniques in liver surgery have improved considerably during the last decades, allowing for liver resections with low morbidity and mortality. Preoperative patient selection, perioperative management, and intraoperative blood-sparing techniques are the cornerstones of modern liver surgery. Multimodal treatment of colorectal liver metastases has expanded the group of patients who are potential candidates for liver resection. Adjunctive techniques, including preoperative portal vein embolization and staged hepatectomy, have facilitated the safe performance of extensive liver resection. This article provides an overview of indications for liver resection and a systematic description of the technical approach to the most commonly performed resections.


docid: jzclrpur

title: Adjudin protects against cerebral ischemia reperfusion injury by inhibition of neuroinflammation and blood-brain barrier disruption.

text: Neuroinflammation mediated by activation of microglia and interruption of the blood-brain barrier (BBB) is an important factor that contributes to neuron death and infarct area diffusion in ischemia reperfusion injury. Finding novel molecules to regulate neuroinflammation is of significant clinical value. We have previously shown that adjudin, a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway. In this study we continued to explore whether adjudin could be neuroprotective by using the transient middle cerebral artery occlusion (tMCAO) model. Adjudin treatment after reperfusion significantly decreased the infarction volume and neuroscore compared to the vehicle group. Staining of CD11b showed that adjudin markedly inhibited microglial activation in both the cortex and the striatum, accompanied by a reduction in the expression and release of cytokines TNF-α, IL-1β and IL-6. Concomitantly, adjudin noticeably prevented BBB disruption after ischemia and reperfusion, as indicated by the reduction of IgG detection in the brain cortex and striatum versus the vehicle group. This finding was also corroborated by immunofluorescence staining and immunoblotting of tight junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously inhibited the elevated MMP-9 activity after stroke. Together these data demonstrate that adjudin protects against cerebral ischemia reperfusion injury, and we present an effective neuroinflammation modulator with clinical potential.


docid: itjthzmk

title: Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of Interventional Management of Stroke (IMS) III Trial.

text: BACKGROUND AND PURPOSE General anesthesia (GA) for endovascular therapy (EVT) of acute ischemic stroke may be associated with worse outcomes. METHODS The Interventional Management of Stroke III trial randomized patients within 3 hours of acute ischemic stroke onset to intravenous tissue-type plasminogen activator±EVT. GA use within 7 hours of stroke onset was recorded per protocol. Good outcome was defined as 90-day modified Rankin Scale ≤2. A multivariable analysis adjusting for dichotomized National Institutes of Health Stroke Scale (NIHSS; 8-19 versus ≥20), age, and time from onset to groin puncture was performed. RESULTS Four hundred thirty-four patients were randomized to EVT, 269 (62%) were treated under local anesthesia and 147 (33.9%) under GA; 18 (4%) were undetermined. The 2 groups were comparable except for median baseline NIHSS (16 local anesthesia versus 18 GA; P<0.0001). The GA group was less likely to achieve a good outcome (adjusted relative risk, 0.68; confidence interval, 0.52-0.90; P=0.0056) and had increased in-hospital mortality (adjusted relative risk, 2.84; confidence interval, 1.65-4.91; P=0.0002). Those with medically indicated GA had worse outcomes (adjusted relative risk, 0.49; confidence interval, 0.30-0.81; P=0.005) and increased mortality (relative risk, 3.93; confidence interval, 2.18-7.10; P<0.0001) with a trend for higher mortality with routine GA. There was no significant difference in the adjusted risks of subarachnoid hemorrhage (P=0.32) or symptomatic intracerebral hemorrhage (P=0.37). CONCLUSIONS GA was associated with worse neurological outcomes and increased mortality in the EVT arm; this was primarily true among patients with medical indications for GA. Relative risk estimates, though not statistically significant, suggest reduced risk for subarachnoid hemorrhage and symptomatic intracerebral hemorrhage under local anesthesia. Although the reasons for these associations are not clear, these data support the use of local anesthesia when possible during EVT. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.