title: A phase 1 study of the anti-CC chemokine receptor 4 antibody, mogamulizumab, in combination with nivolumab in patients with advanced or metastatic solid tumors.

text: PURPOSE Regulatory T-cells (Tregs) expressing CC chemokine receptor 4 (CCR4) can suppress antitumor immune responses and are associated with poor prognoses in several cancers. We assessed the safety and efficacy of combined mogamulizumab (anti-CCR4 antibody) and nivolumab (anti-programmed death-1 [PD-1] antibody) in immunotherapy-naive patients with advanced/metastatic solid tumors. EXPERIMENTAL DESIGN This study (NCT02476123) comprised dose-escalation (3+3 design) and expansion parts. Patients received nivolumab (3.0 mg/kg) every 2 weeks, with mogamulizumab (0.3 or 1.0 mg/kg in dose-escalation, 1.0 mg/kg in expansion) once weekly for 4 weeks, then every 2 weeks, until progression or unacceptable toxicity. Primary objective was safety; secondary objectives were antitumor effects, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses were conducted. RESULTS 96 patients were enrolled (July 2015-November 2016): six patients in the dose-escalation part and 90 in the expansion part. No dose-limiting toxicities were observed in the dose-escalation part. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 29% of patients in the expansion part (no grade 5 TRAEs). The most frequent TRAEs were rash (39%), rash maculo-papular (20%), diarrhea (13%), stomatitis (12%), and pruritus (11%). There were four (27%) confirmed tumor responses among 15 patients with hepatocellular carcinoma, and one confirmed and two unconfirmed responses among 15 patients with pancreatic adenocarcinoma. During treatment, populations of effector Tregs (CD4+CD45RA-FoxP3high) decreased and CD8+ T-cells in tumor-infiltrating lymphocytes increased. CONCLUSIONS Combining an anti-PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer immunotherapy.


title: Young adults with dyskinetic cerebral palsy improve subjectively on pallidal stimulation, but not in formal dystonia, gait, speech and swallowing testing.

text: BACKGROUND Pharmacological treatment of dyskinetic cerebral palsy (CP) is often ineffective. Data about outcome of deep brain stimulation (DBS) in these patients remains scarce. METHODS Eight patients with dyskinetic CP and DBS of the Globus Pallidus internus were investigated. Using pre- and postoperative videos the severity of dystonia and changes thereof during standardized settings ('on') and after the stimulator had been switched off ('off') were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Furthermore, subjective impression (SI) of the extent of postoperative change as well as gait (Leonardo Mechanograph® Gangway), speech (Frenchay Dysarthria) and swallowing performances (fiberoptic laryngoscopy) were assessed during 'on' and 'off'. RESULTS When comparing pre- and postoperative as well as 'on' and 'off', the BFMDRS and most of the gait, speech, and swallowing parameters did not differ significantly. In contrast, patients reported significant improvement of their SI postoperatively (3.1 on a 10-point-scale). CONCLUSION Data show that our CP-patients did not benefit from GPi-DBS when tested formally for dystonia, gait, speech and swallowing. In stark contrast, these patients reported significant subjective improvement. Taken together, and in light of current unsatisfactory medical treatment options, our data suggest that further assessment of the effects of GPi-DBS in dyskinetic CP is warranted.


title: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary.

text: The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.


title: On subclasses of opioid analgesics.

text: BACKGROUND The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. SCOPE A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. FINDINGS By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. CONCLUSION An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.


title: Oxygen therapy with high-flow nasal cannulas in children with acute bronchiolitis.

text: Acute bronchiolitis is a common disease in children below 24 months of age. The most common aetiology of this disease is a respiratory syncytial virus infection. Since there is no effective treatment for bronchiolitis, supportive therapy alleviating symptoms and preventing respiratory failure is recommended. Oxygen therapy and appropriate nutrition during the disease are considered effective, particularly in severe cases. The choice of oxygen support is crucial. The present paper discusses oxygen therapy using high-flow nasal cannulas. Moreover, the safety of the method, its adverse side effects and practical pre-treatment guidelines are discussed.


title: Interplay between host cell and hepatitis C virus in regulating viral replication.

text: Viral life cycle as that of the hepatitis C virus (HCV) completely relies on host cell infrastructure, presupposing that the virus has evolved mechanisms to utilize and control all cellular molecules or pathways required for viral life cycle. Hence, HCV must have acquired the ability to gain access to key pathways controlling processes, such as cell growth, apoptosis and protein synthesis, which are all considered to also be crucial for liver regeneration. This occurs in a balanced way permitting persistent replication of viral genomes and production of infectious particles without endangering host cell viability and survival. In particular during the last decade, accumulating evidence indicates that HCV utilizes signaling pathways of the host with major impact on cellular growth, viability, cell cycle or cellular metabolism, such as epidermal growth factor-receptor mediated signals, the PI3K/Akt cascade or the family of Src kinases. Furthermore, HCV specifically interacts with parts of the cellular machinery involved in protein translation, processing, maturation and transport, such as components of the translation complex, the heat shock protein family, the immunophilins or the vesicle-associated membrane protein-associated proteins A and B. The present review focuses on the interplay between viral proteins and these factors of the host cell enabling the virus to utilize host cell infrastructure.


title: Unilateral pulmonary oedema after minimally invasive mitral valve surgery: a single-centre experience.

text: OBJECTIVES Unilateral pulmonary oedema (UPE) is a rare but potentially life-threatening complication that has been described after minimally invasive mitral valve surgery (MICS). Over the last 8 years, we have witnessed, in our institution, several cases of severe UPE requiring immediate postoperative extracorporeal life support after MICS. Reviewing the available literature, data regarding this complication after MICS are rare. Consequently, we decided to retrospectively analyse patients scheduled for MICS in our institution. METHODS After approval by our institutional review board, 256 MICS patients were analysed. As a primary end-point, we defined a newly developed UPE, radiographically evident within the first 24 h postoperatively. Secondary end-points were length of stay in the intensive care unit, length of stay in the hospital and in-hospital mortality. Chest radiographs were analysed by an independent consultant of radiology. RESULTS Fifty-one (19.9%) patients showed increased right-sided pulmonary vascular congestion in the 1st postoperative chest radiography performed in the intensive care unit. Five (1.95%) patients immediately required extracorporeal life support after admission to the intensive care unit. Cardiopulmonary bypass time was significantly longer in the UPE group [UPE vs non-UPE 213 (49) vs 196 (43) min; P = 0.013]. More patients with UPE showed a preoperative increase of C-reactive protein >0.4265 mg/dl (P = 0.05). Logistic regression analysis identified a preoperative increase in C-reactive protein >0.4265 mg/dl as well as a prolonged cardiopulmonary bypass time (odds ratio 1.009, 95% confidence level 1.002-1.016; P = 0.014) independent risk factors, significantly associated with the development of UPE (odds ratio 2.583, 95% confidence interval 1.275-5.233; P = 0.008), a prolonged cardiopulmonary bypass time (odds ratio 1.009, 95% confidence interval 1.002-1.016; P = 0.014). The presence of pulmonary hypertension (odds ratio 0.273, 95% confidence interval 0.08-0.84; P = 0.02) seemed to be a protective factor regarding the genesis of UPE. CONCLUSIONS In accordance with the rarely available literature regarding UPE after MICS, our analysis led us to hypothesize the possibility of an inflammatory disposition for UPE. The role of pulmonary hypertension remains unclear in our patient population. Clinical Trials Number NCT02655094.


title: Volunteerism during COVID-19.

text: Health care workers have been asked to do their part to make a difference and give back to their community. This personal reflection is a result of an experience as a medical reserve corps nurse volunteer for a local health department in the northeastern United States. Volunteering resulted in positive social and personal benefits for me. It inspired a sense of pride in helping others and knowing that someone's well-being may be enhanced. The individuals whom I spoke with via the phone appreciated the concern for their health, and some individuals seemed to enjoy the interaction with another person, possibly due to their isolation. Descriptions of interactions via phone calls with coronavirus positive individuals are provided that support the benefits of volunteering. Volunteerism has personal value in its ability to inspire someone to continue to make an impact. Volunteerism allowed me to give to others and to gain a sense of purpose.


title: Progrip self-gripping mesh in Rives-Stoppa repair: Are there any differences in outcomes versus a retromuscular polypropylene mesh fixed with sutures? A "case series" study.

text: BACKGROUND Rives-Stoppa repair is widely accepted technique in large midline IH, and appears to be advantageous compared to other surgical techniques concerning complications and recurrence rates. The aim of this case series study was to analyze 1-year outcomes in patients with IH treated with Progrip self-gripping mesh compared to polypropylene (PPL) mesh fixed with sutures during the Rives-Stoppa technique. METHODS Between June 2014 and June 2015, we performed a prospective comparative non-randomized (case series) analysis between 25 patients with IH using retromuscular Progrip self-gripping mesh and 25 patients with retromuscular PPL mesh fixed with sutures, under Rives-Stoppa repair. All intraoperative and perioperative morbidities were reported with particular attention to wound infection, seroma or hematoma formation, duration of hospital stay, presence of abdominal wall pain (VAS) and recurrence during long-term follow-up. RESULTS Mean operative time in Progrip group was shorter than Non-Progrip group (101±29.5 versus 121±39.8min). In Progrip group, the only postoperative complication was seroma in two patients; however, in Non-Progrip group, we reported seroma in three patients, and hematoma in 4 patients (p=0.03). The median hospital stay was shorter in Progrip group (5.8±2.2days versus 6.6±2.9days). Mean VAS score in the first 48h was higher in Non-Progrip group than Progrip group (4.9±2.1 versus 8.1±2)(p=0.01). The median follow-up was 13 months (range 12-20 months) and none of the 50 patients had a hernia recurrence. CONCLUSIONS In Rives-Stoppa repair, retromuscular Progrip mesh causes less postoperative pain in the first 48h and lower rate of hematoma than PPL mesh fixed with sutures in the short term follow-up.


