Disseminated Intravascular Coagulation in Acute Promyelocytic Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals

Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.

Castleman disease- demographics, associations, and outcomes: an analysis of adult 791 cases.

BACKGROUND: Castleman disease (CD), also known as angiofollicular lymph node hyperplasia or large lymph node hyperplasia, is a rare medical condition. Despite its rarity, it exhibits diverse clinical presentations and outcomes, which pose challenges for comprehensive understanding and management. This study aims to shed light on the demographics, associations, and outcomes of CD by conducting a retrospective analysis. METHODS: The National Inpatient Sample (US) was used to identify patients with the diagnosis of Castleman disease using ICD-10 diagnosis code D47.Z2, during the years 2016-2019. Data was collected on demographics, associated diagnoses, treatments and outcomes. Data analysis was performed using STATA Version 17, College Station, TX: Stata Corp LLC. RESULTS: Our study identified 791 hospitalizations involving adult CD patients. The mean age of these patients was 52.4 years, with a male predominance (56.1%). Whites comprised the largest racial group affected (50.1%). Most patients were covered by Medicare (39.6%). The majority received treatment in urban teaching hospitals (84.0%) and large-bed size facilities (62.5%). In-hospital mortality was low at 2.8%, with an average length of stay of 7.5 days and average total charges of $109,308. Common associations included acute kidney injury (27.0%), congestive heart failure (17.1%), sepsis (16.4%), and acute respiratory failure (12.6%). Hematological and lymphatic associations featured anemia (47.5%), thrombocytopenia (12.2%), and other conditions. Red blood cell transfusions were administered to 11.1% of patients. CONCLUSION: This study contributes valuable insights into CD, a rare and clinically heterogeneous disease. It underscores the importance of recognizing its associations and complications. Additionally, it highlights the need for further research and improved diagnostic and treatment guidelines to address the complexity of this condition.

Cytokine Release Syndrome in Patients Treated With Chimeric Antigen Receptor T-cell Therapy: A Retrospective Study Analyzing Risks, Outcomes, and Healthcare Burden.

Background Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapy for various malignancies. However, its use is associated with challenges, including cytokine release syndrome (CRS), a potentially severe complication. This retrospective study aims to analyze the risks, outcomes, and healthcare burden of CRS in patients undergoing CAR-T therapy. Method Data from the 2020 National Inpatient Sample (NIS) were utilized, comprising 415 CAR-T-related hospitalizations. They were categorized into those with CRS (n = 68) and those without CRS (n = 347). Baseline characteristics, including age, gender, race, income, insurance status, and comorbidities, were compared. Outcomes of interest included in-hospital mortality, length of stay (LOS), total hospital charges, and access to complications, associations, and interventions. Statistical analyses, including multivariable models, were employed to assess associations. Results Hospitalizations with CRS did not exhibit significant differences in age, gender, race, income, or insurance status compared to those without CRS. The multivariable analysis showed no statistically significant difference in mortality (adjusted odds ratio (aOR) = 2.48, 95% confidence interval (CI): 0.71 to 8.69, p = 0.151), LOS (coefficient = -2.1 days, 95% CI: -5.43 to 1.21, p = 0.207), or total hospital charges (coefficient = $207,456, 95% CI: $6119 to $421,031, p = 0.057) between the two groups. The CRS group had a higher incidence of fever (aOR = 1.91, 95% CI: 1.15 to 3.17, p = 0.014), acute respiratory failure (aOR = 2.10, 95% CI: 1.01 to 4.40, p= 0.049), and the need for intubation/mechanical ventilation (aOR = 2.59, 95% CI: 1.14 to 5.88, p = 0.024). Hemophagocytic lymphohistiocytosis (HLH) was significantly associated with CRS (aOR = 6.72, 95% CI: 2.03 to 22.18, p = 0.002). Conclusion While the development of CRS in CAR-T-treated patients did not significantly increase mortality, LOS, or total hospital charges, it was associated with specific risks and outcomes, including fever, respiratory failure, and HLH. This study emphasizes the importance of vigilance in recognizing and managing CRS in CAR-T therapy to optimize patient outcomes. The findings contribute valuable insights to guide clinical decision-making in the context of CAR-T therapy.

