Jejunal Perforation following Screening Colonoscopy

Colonoscopy is rarely associated with complications such as colonic perforation. Perforation of the small bowel is extremely rare, especially if the procedure is done without therapeutic interventions. Several factors are associated with this entity. Perforation of the ileum has been reported, but proximal jejunal perforation secondary to rupture of jejunal diverticulum during colonoscopy has not been reported. We present the case of an 88-year-old patient who developed abdominal pain after undergoing colonoscopy without any additional interventions. Urgent exploration revealed perforation of the proximal jejunum secondary to rupture of a jejunal diverticulum. No therapy or biopsies were undertaken during the colonoscopy, which are known predisposing factors

Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function

Bone marrow (BM) hematopoietic stem cells (HSCs) become dysfunctional during aging (i.e., they are increased in number but have an overall reduction in long-term repopulation potential and increased myeloid differentiation) compared with young HSCs, suggesting limited use of old donor BM cells for hematopoietic cell transplantation (HCT). BM cells reside in an in vivo hypoxic environment yet are evaluated after collection and processing in ambient air. We detected an increase in the number of both young and aged mouse BM HSCs collected and processed in 3% O2 compared with the number of young BM HSCs collected and processed in ambient air (~21% O2). Aged BM collected and processed under hypoxic conditions demonstrated enhanced engraftment capability during competitive transplantation analysis and contained more functional HSCs as determined by limiting dilution analysis. Importantly, the myeloid-to-lymphoid differentiation ratio of aged BM collected in 3% O2 was similar to that detected in young BM collected in ambient air or hypoxic conditions, consistent with the increased number of common lymphoid progenitors following collection under hypoxia. Enhanced functional activity and differentiation of old BM collected and processed in hypoxia correlated with reduced “stress” associated with ambient air BM collection and suggests that aged BM may be better and more efficiently used for HCT if collected and processed under hypoxia so that it is never exposed to ambient air O2

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Starvation ketoacidosis in patient with muscular dystrophy

Patients with Muscular Dystrophy have small muscle mass; thus, they have less glycogen stores, and therefore they are more prone to develop ketoacidosis with minimal stress or decreased oral intake. In our case we are presenting a rare presentation of ketoacidosis in a patient with muscular dystrophy, who was treated successfully with Lactated Ringer and Dextrose solution due to her concurrent hyperchloremic non-anion gap metabolic acidosis. Our Patient is forty-eight-year-old female with history of Muscular Dystrophy and Chronic Respiratory Failure dependent on Ventilator, she was referred to our hospital for evaluation of a granulation tissue in her Trachea. She was admitted and found to have non-AG metabolic Acidosis, VBG showed Ph of 7.23 Bicarbonate of 12, BMP showed Cr \u3c0.1, Chloride 114 (high), BMI 18, in addition to leukocytosis with WBC\u3e16000. Next day her labs showed Bicarbonate of 8, Ph of 7.29 and AG of 16 (Na 137, Cl 113), Albumin 4.2. We checked her Beta Hydroxybutyrate (BHB) which came back 6.6 (High). Due to her underlying Muscular Dystrophy and decrease oral intake, she was diagnosed with Starvation Ketoacidosis. Since she had a non-anion gap metabolic acidosis at the time of admission which was most likely secondary to Renal Tubular Acidosis, (Patient labs showed Hypokalemia, Urine AG of 30), we decided to start her on ringer lactate and dextrose solution. After 24 hours, her labs showed significant improvement and her BHB trended down and after 48 hours her labs have been normalized. Few cases have been reported regarding ketoacidosis in patients with muscular dystrophy, all reported cases were treated directly with dextrose and normal saline. In our case we used LR and D5% due to concurrent non anion gap metabolic acidosis which we believe it was due to RTA, in which giving normal saline (hgih Chloride content) will worsen the acidosis. HAGMA in patient with no diabetes and Muscular dystrophy should raise suspicion for Ketoacidosis. Treatment is with Dextrose and normal saline ususally. Using LR solurion sometime is better option in cases with concurrent hyperchloremic acidosis

Starvation ketoacidosis in patient with muscular dystrophy

Few treatment options are avaiable to delay renal replacement therapy for young patients with Type 2 Diabetes and eGFRs approaching End Stage Renal Disease. We describe an ongoing Phase II trial utilizing Neo-Kidney AugmentTM percutaneously injected into kidneys with Pre-Stage 5 T2DM CKD with intent to delay renal replacement therapy. REGEN-003 is a multi-center, non-randomized prospective, openlabel, single-arm study recruiting 10 patients (NCT03270956). Inclusion criteria include T2DM subjects age 30-65 years, eGFR 14 - 20 mL/min/1.73m3, and managed hypertension and HbA1c. Primary objective is safety of NKA injected in one recipient kidney and procedure and/or product related adverse events through 24 months. The method of renal NKA delivery is by real-time image guided percutaneous targeted injection into the subject\u27s kidney with small caliber atraumatic needles in an outpatient setting with moderate sedation. NKA is composed of expanded autologous homologous selected renal cells obtained by kidney biopsy. Trial completion is expected early 2020. Of 6 enrolled subjects to date, mean age is 55.8 years, 66.7% female, 50% Non-Hispanic/Latino. Baseline eGFR, serum creatinine and ACR are shown below. All 6 subjects have undergone renal biopsy, 4 have received injections. There have been no cell product or injection related adverse events to date. 1 subject developed a post biopsy hematoma however successfully underwent NKA injection. Biomarkers measured Baseline values (S.D.) Number eGFR (mean) 22.27 mL/min (7.99) 5 sCreatinine (mean) 3.14 (0.47) 5 ACR (geometric mean) 1391.0 mg/g (911.1) 3 This active Phase 2 trial of pre-stage 5 DKD using novel imaged guided percutaneous targeted autologous homologous cell injection into the kidney offers potential for preservation of renal function and delay of renal replacement therapy

Valued Life Activities, Smoking Cessation, and Mood in Post-Acute Coronary Syndrome Patients

PURPOSE: Continued engagement in valued life activities is a protective factor for depression and has been linked to readiness to quit smoking in medical populations, but has never been examined among Acute Coronary Syndrome (ACS) patients. The purpose of this study is to investigate relationships among valued life activities, mood, and smoking post-ACS. METHODS: Participants were 54 post-ACS patients who were smoking before ACS hospitalization. Data on mood, smoking status, engagement in valued activities, restriction of valued activities, and satisfactory replacement of restricted activities was collected 1-12 months post-ACS. RESULTS: Depressive symptoms were associated with both less valued activity engagement and greater valued activity restriction. Positive affect was associated with greater valued activity engagement and negative affect was associated with greater valued activity restriction. Satisfactory replacement of restricted activities was associated with greater positive affect, fewer depressive symptoms, and quitting smoking post-ACS. The majority of these relationships remained significant after controlling for relevant covariates, including physical functioning. CONCLUSIONS: Valued activity restriction and engagement may contribute to depressed mood and failure to quit smoking in ACS patients. Psychotherapies that target greater engagement in valued life activities deserve further investigation in ACS patients