Ashraf Elsayegh

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

BACKGROUND: Intensivists have been associated with decreased mortality in several studies, but in one major study, centers with intensivist-staffed units reported increased mortality compared with controls. We hypothesized that a closed unit, in which a unit-based intensivist directly provides and coordinates care on all cases, has improved mortality and utilization compared with an open unit, in which individual attendings and consultants provide care, while intensivists serve as supervising consultants. METHODS: We undertook the retrospective study of outcomes in 2 intensive care units (ICUs)-a traditional open unit managed by faculty intensivists and a second closed unit overseen by the same faculty intensivists who coordinated the care on all patients in a large community hospital. PRIMARY OUTCOME: In-hospital mortality. SECONDARY OUTCOMES: Hospital length of stay (LOS), ICU LOS, and relative costs of hospitalization. RESULTS: From January 2006 to December 2007, we identified 2602 consecutive admissions to the 2 medical ICUs. Of all patients admitted to the closed and open units, 19.2% and 24.7%, respectively, did not survive (P < 0.001, adjusted for severity). Median hospital LOS was 10 days for the closed unit and 12 days for the open unit (P < 0.001). Median ICU LOS was 2.2 days for the closed unit and 2.4 days for the open unit (P = NS). The unadjusted cost index for the open unit was 1.11 relative to the closed unit (1.0) (P < 0.001). However, after adjusting for disease severity, cost differences were not significantly different. CONCLUSIONS: We observed significant reductions in mortality and hospital LOS for patients initially admitted to a closed ICU versus an open unit. We did not observe a significant difference in ICU LOS or total cost after adjustment for severity.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Deteriorating pulmonary function as a reflection of progressive respiratory muscle weakness is a common feature, accounting for the majority of deaths. The aim of the study was to describe a trend in initial pulmonary function tests (PFT) of amyotrophic lateral sclerosis (ALS) patients, in addition, differentiating between the types of disease onset, bulbar, limb muscle, and a combination. METHODS: Initial PFT were gathered from 32 consecutive patients in our clinic with the diagnosis of ALS, they were categorized by the type of disease onset. Values obtained were referenced to the 95% confidence limits for normality. RESULTS: There was evidence of significant reductions in both the FEV1 (64.7% predicted) and FVC (61.2%), with preservation of the FEV1/FVC (81.7%). The MVV was significantly reduced (43%). Total lung capacity was 93.2%, the residual volumes was increased at 145.7%. Subgroup analysis failed to show significant differences between types of disease onset. In the bulbar onset group (versus the limb group) there was a trend for the MVV to be further reduced (p = 0.15) and the RV to be higher (157.4% versus 135.9%, P = 0.24). CONCLUSIONS: ALS is a devastating disease that invariably leads to respiratory failure. Abnormal spirometric variables such as the FVC and MVV, likely reflect inspiratory muscle weakness and increased RV likely reflect expiratory muscle weakness. The type of disease onset did not result in a different pattern of PFT abnormalities.