title: Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review.

text: IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm. OBJECTIVE To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm. DESIGN, SETTING, AND PARTICIPANTS OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014. INTERVENTIONS Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay. RESULTS Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, -0.3% to 13.9%]; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]). CONCLUSIONS AND RELEVANCE In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN04386758.


title: Family Presence During Resuscitation: A Double-Edged Sword.

text: PURPOSE To illuminate the meaning of the lived experiences of resuscitation team members with the presence of the patient's family during resuscitation in the cultural context of Iran. DESIGN An interpretative phenomenology was used to discover the lived experiences of the nurses and physicians of Tabriz hospitals, Iran, with family presence during resuscitation (FPDR). A total of 12 nurses and 9 physicians were interviewed over a 6-month period. METHODS The interviews were audio recorded and semistructured, and were transcribed verbatim. Van Manen's technique was used for data analysis. FINDINGS Two major themes and 10 subthemes emerged, including destructive presence (cessation of resuscitation, interference in resuscitation, disruption to the resuscitation team's focus, argument with the resuscitation team, and adverse mental image in the family) and supportive presence (trust in the resuscitation team, collaboration with the resuscitation team, alleviating the family's concern and settling their nerves, increasing the family's satisfaction, and reducing conflict with resuscitation team members). CONCLUSIONS Participants stated that FPDR may work as a double-edged sword for the family and resuscitation team, hurting or preserving quality. It is thus recommended that guidelines be created to protect patients' and families' rights, while considering the positive aspects of the phenomenon for hospitals. CLINICAL RELEVANCE A liaison support person would act to decrease family anxiety levels and would be able to de-escalate any potentially aggressive or confrontational events during resuscitation. Well-trained and expert cardiopulmonary resuscitation team members do not have any stress in the presence of family during resuscitation. Resuscitation events tend to be prolonged when family members are allowed to be present.


title: Basic Immunology may lead to translational therapeutic rationale:: SARS-CoV-2 and Rheumatic Diseases.

text: COVID-19 pandemia is a major concern for patients and health care systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analyzing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, US and Europe, did not reveal an higher risk of infection, either for Rheumatoid Arthritis, Juvenile Idiopathic Arthritis nor for Lupus Erythematosus. Antimalarials, anti-IL6-Anti-IL6-receptor, anti-IL1, anti-GM-CSF-receptor , JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection, suggests that the immunological consequences of the infection need to be strictly understood.


title: Recruitment and retention of underrepresented populations in Alzheimer's disease research: A systematic review.

text: Introduction Alzheimer's disease and related dementias (ADRD) disproportionately impact racial and ethnic minority and socioeconomically disadvantaged adults. Yet, these populations are significantly underrepresented in research. Methods We systematically reviewed the literature for published reports describing recruitment and retention of individuals from underrepresented backgrounds in ADRD research or underrepresented participants' perspectives regarding ADRD research participation. Relevant evidence was synthesized and evaluated for quality. Results We identified 22 eligible studies. Seven studies focused on recruitment/retention approaches, all of which included multifaceted efforts and at least one community outreach component. There was considerable heterogeneity in approaches used, specific activities and strategies, outcome measurement, and conclusions regarding effectiveness. Despite limited use of prospective evaluation strategies, most authors reported improvements in diverse representation in ADRD cohorts. Studies evaluating participant views focused largely on predetermined explanations of participation including attitudes, barriers/facilitators, education, trust, and religiosity. Across all studies, the strength of evidence was low. Discussion Overall, the quantity and quality of available evidence to inform best practices in recruitment, retention, and inclusion of underrepresented populations in ADRD research are low. Further efforts to systematically evaluate the success of existing and emergent approaches will require improved methodological standards and uniform measures for evaluating recruitment, participation, and inclusivity.


title: Percutaneous radiofrequency ablation of a bleeding pseudoaneurysm during CT-guided renal cancer treatment. A case report.

text: We describe a new emergency interventional radiology approach in percutaneous procedure complications. We present the case of an 81-year-old male with small renal cancer, approached with percutaneous radiofrequency ablation (RTA) and complicated by pseudoaneurysm bleeding of a renal artery branch. In the emergency setting, pseudoaneurysm was treated in the CT room by the same RTA needle, without any complications or local tumor recurrence during the next 6-month follow-up.


A historical personal perspective on human retroviruses and their infection of T cells.


title: Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020.

text: An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.


title: Antibacterial, Antitubercular and Antiviral Activity Evaluations of Some Arylidenehydrazide Derivatives Bearing Imidazo[2,1-b]thiazole Moiety.

text: Objectives The aim of this study was to determine the probable antibacterial, antitubercular, and antiviral activities of some N2 -arylidene-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (3a-j). Further structural optimization of the identified lead structures can lead us to new more active potential antibacterial, antitubercular, and antiviral agents. Materials and Methods Antibacterial activities of the title compounds against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922. These molecules were also evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the BACTEC 460 radiometric system and BACTEC 12B medium. Moreover, all the compounds (3a-j) were also evaluated against some DNA and RNA viruses in Madin-Darby Canine Kidney, Crandell-Rees Feline Kidney (CRFK), Vero, human embryonic lung (HEL) and HeLa cells. Results Among the tested compounds, 3i displayed the highest efficacy against S. aureus and E. coli. Compound 3j, 5-nitro-2-furfurylidene derivative showed the highest antituberculosis activity (IC50: 6.16 µg/mL and IC90: 14.390 µg/mL). Compound 3i showed the most potent antiviral activity against feline corona virus in CRFK cell cultures (antiviral EC50: 7.5 µM and SI>13). Furthermore, compounds 3c and 3g displayed activity against herpes simplex virus-1 and vaccinia virus in HEL cell cultures (antiviral EC50 values of 9; 16 and 20; 14 µM, respectively). Conclusion On the basis of aforementioned results, it can be conluded that imidazo[2,1-b]thiazole derivatives bearing hydrazone moieties serve as promising chemical probes to design therapeutic agents with antibacterial, antitubercular, and antiviral properties.


title: Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis.

text: UNLABELLED ♦ BACKGROUND Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA). ♦ METHODS Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 - 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused. ♦ RESULTS The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2). ♦ CONCLUSIONS The findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18-19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.


title: Using gene transcription patterns (bar coding scans) to guide wound debridement and healing.

text: PURPOSE To acquaint wound care practitioners with new information related to debridement of chronic wounds. TARGET AUDIENCE This continuing education activity is intended for physicians and nurses with an interest in wound care. OBJECTIVES After reading this article and taking this test, the reader should be able to: 1. Explain the role of keratinocytes in wound healing. 2. Discuss new research findings on the physiological differences between healing and nonhealing wounds.3. Identify implications of the new research for debridement of chronic wounds.


Commentary: Evolving understanding of coronavirus disease 2019: Molecular biology, immunology, and surgery.


title: Bringing stroke clinical guidelines to life.

text: Clinical practice guidelines are essential for driving evidence-based clinical care to patients. In an era of ever-increasing research evidence, keeping guidelines up to date is a challenging and resource-intensive process. Advances in technological platforms provide opportunities to develop new models of guideline development that will allow for continuous, rapid updates to recommendations as new evidence emerges. As Australia and other countries begin to develop these models, we have an opportunity to work more closely together to ensure the most efficient use of resources.


title: Stress detection using ECG and EMG signals: A comprehensive study.

text: BACKGROUND AND OBJECTIVE In recent years, stress and mental health have been considered as important worldwide concerns. Stress detection using physiological signals such as electrocardiogram (ECG), skin conductance (SC), electromyogram (EMG) and electroencephalogram (EEG) is a traditional approach. However, the effect of stress on the EMG signal of different muscles and the efficacy of combination of the EMG and other biological signals for stress detection have not been taken into account yet. This paper presents a comprehensive review of the EMG signal of the right and left trapezius and right and left erector spinae muscles for multi-level stress recognition. Also, the ECG signal was employed to evaluate the efficacy of EMG signals for stress detection. METHODS Both EMG and ECG signals were acquired simultaneously from 34 healthy students (23 females and 11 males, aged 20-37 years). Mental arithmetic, Stroop color-word test, time pressure, and stressful environment were employed to induce stress in the laboratory. RESULTS The accuracies of stress recognition in two, three and four levels were 100%, 97.6%, and 96.2%, respectively, obtained from the distinct combination of feature selection and machine learning algorithms. CONCLUSIONS The comparison of stress detection accuracies resulted from EMG and ECG indicators demonstrated the strong ability and the effectiveness of EMG signal for multi-level stress detection.


title: Laparoscopic right hemicolectomy.

