Miracle-dz/UniFAR-FTUs huggingface dataset:
Drugs to Minimize Perioperative Blood Loss in Cardiac Surgery: Meta-Analyses Using Perioperative Blood Transfusion As the Outcome

Concern about the side effects of allogeneic red blood cell transfusion has increased interest in methods of minimizing perioperative transfusion.We performed meta-analyses of randomized trials evaluating the efficacy and safety of aprotinin, desmopressin, tranexamic acid, and epsilon-aminocaproic acid in cardiac surgery. All identified randomized trials in cardiac surgery were included in the meta-analyses. The primary outcome was the proportion of patients who received at least one perioperative allogeneic red cell transfusion. Sixty studies were included in the meta-analyses. The largest number of patients (5808) was available for the meta-analysis of aprotinin, which significantly decreased exposure to allogeneic blood (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.25-0.39; P < 0.0001). The efficacy of aprotinin was not significantly different regardless of the type of surgery (primary or reoperation), aspirin use, or reported transfusion threshold. The use of aprotinin was associated with a significant decrease in the need for reoperation because of bleeding (OR 0.44, 95% CI 0.27-0.73; P = 0.001). Desmopressin was not effective, with an OR of 0.98 (95% CI 0.64-1.50; P = 0.92). Tranexamic acid significantly decreased the proportion of patients transfused (OR 0.50, 95% CI 0.34-0.76; P = 0.0009). epsilon-Aminocaproic acid did not have a statistically significant effect on the proportion of patients transfused (OR 0.20, 95% CI 0.04-1.12; P = 0.07). There were not enough patients to exclude a small but clinically important increase in myocardial infarction or other side effects for any of the medications. We conclude that aprotinin and tranexamic acid, but not desmopressin, decrease the number of patients exposed to perioperative allogeneic transfusions in association with cardiac surgery. Implications: Aprotinin, desmopressin, tranexamic acid, and epsilon-aminocaproic acid are used in cardiac surgery in an attempt to decrease the proportion of patients requiring blood transfusion. This meta-analysis of all published randomized trials provides a good estimate of the efficacy of these medications and is useful in guiding clinical practice. We conclude that aprotinin and tranexamic acid, but not desmopressin, decrease the exposure of patients to allogeneic blood transfusion perioperatively in relationship to cardiac surgery. (Anesth Analg 1997;85:1258-67)
Laryngeal abductor muscle reinnervation in a pig model

Objective To develop a large animal model for studies of laryngeal abductor reinnervation. Material and methods Six minipigs underwent unilateral anastomosis of the phrenic nerve–abductor branch of the recurrent laryngeal nerve (RLN). Polyhydroxybutyrate (PHB) conduits were used for repair. At each of 30, 60 and 120 days, 2 animals underwent video laryngeal endoscopy (VLE) and were then killed. VLE was also performed in the 120-day pair at 60 days. Nerve–conduit–nerve–muscle samples were fixed for light and immunofluorescence (pan-neurofilaments, S-100) microscopy. Laryngeal muscles were harvested (myosin heavy chain analysis). Results VLE showed recovery of abductor function in 1 animal at 60 days and in 1 at 120 days. Haematoxylin–eosin staining demonstrated a complex inflammatory response. Eosinophil recruitment was observed. Stepwise regeneration and reorganization of the distal nerve between 30 and 120 days was observed with pan-NF staining. The mean minimum diameter in the reinnervated posterior crico-arytenoids tended to increase for up to 120 days. Conclusions Anastomosis of the phrenic nerve–abductor branch of the RLN with a PHB conduit in a pig can result in functional and histological recovery within 2–4 months and appears to at least sustain abductor muscle fibre morphology. Recovery occurs despite a complex inflammatory response, which may be an essential part of healing rather than inhibitory.
Combined Experimental/Simulation Studies of Cellular and Network Mechanisms of Epileptogenesis In Vitro and In Vivo

The electrical correlates of clinical seizures, and of experimental models of seizures, are recognized because neurons behave differently than normal. Individual neurons do unusual things, and neuronal activities become correlated with each other in ways that are not observed under physiologic conditions. Single neurons may fire bursts of action potentials superimposed on large depolarizations, and the bursts may recur rhythmically over a wide range of frequencies (<1 Hz to 25 Hz); periods of noisy subthreshold activity can occur; and firing can even be suppressed in some neurons. At the population level, nearby neurons tend to fire action potentials, or generate bursts, that are temporally locked together on a few-milliseconds time scale, so that large voltage transients are generated in extracellular fields. Very fast oscillations (>80 Hz) in neuronal aggregates may occur before, during, or after such large field potentials. Finally, cellular activities may even be correlated across large brain regions. The authors review some of the means by which cellular intrinsic properties, synaptic interactions, and electrical coupling via gap junctions, all contribute to the anomalous population activities characteristic of seizures. Also reviewed are some of the data suggesting that the requisite gap junctions are located on the axons of glutamatergic neurons.
Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation

