Discharge Clinical Characteristics and Post-Discharge Events in Patients with Severe COVID-19: A Descriptive Case Series.

BACKGROUND: As the SARS-CoV-2 pandemic continues, little guidance is available on clinical indicators for safely discharging patients with severe COVID-19. OBJECTIVE: To describe the clinical courses of adult patients admitted for COVID-19 and identify associations between inpatient clinical features and post-discharge need for acute care. DESIGN: Retrospective chart reviews were performed to record laboratory values, temperature, and oxygen requirements of 99 adult inpatients with COVID-19. Those variables were used to predict emergency department (ED) visit or readmission within 30 days post-discharge. PATIENTS (OR PARTICIPANTS): Age ≥ 18 years, first hospitalization for COVID-19, admitted between March 1 and May 2, 2020, at University of California, Los Angeles (UCLA) Medical Center, managed by an inpatient medicine service. MAIN MEASURES: Ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, procalcitonin, white blood cell count, absolute lymphocyte count, temperature, and oxygen requirement were noted. KEY RESULTS: Of 99 patients, five required ED admission within 30 days, and another five required readmission. Fever within 24 h of discharge, oxygen requirement, and laboratory abnormalities were not associated with need for ED visit or readmission within 30 days of discharge after admission for COVID-19. CONCLUSION: Our data suggest that neither persistent fever, oxygen requirement, nor laboratory marker derangement was associated with need for acute care in the 30-day period after discharge for severe COVID-19. These findings suggest that physicians need not await the normalization of laboratory markers, resolution of fever, or discontinuation of oxygen prior to discharging a stable or improving patient with COVID-19.

WhatsApp Linking Lilongwe, Malawi to Los Angeles: Impacting Medical Education and Clinical Management.

Background: Subspecialty expertise is often lacking in clinical environments in low-resource settings. As a result, medically complicated patients can receive suboptimal care, local clinicians can feel inadequately supported, and global health engagements can be difficult for medical trainees accustomed to more expert supervision at their home institutions. Objective: We created WhatsApp Messenger discussion groups to connect subspecialists at the University of California, Los Angeles (UCLA) David Geffen School of Medicine with clinicians and rotating global health residents at Partners in Hope (PIH) Medical Center in Lilongwe, Malawi. Methods: Case submitters and subspecialist respondents were surveyed about their experience in the discussion groups. Findings: Over a three-year period, 95 cases were discussed in ten subspecialty groups, with dermatology and radiology/pulmonology receiving the most submissions. Participants were surveyed and reported excellent educational outcomes; large majorities of both case submitters (89%) and experts (71%) agreed or strongly agreed that the case discussions improved their medical education. The surveys also suggested positive impact on medical management decisions and patient outcomes. The major challenge to our intervention was low utilization of this resource by Malawian clinicians in comparison to medical residents. We hope to further address the barriers to participation and adapt the intervention to better support our Malawian colleagues. Conclusion: Because the discussion groups are free to create and require very little maintenance, this intervention can be easily replicated at other institutions looking to augment their global health educational engagements and support their clinical partners abroad.

A machine learning algorithm to increase COVID-19 inpatient diagnostic capacity.

Worldwide, testing capacity for SARS-CoV-2 is limited and bottlenecks in the scale up of polymerase chain reaction (PCR-based testing exist. Our aim was to develop and evaluate a machine learning algorithm to diagnose COVID-19 in the inpatient setting. The algorithm was based on basic demographic and laboratory features to serve as a screening tool at hospitals where testing is scarce or unavailable. We used retrospectively collected data from the UCLA Health System in Los Angeles, California. We included all emergency room or inpatient cases receiving SARS-CoV-2 PCR testing who also had a set of ancillary laboratory features (n = 1,455) between 1 March 2020 and 24 May 2020. We tested seven machine learning models and used a combination of those models for the final diagnostic classification. In the test set (n = 392), our combined model had an area under the receiver operator curve of 0.91 (95% confidence interval 0.87-0.96). The model achieved a sensitivity of 0.93 (95% CI 0.85-0.98), specificity of 0.64 (95% CI 0.58-0.69). We found that our machine learning algorithm had excellent diagnostic metrics compared to SARS-CoV-2 PCR. This ensemble machine learning algorithm to diagnose COVID-19 has the potential to be used as a screening tool in hospital settings where PCR testing is scarce or unavailable.

