Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.     

Effect of wrist position on distal radioulnar joint stability: A biomechanical study

We investigated distal radioulnar joint (DRUJ) stability in different wrist positions and examined the relative contribution of each ligamentous component of the triangular fibrocartilage complex (TFCC) to DRUJ stability. We used nine fresh‐frozen cadavers. The humerus and ulna were fixed at 90° elbow flexion. The radiocarpal unit was translated relative to the ulna in dorsopalmar directions with the wrist in five positions. Displacement of the unit was measured by an electromagnetic tracking device. Magnitudes of displacement were compared between different wrist positions in various sectioning stages: ulnocarpal ligament (UCL) sectioning, radioulnar ligaments (RUL) sectioning, and extensor carpi ulnaris (ECU) floor sectioning. Wrist position and sectioning stage significantly influenced the displacement. In intact wrists, the displacement in wrist extension was significantly lower than that in neutral. However, after UCL sectioning, there were no longer any significant differences. After RUL sectioning, the displacement in radial deviation was significantly lower than that in neutral. Following ECU floor sectioning, there were no longer any significant differences. Thus, in intact wrists, DRUJ stability in wrist extension is likely due to tightening of the UCL. After complete RUL sectioning, DRUJ is stabilized in radial deviation due to tightening of the ECU floor. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1247–1251, 2014.     

New-onset psychiatric disorders after corticosteroid therapy in systemic lupus erythematosus: an observational case-series study

The objective of this study was to clarify the incidence, clinical characteristics, and courses of new-onset psychiatric manifestations after corticosteroid therapy in patients with systemic lupus erythematosus (SLE), including possible ways of differentiating between corticosteroid-induced psychiatric disorders (CIPDs) and central nervous system manifestations of SLE (CNS-SLE). We prospectively followed for 8 weeks 139 consecutive episodes in 135 in-patients who had a non–CNS-SLE flare treated with corticosteroids. Psychiatric events were evaluated once a week using DSM-IV criteria. We then conducted a post hoc etiological analysis of any newly developed psychiatric events during this follow-up period. In the 8 weeks of corticosteroid administration, new psychiatric events occurred in 20 (14.4 %) of the 139 episodes. The mean dosage of corticosteroids administered was prednisolone at 0.98 (range 0.24–1.39) mg/kg/day. Of the 20 psychiatric events, 14 (10.1 %) were suitable for the strict definition of CIPDs, accompanied by mood disorders in 13 (depressive in 2, manic in 9, and mixed in 2) and psychotic disorder in one. Two (1.4 %), both presenting delirium, were diagnosed as CNS-SLE on the basis of evidence of abnormal CNS findings even before psychiatric manifestations, all of which improved in parallel with these patients’ recoveries through augmentation of immunosuppressive therapy. The other four events (2.9 %) could not be etiologically identified. This study suggests that corticosteroid therapy triggers CIPDs and CNS-SLE in patients with SLE. Delirium may be suggestive of CNS-SLE, while mood disorders may be more suggestive of CIPDs. Electroencephalographic abnormalities may possibly be predictive of CNS-SLE.     

Glucokinase activation or inactivation: Which will lead to the treatment of type 2 diabetes?

Glucokinase, which phosphorylates glucose to form glucose-6-phosphate, plays a critical role in regulating blood glucose levels. On the basis of data of glucokinase-knockout and transgenic mice and humans with glucokinase mutations, glucokinase was targeted for drug development aiming to augment its activity, and thereby reduce hyperglycaemia in patients with diabetes. In fact, various small molecule compounds have been developed and clinically tested as glucokinase activators. However, some have been discontinued because of efficacy and safety issues. One of these issues is loss of the drug's efficacy over time. This unsustained glycaemic efficacy may be associated with the excess glycolysis by glucokinase activation in pancreatic beta cells, resulting in beta-cell failure. Recently, we have shown that glucokinase haploinsufficiency ameliorated glucose intolerance by increasing beta-cell function and mass in a mouse model of diabetes. Given that a similar phenotype has been observed in glucokinase-activated beta cells and diabetic beta cells, glucokinase inactivation may be a new therapeutic target for type 2 diabetes.     

Predictive value of preoperative echocardiographic assessment for postoperative atrial fibrillation after esophagectomy for esophageal cancer

Esophagus - Postoperative atrial fibrillation (POAF) after esophagectomy for esophageal cancer is not uncommon. The aim of this study is to examine whether preoperative transthoracic...     