Peribronchiolar Metaplasia: A Marker of Cigarette Smoke-Induced Small Airway Injury in a Rural Cohort.

Background: Peribronchiolar metaplasia (PBM) is considered a reaction to injury characterized by the proliferation of bronchiolar epithelium into immediately adjacent alveolar walls. While an association of PBM with diffuse interstitial lung diseases has been recognized, the clinical significance of PBM remains uncertain. Methods: A cohort (n = 352) undergoing surgical resection of a lung nodule/mass in a rural area was retrospectively reviewed. Multivariate logistic regression analysis was performed to determine the association of PBM with clinical, physiological, radiographic, and histologic endpoints. Results: In the total study cohort, 9.1% were observed to have PBM as a histologic finding in resected lung tissue (n = 32). All but one of these patients with PBM were ever-smokers with a median of 42 pack years. Clinical COPD was diagnosed in two-thirds of patients with PBM. Comorbid gastroesophageal reflux disease (GERD) was significantly associated with PBM. All patients with PBM demonstrated radiologic and histologic evidence of emphysema. Measures of pulmonary function were not impacted by PBM. Mortality was not associated with the histologic observation of PBM. In a logistic regression model, centrilobular-ground glass opacity interstitial lung abnormality and traction bronchiectasis on the CT scan of the chest and histologic evidence of fibrosis, desquamative interstitial pneumonia and anthracosis all strongly predicted PBM in the cohort. Conclusion: A constellation of radiologic and histologic smoking-related abnormalities predicted PBM in study cohort. This confirms a co-existence of lung tissue responses to smoking including PBM, emphysema, and fibrosis. Acknowledging the physiologically "silent" nature of small airway dysfunction on pulmonary function testing, our findings support PBM as a histologic marker of small-airway injury associated with cigarette smoking.

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.

Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38). Twenty-four of 61 (39%) ICB-treated patients who subsequently underwent surveillance colonoscopy had premalignant polyps. Within matched pre-ICB and post-ICB follow-up periods, the overall rate of tumor development was unchanged; however, on subgroup analysis, a decreased incidence of post-ICB visceral tumors was observed. These data suggest that ICB treatment of LS-associated tumors does not eliminate risk of new neoplasia development, and LS-specific surveillance strategies should continue. These data have implications for immunopreventative strategies and provide insight into the immunobiology of dMMR tumors.

Cigarette Smoking, and Blood Monocyte Count Correlate with Chronic Lung Injuries and Mortality.

Background: Cigarette smoking (CS)-related monocytosis contributes to the development of chronic lung injuries via complex mechanisms. We aim to determine correlations between measures of CS and monocytes, their capacities to predict chronic lung diseases, and their associations with mortality. Methods: A single-center retrospective study of patients undergoing surgical resection for suspected lung nodules/masses was performed. CS was quantified as cigarettes smoked per day (CPD), duration of smoking, composite pack years (CPY), current smoking status, and smoking cessation years. A multivariate logistic regression analysis was performed. Results: Of 382 eligible patients, 88% were ever smokers. In this group, 45% were current smokers with mean CPD of 27.2±40.0. CPY and duration of smoking showed positive linear correlations with percentage monocyte count. Physiologically, CPY was associated with progressive obstruction, hyperinflation, and reduced diffusion capacity (DLCO). Across the quartiles of smoking, there was an accumulation of radiologic and histologic abnormalities. Anthracosis and emphysema were associated with CPD, while lung cancer, respiratory bronchiolitis (RB), emphysema, and honeycombing were statistically related to duration of smoking. Analysis using consecutive CPY showed associations with lung cancer (≥10 and <30), fibrosis (≥20 and <40), RB (≥50), anthracosis and emphysema (≥10 and onwards). Percentage monocytes correlated with organizing pneumonia (OP), fibrosis, and emphysema. The greater CPY increased mortality across the groups. Significant predictors of mortality included percentage monocyte, anemia, GERD, and reduced DLCO. Conclusion: Indices of CS and greater monocyte numbers were associated with endpoints of chronic lung disease suggesting a participation in pathogenesis. Application of these easily available metrics may support a chronology of CS-induced chronic lung injuries. While a relative lesser amount of smoking can be associated with lung cancer and fibrosis, greater CPY increases the risk for emphysema. Monocytosis predicted lung fibrosis and mortality. Duration of smoking may serve as a better marker of monocytosis and associated chronic lung diseases.

