Low ALT values amongst hospitalized patients are associated with increased risk of hypoglycemia and overall mortality: a retrospective, big-data analysis of 51 831 patients.

BACKGROUND: Sarcopenia and frailty influence clinical patients' outcomes. Low alanine aminotransferase (ALT) serum activity is a surrogate marker for sarcopenia and frailty. In-hospital hypoglycemia is associated, also with worse clinical outcomes. AIM: We evaluated the association between low ALT, risk of in-hospital hypoglycemia and subsequent mortality. DESIGN: This was a retrospective cohort analysis. METHODS: We included patients hospitalized in a tertiary hospital between 2007 and 2019. Patients' data were retrieved from their electronic medical records. RESULTS: The cohort included 51 831 patients (average age 70.88). The rate of hypoglycemia was 10.8% (amongst diabetics 19.4% whereas in non-diabetics 8.3%). The rate of hypoglycemia was higher amongst patients with ALT < 10 IU/l in the whole cohort (14.3% vs. 10.4%, P < 0.001) as well as amongst diabetics (24.6% vs. 18.8%, P < 0.001). Both the overall and in-hospital mortality were higher in the low ALT group (57.7% vs. 39.1% P < 0.001 and 4.3% vs. 3.2%, P < 0.001). A propensity score matching, after which a regression model was performed, showed that patients with ALT levels < 10 IU/l had higher risk of overall mortality (HR = 1.21, CI 1.13-1.29, P < 0.001). CONCLUSIONS: Low ALT values amongst hospitalized patients are associated with increased risk of in-hospital hypoglycemia and overall mortality.

Reducing drug prescription errors and adverse drug events by application of a probabilistic, machine-learning based clinical decision support system in an inpatient setting.

BACKGROUND: Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts. OBJECTIVE: In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting. MATERIALS AND METHODS: We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department's staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician's real-time responses to alerts generated. RESULTS: The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients' status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders. CONCLUSION: A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.

Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis.

Fibroblast growth factors (FGFs) and vascular endothelial growth factor (VEGF) play a pivotal role in the multistep pathway of tumor progression, metastasis, and angiogenesis. We have identified a porphyrin analogue, 5,10,15,20-tetrakis(methyl-4-pyridyl)-21H,23H-porphine-tetra -p-tosylate salt (TMPP), as a potent inhibitor of FGF2 and VEGF receptor binding and activation. TMPP demonstrated potent inhibition of binding of soluble FGF receptor 1 (FGFR1) to FGF2 immobilized on heparin at submicromolar concentrations. TMPP inhibits binding of radiolabeled FGF2 to FGFR in a cell-free system as well as to cells genetically engineered to express FGFR1. Furthermore, TMPP also inhibits the binding of VEGF to its tyrosine kinase receptor in a dose-dependent manner. In an in vitro angiogenic assay measuring the extent of endothelial cell growth, tube formation, and sprouting, TMPP dramatically reduced the extent of the FGF2-induced endothelial cell outgrowth and differentiation. In a Lewis lung carcinoma model, mice receiving TMPP showed a marked inhibition of both primary tumor progression and lung metastases development, with nearly total inhibition of the metastatic phenotype upon alternate daily injections of TMPP at 25 microg/g of body mass. Finally, novel meso-pyridylium-substituted, nonsymmetric porphyrins, as well as a novel corrole-based derivative, with >50-fold increase in activity in vitro, had a significantly improved efficacy in blocking tumor progression and metastasis in vivo.

Acute eosinophilic interstitial nephritis and uveitis (TINU syndrome) associated with granulomatous hepatitis.

A 23-year-old male presented with renal failure, cholestatic liver enzyme elevation and uveitis. Percutaneous renal biopsy revealed marked eosinophilic infiltration of the renal interstitium, which made the diagnosis of TINU syndrome (Tubulo-Interstitial Nephritis and Uveitis). Percutaneous liver biopsy showed granulomatous hepatitis, which was not described as a part of TINU syndrome. The diagnostic dilemma and the literature are discussed.