Extreme PCR: a breakthrough innovation for outbreaks?


title: Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1.

text: Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.


title: Infections and pathology of free-roaming backyard chickens on St. Kitts, West Indies.

text: Free-roaming chickens on Caribbean islands are important sentinels for local avian diseases and those introduced by birds migrating through the Americas. We studied 81 apparently healthy unvaccinated free-roaming chickens from 9 parishes on St. Kitts, an eastern Caribbean island. Using commercial ELISAs, no chickens had antibodies against avian influenza virus, West Nile virus, or Salmonella Enteritidis, although seropositivity was high to infectious bursal disease virus (86%), infectious bronchitis virus (84%), Mycoplasma (37%), and avian avulavirus 1 (Newcastle disease virus, 31%). Examination of small and large intestinal contents revealed cestodes in 79% and nematodes in 75% of the chickens. Although ectoparasites and endoparasites were common (74% and 79%, respectively), only a few chickens had lesions at postmortem examination, mainly intestinal serosal nodules (12%) and feather loss (6%). Histologic examination of 18 organs from each bird revealed lesions in high percentages of organs, mainly the liver (86%), lung (75%), spleen (60%), small intestine (56%), skin (42%), and kidney (40%). Lesions included degenerative, reactive, inflammatory, and neoplastic, and were not correlated with the serologic status of the chickens except in one case of infectious bursal disease. Microscopically, Paratanaisia bragai was seen in the kidneys of 3 chickens and intestinal coccidiasis in 1 chicken. Pulmonary silicate aggregates were common, were present in intestinal serosal nodules, and were suggestive of environmental exposure.


title: Intra-aneurysmal pressure changes during stent-assisted coiling.

text: We aimed to examine aneurysm hemodynamics with intra-saccular pressure measurement, and compare the effects of coiling, stenting and stent-assisted coiling in proximal segments of intracranial circulation. A cohort of 45 patients underwent elective endovascular coil embolization (with or without stent) for intracranial aneurysm at our department. Arterial pressure transducer was used for all measurements. It was attached to proximal end of the microcatheter. Measurements were taken in the parent artery before and after embolization, at the aneurysm dome before embolization, after stent implantation, and after embolization. Stent-assisted coiling was performed with 4 different stents: LVIS and LVIS Jr (Microvention, Tustin, CA, USA), Leo (Balt, Montmorency, France), Barrel VRD (Medtronic/ Covidien, Irvine, CA, USA). Presence of the stent showed significant reverse correlation with intra-aneurysmal pressure-both systolic and diastolic-after its implantation (r = -0.70 and r = -0.75, respectively), which was further supported by correlations with stent cell size-r = 0.72 and r = 0.71, respectively (P<0.05). Stent implantation resulted in significant decrease in diastolic intra-aneurysmal pressure (p = 0.046). Systolic or mean intra-aneurysmal pressure did not differ significantly. Embolization did not significantly change the intra-aneurysmal pressure in matched pairs, regardless of the use of stent (p>0.05). In conclusion, low-profile braided stents show a potential to divert blood flow, there was significant decrease in diastolic pressure after stent placement. Flow-diverting properties were related to stent porosity. Coiling does not significantly change the intra-aneurysmal pressure, regardless of packing density.


title: Cytokine Blood Filtration Responses in COVID-19.

text: The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.


title: Wound bed preparation 2014 update: management of critical colonization with a gentian violet and methylene blue absorbent antibacterial dressing and elevated levels of matrix metalloproteases with an ovine collagen extracellular matrix dressing.

text: Wound bed preparation (WBP) is a paradigm for holistic patient care that includes treatment of the cause along with patient-centered concerns before optimizing the components of local wound care (debridement, infection/inflammation, moisture balance, and, when required, the edge effect). This review incorporates a methylene blue and gentian violet bound foam dressing for critical colonization and an ovine collagen extracellular matrix dressing for reduction of elevated levels of matrix metalloproteases into the WBP paradigm.


title: A scoping review of Advanced Practice Registered Nurses Consensus Model outcomes: Part four of a four-part series on critical topics identified by the 2015 Nurse Practitioner Research Agenda.

text: BACKGROUND AND PURPOSE The Advanced Practice Registered Nurses (APRN) Consensus Model was produced by the APRN Joint Dialogue Group in 2008. The aim of the Consensus Model is to guide state boards on the implementation of APRN practice components, including licensure, accreditation, certification, and education and to clarify the legal scope of practice and APRN roles. The purpose of this scoping review and gap analysis was to appraise the evidence related to patient, nurse practitioner (NP) and organizational outcomes resulting from the Consensus Model. METHODS A scoping review of research studies and grey literature reports was conducted and focused on the outcomes and key concepts related to the Consensus Model. Areas of foci included patients, NPs, and organizations. A subsequent gap analysis was conducted. CONCLUSIONS Several positive findings related to the Consensus Model, or components thereof, were identified for patient, NP, and organizational outcomes on various levels. Research gaps exist. Additional research is needed to fully evaluate the health outcomes on a broader scale. IMPLICATIONS FOR PRACTICE Existing evidence may support NPs and supporting organizations to further legislative efforts to more fully implement the Consensus Model nationwide.


title: [Postoperative surveillance in neurosurgical patients - usefulness of neurological assessment scores and bispectral index].

text: BACKGROUND AND OBJECTIVES We examined the additive effect of the Ramsay scale, Canadian Neurological Scale (CNS), Nursing Delirium Screening Scale (Nu-DESC), and Bispectral Index (BIS) to see whether along with the assessment of pupils and Glasgow Coma Scale (GCS) it improved early detection of postoperative neurological complications. METHODS We designed a prospective observational study of two elective neurosurgery groups of patients: craniotomies (CG) and non-craniotomies (NCG). We analyze the concordance and the odds ratio (OR) of altered neurological scales and BIS in the Post-Anesthesia Care Unit (PACU) for postoperative neurological complications. We compared the isolated assessment of pupils and GCS (pupils-GCS) with all the neurologic assessment scales and BIS (scales-BIS). RESULTS In the CG (n=70), 16 patients (22.9%) had neurological complications in PACU. The scales-BIS registered more alterations than the pupils-GCS (31.4% vs. 20%; p<0.001), were more sensitive (94% vs. 50%) and allowed a more precise estimate for neurological complications in PACU (p=0.002; OR=7.15, 95% CI=2.1-24.7 vs. p=0.002; OR=9.5, 95% CI=2.3-39.4). In the NCG (n=46), there were no neurological complications in PACU. The scales-BIS showed alterations in 18 cases (39.1%) versus 1 (2.2%) with the pupils-GCS (p<0.001). Altered CNS on PACU admission increased the risk of neurological complications in the ward (p=0.048; OR=7.28, 95% CI=1.021-52.006). CONCLUSIONS Applied together, the assessment of pupils, GCS, Ramsay scale, CNS, Nu-DESC and BIS improved early detection of postoperative neurological complications in PACU after elective craniotomies.


Things We Do for No Reason: Intermittent Pneumatic Compression for Medical Ward Patients?


title: Comparison between transumbilical and transvaginal morcellation of a large uterus during single-port-access total laparoscopic hysterectomy.

text: Objective To compare the perioperative outcomes of transumbilical morcellation (TUM) and transvaginal morcellation (TVM) of a large uterus (≥500 g) during single-port-access total laparoscopic hysterectomy (SPA-TLH). Methods A total of 57 patients who underwent SPA-TLH for a large uterine myoma and/or adenomyosis (uterine weight ≥500 g) between March 2013 and July 2017 were included. For specimen retrieval, TUM was performed for 30 patients and TVM for 27 patients. Results Perioperative outcomes, including total operative time, tissue extraction time, extension of skin incision length, estimated volume of blood loss, changes in postoperative hemoglobin level, length of postoperative hospital stay, postoperative pain, and uterine weight, were compared between the 2 groups. No significant differences were observed in the baseline characteristics except for a history of cesarean section (TUM vs. TVM: 83.3% vs. 14.8%, P=0.002) and history of vaginal delivery (TUM vs. TVM: 6.7% vs. 88.8%, P=0.001). The total operative time, tissue extraction time, extension of skin incision length, estimated volume of blood loss, changes in postoperative hemoglobin level, length of postoperative hospital stay, and postoperative pain did not significantly differ between the two groups. The uterine weight was significantly higher for patients who underwent TUM than for those who had TVM (median [range]: 735 g [520-1,380 g] vs. 622 g [514-975 g]; P=0.042). Conclusion TUM during SPA-TLH is a feasible technique for extracting large uteri weighing ≥500 g. This procedure is suitable for patients without a history of vaginal delivery or a narrow vaginal cavity.


