title: Fluid supplementation for neonatal unconjugated hyperbilirubinaemia.

text: BACKGROUND Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation. OBJECTIVES To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another. DATA COLLECTION AND ANALYSIS We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs). MAIN RESULTS Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 μmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 μmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 μmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension. AUTHORS' CONCLUSIONS There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.


title: Development and validation of a rapid immunochromatographic assay for detection of Middle East respiratory syndrome coronavirus antigen in dromedary camels.

text: We present here a rapid immunochromatographic assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) antigen in the nasal swabs of dromedary camels. The assay is based on the detection of MERS-CoV nucleocapsid protein in a short time frame using highly selective monoclonal antibodies at room temperature. The relative sensitivity and specificity of the assay were found to be 93.90% and 100%, respectively, compared to that of the UpE and open reading frame 1A (Orf1A) real-time reverse transcriptase PCR (RT-PCR). The results suggest that the assay developed here is a useful tool for the rapid diagnosis and epidemiological surveillance of MERS-CoV infection in dromedary camels.


title: A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation.

text: Enveloped viruses such as coronaviruses or influenza virus require proteolytic cleavage of their fusion protein to be able to infect the host cell. Often viruses exhibit cell and tissue tropism and are adapted to specific cell or tissue proteases. Moreover, these viruses can introduce mutations or insertions into their genome during replication that may affect the cleavage, and thus can contribute to adaptations to a new host. Here, we present a fluorogenic peptide cleavage assay that allows a rapid screening of peptides mimicking the cleavage site of viral fusion proteins. The technique is very flexible and can be used to investigate the proteolytic activity of a single protease on many different substrates, and in addition, it also allows exploration of the activity of multiple proteases on one or more peptide substrates. In this study, we used peptides mimicking the cleavage site motifs of the coronavirus spike protein. We tested human and camel derived Middle East Respiratory Syndrome coronaviruses (MERS-CoV) to demonstrate that single and double substitutions in the cleavage site can alter the activity of furin and dramatically change cleavage efficiency. We also used this method in combination with bioinformatics to test furin cleavage activity of feline coronavirus spike proteins from different serotypes and strains. This peptide-based method is less labor- and time intensive than conventional methods used for the analysis of proteolytic activity for viruses, and results can be obtained within a single day.


title: Cord blood ischemia-modified albumin levels in normal and intrauterine growth restricted pregnancies.

text: Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals--"brain sparing effect"). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, "brain sparing effect" is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.


title: Complete radiofrequency ablation of hepatolithiasis-associated cholangiocarcinoma and successful management of post-ablation bronchobiliary fistula.

text: This report documented the use of radiofrequency ablation (RFA) in the treatment of hepatolithiasis-associated cholangiocarcinoma and cyanoacrylate glue in the management of post-ablation bronchobiliary fistula. A 47-year-old Chinese woman with 20 years history of extrahepatic and intrahepatic cholangiolithiasis and multiple hepatic segmentectomy, developed hepatolithiasis-associated cholangiocarcinoma. The tumor was successfully treated with RFA but patient developed bronchobiliary fistula. Cyanoacrylate glue was used for occluding the bronchobiliary fistula. CT scan at 3 months showed complete restoration of physiological separation between the biliary and bronchial system. Repeat CT scan showed complete tumor ablation with no signs of tumor recurrence 10 months after RFA. In conclusion, RFA may be a safe and effective treatment option for patients with hepatolithiasis-associated cholangiocarcinoma who are poor candidates for surgical resection. Protection of the integrity of the bile duct and diaphragm during RFA can minimize postoperative complications. In case of development of post-ablation bronchobiliary fistula, cyanoacrylate glue can be used to occlude the fistula, before surgical resection is considered.


docid: mtmnmwfd

title: Defensins in innate immunity.

text: PURPOSE OF REVIEW Defensins are a major family of antimicrobial peptides expressed predominantly in neutrophils and epithelial cells, and play important roles in innate immune defense against infectious pathogens. Their biological functions in and beyond innate immunity, structure and activity relationships, mechanisms of action, and therapeutic potential continue to be interesting research topics. This review examines recent progress in our understanding of alpha and theta-defensins - the two structural classes composed of members of myeloid origin. RECENT FINDINGS A novel mode of antibacterial action is described for human enteric alpha-defensin 6, which forms structured nanonets to entrap bacterial pathogens and protect against bacterial invasion of the intestinal epithelium. The functional multiplicity and mechanistic complexity of defensins under different experimental conditions contribute to a debate over the role of enteric alpha-defensins in mucosal immunity against HIV-1 infection. Contrary to common belief, hydrophobicity rather than cationicity plays a dominant functional role in the action of human alpha-defensins; hydrophobicity-mediated high-order assembly endows human alpha-defensins with an extraordinary ability to acquire structural diversity and functional versatility. Growing evidence suggests that theta-defensins offer the best opportunity for therapeutic development as a novel class of broadly active anti-infective and anti-inflammatory agents. SUMMARY Defensins are the 'Swiss army knife' in innate immunity against microbial pathogens. Their modes of action are often reminiscent of the story of 'The Blind Men and the Elephant'. The functional diversity and mechanistic complexity, as well as therapeutic potential of defensins, will continue to attract attention to this important family of antimicrobial peptides.


title: LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses.

text: The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) RIG-I, MDA5, and LGP2 stimulate inflammatory and antiviral responses by sensing nonself RNA molecules produced during viral replication. Here, we investigated how LGP2 regulates the RIG-I- and MDA5-dependent induction of type I interferon (IFN) signaling and showed that LGP2 interacted with different components of the RNA-silencing machinery. We identified a direct protein-protein interaction between LGP2 and the IFN-inducible, double-stranded RNA binding protein PACT. The LGP2-PACT interaction was mediated by the regulatory C-terminal domain of LGP2 and was necessary for inhibiting RIG-I-dependent responses and for amplifying MDA5-dependent responses. We described a point mutation within LGP2 that disrupted the LGP2-PACT interaction and led to the loss of LGP2-mediated regulation of RIG-I and MDA5 signaling. These results suggest a model in which the LGP2-PACT interaction regulates the inflammatory responses mediated by RIG-I and MDA5 and enables the cellular RNA-silencing machinery to coordinate with the innate immune response.


title: The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27.

text: MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the atypical box C/D snoRNA U3, which functions as a scaffold during early ribosome assembly, is a miRNA source. We show that a unique stem-loop structure in the 5' domain of U3 is processed to form short RNA fragments that associate with Argonaute. miR-U3 production is independent of Drosha, and an increased amount of U3 in the cytoplasm in the absence of Dicer suggests that a portion of the full length snoRNA is exported to the cytoplasm where it is efficiently processed into miRNAs. Using reporter assays, we demonstrate that miR-U3 can act as a low proficiency miRNA in vivo and our data support the 3' UTR of the sortin nexin SNX27 mRNA as an endogenous U3-derived miRNA target. We further reveal that perturbation of U3 snoRNP assembly induces miR-U3 production, highlighting potential cross-regulation of target mRNA expression and ribosome production.


title: The Optimal Approach for Laparoscopic Adrenalectomy through Mono Port regarding Left or Right Sides: A Comparative Study.

text: Introduction. Several studies have shown the feasibility and safety of both transperitoneal and posterior retroperitoneal approaches for single incision laparoscopic adrenalectomy, but none have compared the outcomes according to the left- or right-sided location of the adrenal glands. Materials and Methods. From 2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through mono port) were analyzed. The surgical outcomes attained using the transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were analyzed and compared. Results and Discussion. On the right side, no significant differences were found between the LAMP-TPA and LAMP-PRA groups in terms of patient characteristics and clinicopathological data. However, outcomes differed in which LAMP-PRA group had a statistically significant shorter mean operative time (84.13 ± 41.47 min versus 116.84 ± 33.17 min; P = 0.038), time of first oral intake (1.00 ± 0.00 days versus 1.21 ± 0.42 days; P = 0.042), and length of hospitalization (2.17 ± 0.389 days versus 3.68 ± 1.38 days; P ≤ 0.001), whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant shorter mean operative time (83.85 ± 27.72 min versus 110.95 ± 29.31 min; P = 0.002). Conclusions. We report that LAMP-PRA is more appropriate for right-sided laparoscopic adrenalectomies due to anatomical characteristics and better surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we propose LAMP-TPA as a more suitable method.