Trends in genital ulcer disease: An observational study at a tertiary care teaching hospital.

Introduction: Genital ulcer disease (GUD) often creates diagnostic difficulty in developing countries like India, with limited resources available in the health-care system. The changing etiology in GUDs over the years makes it imperative that a correct diagnosis is made to establish appropriate treatment and formulate awareness programs. Aims: This study was done to determine the recent trends in the demographic parameters, clinical presentations, etiology of GUDs, and their association with human immunodeficiency virus (HIV). Materials and Methods: An observational cross-sectional study was conducted from October 2021 to August 2022 at the Dermatology Outpatient Department in our hospital. All the patients who presented with GUDs were included after written informed consent. The diagnosis of GUD was confirmed by thorough clinical examination and appropriate laboratory test. Data were entered and analyzed using IBM SPSS software. Results: Out of 135 cases of GUDs, the majority were males (79%). The most common age group was 21-30 years, with a mean age of 35.23 ± 14.98 years. Most of the patients were heterosexual (90%). Multiple sexual partners were found in 40% of cases. Herpes genitalis was the most common GUD (59%), followed by syphilis (15%). HIV infection was found in 6.6% of cases. Conclusion: This study represents the increasing burden of viral GUDs compared to the last three decades. The ulcerative sexually transmitted infection facilitates the transmission of HIV. In this HIV era, there is a need for increased efforts toward acknowledgment, safe sexual practices, periodic screening, and sexual health awareness programs in the high-risk population.

The Spectrum of Cutaneous Adverse Drug Reactions Following the Application of Topical Medications: An Observational Study at a Tertiary Care Center.

Introduction Topical medications are one of the most commonly used therapeutic agents in treating a wide spectrum of dermatological diseases. The misuse of topical medicines for inappropriate indications and an extended period may result in cutaneous adverse drug reactions (ADR). Aims We conducted this study to observe demographic parameters, commonly misused topical medicines, various clinical patterns of cutaneous ADR, and source of drug prescription among study participants. Materials and methods This cross-sectional observational study was conducted from October 2021 to May 2022 at the dermatology outpatient department (OPD) of a tertiary care center. All patients who presented with worsening pre-existing skin diseases or the development of skin disease after the topical application of some cream or ointment were included in the study with written informed consent. A detailed history was taken, and a clinical examination was done. Results We detected 200 cases (1.62%) of cutaneous ADR out of 12,346 OPD patients in the eight-month study period. The most common age group was 21-30 years (30%). Most of the patients had used topical medicines for fungal infections (76%). The most commonly used topical medication was a fixed drug combination (FDC) of steroid, antifungal, and antibacterial agents (40%). Tinea incognito (36%) was the most common cutaneous ADR noted. Conclusion This study shows that misuse of topical medications is rampant in our community because of their free and easy availability. There is an urgent requirement for strict regulations over the manufacturing, sales, and marketing of over-the-counter (OTC) topical medications to reduce the incidence of cutaneous ADR.

Interstitial lung abnormalities and interstitial lung diseases associated with cigarette smoking in a rural cohort undergoing surgical resection.

