Penetrance and outcomes at 1-year following return of actionable variants identified by genome sequencing.

PURPOSE: We estimated penetrance of actionable genetic variants and assessed near-term outcomes following return of results (RoR). METHODS: Participants (n = 2,535) with hypercholesterolemia and/or colon polyps underwent targeted sequencing of 68 genes and 14 single-nucleotide variants. Penetrance was estimated based on presence of relevant traits in the electronic health record (EHR). Outcomes occurring within 1-year of RoR were ascertained by EHR review. Analyses were stratified by tier 1 and non-tier 1 disorders. RESULTS: Actionable findings were present in 122 individuals and results were disclosed to 98. The average penetrance for tier 1 disorder variants (67%; n = 58 individuals) was higher than in non-tier 1 variants (46.5%; n = 58 individuals). After excluding 45 individuals (decedents, nonresponders, known genetic diagnoses, mosaicism), ≥1 outcomes were noted in 83% of 77 participants following RoR; 78% had a process outcome (referral to a specialist, new testing, surveillance initiated); 68% had an intermediate outcome (new test finding or diagnosis); 19% had a clinical outcome (therapy modified, risk reduction surgery). Risk reduction surgery occurred more often in participants with tier 1 than those with non-tier 1 variants. CONCLUSION: Relevant phenotypic traits were observed in 57% whereas a clinical outcome occurred in 19% of participants with actionable genomic variants in the year following RoR.

Incidence and outcomes of prosthetic valve endocarditis in adults with tetralogy of Fallot.

BACKGROUND: The risk of endocarditis varies with CHD complexity and the presence of prosthetic valves. The purpose of the study was therefore to describe incidence and outcomes of prosthetic valve endocarditis in adults with repair tetralogy of Fallot. METHODS: Retrospective review of adult tetralogy of Fallot patients who underwent prosthetic valve implantation, 1990-2017. We defined prosthetic valve endocarditis-related complications as prosthetic valve dysfunction, perivalvular extension of infection such abscess/aneurysm/fistula, heart block, pulmonary/systemic embolic events, recurrent endocarditis, and death due to sepsis. RESULTS: A total of 338 patients (age: 37 ± 15 years) received 352 prosthetic valves (pulmonary [n = 308, 88%], tricuspid [n = 13, 4%], mitral [n = 9, 3%], and aortic position [n = 22, 6%]). The annual incidence of prosthetic valve endocarditis was 0.4%. There were 12 prosthetic valve endocarditis-related complications in six patients, and these complications were prosthetic valve dysfunction (n = 4), systemic/pulmonary embolic events (n = 2), heart block (n = 1), aortic root abscess (n = 1), recurrent endocarditis (n = 2), and death due to sepsis (n = 1). Three (50%) patients required surgery at 2 days, 6 weeks, and 23 weeks from the time of prosthetic valve endocarditis diagnosis. Altogether three of the six (50%) patients died, and one of these deaths was due to sepsis. CONCLUSIONS: The incidence, complication rate, and outcomes of prosthetic valve endocarditis in tetralogy of Fallot patients underscore some of the risks of having a prosthetic valve. It is important to educate the patients on the need for early presentation if they develop systemic symptoms, have a high index of suspicion for prosthetic valve endocarditis, and adopt a multi-disciplinary care approach in this high-risk population.

Impact of atrial arrhythmia on survival in adults with tetralogy of Fallot.

BACKGROUND: Atrial arrhythmia is a late complication after tetralogy of Fallot (TOF) repair, but arrhythmia outcomes data are limited. OBJECTIVES: The purpose of the study was to describe atrial arrhythmia presentations, outcomes of antiarrhythmic therapy, and impact of arrhythmia on transplant-free survival. METHODS: We reviewed the MACHD (Mayo Adult Congenital Heart Disease) Registry and identified 113 patients (age 49 ±â€¯13 years) with documented arrhythmia, and 302 patients without history of arrhythmia, 1990-2017. We classified arrhythmias into atrial fibrillation and atrial flutter/tachycardia based on the rhythm on the first abnormal electrocardiogram. RESULTS: At the time of first documented arrhythmia, 58(51%) had atrial fibrillation while 55(49%) had atrial flutter/tachycardia. Of the 113 patients, 14(12%) received rhythm control with class I/III antiarrhythmic drugs (AAD), 79(70%) had direct current cardioversion, 9(8%) received rate control with class II/IV AAD, and 11(10%) received only anticoagulation. Successful cardioversion occurred in 100(89%) patients, and arrhythmia recurrence rate was 16 per 100 patient-years. The multivariate risk factors for death and/or heart transplant were atrial fibrillation (HR 1.94, CI 1.10-3.15, P = .031) and older age (HR 1.63, CI 1.12-2.43, P = .019) per 5 year increment. CONCLUSIONS: Atrial fibrillation, but not atrial flutter, was associated with reduced survival in our repaired TOF cohort. Further studies are required to determine if more aggressive antiarrhythmic therapy will improve survival in patients with atrial fibrillation.

Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease.

A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.

Prevalence and in-hospital mortality during arrhythmia-related admissions in adults with tetralogy of Fallot.

BACKGROUND: Although outcomes of arrhythmia diagnosis have been described in ambulatory tetralogy of Fallot (TOF) patients, these have not been studied in hospitalized patients. The purpose of this study was to determine the prevalence and in-hospital mortality due to arrhythmias in TOF patients based on a review of the National Inpatient Sample database. METHODS: Admissions in adult TOF patients (2000-2014) were categorized as arrhythmia-related admission (ARA) or non-arrhythmia-related admission (NRA) based on arrhythmia diagnostic codes. RESULTS: Of 18,353 admissions, 5071 (27.6%) were ARA. The most common arrhythmias were atrial fibrillation (15.5%), atrial flutter (8.4%) and ventricular tachycardia (8.2%), and the prevalence of overall ARA as well as specific arrhythmia types increased over time. In-hospital mortality for ARA was 5.4%, and decreased over time. Arrhythmia diagnosis was an independent predictor of in-hospital mortality (odds ratio [OR] 1.63, 1.34-2.01, p = 0.001). Similarly, atrial fibrillation (OR 1.49, 1.18-1.89, p = 0.001) and ventricular tachycardia (OR: 2.01, 1.55-2.98, p = 0.001) were independent predictors of in-hospital mortality. Compared to small bed-size hospital, ARA in large hospital bed-size hospital was associated with a lower in-hospital mortality (OR 0.71, 0.53-0.96, p = 0.03). CONCLUSION: Atrial fibrillation was the most common arrhythmia in hospitalized TOF patients, and arrhythmia diagnosis (specifically atrial fibrillation and ventricular tachycardia) was an independent predictor of in-hospital mortality, while admission to a large bed-size hospital was associated with a lower risk of in-hospital mortality. Further studies are required to determine if a more proactive approach to arrhythmia management in the ambulatory TOF population will reduce hospitalizations and mortality.

Pseudogout: An Autoimmune Paraneoplastic Manifestation of Myelodysplastic Syndrome.

Myelodysplastic syndrome (MDS) is often associated with autoimmune paraneoplastic manifestations. Seronegative arthritis is among one of them. Very rarely, pseudogout demonstrated as paraneoplastic autoimmune manifestations of MDS has been adumbrated so far. Our case would be the another addition in the series. Our patient is an 83-year-old male lately diagnosed with MDS. After six months of initial diagnosis, he had a sudden onset episode of pain and swelling involving left wrist. Synovial fluid analysis from respective radiocarpal joint confirmed the presence of intracellular positively birefringent rhomboid shaped crystals of calcium pyrophosphate dihydrate (CPPD). This was followed by another two flares of pseudogout involving right knee and lumbar spine at separate time intervals. Each of the episodes mentioned above responded well to intravenous and oral steroids. After the third bout, he was started treatment with azacitidine which showed effective abatement of further episodes of pseudogout up until now.

Gastrointestinal Neuroendocrine Tumor, Colon Adenocarcinoma, and Hyperparathyroidism: An Unorthodox Synchronism.

Synchrony of colorectal adenocarcinoma with neuroendocrine tumor (NET) and hyperparathyroidism with colon adenocarcinoma is a rare entity, reported in a handful of cases. We authors would like to report a rare case of coexistence of poorly differentiated colon adenocarcinoma, NET of appendix and hyperparathyroidism. A 43-year-old Caucasian female was diagnosed with metastatic colon adenocarcinoma involving the caecum and appendiceal orifice. The resected specimen also confirmed presence of concurrent well-differentiated NET in distal half of appendix. For this patient, serum chemistry was significant for severe hypercalcemia with elevated parathyroid hormone and fairly normal range parathyroid hormone-related peptide. Importantly, association among the aforementioned conditions remains elusive and warrants further research; nevertheless, surveillance procedures could be performed in patients, if a correlation exists at all.

Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of HLA-Matched Related Donors.

Haploidentical stem cell transplantation provides a plausible alternative for the patients when a fully matched donor is unavailable. Historically, the decision of considering haploidentical transplant has remained elusive; however, with the recent advances, the consideration of haploidentical grafts as a treatment option has become more apparent for both allografting for diseases and engraftment failure. We are reporting here an anecdotal case of a successful haploidentical engraftment in a patient with the prior graft failure of an HLA-matched related donor. Since the patient was severely alloimmunized, desensitization protocol was utilized before the haploidentical transplant, and the patient after 8 months of her second allogeneic transplantation is doing great with successful engraftment, no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent to haploidentical graft have shown favorable outcomes in the graft placement, a decline in the rate of GVHD, and an improvement in the morbidity and mortality in affected individuals. Based on the current reports, haploidentical transplantation might be more feasible and has meaningful implications in the situations where matched donors are infrequent.