Chemotherapy-induced cachexia and model-informed dosing to preserve lean mass in cancer treatment.

Although chemotherapy is a standard treatment for cancer, it comes with significant side effects. In particular, certain agents can induce severe muscle loss, known as cachexia, worsening patient quality of life and treatment outcomes. 5-fluorouracil, an anti-cancer agent used to treat several cancers, has been shown to cause muscle loss. Experimental data indicates a non-linear dose-dependence for muscle loss in mice treated with daily or week-day schedules. We present a mathematical model of chemotherapy-induced muscle wasting that captures this non-linear dose-dependence. Area-under-the-curve metrics are proposed to quantify the treatment's effects on lean mass and tumour control. Model simulations are used to explore alternate dosing schedules, aging effects, and morphine use in chemotherapy treatment with the aim of better protecting lean mass while actively targeting the tumour, ultimately leading to improved personalization of treatment planning and improved patient quality of life.

Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening for Patients with a Diabetic Foot Infection.

Treatment of suspected methicillin-resistant Staphylococcus aureus (MRSA) is a cornerstone of severe diabetic foot infections; however, antibiotics can be associated with toxicity. The objective of this study was to determine the negative predictive value (NPV) of MRSA nares screening in the determination of subsequent MRSA in patients with a diabetic foot infection. This was a retrospective cohort study across Veterans Affairs (VA) medical centers from 1 January 2007 to 1 January 2018. Data from patients with an International Classification of Diseases (ICD) code for a diabetic foot infection with MRSA nares screening, and subsequent cultures were evaluated for the presence of MRSA. NPVs were calculated for the entire cohort, as well as for a subgroup representing deep cultures. Additionally, the distribution of all pathogens isolated from diabetic foot infections was determined. A total of 8,163 episodes were included in the analysis for NPV. The NPV of MRSA nares screening for MRSA diabetic foot infection was 89.6%. For the deep cultures, the NPV was 89.2%. The NPV for cultures originating from the foot was 89.7%, and the NPV for those originating from the toe was 89.4%. There were 17,822 pathogens isolated from the diabetic foot cultures. MRSA was isolated in 7.5% of cultures, and methicillin-susceptible S. aureus was isolated in 24.8%. Enterococcus was identified in 14.7% of cultures, Proteus in 7.3%, and Pseudomonas in 6.8% of cultures. Given the high NPVs, the use of MRSA nares screening may be appropriate as a stewardship tool for deescalation and avoidance of empirical anti-MRSA therapy in patients who are not nasal carries of MRSA.

Epidemiology and Clinical Characteristics of Ocular Tuberculosis in the United States, 1993-2019.

Background: Data regarding ocular tuberculosis (OTB) in the United States have not been previously reported. We evaluated trends of OTB compared with other extrapulmonary TB (EPTB). Methods: We estimated the proportion of all EPTB cases (with or without concurrent pulmonary involvement) with OTB reported to the National Tuberculosis Surveillance System during 1993-2019. We compared demographics and clinical characteristics of people with OTB and other EPTB during 2010-2019. P values were calculated by chi-square test for categorical variables and Kruskal-Wallis for continuous variables. Results: During 1993-2019, 1766 OTB cases were reported, representing 1.6% of 109 834 all EPTB cases: 200 (0.5% of 37 167) during 1993-1999, 395 (1.0% of 41 715) during 2000-2009, and 1171 (3.8% of 30 952) during 2010-2019. In contrast to persons with other EPTB, persons with OTB were older (median, 48 vs 44 years; P < .01), more likely to be US-born (35% vs 28%; P < .01), more likely to have diabetes (17% vs 13%; P < .01), and less likely to have HIV (1% vs 8%; P < .01). OTB was less likely to be laboratory confirmed (5% vs 75%; P < .01), but patients were more likely to be tested by interferon gamma release assay (IGRA; 84% vs 56%; P < .01) and to be IGRA positive (96% vs 80%; P < .01). Conclusions: Reported OTB increased during 1993-2019 despite decreasing TB, including EPTB; the largest increase occurred during 2010-2019. OTB was rarely laboratory confirmed and was primarily diagnosed in conjunction with IGRA results. More research is needed to understand the epidemiology of OTB to inform clinical and diagnostic practices.