Risk factors for adrenal crisis in patients with adrenal insufficiency

Patients with adrenal insufficiency have a life-threatening risk of adrenal crisis, thus preventing adrenal crisis is an important clinical issue. In order to clarify the risk factors for adrenal crisis, the medical records of 137 patients with established adrenal insufficiency were retrospectively investigated. The explanatory variables analyzed were gender, etiology of hypoadrenalism, class of adrenocortical hormone replaced, duration of steroid replacement, age at time of survey, age at time of diagnosis of hypoadrenalism, state of other hormone deficiencies (growth hormone and sex steroids), diabetes insipidus, and mental disorder. Diagnosis of adrenal crisis was based on physical and laboratory findings. Forty (29%) of the 137 patients had at least one episode of adrenal crisis. Based on the Akaike Information Criterion (AIC), steroid replacement therapy of more than 4 yrs' duration was the largest single contributor to the occurrence of an adrenal crisis, followed by mental disorder and sex steroid deficiency. In the subclass of patients with secondary adrenal insufficiency (N = 115), sex steroid deficiency was the greatest risk factor. Patients with untreated hypogonadism had a significantly higher relative risk of 3.70 (95% confidential interval: 1.71-7.98) compared to those without hypogonadism or with treated hypogonadism. Furthermore, among patients with hypogonadism aged younger than 50 yrs, those treated with sex hormone (5/51: 10%) suffered less frequently from adrenal crisis than those untreated (7/11: 64%, p = 0.0004). In conclusion, the present study has, for the first time, clarified the risk factors of adrenal crisis. Among them, sex hormone deficiency has an especially important implication because it can be treated by hormone replacement therapy with the hope of reducing the risk of adrenal crisis.     

Electrophysiological effects of flecainide acetate on stretched guinea pig left atrial muscle fibers

Summary The electrophysiological effects of flecainide acetate (3×10^–6 M) on stretched atrial tissue were investigated using guinea-pig left atrial muscle fibers. Before stretching, the resting membrane potential was not affected by flecainide at 1 Hz, although the overshoot potential (Eov) and the action potential duration at 50% repolarization (APD₅₀) were slightly but significantly decreased by 2±1 mV and 2±1 msec, respectively. The effective refractory period (ERP) was increased by 3±1 msec. The reduction of max was 20.6±1.2%. The half-maximum potential (Vh) of the relationship between max and the resting potential was shifted to become more negative by flecainide (from –60.6±2.1 mV to –63.2±1.7 mV). After 90–120 min of washout with drug-free Tyrode's solution, the tissue was mechanically stretched to 150% of its slack length. Stretching significantly decreased the max by 16.9±3.1%, along with a slight but significant increase in ERP (3±1 msec) and shifted Vh to become more negative (from –60.6±2.1 to –63.1±1.8 mV). In the presence of flecainide, max further decreased by 20.2±2.6%, and Vh shifted from –63.1±1.8 to –65.0±1.5 mV. Comparison with the control unstretched fibers showed that flecainide significantly decreased max by 34.0±2.7%, reduced the resting membrane potential by 3±1 mV, decreased Eov by 4±1 mV, and shifted Vh from –60.6±2.1 to –65.0±1.5 mV, while the APD₅₀ and ERP did not change. In conclusion, the reduction of max in the presence of flecainide was much greater in the stretched atrial muscle fibers than in the unstretched fibers, because the max-resting potential relationship was shifted towards more negative potentials by both flecainide and stretching. These results suggest that flecainide exerts a stronger antiarrhythmic action on stretched atrial muscle fibers than on normal fibers.     

Hepatic steatosis rather than visceral adiposity is more closely associated with insulin resistance in the early stage of obesity

The aim of the present study was to investigate the specific relationship between hepatic steatosis and insulin resistance in the early stage of obesity. Among general health examinees who received an ultrasound scanning, 131 subjects without fatty liver (non-FL group) and 142 subjects with fatty liver (FL group) were selected so that both groups were matched for age, sex, body mass index, and % body fat. The FL group was then subdivided into 2 groups according to the severity of steatosis by ultrasound. Insulin resistance was assessed by homeostasis model assessment for insulin resistance, serum high-molecular-weight (HMW) adiponectin, and insulin-like growth factor binding protein 1 concentrations. Unexpectedly, the non-FL group showed higher waist circumference than the FL group. Nevertheless, homeostasis model assessment for insulin resistance as well as conventional insulin resistance indexes such as serum insulin, free fatty acid, and triglyceride levels demonstrated a stepwise increase, and HMW adiponectin and insulin-like growth factor binding protein 1 demonstrated a stepwise decrease with increasing degree of hepatic steatosis. Overall, insulin resistance markers correlated with obesity indexes, but only HMW adiponectin no longer showed any meaningful correlation in the presence of fatty liver. The prevalence of BP, fasting serum glucose, and high-density lipoprotein cholesterol above or below cutoff points and subjects having 2 or more metabolic syndrome components were higher in the moderate to severe FL group compared to the non-FL group. In conclusion, these results in nondiabetic and relatively normal-body mass index subjects suggest that hepatic steatosis is independently associated with insulin resistance regardless of extrahepatic adiposity and might be the earliest event in pathogenesis of the metabolic syndrome.