Scripps Green Hospital

Despite advances in guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction, challenges with uptitration may delay optimal treatment. Cardiac resynchronization therapy (CRT) improves clinical outcomes, yet optimal sequencing of CRT and GDMT remains uncertain. We sought to characterize longitudinal GDMT titration and evaluate associations between CRT timing and outcomes among US patients. A retrospective cohort study of 6334 Medicare beneficiaries with an identifiable incident HF diagnosis who will receive CRT between 2018 and 2022. Early CRT was defined as implantation within 1 year of diagnosis. Medication use was assessed by medication possession ratios of ≥0.8 in quarterly intervals. Outcomes were compared using propensity score overlap-weighted models. GDMT uptake increased sharply after the incident HF diagnosis but plateaued quickly with consistent medication use remaining low. Early CRT (n = 3777) was associated with lower adjusted risk of composite all-cause death or HF exacerbation (hazard ratio 0.80, 95% confidence interval [CI] 0.72-0.89), all-cause death alone (hazard ratio 0.79, 95% CI 0.69-0.90), and fewer HF exacerbations (incident rate ratio 0.66, 95% CI 0.58-0.75) vs late CRT (n = 2557). Early CRT was also associated with lower inpatient and emergency department use, Medicare expenditures, and HF-related out-of-pocket costs after CRT implant. Early CRT was associated with lower mortality, fewer HF exacerbations, and lower health care use, supporting reconsideration of GDMT and CRT treatment sequencing.

Hypercalcemia may be induced by a variety of etiologies, most commonly primary hyperparathyroidism. Although primary hyperparathyroidism represents a relatively common endocrinological disorder, ectopic PTH secretion is a rare entity that is less well described in literature. We describe the first case to our knowledge of severe, symptomatic hypercalcemia found to be secondary to a PTH-secreting pancreatoblastoma. The patient initially presented with fatigue and progressive upper extremity intermittent muscular twitching. He was found to have biochemical evidence of primary hyperparathyroidism. A computed tomography scan of the neck and a sestamibi nuclear scan failed to definitively demonstrate a parathyroid adenoma or hyperplasia and bilateral surgical parathyroid exploration was unrevealing for any pathology. Abdominal imaging via computed tomography was obtained for evaluation of progressive postoperative epigastric pain, and the patient was found to have a retroperitoneal mass that, after biopsy, was diagnostic for a pancreatoblastoma. This mass was resected resulting in a fall in intraoperative PTH values and subsequent postoperative hypocalcemia secondary to hungry bone syndrome. Upon follow-up, the patient's parathyroid function recovered and doses of supplemental calcium and vitamin D could be tapered. Ectopic PTH-secreting masses represent a rare entity but should be considered in individuals with unclear etiology of recalcitrant primary hyperparathyroidism.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic caused numerous disruptions to routine healthcare maintenance. Specifically, there have been significant delays in scheduling screening colonoscopies secondary to staff shortages and temporary facility closures, resulting in reductions in colonoscopy volume. This reduction is in part due to colonoscopies being listed as an elective medical procedure that should be delayed by The US Surgeon General in March 2020. The delay in screening colonoscopies is further compounded by the increased demand due to new guidelines set forth by the United States Preventative Task Force to start screening colonoscopies at age 45 (previously at age 50). Based on a predictive model of current trends in colonoscopy and breast cancer screenings, it is anticipated that the incidence of colorectal cancer (CRC) may experience an upward trajectory over the next decade. Methods: This single-center retrospective cohort study examined the rates of screening colonoscopy procedures performed in patients between the ages of 45-80 years old during the 1-year interval before the pandemic (March 15, 2019-March 14, 2020) and during the pandemic (March 15, 2020-March 14, 2021). 11,587 patients were screened based on inclusion criteria and were excluded based on history of inflammatory bowel disease, family history of colon cancer, Lynch syndrome, familial adenomatous polyposis, juvenile polyposis syndrome, colonoscopies for evaluation of change in bowel habits or stool caliber, and evaluation of iron deficiency anemia. Results: The total number of elective colonoscopies during COVID-19 was 2,258 compared to 3,729 before COVID-19, indicating a decreased rate of 3.2% (P < 0.001). In a subgroup analysis, there were higher rates of White people getting procedures in the pre-COVID-19 group (75.5% vs 73.2%) and there were higher rates of other non-White races in the post-COVID-19 group (11.1% vs 9.5%, P =0.013). There was no difference in number of colorectal cancer diagnoses before COVID-19 compared to during COVID-19 (127 vs 89, P =0.539). In addition, there was no difference in polyp detection rate before or during COVID-19 except for those detected in the transverse colon (Table 1). Conclusion: The decrease in rates of elective colonoscopies during COVID-19 is consistent with the national trend of COVID-19 pandemic disruption in colon cancer screening. This finding stresses the importance of developing quality improvement initiatives to drive recovery of endoscopic volume to pre-pandemic levels. Table 1. - Colonoscopy findings before and during COVID-19 pandemic Before COVID-19 During COVID-19 P-value Number of colorectal cancer diagnosed, n (%) 127 (1.8%) 89 (2.0%) 0.539 Location, n (%) Appendix 1 (0.0%) 4 (0.1%) 0.081 Cecum 47 (0.7%) 37 (0.8%) 0.359 Ascending colon 82 (1.2%) 52 (1.1%) 0.929 Transverse colon 54 (0.8%) 54 (1.2%) 0.021 Rectum 23 (0.3%) 19 (0.4%) 0.421 Rectalsigmoid junction 8 (0.1%) 5 (0.1%) 0.958 Sigmoid Colon 53 (0.8%) 33 (0.7%) 0.877 Anus and anal canal 4 (0.1%) 1 (0.0%) 0.655 Other 133 (1.9%) 82 (1.8%) 0.752