text: Over the past 20 years, laparoscopic colectomy has become a well-established technique in the surgical armamentarium of colorectal operations, with proven reductions in postoperative pain, time to return of bowel function, and length of hospital stay. After early concerns over its oncologic effects, large prospective, multicenter trials have proven its safety in colorectal adenocarcinoma, with equivalence in nodal harvest, recurrence rates, disease-free survival, and overall survival. Laparoscopic right hemicolectomy in particular is a relatively accessible technique which may be performed by a single surgeon and an assistant/camera operator; this operation serves as an excellent method to develop laparoscopic skills for more complicated colorectal procedures. In this article, we describe the technical aspects of our approach to laparoscopic right hemicolectomy, which utilizes a medial-to-lateral, no-touch technique and either an intracorporeal or extracorporeal anastomosis.


title: Comparison between breast MRI and contrast-enhanced spectral mammography.

text: BACKGROUND The main goal of this study was to compare contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) with histopathological results and to compare the sensitivity, accuracy, and positive and negative predictive values for both imaging modalities. MATERIAL/METHODS After ethics approval, CESM and MRI examinations were performed in 102 patients who had suspicious lesions described in conventional mammography. All visible lesions were evaluated independently by 2 experienced radiologists using BI-RADS classifications (scale 1-5). Dimensions of lesions measured with each modality were compared to postoperative histopathology results. RESULTS There were 102 patients entered into CESM/MRI studies and 118 lesions were identified by the combination of CESM and breast MRI. Histopathology confirmed that 81 of 118 lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and 93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion size estimates on CESM and breast MRI were similar, both slightly larger than those from histopathology. CONCLUSIONS Our results indicate that CESM has the potential to be a valuable diagnostic method that enables accurate detection of malignant breast lesions, has high negative predictive value, and a false-positive rate similar to that of breast MRI.


title: AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA.

text: Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA.IMPORTANCE Autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus arise when cells of the immune system become activated and attack host cells and tissues. We found that DNA generated by endogenous retroviruses and retroelements in inbred mice and mouse cells is recognized by several host proteins found in macrophages that are members of the ALR family and that these proteins both suppress and activate the pathways leading to the generation of cytokines and IFNs. We also show that there is great genetic diversity between different inbred mouse strains in the ALR genes, which might contribute to differential susceptibility to autoimmunity. Understanding how immune cells become activated is important to the control of disease.


APIC Strategic Partner Program.


title: Efficacy and safety of intravascular lithotripsy for the treatment of peripheral arterial disease: An individual patient-level pooled data analysis.

text: BACKGROUND Peripheral arterial disease (PAD) is one of the most common manifestations of atherosclerotic disease worldwide. Peripheral arterial calcification reduces acute success and long-term patency of endovascular therapy for PAD. Several calcium modification devices are available for use in peripheral interventions. Outcomes after peripheral intravascular lithotripsy (IVL), a novel approach using pulsatile sonic waves to treat luminal and medial calcium in patients with PAD, have not been extensively characterized. Therefore, we sought to perform an individual patient-level data (IPD) pooled analysis of available studies to evaluate the efficacy and safety of IVL in the treatment of PAD. METHODS AND RESULTS We pooled IPD, including baseline and procedural variables, from five prospective studies which assessed IVL in the treatment of patients with extensive peripheral artery calcification. Final postprocedural percent diameter stenosis (%DS) and procedural angiographic complications were assessed by independent core laboratory. Efficacy endpoints were analyzed using linear mixed effects models and safety endpoints were tabulated overall and by vascular bed. Among 336 patients who underwent endovascular revascularization with use of IVL, there was a significant reduction between pre-procedural and final %DS of 55.1% (95% confidence interval 53.3-57.0%, p < .0001). Core-laboratory assessed lesion-level complications, including flow-limiting dissections (Types D-F), vessel perforation, distal embolization, thrombus, abrupt closure, and no reflow, occurred in 4/328 (1.22%) of treated lesions. CONCLUSIONS The present IPD of five prospective studies, marking the largest analysis to date evaluating the use of IVL in significantly calcified PAD lesions, demonstrates this treatment strategy to be both effective and safe.


title: The energetic cost of mounting an immune response for Pallas's long-tongued bat (Glossophaga soricina).

text: The acute phase response (APR) is the first line of defense of the vertebrate immune system against pathogens. Mounting an immune response is believed to be energetically costly but direct measures of metabolic rate during immune challenges contradict this assumption. The energetic cost of APR for birds is higher than for rodents, suggesting that this response is less expensive for mammals. However, the particularly large increase in metabolic rate after APR activation for a piscivorous bat (Myotis vivesi) suggests that immune response might be unusually costly for bats. Here we quantified the energetic cost and body mass change associated with APR for the nectarivorous Pallas's long-tongued bat (Glossophaga soricina). Activation of the APR resulted in a short-term decrease in body mass and an increase in resting metabolic rate (RMR) with a total energy cost of only 2% of the total energy expenditure estimated for G. soricina. This increase in RMR was far from the large increase measured for piscivorous bats; rather, it was similar to the highest values reported for birds. Overall, our results suggest that the costs of APR for bats may vary interspecifically. Measurement of the energy cost of vertebrate immune response is limited to a few species and further work is warranted to evaluate its significance for an animal's energy budget.


title: Simulation as a Tool to Facilitate Practice Changes in Teams Taking Care of Patients Under Investigation for Ebola Virus Disease in Spain.

text: INTRODUCTION We analyzed the impact of simulation-based training on clinical practice and work processes on teams caring for patients with possible Ebola virus disease (EVD) in Cantabria, Spain. METHODS The Government of Spain set up a special committee for the management of EVD, and the Spanish Ministry of Health and foreign health services created an action protocol. Each region is responsible for selecting a reference hospital and an in-house care team to care for patients under investigation. Laboratory-confirmed cases of EVD have to be transferred to the Carlos III Health Institute in Madrid. Predeployment training and follow-up support are required to help personnel work safely and effectively. Simulation-based scenarios were designed to give staff the opportunity to practice before encountering a real-life situation. Lessons learned by each team during debriefings were listed, and a survey administered 3 months later assessed the implementation of practice and system changes. RESULTS Implemented changes were related to clinical practice (eg, teamwork principles application), protocol implementation (eg, addition of new processes and rewriting of confusing parts), and system and workflow (eg, change of shift schedule and rearrangement of room equipment). CONCLUSIONS Simulation can be used to detect needed changes in protocol or guidelines or can be adapted to meet the needs of a specific team.


title: Varicella zoster meningitis: an atypical case of zoster reactivation in immunocompetent young adult.

text: Varicella virus is a neurotropic virus that can reactivate later in life to cause zoster or shingles. Typically, it affects elderly, immunocompromised population. We report an unusual case of an immunocompetent young adult presenting with occipital headache and zoster rash, without preherpetic and postherpetic neuralgia, who was diagnosed with varicella meningitis on Polymerase chain reaction (PCR). He was treated with intravenous acyclovir and later discharged on famciclovir. Diagnosis of varicella meningitis is difficult in the absence of typical features of zoster rash and requires high index of suspicion. Rapid diagnostic tests including varicella PCR and antithecal antibody testing can help in the confirmation of varicella zoster meningitis.


docid: ekjfcepg

title: Fear of Ebola: The Influence of Collectivism on Xenophobic Threat Responses.

text: In response to the Ebola scare in 2014, many people evinced strong fear and xenophobia. The present study, informed by the pathogen-prevalence hypothesis, tested the influence of individualism and collectivism on xenophobic response to the threat of Ebola. A nationally representative sample of 1,000 Americans completed a survey, indicating their perceptions of their vulnerability to Ebola, ability to protect themselves from Ebola (protection efficacy), and xenophobic tendencies. Overall, the more vulnerable people felt, the more they exhibited xenophobic responses, but this relationship was moderated by individualism and collectivism. The increase in xenophobia associated with increased vulnerability was especially pronounced among people with high individualism scores and those with low collectivism scores. These relationships were mediated by protection efficacy. State-level collectivism had the same moderating effect on the association between perceived vulnerability and xenophobia that individual-level value orientation did. Collectivism-and the set of practices and rituals associated with collectivistic cultures-may serve as psychological protection against the threat of disease.