title: Understanding risk factors for perioperative ischemic events with carotid stenting: is patient age over 80 years or is unfavorable arch anatomy to blame?

text: OBJECTIVE Several studies have reported increased perioperative risk after carotid artery stenting (CAS) for patients ≥80 years of age; however, most have not considered unfavorable anatomic features noted more frequently in this population as a confounding variable. The purpose of this study was to show a correlation between poor aortic arch anatomy and perioperative ischemic complications after CAS. METHODS Our prospectively maintained database was queried for all CAS procedures performed on symptomatic patients between 2009 and 2011. Retrospective analysis of consecutive CAS procedures was performed. The primary endpoint was perioperative (within 30 days) ischemic events (stroke, transient ischemic attack (TIA)). Event incidence was compared between groups dichotomized by age and anatomical features. Incidence of unfavorable arch (acute angle between aortic arch and treated common carotid artery) was compared between age groups. RESULTS Perioperative ischemic events included four ischemic strokes and three TIAs (all events ipsilateral to the treated vessel). Event incidence was more frequent in patients with unfavorable arch anatomy (7.9%) than in those with favorable aortic arch features (0.7%) (p=0.0073). Event incidence in patients ≥80 years of age (4.5%) was not statistically different than that in patients <80 years (2.3%) (p=0.428). Unfavorable aortic arch anatomy was increased in frequency in patients aged 80 years and over (<80 years, 29%; ≥80 years, 52%; p<0.001). CONCLUSIONS In the present series, the incidence of perioperative complications was increased in patients with unfavorable aortic arch anatomy but not in patients ≥80 years. CAS represents a revascularization option for patients of all ages; however, patients with unfavorable aortic arch anatomy may represent a group at relatively high risk for periprocedural ischemic events.


title: Pyocystis: a systematic review.

text: Pyocystis, empyema cystis, vesical empyema are all terms that describe the purulent filled bladder that may develop in patients with defunctionalized bladders such as after supravesical urinary diversion without cystectomy or in patients with end-stage renal disease with anuria. It is a severe form of lower urinary tract infection. In addition to the local symptoms of suprapubic pain and malodorous discharge, the condition can be more serious with bacterial dissemination into the blood stream and ensuing sepsis and even mortality. The current review will discuss the pathogenesis, risk factors and management of this commonly forgotten complication of urinary diversion.


title: Elective stenting for intracranial stenosis under conscious sedation.

text: BACKGROUND Elective stenting for intracranial stenosis is under study as an effective means of reducing stroke risk. At most institutions, these procedures are performed and monitored after the induction of general anesthesia. OBJECTIVE To report our success with elective intracranial stenting and angioplasty performed in conscious patients after the administration of mild sedatives and local anesthetic agents. METHODS We retrospectively evaluated data from 66 patients who underwent elective intracranial stenting for atherosclerosis. Sixty-one procedures were performed under local anesthesia with mild sedation; 3 were performed under general anesthesia, and 2 were converted from local to general anesthesia during the procedure. Intraprocedural neurological changes were monitored and led to reevaluation of technique, immediate reimaging, modifying the endovascular procedure itself, or possibly mandating conversion to general anesthesia. RESULTS Thirty-nine anterior and 27 posterior circulation stenotic segments were treated. Angiographic success was achieved in 95.5% of patients with an overall reduction in stenosis of 75.5 to 22.3%. Percutaneous angioplasty and stenting were used in 58 cases; 8 patients were treated with stenting alone. Three patients (4.9%) developed neurological deficits mandating alteration or adjustment of endovascular technique or immediate postoperative management to avoid permanent sequelae. A total of 8 periprocedural complications occurred, 2 of which resulted in permanent neurological deficit. The overall mortality rate was 3.2%. CONCLUSIONS Stenting of intracranial atherosclerosis performed under conscious sedation is associated with complication rates and effectiveness similar to historical rates for general anesthesia. Conscious sedation confers the additional benefit of continuous neurological assessment during the procedure.


title: Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+).

text: To review the literature about febrile seizures and GEFS plus with special emphasis on management and outcome. Selected literature review. Febrile seizures are the most common convulsive event in humans, occurring in 2-6% of the population. The aetiology is complex with strong evidence for a heterogeneous genetic predisposition interacting with fever of any cause, with certain viral infections having a greater effect. A large amount of literature has established that febrile seizures have no long-term consequences on cognition or behaviour. Unfortunately, about 40% of children with a first febrile seizure will have a recurrence. The strongest predictor of recurrence is age <14-16 months at the time of the first febrile seizure. Epilepsy follows febrile seizures in ∼3% cases, with the concepts of simple and complex febrile seizures providing relatively weak prediction. Very prolonged febrile seizures may lead to mesial temporal sclerosis and temporal lobe epilepsy although the degree of risk remains uncertain. Investigations beyond establishing the cause of the provoking fever are nearly always unnecessary. Treatment is mainly reassurance and there is some evidence that parents eventually "come to grips" with the fear that their children are dying during a febrile seizure. Antipyretic medications are remarkably ineffective to prevent recurrences. Daily and intermittent prophylactic medications are ineffective or have unacceptable side effects or risks. "Rescue" benzodiazepines may prevent prolonged recurrences for selected patients with a first prolonged febrile seizure although this has not been proven. Genetic epilepsy with febrile seizures plus (GEFS+) is a complex autosomal dominant disorder usually caused by mutations in SCN1A (a voltage-gated sodium channel). One third of patients have febrile seizures only; two thirds have a variety of epilepsy syndromes, both focal and generalized. Febrile seizures may distress parents but rarely have any long-term consequences. Reassurance is the only treatment for the vast majority. Identifying patients with GEFS plus may lead to further investigations and counselling.


title: Phosphorylation of the antiviral protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination.

text: Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents virus fusion, although mechanisms controlling its trafficking to this cellular compartment are not fully understood. We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr(20)) and that mouse IFITM3 is also phosphorylated on the non-conserved Tyr(27). Phosphorylation led to a cellular redistribution of IFITM3, including plasma membrane accumulation. Mutation of Tyr(20) caused a similar redistribution of IFITM3 and resulted in decreased antiviral activity against influenza virus, whereas Tyr(27) mutation of mouse IFITM3 showed minimal effects on localization or activity. Using FYN knockout cells, we also found that IFITM3 phosphorylation is not a requirement for its antiviral activity. Together, these results indicate that Tyr(20) is part of an endocytosis signal that can be blocked by phosphorylation or by mutation of this residue. Further mutagenesis narrowed this endocytosis-controlling region to four residues conforming to a YXXΦ (where X is any amino acid and Φ is Val, Leu, or Ile) endocytic motif that, when transferred to CD4, resulted in its internalization from the cell surface. Additionally, we found that phosphorylation of IFITM3 by FYN and mutagenesis of Tyr(20) both resulted in decreased IFITM3 ubiquitination. Overall, these results suggest that modification of Tyr(20) may serve in a cellular checkpoint controlling IFITM3 trafficking and degradation and demonstrate the complexity of posttranslational regulation of IFITM3.


Laparoscopic surgery in a patient with atypical presentation of COVID-19: salient points to reduce the perils of surgery.


title: Molecular basis of the beta-lactamase protein using comparative modelling, drug screening and molecular dynamics studies to understand the resistance of β-lactam antibiotics.

text: Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the β-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against β-lactam antibiotics. These β-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of - 11.44 kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.


title: Sitagliptin Repositioning in SARS-CoV-2: Effects on ACE-2, CD-26, and Inflammatory Cytokine Storms in the Lung.

text: No Abstract.


title: Viral lung infections: epidemiology, virology, clinical features, and management of avian influenza A(H7N9).

text: PURPOSE OF REVIEW The avian influenza A(H7N9) virus has jumped species barrier and caused severe human infections. Here, we present the virological features relevant to clinical practice, and summarize the epidemiology, clinical findings, diagnosis, treatment, and preventive strategies of A(H7N9) infection. RECENT FINDINGS As of 18 February 2014, A(H7N9) virus has caused 354 infections in mainland China, Taiwan, and Hong Kong with a case-fatality rate of 32%. Elderly men were most affected. Most patients acquired the infection from direct contact with poultry or from a contaminated environment, although person-to-person transmission has likely occurred. A(H7N9) infection has usually presented with severe pneumonia, often complicated by acute respiratory distress syndrome and multiorgan failure. Mild infections have been reported in children and young adults. Nasopharyngeal aspirate and sputum samples should be collected for diagnosis, preferably using reverse transcriptase-PCR. Early treatment with neuraminidase inhibitors improved survival, but the efficacy of antivirals was hampered by resistant mutants. The closure of live poultry markets in affected areas has significantly contributed to the decline in the incidence of human cases. SUMMARY The emergence of A(H7N9) virus represents a significant health threat. High vigilance is necessary so that appropriate treatment can be instituted for the patient and preventive measures can be implemented.


title: COVID-19 and Its Potential Effect on Patients With Rheumatic Diseases in Latin America.