The hepatopulmonary syndrome (HPS) occurs in a subgroup of patients with cirrhosis and results from intrapulmonary vasodilatation, which may cause significant hypoxemia. Liver transplantation has emerged as a therapeutic option for patients with HPS based on retrospective case series and reports. However, morbidity and mortality appear to be increased after transplantation for HPS, and no prospective studies evaluating clinical features that may predict poor surgical outcome are available. Therefore, we prospectively evaluated the utility of the degree of hypoxemia, the arterial oxygen response to 100% oxygen administration, and the macroaggregated albumin (MAA) scan quantification of intrapulmonary shunting as predictors for outcome after liver transplantation. Our cohort consisted of 24 patients with cirrhosis and HPS who underwent liver transplantation over a 5‐year period at 2 transplant centers who were followed at least 1 year after transplantation. All patients underwent preoperative evaluation for HPS with standardized methods. Seven patients (29%) died postoperatively, 5 of cardiorespiratory complications. All deaths occurred within 10 weeks after transplantation. A preoperative arterial oxygen tension (PaO2) of ≤ 50 mm Hg alone or in combination with a MAA shunt fraction ≥ 20% were the strongest predictors of postoperative mortality. In conclusion, we found that mortality is increased after liver transplantation for HPS, particularly in patients with more severe hypoxemia and significant intrapulmonary shunting. Preoperative testing for the severity of HPS can be used to stratify patients according to the risk for postoperative mortality.
Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice

Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)–like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)–fed mice. Glucoraphanin supplementation attenuated weight gain, decreased hepatic steatosis, and improved glucose tolerance and insulin sensitivity in HFD-fed wild-type mice but not in HFD-fed Nrf2 knockout mice. Compared with vehicle-treated controls, glucoraphanin-treated HFD-fed mice had lower plasma lipopolysaccharide levels and decreased relative abundance of the gram-negative bacteria family Desulfovibrionaceae in their gut microbiomes. In HFD-fed mice, glucoraphanin increased energy expenditure and the protein expression of uncoupling protein 1 (Ucp1) in inguinal and epididymal adipose depots. Additionally, in this group, glucoraphanin attenuated hepatic lipogenic gene expression, lipid peroxidation, classically activated M1-like macrophage accumulation, and inflammatory signaling pathways. By promoting fat browning, limiting metabolic endotoxemia-related chronic inflammation, and modulating redox stress, glucoraphanin may mitigate obesity, insulin resistance, and NAFLD.
A UspA2H-Negative Variant of Moraxella catarrhalis Strain O46E Has a Deletion in a Homopolymeric Nucleotide Repeat Common to uspA2H Genes

ABSTRACT Moraxella catarrhalis strains can express either a UspA2 protein or a UspA2H protein. The latter protein is encoded by a gene that possesses a homopolymeric nucleotide tract containing eight adenine (A) residues [i.e., a poly(A) tract] which is located near the 5′ end. A spontaneous UspA2H-negative variant of M. catarrhalis strain O46E, designated O46E.U2V, was found to have a uspA2H poly(A) tract that contained seven A residues. Northern blot analysis of total RNA from the O46E parent strain revealed a readily detectable uspA2H mRNA transcript, whereas little or no uspA2H transcript was detectable in total RNA from the UspA2H-negative variant O46E.U2V. The 5′ end of the uspA2H genes from both the O46E parent strain and the O46E.U2V variant were ligated to a promoterless lacZ gene to prepare translational fusions for use as reporter constructs. The level of β-galactosidase activity expressed by the fusion construct containing eight A residues in its poly(A) tract was 200-fold greater than that obtained with the construct that had seven A residues. Site-directed mutagenesis of the 5′ end of the uspA2H gene confirmed that translation was initiated at a GTG codon located 21 nucleotides (nt) upstream of the poly(A) tract. Primer extension analysis determined that the transcriptional start site of the uspA2H gene was located 291 nt upstream from the GTG translational start codon. This poly(A) tract was also found to be present in the uspA2H genes of other M. catarrhalis strains.
Quality of Local Excision for Rectal Neoplasms Using Transanal Endoscopic Microsurgery Versus Transanal Minimally Invasive Surgery: A Multi-institutional Matched Analysis

