Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost

Background:Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost.Materials and methods:Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum β-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics—oral ciprofloxacin and intravenous gentamicin.Results:Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711.Conclusions:We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.     

Anatomic and experimental basis for the insertion of a screw at the first sacral vertebra

Summary The authors present the anatomic and experimental basis of an original technique for screwing at the first sacral level employed in lumbosacral fusion. The anatomic studies were based on specimens from the anatomy museum, frozen sections of the sacrum and CT examinations with three-dimensional reconstruction and assessment of the density of the different structures of S1 in Hounsfield units (HU). The findings were that the ala and lateral portions of S1 contain yellow marrow forming what amounts to a fatty sphere bounded by the cortical bone of the sacroiliac joint, the linea terminalis and the spongy bone of the pedicles and of the body of S1. The experimental study was made by avulsion of sacral screws (system of Cotrel Dubousset), each of 7mm diameter. No screw perforated the sacral cortex. Three directions were tested. The insertion of a screw through the pedicle and body of S1 is advised, with the point of insertion below and lateral to the articular process of S1 and an oblique course forward and inward at an angle of 10° to the sagittal plane. This internal obliquity is limited by the posterior prominence of the iliac ala.

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Bases anatomiques et expérimentales de la mise en place d'une vis d'ostéosynthèse au niveau de la première vertèbre sacrée

Résumé Les auteurs présentent les bases anatomiques et expérimentales d'une technique originale de vissage en S1 employée pour les ostéosynthèses lombo-sacrées. Les études anatomiques portent sur des pièces du musée d'Anatomie, sur des coupes congelées de sacrum, des examens tomodensitométriques computérisés avec reconstruction en 3 dimensions et appréciation de la densité exprimée en unité Hounsfield (uH) des différentes structures de S1. Les constatations sont les suivantes : les ailerons et la partie latérale de S1 continennent de la moëlle jaune formant une véritable boule graisseuse limitée latéralement par l'os cortical de l'articulation sacro-iliaque, médialement par l'os spongieux des pédicules et du corps de S1, ventralement et dorsalement par les corticales de la partie latérale de S1. L'étude expérimentale est faite par arrachement de vis sacrées (matériel de Cotrel Dubousset), faisant chacune 7mm de diamètre. Aucune vis ne perfore la corticale sacrée. Trois directions sont testées. Nous conseillons la mise en place d'une vis pédiculo-corporéale en S 1 ; le point d'introduction est au-dessous et en dehors du processus articulaire de S 1, le trajet est oblique en avant et en dedans faisant 10° avec le plan sagittal. Cette obliquité interne est limitée par la saillie postérieure de l'aile iliaque.

     

Synthesis of new xanthenone derivatives of expected antibilharzial activity

Some new 9H-thioxanthen-9-one incorporated into heterocyclic systems such as pyridone8, pyrazoline9, pyranone11, iminopyrane12, furopyrimidine17, imidazothiazole19, thiazole21, triazine24 and other related compounds through a para imminophenyl grouping at position-1 of the thioxanthenone ring were synthesized and tested as antitumor agents, against L 1210 leukemia in mice. Some of the new compounds showed considerable antitumor activity.     

Synthesis of 1-(heterocyclic substituted anilino)-9H-thioxanthon-9-ones and their antitumor activity

Some new 9H-thioxanthen-9-one incorporated into heterocyclic systems such as pyridone8, pyrazoline9, pyranone11, iminopyrane12, furopyrimidine17, imidazothiazole19, thiazole21, triazine24 and other related compounds through a para imminophenyl grouping at position-1 of the thioxanthenone ring were synthesized and tested as antitumor agents, against L 1210 leukemia in mice. Some of the new compounds showed considerable antitumor activity.     

Adrenergic,purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125–1.0 × 10^–8 M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous -adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly ₂-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.NIH grant number supporting these studies: USPHS # DK37050.     

Analysing repeated measurements data: a practical comparison of methods.

A variety of methods are available for analysing repeated measurements data where the outcome is continuous. However, there is little information on how established methods, such as summary statistics and repeated measures analysis of variance (RMAOV), compare in practice with methods that have become available to applied statisticians more recently, such as marginal models (based on generalized estimating equation methodology) and multilevel models (that is, hierarchical random effects models). The aim of this paper is to exemplify the use of these methods, and directly compare their results by application to a clinical trial data set. The focus is on practical aspects rather than technical issues. The data considered were taken from a clinical trial of treatments for asthma in 240 children, in which a baseline and four post-randomization measurements of outcomes were taken. The simplicity of the method of summary statistics using the post-randomization mean of observations provided a useful initial analysis. However, fixed time effects or treatment-time interactions cannot be included in such an analysis, and choice of appropriate weighting when there is substantial missing data is problematic. RMAOV, marginal models and multilevel models generally provided similar estimates and standard errors for the treatment effects, although in one example with a relatively complex variance structure the marginal model produced less efficient estimates. Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right, and that they can be naturally extended to handle multivariate outcomes.     

The role of hyperthermia in regional alkylating agent chemotherapy.

The role of hyperthermia during regional alkylating agent chemotherapy is controversial. The aim of this study was to determine the exact contribution of hyperthermia to tumor response during isolated limb infusion with l-phenylalanine mustard. Rats bearing rodent fibrosarcoma on the hindlimb underwent isolated limb infusion with saline, saline plus heat, l-phenylalanine mustard, l-phenylalanine mustard under conditions of normothermia, or l-phenylalanine mustard plus hyperthermia. Heat was administered locally using an in-line hot water circulation loop. Treatment with l-phenylalanine mustard at a concentration of 15 or 50 micrograms/mL was ineffective at producing tumor growth delay (P = 0.24 and 0.41, respectively). Furthermore, thermal enhancement of l-phenylalanine mustard activity was not seen at 15 micrograms/mL. However, administration of high-dose l-phenylalanine mustard, 50 micrograms/mL, with increasing amounts of heat yielded increasing tumor growth delay, increased regressions, and decreased proliferative index. Although l-phenylalanine mustard infusion under normothermia yielded a tumor growth delay of 7.1 days, combination l-phenylalanine mustard + hyperthermia treatment produced tumor growth delay of 27.0 days (P < 0.01; with two of five animals showing a complete response). Four hours after isolated limb infusion, 50.9% of cells in tumor treated with l-phenylalanine mustard + hyperthermia experienced apoptosis, whereas only 18.1, 16, and 4.4% of cells underwent apoptosis after treatment with l-phenylalanine mustard, saline + hyperthermia, or saline. The mean concentration of l-phenylalanine mustard within tumor relative to perfusate following isolated limb infusion was found to be similar among all groups at 0.023, 0.025, and 0.032 in animals undergoing isolated limb infusion with l-phenylalanine mustard, l-phenylalanine mustard + normothermia, and l-phenylalanine mustard + hyperthermia, respectively. These data indicate a synergistic cytotoxic effect of l-phenylalanine mustard + hyperthermia in isolated limb infusion, which is not attributable to enhanced tumor drug uptake.