text: The COVID-19 (coronavirus disease 2019) pandemic has dramatically affected the entire world. Because of significant disparity levels in Latin American countries with deficient health care access and significant poverty, their population may end up among the most severely impacted. Patients with chronic conditions such as rheumatic diseases are quite vulnerable because of their high flaring risks and subsequent poor outcomes. Additionally, an overuse of antimalarials for the treatment of COVID-19 could lead to shortages in our region. Telemedicine, personal protective equipment use by patients and providers, web conferences, and comprehensive care are tools that will contribute to reduce the risk of infections and other complications in rheumatic disease patients, as well as to improve the knowledge and experience of rheumatologists at a global level.


title: Quality of evidence matters: is it well reported and interpreted in infertility journals?

text: PURPOSE To evaluate if the authors of published systematic reviews (SRs) reported the level of quality of evidence (QoE) in the top 5 impact factor infertility journals and to analyze if they used an appropriate wording to describe it. METHODS This is a cross-sectional study. We searched in PubMed for SRs published in 2017 in the five infertility journals with the highest impact factor. We analyzed the proportion of SRs published in the top 5 impact factor infertility journals that reported the SRs' QoE, and the proportion of those SRs in which authors used consistent wording to describe QoE and magnitude of effect. RESULTS The QoE was reported in only 21.4% of the 42 included SRs and in less than 10% of the abstracts. Although we did not find important differences in the report of QoE of those that showed statistically significant differences or not, p value was associated with the wording chosen by the authors. We found inconsistent reporting of the size the effect estimate in 54.8% (23/42) and in the level of QoE in 92.9% (39/42). Whereas the effect size was more consistently expressed in studies with statistically significant findings, QoE was better expressed in those cases in which the p value was over 0.05. CONCLUSION We found that in 2017, less than 25% of the authors reported the overall QoE when publishing SRs. Authors focused more on statistical significance as a binary concept than on methodological limitations like study design, imprecision, indirectness, inconsistency, and publication bias. Authors should make efforts to report the QoE and interpret results accordingly.


This usually goes much better than this.


title: Mental health burden for the public affected by the COVID-19 outbreak in China: Who will be the high-risk group?

text: In December, 2019, an outbreak of respiratory illness caused by Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread rapidly to other parts of China and around the world. We aimed to identify high-risk groups whose mental health conditions were vulnerable to the COVID-19 outbreak. Data were collected from 7,236 self-selected participants measured by anxiety symptoms, depressive symptoms, and sleep quality. The overall prevalence of anxiety symptoms, depressive symptoms, and poor sleep quality were 35.1%, 20.1%, and 18.2%, respectively. People aged < 35 years reported a higher prevalence of anxiety symptoms and depressive symptoms than people aged ≥ 35 years. Healthcare workers have the highest rate of poor sleep compared to other occupations. Healthcare workers/younger people who spent a high level of time (≥ 3 hours/day) had a particular higher prevalence of anxiety symptoms than in those who spent less time (< 1 hours/day and 1-2 hours/day) on the outbreak. During the COVID-19 outbreak, healthcare workers and younger people were at an especially high-risk of displaying psychological impact when they spent too much time thinking about the outbreak. Continuous monitoring of the psychological consequences for high-risk population should become routine as part of targeted interventions during times of crisis.I.


title: Ultrasonographic imaging of abomasal milk clotting and abomasal diameter in healthy and diarrheic calves.

text: In case of diarrhea calves are treated with oral rehydration solutions (ORS), which are known to increase abomasal pH and inhibit milk clotting in vitro. Nevertheless, recent studies have shown that ORS with HCO3(-) ≤ 62 mmol/L do not interfere with abomasal milk clotting in healthy calves. However, in diarrheic calves, feeding ORS and milk simultaneously may disturb abomasal curd formation and exacerbate diarrhea due to faster abomasal passage of ingesta. Therefore, the aim of the present study was to ultrasonographically examine abomasal milk clotting and diameter after feeding milk and milk replacer (MR) with and without ORS to healthy and diarrheic calves. Abomasal curd formation and diameter in healthy and diarrheic calves were ultrasonographically imaged before and after feeding milk, MR and ORS prepared in milk or MR. Feeding mixtures of milk or MR with ORS did not cause any remarkable differences in the ultrasonographic images of abomasal content. Moreover, abomasal milk clotting was not disturbed due to diarrhea. Statistically significant differences of abomasal diameter after feeding between healthy and diarrheic calves indicated that abomasal emptying is delayed in diarrheic calves. Hence, further studies are needed to determine reasons for decelerated abomasal passage in calves suffering from diarrhea.


title: Endovascular treatment of cerebral aneurysms using the Woven EndoBridge technique in a single center: preliminary results.

text: OBJECTIVE The Woven EndoBridge (WEB) is an innovative new technique for securing cerebral aneurysms. It is designed particularly for wide-necked bifurcation aneurysms that otherwise would be difficult to treat. There is a paucity of follow-up data in the literature due to the novelty of this technique. The authors reviewed their data from cases involving patients treated at Leeds General Infirmary with the WEB device. They assessed the safety and complication risk associated with the device and clinical and radiological follow-up outcomes in their patients. This is, to their knowledge, the first publication to include the new single-layer sphere device (WEB SLS) in addition to the original dual-layer (WEB DL) and the (nonsphere) single-layer (WEB SL) devices. METHODS Data from 22 patients who underwent 25 WEB treatments were analyzed. Of the 25 WEB procedures, 3 were performed on an acute basis, 1 was performed on a semiacute basis, and the remaining 21 were elective. A novel 6-point scoring system called the Leeds WEB aneurysm occlusion scale was created to ensure accurate assessment based on the morphology of the WEB device. Outcome was assessed at follow-up by MR angiography with or without digital subtraction angiography and the modified Rankin Scale (mRS). RESULTS Deployment of the WEB device was successful in 22 (88%) of 25 procedures; 3 (12%) of the attempts at WEB treatment were abandoned. One of the patients in whom treatment was abandoned underwent a successful second attempt. Immediately after the 22 procedures with successful deployment, 4 (18%) of the patients had a complete occlusion of the aneurysm and WEB device; 10 (45%) had varying degrees of occlusion within the WEB device but no aneurysm neck or remnant; 3 (14%) had a neck remnant; and 5 (23%) had an aneurysm remnant. Of the patients with an aneurysm remnant, 1 had a complete aneurysm occlusion at ≥ 3-months follow-up. In total, 6 (27%) patients had a residual aneurysm at ≥ 3-months radiological follow-up. One of these patients was admitted with hydrocephalus secondary to a recurrent aneurysm and later received a second WEB treatment with additional coiling. Only 1 patient developed new neurological symptoms. This patient went from an mRS score of 0 to a score of 1 and had radiological evidence of a thromboembolic event. Two patients showed radiological evidence of a new thromboembolic event on follow-up MRI but were clinically asymptomatic. CONCLUSIONS The WEB has shown itself to be a promising new device with the potential to increase the scope of treatment for difficult wide-necked bifurcation aneurysms. The technique is safe, and short-term results show effective occlusion of complex aneurysms with minimal complications associated with the procedure. Long-term efficacy, however, still needs to be assessed.


Covid-19: Trump fumes as adviser speaks out against lifting of US lockdowns.


title: Posterior Inferior Cerebellar Artery Patency after Flow-Diverting Stent Treatment.

text: BACKGROUND AND PURPOSE The rate of PICA occlusion after flow-diverting stent placement for vertebral and vertebrobasilar artery aneurysms is not known. The purpose of this study is to determine the medium-term rate of PICA patency and risk factors for occlusion after such aneurysm treatment. MATERIALS AND METHODS Patients were identified who had vertebral or vertebrobasilar artery aneurysms and who were treated by placing a flow-diverting stent across the PICA ostium. Demographic and procedural factors associated with stent placement were recorded. Patency of the PICA was evaluated immediately after stent placement and on follow-up angiography. RESULTS Thirteen patients with vertebral or vertebrobasilar artery aneurysms were treated in the study period, of whom 4 presented with subarachnoid hemorrhage. The average number of devices that spanned the PICA ostium was 1.77 (range, 1-3), with no immediate PICA occlusions. There were no postoperative strokes in the treated PICA territory, although there was 1 contralateral PICA-territory stroke of unclear etiology without clinical sequelae. In 11 patients with follow-up angiography at a mean of 10.6 months (range, 0.67-27.9 months), the PICA patency rate remained 100%. CONCLUSIONS Flow-diverting stent placement across the PICA ostium in the treatment of vertebral and vertebrobasilar artery aneurysms may not result in immediate or midterm PICA occlusion.


title: Food for Thought: Reward Mechanisms and Hedonic Overeating in Obesity.

text: PURPOSE OF REVIEW This review examines the food addiction model and the role of food hedonic pathways in the pathogenesis and treatment of obesity. RECENT FINDINGS The hedonic pathway interacts with the obesogenic environment to override homeostatic mechanisms to cause increase in body weight. Weight gain sustained over time leads to "upward setting" of defended level of body-fat mass. There are neurobiological and phenotypic similarities and differences between hedonic pathways triggered by food compared with other addictive substances, and the entity of food addiction remains controversial. Treatment for obesity including pharmacotherapy and bariatric surgery impacts on neural pathways governing appetite and hedonic control of food intake. The food addiction model may also have significant impact on public health policy, regulation of certain foods, and weight stigma and bias. Recent rapid progress in delineation of food hedonic pathways advances our understanding of obesity and facilitates development of effective treatment measures against the disease.