BACKGROUND: There are no data comparing the quality of local excision of rectal neoplasms using transanal endoscopic microsurgery and transanal minimally invasive surgery. OBJECTIVE: The purpose of this study was to compare the incidence of tumor fragmentation and positive margins for patients undergoing local excision of benign and malignant rectal neoplasms using transanal endoscopic microsurgery versus transanal minimally invasive surgery. DESIGN: This was a multi-institutional cohort study using coarsened exact matching. SETTINGS: The study was conducted at high-volume tertiary institutions with specialist colorectal surgeons. PATIENTS: Patients undergoing full-thickness local excision for benign and malignant rectal neoplasms were included. INTERVENTIONS: Transanal endoscopic microsurgery and transanal minimally invasive surgery were the included interventions. MAIN OUTCOME MEASURES: The incidence of poor quality excision (composite measure including tumor fragmentation and/or positive resection margin) was measured. RESULTS: The matched cohort consisted of 428 patients (247 with transanal endoscopic microsurgery and 181 with transanal minimally invasive surgery). Transanal minimally invasive surgery was associated with shorter operative time and length of stay. Poor quality excision was similar (8% vs 11%; p = 0.233). There were also no differences in peritoneal violation (3% vs 3%; p = 0.965) and postoperative complications (11% vs 9%; p = 0.477). Cumulative 5-year disease-free survival for patients undergoing transanal endoscopic microsurgery was 80% compared with 78% for patients undergoing transanal minimally invasive surgery (log rank p = 0.824). The incidence of local recurrence for patients with malignancy who did not undergo immediate salvage surgery was 7% (8/117) for transanal endoscopic microsurgery and 7% (7/94) for transanal minimally invasive surgery (p = 0.864). LIMITATIONS: All of the procedures were also performed at high-volume referral centers by specialist colorectal surgeons with slightly differing perioperative practices and different time periods. CONCLUSIONS: High-quality local excision for benign and rectal neoplasms can be equally achieved using transanal endoscopic microsurgery or transanal minimally invasive surgery. The choice of operating platform for local excisions of rectal neoplasms should be based on surgeon preference, availability, and cost. See Video Abstract at http://links.lww. com/DCR/A382.
Reference values for fetal penile length and width from 22 to 36 gestational weeks

Current reference range values for fetal penile growth are based on length measurements. However, methodologies for measuring penile length differ among studies and from the standard technique used in children. We propose that the measurement of penile width may aid in its evaluation. The aim of the study was to create normograms for penile length and width.
Postural control in patients with liver cirrhosis: a posturographic study

Background Ataxia has been suggested in the literature to be a symptom of hepatic encephalopathy (HE), but so far has not been objectively quantified. In this study, we wanted to objectively quantify ataxia in patients with liver cirrhosis. Methods One hundred and seven patients with liver cirrhosis were tested for postural control using posturography and compared with 25 controls. For quantification of HE, we used the number connection tests A and B, ammonia levels (NH3), and the partial pressure of ammonia in the arterial blood (pNH3). Results Patients showed an impaired postural control compared with controls. Patients with Child C cirrhosis had lower scores in the posturography than those with Child A or B cirrhosis. Patients with alcohol-induced (AIC) Child B cirrhosis achieved lower scores in the posturography than those with non-alcohol-induced (NAIC) Child B cirrhosis. Patients with AIC Child C had lower scores than the corresponding NAIC patients, although this did not reach statistical significance. In the NAIC group Child C patients, in the AIC group Child B and C patients had lower scores than the controls. Patients with abnormal results in the number connection tests, as well as those with high NH3 and pNH3 levels showed worse postural control than those with normal results. Conclusion Patients with cirrhosis have an impaired postural control compared with controls and this impairment deteriorates with progression of liver disease. HE as well as past alcohol abuse contribute to the pathogenesis of ataxia in liver cirrhosis and past alcohol abuse leads to an earlier and more pronounced manifestation of ataxia in the affected patients.
Should the skin cancer examination be taught in medical school?

BACKGROUND The fact that thin melanomas are associated with a greater than 95% survival rate, while later, more deeply invasive melanomas have a 5-year survival rate of less than 10%, demonstrates the potential personal and public health impact of early detection. The majority of patients with skin lesions are seen by nondermatologists who infrequently counsel patients about skin cancer prevention or perform a complete skin examination as part of routine care. We documented the antecedents of physician practice by evaluating medical students' observation, training, performance, and self-reported skill level for the skin cancer examination and sun protection counseling. METHODS Surveys were administered and completed in classrooms and student workshops in each of the 4 medical school years during the spring of 1996 and 1997. We concentrate our analysis on the graduating fourth-year students. RESULTS Of the 302 fourth-year students enrolled at Boston University School of Medicine, Boston, Mass, in 1996 and 1997, 223 (74%) completed surveys. Among fourth-year students, 52% rated themselves as unskilled in skin cancer examinations. Twenty-eight percent of fourth-year students had never observed a skin cancer examination, 40% had received no training, and 35% had never practiced the examination. However, fourth-year students reporting at least 1 opportunity to observe, train, or practice an examination were 3 times as likely to report themselves as moderately to very skilled as students without such opportunities. CONCLUSION If medical student training rates for the skin cancer examination are equally low elsewhere, as is likely, the present data suggest that even brief additions to the current curriculum, integrated into systems teaching, would augment student exposure and likely boost student skill levels.
Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells1