Critical changes to services for TB patients during the COVID-19 pandemic.


title: Novel Receptor Specificity of Avian Gammacoronaviruses That Cause Enteritis.

text: UNLABELLED Viruses exploit molecules on the target membrane as receptors for attachment and entry into host cells. Thus, receptor expression patterns can define viral tissue tropism and might to some extent predict the susceptibility of a host to a particular virus. Previously, others and we have shown that respiratory pathogens of the genus Gammacoronavirus, including chicken infectious bronchitis virus (IBV), require specific α2,3-linked sialylated glycans for attachment and entry. Here, we studied determinants of binding of enterotropic avian gammacoronaviruses, including turkey coronavirus (TCoV), guineafowl coronavirus (GfCoV), and quail coronavirus (QCoV), which are evolutionarily distant from respiratory avian coronaviruses based on the viral attachment protein spike (S1). We profiled the binding of recombinantly expressed S1 proteins of TCoV, GfCoV, and QCoV to tissues of their respective hosts. Protein histochemistry showed that the tissue binding specificity of S1 proteins of turkey, quail, and guineafowl CoVs was limited to intestinal tissues of each particular host, in accordance with the reported pathogenicity of these viruses in vivo. Glycan array analyses revealed that, in contrast to the S1 protein of IBV, S1 proteins of enteric gammacoronaviruses recognize a unique set of nonsialylated type 2 poly-N-acetyl-lactosamines. Lectin histochemistry as well as tissue binding patterns of TCoV S1 further indicated that these complex N-glycans are prominently expressed on the intestinal tract of various avian species. In conclusion, our data demonstrate not only that enteric gammacoronaviruses recognize a novel glycan receptor but also that enterotropism may be correlated with the high specificity of spike proteins for such glycans expressed in the intestines of the avian host. IMPORTANCE Avian coronaviruses are economically important viruses for the poultry industry. While infectious bronchitis virus (IBV), a respiratory pathogen of chickens, is rather well known, other viruses of the genus Gammacoronavirus, including those causing enteric disease, are hardly studied. In turkey, guineafowl, and quail, coronaviruses have been reported to be the major causative agent of enteric diseases. Specifically, turkey coronavirus outbreaks have been reported in North America, Europe, and Australia for several decades. Recently, a gammacoronavirus was isolated from guineafowl with fulminating disease. To date, it is not clear why these avian coronaviruses are enteropathogenic, whereas other closely related avian coronaviruses like IBV cause respiratory disease. A comprehensive understanding of the tropism and pathogenicity of these viruses explained by their receptor specificity and receptor expression on tissues was therefore needed. Here, we identify a novel glycan receptor for enteric avian coronaviruses, which will further support the development of vaccines.


title: The emerging role of the ubiquitin proteasome in pulmonary biology and disease.

text: Derangements in normal cellular homeostasis at the protein level can cause or be the consequence of initiation and progression of pulmonary diseases related to genotype, infection, injury, smoking, toxin exposure, or neoplasm. We discuss one of the fundamental mechanisms of protein homeostasis, the ubiquitin proteasome system (UPS), as it relates to lung disease. The UPS effects selective degradation of ubiquitinated target proteins via ubiquitin ligase activity. Important pathobiological mechanisms relating to the UPS and lung disease have been the focus of research, with inappropriate cellular proteolysis now a validated therapeutic target. We review the contributions of this system in various lung diseases, and discuss the exciting area of UPS-targeting drug development for pulmonary disease.


title: Robotic pancreas transplantation in a type 1 diabetic patient with morbid obesity: A case report.

text: RATIONALE Obesity is considered a relative contraindication to pancreas transplantation due to increased risks of wound-related complications. Robotic surgeries have never been applied for pancreas transplantation in obese recipients though robotic kidney transplantation did and already proved its value in reducing wound-related complications in obese recipients. PATIENT CONCERNS & DIAGNOSES We performed the first robotic pancreas after kidney transplantation for a 34-year-old Hispanic type 1 diabetic male with class III obesity (BMI = 41 kg/m). INTERVENTIONS The pancreas graft was procured and benched in the standard fashion. Methylene blue was used to detect any vascular leaks. The operation was completed via two 12-mm ports (camera, laparoscopic bed-side assistance), two 8-mm ports for robotic arms, and a 7-cm epigastric incision for hand port. The portal vein and arterial Y-graft of the pancreas were anastomosed to the recipient's left external iliac vein and artery, respectively. Duodenum-bladder drainage was performed with a circular stapler. OUTCOMES Duration of warm and cold ischemia was: 45 minutes and 7 hours, respectively. The patient was discharged uneventfully without wound-related complications. Excellent metabolic control was achieved with hemoglobin A1c lowering from 9% before transplantation to 4.4% on day 120. The patient remained in nondiabetic status in 1-year follow-up. LESSONS In conclusion, robotic pancreas transplantation is feasible in patients with morbid obesity.


title: LPS-stimulated cytokine production in type I cells is modulated by the renin-angiotensin system.

text: The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin-angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells can produce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-α, IL-6, or IL-1β at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of the lung.


title: The Endovascular Management of an Iatrogenic Superior Gluteal Artery Rupture Following Bone Marrow Biopsy.

text: We herein report an uncommon case of a life-threatening retroperitoneal hematoma after a bone marrow biopsy. Two hours after iliac crest bone harvesting, the patient experienced syncope and severe hypotension. Urgent contrast-enhanced computed tomography demonstrated extravasation from the superior gluteal artery. Transcatheter coil embolization was performed successfully, without complications. Life-threatening complications caused by retroperitoneal bleeding after bone marrow biopsy are very rare. There are few reports on the use of endovascular treatment in the management of life-threatening hemorrhagic complications after bone marrow biopsy.


title: Positive pressure device treatment for Menière's disease: an overview of the current evidence and a meta-analysis.

text: OBJECTIVE The objective was to critically assess the current evidence investigating the efficacy of using a positive pressure device in patients with definite or probable Menière's disease. METHODS We performed a systematic literature search in MEDLINE, EMBASE and PsycINFO up to February 2018. We included both systematic reviews and primary literature [randomized controlled trials (RCTs)] investigating positive pressure treatment, in patients (≥ 18 years of age), with Menière's disease. We assessed the internal validity of systematic reviews using the AMSTAR tool and risk of bias of primary studies using the Cochrane Risk of bias tool. We performed a meta-analysis for each outcome based on the identified studies. The overall certainty of evidence for the outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS The search for systematic reviews identified four relevant reviews. These all included the same four RCTs. An updated search identified one additional RCT. In total, five RCTs were included in the data synthesis. Our data synthesis showed no effect of positive pressure treatment on primary nor secondary outcomes. No serious adverse events were reported. The overall certainty of evidence ranged from very low to low, due to the serious risk of bias and imprecision. CONCLUSION The current available evidence does not support positive pressure device treatment in patients with Menière's disease. However, the limitations of the current literature hinder the possibility of any solid conclusion. There remains a need for randomized controlled trials of high quality to fully access the utility of this treatment.


title: Screening for Dental Infections Achieves 6-Fold Reduction in Dental Emergencies During Induction Chemotherapy for Acute Myeloid Leukemia.

text: PURPOSE Patients with newly diagnosed acute myeloid leukemia (AML) are at risk of infection, including odontogenic infections, during induction chemotherapy. It is unknown whether clinical dental screening to diagnose and treat odontogenic disease in these patients can reduce the incidence of dental emergencies. METHODS Between November 1, 2014, and December 31, 2016, we screened 147 patients with newly diagnosed AML before their admission for induction chemotherapy (n1 = 147, "screened" group). The patients not screened acted as controls (n2 = 190, "unscreened" group), as did patients diagnosed with AML in the 26 months before the initiation of the screening program (n3 = 304, "prescreening" group). The number of patients in each group who presented for emergency dental assessment during admission for induction chemotherapy was determined by 2 independent reviewers. RESULTS Among the 147 patients in the screened group, only 1 patient presented with an infectious odontogenic emergency (0.68% [95% CI, -0.64% to 1.98%]). In the unscreened group, 8 developed an infectious odontogenic emergency during induction chemotherapy (4.21% [95% CI, 1.37% to 7.15%]), a statistically significant difference (P = .046, a = 0.05). A similar rate of infectious dental emergencies was observed in the prescreening group (4.28% [95% CI, 2.0% to 7.2%]). CONCLUSION Clinical dental screening before induction chemotherapy in patients with AML resulted in a 6-fold reduction in infectious dental emergencies during the induction period.


docid: htdgmwox

title: Appendiceal stump closure with polymeric clips is a reliable alternative to endostaplers.