[Thallium scan and pulmonary carcinoma].

A 70-year-old man was admitted for exacerbation of congestive heart failure. In his assessment thallium scan of the heart was performed. An incidental finding was a focus of absorption in the right lung. The lesion was later diagnosed as adenocarcinoma based on the cytological findings.

Remission of positive symptoms according to the "remission in Schizophrenia Working Group" criteria: a longitudinal study of cognitive functioning.

Schizophrenia patients in positive symptomatic remission (PSR; n=39) were assessed using a longitudinal research design. The patients were found to exhibit widespread cognitive impairments that were stable over the three-year follow-up period. The findings support a generalized and stable cognitive impairment profile among schizophrenia patients in partial symptomatic remission.

Neurocognitive functions of heavy cannabis using schizophrenia patients.

This current study assessed neurocognitive functioning in a carefully selected sample of schizophrenia patients with and without heavy cannabis use and healthy controls. All subjects were negative for any other substance use. Schizophrenia subjects had impaired neurocognitive functions across a wide range of tasks compared to healthy controls. Cannabis using schizophrenia patients had focused impairments on tasks of attention, and the findings suggest an impulsive pattern of response among these patients.

Downregulation of gene expression in the ageing lens: a possible contributory factor in senile cataract.

PURPOSE: To study the molecular characteristics of lens epithelial cells from patients with senile cataract by cDNA microarray technique. METHODS: Lens epithelial cells adhering to anterior capsules taken during cataract surgery collected from 108 patients, aged 56-92 years (senile cataract group), were pooled. Pooled epithelial cells of normal, noncataractous lenses from one patient with ocular trauma, one patient with lens subluxation, and 25 cadaveric eyes, all under the age of 55 years, served as a control. Total RNA was extracted by conventional methods from the two groups of cells, and a fluorescent probe was prepared for each group. The probes were hybridized on 9700 known human cDNA clones. Hybridized clones were analysed using a scanning laser and the results were processed by GEMTools (Incyte Genomics) software. RESULTS: A total of 1827 clones hybridized with the two probes. Of these, 400 showed differences of more than two-fold in gene expression between the two probes. Relative to controls, gene expression in the senile cataract lenses was upregulated in 318 clones and downregulated in 82. Three genes-filensin, inwardly rectifying potassium channel (IRPC), and pigment epithelium-derived factor (PEDF) were strongly downregulated (by 41.3-, 6.8-, and 5.9-fold, respectively) in senile cataract. CONCLUSIONS: Cataractogenesis is associated with numerous changes in the genetic profile of the lens epithelial cells. Since filensin, IRPC, and PEDF genes are known to have important roles in the physiology and morphology of the transparent lens, substantial downregulation of their expression might contribute to the formation of senile cataract.

Staphylococcus aureus bacteremia as a cause of early relapse of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a multisystem disease characterized by the sudden onset of hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic dysfunction, occurring in various combinations. The most effective treatment of TTP is plasma exchange and the administration of corticosteroids, which reduces mortality from the 90 percent seen in untreated patients to 10 percent. CASE REPORTS: Two patients responded favorably to plasma exchange and corticosteroid therapy, but their TTP relapsed during treatment. In both cases, the early relapse of TTP was associated with Staphylococcus aureus bacteremia secondary to central line infection. Treatment of the infection and intensification of the plasma exchange regimen resulted in a sustained remission. CONCLUSION: Infection should be actively sought and treated in TTP patients who are refractory to treatment or in whom an exacerbation of the disease occurs while they are undergoing plasma exchange.

Lupus-like syndrome with submassive hepatic necrosis associated with hepatitis A.

Hepatitis A is a common self-limited liver disease. However, 15% of patients may have some complications. Autoimmune hepatitis that is triggered by viral hepatitis has been reported. We hereby describe an unrecognized association of hepatitis A with a full blown lupus-like syndrome manifested by the appearance of arthralgia, exudative pleural effusion with the presence of lupus erythematosus cells and autoantibodies. All these findings disappeared after a short course of steroid treatment. The case is presented and the literature is reviewed.