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Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge. From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05). In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

All Texans, or their ancestors, started as something else. The families that came here molded the state and were molded by it. Anne H. Sutherland explores just how the experiences of two of the early Anglo land-grant families—the Robertsons and the Sutherlands—shaped Texas events and how they handed down those experiences from one generation to another, transforming two Scots-Irish families into what in hindsight we have branded Anglo-Texans. The story of these two pioneering families, told through their letters, poems, diaries, and oral histories, embodies western expansion and political upheaval. Settling in central and southeast Texas, these families struggled to build a new Texas and make a life for their children. The Texas revolution and the Civil War acted as catalysts for the emergence of their Texan identity. A unique blend of family and Texas history, Sutherland’s Made in Texas: A Family Tale positions personal stories as windows of insight onto Texan identity. She peels back the layers of family tradition and textbook history to show how her forebears experienced the transforming events of the settlement of Texas and its war for independence. As new generations emerged, each contributed its own anecdotes and historical context from the time period. By placing the families within Texas history, Sutherland effectively and innovatively traces identity from the early nineteenth century to today. As settlers in the western wilderness, the Robertsons, the Sutherlands, and others like them actively shaped Texas, even as they were changed themselves.

Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment. •Viscoelastic methods (VEM) proficiently assess coagulopathy of cirrhotic patients.•Conventional coagulation tests may poorly assess coagulopathy in cirrhotic patients.•VEM is more fit to assess the need to transfuse in patients with cirrhosis.•VEM better indicates which blood components to transfuse in cirrhotic patients.

Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in quarterly National HIV Surveillance System datasets from December 2015 to December 2019. Priority clusters were identified quarterly. To understand populations recently affected by rapid transmission, we described the transmission risk and race/ethnicity of people in clusters first detected in 2018–2019. During December 2015 to December 2019, national sequence completeness increased from 26% to 45%. Of the 1212 people in the 136 clusters first detected in 2018–2019, 69% were men who have sex with men (MSM) and 11% were people who inject drugs (PWID). State-by-state analysis showed substantial variation in transmission risk and racial/ethnic groups in clusters of rapid transmission. HIV sequence reporting has increased nationwide. Molecular cluster analysis identifies rapid transmission in varied populations and identifies emerging patterns of rapid transmission in specific population groups, such as PWID, who, in 2015–2016, comprised only 1% of people in such molecular clusters. These data can guide efforts to focus, tailor, and scale up prevention and care services for these populations.

Background: New-onset diabetes mellitus (DM) and severe metabolic complications in association with COVID-19 has been reported in the literature. Studies indicate a bidirectional relationship between COVID-19 and DM. Not only does severe DM lead to an increased risk for COVID-19 complications, but COVID-19 infection itself may precipitate new-onset DM. Clinical Case: A 45-year-old male with no known past medical history and normal body mass index presented after being found unresponsive at home. One week prior to admission, he tested positive for SARS-CoV-2 virus. On admission, laboratory evaluation showed: serum glucose 1090 mg/dl [70–109 mg/dL], anion gap 31 [<12], serum sodium 159 meq/L [133–145 meq/L], serum bicarbonate 18 meq/L [23–30 meq/L], creatinine 2.9 mg/dL [0.7–1.2 mg/dL], serum osmolality 438 mosm/k [280–295 mosm/k], venous pH 7.29 [7.32–7.42], venous bicarbonate 20 mmol/L [24–28 mmol/L], lactic acid 5.0 mmol/L [0.5–2.2 mmol/L], serum acetone positive 1+, urine ketone 20, hemoglobin 16.1 g/dL [14–18.0 g/dL] and HbA1c 13.5% [4.8–5.9%]. A diagnosis of diabetes with hyperosmolarity was made and he was admitted to the medical intensive care unit for treatment. Rapid resolution of hyperglycemia and hyperosmolarity was achieved with insulin infusion and intravenous fluids. He was transitioned to subcutaneous insulin on hospital day 2 and glycemic control was maintained using a basal/bolus insulin regimen. However, he experienced a prolonged two-month hospitalization due to complications including acute respiratory distress syndrome requiring mechanical ventilation and tracheostomy placement, pleural effusions with need for chest tube placement, and acute renal failure requiring short-term hemodialysis support. He was discharged to a rehabilitation facility on insulin glargine 15 units daily. Two-months after discharge, no weight changes were noted. Insulin was discontinued due to fasting serum glucose around 100 mg/dL and HbA1c 5.9%. Six-weeks later, a random serum glucose was 135 mg/dL and HbA1c 6.6%. He remains off glucose-lowering medications to date. Conclusion: We report an interesting case of new-onset diabetes with hyperosmolarity associated with COVID-19 infection with rapid achievement of euglycemia upon resolution of viral infection. Our case adds to growing evidence demonstrating a possible diabetogenic effect due to COVID-19 infection. There is also a complex interplay between SARS-CoV-2 virus and DM leading to a higher risk for complications. Questions remain regarding the long-term effects of COVID-19 on glucose metabolism. Patients with similar clinical presentations warrant close follow-up since it may be possible to de-escalate or discontinue hypoglycemic agents.

BackgroundCoronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients.MethodsIn an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge.ResultsFrom October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05).ConclusionIn this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

Traumatic spinal cord injury （SCI） is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI （n = 9）, sham surgery （n = 8）, or no surgery （n = 8）. Spinal cord and brain tissues were fixed and cut at six regions of the neuroaxis. Immunohistochem- istry showed increased reactivity of neural progenitor cell marker nestin in the central canal at all levels of the spinal cord. Increased reactivity of astrocyte-specific marker glial fibrillary acidic protein was found only at the lesion epicenter. The number of activated microglia was significantly increased at the lesion site, and activated microglia extended to the lumbar enlargement. Phagocytic microglia and macrophages were significantly increased only at the lesion site. There were no changes in nestin, glial fibrillary acidic protein, microglia and macrophage response in the third ventricle of rats subjected to mild-contusion thoracic SCI compared to the sham surgery or no surgery. These findings indicate that neural progenitor cells, astrocytes and microglia respond differently to a localized SCI, presumably due to differences in inflammatory signaling. These different cellular responses may have implications in the way that neural progenitor cells can be manipulated for neuroregeneration after SCI. This needs to be further investigated.