JCVI response on hepatitis B vaccination.


title: Clinical Indicators of the Need for Telemetry Postoperative Monitoring in Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee Arthroplasty.

text: BACKGROUND AND OBJECTIVES Obstructive sleep apnea is associated with increased complication rates postoperatively. Current literature does not provide adequate guidance on management of these patients. This study used the STOP-Bang questionnaire to diagnose patients with possible obstructive sleep apnea (score ≥3). We hypothesized that a STOP-Bang score of 3 or greater would significantly correlate with the number of oxygen desaturation episodes during the first 48 hours after total knee arthroscopy. METHODS The STOP-Bang questionnaire was administered to 110 patients preoperatively. All patients underwent spinal-epidural anesthesia with a saphenous nerve block and sedation and were connected to the Nellcor OxiMax N-600x pulse oximeter for 48 hours postoperatively. RESULTS Final analysis included 98 patients. There was no significant difference in the total number of desaturation events between STOP-Bang groups (score <3 vs ≥3 and score <5 vs ≥5). The total number of desaturation events on postoperative day 1 was greater than that on day 0 (32.8 ± 42.7 vs 4.1 ± 10.0, P < 0.0001). The total number of desaturation events correlated with length of hospital stay (r = 0.329, P = 0.0001). Patients with a preoperative serum CO2 of 30 mmol/L or greater had significantly longer episodes of desaturation on postoperative day 0 compared with CO2 of less than 30 mmol/L (233.7 ± 410.1 vs 82.0 ± 126.2 seconds, P = 0.044). CONCLUSIONS A high preoperative value of CO2 should be a warning for possible prolonged episodes of desaturation postoperatively. An attempt to limit postoperative desaturation events should be made to minimize length of stay.


title: Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.

text: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).


title: The COVID-19 Epidemic and the Prison System in Italy.

text: The Italian Ministry of Justice and that of Health have established two strategies to limit the spread of COVID-19 in prisons: progressive isolation from the external world and adoption of practices to identify possible cases and to treat infected subjects. After the announcement of regulations revolts erupted in numerous Italian prisons. The motivations and effects of these strategy are discussed critically into the search for a balance between the right to health and other rights of prisoners in Italian prisons with the problem of an occupancy level of 121.75%.


title: TransForm occlusion balloon catheter for the treatment of intracranial aneurysms, initial experience.

text: INTRODUCTION The technique of balloon remodeling allows the endovascular treatment of wide-neck intracranial aneurysms. For many years the only available devices were the Hyperform and the Hyperglide balloon catheters. Recently, other companies have developed newer devices, single or dual-lumen. We present our initial experience with the TransForm occlusion balloon catheter for the treatment of intracranial aneurysms. METHODS We retrospectively analysed from our prospectively gathered aneurysm database all aneurysms that were treated with balloon remodelling using TransForm occlusion balloon catheters from January 2013 to February 2014. We assessed patient demographics, morphological features of the aneurysms, procedure feasibility, technical and clinical complications. RESULTS Thirty-three patients harbouring 36 intracranial saccular aneurysms were treated during 33 procedures. Clinical finding were: 15 incidental discovery, 13 subarachnoid haemorrhage (SAH), five aneurysms with mass effect, one ruptured aneurysm with SAH and mass effect, one recanalisation and one intraparenchymal haematoma. Thirty-five aneurysms were in the anterior and one in the posterior circulation. Mean dome and neck size were, respectively, 5.8 mm and 3.6 mm. Twenty-three aneurysms were treated with TransForm C and 13 with TransForm SC. We had two procedural thromboembolic complications, without permanent clinical events. No early rebleeding occurred. CONCLUSIONS In our small series, the TransForm occlusion balloon catheter seems to be safe and effective for the treatment of intracranial aneurysms, in ruptured and unruptured cases.


title: Comparison of thromboelastography parameters between different catheter lumen diameters in an uncontrolled haemorrhagic shock model in swine.

text: Sampling technique is a concern for standardization of thromboelastography (TEG), as it contributes towards preanalytical variation in TEG tracings. The objective of this study was to assess the influence of catheter lumen diameter on TEG parameters with kaolin-activated native blood in a swine haemorrhagic shock model, using standardized sampling techniques. We hypothesized that one or more TEG parameters will differ between venous samples collected from catheters with different diameter lumens. Ten male landrace swine were included in the study. Standard cut-down techniques on both femoral veins were performed and catheterized with a 14-gauge (14G) and a 20-gauge (20G) catheter of the same length. Blood withdrawal times were standardized to 3 s and TEG parameters (R, K, α, maximum amplitude, G and coagulation index) were measured or calculated. Significant differences were detected for R (14G < 20G; P = 0.002), K (14G < 20G; P = 0.026), maximum amplitude (14G > 20G; P = 0.02), G (14G > 20G; P = 0.001) and coagulation index (14G > 20G; P < 0.001). No significant differences were measured for α (P = 0.058). Bias values (method A: 20G; method B: 14G) for R, K, α, maximum amplitude, G and coagulation index were 1.00, 0.14, -1.88, -1.56, -1.39 and -1.07, respectively. Using TEG analysis, kaolin-activated native whole blood samples obtained from 14G catheters are hypercoagulable (clotted faster and stronger clot) compared with samples obtained from 20G catheters. Sampling methodology should be standardized and systematic when comparing TEG parameters.


title: Detection of Nipah virus RNA in fruit bat (Pteropus giganteus) from India.

text: The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.


docid: lofrebwi

title: Principled leadership in public health: integrating ethics into practice and management.

text: Public health officials frequently face ethical tensions and conflicting obligations when making decisions and managing health departments. Leadership requires an ongoing approach to ethics that focuses on two dimensions of practice: the professional relationships of officials developed over time with their communities and the ethical aspects of day-to-day public health activities. Education and competencies in ethics may be helpful in practice, by providing, at a minimum, frameworks and ethical principles to help structure analysis, discussion, and decision making in health departments and with community stakeholders. Such a "practical ethics" approach in public health practice begins with a focus on public health values and an agency mission statement and integrates ethics throughout the organization by, for example, setting performance measures based on them. Using a case in emergency preparedness, this article describes ways in which ethical frameworks and the Code of Ethics can be used as tools for education and to integrate ethics into agency activities and programs.


title: Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

text: BACKGROUND Post-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex difference. METHODS Using two standard measures of PTSD-like responses in rats, the acoustic startle response (ASR) and dexamethasone suppression test (DST), we tested the effects of traumatic stress in adult male and female rats using two rodent models of PTSD, single prolonged stress and predator exposure. We then examined the neural correlates underlying these responses with cFos and glucocorticoid receptor immunohistochemistry in brain regions implicated in the traumatic stress response. RESULTS We now report that adult male and female rats across two models of PTSD show consistent sex-specific responses that recapitulate fundamental differences of PTSD in men and women. Trauma-exposed males showed the well-established hyper-responsive phenotype of enhanced ASR and exaggerated negative feedback control of the hypothalamic-pituitary-adrenal axis, while the same traumatic event had little effect on these same measures in females. Dramatic sex differences in how trauma affected cFos and glucocorticoid receptor expression in the brain lend further support to the idea that the trauma response of male and female rats is fundamentally different. CONCLUSIONS Two standard measures, ASR and DST, might suggest that females are resilient to the effects of traumatic stress, but other measures make it clear that females are not resilient, but simply respond differently to trauma. The next important question to answer is why. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience. The divergent effects of trauma in the brains of males and females begin to shed light on the neurobiological underpinnings of these sex differences, paving the way for improved diagnostics and therapeutics that effectively treat both men and women.


title: Finding Camel-ot: A Holy Grail against pandemic SARS-CoV-2?

text: Engineered camelid antibody multimers can potently block SARS-CoV-2 viral entry.


title: Laparoscopic hernia complexity predicts operative time and length of stay.

text: PURPOSE Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS). METHODS The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures. RESULTS Indications for surgery were recurrent incisional hernia in 33 % of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348 cm(2) (±214; range 113-1,036) was used. Mean operative time was 132 min (±66.1; range 53-412). The mean LOS was 4.0 days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5 % and no mortality. There was one recurrence in 30 days (1.1 %). Patients who had a surgery >120 min or a LOS >1 day were statistically more likely to have multiple hernias, larger defect sizes (>40 cm(2)), larger mesh sizes (>300 cm(2)) or a history of recurrent hernia (P < 0.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS. CONCLUSIONS LVHR is safe with a low incidence of perioperative complications. Patients with multiple, larger and recurrent hernias have longer operative times and LOS. This information can be used to guide preoperative planning for the patient, surgeon and treating institution.


title: Effectiveness of Revive SE in the RAPID registry : Revive Acute Ischemic Stroke Patients ImmeDiately (RAPID) Prospective Multicenter Trial.

