Non-celiac Enteropathy and Olmesartan: An Essential Consideration.

Emerging evidence has shed light on non-celiac causes of enteropathy in recent years, presenting a diagnostic challenge for clinicians. This study discusses the diagnostic challenges related to non-celiac enteropathy, specifically focusing on olmesartan-induced enteropathy (OIE). A 73-year-old lady presented to the emergency department with a six-month history of watery diarrhea exacerbated by food intake and significant weight loss. The patient at admission was found to be dehydrated with severe hypokalemia and hypocalcemia. The extensive testing that was performed was unremarkable, including celiac disease panel, enteric panel, ova and parasites, Clostridium difficile, fecal calprotectin, and computed tomography of the abdomen and pelvis. A significant electrolyte imbalance was corrected at admission, and subsequent upper endoscopy investigation with duodenal biopsies revealed moderate to severe villi blunting with a significant intraepithelial infiltrate of CD3+ lymphocytes. A colonoscopy that was performed at the same time was unremarkable, with negative biopsies for microscopic colitis. Given the suspicion of OIE, olmesartan was discontinued. One-month follow-up revealed resolution of malabsorption, with electrolyte normalization and duodenal biopsies showing improved duodenitis. This study emphasizes the importance of considering medication history and ruling out other potential causes of enteropathy. Olmesartan is an angiotensin II receptor antagonist that is commonly prescribed for hypertension. However, in rare cases, it may induce enteropathy, which often remains underdiagnosed. This rare side effect may present as chronic diarrhea, weight loss, and signs of malabsorption. Interestingly, OIE presents with overlapping clinical and histopathological features to celiac disease and, therefore, may mislead physicians to an extensive diagnostic investigation. Greater awareness of medication-related diarrheal syndromes such as OIE should be promoted, given that simple discontinuation of the medication can lead to dramatic clinical improvement.

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries.

According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1ß levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.

Exosomal MicroRNA-223, MicroRNA-146, and MicroRNA-21 Profiles and Biochemical Changes in Laryngeal Cancer.

Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers, and its early diagnosis is urgent. Exosomes are believed to have diagnostic significance in cancer. However, the role of serum exosomal microRNAs, miR-223, miR-146, and miR-21, and phosphatase and tensin homologue (PTEN) and hemoglobin subunit delta (HBD) mRNAs in LSCC is unclear. Exosomes were isolated from the blood serum of 10 LSCC patients and 10 healthy controls to perform scanning electron microscopy and liquid chromatography quadrupole time-of-flight mass spectrometry analyses to characterize them and to undergo reverse transcription polymerase chain reaction to identify miR-223, miR-146, miR-21, and PTEN and HBD mRNA expression phenotypes. Biochemical parameters, including serum C-reactive protein (CRP) and vitamin B12, were also obtained. Serum exosomes of 10-140 nm were isolated from LSCC and controls. Serum exosomal miR-223, miR-146, and PTEN were found to be significantly decreased (p < 0.05), in contrast to serum exosomal miRNA-21 (p < 0.01), and serum vitamin B12 and CRP (p < 0.05) were found to be significantly increased, in LSCC vs controls. Our novel data show that the combination of reduced serum exosomal miR-223, miR-146, and miR-21 profiles and biochemical alterations in CRP and vitamin B12 levels may be useful indicators of LSCC that could be validated by large studies. Our findings also suggest a possible negative regulatory effect of miR-21 on PTEN in LSCC, encouraging a more extensive investigation of its role.

Gastric cancer after Bariatric Bypass Surgery. Do they relate? (A Systematic Review).

Bariatric bypass surgery has been an effective treatment for morbid obesity. However, there is an increasing number of reported cases of gastric cancer after bypass surgery. Our systematic review showed an increasing trend of gastric cancer cases after bariatric bypass surgery in the last decade, mostly located in the excluded stomach (77%) and diagnosed in an advanced stage. In addition to known risk factors such as tobacco smoking (17%), H. pylori infection (6%), and family history of gastric cancer (3%), bile reflux, a recently proposed cancer-promoting factor, was also estimated in 18% of the cases. Our data suggest that gastric cancer risk assessment should be considered before gastric bypass surgery, and further investigations are needed to determine the value of post-operative gastric cancer surveillance.

