Levels of Ca\u3csub\u3ev\u3c/sub\u3e1.2 L-Type Ca\u3csup\u3e2+\u3c/sup\u3e Channels Peak in the First Two Weeks in Rat Hippocampus Whereas Ca\u3csub\u3ev\u3c/sub\u3e1.3 Channels Steadily Increase through Development

Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonly modulated by G-protein-coupled receptors such as GABAB receptors. Of the four isoforms of L-type channels, only Cav1.2 and Cav1.3 are predominately expressed in the nervous system. Both isoforms are inhibited by the same pharmacological agents, so it has been difficult to determine the role of specific isoforms in physiological processes. In the present study, Western blot analysis and confocal microscopy were utilized to study developmental expression levels and patterns of Cav1.2 and Cav1.3 in the CA1 region of rat hippocampus. Steady-state expression of Cav1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of Cav1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against Cav1.2 and Cav1.3 demonstrated the highest intensity of labeling in the proximal dendrites at all ages studied (P1–72). Immunohistochemical studies on one-week-old hippocampi demonstrated significantly more colocalization of GABAB receptors with Cav1.2 than with Cav1.3, suggesting that modulation of L-type calcium current in early development is mediated through Cav1.2 channels

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009

Prosthetic Joint Infection due to Mycobacterium avium-intracellulare in a Patient with Rheumatoid Arthritis: A Case Report and Review of the Literature

Nontuberculous mycobacteria (NTM) are a rare cause of prosthetic joint infections (PJI). However, the prevalence of NTM infections may be increasing with the rise of newer immunosuppressive medications such as biologics. In this case report, we describe a rare complication of immunosuppressive therapies and highlight the complexity of diagnosing and treating PJI due to NTM. The patient is a 79-year-old Caucasian male with a history of severe destructive rheumatoid arthritis on several immunosuppressive agents and right hip osteoarthritis s/p total hip arthroplasty 15 years previously with several complex revisions, presenting with several weeks of worsening right hip and abdominal pain. A right hip CT scan revealed periprosthetic fluid collections. Aspiration of three fluid pockets was AFB smear-positive and grew Mycobacterium avium-intracellulare. The patient was deemed a poor surgical candidate. He underwent a limited I&D and several months of antimycobacterial therapy but clinically deteriorated and opted for hospice care. PJI caused by NTM are rare and difficult to treat. The increased use of biologics and prosthetic joint replacements over the past several decades may increase the risk of PJI due to NTM. A high index of suspicion for NTM in immunosuppressed patients with PJI is needed

Serum Levels of Acylcarnitines and Amino Acids Are Associated with Liberation from Organ Support in Patients with Septic Shock

Sepsis-induced metabolic dysfunction is associated with mortality, but the signatures that differentiate variable clinical outcomes among survivors are unknown. Our aim was to determine the relationship between host metabolism and chronic critical illness (CCI) in patients with septic shock. We analyzed metabolomics data from mechanically ventilated patients with vasopressor-dependent septic shock from the placebo arm of a recently completed clinical trial. Baseline serum metabolites were measured by liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance. We conducted a time-to-event analysis censored at 28 days. Specifically, we determined the relationship between metabolites and time to extubation and freedom from vasopressors using a competing risk survival model, with death as a competing risk. We also compared metabolite concentrations between CCI patients, defined as intensive care unit level of care ≥ 14 days, and those with rapid recovery. Elevations in two acylcarnitines and four amino acids were related to the freedom from organ support (subdistributional hazard ratio < 1 and false discovery rate < 0.05). Proline, glycine, glutamine, and methionine were also elevated in patients who developed CCI. Our work highlights the need for further testing of metabolomics to identify patients at risk of CCI and to elucidate potential mechanisms that contribute to its etiology

Improving capacity to identify, assess, and manage adolescents engaging in non-suicidal self-injury using patient avatars.