text: PURPOSE The prospective, multicenter Revive Acute ischemic stroke Patients ImmeDiately (RAPID) trial was carried out to evaluate the real-world safety and efficacy of the Revive SE stent retriever. METHODS From January 2017 the study planned to enroll 100 patients with acute ischemic stroke who were treated with the Revive SE as a first pass. The study primary outcomes were rates of favorable reperfusion using the modified thrombolysis in cerebral infarction score [mTICI] 2b/3 and rates of favorable outcome with the modified Rankin Scale (mRS) ≤2 at 3 months. The secondary outcomes were time interval from puncture to vascular reperfusion, number of passes by Revive SE stent-retriever, incidence of distal embolization and into new territories and rate of symptomatic intracranial hemorrhage (SICH) within 24 h post intervention. RESULTS A total of 100 treated patients (mean age: 65.6 ± 11.3 years) were enrolled. The median National Institutes of Health Stroke Scale before the procedure was 16. Target vessel occlusions were as follows: middle cerebral artery (MCA) M1 in 48, M2 in 6, anterior cerebral artery (ACA) in 3, internal carotid artery (ICA) in 22, basilar artery (BA) in 17, and vertebral artery (VA) in 4. Reperfusion rate with Revive SE without rescue devices was 69%. Reperfusion rate with Revive SE only was 83.3% in MCA M2, followed by 82.4% in BA. Thromboembolic complications and SICH developed in 10% and 2% of patients, respectively. Overall, a satisfactory reperfusion was achieved in 92% and a favorable outcome at 90 days in 48%. CONCLUSION Use of the Revive SE for thrombectomy appeared to be effective and safe but these findings need be confirmed in larger clinical trials (RAPID ClinicalTrials.gov number, NCT03007082).


title: Use of failure modes, effects, and criticality analysis to compare the vulnerabilities of laparoscopic versus open appendectomy.

text: PURPOSE To measure the feasibility of using FMECA applied to the surgery and then compare the vulnerabilities of laparoscopic versus open appendectomy by using FMECA. METHODS The FMECA study was performed on each single selected phase of appendectomy and on complication-related data during the period January 1, 2009, to December 31, 2010. The risk analysis phase was completed by evaluation of the criticality index (CI) of each appendectomy-related failure mode (FM). The CI is calculated by multiplying the estimated frequency of occurrence (O) of the FM, by the expected severity of the injury to the patient (S), and the detectability (D) of the FM. RESULTS In the first year of analysis (2009), 177 appendectomies were performed, 110 open and 67 laparoscopic. Eleven adverse events were related to the open appendectomy: 1 bleeding (CI: 8) and 10 postoperative infections (CI: 32). Three adverse events related to the laparoscopic approach were recorded: 1 postoperative infection (CI: 8) and 2 incorrect extractions of the appendix through the umbilical port (CI: 6). In the second year of analysis (2010), 158 appendectomies were performed, 69 open and 89 laparoscopic. Four adverse events were related to the open appendectomy: 1 incorrect management of the histological specimen (CI: 2), 1 dehiscence of the surgical wound (CI: 6), and 2 infections (CI: 6). No adverse events were recorded in laparoscopic approach. CONCLUSION FMECA helped the staff compare the 2 approaches through an accurate step-by-step analysis, highlighting that laparoscopic appendectomy is feasible and safe, associated with a lower incidence of infection and other complications, reduced length of hospital stay, and an apparent lower procedure-related risk.


title: Successful laparoscopic gastric resection and safe introduction of a single-incision technique for gastric submucosal tumors located near the esophagogastric junction.

text: PURPOSE Laparoscopic gastric resection cannot be easily applied for submucosal tumors near the esophagogastric junction (NEJ-SMTs). Furthermore, there have been no reports of single-incision laparoscopic surgery (SILS) for NEJ-SMTs. We evaluated our laparoscopic surgical outcomes for NEJ-SMTs, including a newly introduced phase of SILS. METHODS We retrospectively reviewed a total of 18 patients diagnosed with NEJ-SMTs who underwent laparoscopic surgery between April 2002 and September 2013. RESULTS All patients underwent laparoscopic gastric resection without local complications and with a negative surgical margin, including 12 patients treated with conventional laparoscopic surgery (CLS) and six patients treated with SILS. The mean length of the operation was 184.3 ± 52.3 min, and the mean blood loss was 19.2 ± 17.7 mL. All patients underwent complete resection. There were no statistically significant differences between the CLS and SILS groups in terms of the surgical outcomes. CONCLUSION Despite this challenging location of the tumor, laparoscopic gastric resection for NEJ-SMTs is safe and feasible. Furthermore, SILS can provide a better cosmetic result, which can lead to better global patient satisfaction in carefully selected patients with NEJ-SMTs.


title: The hepatitis C virus RNA-dependent RNA polymerase directs incoming nucleotides to its active site through magnesium-dependent dynamics within its F motif.

text: RNA viruses synthesize new genomes in the infected host thanks to dedicated, virally-encoded RNA-dependent RNA polymerases (RdRps). As such, these enzymes are prime targets for antiviral therapy, as has recently been demonstrated for hepatitis C virus (HCV). However, peculiarities in the architecture and dynamics of RdRps raise fundamental questions about access to their active site during RNA polymerization. Here, we used molecular modeling and molecular dynamics simulations, starting from the available crystal structures of HCV NS5B in ternary complex with template-primer duplexes and nucleotides, to address the question of ribonucleotide entry into the active site of viral RdRp. Tracing the possible passage of incoming UTP or GTP through the RdRp-specific entry tunnel, we found two successive checkpoints that regulate nucleotide traffic to the active site. We observed that a magnesium-bound nucleotide first binds next to the tunnel entry, and interactions with the triphosphate moiety orient it such that its base moiety enters first. Dynamics of RdRp motifs F1 + F3 then allow the nucleotide to interrogate the RNA template base prior to nucleotide insertion into the active site. These dynamics are finely regulated by a second magnesium dication, thus coordinating the entry of a magnesium-bound nucleotide with shuttling of the second magnesium necessary for the two-metal ion catalysis. The findings of our work suggest that at least some of these features are general to viral RdRps and provide further details on the original nucleotide selection mechanism operating in RdRps of RNA viruses.


title: The mechanism and energetics of a ligand-controlled hydrophobic gate in a mammalian two pore channel.

text: In the last decade two-pore intracellular channels (TPCs) attracted the interest of researchers, still some key questions remain open. Their importance for vacuolar (plants) and endo-lysosomal (animals) function highlights them as a very attractive system to study, both theoretically and experimentally. Indicated as key players in the trafficking of the cell, today they are considered a new potential target for avoiding virus infections, including those from coronaviruses. A particular boost for theoretical examinations has been made with recent high-resolution X-ray and cryo-EM structures. These findings have opened the way for efficient and precise computational studies at the atomistic level. Here we report a set of multiscale-calculations performed on the mTPC1, a ligand- and voltage-gated sodium selective channel. The molecular dynamics and enhanced molecular dynamics simulations were used for a thorough analysis of the mammalian TPC1 behaviour in the presence and absence of the ligand molecule, with a special accent on the supposed bottleneck, the hydrophobic gate. Moreover, from the reconstructed free energy obtained from enhanced simulations, we have calculated the macroscopic conductance of sodium ions through the mTPC1, which we compared with measured single-channel conductance values. The hydrophobic gate works as a steric barrier and the key parameters are its flexibility and the dimension of the sodium first hydration shell.


title: Effects of sleep disordered breathing on functional capacity and quality of life in chronic kidney disease Egyptian patients.

text: PURPOSE We assessed the prevalence of sleep disordered breathing (SDB) and investigated its effects on the muscle functional capacity and quality of life (QoL) among chronic kidney disease (CKD) Egyptian patients, either maintained or not maintained on hemodialysis (HD). METHODS The study population comprised 100 CKD patients who were divided into patients maintained on HD (n = 60; M/F = 28:32) and patients not maintained on HD (n = 40; M/F = 24:16). Patients were observed overnight using the pulse-oximetry technique and further subdivided into patients with SDB and patients without SDB, according to their calculated oxygen desaturation index (cutoff 5). All patients were subjected also to estimation of Kt/V ratio (which is a measure for the efficiency of HD), body-composition analysis, biochemical analysis, muscle functional capacity, and QoL measurements using standard methods and questionnaires, respectively. RESULTS Primary outcomes were intergroup differences regarding physical capacity and muscle performance, QoL, and body-composition measurements. CKD patients in general, either maintained on HD or not, suffer from SDB, and the levels of urea and creatinine may increase the incidence of SDB in CKD patients not maintained on HD. CKD patients maintained on HD with SDB had poorer functional capacity, physical performance, and muscle composition, in comparison with those without SDB. CONCLUSIONS Overall, SDB appears to partly contribute to the total diminished functional capacity of HD patients. Thus, CKD patients maintained on HD with SDB had significantly lower sleep quality and QoL as compared to those not maintained on HD with or without SDB.