BACKGROUND: Cigarette smoking is a risk factor for interstitial lung abnormalities (ILAs) and interstitial lung diseases (ILDs). Investigation defining the relationships between ILAs/ILDs and clinical, radiographic, and pathologic findings in smokers have been incomplete. Employing a cohort undergoing surgical resection for lung nodules/masses, we (1) define the prevalence of ILAs/ILDs, (2) delineate their clinical, radiographic and pathologic predictors, and (3) determine their associations with mortality. METHODS: Patients undergoing resection of lung nodules/masses between 2017 and 2020 at a rural Appalachian, tertiary medical center were retrospectively investigated. Predictors for ILAs/ILDs and mortality were assessed using multivariate logistic regression analysis. RESULTS: In the total study cohort of 352 patients, radiographic ILAs and ILDs were observed in 35.2% and 17.6%, respectively. Among ILA patterns, subpleural reticular changes (14.8%), non-emphysematous cysts, centrilobular (CL) ground glass opacities (GGOs) (8% each), and mixed CL-GGO and subpleural reticular changes (7.4%) were common. ILD patterns included combined pulmonary fibrosis emphysema (CPFE) (3.1%), respiratory bronchiolitis (RB)-ILD (3.1%), organizing pneumonitis (2.8%) and unclassifiable (4.8%). The group with radiographic ILAs/ILDs had a significantly higher proportion of ever smokers (49% vs. 39.9%), pack years of smoking (44.57 ± 36.21 vs. 34.96 ± 26.22), clinical comorbidities of COPD (35% vs. 26.5%) and mildly reduced diffusion capacity (% predicated 66.29 ± 20.55 vs. 71.84 ± 23). Radiographic centrilobular and paraseptal emphysema (40% vs. 22.2% and 17.6% vs. 9.6%, respectively) and isolated traction bronchiectasis (10.2% vs. 4.2%) were associated with ILAs/ILDs. Pathological variables of emphysema (34.9% vs. 18.5%), any fibrosis (15.9% vs. 4.6%), peribronchiolar metaplasia (PBM, 8% vs. 1.1%), RB (10.3% vs. 2.5%), and anthracosis (21.6% vs. 14.5%) were associated with ILAs/ILDs. Histologic emphysema showed positive correlations with any fibrosis, RB, anthracosis and ≥ 30 pack year of smoking. The group with ILAs/ILDs had significantly higher mortality (9.1% vs. 2.2%, OR 4.13, [95% CI of 1.84-9.25]). CONCLUSIONS: In a rural cohort undergoing surgical resection, radiographic subclinical ILAs/ILDs patterns were highly prevalent and associated with ever smoking and intensity of smoking. The presence of radiographic ILA/ILD patterns and isolated honeycomb changes were associated with increased mortality. Subclinical ILAs/ILDs and histologic fibrosis correlated with clinical COPD as well as radiographic and pathologic emphysema emphasizing the co-existence of these pulmonary injuries in a heavily smoking population.

Early age of onset and broad cancer spectrum persist in MSH6- and PMS2-associated Lynch syndrome.

PURPOSE: This study aimed to characterize MSH6/PMS2-associated mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) tumors, given revised guidelines suggesting more modest phenotypes. METHODS: Patients who consented to Institutional Review Board-approved protocols of tumor/germline sequencing or Lynch syndrome registry at a single institution from February 2005 to January 2021 with germline, heterozygous MSH6/PMS2 pathogenic/likely pathogenic variants were identified. Clinical data were abstracted and correlated with MMR/microsatellite instability status using nonparametric tests. RESULTS: We identified 243 patients (133 sequencing, 110 registry) with germline MSH6/PMS2 pathogenic/likely pathogenic variants; 186 (77%) had >1 cancer. Of 261 pooled tumors, colorectal cancer (CRC) and endometrial cancer (EC) comprised 55% and 43% of cancers in MSH6 and PMS2, respectively; 192 tumors underwent molecular assessments and 122 (64%) were MMR-D/MSI-H (77 in MSH6, 45 in PMS2). MMR-D/MSI-H cancers included CRC (n = 56), EC (n = 35), small bowel cancer (n = 6), ovarian cancer (n = 6), urothelial cancer (n = 5), pancreas/biliary cancer (n = 4), gastric/esophageal cancer (n = 3), nonmelanoma skin tumors (n = 3), prostate cancer (n = 2), breast cancer (n = 1), and central nervous system/brain cancer (n = 1). Among MMR-D/MSI-H CRC and EC, median age of diagnosis was 51.5 (range = 27-80) and 55 (range = 39-74) years, respectively; 9 of 56 (16%) MMR-D/MSI-H CRCs were diagnosed at age <35 years. CONCLUSION: MSH6/PMS2 heterozygotes remain at risk for a broad spectrum of cancers, with 16% of MMR-D/MSI-H CRCs presenting before upper threshold of initiation of colonoscopy per guidelines.

MusicCohort: Pilot feasibility of a protocol to assess students' physical and mental health in a Canadian post-secondary school of music.