Estimating global epidemiology of low pathogenic human coronaviruses relating to the COVID-19 context.


Facing up to the uncertainties of COVID-19.


title: Diversity of MHC class I haplotypes in cynomolgus macaques.

text: Cynomolgus macaques are widely used as a primate model for human diseases associated with an immunological process. Because there are individual differences in immune responsiveness, which are controlled by the polymorphic nature of the major histocompatibility (MHC) locus, it is important to reveal the diversity of MHC in the model animal. In this study, we analyzed 26 cynomolgus macaques from five families for MHC class I genes. We identified 32 Mafa-A, 46 Mafa-B, 6 Mafa-I, and 3 Mafa-AG alleles in which 14, 20, 3, and 3 alleles were novel. There were 23 MHC class I haplotypes and each haplotype was composed of one to three Mafa-A alleles and one to five Mafa-B alleles. Family studies revealed that there were two haplotypes which contained two Mafa-A1 alleles. These observations demonstrated further the complexity of MHC class I locus in the Old World monkey.


COVID-19 reveals vulnerability of small-scale fisheries to global market systems.


title: Endoscopic Bariatric and Metabolic Therapies: Surgical Analogues and Mechanisms of Action.

text: Obesity is a worsening pandemic with numerous related comorbid illnesses. Conservative management including lifestyle modification and medications have limited efficacy. In contradistinction, bariatric surgery is effective, however, with substantial cost and non-negligible morbidity and mortality. As such, a small percentage of eligible patients undergo surgery. Over the past decade, endoscopic bariatric and metabolic therapies have been introduced as a less invasive option for the treatment of obesity and its related comorbid illnesses. This article reviews major endoscopic bariatric and metabolic therapies, their surgical analogues, and proposed mechanisms of action. Clinical trial data for each device also are discussed.


Covid-19 and ethnicity: it's too early to point to healthcare provider attitudes as a cause of poorer outcomes.


title: Effect of movement-related pain on behaviour and corticospinal excitability changes associated with arm movement preparation.

text: KEY POINTS Experimental pain or its anticipation influence motor preparation processes as well as upcoming movement execution, but the underlying physiological mechanisms remain unknown. Our results showed that movement-related pain modulates corticospinal excitability during motor preparation. In accordance with the pain adaptation theory, corticospinal excitability was higher when the muscle has an antagonist (vs. an agonist) role for the upcoming movement associated with pain. Anticipation of movement-related pain also affects motor initiation and execution, with slower movement initiation (longer reaction times) and faster movement execution compared to movements that do not evoke pain. These results confirm the implementation of protective strategies during motor preparation known to be relevant for acute pain, but which may potentially have detrimental long-term consequences and lead to the development of chronic pain. ABSTRACT When a movement repeatedly generates pain, we anticipate movement-related pain and establish self-protective strategies during motor preparation, but the underlying mechanisms remains poorly understood. The current study investigated the effect of movement-related pain anticipation on the modulation of behaviour and corticospinal excitability during the preparation of arm movements. Participants completed an instructed-delay reaction-time (RT) task consisting of elbow flexions and extensions instructed by visual cues. Nociceptive laser stimulations (unconditioned stimuli) were applied to the lateral epicondyle during movement execution in a specific direction (CS+) but not in the other (CS-), depending on experimental group. During motor preparation, transcranial magnetic stimulation was used to measure corticospinal excitability in the biceps brachii (BB). RT and peak end-point velocity were also measured. Neurophysiological results revealed an opposite modulation of corticospinal excitability in BB depending on whether it plays an agonist (i.e. flexion) or antagonist (i.e. extension) role for the CS+ movements (P < 0.001). Moreover, behavioural results showed that for the CS+ movements RT did not change relative to baseline, whereas the CS- movements were initiated more quickly (P = 0.023) and the CS+ flexion movements were faster relative to the CS- flexion movements (P < 0.001). This is consistent with the pain adaptation theory which proposes that in order to protect the body from further pain, agonist muscle activity is reduced and antagonist muscle activity is increased. If these strategies are initially relevant and lead to short-term pain alleviation, they may potentially have detrimental long-term consequences and lead to the development of chronic pain.


docid: jxzckcpc

title: Pediatric nasal injuries and management.

text: Although serious trauma injuries are uncommon in the pediatric population, nasal injuries are a more common problem. In this population, many physicians are uncomfortable managing these injuries. The evaluation and treatment of nasal trauma differ considerably in children compared with adult nasal fractures. Poor patient cooperation during the physical exam coupled with significant anatomic differences can present the nasal surgeon with a difficult diagnostic dilemma. The surgical management of pediatric nasoseptal injuries is not without controversy, as disturbing the nasal growth centers can have significant effect on future nasal and midfacial development. This article reviews the diagnostic and therapeutic challenges presented by these injuries for children and provides recommendations to successfully manage nasal injuries in this population.


title: Thrombus aspiration in primary angioplasty for ST-segment elevation myocardial infarction.

text: Mechanical reperfusion with primary percutaneous coronary intervention in acute ST-segment-elevation myocardial infarction is superior to fibrinolysis in terms of short-term and long-term outcome, provided that it can be delivered on time and by an experienced team. Balloon angioplasty and stent implantation of an occluded epicardial vessel during ST-segment-elevation myocardial infarction can cause disruption of the frail thrombus containing lesions associated with suboptimal myocardial reperfusion and microcirculatory obstruction. Distal embolization of atherothrombotic material can be prevented by thrombus aspiration during primary angioplasty. Mechanical aspiration via end-hole large-lumen thrombectomy catheters has been shown to improve Thrombolysis in Myocardial Infarction (TIMI) flow and result in a more consistent early resolution of ST-segment elevation in multiple registries. More recently, a more sophisticated quantification of the myocardial damage has been applied using myocardial scintigraphy and magnetic resonance, with no difference between patients treated with thrombectomy and patients treated with conventional therapy. The expectations in terms of lasting mortality benefit raised by the first Dutch single-center randomized trial of thrombectomy versus predilation with plain old balloon angioplasty (Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction, TAPAS) were not confirmed by a much larger Swedish trial (Thrombus Aspiration ST-Segment Elevation Myocardial Infarction, TASTE) showing no outcome changes. Although we are waiting for new trials to clarify these controversial results, thrombectomy is still used in selected patients with high thrombus load or with persistent occlusion of the infarct-related artery after wire passage. Here we review the various systems available and discuss their relative merits and the reported results.


title: Host - hepatitis C viral interactions: The role of genetics.

text: Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.


title: Exogenous Neural Precursor Cell Transplantation Results in Structural and Functional Recovery in a Hypoxic-Ischemic Hemiplegic Mouse Model.

text: Cerebral palsy (CP) is a common pediatric neurodevelopmental disorder, frequently resulting in motor and developmental deficits and often accompanied by cognitive impairments. A regular pathobiological hallmark of CP is oligodendrocyte maturation impairment resulting in white matter (WM) injury and reduced axonal myelination. Regeneration therapies based on cell replacement are currently limited, but neural precursor cells (NPCs), as cellular support for myelination, represent a promising regeneration strategy to treat CP, although the transplantation parameters (e.g., timing, dosage, mechanism) remain to be determined. We optimized a hemiplegic mouse model of neonatal hypoxia-ischemia that mirrors the pathobiological hallmarks of CP and transplanted NPCs into the corpus callosum (CC), a major white matter structure impacted in CP patients. The NPCs survived, engrafted, and differentiated morphologically in male and female mice. Histology and MRI showed repair of lesioned structures. Furthermore, electrophysiology revealed functional myelination of the CC (e.g., restoration of conduction velocity), while cylinder and CatWalk tests demonstrated motor recovery of the affected forelimb. Endogenous oligodendrocytes, recruited in the CC following transplantation of exogenous NPCs, are the principal actors in this recovery process. The lack of differentiation of the transplanted NPCs is consistent with enhanced recovery due to an indirect mechanism, such as a trophic and/or "bio-bridge" support mediated by endogenous oligodendrocytes. Our work establishes that transplantation of NPCs represents a viable therapeutic strategy for CP treatment, and that the enhanced recovery is mediated by endogenous oligodendrocytes. This will further our understanding and contribute to the improvement of cellular therapeutic strategies.


