Risk factors for adverse outcomes following paraesophageal hernia repair among obese patients.

BACKGROUND: Although obesity is an established risk factor for adverse outcomes after paraesophageal hernia repair (PEHR), many obese patients nonetheless receive PEHR. The purpose of this study was to explore risk factors for adverse outcomes of PEHR among this high-risk cohort. We hypothesized that obese patients may have other risk factors for adverse outcomes following PEHR. METHODS: A retrospective study of adult obese patients who underwent minimally invasive PEHR from 2017 to 2019 was performed. Patients were excluded for BMI < 30 or if they had concomitant bariatric surgery at time of PEHR. The primary outcome of interest was a composite adverse outcome (CAO) defined as having any of the four following outcomes after PEHR: persistent GERD > 30 d, persistent dysphagia > 30 d, recurrence, or reoperation. Chi-square and t-test analysis was used to compare demographic and clinical characteristics. Multivariable logistic regression analysis was used to evaluate independent predictors of CAO. RESULTS: In total, 139 patients met inclusion criteria with a median follow-up of 19.7 months (IQR 8.8-81). Among them, 51/139 (36.7%) patients had a CAO: 31/139 (22.4%) had persistent GERD, 20/139 (14.4%) had persistent dysphagia, 24/139 (17.3%) had recurrence, and 6/139 (4.3%) required reoperation. On unadjusted analysis, patients with a CAO were more likely to have a history of prior abdominal surgery (86.3% vs 70.5%, p = 0.04) and were less likely to have undergone a preoperative CT scan (27.5% vs 45.5%, p = 0.04). On multivariable analysis, previous abdominal surgery was independently associated with an increased likelihood of CAO whereas age and preoperative CT scan had a decreased likelihood of CAO. CONCLUSIONS: Although there were adverse outcomes among obese patients, minimally invasive PEHR may be feasible in a subset of patients at specialized centers. These findings may help guide the appropriate selection of obese patients for PEHR.

The evolving role of transplantation in multiple myeloma: the need for a heterogeneous approach to a heterogeneous disease.

Autologous stem cell transplant (ASCT) is an established frontline standard of care for the younger, fitter patients with newly diagnosed multiple myeloma (NDMM) who are eligible for the procedure, and has contributed to improved overall survival. In the current era of novel therapies, the treatment landscape and prognosis have changed. The outstanding efficacy seen with regimens based on novel agents has led to a questioning of the frontline treatment paradigm with respect to ASCT. A key current question is whether to use transplant early or to collect stem cells early but save ASCT for salvage therapy. In this review, we evaluate the clinical data for each approach as well as the arguments in favor of early or delayed ASCT. We also consider the clinical/clonal heterogeneity of myeloma and review the evidence regarding which patient subgroups may benefit most from each approach. We summarize current treatment guidelines for transplant-eligible patients with NDMM and review the evolving role of minimal residual disease evaluation and its potential effect on the debate over early vs delayed ASCT. We conclude that frontline ASCT remains a standard of care for a substantial proportion of patients; however, delayed/salvage ASCT is increasingly being used in the context of highly active frontline regimens based on novel agents and the ongoing personalization of myeloma treatment.

Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias.

BACKGROUND: Although dofetilide labeling states that the drug must be initiated or reinitiated with continuous electrocardiographic monitoring and in the presence of trained personnel, the risks of dofetilide reloading justifying repeat hospitalization have not been investigated. METHODS AND RESULTS: Patients admitted for dofetilide reloading for atrial arrhythmias were retrospectively reviewed. The need for dose adjustment and the incidence of torsades de pointes (TdP) were identified. The incidence of TdP in dofetilide reloading was compared with patients admitted for dofetilide initial loading. Of 138 patients admitted for dofetilide reloading for atrial arrhythmias, 102 were reloaded at a previously tolerated dose, 30 with a higher dose from a previously tolerated dose and 2 at a lower dose; prior dosage was unknown in 4 patients. Dose adjustment or discontinuation was required in 44 patients (31.9%). No TdP occurred in the same dose reloading group, but TdP occurred in 2 patients admitted to increase dofetilide dosage (0% versus 6.7%; P=0.050). Dofetilide dose adjustment or discontinuation was required in 30 of 102 patients (29.4%) reloaded at a previously tolerated dose and in 11 of 30 patients (36.7%) admitted for an increase in dose. CONCLUSIONS: Although no TdP occurred in patients admitted to reload dofetilide at the same dose as previously tolerated, dosage adjustments or discontinuation was frequent and support the need for hospitalization for dofetilide reloading. Patients admitted for reloading with a higher dose tended to be at higher risk for TdP than patients reloaded at a prior tolerated dose.

Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.

BACKGROUND: Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation, there is limited postapproval safety data in the atrial fibrillation population despite its known risk of Torsade de pointes (TdP). METHODS AND RESULTS: We conducted a retrospective chart review of a cohort of 1404 patients initially loaded on dofetilide for atrial fibrillation suppression at the Cleveland Clinic from 2008 to 2012 to evaluate the incidence and risk factors for in-hospital adverse events and the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (1 death), 5 had syncope/presyncope, and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) because of QTc prolongation or TdP. Variables correlated with TdP were (1) female sex, 2) 500-µg dose, (3) reduced ejection fraction, and (4) increase in QTc from baseline. One-year all-cause mortality was higher in patients who continued dofetilide compared with those who discontinued use (hazard ratio, 2.48; 95% confidence interval, 1.08-5.71; P=0.03). Those patients who had a TdP event had higher one-year all-cause mortality than those who did not (17.6% versus 3% at 1 year; P<0.001). CONCLUSIONS: Dofetilide loading has a low but finite risk of TdP and other adverse events that warrant the current Food and Drug Administration-mandated practice of inpatient monitoring during drug loading. In this cohort, all-cause mortality was higher at 1 year in those patients continued on dofetilide and in those patients who experienced TdP while loading.