Mycobacterium szulgai cavitary lung disease progression over a three year period - A case report.

Mycobacterium szulgai is a slow growing non-tuberculous mycobacterium associated with rare but severe infections. It most commonly presents as pulmonary disease in people with underlying structural lung disease. We report a case of progressive cavitary lung disease over a three year period due to Mycobacterium szulgai and the subsequent outcome.

Antibody dependent cell cytotoxicity is maintained by the unmutated common ancestor of 6F5, a Gp41 conformational epitope targeting antibody that utilizes heavy chain VH1-2.

In studies on monoclonal IgG antibodies (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 the N terminal and C terminal heptad repeat helices. Despite using the VH1-2 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization. Because of the high number of mutations and use of VH1-2, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess if targeting of the epitope correlates with LTNP, and to assess the maturation of these Abs by comparison to their predicted common ancestor. Serum competition assays showed group 76C Abs were enriched in LTNPs, in comparison to VRC-01. Specific group 76C clones 6F5 and 6F11, expressed as recombinant Abs, both have robust ADCC activity, despite their sequence disparity. Sequence analysis predicted the common ancestor of this clonal group would utilize the germline non-mutated variable gene. We produced a recombinant ancestor Ab (76Canc) with a heavy chain utilizing the germline variable gene sequence paired to the 6F5 light chain. Competition with group 76C recombinant Ab 6F5 confirms 76Canc binds HIV envelope constructs near the original group C epitope. 76Canc demonstrates comparable ADCC to 6F5 and 6F11 when using gp41 constructs of both clade B and clade C. The functional capability of Abs utilizing germline VH1-2 has implications for disease control and vaccine development.

Serum Responses of Children With Kawasaki Disease Against Severe Acute Respiratory Syndrome Coronavirus 2 Proteins.

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.

The Missing Record of Mental Status in Written Sign-Outs.

OBJECTIVE: The aim of the study was to determine how frequently mental status and mental status changes are documented in the written patient summary ("sign-out") provided to covering physicians. PATIENTS AND METHODS: This was a retrospective cohort study of general medical patients hospitalized between March 16, 2009, and March 15, 2010, conducted at 2 teaching hospitals. Participants included patients with mental status change adverse events (MSAEs) and their providers. Chart review was performed to identify patients with MSAEs and details about these events. Sign-outs were reviewed for documentation of mental status. Main outcome measures were (1) proportion of patients with MSAEs who had mental status ever recorded in sign-out entries and (2) the proportion of patients with MSAEs whose change in mental status was recorded in the sign-out. RESULTS: Sixty-eight patients had MSAEs and were included in the sample. Fifty percent of MSAEs were attributed to medications; 75% of these events were first detected by nurses. Only 25% of patients with MSAEs had their change in mental status recorded in sign-outs. CONCLUSIONS: Recording mental status in written sign-outs is uncommon. Particularly concerning is that patients with MSAEs identified by chart review seldom had sign-outs that reflected those events. Interventions should be designed to increase the recording of this information in sign-outs.

Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome Associated With Anti-N-methyl-D-aspartate Receptor Encephalitis.

BACKGROUND: The full clinical spectrum of anti-N-methyl-D-aspartate receptor encephalitis is unknown in the pediatric population. PATIENT: We describe a previously healthy 4-year-old girl presenting with opsoclonus-myoclonus together with ataxia who had NR1-specific, anti-N-methyl-D-aspartate receptor antibodies in the cerebral spinal fluid. CONCLUSION: The presence of NR1-specific, anti-N-methyl-D-aspartate receptor antibodies in the setting of opsoclonus-myoclonus and ataxia syndrome may represent an expansion of the clinical presentations of anti-N-methyl-D-aspartate receptor encephalitis.