The Effect of Tobacco Smoke N-Nitrosamines, NNK and NDEA, and Nicotine, on DNA Mismatch Repair Mechanism and miRNA Markers, in Hypopharyngeal Squamous Cell Carcinoma: An In Vivo Model and Clinical Evidence.

Deregulation of the DNA mismatch repair (MMR) mechanism has been linked to poor prognosis of upper aerodigestive tract cancers. Our recent in vitro data have provided evidence of crosstalk between deregulated miRNAs and MMR genes, caused by tobacco smoke (TS) N-Nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in hypopharyngeal cells. Here, we explored whether chronic exposure to TS components can affect MMR mechanism and miRNA profiles in hypopharyngeal mucosa. Using a mouse model (C57Bl/6J wild type) of in vivo 14-week exposure to NNK (0.2 mmol/L) and N-Nitrosodiethylamine (NDEA; 0.004 mmol/L), with or without nicotine (0.02 µmol/L), we provide direct evidence that TS components can promote dysplasia, significant downregulation of Msh2 and Mlh1 genes and deregulation of miR-21, miR-155, miR-34a, and miR-451a. By analyzing eight human specimens from tobacco smokers and eight controls, we provide clinical evidence of a significant reduction in hMSH2 and hMLH1 mRNAs in hypopharyngeal squamous cell carcinoma (HSCC). In summary, deregulation of the MMR mechanism and miRNAs is caused by chronic exposure to TS-related N-Nitrosamines, with or without nicotine, in the early stages of upper aerodigestive tract carcinogenesis, and can also be detected in human HSCC. Thus, we encourage future studies to further elucidate a possible in vivo dose-dependent effect of individual or combined N-Nitrosamines, NNK and/or NDEA, and nicotine, on the MMR mechanism and their clinical testing to elaborate prognosis and risk assessment.

Hemophagocytic lymphohistiocytosis diagnosed by bone marrow trephine biopsy in living post-COVID-19 patients: case report and mini-review.

Hemophagocytic lymphohistiocytosis (HLH) constitutes a life-threatening inflammatory syndrome. Postmortem histological findings of bone marrow (BM) from COVID-19 patients showed histiocytosis and hemophagocytosis and supported the hypothesis that secondary HLH (sHLH) may be triggered by SARS-CoV-2 infection. However, there are a limited number of sHLH cases in which trephine has been performed in living post-COVID-19 patients. Here we present a recent case and a mini-review of sHLH diagnosed by trephine biopsy in living patients after COVID-19. An 81-year-old man with a past medical history of hypertension, diabetes, ischemic stroke, was referred to the hospital to evaluate leukocytosis, pyuria, and elevation of inflammatory markers four weeks after recovering from COVID-19. Computed tomography of the abdomen did not reveal focal signs of infection or hepatosplenomegaly. The patient received intravenous meropenem and two packed red blood cell units. Leukocytes and C-reactive protein were gradually decreased. A BM biopsy was performed and the patient was discharged on cefixime. BM smear revealed severe anemia, lymphopenia, and dysplastic morphologic findings of erythroblasts, neutrophils, and megakaryocytes. Trephine biopsy revealed hypercellular marrow dyserythropoiesis, plasmacytosis, lymphocytosis, histiocytosis, hemophagocytosis, and the absence of granulomas or carcinoma. Immunohistochemistry documented a mixed population of T lymphocytes (CD3+) and B lymphocytes (CD20+). Strong positivity for CD68 confirmed histiocytosis. CD138 κ, λ staining proved polyclonal plasmacytosis. Perl's staining showed excess hemosiderin deposits. Based on our findings, we document sHLH in trephine BM biopsy of a living post-COVID-19 patient and persistent leukocytosis, underscoring the diagnostic value of trephine biopsy in preventing life-threatening conditions such as COVID-19.

Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo.

Tobacco smoking is the most known risk factor for hypopharyngeal cancer. Bile reflux has recently been documented as an independent risk factor for NFκB-mediated hypopharyngeal squamous cell carcinoma. However, the carcinogenic effect of tobacco smoke on the hypopharynx and its combination with bile has not yet been proven by direct evidence. We investigated whether in vivo chronic exposure (12-14 weeks) of murine (C57Bl/6J) hypopharyngeal epithelium to tobacco smoke components (TSC) [N-nitrosamines; 4-(N-Methyl-N-Nitrosamino)-1-(3-pyridyl)-1-butanone (0.2 mmol/L), N-nitrosodiethylamine (0.004 mmol/L)], as the sole drinking fluid 5 days per week, along with topically applied (two times/day) bile [deoxycholic acid (0.28 mmol/L)], can accelerate a possible TSC-induced neoplastic process, by enhancing NFκB activation and the associated oncogenic profile, using histologic, IHC, and qPCR analyses. We provide direct evidence of TSC-induced premalignant lesions, which can be exacerbated by the presence of bile, causing invasive carcinoma. The combined chronic exposure of the hypopharynx to TSC with bile causes advanced NFκB activation and profound overexpression of Il6, Tnf, Stat3, Egfr, Wnt5a, composing an aggressive phenotype. We document for the first time the noxious combination of bile with a known risk factor, such as tobacco smoke nitrosamines, in the development and progression of hypopharyngeal cancer, via NFκB, in vivo. The data presented here encourage further investigation into the incidence of upper aerodigestive tract cancers in smokers with bile reflux and the early identification of high-risk individuals in clinical practice. This in vivo model is also suitable for large-scale studies to reveal the nature of inflammatory-associated aerodigestive tract carcinogenesis and its targeted therapy. PREVENTION RELEVANCE: Early assessment of bile components in refluxate of tobacco users can prevent the chronic silent progression of upper aerodigestive tract carcinogenesis. This in vivo model indicates that bile reflux might have an additive effect on the tobacco-smoke N-nitrosamines effect and could be suitable for large-scale studies of diagnostic and therapeutic interventions.

A Rare Case of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Transverse Myelitis in a 40-Year-Old Patient With COVID-19.

The coronavirus disease 2019 (COVID-19) includes an extensive spectrum of clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Previous studies have shown that SARS-CoV-2 often exhibits central nervous system (CNS) manifestations, including encephalitis, meningitis, and spinal cord pathologies. To date, few cases of COVID-19-associated transverse myelitis (TM) have been described. A 40-year-old unvaccinated man with no significant medical history presented to the emergency department complaining of fever, worsening burning sensation in his lower extremities, unsteady gait, and difficulty initiating urination for five days. Twelve days before presentation, the patient had tested positive for SARS-CoV-2 infection. Physical examination revealed hyperesthesia, starting around the nipple line (T4) and extending distally, involving the lower extremities, accompanied by symmetric weakness in the lower extremities. Magnetic resonance imaging of the thoracic spine with and without contrast revealed mild intramedullary signal abnormality at T3-T4 and T6-T8, confirming the suspicion of TM. Further laboratory testing revealed a C-reactive protein level of 67 mg/L, lactate dehydrogenase level of 181 mg/L, serum B12 level of 781 pg/mL, methylmalonic acid level of 165 nmol/L, folate of >24.5 ng/mL, and thyroid-stimulating hormone level of 0.481 µIU/L. Lumbar puncture was performed, and cerebrospinal fluid analysis revealed a cell count of 14 cells/µL, with 69% lymphocytes, glucose level of 81 mg/dL, protein level of 32 mg/dL, and negative cultures. Human immunodeficiency virus, antinuclear antibody screening, anti-DNA, rapid plasma reagin, Lyme serology, anti-SSA, and anti-SSB antibodies were unremarkable. Serum aquaporin-4 immunoglobulin G was negative, and myelin oligodendrocyte glycoprotein (MOG) antibodies were positive. The patient was treated with intravenous methylprednisolone and oral gabapentin and was discharged after five days when his urinary retention improved. Most previously reported cases of COVID-19-related TM were negative for autoimmune workup. Although the exact pathophysiology of COVID-19-related TM remains unclear, one hypothesis suggests that it is a consequence of the direct viral invasion. However, our patient had MOG antibodies, suggesting the possible involvement of a different mechanism. In MOG-associated TM, it has been suggested that MOG antibodies gain access to the CNS through disruption of the blood-brain barrier. This unique presentation demonstrates that further studies are needed to understand the effects of SARS-CoV-2 infection on the immune and nervous systems. It also highlights that young and otherwise healthy patients are at risk of severe COVID-19-related complications, including CNS disorders.