title: Radiation exposure from CT-guided ablation of renal masses: effects on life expectancy.

text: OBJECTIVE. The purpose of this article is to project the effects of radiation exposure on life expectancy (LE) in patients who opt for CT-guided radiofrequency ablation (RFA) instead of surgery for renal cell carcinoma (RCC). MATERIALS AND METHODS. We developed a decision-analytic Markov model to compare LE losses attributable to radiation exposure in hypothetical 65-year-old patients who undergo CT-guided RFA versus surgery for small (≤ 4 cm) RCC. We incorporated mortality risks from RCC, radiation-induced cancers (for procedural and follow-up CT scans), and all other causes; institutional data informed the RFA procedural effective dose. Radiation-induced cancer risks were generated using an organ-specific approach. Effects of varying model parameters and of dose-reduction strategies were evaluated in sensitivity analysis. RESULTS. Cumulative RFA exposures (up to 305.2 mSv for one session plus surveillance) exceeded those from surgery (up to 87.2 mSv). In 65-year-old men, excess LE loss from radiation-induced cancers, comparing RFA to surgery, was 11.7 days (14.6 days for RFA vs 2.9 days for surgery). Results varied with sex and age; this difference increased to 14.6 days in 65-year-old women and to 21.5 days in 55-year-old men. Dose-reduction strategies that addressed follow-up rather than procedural exposure had a greater impact. In 65-year-old men, this difference decreased to 3.8 days if post-RFA follow-up scans were restricted to a single phase; even elimination of RFA procedural exposure could not achieve equivalent benefits. CONCLUSION. CT-guided RFA remains a safe alternative to surgery, but with decreasing age, the higher burden of radiation exposure merits explicit consideration. Dose-reduction strategies that target follow-up rather than procedural exposure will have a greater impact.


Why does the coronavirus spread so easily between people?


docid: vfgdoqqo

title: Can we do better?


title: Almanac 2013: novel non-coronary cardiac interventions.

text: Recent innovations in interventional cardiology have dramatically expanded the therapeutic options for patients with cardiac conditions. Interventional cardiology is no longer limited to the treatment of coronary artery disease but allows also treatment of valvular disease, stroke prevention, hypertension, etc. One of the most important new treatment options is the percutaneous treatment for aortic valve stenosis (transcatheter aortic valve implantation), since aortic valve disease is a rather common problem in elderly patients, with many of them at high risk for surgery. Similarly, mitral regurgitation is often associated with comorbidities which make surgery high risk. The MitraClip is a promising percutaneous alternative to surgical valve repair or replacement. Other procedures discussed in this review are the percutaneous left atrial appendage closure as a non-pharmacologic therapy to prevent strokes, and renal denervation for resistant hypertension. This review explains the basic principles of these procedures, the most important clinical evidence, and also provides additional recent clinical data on each of these them.


title: Protein A-conjugated iron oxide nanoparticles for separation of Vibrio cholerae from water samples.

text: Pathogen separation is of great significance for precise detection and prevention of disease outbreaks. For the first time, protein A conjugated with chitosan-coated iron oxide nanoparticles was prepared for pathogen separation at low concentrations from liquid samples. Vibrio cholerae O1 (VO1) bacteria were used for testing the effectiveness of this conjugate. Transmission electron microscopy (TEM) was used to confirm the presence of captured VO1. The results showed that, after binding with a specific antibody, the conjugate allows separation of VO1 bacteria from water samples at a concentration as low as 10 cfu mL(-1). Moreover, the conjugate can be used in parallel with conventional or modern diagnostic tests for quick and accurate detection of pathogens.


title: Proteome-wide Data Analysis Reveals Tissue-specific Network Associated with SARS-CoV-2 Infection.

text: For patients with COVID-19 caused by SARS-CoV-2, the damages to multiple organs have been clinically observed. Since most of current investigations for virus-host interaction are based on cell level, there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection. Based on collected proteomic datasets from human lung, colon, kidney, liver and heart, we constructed a virus-receptor network, a virus-interaction network and a virus-perturbation network. In the tissue-specific networks associated with virus-host crosstalk, both common and different key hubs are revealed in diverse tissues. Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation. Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction. The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues, and the treatment of COVID-19 would be a complex task.


title: Experimental evaluation of immediate recanalization effect and recanalization efficacy of a new thrombus retriever for acute stroke treatment in vivo.

text: BACKGROUND AND PURPOSE Currently, several new stent retriever devices for acute stroke treatment are under development and early clinical evaluation. Preclinical testing under standardized conditions is an important first step to evaluate the technical performance and potential of these devices. The aim of this study was to evaluate the immediate recanalization effect, recanalization efficacy, thrombus-device interaction, and safety of a new stent retriever intended for thrombectomy in patients with acute stroke. MATERIAL AND METHODS The pREset thrombectomy device (4 × 20 mm) was evaluated in 16 vessel occlusions in an established swine model. Radiopaque thrombi (10-mm length) were used for visualization of thrombus-device interaction during application and retrieval. Flow-restoration effect immediately after deployment and after 5-minute embedding time before retrieval, recanalization rate after retrieval, thromboembolic events, and complications were assessed. High-resolution FPCT was performed to illustrate thrombus-device interaction during the embedding time. RESULTS Immediate flow restoration was achieved in 75% of occlusions. An increase or stable percentage of recanalizations during embedding time before retrieval was seen in 56.3%; a decrease, in 12.5%; reocclusion of a previously recanalized vessel, in 18.8%; and no recanalization effect at all, in 12.5%. Complete recanalization (TICI 3) after retrieval was achieved in 93.8%; partial recanalization (TICI 2b), in 6.2%. No distal thromboembolic events were observed. High-resolution FPCT illustrated entrapment of the thrombus between the stent struts and compression against the contralateral vessel wall, leading to partial flow restoration. During retrieval, the thrombus was retained in a straight position within the stent struts. CONCLUSIONS In this experimental study, the pREset thrombus retriever showed a high recanalization rate in vivo. High-resolution FPCT allows detailed illustration of the thrombus-device interaction during embedding time and is advocated as an add-on tool to the animal model used in this study.


title: Reducing surgical site infections following craniotomy: examination of the use of topical vancomycin.

text: OBJECT Although the use of topical vancomycin has been shown to be safe and effective for reducing postoperative infection rates in patients after spine surgery, its use in cranial wounds has not been studied systematically. The authors hypothesized that topical vancomycin, applied in powder form directly to the subgaleal space during closure, would reduce cranial wound infection rates. METHODS A cohort of 150 consecutive patients who underwent craniotomy was studied retrospectively. Seventy-five patients received 1 g of vancomycin powder applied in the subgaleal space at the time of closure. This group was compared with 75 matched-control patients who were accrued over the same time interval and did not receive vancomycin. The primary outcome measure was the presence of surgical site infection within 3 months. Secondary outcome measures included tissue pH from a subgaleal drain and vancomycin levels from the subgaleal space and serum. RESULTS Vancomycin was associated with significantly fewer surgical site infections (1 of 75) than was standard antibiotic prophylaxis alone (5 of 75; p < 0.05). Cultures were positive for typical skin flora species. As expected, local measured vancomycin concentrations peaked immediately after surgery (mean ± SD 499 ± 37 μg/ml) and gradually decreased over 12 hours. Vancomycin in the circulating serum remained undetectable. Subgaleal topical vancomycin was associated with a lower incidence of surgical site infections after craniotomy. The authors attribute this reduction in the infection rate to local vancomycin concentrations well above the minimum inhibitory concentration for antimicrobial efficacy. CONCLUSIONS Topical vancomycin is safe and effective for reducing surgical site infections after craniotomy. These data support the need for a prospective randomized examination of topical vancomycin in the setting of cranial surgery.


title: Under Allocation: Critical Supply Chain Hurdles Negatively Impact the Ability of Community Hospitals to Perform Repeat SARS-CoV-2 Testing.

