Unusual painful pelvic masses: Extramedullary hematopoiesis with extramedullary multiple myeloma.

The coexistence of extramedullary hematopoiesis and extramedullary multiple myeloma can occur and present as painful pelvic masses. In such a case, normal hematopoietic cells may outnumber clonal plasma cells, posing a diagnostic challenge.

Impact of Body Composition on Esophagogastric Junction Opening Measures: Discordant FLIP and Manometric Findings Are More Common With Increased Body Mass Index.

INTRODUCTION: Increased intra-abdominal pressure in patients with elevated body mass index (BMI) may affect measurements of esophagogastric junction (EGJ) opening. METHODS: Findings from adult patients who underwent both impedance planimetry with functional luminal imaging probe (FLIP) and high-resolution manometry (HRM) were compared by BMI. RESULTS: Among patients with no EGJ outflow obstruction on HRM, abnormal EGJ classifications on FLIP were more common among those with elevated than normal BMI (61.1% vs 31.6%, P = 0.037). DISCUSSION: Discordant results between FLIP and HRM on EGJ opening are more common in patients with elevated BMI. Body composition may impact EGJ function and measures on current testing modalities.

The Impact of Gastroesophageal Reflux Disease and Proton Pump Inhibitor Use on the Risk of Repeat Catheter Ablation for Atrial Fibrillation.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has been associated with increased incidence/recurrence of atrial fibrillation (AF). However, the impact of GERD and proton pump inhibitor (PPI) therapy on outcomes of AF catheter ablation remains unclear. We aimed to assess the association between the presence of GERD and risk of repeat AF ablation, stratified by PPI therapy. METHODS: A retrospective cohort study was conducted on patients with paroxysmal/persistent AF undergoing initial ablation in January 2011-September 2015. GERD was defined by endoscopic findings, objective reflux testing, or clinical symptoms. The association between GERD/PPI use and time to repeat ablation was evaluated by time-to-event analysis with censoring at the last clinic follow-up within 1 year. RESULTS: Three hundred eighty-one subjects were included. Patients with GERD (n = 80) had a higher 1-year repeat ablation rate compared with those with no GERD (25% vs 11.3%, P = 0.0034). Stratifying by PPI use, patients with untreated GERD (37.5%) more likely needed repeat ablation compared with reflux-free (11.3%, P = 0.0003) and treated GERD (16.7%, P = 0.035) subjects. On multivariable Cox regression analyses, GERD was an independent risk factor of repeat ablation (hazard ratio [HR] 3.30, confidence interval [CI] 1.79-6.08, P = 0.0001). Specifically, untreated GERD was associated with earlier repeat ablation compared with no GERD (HR 4.02, CI 1.62-12.05, P = 0.0013). However, no significant difference in repeat ablation risk was noted between reflux-free and PPI-treated GERD groups. DISCUSSION: GERD was an independent predictor for risk of repeat AF ablation within 1 year, even after controlling for major cardiovascular comorbidities and confounders. PPI therapy modulated this risk, as repeat ablation-free survival for PPI-treated GERD was noninferior to reflux-free patients.

Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

Unexpected coccidioidomycosis presenting as lung nodules with presumptive diagnosis of malignancy.

Coccidioidomycosis can present as fluorodeoxyglucose (FDG) avid lung nodules which may be mistaken as relapse in patients with a history of malignancy. Detailed clinical history, relevant laboratory testing, and/or tissue biopsy with histologic evaluation are necessary for correct diagnosis.

Diffuse large B-cell lymphoma presenting as postmenopausal bleeding.

Key Clinical Message: Endometrial lymphoma is a rare etiology of abnormal uterine bleeding and endometrial thickening, and often shares similar clinical and imaging characteristics with other uterine malignancies such as endometrial carcinoma. Chemotherapy appears adequate for treating primary endometrial lymphoma. Abstract: We report a case of primary endometrial diffuse large B-cell lymphoma to increase awareness of this condition which is essential for correct diagnosis and treatment.

The burden of nonalcoholic steatohepatitis (NASH) in the United States.

