Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Burkholderia pseudomallei Isolates in 2 Pet Iguanas,California, USA

Burkholderia pseudomallei, the causative agent of melioidosis, was isolated from abscesses of 2 pet green iguanas in California, USA. The international trade in iguanas may contribute to importation of this pathogen into countries where it is not endemic and put persons exposed to these animals at risk for infection.Key words: Burkholderia pseudomallei, iguana, zoonoses, abscess, melioidosis, bacteriaBurkholderia pseudomallei, a gram-negative bacterium, is the causative agent of melioidosis. Melioidosis is endemic in countries in Southeast Asia and in northern Australia, and has been sporadically reported from Central and South America (1). In the United States, most case-patients have traveled to disease-endemic areas (2).B. pseudomallei infection occurs through direct cutaneous inoculation with soil or water containing B. pseudomallei and through ingestion or inhalation of aerosolized bacteria. In humans, the incubation period is typically 1–21 days, but some patients demonstrate clinical signs years after exposure (1). Acute melioidosis can manifest as a severe pneumonia and septicemia, with death rates >40% in countries where access to medical care is limited. In chronic melioidosis, abscesses occur in various organs, including the lungs, liver, spleen, and cutaneous sites (1,3). In animals, abscesses and acute illness are common (4).B. pseudomallei is classified by US federal agencies as a tier 1 select agent. Tier 1 agents are believed to pose the greatest threat for deliberate misuse and potential harm to public health. Multiple regulations restrict access to these agents and reduce the risk of their release from secure settings (5). Infection is generally diagnosed by culture. Commercially available bacterial identification systems may provide initial identification; however, B. pseudomallei may be misidentified by some systems (6). Other identification tests are available, including PCR and antigen detection; these are not commonly used outside disease-endemic regions (3,7,8).     

Reverse LISS plating for intertrochanteric Hip Fractures in elderly patients

Background  

Fractures of the intertrochanteric hip are common and the treatment of unstable fractures generally requires an operative approach. In elderly patients, osteoporosis makes internal fixation problematic and frequently contributes to failed fixation and poor clinical results. We have attempted to apply the Less Invasive Stabilization System (LISS) in reverse position for the repair of intertrochanteric hip fractures in elderly patients with osteoporotic bones. A retrospective review is presented of the cases of 28 elderly patients with stable and unstable fractures of the intertrochanteric hip treated using the reverse LISS.     

Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism

Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Prediatr 1994;83:618–22. Stockholm. ISSN 0803–5253
The aim of this investigation was to study if bone age development (assessed by the Greulich & Pyle atlas) was related to L-thyroxine treatment in 47 children with congenital hypothyroidism, treated early and according to general recommendations. In spite of frequent delay in skeletal maturation at diagnosis, the delay in mean bone age at a mean chronological age of 1.5 years was slight (0.5 months), and 30% of the variation in bone age SD score (SDS) at 1.5 years was accounted for by the dose of L-thyroxine and serum thyroxine during the first year. The children with a bone age within ± 1 SDS had a prescribed mean dose of L-thyroxine per kg body weight from 3 to 12 months of age of 5.4 ± 1.7 pg/kg/day, and their mean serum thyroxine concentration during the first year was 175 ± 29 nmol/l. We conclude that bone age at 1.5 years of age was positively correlated with the dose of L-thyroxine and the serum thyroxine concentration during the first year. This supports the general use of bone age assessments as a complement to other treatment variables in the follow-up of children with congenital hypothyroidism.     

Perspectives on factor Xa inhibition

Blood coagulation involves a complex cascade of enzymatic reactions, ultimately generating fibrin, the basis of all blood clots. This cascade is comprised of two arms, the intrinsic and extrinsic pathways which converge at factor Xa to form the common pathway. Factor Xa activates prothrombin to thrombin, which in turn catalyzes the conversion of fibrinogen to fibrin. Recently, both natural and synthetic factor Xa inhibitors have shown promising pharmacological effects in animal models of thrombosis. Accordingly, factor Xa has emerged as a compelling target for pharmacological intervention and much recent effort has focused on selective and potent inhibition of this key enzyme. Factor Xa and other enzymes in the coagulation cascade belong to the trypsin-like serine protease family, the various members of which are involved in numerous physiological functions in the body. Hence, to avoid toxicity and adverse side effects, it is important to selectively inhibit the target enzyme. Achieving the needed selectivity has proved challenging due to the high degree of structural homology around the active site of this class of enzymes. This article provides a brief review of the strategies currently being employed to develop oral anticoagulants and, more specifically, the structural features of protein-ligand binding that have been utilized to achieve potency and selectivity toward factor Xa. Additionally, selected lead molecules will be discussed to highlight binding motifs used to attain both potency and selectivity in drug candidates.     

Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and Oseltamivir by suppressing the expression of Carboxylesterases HCE1 and HCE2

Carboxylesterases constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics, patients with liver conditions such as cirrhosis show increased secretion of proinflammatory cytokines [e. g., interleukin-6 （IL- 6）] and decreased capacity of hydrolysis. In this sfudy, we provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation. In both primary hepatocytes and HepG2 cells, treatment with IL-6 decreased the expression of human carboxylesterases HCE1 and HCE2 by as much as 60%. The decreased expression occurred at both mRNA and protein levels, and it was confirmed .by enzymatic assay. In cotransfection experiments, both HCE1 and HCE2 promoters were significantly repressed, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting that transrepression is responsible for the suppressed expression. In addition, pretreatment with IL-6 altered the cellular responsiveness in an opposite manner of overexpression of HCE1 and HCE2 toward various ester therapeutic agents （ e. g., clopidogrel）. Transfection of HCE1, for example, decreased the cytotoxicity induced by antithrombogenic agent clopidogrel, whereas pretreatment with IL-6 increased the cytotoxicity. Such a reversal was observed with other ester drugs, including anticancer agent irinotecan and anti-influenza agent oseltamivir. The altered cellular responsiveness was observed when drugs were assayed at sub-and low-micromolar concentrations, suggesting that suppressed expression of carboxylesterases by IL-6 has profound pharmacological consequences, particularly with those that are hvdrolvzed in an isoform-specific manner.     

Reciprocal regulation of endothelial substrate adhesion and barrier function.

OBJECTIVE: To examine how cell-substrate adhesion is regulated during barrier changes produced by exposure to inflammatory mediators. METHODS: Lung microvascular endothelial monolayers were treated with test agents +/- blockers, and barrier was measured by transendothelial resistance; cell-substrate adhesion was assessed by surface area conservation after trypsin treatment of monolayers. Protein phosphorylation and distribution were assayed by immunoblotting and fluorescent microscopy, respectively. RESULTS: H2O2, histamine, bradykinin, and thrombin, decreased endothelial barrier function, and enhanced adhesion to the substratum. H2O2 enhanced cell adhesion to the substrate in a concentration (0-1 mM)- and time (0-60 minutes)-dependent fashion. This effect of H2O2 reversed within 120 minutes of removal of H2O2 and was blocked by the mean arterial pressure (MAP) kinase inhibitor, PD98059 and by chelating cytoplasmic Ca2+ but not PKC or PKG inhibition. H2O2 also stimulated tyrosine phosphorylation of several proteins and increased the association of the focal adhesive proteins paxillin, talin, and vinculin with the cytoskeleton and may promote localization of these proteins to junctions. CONCLUSIONS: Our data indicate that inflammatory mediators reduce cell-cell contact, contributing to reduced solute barrier and simultaneously enhanced substrate binding, which may be reciprocal events in barrier regulation in vitro and in vivo.     

7-溴乙氧苯四氢巴马汀对离体豚鼠工作心脏的作用

用Tris-丙酮酸钠液灌流离体豚鼠工作心脏,记录左室压的导管从左房灌流管插入,可使心脏有效工作时间达70min。用Tris-丙酮酸钠液加0.5%的氟碳液能使有效工作时间延长至90min。7-溴乙氧苯四氢巴马汀(7-bromoethyoxybenzene tetrahydropalmatine,EBP)及哌唑嗪0.1μmol/L对工作心脏各项指标均无显著影响。甲氧胺1μmol/L,多巴胺1μmol/L对LVP,ABF,T-CO等指标均有明显的药理作用。EBP 10μmol/L能对抗甲氧胺、多巴胺对上述指标的影响。