text: There is increasing recognition that not all SARS-CoV-2 RT-PCR assays are created equal with respect to test performance (1).….


docid: unfhtwpe

title: Laparoscopic Repair of Small Ventral Hernias Using the "Ventralex™ Hernia Patch".

text: Laparoscopy of abdominal wall defects becomes more and more actual, considering the well-known advantages of minimally invasive surgery, and the reduced incidence of post-operative ventral infections and recurrence rates compared to the the open repair with or without mesh. We hereby present the technique of the laparoscopic repair of small ventral hernias (defect 2 centimetres), using the Ventralex mesh, which is bi-faceted, polypropylene and PTFE, circular preformed, it has 8 centimeters in diameter, fixated with 4 transparietal sutures. The mesh is created for open surgery but it is placed in the intraperitoneal cavity. This technique was used for 28 patients,16 women and 12 men, with an average age of 53,3 years (29-72 years), consisting of: 22 umbilical hernias (UH), 2 epigastric hernias (EH), one left-side Spiegelian hernia, one incisional hernia after an open surgery for an umbilical hernia with a Ventralex mesh, and 2 trocar eventrations (TE) after a laparoscopic cholecystectomy. Mean operating time was 52 minutes (42-70 minutes), post-operative hospital stay of 1,8 days (1-5 days). The main advantages are: circular preformed mesh, diameter of 8 centimeters, transfascial suture fixation, correct mesh placement and unfolding may be verified by laparoscopy, reduced costs. The technique is easy to reproduce.


docid: ifgopxfy

title: [SECOT consensus on thromboembolisms in knee and hip replacement surgery].

text: The purpose of this paper is to develop a professional consensus that proposes, in the light of the current scientific evidence and the clinical experience of an expert panel, some clinical recommendations directed at the Orthopaedic and Trauma Surgery (OTS) specialist and with the aim of reducing the variability in the prophylactic management of venous thromboembolic disease in knee and hip arthroplasty in clinical practice. The Delphi method was used, which consisted of two rounds of an e-mail questionnaire. Of the 55 items considered, a consensus was reached in 37 (67.2%) of them. In 31 cases there was consensus with the formulation of the item, and in 6 cases there was no agreed consensus. It was observed that there was a consensus in multiple clinical recommendations that could help OTS specialists in the making of decisions in their clinical practice.


Acute Respiratory Distress Syndrome.


Safety and role of chest CT in COVID-19 patients.


Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Japan.


title: Reducing unpleasant side effects of topical 5-Fluorouracil treatment for actinic keratosis: a randomized controlled trial.

text: INTRODUCTION 5-Fluorouracil (5-FU) for prophylactic treatment of diffuse actinic keratosis results in an exuberant inflammatory reaction, contributing to patient noncompliance and dissatisfaction. DESIGN This 5-week split-faced, double-blind, randomized controlled trial involved 30 subjects with diffuse facial AK who received twice daily 5-FU treatment for 2 weeks. This was followed by pre-randomized twice daily use of one of three topical interventions on one half of the face. TEWL, pH, and hydration were assessed on each quadrant of the face at all visits. Additionally, photographs were subjectively graded by three blinded trained observers. RESULTS Thirty subjects were enrolled, and had an average 27.1 (SD 11.8, range: 13-62) palpable AKs at baseline. Average resolution of baseline AK count was 98.1% by week 4. Clobetasol propionate is best at decreasing TEWL (p = .034), while petrolatum jelly most significantly improves hydration (p = .019) and erythema (p = .014). Though controlled release skin barrier emulsion trended towards improvement in TEWL (p = .17) and hydration (p = .19), there was no significant decrease in erythema (p = .257). Patient free-text response identified erythema as the most bothersome symptom. CONCLUSIONS Given the low cost, wide availability, and ability to significantly reduce erythema, petrolatum should be used for post-5-FU treatment for diffuse AK.


title: Thermal epiphysiodesis performed with radio frequency in a porcine model.

text: BACKGROUND AND PURPOSE Current techniques for epiphysiodesis involve opening of cortical windows; use of staples, screws, and tension devices; and fusion with curettes or drills. Complications may have serious consequences. There is a need for a more reliable, precise, and less traumatic procedure that overcomes the known complications from existing techniques. We analyzed a new epiphysiodesis technique using radio-frequency ablation (RFA) in a porcine model. METHODS Six 35-kg and two 25-kg immature pigs were used. 1 hind leg of each animal was randomly selected and the proximal tibia growth plate was ablated laterally and medially. The contralateral leg was used as a control. MR images were obtained immediately after the ablation and 12 weeks later for 6 animals, and 24 weeks later for the other 2 animals. CT was done for the 2 animals that were followed for 24 weeks for proof of bone bridges. RESULTS Both tibias were equal in length initially. At the 12-week follow-up, there was an average leg length discrepancy of 3.9 mm (95% CI: 3.0-4.8), and at 24 weeks the difference was 8.4 mm and 7.5 mm. No damage to the adjacent tissue was found. Bone bridges and physeal closure were found after 24 weeks. The pigs showed no discomfort after the intervention. INTERPRETATION We found RFA to be feasible for epiphysiodesis in a pig model. The method is minimally invasive and recovery may be quick compared to conventional methods. We recommend that the method should be tested in larger-scale safety studies before clinical application.


title: The effect of using the Partners for Change Outcome Management System as feedback tool in psychotherapy-A systematic review and meta-analysis.

text: OBJECTIVE The aims of the study were to evaluate the effects of using the Partners for Change Outcome Management System (PCOMS) in psychotherapy and to explore potential moderators of the effect. METHOD A comprehensive literature search including grey literature was conducted to identify controlled outcome studies on the PCOMS, randomized (RCTs), or non-randomized trials (N-RCT). RESULTS The literature search identified 18 studies, 14 RCTs, and four N-RCTs, including altogether 2910 participants. The meta-analysis of all studies found a small overall effect of using the PCOMS on general symptoms (g = 0.27, p = .001). The heterogeneity of the results was substantial. Moderation analyses revealed no effect of the PCOMS in psychiatric settings (g = 0.10, p = .144), whereas a positive effect was found in counseling settings (g = 0.45, p < .001), although almost all of these studies were characterized by a positive researcher allegiance and using the PCOMS Outcome Rating Scale (ORS) as the only outcome measure. CONCLUSION The meta-analysis revealed a small overall effect of using the PCOMS, but no effect in psychiatric settings. The positive results in counseling settings might be biased due to researcher allegiance and use of the ORS as the only outcome measure.


title: The I in COVID: The importance of community and patient involvement in COVID-19 research.

text: The call for community and patient involvement in the COVID-19 response is yet to be heard and answered. There are practical and ethical reasons for researchers not to neglect patient and public involvement (PPI), which has become an important cornerstone of UK-based clinical research. There has been a commendable effort towards driving evidence-based research, particularly through clinical trials in the UK. This article presents a brief background to PPI and points for consideration for clinical researchers currently active in or planning COVID-19 research.


[From Tuberculosis to COVID-19: Legal and Constitutional Framework Regarding Compulsory Isolation/Treatment due to Contagious Diseases in Portugal].


Covid-19: UK needs flexible local plans to come out of lockdown, say public health experts.


title: Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis.

text: OBJECTIVE. The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia. MATERIALS AND METHODS. We reviewed the clinical data and CT examinations of 15 consecutive pregnant women with COVID-19 pneumonia in our hospital from January 20, 2020, to February 10, 2020. A semiquantitative CT scoring system was used to estimate pulmonary involvement and the time course of changes on chest CT. Symptoms and laboratory results were analyzed, treatment experiences were summarized, and clinical outcomes were tracked. RESULTS. Eleven patients had successful delivery (10 cesarean deliveries and one vaginal delivery) during the study period, and four patients were still pregnant (three in the second trimester and one in the third trimester) at the end of the study period. No cases of neonatal asphyxia, neonatal death, stillbirth, or abortion were reported. The most common early finding on chest CT was ground-glass opacity (GGO). With disease progression, crazy paving pattern and consolidations were seen on CT. The abnormalities showed absorptive changes at the end of the study period for all patients. The most common onset symptoms of COVID-19 pneumonia in pregnant women were fever (13/15 patients) and cough (9/15 patients). The most common abnormal laboratory finding was lymphocytopenia (12/15 patients). CT images obtained before and after delivery showed no signs of pneumonia aggravation after delivery. The four patients who were still pregnant at the end of the study period were not treated with antiviral drugs but had achieved good recovery. CONCLUSION. Pregnancy and childbirth did not aggravate the course of symptoms or CT features of COVID-19 pneumonia. All the cases of COVID-19 pneumonia in the pregnant women in our study were the mild type. All the women in this study-some of whom did not receive antiviral drugs-achieved good recovery from COVID-19 pneumonia.


docid: fuljgago

title: [Potential antiviral therapeutics for 2019 Novel Coronavirus].

text: The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.


docid: bdyridkh

title: Covert coronavirus infections could be seeding new outbreaks.


title: Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

text: BACKGROUND Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. METHODS PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. RESULTS The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). CONCLUSIONS Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction.