title: An update on zolpidem abuse and dependence.

text: In 2004, the health authorities (French National Agency for Medicines and Health Products Safety-ANSM) modified the summary of zolpidem characteristics. Particularly it now includes the sentence "a pharmacodependence may materialize." The current article aims to show that despite this modification, zolpidem continues to be associated with problematic drug use, as the official system (Center for Evaluation and Information on Pharmacodependence-Addictovigilance network) providing information on the abuse and dependence potential of drugs informs us. The authors reviewed the literature on this topic and analyzed French data from zolpidem's postmarketing period that were collected by the Addictovigilance network from 2003 to 2010. Postmarketing data and the 30 case reports yielded from the literature review highlight a significant dependence and abuse potential for zolpidem. This survey led to propose in stronger additional rules in France to try to mitigate the abuse potential of zolpidem.


title: Watershed Hepatocellular Carcinomas: The Risk of Incomplete Response following Transhepatic Arterial Chemoembolization.

text: PURPOSE Hepatocellular carcinomas (HCCs) bridging two or more Couinaud-Bismuth segments of the liver ("watershed tumors") can recruit multiple segmental arteries. The primary hypothesis of this study was that fewer watershed tumors show complete response (CR) after chemoembolization, with shorter time to local recurrence. Secondary analysis on the impact on transplantation eligibility in the presence of progressive disease was also performed. MATERIALS AND METHODS A total of 155 transplantation-eligible patients whose HCC met Milan criteria (watershed, n = 83; nonwatershed, n = 72) and was treated with chemoembolization were included. Cone-beam computed tomography (CT) was used for guidance and for confirmation of circumferential uptake. Local response to chemoembolization per modified Response Evaluation Criteria In Solid Tumors and local disease-free survival (DFS) for the index tumor were calculated. Differences were assessed by univariate and multivariate analyses. RESULTS CR after a single of chemoembolization was observed in 55.4% of watershed tumors and in 72.2% of nonwatershed tumors (P = .045). Estimated DFS intervals were 151 days (95% confidence interval [CI], 93-245 d) and 336 days (95% CI, 231-747 d; P = .040) in the watershed and nonwatershed groups, respectively. Worse DFS was observed with a Model for End-Stage Liver Disease score > 20 (P = .0001), higher Child-Pugh-Turcotte score (P = .049), and watershed location (P = .040). Waiting list drop-off rates were statistically similar between groups. CONCLUSIONS Hepatocellular carcinomas located in the watershed region of the liver have a poorer response to chemoembolization than those located elsewhere. These tumors are associated with worse DFS and require additional treatments to maintain transplantation eligibility per Milan criteria. Cone-beam CT can identify crossover supply and confirm complete geographic drug uptake, possibly reducing (but not eliminating) the risk of incomplete response.


title: Is Outpatient Thyroid Surgery for Everyone?

text: Thyroidectomy is a common surgical procedure. Traditionally, surgeons have performed thyroidectomy on an inpatient basis. However, consistent with current trends in surgery, some practices are transitioning thyroidectomy to an outpatient setting. Although concerns for hypocalcemia and postoperative bleeding exist regardless of surgeon experience, multiple studies demonstrate that outpatient thyroidectomy is safe in the hands of high-volume surgeons. Indeed, experienced thyroid surgeons who perform thyroidectomy in an outpatient setting experience excellent patient outcomes and reduced costs. However, outpatient thyroidectomy may not be suitable for all surgeons, hospitals, or patients. When evaluating whether to implement an outpatient thyroid program, a practice should consider a number of important factors including the team performing the procedure, the hospital, and the patient. With the appropriate staff education and experience, hospital setting, and patient selection, practices in a multitude of settings can successfully develop a safe, cost-effective outpatient thyroid program.


title: Adhesive performance of biomimetic adhesive-coated biologic scaffolds.

text: Surgical repair of a discontinuity in traumatized or degenerated soft tissues is traditionally accomplished using sutures. A current trend is to reinforce this primary repair with surgical grafts, meshes, or patches secured with perforating mechanical devices (i.e., sutures, staples, or tacks). These fixation methods frequently lead to chronic pain and mesh detachment. We developed a series of biodegradable adhesive polymers that are synthetic mimics of mussel adhesive proteins (MAPs), composed of 3,4-dihydroxyphenylalanine (DOPA)-derivatives, polyethylene glycol (PEG), and polycaprolactone (PCL). These polymers can be cast into films, and their mechanical properties, extent of swelling, and degradation rate can be tailored through the composition of the polymers as well as blending with additives. When coated onto a biologic mesh used for hernia repair, these adhesive constructs demonstrated adhesive strengths significantly higher than fibrin glue. With further development, a precoated bioadhesive mesh may represent a new surgical option for soft tissue repair.


title: Intra-Rater and Inter-Rater Reliability of Tongue Coating Diagnosis in Traditional Chinese Medicine Using Smartphones: Quasi-Delphi Study.

text: BACKGROUND There is a growing trend in the use of mobile health (mHealth) technologies in traditional Chinese medicine (TCM) and telemedicine, especially during the coronavirus disease (COVID-19) outbreak. Tongue diagnosis is an important component of TCM diagnosis. However, the procedure of obtaining tongue images has not been standardized and the reliability of tongue diagnosis by smartphone tongue images has yet to be evaluated. OBJECTIVE The first objective of this study was to develop an operating classification scheme for tongue coating diagnosis. The second and main objective of this study was to determine the intra-rater and inter-rater reliability of tongue coating diagnosis using the operating classification scheme. METHODS An operating classification scheme for tongue coating was developed using a stepwise approach and a quasi-Delphi method. First, tongue images (n=2023) were analyzed by 2 groups of assessors to develop the operating classification scheme for tongue coating diagnosis. Based on clinicians' (n=17) own interpretations as well as their use of the operating classification scheme, the results of tongue diagnosis on a representative tongue image set (n=24) were compared. After gathering consensus for the operating classification scheme, the clinicians were instructed to use the scheme to assess tongue features of their patients under direct visual inspection. At the same time, the clinicians took tongue images of the patients with smartphones and assessed tongue features observed in the smartphone image using the same classification scheme. The intra-rater agreements of these two assessments were calculated to determine which features of tongue coating were better retained by the image. Using the finalized operating classification scheme, clinicians in the study group assessed representative tongue images (n=24) that they had taken, and the intra-rater and inter-rater reliability of their assessments was evaluated. RESULTS Intra-rater agreement between direct subject inspection and tongue image inspection was good to very good (Cohen K range 0.69-1.0). Additionally, when comparing the assessment of tongue images on different days, intra-rater reliability was good to very good (K range 0.7-1.0), except for the color of the tongue body (K=0.22) and slippery tongue fur (K=0.1). Inter-rater reliability was moderate for tongue coating (Gwet AC2 range 0.49-0.55), and fair for color and other features of the tongue body (Gwet AC2=0.34). CONCLUSIONS Taken together, our study has shown that tongue images collected via smartphone contain some reliable features, including tongue coating, that can be used in mHealth analysis. Our findings thus support the use of smartphones in telemedicine for detecting changes in tongue coating.


title: Funding vaccines for emerging infectious diseases.

text: Immunization has played a large role in substantially reducing the infected and death tolls from infectious diseases. In the case of emerging diseases, the identity of the pathogen responsible, as well as the time and location for the next outbreak, cannot be accurately predicted using current means. Coupled with disjointed efforts towards the development of vaccines and a lack of funds and desire to advance promising products against known emerging pathogens to clinical trials, there has been a shortage of approved products ready for emergency use. Recent outbreaks have exposed these weaknesses, and the Coalition for Epidemic Preparedness Innovations (CEPI) was created in 2016 to address these issues. In this commentary, we discuss the establishment of such a global vaccine fund, and provide some additional points to consider for stimulating further discussion on this comprehensive, ambitious initiative.


title: The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance.

text: The developmental history of the gadolinium chelates, which spans 30 years, is described, focusing, in part, on the seminal work with each of the major agents in use today. By examining this history, insight is gained into important issues of efficacy and safety, with valuable lessons to be learned from the mistakes made during this period. An overview of physicochemical characteristics and chemical structures is also provided. The review concludes with a discussion of current research directions involving this field, which is that of the intravenous contrast media for magnetic resonance, in the past 5 years.


title: Structure-activity relationships and design of viral mutagens and application to lethal mutagenesis.

text: While mutation is the driving force behind evolution, most mutations are detrimental; therefore, elevating the mutation rate of a virus should diminish fitness. Because riboviruses and retroviruses have high mutation rates, a small increase in their mutation rates could exceed their threshold of viability. This approach, elevation of the viral mutation rate beyond the threshold of viability, extinction catastrophe or lethal mutagenesis, was proposed over a decade ago as a novel chemotherapeutic strategy. Extinction catastrophe induced by promutagenic nucleosides has been demonstrated in cell culture models, but most mutagens are carcinogenic and are poorly tolerated. Thus, clinical translation of viral mutagens has been difficult, casting doubt on the clinical viability of this strategy. This Perspective covers recent advances in the use of promutagenic nucleosides and the Vif-APOBEC interaction as chemotherapeutic strategies for targeting viral mutation rates.