OBJECTIVE: Music-related physical and mental health conditions are common among post-secondary music students, with many studies reporting a prevalence greater than 70%. However, there is currently no consensus on appropriate, validated assessments for this population. The aim of this pilot study was to test the feasibility of an assessment protocol developed for a German longitudinal study with Canadian post-secondary music students, and to compare the health of music students to non-music students. Using a cross-sectional design, first-semester music and non-music control students were recruited at two campuses at the same university. Both groups completed questionnaires and physical testing, including range of motion, core strength, and pressure pain threshold. Nineteen music students and 50 non-music student controls participated in this study. RESULTS: The German protocol is feasible in a Canadian post-secondary setting. Canadian music students demonstrated similar health outcomes to those in the parent study. All participants demonstrated poorer mental and physical quality of life than the Canadian norms, though this was not statistically significant. The results of this study should be confirmed in a larger study. Future studies with larger sample sizes can provide further insight into the health of Canadian music students, providing a basis for prevention and intervention.

Cement pulmonary embolism after percutaneous kyphoplasty: An unusual culprit for non-thrombotic pulmonary embolism.

Non-thrombotic pulmonary embolism can occur from rare but diverse etiology and is not well understood. Increasing prevalence of osteoporosis in the aging population has contributed to increased utilization of percutaneous vertebral augmentation procedures of vertebroplasty and its recent modification, kyphoplasty. Though these procedures are relatively well tolerated, there is risk of potentially fatal complication of bone cement embolization to distant vasculature. We report a case of symptomatic pulmonary cement emboli developed 2 day's post kyphoplasty and its successful treatment with novel anticoagulant for 6 months. We also summarize evidence to assist clinicians and radiologists for early identification, treatment, and prevention of cement pulmonary emboli.

A primary solitary vascular tumor of calcaneum: case report and review of literature.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with metastatic potential and estimated prevalence of less than one case per million. Among the musculoskeletal system, the long bones are commonly involved with approximately half patients experiencing multicentric involvement. Clinical course of EHE is often variable and nonspecific. Poorly demarcated osteolytic lesions are most commonly seen radiologically. Diagnostic confirmation is usually obtained by biopsy and histopathological exam, including immunostaining for endothelial markers. We present a rare case of unicentric EHE involving the calcaneum. Our patient had an indolent course of disease after surgical resection and no recurrence in seven years on clinical and radiological surveillance.

Prevalence and Characterization of Biallelic and Monoallelic NTHL1 and MSH3 Variant Carriers From a Pan-Cancer Patient Population.

NTHL1 and MSH3 have been implicated as autosomal recessive cancer predisposition genes. Although individuals with biallelic NTHL1 and MSH3 pathogenic variants (PVs) have increased cancer and polyposis risk, risks for monoallelic carriers are uncertain. We sought to assess the prevalence and characterize NTHL1 and MSH3 from a large pan-cancer patient population. MATERIALS AND METHODS: Patients with pan-cancer (n = 11,081) underwent matched tumor-normal sequencing with consent for germline analysis. Medical records and tumors were reviewed and analyzed. Prevalence of PVs was compared with reference controls (Genome Aggregation Database). RESULTS: NTHL1-PVs were identified in 40 patients including 39 monoallelic carriers (39/11,081 = 0.35%) and one with biallelic variants (1/11,081 = 0.009%) and a diagnosis of isolated early-onset breast cancer. NTHL1-associated mutational signature 30 was identified in the tumors of the biallelic patient and two carriers. Colonic polyposis was not identified in any NTHL1 patient. MSH3-PVs were identified in 13 patients, including 12 monoallelic carriers (12/11,081 = 0.11%) and one with biallelic MSH3 variants (1/11,081 = 0.009%) and diagnoses of later-onset cancers, attenuated polyposis, and abnormal MSH3-protein expression. Of the 12 MSH3 carriers, two had early-onset cancer diagnoses with tumor loss of heterozygosity of the wild-type MSH3 allele. Ancestry-specific burden tests demonstrated that NTHL1 and MSH3 prevalence was not significantly different in this pan-cancer population versus controls. CONCLUSION: NTHL1 and MSH3 germline alterations were not enriched in this pan-cancer patient population. However, tumor-specific findings, such as mutational signature 30 and loss of heterozygosity of the wild-type allele, suggest the potential contribution of monoallelic variants to tumorigenesis in a subset of patients.

