Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Metabolic and Metabolomic Effects of Metformin in Murine Model of Pulmonary Adenoma Formation.

Epidemiologic studies of diabetic patients treated with metformin identified significantly lower incidences of cancer. From this, there is growing interest in the use of metformin to treat and prevent cancer. Studies have investigated chemopreventive mechanisms including alterations in calorie intake, cancer metabolism, and cell signaling. Repurposing the drug is challenging due to its metabolic effects and non-uniform effects on different types of cancer. In our previously published studies, we observed that benzo[a]pyrene treated mice receiving metformin significantly reduced lung adenomas; however, mice had reduced weight gain. In this study, we compared chemoprevention diets with and without metformin to evaluate the effects of diet vs. effects of metformin. We also performed tandem mass spectrometry on mouse serum to assess metabolomic alterations associated with metformin treatment. In metformin cohorts, the rate of weight gain was reduced, but weights did not vary between diets. There was no weight difference between diets without metformin. Interestingly, caloric intake was increased in metformin treated mice. Metabolomic analysis revealed metabolite alterations consistent with metformin treatment. Based on these results, we conclude that previous reductions in lung adenomas may have been occurred from anticancer effects of metformin rather than a potentially toxic effect such as calorie restriction.

Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Importance: In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients. Objective: To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up. Design, Setting, and Participants: This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data. Exposures: CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant. Main Outcomes and Measures: Composite of ventricular arrhythmic events and composite of heart failure events. Results: Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF. Conclusions and Relevance: This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

Observations of increased gastroesophageal reflux symptomology in an anhydrous ammonia exposed population.

OBJECTIVE: This case series describes a cohort of patients exposed to anhydrous ammonia vapors with clinical findings of laryngopharyngeal reflux (LPR). The study characterizes the identification of LPR as a consequence of vapor inhalation and the utility of PPI therapy in LPR secondary to inhalational ammonia exposure. METHODS: This is a case series of 15 patients exposed to anhydrous ammonia from a single chemical spill who experienced LPR several months after exposure. Symptoms of LPR were assessed at their initial consultation and by phone at least 30 days after treatment with low-dose PPI or diet modification. At this visit, patients underwent complete head and neck examination and flexible direct laryngoscopy. RESULTS: 15 patients were available for analysis before and after treatment. 93.3 % experienced at least three cardinal symptoms of LPR. 66 % of these patients had at least one LPR finding on flexible laryngoscopy. 73 % were treated with daily standard dose PPI, and 82 % of these patients experienced reduction of symptoms after 30 days of PPI treatment. Four of 15 patients were not taking the PPI as prescribed, and only one of these patients had resolution of LPR symptoms. CONCLUSION: We conclude that there is an association between anhydrous ammonia exposure and the development of LPR symptoms. In this study, treatment with PPIs was successful in reducing symptoms for most patients, and patients who did not receive PPIs experienced symptoms for a longer time.

Medical scribes improve documentation consistency and efficiency in an otolaryngology clinic.

OBJECTIVE: Scribes in medical practice enable more efficient documentation requirements but insufficient analyses have occurred to fully evaluate their efficacy in otolaryngology. We analyzed pre/post metrics of scribe implementation that may aid practitioners in determining feasibility for use in their practices. METHODS: 1808 patient charts were analyzed in The Epic Electronic Medical Record system (EMR) (903 pre and 905 post scribe implementation). We measured: clinic volumes, time saved in documentation, chart billing level, and lag days of chart closure. RESULTS: Patient volumes increased by 3.02% with an 11-17% decrease in time spent in clinic/day and lag days for billing. The distribution of visits for new patients was 17.75% level 2, 51.45% level 3, 29.71% level 4 before the scribe and was 6.83% level 2, 89.21% level 3, 3.96% level 4 after the scribe. For established patients it was 3.97% level 2, 84.92% level 3, 8.93% level 4 before and 0.34% level 2, 91.76% level 3, 7.73% level 4 after. The change in level of documentation for established and new patients pre and post scribe implementation was not statistically significant (p = 0.821, 0.063, respectively). Charts were closed within 0 to 7 days with the implementation of a scribe instead of 7-21 days when awaiting dictations for transcription. CONCLUSIONS: The implementation of a scribe in an academic otolaryngology clinic facilitated more rapid completion of documentation while decreasing provider hours/day in clinic. We feel the analysis can be generalized to otolaryngology practitioners in general and the data structures we implemented are usable for others.

Large cell neuroendocrine carcinoma originating in the subglottic larynx.

Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an exceedingly rare cancer of the head and neck that is difficult to diagnose. Few case reports of laryngeal LCNEC exist within the literature, and it was not until recently that LCNEC was recognized as a discrete subtype of neuroendocrine carcinoma. Given its recent recognition as a distinct subtype, histologic characteristics distinguishing LCNEC from other poorly differentiated carcinomas remain under investigation. Various reports have shown genetic alterations such as p53 and/or p16 overexpression, which are typically associated with infection by human papilloma virus (HPV). However, some reports have shown p53 and/or p16 overexpression in HPV negative samples. In this case, we discuss a 67-year-old patient with a history of extensive alcohol and tobacco use with a newly diagnosed T4N0M0, high grade, LCNEC of the subglottic larynx. Tumor pathology demonstrated positive staining for typical neuroendocrine (NE) markers like synaptophysin and chromogranin A; however, there was diffuse CK34ßE12 and p16 expression. LCNEC is a newly classified subtype of poorly differentiated neuroendocrine (NE) tumors, and the diagnosis requires consideration of the clinical presentation, microscopic features, and immunostaining markers.

Cerebrofacial vascular metameric syndrome is caused by somatic pathogenic variants in PIK3CA.

Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K-RAS-MAPK pathway (Padia et al., Laryngoscope Investig Otolaryngol 4: 170-173 [2019]). Activating pathogenic variants in the gene PIK3CA, which encodes for the catalytic subunit of phosphatidylinositol 3-kinase, are present in both lymphatic and venous malformations as well as arteriovenous malformations in other complex disorders such as CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal anevi, scoliosis) (Luks et al., Pediatr Dev Pathol 16: 51 [2013]; Luks et al., J Pediatr 166: 1048-1054.e1-5 [2015]; Al-Olabi et al., J Clin Invest 128: 1496-1508 [2018]). These vascular malformations are part of the PIK3CA-related overgrowth spectrum, a spectrum of entities that have regionalized disordered growth due to the presence of tissue-restricted postzygotic PIK3CA pathogenic variants (Keppler-Noreuil et al., Am J Med Genet A 167A: 287-295 [2015]). Cerebrofacial vascular metameric syndrome (CVMS; also described as cerebrofacial arteriovenous metameric syndrome, Bonnet-Dechaume-Blanc syndrome, and Wyburn-Mason syndrome) is the association of retinal, facial, and cerebral vascular malformations (Bhattacharya et al., Interv Neuroradiol 7: 5-17 [2001]; Krings et al., Neuroimaging Clin N Am 17: 245-258 [2007]). The segmental distribution, the presence of tissue overgrowth, and the absence of familial recurrence are all consistent with CVMS being caused by a postzygotic mutation, which has been hypothesized by previous authors (Brinjiki et al., Am J Neuroradiol 39: 2103-2107 [2018]). However, the genetic cause of CVMS has not yet been described. Here, we present three individuals with CVMS and mosaic activating pathogenic variants within the gene PIK3CA We propose that CVMS be recognized as part of the PIK3CA-related overgrowth spectrum, providing justification for future trials using pharmacologic PIK3CA inhibitors (e.g., alpelisib) for these difficult-to-treat patients.

Sex Differences in Patients With Suspected Cardiac Sarcoidosis Assessed by Cardiovascular Magnetic Resonance Imaging.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P=0.010) and palpitations (39.3% versus 26.1%; P=0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P=0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P=0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P=0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P=0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P=0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P=0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77­2.43]; P=0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

Acute-Onset Eosinophilic Gastroenteritis and Ascites Secondary to Occult Toxocariasis.

Eosinophilic gastroenteritis is a rare entity, and although usually idiopathic, it may arise from gastrointestinal infections. We report a case of a 33-year-old woman from Vietnam presenting with acute abdominal pain, new-onset eosinophilic ascites, peripheral eosinophilia, and a positive Toxocara antibody. The patient had no recent international travel, known animal host contact, or other toxocariasis risk factors. She was treated with ivermectin and mebendazole with complete resolution of symptoms. This case emphasizes the consideration of a broad differential for eosinophilic ascites, including atypical presentations of infectious pathogens.

New Diagnosis of AIDS Based on Salmonella enterica subsp. I (enterica) Enteritidis (A) Meningitis in a Previously Immunocompetent Adult in the United States.

Salmonella meningitis is a rare manifestation of meningitis typically presenting in neonates and the elderly. This infection typically associates with foodborne outbreaks in developing nations and AIDS-endemic regions. We report a case of a 19-year-old male presenting with altered mental status after 3-day absence from work at a Wisconsin tourist area. He was febrile, tachycardic, and tachypneic with a GCS of 8. The patient was intubated and a presumptive diagnosis of meningitis was made. Treatment was initiated with ceftriaxone, vancomycin, acyclovir, dexamethasone, and fluid resuscitation. A lumbar puncture showed cloudy CSF with Gram negative rods. He was admitted to the ICU. CSF culture confirmed Salmonella enterica subsp. I (enterica) Enteritidis (A). Based on this finding, a 4th-generation HIV antibody/p24 antigen test was sent. When this returned positive, a CD4 count was obtained and showed 3 cells/mm3, confirming AIDS. The patient ultimately received 38 days of ceftriaxone, was placed on elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya) for HIV/AIDS, and was discharged neurologically intact after a 44-day admission.