title: No Love Lost Between Viruses and Interferons.

text: The interferon system protects mammals against virus infections. There are several types of interferons, which are characterized by their ability to inhibit virus replication and resultant pathogenesis by triggering both innate and cell-mediated immune responses. Virus infection is sensed by a variety of cellular pattern-recognition receptors and triggers the synthesis of interferons, which are secreted by the infected cells. In uninfected cells, cell surface receptors recognize the secreted interferons and activate intracellular signaling pathways that induce the expression of interferon-stimulated genes; the proteins encoded by these genes inhibit different stages of virus replication. To avoid extinction, almost all viruses have evolved mechanisms to defend themselves against the interferon system. Consequently, a dynamic equilibrium of survival is established between the virus and its host, an equilibrium that can be shifted to the host's favor by the use of exogenous interferon as a therapeutic antiviral agent.


title: Expert Intraoperative Judgment and Decision-Making: Defining the Cognitive Competencies for Safe Laparoscopic Cholecystectomy.

text: BACKGROUND Bile duct injuries from laparoscopic cholecystectomy remain a significant source of morbidity and are often the result of intraoperative errors in perception, judgment, and decision-making. This qualitative study aimed to define and characterize higher-order cognitive competencies required to safely perform a laparoscopic cholecystectomy. STUDY DESIGN Hierarchical and cognitive task analyses for establishing a critical view of safety during laparoscopic cholecystectomy were performed using qualitative methods to map the thoughts and practices that characterize expert performance. Experts with more than 5 years of experience, and who have performed at least 100 laparoscopic cholecystectomies, participated in semi-structured interviews and field observations. Verbal data were transcribed verbatim, supplemented with content from published literature, coded, thematically analyzed using grounded-theory by 2 independent reviewers, and synthesized into a list of items. RESULTS A conceptual framework was created based on 10 interviews with experts, 9 procedures, and 18 literary sources. Experts included 6 minimally invasive surgeons, 2 hepato-pancreatico-biliary surgeons, and 2 acute care general surgeons (median years in practice, 11 [range 8 to 14]). One hundred eight cognitive elements (35 [32%] related to situation awareness, 47 [44%] involving decision-making, and 26 [24%] action-oriented subtasks) and 75 potential errors were identified and categorized into 6 general themes and 14 procedural tasks. Of the 75 potential errors, root causes were mapped to errors in situation awareness (24 [32%]), decision-making (49 [65%]), or either one (61 [81%]). CONCLUSIONS This study defines the competencies that are essential to establishing a critical view of safety and avoiding bile duct injuries during laparoscopic cholecystectomy. This framework may serve as the basis for instructional design, assessment tools, and quality-control metrics to prevent injuries and promote a culture of patient safety.


title: Anchoring Pipeline Flow Diverter Construct in the Treatment of Traumatic Distal Cervical Carotid Artery Injury.

text: Background Traumatic extracranial internal carotid artery (ICA) dissections are uncommon and can be difficult to treat. Thinning of adventitia and dilatation may occur following arterial dissection, thus resulting in a fusiform pseudoaneurysm, which can subsequently cause bleeding, expanding, or pulsatile hematoma. Currently, medical management with anticoagulation remains the first line of treatment and yields good outcomes in 75% of cases with a mortality rate of 3-4%. Endovascular intervention is indicated with failure of medical therapy, progressive enlargement of a traumatic pseudoaneurysm, acute flow-related infarcts due to vessel occlusion, or when anticoagulation is contraindicated due to risk of pseudoaneurysm rupture and hemorrhage. Recognized interventional treatments include parent artery occlusion with or without revascularization, endovascular coil embolization, and covered stenting. Summary A wide variety of endovascular stents are available that are capable of opening a stenosed vessel while obliterating the associated false lumen and providing a scaffold for embolization of the pseudoaneurysm. The use of the Pipeline Embolization Device (PED) in the management of traumatic intracranial pseudoaneurysms has been described. However, there are few reports on the usage of the PED for treating traumatic extracranial ICA dissection and/or pseudoaneurysms. However, a potential complication of the use of PED in the extracranial ICA is a hypothetical tendency to migrate in a mobile vessel. Thus, the risk of migration of the PED has encouraged practitioners to adopt strategies to limit this risk. Key Messages We describe different techniques employed to anchor the flow-diverting construct within tortuous, mobile vessels.


Research on covid-19 is suffering "imperfect incentives at every stage".


title: Acute effects of insulin on circulating natriuretic peptide levels in humans.

text: BACKGROUND The natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production. OBJECTIVE We sought to determine the acute effects of insulin administration on natriuretic peptide concentrations. METHODS 31 men and women (11 lean, 10 overweight, and 10 obese), ages 30-70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol). RESULTS From baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 μU/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41). CONCLUSION Insulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.


title: The changes of endotracheal tube cuff pressure by the position changes from supine to prone and the flexion and extension of head.

text: BACKGROUND The proper cuff pressure is important to prevent complications related to the endotracheal tube (ETT). We evaluated the change in ETT cuff pressure by changing the position from supine to prone without head movement. METHODS Fifty-five patients were enrolled and scheduled for lumbar spine surgery. Neutral angle, which was the angle on the mandibular angle between the neck midline and mandibular inferior border, was measured. The initial neutral pressure of the ETT cuff was measured, and the cuff pressure was subsequently adjusted to 26 cmH2O. Flexed or extended angles and cuff pressure were measured in both supine and prone positions, when the patient's head was flexed or extended. Initial neutral pressure in prone was compared with adjusted neutral pressure (26 cmH2O) in supine. Flexed and extended pressure were compared with adjusted neutral pressure in supine or prone, respectively. RESULTS There were no differences between supine and prone position for neutral, flexed, and extended angles. The initial neutral pressure increased after changing position from supine to prone (26.0 vs. 31.5 ± 5.9 cmH2O, P < 0.001). Flexed and extended pressure in supine were increased to 38.7 ± 6.7 (P < 0.001) and 26.7 ± 4.7 cmH2O (not statistically significant) than the adjusted neutral pressure. Flexed and extended pressure in prone were increased to 40.5 ± 8.8 (P < 0.001) and 29.9 ± 8.7 cmH2O (P = 0.002) than the adjusted neutral pressure. CONCLUSIONS The position change from supine to prone without head movement can cause a change in ETT cuff pressure.


title: Reduction of CT beam hardening artefacts of ethylene vinyl alcohol copolymer by variation of the tantalum content: evaluation in a standardized aortic endoleak phantom.

text: OBJECTIVES Our aim was to develop an aortic stent graft phantom to simulate endoleak treatment and to find a tantalum content (TC) of ethylene-vinyl-alcohol-copolymer that causes fewer computed tomography (CT) beam hardening artefacts, but still allows for fluoroscopic visualization. METHODS Ethylene-vinyl-alcohol-copolymer specimens of different TC (10-50 %, and 100 %) were injected in an aortic phantom bearing a stent graft and endoleak cavities with simulated re-perfusion. Fluoroscopic visibility of the ethylene-vinyl-alcohol-copolymer specimens was analyzed. In addition, six radiologists analyzed endoleak visibility, and artefact intensity of ethylene-vinyl-alcohol-copolymer in CT. RESULTS Reduction of TC significantly decreased CT artefact intensity of ethylene-vinyl-alcohol-copolymer and increased visibility of endoleak re-perfusion (p < 0.000). It also significantly decreased fluoroscopic visibility of ethylene-vinyl-alcohol-copolymer (R = 0.883, p ≤ 0.01), and increased the active embolic volumes prior to visualization (Δ ≥ 40 μl). Ethylene-vinyl-alcohol-copolymer specimens with a TC of 45-50 % exhibited reasonable visibility, a low active embolic volume and a tolerable CT artefact intensity. CONCLUSIONS The developed aortic stent graft phantom allows for a reproducible simulation of embolization of endoleaks. The data suggest a reduction of the TC of ethylene-vinyl-alcohol-copolymer to 45 -50 % of the original, to interfere less with diagnostic imaging in follow-up CT examinations, while still allowing for fluoroscopic visualization.


title: The influence of mood and information processing strategies on recall, persuasion, and intention to get a flu vaccine.

text: This study investigates the interactions between mood (positive/negative) and information processing style (item-specific/relational/narrative processing) on responses to three types of advertising messages (ungrouped list/grouped list/narrative ads). A mood congruency effect was postulated and found to influence recall, persuasion and behavioral intention. Results supported the hypothesis that message effectiveness was moderated by mood in the direction of congruency. That is, participants in a positive mood recalled more information, were more persuaded, and were more likely to adopt the recommended behavior after exposure to advertisements with a grouped list format. Evidence regarding similarity of factors influencing relational and narrative processing is presented.