New-Onset Hypothyroidism Manifesting As Myxedema Coma: Fighting an Old Enemy.

Myxedema coma (MC) is a rare manifestation of severe hypothyroidism. This is a true endocrine emergency that may remain unrecognized. We present a case of a 49-year-old man who presented to the emergency department with generalized weakness and confusion. He was found to have low temperature, bradycardia, hypoxia, hypotension, glucose of 59 mg/dL, normal electrolytes, thyroid-stimulating hormone of 154 IU/mL, and free T4 of 0.1 ng/dL. His anti-peroxidase antibody level was 99 IU/mL. Echocardiography revealed a normal ejection fraction and no evidence of pericardial effusion. On the basis of his presentation and laboratory findings, he was diagnosed with MC, intubated, and admitted to the intensive care unit. Thyroid hormone replacement and glucocorticoid treatment were initiated immediately. After the clinical improvement, the patient was extubated. MC is associated with a high mortality rate and requires prompt recognition and treatment. This rare case reminds us that MC might still be the first manifestation of primary hypothyroidism, although considered an "old enemy".

Abdominal Pain and Examination of Hernial Orifices: The Forgotten Art of Physical Diagnosis.

INTRODUCTION: Acute abdominal pain can be the first manifestation of a hernial pathology. The estimated risk of incarcerated hernia is 1%-3% over a person's lifetime. Therefore, hernial orifice examination should be conducted routinely, especially in cases of abdominal pain. We hypothesized that physical examination of hernial orifices is not routinely performed and documented in patients presenting with acute abdominal pain. METHODS: A retrospective chart review of 100 patients who were evaluated for abdominal pain over a three-month time frame at our institution. RESULTS: From the 100 reviewed cases, the hernial orifice examination was performed in two cases by an Internal Medicine or Emergency Medicine physician (2%). Out of the eight cases with General Surgery consultation, only one case had hernial orifices examination (12.5%). In the 10 cases with Gastroenterology consultation, not a single case had hernial orifice examination. CONCLUSION: We demonstrate that hernial examination is infrequently performed in clinical practice and suggest that emphasis should be placed on the efficient performance of physical examination and maintain the art of physical diagnosis.

Combined Use of Wells Scores and D-dimer Levels for the Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism in COVID-19: A Retrospective Cohort Study.