title: A randomised controlled trial of the effect of laryngeal mask airway manometry on postoperative sore throat in spontaneously breathing adult patients presenting for surgery at a university teaching hospital.

text: Background Laryngeal mask airways (LMAs) are widely used in anaesthesia and are considered to be generally safe. Postoperative sore throat (POST) is a frequent complication following LMA use and can be very distressing to patients. The use of an LMA cuff pressure of between 30 and 32cm of H2O in alleviating post-operative sore throat has not been investigated. Objective To compare the occurrence of POST between the intervention group in which LMA cuff pressures were adjusted to 30-32cm of H2O and the control group in which only monitoring of LMA cuff pressures was done, to compare the severity of POST between the two study groups and to compare the LMA cuff pressures between the two study groups. Methods Eighty consenting adult patients scheduled to receive general anaesthesia with use of an LMA were randomized into two groups of 40 patients each. Intervention group: LMA airway cuff pressures were adjusted to 30 to 32cm of H2O. Control group: Only had LMA cuff pressures monitored throughout the surgery. All patients were interviewed postoperatively at two, six and twelve hours. Data of their baseline characteristics, occurrence and severity of POST was collected. If POST was present; a Numerical Rating Scale (NRS) was used to assess the severity. Cuff pressures between the two study groups were also determined. Results The baseline demographic characteristics of the participants were similar. The use of manometry to limit LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduced POST in surgical patient's by 62% at 2 hours and 6 hours (Risk Ratio 0.38 95%CI 0.21-0.69)in the intervention group. The median POST pain score in the intervention group was significantly lower than the control group with scores of 0 at 2, 6 and 12 hours post operatively. Routine practice of LMA cuff inflation by anesthesiologists is variable, and the intracuff pressures in the control group were higher than in the intervention group. (P<0.001). Conclusion Among this population, reduction of LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduces the occurrence and severity of POST. The LMA cuff pressures should be measured routinely using manometry and reducing the intracuff pressures to 30-32 cm of H2O recommended as best practice.


title: High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

text: Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle.


title: Cross-allele cytotoxic T lymphocyte responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals.

text: Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24(+) population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11(+) and HLA-A24(+) donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11(+) population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.


title: Corrigendum: A Multicenter Phase II RCT to Compare the Effectiveness of EMDR Versus TAU in Patients With a First-Episode Psychosis and Psychological Trauma: A Protocol Design.

text: [This corrects the article DOI: 10.3389/fpsyt.2019.01023.].


title: Overcoming the blood-brain tumor barrier for effective glioblastoma treatment.

text: Gliomas are the most common primary brain tumors. Particularly in adult patients, the vast majority of gliomas belongs to the heterogeneous group of diffuse gliomas, i.e. glial tumors characterized by diffuse infiltrative growth in the preexistent brain tissue. Unfortunately, glioblastoma, the most aggressive (WHO grade IV) diffuse glioma is also by far the most frequent one. After standard treatment, the 2-year overall survival of glioblastoma patients is approximately only 25%. Advanced knowledge in the molecular pathology underlying malignant transformation has offered new handles and better treatments for several cancer types. Unfortunately, glioblastoma multiforme (GBM) patients have not yet profited as although numerous experimental drugs have been tested in clinical trials, all failed miserably. This grim prognosis for GBM is at least partly due to the lack of successful drug delivery across the blood-brain tumor barrier (BBTB). The human brain comprises over 100 billion capillaries with a total length of 400 miles, a total surface area of 20 m(2) and a median inter-capillary distance of about 50 μm, making it the best perfused organ in the body. The BBTB encompasses existing and newly formed blood vessels that contribute to the delivery of nutrients and oxygen to the tumor and facilitate glioma cell migration to other parts of the brain. The high metabolic demands of high-grade glioma create hypoxic areas that trigger increased expression of VEGF and angiogenesis, leading to the formation of abnormal vessels and a dysfunctional BBTB. Even though the BBTB is considered 'leaky' in the core part of glioblastomas, in large parts of glioblastomas and, even more so, in lower grade diffuse gliomas the BBTB more closely resembles the intact blood-brain barrier (BBB) and prevents efficient passage of cancer therapeutics, including small molecules and antibodies. Thus, many drugs can still be blocked from reaching the many infiltrative glioblastoma cells that demonstrate 'within-organ-metastasis' away from the core part to brain areas displaying a more organized and less leaky BBTB. Hence, drug delivery in glioblastoma deserves explicit attention as otherwise new experimental therapies will continue to fail. In the current review we highlight different aspects of the BBTB in glioma patients and preclinical models and discuss the advantages and drawbacks of drug delivery approaches for the treatment of glioma patients. We provide an overview on methods to overcome the BBTB, including osmotic blood-brain barrier disruption (BBBD), bradykinin receptor-mediated BBTB opening, inhibition of multidrug efflux transporters, receptor-mediated transport systems and physiological circumvention of the BBTB. While our knowledge about the molecular biology of glioma cells is rapidly expanding and is, to some extent, already assisting us in the design of tumor-tailored therapeutics, we are still struggling to develop modalities to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, we must expand our knowledge about the fundamentals of the BBTB as a step toward the design of practical and safe devices and approaches for enhanced drug delivery into the diseased brain area.


title: Effectiveness of a COVID-19 screening questionnaire for pregnant women at admission to an obstetric unit in Milan.

text: Sutton et al. [1] recently reported on universal testing with nasopharyngeal swabs to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in 215 women admitted for delivery at the Presbyterian Allen Hospital in New York, USA. They identified 33 (15.3%) infected women, of whom only four had fever or symptoms suggesting coronavirus disease 2019 (COVID-19). These findings suggest that only universal testing can reliably recognize infected cases. However, this approach is only feasible in major hospitals in high-resource countries with efficient lab facilities in-house. Alternative approaches deserve consideration.


Status of a real-life cohort of patients with moderate-to-severe plaque psoriasis treated with secukinumab and considerations on the use of biological agents in the Covid-19 era.


title: Laparoendoscopic single-site versus conventional laparoscopic total extraperitoneal hernia repair: a prospective randomized clinical trial.

text: BACKGROUND This study aimed to compare laparoendoscopic single-site (LESS) total extraperitoneal (TEP) repair with conventional laparoscopic TEP repair for the treatment of inguinal hernias. To date, no other studies have compared the LESS and conventional laparoscopic TEP approaches for the treatment of inguinal hernia in a prospective randomized study setting. METHODS For this study, 100 patients undergoing inguinal hernia repair were prospectively randomized into either the LESS TEP group or the conventional laparoscopic TEP group. Pre-, intra-, and postoperative factors were recorded. The primary end point was postoperative pain. The patients were interviewed at outpatient clinics at 1 week, 3 months, and 6 months postoperatively. RESULTS The demographic data were comparable between the two groups. The median operative time was longer in the LESS TEP group (63.5 min) than in the conventional TEP group (50.5 min) (p = 0.001). No conversion was performed in either group. The mean pain score 2 h postoperatively during rest was significantly higher in the conventional TEP group than in the LESS TEP group (3.9 vs. 2.6; p = 0.02). The postoperative results were comparable between the groups in terms of analgesic requirements, systemic stress responses, complications, and postoperative convalescence. CONCLUSIONS The LESS TEP technique is associated with a longer operative time but offers the minor benefit of a reduction in immediate postoperative pain.


title: Neurothrombectomy in the treatment of acute ischaemic stroke.

text: Major ischaemic stroke is a leading cause of morbidity and mortality in industrialized countries. For patients with acute stroke, fast and effective vessel recanalization is important for successful treatment. Neurothrombectomy--that is, angiographically performed mechanical thrombus removal from intracranial arteries--results in higher recanalization rates than with pharmaceutical thrombolysis alone, but the value of this treatment in terms of clinical outcome remains to be established. This article summarizes the history of intra-arterial stroke treatment, outlines the recent developments and the different techniques used, and discusses the results of current studies on neurothrombectomy. Owing to the high morphological and clinical variability of stroke, careful patient selection in future randomized controlled trials will be crucial for assessment of the true potential of neurothrombectomy.


title: Chronic Vomiting in Cats: Etiology and Diagnostic Testing.