Introduction: Eosinophilic esophagitis (EoE) is a progressive, allergen-mediated chronic disease that results in fibrostenotic EoE. EoE patients present with symptoms of esophageal dysfunction, e.g., dysphagia and food impaction. More serious and rare EoE complications may include esophageal dissection, esophageal rupture, and upper gastrointestinal bleeding. Herein, we present a case of spontaneous hematemesis in a healthy young man as a rare initial presentation of EoE. Case Description/Methods: Patient is a healthy 33-year-old man with intermittent heartburn who presented to the emergency room (ER) elsewhere with acute onset of intense heartburn, nausea without vomiting or retching, and several episodes of hematemesis with bright red blood after ingesting food. Lab studies showed stable hemoglobin 13.1 g/dL, platelet 181 K/mcL and INR 1.0. Computed tomography imaging was unrevealing except for distal esophageal wall thickening. Given clinical stability, patient was treated empirically with a proton-pump inhibitor (PPi), fluid resuscitated, and discharged with urgent outpatient evaluation. Further history obtained in the clinic revealed chronic dysphagia to solid food and pills. Esophagogastroduodenoscopy (EGD) at ∼2 weeks after the ER visit showed a severely narrowed proximal esophagus. Ultra-thin gastroscopy demonstrated a narrow-caliber esophagus with a proximal stricture, edema, diffuse linear furrows, and diffuse esophageal rings. Careful inspection showed an area of healing linear mucosal tear proximally, which likely represents recent spontaneous esophageal stretching and injury, causing hematemesis. Esophageal biopsies showed >50 eosinophils/hpf, confirming the diagnosis of EoE. Post-EGD, he was managed with high-dose PPi twice daily and milk/dairy elimination per patient’s preference. On follow-up EGD, endoscopic severity persisted with no histologic response. He was treated with Savary dilation to 30-French. Discussions of step-up EoE therapy with topical corticosteroids or biologic therapy are ongoing. Discussion: Spontaneous hematemesis from mucosal injury related to food bolus dilation of a narrowed esophagus is a rare complication of fibrostenotic EoE. Our patient received a new diagnosis of EoE, with spontaneous hematemesis as his initial presentation, having had previously unrecognized symptoms of chronic dysphagia. EoE is rising rapidly in both incidence and prevalence. This case highlights the importance of prompt recognition and treatment of EoE to prevent future complications.

Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for “all-comers” (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.

T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection.

BackgroundPublished studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer.MethodsThe primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity‐related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity‐related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high‐density lipoprotein (HDL)‐cholesterol, low‐density lipoprotein (LDL)‐cholesterol, and non‐HDL‐cholesterol. Outcomes were all cause, cancer‐specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables.ResultsAmong women with obesity‐related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05–10 years). LDL‐C values above the 95th percentile were associated with higher risk of all‐cause mortality (p < 0.001), and cancer‐specific mortality (p < 0.001), but not mortality due to CVD. Non‐HDL‐C values above the 65th percentile were associated with higher risk of all‐cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer‐specific mortality (p = 0.37). HDL‐C values above the 95th percentile were associated with lower all‐cause mortality (p = 0.002), and above the 65th percentile with lower cancer‐specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed.ConclusionsThe relationship between pre‐diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti‐lipid medications could have a meaningful impact on outcomes after cancer.