Introduction Deep vein thrombosis (DVT) and pulmonary embolism (PE) are key complications of coronavirus disease 2019 (COVID-19). The study's primary outcome was assessing the utility of Wells DVT, Wells PE scores, and D-dimers in diagnosing DVT and PE. Secondary outcomes were the risk factors for the development of PE and DVT in COVID-19 patients. Materials and methods We compared COVID-19 patients with a positive and negative lower extremity (LE) duplex. A similar approach was made for patients who underwent imaging for PE. Results The prevalence of PE was 23.8% (26 out of 109 patients), and the prevalence of DVT was 33% (35 out of 106). A D-dimer of 500 ng/mL had a sensitivity of 95.6% and 93.7% for the diagnosis of PE and DVT, respectively. A Wells DVT score of 3 points had a specificity of 92.9% and sensitivity of 8.8% for DVT diagnosis in COVID-19. A Wells PE score of 4 had a specificity of 100% and a sensitivity of 20% for the diagnosis of PE. The combined approach of using a Wells DVT score of 3 in suspected DVT and a Wells PE score of 4 in suspected PE and D-dimers of 500 ng/ml has a sensitivity of 94.2% and 96.1%, respectively. In the suspected DVT group, male gender (OR 3.88, 95% CI 1.55-9.7, P=0.004), lower body mass index (BMI) (OR 0.92, 95% CI 0.86-0.99, P=0.037), antiplatelet use (OR 0.19, 95% CI 0.04-0.88, P=0.035), systolic blood pressure ≤100 mmhg (OR 4.96, 95% CI 1.37-17.86, P=0.014), absolute lymphocytes ≤1 (OR 2.57, 95% CI 1.07-6.12, P=0.033), D-dimer ≥500 ng/ml (OR 6.42, 95% CI 1.40-29.38, P=0.016), blood urea nitrogen (BUN) ≥20 mg/dl (OR 2.33, 95% CI 1.00-5.41, P=0.048), and intubation (OR 3.32, 95% CI 1.26-8.78, P=0.015) were found to be statistically significant for DVT. In the suspected PE group, history of cancer (OR 10.69, 95% CI 1.06-107.74, P=0.044), total WBC count (OR 1.07, 95% CI 0.95-1.21, P=0.032), platelets ≥ 400,000 (OR 5.13, 95% CI 1.79-14.68, P=0.002), D-dimer levels ≥ 500 ng/ml (OR 25.47, 95% CI 3.27-197.97, P=0.002), Wells PE score (OR 2.46, 95% CI 1.50-4.06, P<0.001), pulmonary embolism rule-out criteria (PERC) score (OR 1.79, 95% CI 1.05-3.05, P=0.054), and Sequential Organ Failure Assessment (SOFA) score (OR 1.91, 95% CI 1.16-3.12, P=0.002) were statistically significant. Conclusions The combined approach of using a Wells DVT score of 3 in suspected DVT and Wells PE score of 4 in suspected PE and D-dimers of 500 ng/ml may be used to diagnose PE and DVT in COVID-19. Venous thromboembolism (VTE) occurrence in COVID-19 is associated with non-traditional risk factors such as intubation and higher severity of systemic inflammation, and these patients may benefit from more aggressive testing for VTE.

Bile reflux and hypopharyngeal cancer (Review).

Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are frequently present in the gastroesophageal refluxate and their effect has been associated with inflammatory and neoplastic changes in the upper aerodigestive tract. Recent in vitro and in vivo studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NF­κB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting anti­apoptotic effects and causing precancerous lesions. The most important findings that strongly support bile reflux as an independent risk factor for hypopharyngeal cancer are presented in the current review and the underlying mechanisms are provided.

Rapidly Progressing Primary Membranous Nephropathy in a Hispanic Male With Elevated Levels of Anti-phospholipase A2 Receptor Antibodies.

A 49-year-old Hispanic male presented to the Emergency Department with progressively worsening swelling in his extremities for the past two months. Physical examination was significant for diffuse edema, with concomitant initial laboratory tests revealing hypoalbuminemia, hypercholesteremia, and proteinuria. A renal biopsy was performed, and the histopathology confirmed a diagnosis of membranous nephropathy through immunofluorescence and electron microscopy. Anti-phospholipase A2 receptor (anti-PLA2R) antibodies were detected on immunofluorescence, as well as high levels being discovered in the patient's serum, indicating a diagnosis of primary membranous nephropathy. The patient underwent adequate diuresis and was discharged. The patient presented six months later due to severe anasarca with laboratory tests indicating a rapid decline in renal function. He was then started on immunosuppressive therapy. Our rare case of a Hispanic male presenting with rapidly deteriorating renal function secondary to primary membranous nephropathy seeks to highlight the possibility of using anti-PLA2R antibodies as a marker for early initiation of immunosuppressive therapy as well as to encourage additional research on the course of disease progression in the Hispanic population.