On Masochism: A Resident's Conflict Between Sacrifice and Self-Preservation During the COVID-19 Pandemic.


title: Antiviral innate immune response of RNA interference.

text: RNA interference (RNAi) is an ancient, natural process conserved among species from different kingdoms. RNAi is a transcriptional and post-transcriptional gene silencing mechanism in which, double-stranded RNA or hairpin RNA is cleaved by an RNase III-type enzyme called Dicer into small interfering RNA duplex. This subsequently directs sequence-specific, homology dependent, Watson-Crick base-pairing post-transcriptional gene silencing by binding to its complementary RNA and initiating its elimination through degradation or by persuading translational inhibition. In plants, worms, and insects, RNAi is the main and strong antiviral defense mechanism. It is clear that RNAi silencing, contributes in restriction of viral infection in vertebrates. In a short period, RNAi has progressed to become a significant experimental tool for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has then been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. RNAi machinery required for robust RNAi-mediated antiviral response are conserved throughout evolution in mammals and plays a crucial role in antiviral defense of invertebrates, but despite these important functions RNAi contribution to mammalian antiviral innate immune defense has been underestimated and disputed. In this article, we review the literature concerning the roles of RNAi as components of innate immune system in mammals and how, the RNAi is currently one of the most hopeful new advances toward disease therapy. This review highlights the potential of RNAi as a therapeutic strategy for viral infection and gene regulation to modulate host immune response to viral infection.


title: The expanded role of extracellular matrix patch in malignant and non-malignant chest wall reconstruction in thoracic surgery.

text: OBJECTIVES The extracellular matrix (XCM Biologic Tissue Matrix) is a non-cross-linked 3D patch derived from porcine dermis. Once implanted, it is infiltrated by recipient's cells and becomes incorporated in the repair. Here, we report the first series of using this device for chest wall reconstruction. METHODS The XCM Biologic Tissue Matrix was utilized to provide the restoration of chest wall defects. It was used either alone or in conjunction with the Synthes titanium system to provide additional support. The decision was made intraoperatively. RESULTS Since April 2010, 21 (12 females) patients received the device. Average age at operation was 47 ± 17 years. Eleven (52%) patients had the patch inserted alone, while the remaining 10 received it in combination with another implantable medical device. The biological tissue matrix was used to reconstruct chest wall defects in cancer involving chest wall (n = 9), chest wall deformity (n = 6), chest wall hernia (n = 5) and chest wall repair following empyema drainage (n = 1). Complications were witnessed in 3 patients receiving the combined XCM and Synthes bar mechanisms; infection (n = 2) and bar displacement and infection (n = 1). CONCLUSIONS The XCM patch can be safely used to provide the strength required for chest wall reconstruction and to replace previously infected reconstructions.


title: Timely detection of localized excess influenza activity in Northern California across patient care, prescription, and laboratory data.

text: Timely detection of clusters of localized influenza activity in excess of background seasonal levels could improve situational awareness for public health officials and health systems. However, no single data type may capture influenza activity with optimal sensitivity, specificity, and timeliness, and it is unknown which data types could be most useful for surveillance. We compared the performance of 10 types of electronic clinical data for timely detection of influenza clusters throughout the 2007/08 influenza season in northern California. Kaiser Permanente Northern California generated zip code-specific daily episode counts for: influenza-like illness (ILI) diagnoses in ambulatory care (AC) and emergency departments (ED), both with and without regard to fever; hospital admissions and discharges for pneumonia and influenza; antiviral drugs dispensed (Rx); influenza laboratory tests ordered (Tests); and tests positive for influenza type A (FluA) and type B (FluB). Four credible events of localized excess illness were identified. Prospective surveillance was mimicked within each data stream using a space-time permutation scan statistic, analyzing only data available as of each day, to evaluate the ability and timeliness to detect the credible events. AC without fever and Tests signaled during all four events and, along with Rx, had the most timely signals. FluA had less timely signals. ED, hospitalizations, and FluB did not signal reliably. When fever was included in the ILI definition, signals were either delayed or missed. Although limited to one health plan, location, and year, these results can inform the choice of data streams for public health surveillance of influenza.


Neutrophil-to-lymphocyte ratio predicts the clearance of SARS-CoV-2 RNA in mild COVID-19 patients - a retrospective analysis from Dongxihu Fangcang Hospital in Wuhan, China.


title: Standardization of operative equipment reduces cost.

text: BACKGROUND We hypothesize that standardizing operative equipment, and reducing variability can safely achieve cost reduction. METHODS We retrospectively measured supply costs, operative time, intra-operative complications, and length of stay in a cohort of 145 patients at a children's hospital who underwent a laparoscopic appendectomy. A standardized preference card for laparoscopic appendectomy was developed and implemented. Data were prospectively collected on 101 consecutive patients and compared to the retrospective cohort using multiple linear regression. A survey assessing the perception of surgeons, nurses and scrub technologists of the impact of standardization on patient safety, patient care, OR efficiency, and cost was conducted. Wilcoxon rank sum test was used to evaluate associations between clinical role and years of experience with the total level of agreement on the survey. RESULTS A 20% average reduction was achieved in supply cost per case, with no significant change in operative time (p=0.14), total time in OR (p=0.15), or length of stay (p=0.60). No intra-operative complications were identified in either group. Survey participants agreed that standardization improves cost and safety. Nurses tended to have greater agreement that standardization improved efficiency and patient care compared to other roles (p=0.06). CONCLUSIONS Standardization of operative equipment can result in a significant cost reduction without impacting quality or delivery of care. Based on average case number per year, a total annual cost savings of >$41,000 could be realized. Survey participants agree that standardization improves cost and patient safety, yet perceptions regarding the impact on efficiency and patient care varied by occupation.


title: IRE1α promotes viral infection by conferring resistance to apoptosis.

text: The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis. The ability to undergo apoptosis limited infection in wild-type cells. Xbp1-deficient cells were generally resistant to the intrinsic pathway of apoptosis through an indirect mechanism involving activation of the nuclease IRE1α. We observed an IRE1α-dependent reduction in the abundance of the proapoptotic microRNA miR-125a and a corresponding increase in the amounts of the members of the antiapoptotic Bcl-2 family. The activation of IRE1α by the hepatitis C virus (HCV) protein NS4B in XBP1-proficient cells also conferred apoptosis resistance and promoted viral replication. Furthermore, we found evidence of IRE1α activation and decreased miR-125a abundance in liver biopsies from patients infected with HCV compared to those in the livers of healthy controls. Our results reveal a prosurvival role for IRE1α in virally infected cells and suggest a possible target for IFN-independent antiviral therapy.


title: Risk of distal embolization with stent retriever thrombectomy and ADAPT.