PURPOSE: We developed and evaluated a training comprising a didactic and virtual practice session with human-guided patient avatars to increase pediatric residents\u27 competence to identify and assess non-suicidal self-injury (NSSI) and suicide risk. METHODS: Thirty pediatric residents at three children\u27s hospitals in Florida participated in the training and completed pre-, one-month post-, and three-months post-training surveys. One-way repeated measures ANOVA with post-hoc comparisons determined changes in confidence, comfort, behavioral intentions, attitudes, knowledge, and behavior over time. Qualitative responses provided feedback on the training, especially the novel practice session with adolescent patient avatars. RESULTS: Three-months post-training residents expressed significantly greater confidence in talking to adolescents who self-injure, applying the SOARS method to assess self-injury, and assessing functions/reasons for self-injury; reported feeling significantly more comfortable asking about self-injury, well-equipped to handle the emotional aspects of self-injury, and comfortable treating adolescents who self-injure; reported greater behavioral intentions to talk to adolescents about self-injury, assess an adolescent\u27s stage of change for stopping self-injury, and provide brief interventions for adolescents who self-injure; and used SOARS to evaluate current NSSI with a greater proportion of adolescent patients. Qualitative feedback expressed positive perceptions, especially related to the virtual-reality role-play session. CONCLUSIONS: Incorporating an interactive, human-guided virtual experience using role-playing and feedback with patient avatars represents a viable option comparable to using typical standardized patients to expand the scalability of NSSI trainings for pediatric residents, especially when they occur virtually

Predictors of discharge disposition and mortality following hospitalization with SARS-CoV-2 infection

Importance The SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition. Objective Characterization of disposition associated factors following SARS-CoV-2. Design Retrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization. Setting Midwest academic health-system. Participants Patients above the age 18 years admitted with PCR + SARS-CoV-2. Intervention None. Main outcomes Discharge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH). Results We identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH). Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6–85.1) compared to those discharged home (57.0 years, IQR: 38.2–69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9). Older age (RRR:1.04, 95% CI:1.041–1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168–1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060–1.077) and higher EI (RRR:1.09, 95% CI:1.071–1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47–0.88), (RRR 0.48 CI 0.34–0.67) and (RRR 0.586 CI 0.352–0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444–780). The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99–0.99) and albumin levels 0.342 (CI 0.26–0.45), and higher with increased CRP (RRR 1.006 CI 1.004–1.007) and D-Dimer (RRR 1.070 CI 1.039–1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497–0.798. An increase in D-Dimer (RRR1.033 CI 1.002–1.064) and CRP (RRR1.002 CI1.001–1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC. Conclusion Older age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH

Predictors of discharge disposition and mortality following hospitalization with SARS-CoV-2 infection.

ImportanceThe SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition.ObjectiveCharacterization of disposition associated factors following SARS-CoV-2.DesignRetrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization.SettingMidwest academic health-system.ParticipantsPatients above the age 18 years admitted with PCR + SARS-CoV-2.InterventionNone.Main outcomesDischarge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH).ResultsWe identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH). Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6-85.1) compared to those discharged home (57.0 years, IQR: 38.2-69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9). Older age (RRR:1.04, 95% CI:1.041-1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168-1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060-1.077) and higher EI (RRR:1.09, 95% CI:1.071-1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47-0.88), (RRR 0.48 CI 0.34-0.67) and (RRR 0.586 CI 0.352-0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444-780). The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99-0.99) and albumin levels 0.342 (CI 0.26-0.45), and higher with increased CRP (RRR 1.006 CI 1.004-1.007) and D-Dimer (RRR 1.070 CI 1.039-1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497-0.798. An increase in D-Dimer (RRR1.033 CI 1.002-1.064) and CRP (RRR1.002 CI1.001-1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC.ConclusionOlder age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH

Comparison of vaccinated and non-vaccinated SARS-CoV-2 patients admitted to hospital.

Categorical variables expressed as count and percentage, and continuous variables as median and IQR.</p

Descriptive Table: Comparison of the SARS-CoV-2 to influenza patients admitted to hospital.

Categorical variables expressed as count and percent, and continuous variables as median and IQR.</p