Hemodynamic characteristics of cyanotic adults with single-ventricle physiology without Fontan completion.

OBJECTIVE: The aim of the current study is to describe the long-term clinical and hemodynamic characteristics of adult patients with single-ventricle physiology who have not undergone the Fontan operation and consequently have remained cyanotic. DESIGN: Adult patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center with non-Fontan single-ventricle physiology who had undergone cardiac catheterization between 2005 and 2011 were included. Echocardiographic and cardiac catheterization data were reviewed. RESULTS: Mean estimated single ejection fraction was 56 ± 8%. Eight of 13 subjects had documented E/E' data with a mean of 6.44. Seven subjects had both A' and E' data documented, of which two subjects exhibited A' > E'. Mean ventricular end-diastolic pressure (MVEDP) was 15.77 ± 4.91 mm Hg, and was >12 mm Hg in eight of the 13 patients (62%). MVEDP was also analyzed by age, and in the single-ventricle patients was 13.55 ± 4.12 mm Hg in those <50 years of age, compared with 20.75 ± 1.89 mm Hg in those >50 years of age (P = .003). MVEDP prior to inhaled pulmonary vasodilator administration was 14.75 ± 5.5 mm Hg, compared to 15.00 ± 6.78 mm Hg in the postvasodilator group (P = .48). Subjects with end-diastolic pressure (EDP) <12 had a mean brain natriuretic peptide (BNP) of 108 ± 197 pg/mL, while subjects with EDP >12 had a mean BNP of 234.5 ± 127.36 pg/mL (P = .11). CONCLUSIONS: Cyanotic adult single-ventricle patients not palliated with Fontan completion have preserved single-ventricle systolic function but develop elevated ventricular filling pressure with increasing age. Only invasive hemodynamic measurements demonstrated elevated ventricular filling pressures, while traditional echo/Doppler criteria for diastolic dysfunction were not met. Aging with cyanotic single-ventricle physiology is associated with a greater degree of filling pressure elevations than in the general population. Single-ventricle patients with EDP >12 exhibited markedly elevated BNP compared to those with normal EDP.

A role for calcium-permeable AMPA receptors in synaptic plasticity and learning.

A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca(2+)-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice). Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP) that was independent of NMDARs and mediated by GluR2-lacking Ca(2+)-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca(2+)-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs.

The alpha1 subunit of the GABA(A) receptor modulates fear learning and plasticity in the lateral amygdala.

Synaptic plasticity in the amygdala is essential for emotional learning. Fear conditioning, for example, depends on changes in excitatory transmission that occur following NMDA receptor activation and AMPA receptor modification in this region. The role of these and other glutamatergic mechanisms have been studied extensively in this circuit while relatively little is known about the contribution of inhibitory transmission. The current experiments addressed this issue by examining the role of the GABA(A) receptor subunit alpha1 in fear learning and plasticity. We first confirmed previous findings that the alpha1 subunit is highly expressed in the lateral nucleus of the amygdala. Consistent with this observation, genetic deletion of this subunit selectively enhanced plasticity in the lateral amygdala and increased auditory fear conditioning. Mice with selective deletion of alpha1 in excitatory cells did not exhibit enhanced learning. Finally, infusion of a alpha1 receptor antagonist into the lateral amygdala selectively impaired auditory fear learning. Together, these results suggest that inhibitory transmission mediated by alpha1-containing GABA(A) receptors plays a critical role in amygdala plasticity and fear learning.