text: BACKGROUND There is a discrepancy in clinical outcomes and the achieved recanalization rates with stent retrievers in the endovascular treatment of ischemic stroke. It is our hypothesis that procedural release of embolic particulate may be one contributor to poor outcomes and is a modifiable risk. The goal of this study is to assess various treatment strategies that reduce the risk of distal emboli. METHODS Mechanical thrombectomy was simulated in a vascular phantom with collateral circulation. Hard fragment-prone clots (HFC) and soft elastic clots (SECs) were used to generate middle cerebral artery (MCA) occlusions that were retrieved by the Solitaire FR devices through (1) an 8 Fr balloon guide catheter (BGC), (2) a 5 Fr distal access catheter at the proximal aspect of the clot in the MCA (Solumbra), or (3) a 6 Fr guide catheter with the tip at the cervical internal carotid artery (guide catheter, GC). Results from mechanical thrombectomy were compared with those from direct aspiration using the Penumbra 5MAX catheter. The primary endpoint was the size distribution of emboli to the distribution of the middle and anterior cerebral arteries. RESULTS Solumbra was the most efficient method for reducing HFC fragments (p<0.05) while BGC was the best method for preventing SEC fragmentation (p<0.05). The risk of forming HFC distal emboli (>1000 µm) was significantly increased using GC. A non-statistically significant benefit of direct aspiration was observed in several subgroups of emboli with size 50-1000 µm. However, compared with the stent-retriever mechanical thrombectomy techniques, direct aspiration significantly increased the risk of SEC fragmentation (<50 µm) by at least twofold. CONCLUSIONS The risk of distal embolization is affected by the catheterization technique and clot mechanics.


title: The development and reform of public health in China from 1949 to 2019.

text: BACKGROUND Public health system plays a vital role in the development of health sector in China and protects the health of Chinese people. However, there are few comprehensive reviews and studies focusing on its evolution and reform. It is worthwhile to pay attention to the public health development in China, given that the history and structure of public health system have their own characteristics in China. METHODS The study is a retrospective review of the development public health over seven decades in China. It presents the findings from some national or provincial survey data, interviews with key informants, reviews of relevant published papers and policy contents. RESULTS This study identified four key stages that public health experienced in China: the initial stage centering on prevention, the stage of deviation with more attention to treatment but little to prevention, the recovery stage after SARS(Severe Acute Respiratory Syndromes) Crisis, and the new stage to an equitable and people-centered system. In the latest stage, the National Basic Public Health Service Program (NBPHSP) is implemented to respond the threat of noncommunicable diseases (NCDs) and has achieved some initial results, while there are still many challenges including service quality, poor integration among service items and IT system, lack of quality professionals and insufficient intersectoral endeavor. DISCUSSION There are unique Chinese wisdom and remarkable achievements as well as twists and turns on the development of China's public health. Prevention-first, flexible structure of the system, multi-agency collaboration and mass mobilization and society participation are the main experience of public health in early stage. Despite twists and turns since 1980s, public health system in China shows substantial resilience which may be from the government's continuous commitment to social development and people's livelihoods and its flexible governance. In 2010s, in order to achieve the well-off society, Chinese government pays unprecedented attention to health sector, which bring a new wave of opportunities to public health such as remaining the NBPHSP for priority. The evolution and reform of China's public health is based on its national condition, accumulates rich experience but also faces many common worldwide challenges. Getting this development and reform right is important to China's social and economic development in future, and China's experience in public health may provide many lessons for other countries. CONCLUSION Public health in China needs to focus on prevention, strengthen multi-agency coordination mechanism, improve the quality of public health services in the future.


title: Ethics of Outbreaks Position Statement. Part 2: Family-Centered Care.

text: OBJECTIVES Continue the dialogue presented in Ethics of Outbreaks Position Statement. Part 1, with a focus on strategies for provision of family-centered care in critical illness during Pubic Health Emergency of International Concern. DESIGN Development of a Society of Critical Care Medicine position statement using literature review, expert consensus from the Society of Critical Care Medicine Ethics Committee. A family member of a patient who was critically ill during a natural disaster served on the writing panel and provided validation from a family perspective to the recommendations. SETTING Provision of family-centered care and support for patients who are critically ill or who have the potential of becoming critically ill, and their families, during a Pubic Health Emergency of International Concern. INTERVENTIONS Communication; family support. MEASUREMENTS AND MAIN RESULTS Family-centered interventions during a Pubic Health Emergency of International Concern include understanding how crisis standards may affect regional and local traditions. Transparently communicate changes in decision-making authority and uncertainty regarding treatments and outcomes to the family and community. Assess family coping, increase family communication and support, and guide families regarding possible engagement strategies during crisis. Prepare the public to accept survivors returning to the community.


title: [Intensive Care During a Global Epidemic].

text: The global spread of coronavirus disease 2019 (COVID-19) is rapidly increasing the number of patients who are critically ill with this disease, with the related rate of mortality expected to peak in 2020 (Alhazzani et al., 2020). As severe acute respiratory syndrome is the major cause of mortality after COVID-19 infection, patients with COVID-19 who are prone to severe acute respiratory problems may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO; Alhazzani et al., 2020). Ongoing advances in intensive care medicine are continuing to improve survival in critically ill patients (Kaukonen, Bailey, Suzuki, Pilcher, & Bellomo, 2014). However, intensive care unit (ICU) survivors may experience complications and problems related to their disease and treatment such as critical illness polyneuropathy, critical illness myopathy, and post intensive care syndrome (PICS; Alhazzani et al., 2020). Harvey (2012) reported that 85%-95% of ICU patients have ICU-acquired weakness after ICU discharge and 74% of ICU patients with acute respiratory distress syndrome have cognitive impairment after ICU discharge. Physical disabilities, cognitive impairment, and mental or psychological distress (e.g., anxiety, depression, and post-traumatic stress disorder) after ICU discharge may be symptoms of PICS, and may continue to affect surviving patients for several years after ICU discharge (Elliott et al., 2014; Held & Moss, 2019; Jackson et al., 2014; Jubran et al., 2010). Efforts to prevent and treat COVID-19 in Taiwan have proven more effective compared to most other places in the world. In addition to the low number of diagnosed cases, the mortality rate (seven of 440 confirmed cases) in Taiwan has been significantly lower than in most other countries (Taiwan Centers for Disease Control, ROC, 2020, May 14). However, post-discharge care for ICU survivors, especially those hospitalized after a sudden onset of severe disease symptoms and then discharged after a long ICU stay or after receiving mechanical ventilation, require specialized care to minimize PICS. Nurses are responsible not only for treating patients with the disease but also for preventing the further spread of disease. Therefore, providing continued care to patients discharged from the ICU is essential. Specifically, interventions to avoid PICS must be implemented rapidly by multidisciplinary medical teams during and immediately after ICU discharge.


title: Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.

text: The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid protein, which packages viral RNA into new virions. We determined a 1.4 å resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS-CoV. While the N2b domain forms a dimer in solution, addition of the C-terminal spacer B/N3 domain mediates formation of a homotetramer. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α-helix that self-associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS-CoV-2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle, with implications for both drug design and antibody-based testing. This article is protected by copyright. All rights reserved.


title: Calculation of the Respiratory Modulation of the Photoplethysmogram (DPOP) Incorporating a Correction for Low Perfusion.

text: DPOP quantifies respiratory modulations in the photoplethysmogram. It has been proposed as a noninvasive surrogate for pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. The correlation between DPOP and PPV may degrade due to low perfusion effects. We implemented an automated DPOP algorithm with an optional correction for low perfusion. These two algorithm variants (DPOPa and DPOPb) were tested on data from 20 mechanically ventilated OR patients split into a benign "stable region" subset and a whole record "global set." Strong correlation was found between DPOP and PPV for both algorithms when applied to the stable data set: R = 0.83/0.85 for DPOPa/DPOPb. However, a marked improvement was found when applying the low perfusion correction to the global data set: R = 0.47/0.73 for DPOPa/DPOPb. Sensitivities, Specificities, and AUCs were 0.86, 0.70, and 0.88 for DPOPa/stable region; 0.89, 0.82, and 0.92 for DPOPb/stable region; 0.81, 0.61, and 0.73 for DPOPa/global region; 0.83, 0.76, and 0.86 for DPOPb/global region. An improvement was found in all results across both data sets when using the DPOPb algorithm. Further, DPOPb showed marked improvements, both in terms of its values, and correlation with PPV, for signals exhibiting low percent modulations.


title: Intraoperative experiments combined with gait analyses indicate that active state rather than passive dominates the spastic gracilis muscle's joint movement limiting effect in cerebral palsy.