BACKGROUND: There is limited data on the comparative economic and humanistic burden of non-alcoholic steatohepatitis (NASH) in the United States. The objective was to examine the burden of disease comparing NASH to a representative sample of the general population and separately to a type 2 diabetes mellitus (T2DM) cohort by assessing health-related quality of life (HRQoL) measures, healthcare resource use (HRU) and work productivity and activity impairment (WPAI). METHODS: Data came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey conducted in the United States. Respondents with physician-diagnosed NASH, physician-diagnosed T2DM, and respondents from the general population were compared. Humanistic burden was examined with mental (MCS) and physical (PCS) component summary scores from the Short-Form (SF)-36v2, concomitant diagnosis of anxiety, depression, and sleep difficulties. Economic burden was analysed based on healthcare professional (HCP) and emergency room (ER) visits, hospitalizations in the past six months; absenteeism, presenteeism, overall work impairment, and activity impairment scores on WPAI questionnaire. Bivariate and multivariable analysis were conducted for each outcome and matched comparative group. RESULTS: After adjusting for baseline demographics and characteristics, NASH (N = 136) compared to the matched general population cohort (N = 544), reported significantly lower (worse) mental (MCS 43.19 vs. 46.22, p = 0.010) and physical (PCS 42.04 vs. 47.10, p < 0.001) status, higher % with anxiety (37.5% vs 25.5%, p = 0.006) and depression (43.4% vs 30.1%, p = 0.004), more HCP visits (8.43 vs. 5.17), ER visits (0.73 vs. 0.38), and hospitalizations (0.43 vs. 0.2) all p's < 0.05, and higher WPAI scores (e.g. overall work impairment 39.64% vs. 26.19%, p = 0.011). NASH cohort did not differ from matched T2DM cohort (N = 272) on mental or work-related WPAI scores, but had significantly worse physical status (PCS 40.52 vs. 44.58, p = 0.001), higher % with anxiety (39.9% vs 27.8%, p = 0.043), more HCP visits (8.63 vs. 5.68, p = 0.003) and greater activity impairment (47.14% vs. 36.07%, p = 0.010). CONCLUSION: This real-world study suggests that burden of disease is higher for all outcomes assessed among NASH compared to matched general controls. When comparing to T2DM, NASH cohort has comparable mental and work-related impairment but worse physical status, daily activities impairment and more HRU.

The Cost of Diagnosing and Managing Non-alcoholic Steatohepatitis in Europe and the United States.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is acknowledged as a severe disease that is associated with a significant burden on patients, payers, and society. However, limited evidence exists on the cost associated with NASH across different countries. This analysis aims to describe the cost associated with the routine care of patients with NASH in France, Germany, and the United States. METHODS: Data was sourced from the Gesellschaft für Konsumforschung (now Ipsos) Disease Atlas Real- World Evidence program collected from July through November 2017 in France, Germany, and the United States. Country-level unit cost was estimated from national databases for diagnostic tests and procedures, prescription drugs, hospital stays, and outpatient visits in respective local currency based on 2017 values. These were combined to provide an estimate of the cost of management of confirmed NASH in this specific patient population and are presented as mean cost per patient per year for each country in local currency and as USD adjusted for purchasing power parity for comparison. RESULTS: Annual mean ± standard deviation cost of non-alcoholic steatohepatitis ranged from purchasing power parity USD 1,049±2,461 in Germany to USD 1,723±2,988 in the United States. In all markets, the predominant contributor to cost is healthcare resource use represented by hospitalisation and outpatient visits. CONCLUSIONS: This study reveals that costs associated with NASH treatment and management vary across the three countries studied, in part due to differences in healthcare systems but also due to different approaches in managing this disease. Our analysis represents the costs for a specific cohort of patients and further studies are warranted to better understand the progressive impact of NASH on healthcare systems and society.

Conventional Karyotyping and Fluorescence In Situ Hybridization for Detection of Chromosomal Abnormalities in Multiple Myeloma.

Background: Multiple myeloma (MM) is a genetically heterogeneous disease, with cytogenetic findings that determine disease behavior. Genetic abnormalities can be assessed by fluorescence in situ hybridization (FISH) analysis and/or G-banded karyotyping. The two methods produce unique and overlapping information, and the clinical utility of using both is investigated here. Methods: Seventy patients diagnosed with MM at a hospital in Southern California were retrospectively reviewed for the FISH and G-banded karyotyping results obtained from bone marrow specimens. Results: Karyotype was normal in 71% (50/70), abnormal in 27% (19/70), and inadequate in 1% (1/70). Among patients with abnormal karyotype, FISH provided additional information about genetic aberrations in 95% of cases (18/19). Among cases with abnormal FISH, karyotype provided additional information about genetic aberrations in 27% of cases (18/66). When numerical abnormalities were present (detected by FISH and/or karyotype), FISH detected them in 95% (54/57), of which karyotype missed 70% (38/54) of the time. Karyotyping detected numerical abnormalities in 33% (19/57), which FISH missed 16% (3/19) of the time. Conclusions: Karyotyping and FISH analysis in MM each provide unique information. For most patients, performing both tests together will provide more information than either test alone.

Symptoms classically attributed to laryngopharyngeal reflux correlate poorly with pharyngeal reflux events on multichannel intraluminal impedance testing.

Laryngopharyngeal reflux (LPR) is thought to be a common etiology of throat and airway symptoms. Diagnosis of LPR is challenging, given the variable symptomatology and response to therapy. Identifying symptoms that better correlate with LPR may inform management strategies. We aimed to examine the association between patient-reported symptoms and objectively identified LPR on ambulatory reflux monitoring. This was a retrospective cohort study of consecutive adults with suspected LPR undergoing combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing (HEMII-pH) at a tertiary center. All patients completed standardized symptom surveys for presenting symptoms, reflux symptom index (RSI), and voice handicap index (VHI). LPR was defined as >1 full-column pharyngeal reflux event on HEMII-pH over 24 hours. Univariate and multivariable analyses were performed. A total of 133 patients were included (mean age = 55.9 years, 69.9% female). Of this 83 (62.4%) reported concomitant esophageal symptoms. RSI and VHI did not correlate with proximal esophageal or pharyngeal reflux events (Kendall's tau correlations P > 0.05), although the mean RSI was higher in the LPR group (21.1 ± 18.9 vs. 17.1 ± 8.3, P = 0.044). Cough, but not other laryngeal symptoms, was more common among patients with esophageal symptoms (58% vs. 36%, P = 0.014). Neither laryngeal symptoms nor esophageal symptoms of reflux predicted LPR on univariate or multivariable analyses (all P > 0.05). Neither laryngeal symptoms classically attributed to LPR nor typical esophageal symptoms correlated with pharyngeal reflux events on HEMII-pH. Clinical symptoms alone are not sufficient to make an LPR diagnosis. Broad evaluation for competing differential diagnoses and objective reflux monitoring should be considered in patients with suspected LPR symptoms.

Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors.

BACKGROUND: Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI. METHODS: We identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model. RESULTS: A total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30-2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44-0.88; P = 0.008). CONCLUSIONS: ICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival. PRECIS: Thyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes.

Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation.

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Eating and Psychiatric Disorders Are Independent Risk Factors for Rumination Syndrome.

GOAL: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS). BACKGROUND: RS is a disorder of gut-brain interaction characterized by an effortless postprandial retrograde flow of ingested contents. Disorder of gut-brain interactions have been associated with psychiatric and behavioral comorbidities. No prior comparative study has assessed the relationship between RS and ED or PD. METHODS: This was a case-control study of adults with RS at a tertiary center in January 2013 to January 2018. Two age-matched/gender-matched controls per RS case were identified. The Fisher exact test (categorical)/Student t test (continuous) and forward stepwise logistic regression were performed for univariate and multivariable analyses, respectively. RESULTS: Seventy-two patients (24 cases/48 controls) were included. Baseline demographics and characteristics were similar between cases and controls. Among RS patients, 9 (37.5%) had a history of ED, including 3 (12.5%) anorexia nervosa and 4 (16.7%) bulimia nervosa; and 20 (83.3%) had a PD, including 9 (37.5%) anxiety and 7 (29.2%) depression. Prevalence of ED (37.5% vs. 4.2%, P=0.0002) and PD (83.3% vs. 50.0%, P=0.0062) were higher among RS patients than controls. Specifically, the risks of anorexia nervosa (16.7% vs. 0%, P=0.005) and bulimia nervosa (21.1% vs. 0%, P=0.001) were both increased in RS patients. On multivariable analysis, ED (adjusted odds ratio=16.4, P=0.0033) and PD (adjusted odds ratio=4.47, P=0.029) remained independent predictors for RS. CONCLUSIONS: A history of ED and PD were independent risk factors for RS. Abnormal eating behaviors and psychiatric comorbidities may contribute to the pathogenesis of RS. Evaluation of RS should include a detailed history for ED and PD.

Impaired Proximal Esophageal Contractility Predicts Pharyngeal Reflux in Patients With Laryngopharyngeal Reflux Symptoms.

OBJECTIVES: The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics. METHODS: We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed. RESULTS: We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69-0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42-0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (ß = -0.0094, P = 0.03) and total reflux events (ß = -0.0172, P = 0.05), after adjusting for confounders. DISCUSSION: Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder.

Abnormal eosinophils with immature eosinophilic granules in chronic myeloid leukemia in accelerated phase.

Abnormal eosinophils with immature eosinophilic granules are typically observed in acute myeloid leukemia with inv (16) (p13.1q22) or t (16;16) (p13.1;q22) but can also be seen in chronic myeloid leukemia without inv (16) or t (16;16).