In vitro activity of ceftriaxone and other cephalosporins against 602 clinical isolates of staphylococci from geographically diverse medical centers

The in vitro activity of ceftriaxone and six additional antimicrobial agents (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of staphylococci from six geographically distinct medical centers in North America. All seven antimicrobial agents were active (90–100% of strains susceptible) against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and coagulase-negative staphylococci (OSCNS) but had limited activity against oxacillin resistant (OR) staphylococci. Our assessment of the in vitro antistaphylococcal activity of ceftriaxone against contemporary isolates of Staphylococcus aureus and coagulase-negative staphylococci indicates that the activity versus OS staphylococci has not changed over the past decade despite widespread use of the drug. It appears that these agents will continue to be useful for empiric therapy in those centers in which OR strains are uncommon.Corresponding author.     

Reproducibility of Immunological Tests Used To Assess Multiple Chemical Sensitivity Syndrome

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by ≤3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4⁺ cells, ranging from minor to eightfold for CD25⁺ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.     

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     

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.     

Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy

Cytotoxic T lymphocytes (CTLs) are an important defense against human immunodeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppressing replication, the evolution of T cell phenotypes and HIV-specific CD8+ lymphocytes was prospectively investigated in 41 patients initiating combination therapy. Suppression of viremia to <200 copies/mL was associated with increases in naive cells (CD45RA+62L+) and declines in activated T cells (CD95+ cell counts and CD38+ HLA-DR+). HIV-specific tetramer-staining CD8+ T cells were detected in 6 of 10 HLA-A*0201-positive persons, which declined in 5 with treatment. CTL precursor frequencies were markedly consistent before and after treatment. Eight (72%) of 11 recognized > or =1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8+ T cells, including those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capable of differentiating into effectors remains stable, and the recognition of new epitopes may occur.     

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.     

The use of neuromuscular blocking agents to facilitate prehospital intubation does not impair outcome after traumatic brain injury

BACKGROUND: Several studies have demonstrated that the success rate of prehospital intubation is improved by the use of neuromuscular blocking agents (NMBAs). However, a recent study has reported that prehospital intubation with NMBAs worsens outcome after traumatic brain injury (TBI). We sought to determine the effect of the use of NMBAs to facilitate prehospital intubation on outcome after TBI. METHODS: All patients admitted to our Level I trauma center with a head Abbreviated Injury Scale score >/= 3 were identified by the trauma registry (January 1998-June 2003). Patient records were matched with prehospital databases. Patients were further stratified on the basis of prehospital Glasgow Coma Scale (GCS) score into mild (GCS score of 14/15), moderate (GCS score of 9-13), and severe (GCS score < 9) TBI. Outcome included mortality and good outcome (survival to discharge with a GCS score of 14/15). RESULTS: There were 3,052 patients who were identified as having been transported directly from the field. Complete prehospital data were available for 2,012 patients (66%). Of these, 920 were mild TBI (intubation rate, 17.4%), 293 moderate TBI (intubation rate, 57.7%), and 799 severe TBI (intubation rate, 95%). Overall, 72% of intubated patients received NMBAs. There were no significant differences in demographics or injury severity between the groups. Patients not receiving NMBAs were more likely to be hypotensive and have prehospital cardiopulmonary resuscitation (p = 0.001). The unadjusted mortality for the patients intubated with NMBAs was 25% versus 37% for those not receiving NMBAs (p < 0.001). When adjusted for confounding variables, patients intubated with NMBAs were more likely to survive (odds ratio, 0.63; 95% confidence interval, 0.41-0.97; p = 0.04) and have a good outcome (odds ratio, 1.7; 95% confidence interval, 1.2-2.6; p = 0.006) than those in the no-NMBA group. CONCLUSION: The use of NMBAs to facilitate prehospital intubation improves outcome for patients with TBI. The value of prehospital intubation for TBI remains to be determined; however, any trial evaluating nonintubation for TBI must be compared with NMBA-facilitated intubation to be valid.     

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.