Outcomes of Idiopathic Pulmonary Fibrosis Improve with Obesity: A Rural Appalachian Experience.

OBJECTIVES: Obesity can be an independent predictor of fibrosis in tissues, including the liver, heart, and skin. We evaluated a rural Appalachian cohort of idiopathic pulmonary fibrosis (IPF) for its relation to obesity. METHODS: Using American Thoracic Society 2018 diagnostic guidelines, an IPF cohort was systematically identified at an Appalachian academic medical center (2015-2019). The cohort was categorized in subgroups of body mass index (BMI) <30 or BMI ≥30 kg/m2. Demographics, clinical variables, and treatment details were collected retrospectively and evaluated for their associations with obesity. RESULTS: In our IPF cohort (N = 138), a usual interstitial pneumonia pattern was less prevalent in the obese group (n = 49) relative to the nonobese group (69% vs 85%, respectively). The obese group was younger (mean age 73.27 ± 9.12 vs 77.97 ± 9.59 years) and had a higher prevalence of hypertension (90% vs 72%), hyperlipidemia (83% vs 68%), diabetes mellitus (47% vs 25%), sleep-disordered breathing (47% vs 25%), chronic pain disorders (28% vs 15%), and deep vein thrombosis (19% vs 7%). An increased proportion of obese-IPF patients was seen at a tertiary or an interstitial lung disease center, with more surgical lung biopsies performed and incident diagnosis (ie, within 6 months of presentation) assigned. Only a minority of patients underwent lung transplantation (3.6%), all of them from the obese-IPF subgroup. Approximately 30% of the total IPF cohort died, with a lower mortality observed in the obese group (35% vs 20%, P = 0.017). An increasing BMI predicted a better survival in the total IPF cohort (BMI 25-29.9, 20-24.9, and <20 had mortality rates of 20%, 47%, and 75%, respectively; P < 0.001). CONCLUSIONS: Our study represents a first known effort to develop an IPF cohort in a rural Appalachian region. Although they shared an increased burden of comorbidities, the obese subgroup showed less advanced fibrosis with a lower mortality rate relative to nonobese subgroup, suggesting a potential "obesity paradox" in IPF. The study findings significantly advance our understanding of challenges posed by IPF in a rural population that also suffers from an alarming rate of obesity. We highlight the need for the multidisciplinary management of these patients and prospective studies to better define this complex relation.

Combined Pulmonary Fibrosis Emphysema: Role of Cigarette Smoking and Pulmonary Hypertension in a Rural Cohort.

Background: Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations. Objective: To describe combined pulmonary fibrosis emphysema (CPFE) phenotype in a rural Appalachian IPF cohort with the highest smoking rates in the United States. Methods: CPFE patients (n = 60) in a developed IPF cohort (n = 153) were characterized. Groups (CPFE vs IPF without emphysema) were categorized based on the predominant HRCT patterns of UIP (n = 109). Demographics, clinical variables, and treatment details were recorded. Kaplan-Meier survival and multivariate logistic regression analysis were performed. Results: The prevalence of CPFE in our IPF cohort was 45% (n = 49). The CPFE group was younger (73.9 vs 78.2), had a more extensive smoking history (93.9% vs 53.3%) with greater mean smoking pack years (49.09 vs 15.39) and had lower percentage predicted DLCO on presentation (38.35 vs 51.09) compared to IPF without emphysema group. Both groups shared equivalent higher burden of comorbidities, including pulmonary hypertension (PH) (46.9% vs 33.3%). One-fifth of patients were prescribed antifibrotics and only a subset (5%) of patients underwent lung transplantation. There was a non-significant trend towards reduced survival in CPFE (p = 0.076). Smoking status and DLCO predicted CPFE in our cohort. Body mass index (BMI), PH, and pirfenidone use were significant predictors of mortality. Conclusion: CPFE was highly prevalent in our rural IPF cohort. In contrast to previous studies, CPFE group was older and had higher female (approx. 30%) occurrence. A greater exposure to cigarette smoke and reduced DLCO at diagnosis predicted CPFE. Lower BMI and PH predicted higher mortality whereas use of pirfenidone improved survival in our cohort. This study highlights a complex interaction of cigarette smoking, advanced fibrosis of UIP, PH and potential utility of antifibrotic agents in CPFE phenotype. Substantial burden of comorbidities, older age, and the limited utilization of advanced therapeutics in the cohort emphasize the challenges faced by rural Appalachian patients.