Suicide Mortality and Coronavirus Disease 2019-A Perfect Storm?


title: Long-Term Effect of Flow Diversion on Large and Giant Aneurysms: MRI-DSA Clinical Correlation Study.

text: BACKGROUND The long-term effect of flow diversion (FD) on aneurysms has not been well studied. OBJECTIVE We aimed to assess the effect of the Pipeline embolization device (Covidien, Irvine, California, USA) on large and giant intracranial aneurysms with magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) and then correlate with clinical follow-up. METHODS We conducted a retrospective analysis of aneurysms treated solely with Pipeline without adjunctive therapy. The largest aneurysm diameters were compared with pretreatment and post treatment MRI and correlated with DSA and clinical symptoms. RESULTS Twelve patients harboring large and giant saccular unruptured aneurysms, treated with Pipeline, were included. Mean follow-up times were as follows: MRI 22.8 months (range 1-57), DSA 18.2 months (range 1-33), and clinical 29 months (range 1-48). Ten (83%) of 12 treated aneurysms decreased in size on MRI, which was first seen at an average of 17 months (range 4-57). In 70% of patients the change was noted on MRI ≤1 year after treatment, at an average of 9.1 months (range 4-12). MRI reduction was more likely in angiographically occluded aneurysms. Five aneurysms with complete occlusion on early angiogram showed size reduction on MRI only at ≥12 months. Mean aneurysm size reduction was 57% (range 19.6-94.2), which correlated well with improvement of cranial neuropathies in 75% and headaches in 100% of patients. CONCLUSION Most aneurysms treated with Pipeline decreased in size, correlating with clinical improvement. Some aneurysms remained unchanged on MRI until a later time point despite early DSA occlusion. It may be reasonable to eliminate early postprocedural imaging and start follow-up only as late as 1 year after FD treatment in clinically stable, asymptomatic patients.


title: Prevalence of Dumping Syndrome After Laparoscopic Sleeve Gastrectomy and Comparison with Laparoscopic Roux-en-Y Gastric Bypass.

text: BACKGROUND Dumping syndrome is a well-known side effect of laparoscopic gastric bypass (LRYGB), and it is commonly believed that dumping syndrome is less likely to occur after laparoscopic sleeve gastrectomy (LSG), due to the preservation of the pyloric sphincter. However, it is not uncommon for patients undergoing LSG at our center to report symptoms suggestive of dumping syndrome. OBJECTIVE To assess the prevalence of symptoms of dumping syndrome after LSG compared with LRYGB. SETTING A single surgical group at a high-volume (700 cases per year) Bariatric and Metabolic Surgery Center of Excellence. METHODS One thousand four hundred seventy-one LRYGB (366) and LSG (1105) patients received a questionnaire to assess symptoms of dumping syndrome, utilizing a modified version of the Sigstad scoring system. Dumping syndrome was considered to be present when the questionnaire score exceeded a threshold value. RESULTS A total of 360 responses were received (249 LSG, 111 LRYGB). 26.5% (66) LSG and 41.4% (46) LRYGB exceeded the threshold for dumping syndrome (p < 0.01). 84.8% (56) LSG and 84.7% (39) LRYGB reported early dumping syndrome (p > 0.05). Thirty-six percent (24) LSG and 28% (13) LRYGB reported late dumping syndrome (p > 0.05). Twenty-seven percent (62) LSG and 44.4% (44) LRYGB reported at least one symptom of dumping syndrome with sweets (p < 0.05). 34.3% (85) LSG and 35.5% (39) LRYGB reported symptoms when drinking with or within 30 min of a meal (p > 0.05). 14.5% (36) LSG and 17.3% (19) LRYGB reported symptoms after alcohol consumption (p > 0.05). CONCLUSION Dumping syndrome after LSG is prevalent but has not been widely reported. This finding may impact clinicians and patients in their choice of procedure and has relevance in post-operative education and care.


title: Watertight Sealing Without Lumbar Drainage for Incidental Ventral Dural Defect in Transthoracic Spine Surgery: A Retrospective Review of 53 Cases.

text: STUDY DESIGN A retrospective review. OBJECTIVES To evaluate the therapeutic efficacy of the triple layer closure technique to establish watertight sealing without diversion of lumbar drainage, in preventing persistent incidental subarachnoid-pleural fistula and other neurological complications related to excessive drainage of cerebrospinal fluid (CSF) after dural defect in transthoracic ossified posterior longitudinal ligament (OPLL) surgery. SUMMARY OF BACKGROUND DATA CSF leakage into the pleural cavity leads to unfavorable conditions for natural healing of incidental durotomy due to the negative pressure environment of the pleural space and lack of wound healing around the bony cavity near the decompressed spinal cord. This often leads to a persistent incidental subarachnoid-pleural fistula. In addition, diversion of lumbar drainage may lead to excessive CSF drainage resulting in intracranial hypotension. To avoid this, we studied the efficacy of a modified sealing method to establish a more watertight covering at the ventral dural defect without lumbar CSF drainage. METHODS Fifty-three patients who had CSF leakage from the ventral aspect of the spinal cord during transthoracic spine surgery for thoracic OPLL between 2004 and 2013 were retrospectively reviewed. Patients were divided into 2 groups: a conventional group (group A) and a triple layer closure group (group B). In group A (n=33 patients), the dural defect was covered with fibrin glue (Beriplast P) mixed with gelfoam (Spongostan Standard) with subsequent subarachnoid lumbar drainage. In group B (n=20 patients), the dural defect was sealed using the triple layer technique with 2 layers of fibrin glue and gelatin sponge plus a third layer of synthetic hydrogel (Duraseal, Dural Sealant System) without subsequent subarachnoid lumbar drainage. Both groups had chest tubes that drained through an underwater seal. Clinical data including duration and total amount of drainage (chest tube and lumbar drainage), related complications, and duration of hospital stay were compared between the 2 groups. RESULTS Compared with the patients in group A, group B had a significantly smaller total volume of drainage and shorter chest tube drainage time (P<0.05) during their hospital stay. In group A, complications occurred in 6 cases (18.2%), including 3 cases of intracranial hypotension combined with transient mental status alteration, postural headache, and dizziness, 1 case of regional atelectasis with pneumonia, and 2 cases of revision thoracotomy. Revision thoracotomy was performed to treat persistent subarachnoid-pleural fistula due to significant and prolonged CSF leakage. In group B, there were no complications and no revision thoracotomy was needed. The mean duration of hospital stay was shorter in group B (15.6 d) compared with group A (22.4 d). CONCLUSIONS The established watertight closure of the dural defect using the triple layer sealing method without lumbar drainage was more effective and safe.


title: An investigation of sound levels on intensive care units with reference to the WHO guidelines.

text: INTRODUCTION Patients in intensive care units (ICUs) suffer from sleep deprivation arising from nursing interventions and ambient noise. This may exacerbate confusion and ICU-related delirium. The World Health Organization (WHO) suggests that average hospital sound levels should not exceed 35 dB with a maximum of 40 dB overnight. We monitored five ICUs to check compliance with these guidelines. METHODS Sound levels were recorded in five adult ICUs in the UK. Two sound level monitors recorded concurrently for 24 hours at the ICU central stations and adjacent to patients. Sample values to determine levels generated by equipment and external noise were also recorded in an empty ICU side room. RESULTS Average sound levels always exceeded 45 dBA and for 50% of the time exceeded between 52 and 59 dBA in individual ICUs. There was diurnal variation with values decreasing after evening handovers to an overnight average minimum of 51 dBA at 4 AM. Peaks above 85 dBA occurred at all sites, up to 16 times per hour overnight and more frequently during the day. WHO guidelines on sound levels could be only achieved in a side room by switching all equipment off. CONCLUSION All ICUs had sound levels greater than WHO recommendations, but the WHO recommended levels are so low they are not achievable in an ICU. Levels adjacent to patients are higher than those recorded at central stations. Unit-wide noise reduction programmes or mechanical means of isolating patients from ambient noise, such as earplugs, should be considered.


title: Vancomycin lung concentration in acute and hyperacute rejection models of lung transplantation in rats.

text: OBJECTIVES This study assesses vancomycin concentrations in allogenic transplanted rat lung tissue in acute and hyperacute rejection models of the lung. METHODS Left lung allotransplantation was performed from a male Brown Norway donor to a male Fisher F344 recipient in the case of an acute rejection model (the animals were sacrificed 5 days after transplantation) as well as a male Brown Norway donor to a male Wistar recipient in the case of hyperacute rejection (the animals were sacrificed 2 days after transplantation). Control rats were sham-operated and sacrificed on day 2 or 5, respectively, of the experimental model. Rejection was confirmed by blood gas assessment and lung histological examination. A single intraperitoneal dose of vancomycin 30 mg kg(-1) body weight was administered on the day of autopsy (day 2 or 5 from transplantation, respectively, of the experimental model), and then the blood and lung specimens were sampled at 0, 5, 1, 2, 4 and 6h from the time of drug injection. RESULTS Arterial blood gas assessment (Wistar rats - pO(2): 44.33 ± 21.73 mmHg (mean ± standard deviation (SD)); Fisher rats - pO(2:) 50.67 ± 14.30 mmHg (mean ± SD)) as well as histopathologic examinations of lung grafts confirmed rejection. Vancomycin lung/plasma concentration ratio was significantly higher in transplanted rats than in sham-operated animals. CONCLUSIONS Both acute and hyperacute lung rejection affect the lung/serum of vancomycin in the transplanted lung resulting in higher drug accumulation, especially in late post-dosage time.


title: Laparoscopic resection for Meckel's diverticulum causing intestinal obstruction.