text: Chronic vomiting in cats is a common presenting problem seen in veterinary practice today. The initial step when presented with a vomiting patient is to differentiate between vomiting and regurgitation or dysphagia. There are numerous causes for chronic vomiting in cats, and therefore a detailed and comprehensive patient history and a systematic diagnostic approach are key steps in determining the cause for vomiting and the most appropriate treatment plan. Common causes for chronic vomiting in cats may include inflammatory bowel disease, food allergy, gastrointestinal motility disorders, neoplasia, and extra-gastrointestinal diseases, such as renal disease, hepatobiliary disease, and hyperthyroidism.


title: Epidemiology of bacteria and viruses in the respiratory tract of humans and domestic pigs.

text: Bacteria and viruses were analysed in the upper respiratory tract of symptomatic pig-farmers and their domestic pigs. 86 human nasal and 495 (50 pools) porcine snout swabs were collected in Schleswig-Holstein, Germany. Staphylococcus (S.) aureus (62.8%, 54/86), human rhino- and coronaviruses (HRV, 29.1%, 25/86; HCoV, 16.3%, 14/86) were frequently detected in humans while Haemophilus parasuis (90.0%, 45/50), Mycoplasma hyorhinis (78.6%, 11/14), Enterovirus G (EV-G, 56.0%, 28/50), and S. aureus (36.0%, 18/50), respectively, were highly prevalent in pigs. The detection of S. aureus in human follow-up samples indicates a carrier status. The methicillin-resistant phenotype (MRSA) was identified in 33.3% (18/54) of nasal swabs and in one of 18 (5.6%) of pooled snout swabs tested positive for S. aureus. Strains were indicative of the livestock-associated clonal complex CC398, with t011 being the most common staphylococcal protein a type. Enterobacterales and non-fermenters were frequently isolated from swabs. Their detection in follow-up samples suggests a carrier status. All were classified as being non-multiresistant. There was no example for cross-species transmission of viruses. In contrast, transmission of S. aureus through occupational contact to pigs seems possible. The study contributes to the "One Health" approach.


title: [Prevention and control program on 2019 novel coronavirus infection in Children's digestive endoscopy center].

text: 2019年12月开始，湖北省武汉市陆续出现新型冠状病毒（2019-nCoV）感染病例，疫情蔓延至我国各地及境外。人群普遍易感，已陆续发现儿童病例。发热不再是早期的主要表现，也可表现为乏力、干咳和恶心、呕吐等症状，少数感染者以消化道症状为首发表现而就诊。在鼻咽拭子、痰、下呼吸道分泌物、血液、粪便等标本中可检测出2019-nCoV核酸。疫情流行期间，原则上如非必须，应推迟消化内镜诊疗。但病情需要或需急诊消化内镜诊疗时，应认真评估，掌握诊疗指征，做好个人防护，严格执行消毒隔离规范。现结合儿童消化内镜诊疗特点，制定疫情流行期间儿童消化内镜中心应对2019-nCoV感染的防控方案，防止医院感染发生。以期能对儿童消化内镜一线医务人员在2019-nCoV流行期间的工作及疫情防控起到建议与指导作用。.


title: Planned Treatment of Advanced Metastatic Disease with Completion Ablation After Hepatic Resection.

text: PURPOSE The aim of this study is to describe a modified treatment strategy with image-guided percutaneous ablation after hepatic resection as a completion method to surgical eradication of liver metastases ("completion ablation [CA]"). METHODS We conducted a retrospective analyses of patients who underwent CA within 180 days from the liver surgical resection to eradicate liver metastases present on the pre-surgical cross-sectional imaging or identified during intraoperative ultrasound that were not resected due to various reasons. Lesions treated with CA were evaluated for local tumor progression (LTP). Patients were evaluated for hepatic- and overall-recurrence-free survivals (hepatic-RFS and overall-RFS, respectively) and overall survival (OS). RESULTS Sixteen patients (10 females; median age 55 years, range 28-69) underwent CA of 21 lesions (median size 8 mm, range 6 to 22). Indications for the use of CA were small future liver remnant in 10 (63%), inability to identify the lesion during surgical exploration in 3 (19%), and technical difficulty of resection in 3 (19%) patients. No liver-related complications were recorded following the surgical resection or the CA procedures. Primary and secondary CA efficacy rates were 95 and 100%, respectively. LTP was 0% at a median clinical follow-up of 27 months (range 4.0-108 months). Five-year hepatic-RFS, overall-RFS, and OS were 36, 16, and 51%, respectively. CONCLUSION The use of CA as a complement to surgical resection is safe and effective. Such approach could potentially expand the surgical candidacy for patients with limited liver functional reserve and reduce postoperative morbidity and mortality in this selected patient population with more advanced disease.


docid: ljypdcxr

title: Duodenal switch with omentopexy and feeding jejunostomy--a safe and effective revisional operation for failed previous weight loss surgery.

text: BACKGROUND As the number of weight loss operations has increased, the number of patients who have failed to maintain sufficient weight loss has also increased, providing a management challenge to the bariatric surgeon. Conversion to a duodenal switch with omentopexy and feeding jejunostomy was performed for these patients. METHODS Between September 2006 and January 2010, 41 revisional operations were performed at 1 institution and by 1 operating surgeon. The data were prospectively collected and reviewed for several parameters, including excess weight loss, mortality, and morbidity. These results are reported. RESULTS A total of 41 patients underwent conversion of their original bariatric operation to a duodenal switch with omentopexy and feeding jejunostomy. The initial operations had been gastric bypass in 32 patients, vertical banded gastroplasty in 5, and laparoscopic adjustable gastric banding in 4. The average excess weight loss was 54% in 31 patients at 6 months, 66% in 22 patients at 1 year, and 75% in 9 patients at 2 years. No patients died. The average hospital stay was 6.4 days. A total of 9 proven or suspected leaks (22%) developed. One was at the enverted staple line of a jejunojejunostomy that was diagnosed and treated the next day with little subsequent morbidity. The others were at the gastrogastrostomy or lateral gastric staple line and all occurred in conversions from gastric bypass. They were all ischemic type leaks and presented 5-11 days after surgery and closed relatively uneventfully with J-tube feedings and antibiotic/antifungal treatment. Other major complications included 1 pulmonary embolism (2%), 1 small bowel obstruction at the site of the feeding jejunostomy (2%), 2 stenoses (4%)-1 at the duodenoenterostomy and 1 in the body of the vertical gastrectomy. This gives a total major complication rate of 30%. A total of 3 patients required reoperation because of a jejunojejunostomy leak, small bowel obstruction, and stenosis at the vertical gastrectomy. No gastrogastrostomy leaks required surgical or radiologic intervention. One required revision for malnutrition, but otherwise the nutrition remained good. CONCLUSION Revisional surgery to a duodenal switch is a complex operation and carries a high potential for major complications. Nonetheless, it can be accomplished safely with good long-term results. Omentopexy, drainage, and feeding jejunostomy should be considered at surgery to treat the high potential for delayed ischemic leaks.


docid: dhipzpxi

title: Characteristics of intra-arterial thrombectomy service provision in England.


title: Laparoendoscopic single-site radical hysterectomy with pelvic lymphadenectomy: initial multi-institutional experience for treatment of invasive cervical cancer.

text: STUDY OBJECTIVE To describe the feasibility, safety, and outcomes of women with stage I cervical cancer treated with laparoendoscopic single-site surgery radical hysterectomy (LESS-RH). DESIGN A retrospective descriptive study (Canadian Task Force classification III). SETTING Multiple academic teaching hospitals. PATIENTS Women with Fédération Internationale de Gynécologie et d'Obstétrique FIGO stage IA1 to IB1 cervical cancer. INTERVENTIONS LESS-RH as the primary therapy for cervical cancer performed by a gynecologic oncologist with expertise in LESS. A multichannel, single-port access device; a flexible-tipped 5-mm laparoscope; and a multifunctional instrument were used in all cases. Clinicopathologic, surgical, and perioperative outcomes were analyzed. MEASUREMENTS AND MAIN RESULTS Twenty-two women were identified in whom a LESS-RH was attempted; 20 (91%) successfully underwent the procedure, including 19 in whom pelvic lymphadenectomy (PLND) was completed. Of the 2 converted procedures, 1 patient underwent 2-port laparoscopy secondary to truncal obesity, and 1 patient underwent conversion to laparotomy secondary to external iliac vein laceration during PLND. The median age and body mass index were 46 years and 23.3 kg/m(2), respectively. The median number of pelvic lymph nodes removed was 22. One patient experienced an intraoperative complication, and no patient required reoperation. The margins of excision were negative. One patient with 2 positive pelvic nodes and 1 patient with microscopic parametrial disease received adjuvant chemosensitized radiation; 3 additional patients received adjuvant radiation therapy secondary to an intermediate risk for recurrence. After a median follow up of 11 months, no recurrences were detected. CONCLUSION LESS-RH/PLND is feasible and safe for select patients with stage I cervical cancer. Larger studies are needed to confirm whether the increased technical difficulty of this procedure justifies its use in routine gynecologic oncology practice.


Introducing the Zoom interview: tips for job hunting during the coronavirus pandemic.


title: Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis.

text: Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.


title: Pregnant women's knowledge and practice of preventive measures against COVID-19 in a low-resource African setting.

text: Since the emergence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, the virus that causes it (SARS-Cov-2) has spread to over 110 countries, including Nigeria [1-3]. Although the impact of COVID-19 on pregnant women is not yet clear, there are concerns over its potential effect on maternal and perinatal outcomes due to unique immunological suppression during pregnancy [4,5].


title: Video-assisted thoracic surgery of major pulmonary resections for lung cancer: the Southampton experience.

text: OBJECTIVE Despite proven safety and long-term results of video-assisted thoracic surgery (VATS) lobectomy, the technique is not widely adopted in the UK. We set out to start a VATS lobectomy programme against financial and time constraints to meet cancer waiting times. We present clinical outcomes of patients undergoing VATS major pulmonary resections (VMPRs) with emphasis on postoperative events. METHODS Patients were deemed suitable for VMPR if on computed tomography (CT)/positron emission tomography (PET); the lesion was suspected to represent lung cancer T1-2, N0-1 and M0. VMPR involved individual hilar structures dissection without rib spreading. Systematic mediastinal nodal dissection was added in the last 64 cases. RESULTS Between April 2005 and December 2009, 165 patients were considered suitable for first-time VMPR. Seventy were males and 95 were females. Mean age was 67.5 ± 10.1 (range 34.9-85.5 years) years. Nine patients were not suitable after initial videoscopic assessment and 156 proceeded to VMPR: 150 lobectomies, four bilobectomies, one pneumonectomy and one patient with poor lung function who underwent segmentectomy. There were 23 (14.7%) conversions to thoracotomy. The median operative time for VATS lobectomy was 03:20 ± 00:56 (hh:mm). The median length of hospital stay was 4.0 ± 4.0 days (range 1-25 days, mode 3 days). There were no in-hospital deaths and three (1.9%) out-of-hospital <30 days' mortality. Complications included protracted air leak >3 days in 18 (11.5%) cases, intensive care unit (ICU) admission in 18 (11.5%), pneumothorax in 24 (15.4%) respiratory complications in 14 (9%), bronchial complications in six (3.8%) and bleeding requiring exploration in one (0.6%). The median follow-up was 13.6 months (range 0.1-54.4 months). The actuarial survival at 1, 2 and 3 years for all stages was 85.0 ± 3.8%, 82.2 ± 4.2% and 73.5 ± 7.0%, respectively. CONCLUSION High postoperative events are to be expected when starting a VATS lobectomy programme. Nevertheless, VATS major pulmonary resections are safe and long-term results are not compromised. They should be considered the first choice for T1-2, N0-1 and M0 lung lesions. An aggressive approach to postoperative complications reduced the length of hospital stay to a median of 4 days. Air leak remains the most important cause for prolonged hospital stay.


The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy.


title: Olfactory Detection Thresholds for Primary Aliphatic Alcohols in Mice.

text: Probing the neural mechanisms that underlie each sensory system requires the presentation of perceptually appropriate stimulus concentrations. This is particularly relevant in the olfactory system as additional odorant receptors typically respond with increasing stimulus concentrations. Thus, perceptual measures of olfactory sensitivity provide an important guide for functional experiments. This study focuses on aliphatic alcohols because they are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination and assess odor-structure activity relationships in mice. However, despite their frequent use, a systematic study of the relative sensitivity of these odorants in mice is not available. Thus, we assayed the ability of C57BL/6J mice to detect a homologous series of primary aliphatic alcohols (1-propanol to 1-heptanol) using a head-fixed Go / No-Go operant conditioning assay combined with highly reproducible stimulus delivery. To aid in the accessibility of our data, we report the animal's threshold to each odorant according to the 1) ideal gas condition, 2) non-ideal gas condition (factoring in the activity of the odorant in the solvent), and 3) the liquid dilution of the odorant in the olfactometer. Of the odorants tested, mice were most sensitive to 1-hexanol and least sensitive to 1-butanol. These updated measures of murine sensitivity will hopefully guide experimenters in choosing appropriate stimulus concentrations for experiments using these odorants.


title: Periprocedural Heparin During Endovascular Treatment of Tandem Lesions in Patients with Acute Ischemic Stroke: A Propensity Score Analysis from TITAN Registry.

text: BACKGROUND AND PURPOSE Data on safety and efficacy of periprocedural use of heparin are limited during treatment of acute ischemic stroke patients with anterior circulation tandem occlusion. This study aimed to investigate the impact of heparin use during endovascular therapy of anterior circulation tandem occlusions on the functional and safety outcomes. METHODS A retrospective analysis of the multicenter observational TITAN registry was performed. Patients with anterior circulation tandem occlusion and treated with endovascular therapy (EVT) were included, with or without extracranial carotid intervention. We divided patients into two groups based on periprocedural heparin use (heparin vs. non-heparin). The dose of intravenous unfractionated heparin ranged from 1500 to 2500 I.U. Primary study endpoint was 90-day Modified Rankin Scale (mRS). Secondary study endpoint included angiographic and safety endpoints such as hemorrhagic complications. A propensity-score-matched analysis was performed. RESULTS Among 369 patients, heparin was used in 68 patients (18.4%). In the propensity-score-matched cohort, favorable outcome (mRS 0-2) occurred in 51.3% in heparin group and 58.0% in non-heparin group (matched OR, 0.76; 95% CI, 0.32-1.78; P = 0.52). Similar result was found in propensity-score-adjusted cohort (adjusted OR, 0.72; 95%CI, 0.39-1.32; P = 0.28). Likewise, there was no difference in the rate of successful reperfusion (mTICI 2b-3) (propensity-score-adjusted OR, 1.03; 95%CI, 0.50-2.09; P = 0.93) neither in safety endpoints between the two groups. CONCLUSIONS Periprocedural heparin use during EVT of anterior circulation tandem occlusions was not associated with better functional, angiographic or safety outcomes. These findings are applicable for low doses of heparin, and further studies are warranted.


Audio Interview: Finding Reliable Information about Covid-19.


title: Perioperative pain management and chronic postsurgical pain after elective foot and ankle surgery: a scoping review.

text: PURPOSE Chronic postsurgical pain (CPSP) can occur after elective mid/hindfoot and ankle surgery. Effective treatment approaches to prevent the development of CPSP in this population have not been extensively investigated. The impact of multimodal strategies to prevent CPSP following elective mid/hindfoot surgery is unknown because of both the heterogeneity of acute pain management and the lack of a recognized definition particular to this surgery. This review aimed to identify and evaluate current pain management strategies after elective mid/hindfoot and ankle surgery. SOURCES Manual and electronic searches (MEDLINE, Embase, and Cochrane Library) were conducted of literature published between 1990 and July 2017. Comparative studies of adults undergoing elective mid/hindfoot and ankle surgery were included. Two reviewers independently reviewed studies and assessed their methodological quality. PRINCIPAL FINDINGS We found seven randomized-controlled trials meeting our inclusion criteria. Interventions focused on regional anesthesia techniques such as continuous popliteal sciatic and femoral nerve blockade. Participants were typically followed up to 48 hr postoperatively. Only one study assessed pain six months following elective mid/hindfoot and ankle surgery. CONCLUSION There is an overwhelming lack of evidence regarding CPSP and its management for patients undergoing elective mid/hindfoot and ankle surgery. The lack of a recognized and standard definition of CPSP after this group of surgeries precludes accurate and consistent evaluation.


title: Model calculations to quantify clinical and economic effects of pathogen inactivation in platelet concentrates.