After interaction with its receptor, GM-CSF induces phosphorylation of the β-chain in two distinct domains in macrophages. One induces activation of mitogen-activated protein kinases and the PI3K/Akt pathway, and the other induces JAK2-STAT5. In this study we describe how trichostatin A (TSA), which inhibits deacetylase activity, blocks JAK2-STAT5-dependent gene expression but not the expression of genes that depend on the signal transduction induced by the other domain of the receptor. TSA treatment inhibited the GM-CSF-dependent proliferation of macrophages by interfering with c-myc and cyclin D1 expression. However, M-CSF-dependent proliferation, which requires ERK1/2, was unaffected. Protection from apoptosis, which involves Akt phosphorylation and p21waf-1 expression, was not modified by TSA. GM-CSF-dependent expression of MHC class II molecules was inhibited because CIITA was not induced. The generation of dendritic cells was also impaired by TSA treatment because of the inhibition of IRF4, IRF2, and RelB expression. TSA mediates its effects by preventing the recruitment of RNA polymerase II to the promoter of STAT5 target genes and by inhibiting their expression. However, this drug did not affect STAT5A or STAT5B phosphorylation or DNA binding. These results in GM-CSF-treated macrophages reveal a relationship between histone deacetylase complexes and STAT5 in the regulation of gene expression.
Renal Cell Apoptosis and New Treatment Options in Sepsis-Induced Acute Kidney Injury

Sepsis is a common and important cause of mortality in critically ill patients. Acute kidney injury (AKI) is one of the most important factors determining morbidity and mortality in the prognosis of sepsis. Recent studies have indicated that the pathogenetic mechanism in septic AKI is totally different from that in non-septic AKI. Our understanding of sepsis-associated AKI pathophysiology is shifting from renal vasoconstriction, ischemia, and acute tubular necrosis to heterogeneous vasodilation, hyperemia, and acute tubular apoptosis. Especially, apoptosis is gradually gaining importance in the understanding of the development of renal injury. The frequency of renal tubular apoptosis on biopsies of septic patients has been pointed out in recently published studies. Apoptosis can be triggered by ischemia, exogen toxins, or endogen mediators. It has been shown in some animal models that hyperglycemia, which is common in critically ill patients, causes apoptosis in renal tubular cells. New treatment options have emerged in the light of recent findings. Ghrelin that inhibits pro-inflammatory cytokines, caspase inhibitors that block the apoptotic pathway, and suppression of anti-inflammatory reactions are under study. Among the existing methods of treatment, usage of arginine, which is a vasopressor agent, ventilation with a low tidal volume, and hemofiltration methods cleaning toxic mediators from the circulation should be considered in the first place. Hyperglycemia treatment is of major importance, since, besides its anti-inflammatory effect, it has a protective role on the kidney. Regarding pathogenesis, rates of morbidity and mortality are aimed to be reduced through the new agents of therapy that have been studied on.
Vessel sealing versus suture ligation for canine ovarian pedicle haemostasis: a randomised clinical trial

Vessel sealing (VS) is well established in laparoscopic ovariectomy (OVE) in dogs. The objectives of this study were to evaluate the efficacy of ovarian pedicle haemostasis by VS using a commercially available VS tool in open OVE and compare it with suture ligation (SL). A prospective, randomised clinical trial including 20 female dogs was designed. Open OVE was performed via a standard mid-line celiotomy by a single surgeon using a standardised protocol. At random, the right ovarian pedicle was sealed (VS) or ligated (SL) whereas the left pedicle was treated by the alternative technique. Surgical times for procedural stages and intra-operative complications were recorded and statistically evaluated. Total surgical time was 29.28±11.13 minutes (range 12.50–62.13 minutes) and time from identification to removal of the ovary was significantly less when sealing (VS 2.22±0.58 minutes) than when ligating (SL 4.10±1.13 minutes P=0.0001). Intra-operative complications were rare for both techniques (failure of the electrode of the VS device (n=3); ovarian pedicle haemorrhage due to ligature slippage (n=1)). The results of the current study indicate that ovarian pedicle haemostasis achieved by VS is significantly faster than by placement of ligatures without appearing to compromise safety.