Appendicitis in an incisional hernia sac following renal transplantation: A case report and brief review of the literature.

Acute appendicitis is a surgical emergency. However, the presence of vermiform appendix in a hernial sac is rare. It is even rarer to find inflamed appendix in an hernial sac. The most common site is right groin hernia (Inguinal > Femoral). There is low incidence of an incisional hernia following renal transplantation, as compared to patients with laparotomy. Appendicitis in hernial sac masquerades clinical presentation of an incarcerated hernia. Computed tomography plays a pivotal role in early diagnosis, demonstrating a dilated appendix with wall thickening and peri-appendiceal fat stranding. Patients are managed with appendectomy. The management of appendiceal hernias without inflammation remains controversial, with few reported cases managed with hernia sac repair or appendectomy. In this report were described a case of appendicitis in an incisional hernia following renal transplantation which was managed with appendectomy.

Characterization and Clinical Outcomes of DNA Mismatch Repair-deficient Small Bowel Adenocarcinoma.

PURPOSE: The prevalence and clinical characteristics of small bowel adenocarcinomas (SBA) in the setting of Lynch syndrome have not been well studied. We characterized SBA according to DNA mismatch repair and/or microsatellite instability (MMR/MSI) and germline mutation status and compared clinical outcomes. EXPERIMENTAL DESIGN: A single-institution review identified 100 SBAs. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via IHC staining. Germline DNA was analyzed for mutations in known cancer predisposition genes, including MMR (MLH1, MSH2, MSH6, PMS2, and EPCAM). Clinical variables were correlated with MMR/MSI status. RESULTS: Twenty-six percent (26/100; 95% confidence interval, 18.4-35.4) of SBAs exhibited MMR deficiency (MMR-D). Lynch syndrome prevalence was 10% overall and 38.5% among MMR-D SBAs. Median age at SBA diagnosis was similar in non-Lynch syndrome MMR-D versus MMR-proficient (MMR-P) SBAs (65 vs. 61; P = 0.75), but significantly younger in Lynch syndrome (47.5 vs. 61; P = 0.03). The prevalence of synchronous/metachronous cancers was 9% (6/67) in MMR-P versus 34.6% (9/26) in MMR-D SBA, with 66.7% (6/9) of these in Lynch syndrome (P = 0.0002). In the MMR-P group, 52.2% (35/67) of patients presented with metastatic disease, compared with 23.1% (6/26) in the MMR-D group (P = 0.008). In MMR-P stage I/II patients, 88.2% (15/17) recurred, compared with 18.2% (2/11) in the MMR-D group (P = 0.0002). CONCLUSIONS: When compared with MMR-P SBA, MMR-D SBA was associated with earlier stage disease and lower recurrence rates, similar to observations in colorectal cancer. With a 38.5% prevalence in MMR-D SBA, germline Lynch syndrome testing in MMR-D SBA is warranted.

Nasal congestion and nasal obstruction: An unusual presentation of renal cell carcinoma.

Renal cell cancer (RCC) is among the 10 most common cancers affecting both genders in the United States. Advanced RCC often remains clinically silent for much of its natural history. This can make the diagnosis challenging, especially when presenting symptoms arise from a metastasis. Sinonasal malignancies are rare, accounting for <1% of all malignant tumors and 3% of malignant tumors of the upper aerodigestive tract. RCC is the most common infraclavicular malignant primary tumor that metastasizes to the nasal cavity and paranasal sinus, followed by breast and lung. We describe a case of a 59 year-old male presenting with nasal congestion and allergy-like symptoms for 6 months duration. CT examination revealed a large hyper-vascular mass within the right maxillary and ethmoid sinuses and nasal cavity. Primary RCC was recognized only after surgical removal of sinonasal mass. We discuss the epidemiology, clinical presentation, differential diagnosis, imaging, pathology, and treatment for sinonasal RCC.