text: BACKGROUND In cerebral palsy, spastic muscle's passive forces are considered to be high but have not been assessed directly. Although activated spastic muscle's force-joint angle relations were studied, this was independent of gait relevant joint positions. The aim was to test the following hypotheses intraoperatively: (i) spastic gracilis passive forces are high even in flexed knee positions, (ii) its active state forces attain high amplitudes within the gait relevant knee angle range, and (iii) increase with added activations of other muscles. METHODS Isometric forces (seven children with cerebral palsy, gross motor function classification score = II) were measured during surgery from knee flexion to full extension, at hip angles of 45° and 20° and in four conditions: (I) passive state, after gracilis was stimulated (II) alone, (III) simultaneously with its synergists, and (IV) also with an antagonist. FINDINGS Directly measured peak passive force of spastic gracilis was only a certain fraction of the peak active state forces (maximally 26%) measured in condition II. Conditions III and IV caused gracilis forces to increase (for hip angle = 45°, by 32.8% and 71.9%, and for hip angle = 20°, by 24.5% and 45.1%, respectively). Gait analyses indicated that intraoperative data for knee angles 61-17° and 33-0° (for hip angles 45° and 20°, respectively) are particularly relevant, where active state force approximates its peak values. INTERPRETATION Active state muscular mechanics, rather than passive, of spastic gracilis present a capacity to limit joint movement. The findings can be highly relevant for diagnosis and orthopaedic surgery in individuals with cerebral palsy.


title: A prospective, multi-institutional study of flexible ureteroscopy for proximal ureteral stones smaller than 2 cm.

text: PURPOSE Flexible ureteroscopy is rapidly becoming a first line therapy for many patients with renal and ureteral stones. However, current understanding of treatment outcomes in patients with isolated proximal ureteral stones is limited. Therefore, we performed a prospective, multi-institutional study of ureteroscopic management of proximal ureteral stones smaller than 2 cm to better define clinical outcomes associated with this approach. MATERIALS AND METHODS Adult patients with proximal ureteral calculi smaller than 2 cm were prospectively identified. Patients with concomitant ipsilateral renal calculi or prior ureteral stenting were excluded from study. Flexible ureteroscopy, holmium laser lithotripsy and ureteral stent placement was performed. Ureteral access sheath use, laser settings and other details of perioperative and postoperative management were based on individual surgeon preference. Stone clearance was determined by the results of renal ultrasound and plain x-ray of the kidneys, ureters and bladder 4 to 6 weeks postoperatively. RESULTS Of 71 patients 44 (62%) were male and 27 (38%) were female. Mean age was 48.2 years. ASA(®) score was 1 in 12 cases (16%), 2 in 41 (58%), 3 in 16 (23%) and 4 in 2 (3%). Mean body mass index was 31.8 kg/m(2), mean stone size was 7.4 mm (range 5 to 15) and mean operative time was 60.3 minutes (range 15 to 148). Intraoperative complications occurred in 2 patients (2.8%), including mild ureteral trauma. Postoperative complications developed in 6 patients (8.7%), including urinary tract infection in 3, urinary retention in 2 and flash pulmonary edema in 1. The stone-free rate was 95% and for stones smaller than 1 cm it was 100%. CONCLUSIONS Flexible ureteroscopy is associated with excellent clinical outcomes and acceptable morbidity when applied to patients with proximal ureteral stones smaller than 2 cm.


docid: eesxyaks

title: More stapler firings increase the risk of perioperative morbidity after laparoscopic sleeve gastrectomy.

text: Introduction Staple-line bleeding and leakage are the most common serious complications of laparoscopic sleeve gastrectomy. The relationship between multiple stapler firings and higher risk of postoperative complications is well defined in colorectal surgery but has not been addressed in bariatric procedures so far. Identification of new factors such as "the numbers of stapler firings used during laparoscopic sleeve gastrectomy (LSG)" as a predictor for complications can lead to optimization of the patient care at bariatric centers. Aim To determine the association between perioperative morbidity and the number of stapler firings during laparoscopic sleeve gastrectomy. Material and methods This observational study was based on retrospective analysis of prospectively collected data in patients operated on for morbid obesity in a teaching hospital/tertiary referral center for general surgery. The patients who underwent LSG were analyzed in terms of the number of stapler firings used as a new potential risk predictor for postoperative complications after surgery, adjusting for other patient- and treatment-related factors. The study included 333 patients (209 women, 124 men, mean age: 40 ±11). Results During the first 30 days after surgery, complications were observed in 18 (5.41%) patients. Multivariate analysis showed that prolonging operative time increased morbidity (every minute, OR = 1.01; 95% CI: 1.00-1.02) and the complication rate increased with the number of stapler firings (every firing, OR = 1.91; 95% CI: 1.09-3.33; p = 0.023). Conclusions Additional stapler firings above the usual number and a prolonged operation should alert a surgeon and the whole team about increased risk of postoperative complications.


title: Genome-wide analysis of transcript isoform variation in humans.

text: We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternative splice site use, intron retention), differential 5' UTR (initiation of transcription) use, and differential 3' UTR (alternative polyadenylation) use. These results demonstrate that the regulatory effects of genetic variation in a normal human population are far more complex than previously observed. This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility.


title: Use of humanized severe combined immunodeficient mice for human vaccine development.

text: The severe combined immunodeficient (SCID) mouse has no adaptive immunity, lacking mature T and B cells in the peripheral blood or the lymphoid organs. It has been used extensively in biomedical research as a valuable translational model for xeno-engraftment of human tissues and cells. This review focuses on the engraftment of human peripheral blood cells and tissues in SCID mice, as well as in the newly established and more permissive SCID mice deficient in the IL-2 receptor gamma-chain. Human immune responses could be elicited and assessed in these humanized SCID mice upon vaccination or sensitization with allogeneic tissues. A translational model is proposed to attain preclinical data for testing human vaccines.


title: Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction.

text: RATIONALE The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD. OBJECTIVES To test the association of soluble RAGE (sRAGE) levels with PGD in a prospective, multicenter cohort study. METHODS We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) within the first 72 hours after transplantation. MEASUREMENTS AND MAIN RESULTS Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearman's rho = 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02). CONCLUSIONS Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.


title: The Battle against COVID 19 Pandemic: What we Need to Know Before we "Test Fire" Ivermectin.

text: The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.


title: Dissecting mammalian immunity through mutation.

text: Although mutation and natural selection have given rise to our immune system, a well-placed mutation can also cripple it, and within an expanding population we are recognizing more and more cases of single-gene mutations that compromise immunity. These mutations are an ideal tool for understanding human immunology, and there are more ways than ever to measure their physiological effects. There are also more ways to create mutations in the laboratory, and to use these resources to systematically define the function of every gene in our genome. This review focuses on the discovery and creation of mutations in the context of mammalian immunity, with an emphasis on the use of genome-wide chemical and CRISPR/Cas9 mutagenesis to reveal gene function.


title: Histopathologic host response to polypropylene-based surgical mesh materials in a rat abdominal wall defect model.

text: Composite polypropylene-based surgical mesh materials including various synthetic polymers and naturally occurring biomaterials have been developed to ameliorate device-associated inflammatory response and associated reduced compliance of pure polypropylene meshes. This study evaluated the histomorphologic response of three composite polypropylene-based surgical meshes, Revive™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold, Assure™, a polycarbonate polyurethane reinforced monofilamentous polypropylene scaffold with a resorbable anti-adhesion layer of lactide caprolactone copolymer, and Proceed™, a polypropylene mesh modified with oxidized cellulose, in a soft tissue repair model in the rat. The host inflammatory response and neotissue formation were evaluated by semiquantitative histologic scoring including the amount of cellular infiltration, angiogenesis, presence of multinucleate giant cells, fibrous connective tissue formation, and host neo-extracellular matrix deposition for up to 26 weeks. All three composite surgical mesh materials showed good integration with host tissue as indicated by rapid cellular infiltration, abundant neo-vascularization, minimal shrinkage, and the lack of visible mesh degradation. The devices elicited a similar inflammatory response and the presence of a mild foreign body response in spite of the different composition and morphology of these composite mesh materials.


title: Robotic Sacrocolpopexy for Treatment of Apical Compartment Prolapse.

text: Abdominal sacrocolpopexy is the gold-standard treatment for apical compartment prolapse, as it is more effective and durable than the transvaginal approach. In the current era of minimally invasive surgery, laparoscopic sacrocolpopexy techniques have been described, but have not gained popularity due to their complexity and steep learning curves. To overcome this problem, robotic sacrocolpopexy was introduced, and has shown equivalent outcomes and safety compared to open and laparoscopic sacrocolpopexy based on findings that have been accumulated over 15 years.