Hyperglycemia-induced cardiomyocyte death is mediated by lysosomal membrane injury and aberrant expression of cathepsin D.

Hyperglycemia is an independent risk factor for diabetic heart failure. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Previous studies have shown an association between lysosomal dysfunction and diabetic heart injury. The present study examined if mimicking hyperglycemia in cultured cardiomyocytes could induce lysosomal membrane permeabilization (LMP), leading to the release of lysosome enzymes and subsequent cell death. High glucose (HG) reduced the number of lysosomes with acidic pH as shown by a fluorescent pH indicator. Also, HG induced lysosomal membrane injury as shown by an accumulation of Galectin3-RFP puncta, which was accompanied by the leakage of cathepsin D (CTSD), an aspartic protease that normally resides within the lysosomal lumen. Furthermore, CTSD expression was increased in HG-cultured cardiomyocytes and in the hearts of 2 mouse models of type 1 diabetes. Either CTSD knockdown with siRNA or inhibition of CTSD activity by pepstatin A markedly diminished HG-induced cardiomyocyte death, while CTSD overexpression exaggerated HG-induced cell death. Together, these results suggested that HG increased CTSD expression, induced LMP and triggered CTSD release from the lysosomes, which collectively contributed to HG-induced cardiomyocyte injury.

Implementing a Telehospitalist Program Between Veterans Health Administration Hospitals: Outcomes, Acceptance, and Barriers to Implementation.

BACKGROUND: Telehospitalist services are an innovative alternative approach to address staffing issues in rural and small hospitals. OBJECTIVE: To determine clinical outcomes and staff and patient satisfaction with a novel telehospitalist program among Veterans Health Administration (VHA) hospitals. DESIGN, SETTING, AND PARTICIPANTS: We conducted a mixed-methods evaluation of a quality improvement program with pre- and postimplementation measures. The hub site was a tertiary (high-complexity) VHA hospital, and the spoke site was a 10-bed inpatient medical unit at a rural (low-complexity) VHA hospital. All patients admitted during the study period were assigned to the spoke site. INTERVENTION: Real-time videoconferencing was used to connect a remote hospitalist physician with an on-site advanced practice provider and patients. Encounters were documented in the electronic health record. MAIN OUTCOMES: Process measures included workload, patient encounters, and daily census. Outcome measures included length of stay (LOS), readmission rate, mortality, and satisfaction of providers, staff, and patients. Surveys measured satisfaction. Qualitative analysis included unstructured and semi-structured interviews with spoke-site staff. RESULTS: Telehospitalist program implementation led to a significant reduction in LOS (3.0 [SD, 0.7] days vs 2.3 [SD, 0.3] days). The readmission rate was slightly higher in the telehospitalist group, with no change in mortality rate. Satisfaction among teleproviders was very high. Hub staff perceived the service as valuable, though satisfaction with the program was mixed. Technology and communication challenges were identified, but patient satisfaction remained mostly unchanged. CONCLUSION: Telehospitalist programs are a feasible and safe way to provide inpatient coverage and address rural hospital staffing needs. Ensuring adequate technological quality and addressing staff concerns in a timely manner can enhance program performance.

An Initiative to Improve 30-Day Readmission Rates Using a Transitions-of-Care Clinic Among a Mixed Urban and Rural Veteran Population.

BACKGROUND/OBJECTIVE: Hospital readmissions in the United States, especially in patients at high-risk, cost more than $17 billion annually. Although care transitions is an important area of research, data are limited regarding its efficacy, especially among rural patients. In this study, we describe a novel transitions-of-care clinic (TOCC) to reduce 30-day readmissions in a Veterans Health Administration setting that serves a high proportion of rural veterans. METHODS: In this quality improvement initiative we conducted a pre-post study evaluating clinical outcomes in adult patients at high risk for 30-day readmission (Care Assessment Needs score > 85) discharged from the Iowa City Veterans Affairs (ICVA) Health Care System from 2017 to 2020. The ICVA serves 184,000 veterans across 50 counties in eastern Iowa, western Illinois, and northern Missouri, with more than 60% of these patients residing in rural areas. We implemented a multidisciplinary TOCC to provide in-person or virtual follow-up to high-risk veterans after hospital discharge. The main purpose of this study was to assess how TOCC follow-up impacted the monthly 30-day patient readmission rate. RESULTS: The TOCC resulted in a 19.2% relative reduction in 30-day readmission rates in the 12-month postimplementation period compared to the preimplementation period (9.2% vs 11.4%, P = .04). Virtual visits were more popular than in-person visits among both urban and rural veterans. There was no difference in outcomes between these two follow-up options, and both groups had reduced readmission rates compared to non-TOCC follow-up. CONCLUSIONS: A multidisciplinary TOCC within the ICVA featuring both virtual and in-person visits reduced the 30-day readmission rate. This reduction was particularly notable among patients with congestive heart failure.

An 85-year old male with levodopa-responsive parkinsonism followed by dementia and supranuclear ophthalmoplegia caused by alzheimer-type pathology without Lewy bodies.

An 85-year-old man developed l-dopa responsive parkinsonism indistinguishable from Parkinson's disease and subsequent dementia, followed by supranuclear ophthalmoplegia and neck dorsiflexion at the terminal stage. Midbrain tegmentum and medial temporal lobe were atrophic on magnetic resonance imaging, while decreased blood flow was predominant in frontotemporal lobes, detected by 3D-SSP of 123I- IMP SPECT. Alzheimer-type pathology without Lewy body pathology was confirmed at autopsy. Substantia nigra showed mild degeneration and several neurofibrillary tangles without Lewy body pathology or progressive supranuclear palsy cytopathology. L-dopa responsive parkinsonism could be an initial manifestation of Alzheimer's disease, which should be included in the differential diagnosis.