text: Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal system with an estimated incidence of approximately 2% of the population. Although most cases are asymptomatic, it has the potential to create complications, such as hemorrhage, inflammation, intestinal obstruction, perforation, and intussusception. Meckel's diverticulum is generally diagnosed incidentally or upon investigation of unexplained gastrointestinal bleeding, perforation, inflammation, or obstruction for both pediatric and adult patients. Complications are often present as surgical emergencies and require resection of the diseased intestinal segment. In doubtful cases, laparoscopy should be the surgical method for both diagnosing and treating MD. Here we present a case of MD causing intestinal obstruction and that was treated by laparoscopic resection.


title: Ultrasensitive electrochemical immunosensor for alpha fetoprotein detection based on platinum nanoparticles anchored on cobalt oxide/graphene nanosheets for signal amplification.

text: An ultrasensitive sandwich-type electrochemical immunosensor was developed for quantitative monitoring of Alpha fetoprotein (AFP). To achieve this objective, an incorporated signal amplification strategy of platinum nanoparticles anchored on cobalt oxide/graphene nanosheets (Pt NPs/Co3O4/graphene) was proposed by acting as the label of secondary antibodies. The prepared label not only empowered by advantages of each component but exhibited better electrochemical performance than single Pt NPs, Co3O4 and graphene, which has shown large specific surface area and good catalytic activity towards the reduction of H2O2. Meanwhile, the nanocomposite of gold nanoparticles adhered on 3-mercaptopropyltriethoxysilane functionalized graphene sheets (Au@MPTES-GS) was used as matrix to accelerate electron transfer and immobilize primary antibodies in this system. The signal amplification mechanism of the matrix and the label were explored successfully. Under optimal conditions, the electrochemical immunosensor exhibited a wide linear range from 0.1 pg mL-1 to 60 ng mL-1 with a low detection limit of 0.029 pg mL-1for AFP. The proposed immunosensor may have promising application in the clinical diagnosis of AFP and other tumor markers.


title: Culture-Independent Diagnostics for Health Security.

text: The past decade has seen considerable development in the diagnostic application of nonculture methods, including nucleic acid amplification-based methods and mass spectrometry, for the diagnosis of infectious diseases. The implications of these new culture-independent diagnostic tests (CIDTs) include bypassing the need to culture organisms, thus potentially affecting public health surveillance systems, which continue to use isolates as the basis of their surveillance programs and to assess phenotypic resistance to antimicrobial agents. CIDTs may also affect the way public health practitioners detect and respond to a bioterrorism event. In response to a request from the Department of Homeland Security, Los Alamos National Laboratory and the Centers for Disease Control and Prevention cosponsored a workshop to review the impact of CIDTs on the rapid detection and identification of biothreat agents. Four panel discussions were held that covered nucleic acid amplification-based diagnostics, mass spectrometry, antibody-based diagnostics, and next-generation sequencing. Exploiting the extensive expertise available at this workshop, we identified the key features, benefits, and limitations of the various CIDT methods for providing rapid pathogen identification that are critical to the response and mitigation of a bioterrorism event. After the workshop we conducted a thorough review of the literature, investigating the current state of these 4 culture-independent diagnostic methods. This article combines information from the literature review and the insights obtained at the workshop.


title: Varied application of intercostal trans-diaphragmatic ports for laparoscopic hepatectomy.

text: BACKGROUND The ribcage and diaphragm are mechanical barriers for laparoscopic access during hepatectomy. Here, we introduce the varied application of intercostal trans-diaphragmatic ports during laparoscopic hepatectomy, and describe the management of intercostal ports with key technical points. METHODS From January 2013 to December 2017, 180 patients underwent laparoscopic hepatectomy. In 32 of these patients (17.8%), intercostal ports (31 right and one left) were applied, and we analyzed the feasibility and safety of intercostal ports during laparoscopic hepatectomy. RESULTS The main tumor location was segment VII and VIII (78%). The major type of laparoscopic hepatectomy was partial hepatectomy (91%). In the majority of cases (66%) the number and size of intercostal trocars was a single 5-mm port. The median operative time and blood loss were 232 min and 50 mL, respectively. A chest drain was placed via the hole of the intercostal port on the chest wall in two cases (6.3%). The median duration of the post-operative hospital stay was 6 days. There was no conversion, and a pure laparoscopic hepatectomy was achieved in all cases. There was no mortality. As for complications due to the application of intercostal ports, an asymptomatic pneumothorax was detected in only one case, and it was cured by conservative treatment. CONCLUSIONS The ribcage and diaphragm could be overcome as barriers to laparoscopic access by the placement of intercostal ports with minimal access during laparoscopic hepatectomy. The use of an intercostal port and proper management allows for a feasible approach and safe resection during laparoscopic hepatectomy.


title: The effect of intraoperative lidocaine versus esmolol infusion on postoperative analgesia in laparoscopic cholecystectomy: a randomized clinical trial.

text: BACKGROUND As a part of multimodal analgesia for laparoscopic cholecystectomy, both intraoperative lidocaine and esmolol facilitate postoperative analgesia. Our objective was to compare these two emerging strategies that challenge the use of intraoperative opioids. We aimed to assess if intraoperative esmolol infusion is not inferior to lidocaine infusion for opioid consumption after laparoscopic cholecystectomy. METHODS In this prospective, randomized, double-blind, non-inferiority clinical trial, 90 female patients scheduled for elective laparoscopic cholecystectomy received either intravenous (IV) lidocaine bolus 1.5 mg/kg at induction followed by an infusion (1.5 mg/ kg/h) or IV bolus of esmolol 0.5 mg/kg at induction followed by an infusion (5-15 μg/kg/min) till the end of surgery. Remaining aspect of anesthesia followed a standard protocol apart from no intraoperative opioid supplementation. Postoperatively, patients received either morphine or tramadol IV to maintain visual analogue scale (VAS) scores ≤3. The primary outcome was opioid consumption (in morphine equivalents) during the first 24 postoperative hours. Pain and sedation scores, time to first perception of pain and void, and occurrence of nausea/vomiting were secondary outcomes measured up to 24 h postoperatively. RESULTS Two patients in each group were excluded from the analysis. The postoperative median (IQR) morphine equivalent consumption in patients receiving esmolol was 1 (0-1.5) mg compared to 1.5 (1-2) mg in lidocaine group (p = 0.27). The median pain scores at various time points were similar between the two groups (p > 0.05). More patients receiving lidocaine were sedated in the post-anesthesia care unit (PACU) than those receiving esmolol (p < 0.05); however, no difference was detected later. CONCLUSION Infusion of esmolol is not inferior to lidocaine in terms of opioid requirement and pain severity in the first 24 h after surgery. Patients receiving lidocaine were more sedated during their stay in PACU than those receiving esmolol. TRIAL REGISTRATION ClinicalTrials.gov - NCT02327923. Date of registration: December 31, 2014.


title: Oxygen injection site affects FIO2 during noninvasive ventilation.

text: BACKGROUND Most portable bi-level positive airway pressure devices are not equipped with air-oxygen blenders for precisely regulating oxygen concentrations, and supplemental oxygen must be added to increase the F(IO2). Very few studies have investigated the factors that affect F(IO2), and their conclusions have been inconsistent. We investigated in vitro noninvasive ventilation (NIV) parameters and their effects on F(IO2), particularly the effect of the oxygen injection site. METHODS NIV was simulated with a test lung and manikin setup. F(IO2) was measured with 4 oxygen injection sites (mask, in front of the exhalation valve, at the humidifier outlet, and proximal to the ventilator), with 3 exhalation valve types, with 2 oxygen flows, and with 4 combinations of inspiratory and expiratory pressure. RESULTS Oxygen flow, inspiratory and expiratory pressure, and exhalation valve type all affected F(IO2). For a given oxygen flow, the oxygen injection site was the most important factor that affected F(IO2). The oxygen injection site that was closest to the patient (on the mask) had the higher F(IO2) (P < .001). CONCLUSIONS The oxygen injection site had the greatest effect on F(IO2) during NIV.


title: Exploring optimistic bias and the integrative model of behavioral prediction in the context of a campus influenza outbreak.

text: This study aims to determine the utility of constructs from the Integrative Model of Behavioral Prediction in predicting behaviors associated with flu prevention in a college campus. Building on previous studies that document substantial optimistic bias among college students, this study explores possible roles for optimistic bias in the Integrative Model of Behavioral Prediction. The authors conducted an online survey among a stratified random sample (N = 429) of undergraduate students in a university that experienced a large H1N1 influenza outbreak in the fall of 2009. The authors offer 3 major findings: (a) the 3 primary components in the Integrative Model of Behavioral Prediction predicted the intention to perform hand washing and sanitizing, with self-efficacy being the strongest predictor; (b) unrealistic optimists had significantly lower intentions to perform hand hygiene practices compared with realists or unrealistic pessimists; and (c) comparative optimism was a significant moderator of the relation between self-efficacy and behavioral intention, controlling for perceived risk. Theoretical and practical implications of these findings are discussed.


title: In vivo endoscopic tissue identification by rapid evaporative ionization mass spectrometry (REIMS).

text: Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer-related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.


title: Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.

text: Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (μCT)-based trabecular architecture with finite element analysis (FEA), μCT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D μCT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy.