Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Insulin Edema Syndrome due to Rapid Glucose Correction in a Diabetic Patient

Edema resulting from the initiation of insulin therapy or intensification of glycemic control is a rare and under-recognized complication. In this report, we present a case of a 46-year-old patient with insulin-dependent diabetes mellitus (IDDM) who avoided insulin treatment due to associated peripheral edema. Though rare, this phenomenon is typically seen in patients with elevated glucose levels who are initiated on insulin treatment, resulting in rapid correction and tight control of glucose levels. The diagnosis of insulin-induced edema is made after other causes of acute edema are ruled out. Furthermore, in this case report, we will also discuss the postulated mechanisms for the edema-causing property of insulin

Carcinoid tumor causing ileoceccal intussusception in an adult patient

Introduction: Little is known about adult intussusception, but current evidence suggests that malignancy, polyps, and diverticula are usual etiologies. We present a case of adult ileoceccal intussusception secondary to carcinoid tumor. Case Presentation: A 53-year-old African American male presented with hematochezia and non-radiating constant left upper quadrant pain accompanied by nausea and vomiting. CT of the pelvis demonstrated a pathognomic ‘target’ sign, consistent with ileoceccal intussusception and early small bowel obstruction. Two years prior to this current presentation, the patient had experienced an episode of hematochezia for which he underwent colonoscopy and polypectomy, with subsequent pathology results negative for colon cancer. He denies diarrhea, constipation, weight loss, decreased appetite or skin flushing. Due to persistent symptoms of bowel obstruction, he underwent exploratory laparotomy. During the surgery a white-colored, chalky mass indicative of penetrating tumor was noted 13 cm proximal to the ileocecal valve. An extended right hemi-colectomy followed the discovery of the mass. Pathology showed a well-differentiated neuroendocrine tumor consistent with carcinoid tumor. Evaluation for metastatic disease using 5-HIAA and chromogranin A was unremarkable, and the resection of the right colon carcinoid tumor was felt to be curative. Conclusion: It is uncommon for adults to present with intussusception; in such cases, malignancy should be ruled out as an underlying cause. Carcinoid should be listed among the other secondary causes, which include inflammatory bowel disease, diverticulitis, polyps, scar tissue, adhesions, and lipomas. Abbreviation: CT (Computer tomography), 5-HIAA (5-hydroxyindole acetic acid), NCCN (National Comprehensive Cancer Network

Guillain‐Barre syndrome secondary to COVID‐19 infection: A case report

Abstract Guillain‐Barre syndrome (GBS) is a rare autoimmune disease that often manifests as a post‐viral complication. However, its association with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is unclear. We present a rare case of GBS secondary to COVID‐19 infection complicated by rapidly progressive sensorimotor deterioration resistant to plasma exchange therapy

A case of fatal disseminated adenovirus and drug‐resistant Pneumocystis pneumonia in a patient who received chemotherapy for mantle cell lymphoma

Abstract Adenovirus (ADV) may cause severe complications in hematopoietic stem cell transplant recipients, but disseminated ADV infections in patients who received chemotherapy alone for hematological malignancies are poorly understood due to the rarity of cases. Concomitant infection with Pneumocystis (PCP) is extremely rare. Despite being diagnostically challenging, a more specific workup needs to be initiated with a low threshold in patients who are exposed to agents with the potential to suppress T cells. We report a fatal case of disseminated ADV and drug‐resistant PCP pneumonia in a patient with mantle cell lymphoma who had only received combination chemotherapy. A 75‐year‐old man who was diagnosed with mantle cell lymphoma 10 months prior was admitted for mild hypoxic respiratory failure. Bendamustine, Rituximab, Cytarabine regimen had resulted in complete remission of his lymphoma, with the last cycle of chemotherapy administered 3 months prior to admission. CT of the chest revealed ground‐glass opacities concerning pneumonia. Initial laboratory tests were remarkable for mild leukopenia. The respiratory viral panel was only positive for ADV. He did not respond to empiric antibiotics for community‐acquired pneumonia and Trimethoprim / Sulfamethoxazole given later for positive Beta D Glucan (BDG) suggestive of Pneumocystis pneumonia. Then, he developed hemorrhagic cystitis, followed by liver and renal function derangement that prompted checking serum ADV viral load by polymerase chain reaction (PCR). This test took 1 week to return, with a viral load of 50, 000 copies/mL suggesting disseminated ADV infection. Despite initiation of Cidofovir, multi‐organ failure continued to progress, and the follow‐up viral load had doubled on Day 2. The patient passed away the same day shortly after transition to comfort care. T cell suppression seems to be a risk factor for disseminated ADV disease. Clinicians may need to maintain a low threshold to send serum quantitative ADV PCR when symptoms are not improved by antimicrobial treatment for more conventional infections in patients who received agents that are known to suppress T cells, such as Bendamustine

Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury.

We reported previously that neural progenitor cell (NPC) grafts form neural relays across sites of subacute spinal cord injury (SCI) and support functional recovery. Here, we examine whether NPC grafts after chronic delays also support recovery and whether intensive rehabilitation further enhances recovery. One month after severe bilateral cervical contusion, rats received daily intensive rehabilitation, NPC grafts, or both rehabilitation and grafts. Notably, only the combination of rehabilitation and grafting significantly improved functional recovery. Moreover, improved functional outcomes were associated with a rehabilitation-induced increase in host corticospinal axon regeneration into grafts. These findings identify a critical and synergistic role of rehabilitation and neural stem cell therapy in driving neural plasticity to support functional recovery after chronic and severe SCI

A successful case of extracorporeal membrane oxygenation for COVID-19: walking home without oxygen supplementation

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China in December 2019 and is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19). Approximately one-third of the patients with COVID-19 require intensive care unit (ICU) admission, and almost 30% of the patients develop acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is used as salvage therapy for severe ARDS. The role of ECMO in the treatment of COVID-19 remains unclear, although there is emerging evidence that this approach may be an effective salvage therapy for severe ARDS. Case Presentation: We present a case of a previously healthy 39-year-old Hispanic male who presented to the hospital with flu-like symptoms, including headache, fatigue, and myalgia for 8 days in late April 2020. He denied dyspnea on exertion. The patient’s symptoms progressed, resulting in pneumonia and acute respiratory distress syndrome (ARDS). The patient was managed with prone positioning, convalescent plasma and veno-venous extracorporeal membrane oxygenation (VV-ECMO) for 35 days. The patient successfully recovered and was able to ambulate independently and was discharged home from an acute care hospital without oxygen supplementation on hospital day 63. Conclusion: We present one of the first few documented cases of ECMO for severe ARDS due to COVID-19. After a prolonged hospital course requiring VV-ECMO, the patient was discharged home from an acute care hospital without oxygen requirement and ambulated independently, likely as a result of daily aggressive mobility-focused rehabilitation

Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder

PURPOSE: SRRM2 encodes the SRm300 protein, a splicing factor of the SR-related protein family characterized by its serine- and arginine-enriched domains. It promotes interactions between messenger RNA and the spliceosome catalytic machinery. This gene, predicted to be highly intolerant to loss of function (LoF) and very conserved through evolution, has not been previously reported in constitutive human disease. METHODS: Among the 1000 probands studied with developmental delay and intellectual disability in our database, we found 2 patients with de novo LoF variants in SRRM2. Additional families were identified through GeneMatcher. RESULTS: Here, we report on 22 patients with LoF variants in SRRM2 and provide a description of the phenotype. Molecular analysis identified 12 frameshift variants, 8 nonsense variants, and 2 microdeletions of 66 kb and 270 kb. The patients presented with a mild developmental delay, predominant speech delay, autistic or attention-deficit/hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight, and dysmorphic facial features. Intellectual disability was variable and mild when present. CONCLUSION: We established SRRM2 as a gene responsible for a rare neurodevelopmental disease