text: BACKGROUND Future shortages in platelet supply are expected in Germany due to demographic changes. A rising cancer incidence will lead to an increasing demand for platelet concentrates (PCs) while the number of potential donors will decrease. Pathogen inactivation (PI) aims to inactivate various infectious agents including emerging pathogens to extend the shelf-life of PCs and reduce the frequency of acute transfusion reactions (ATRs). In this context, the clinical and economic impact of PI on platelet transfusion was evaluated. MATERIAL AND METHODS Model calculations were conducted for 2 scenarios considering different production settings. Frequencies of ATRs were based on literature analyses, platelet and ATR costs on cost analyses. RESULTS The estimated average costs for ATRs of grade 1 and 2, irrespective of origin, and grade 3 (allergic) were € 104, € 238, and € 1,200, respectively. Approximately 400 PC-related ATRs per 10(5) transfusions can be avoided, with estimated savings amounting to € 77,000. The total cost increase was calculated to approximately € 30-50 per PI-treated PC. CONCLUSION PI potentially saves plasma, prolongs shelf-life, decreases donor deferral, and reduces ATRs. Model calculations considering clinical and safety benefits of PI show a rational cost increase. The impact of PI should be further evaluated from a societal perspective regarding future blood supply and infectious disease globalization.


title: Discovering novel zoonotic viruses.

text: From the emergence of Hendra virus and Menangle virus in Australia to the global pandemics of severe acute respiratory syndrome and influenza viruses (both H5N1 and H1N1), there has been a surge of zoonotic virus outbreaks in the last two decades. Although the drivers for virus emergence remain poorly understood, the rate of discovery of new viruses is accelerating. This is due to a combination of true emergence of new pathogens and the advance of new technologies making rapid detection and characterisation possible. While molecular approaches will continue to lead the way in virus discovery, other technological platforms are required to increase the chance of success. The lessons learnt in the last 20 years confirm that the One Health approach, involving inclusive collaborations between physicians, veterinarians and other health and environmental professionals, will be the key to combating future zoonotic disease outbreaks.


title: Identification and retrospective validation of T-cell epitopes in the hepatitis C virus genotype 4 proteome: an accelerated approach toward epitope-driven vaccine development.

text: With over 150 million people chronically infected worldwide and millions more infected annually, hepatitis C continues to pose a burden on the global healthcare system. The standard therapy of hepatitis C remains expensive, with severe associated side effects and inconsistent cure rates. Vaccine development against the hepatitis C virus has been hampered by practical and biological challenges posed by viral evasion mechanisms. Despite these challenges, HCV vaccine research has presented a number of candidate vaccines that progressed to phase II trials. However, those efforts focused mainly on HCV genotypes 1 and 2 as vaccine targets and barely enough attention was given to genotype 4, the variant most prevalent in the Middle East and central Africa. We describe herein the in silico identification of highly conserved and immunogenic T-cell epitopes from the HCV genotype 4 proteome, using the iVAX immunoinformatics toolkit, as targets for an epitope-driven vaccine. We also describe a fast and inexpensive approach for results validation using the empirical data on the Immune Epitope Database (IEDB) as a reference. Our analysis identified 90 HLA class I epitopes of which 20 were found to be novel and 19 more had their binding predictions retrospectively validated; empirical data for the remaining 51 epitopes was insufficient to validate their binding predictions. Our analysis also identified 14 HLA class II epitopes, of which 8 had most of their binding predictions validated. Further investigation is required regarding the efficacy of the identified epitopes as vaccine targets in populations where HCV genotype 4 is most prevalent.


title: Initial Experience with Neuroform EZ in the Treatment of Wide-neck Cerebral Aneurysms.

text: PURPOSE Stent-assisted coiling allows embolization and parent vessel reconstruction of wide-necked intracranial aneurysms. The Neuroform EZ (Boston Scientific, Fremont, CA, U.S.A.) stent delivery system offers deployment of a Neuroform stent with fewer steps and improved operator control. Initial experience, technical considerations, and treatment outcomes using the Neuroform EZ stent delivery system in combination with coil embolization are reported. MATERIALS AND METHODS Seventeen consecutive patients harboring 21 wide-necked saccular cerebral aneurysms were treated with stent reconstruction. Twenty aneurysms were unruptured; one was treated within 24 hours of diagnosis of rupture. Twenty aneurysms were located in the anterior circulation; one was in the posterior circulation. Immediate and six-month post-treatment angiography and clinical assessment were performed. RESULTS In all cases, the stents were delivered and positioned without difficulty in deployment. Technical complications occurred in 4 patients, but none were directly related to the stent delivery system. On immediate post-treatment angiography, 5 of 21 aneurysms showed complete occlusion, 5 of 21 showed residual neck, and 11 of 21 showed residual contrast filling of the aneurysm sac. At six month follow-up, all 17 patients were clinically stable. Angiography of 18 of the aneurysms showed total occlusion in 12, residual neck in 3, and residual aneurysm filling in 3. Retreatment was performed in the three with residual aneurysm. CONCLUSION The Neuroform EZ stent system offers improved anchoring and support in stent delivery, which is particularly useful when multiple stents are overlapped to further protect the parent vessel and increase flow diversion away from the aneurysm sac. The only significant problem encountered was coil prolapse, which could be treated with a second stent when necessary. The ease of deployment improves upon the already clinically successful Neuroform design.


title: Asthma increases risk of severity of COVID-19.

text: Current Centers for Disease Control and Prevention guidelines state that patients with moderate to severe asthma may be at greater risk for more severe disease if infected with SARS-CoV-2; however, no published data support this suggestion. During this pandemic, it is recommended that patients with asthma continue taking all controller inhalers and other asthma medication as prescribed to prevent exacerbations and limit outpatient clinic and emergency room exposure. Symptoms that may differentiate COVID-19 from asthma exacerbations caused by another trigger may include fever, fatigue, anorexia, or myalgias. Patients with suspected or confirmed COVID-19 should avoid nebulizer treatments due to the risk of aerosolization.


title: Public response to an anthrax attack: reactions to mass prophylaxis in a scenario involving inhalation anthrax from an unidentified source.

text: An attack with Bacillus anthracis ("anthrax") is a known threat to the United States. When weaponized, it can cause inhalation anthrax, the deadliest form of the disease. Due to the rapid course of inhalation anthrax, delays in initiation of antibiotics may decrease survival chances. Because a rapid response would require cooperation from the public, there is a need to understand the public's response to possible mass dispensing programs. To examine the public's response to a mass prophylaxis program, this study used a nationally representative poll of 1,092 adults, supplemented by a targeted focus on 3 metropolitan areas where anthrax attacks occurred in 2001: New York City (n=517), Washington, DC (n=509), and Trenton/Mercer County, NJ (n=507). The poll was built around a "worst-case scenario" in which cases of inhalation anthrax are discovered without an identified source and the entire population of a city or town is asked to receive antibiotic prophylaxis within a 48-hour period. Findings from this poll provide important signs of public willingness to comply with public health recommendations for obtaining antibiotics from a dispensing site, although they also indicate that public health officials may face several challenges to compliance, including misinformation about the contagiousness of inhalation anthrax; fears about personal safety in crowds; distrust of government agencies to provide sufficient, safe, and effective medicine; and hesitation about ingesting antibiotic pills after receiving them. In general, people living in areas where anthrax attacks occurred in 2001 had responses similar to those of the nation as a whole.


title: Hemorrhagic complications of percutaneous radiofrequency ablation for liver tumors.

text: BACKGROUND Although radiofrequency ablation (RFA) is widely accepted as a percutaneous treatment for liver tumors; serious complications may occur resulting in 0.1% to 0.5% mortality. This study analyzed the risk factors and management of hemorrhagic complications, such as hemoperitoneum, hemothorax, and hemobilia. METHODS We performed 4133 RFA treatments in 2154 patients with primary and metastatic liver tumors from February 1999 to December 2007. Of these, we enrolled patients with hemorrhagic complications and reviewed their medical records thoroughly. The risk factors for each hemorrhagic complication were analyzed using unconditional logistic regression. RESULTS Hemorrhagic complications occurred in 63 out of 4133 treatments (1.5%), including hemoperitoneum in 29 (0.7%), hemothorax in 14 (0.3%), and hemobilia in 20 (0.5%). Eleven, 8, and 4 of these patients, respectively, were categorized as major complications requiring blood transfusion or drainage. Two patients died after hemoperitoneum. Logistic regression analysis revealed large tumor size [odds ratio (OR) 1.06 per 1 mm increase in diameter] and low platelet count (OR 0.88 per 10,000/microL increase) were significant risk factors for hemoperitoneum. The location of tumor nodules was a significant risk factor for hemothorax (segment 7, OR 2.31) and hemobilia (segment 1, OR 3.30). Other factors, including the number of needle insertions or the duration of ablation, were not significant. CONCLUSIONS Although hemorrhagic complications were relatively rare with percutaneous RFA, specific treatments, such as blood transfusion and drainage, were required in some cases. Care must be taken, especially in high-risk patients.