Controlled ovarian stimulation therapy as a potential risk for the development and progression of renal cell carcinomas: A case report and literature review.

Renal Cell Carcinoma (RCC) is the most common type of cancer in the kidney and is mostly asymptomatic. Previous studies have supported the important role of sex hormones in RCC pathophysiology and that targeted hormone receptor therapy, such as estrogen receptor targeting, is a promising treatment strategy. However, to the best of our knowledge, it remains unknown whether hormonal therapy, such as controlled ovarian stimulation for in vitro fertilization, serves a role in the development and progression of RCC. The present report describes a case of RCC developed after a fertility stimulation therapy and provides a summary of the known literature on the role of hormone receptors in the development and progression of RCC. A 35-year-old woman received fertility stimulation treatment with follitropin alfa 900 units, human chorionic gonadotropic hormone 5,000 units, injectable leuprolide 1 mg/0.2 ml and cetrotide 0.25 mg. The patient presented to the hospital with shortness of breath and weight loss. The patient had no known genetic predisposition or family history of malignancies and no exposure to chemicals. The patient never used tobacco, alcohol or recreational drugs. Imaging revealed a 17x19 mm, heterogeneously enhancing, and partially exophytic mass in the right kidney. After partial nephrectomy, the pathological evaluation confirmed the diagnosis of clear cell RCC. To the best of our knowledge, this was the first time that a case of ovarian stimulation therapy was associated with the development of RCC. This case raises concerns about the potential oncogenic effect of controlled ovarian stimulation therapy in RCC promotion, suggesting a need for systematic research to clarify the clinical significance of existing pre-clinical data.

Weakly Acidic Bile Is a Risk Factor for Hypopharyngeal Carcinogenesis Evidenced by DNA Damage, Antiapoptotic Function, and Premalignant Dysplastic Lesions In Vivo.

BACKGROUND: There is recent in vivo discovery documenting the carcinogenic effect of bile at strongly acidic pH 3.0 in hypopharynx, while in vitro data demonstrate that weakly acidic bile (pH 5.5) has a similar oncogenic effect. Because esophageal refluxate often occurs at pH > 4.0, here we aim to determine whether weakly acidic bile is also carcinogenic in vivo. METHODS: Using 32 wild-type mice C57B16J, we performed topical application of conjugated primary bile acids with or without unconjugated secondary bile acid, deoxycholic acid (DCA), at pH 5.5 and controls, to hypopharyngeal mucosa (HM) twice per day, for 15 weeks. RESULTS: Chronic exposure of HM to weakly acidic bile, promotes premalignant lesions with microinvasion, preceded by significant DNA/RNA oxidative damage, γH2AX (double strand breaks), NF-κB and p53 expression, overexpression of Bcl-2, and elevated Tnf and Il6 mRNAs, compared to controls. Weakly acidic bile, without DCA, upregulates the "oncomirs", miR-21 and miR-155. The presence of DCA promotes Egfr, Wnt5a, and Rela overexpression, and a significant downregulation of "tumor suppressor" miR-451a. CONCLUSION: Weakly acidic pH increases the risk of bile-related hypopharyngeal neoplasia. The oncogenic properties of biliary esophageal reflux on the epithelium of the upper aerodigestive tract may not be fully modified when antacid therapy is applied. We believe that due to bile content, alternative therapeutic strategies using specific inhibitors of relevant molecular pathways or receptors may be considered in patients with refractory GERD.

Psoas Abscess Presented as Right Hip Pain in a Young Adult With Crohn's Disease.

A 27-year-old man with a past medical history of Crohn's disease presented in the Emergency Department complaining of right hip pain that has been going on for one month. At presentation, the patient was tachycardic. Physical examination revealed a positive psoas sign. Laboratory tests showed elevated white blood cells, C-reactive protein, and erythrocyte sedimentation rate. Computed tomography of the abdomen and pelvis revealed ileo-psoas fistula and psoas abscess. This rare case aims to provide awareness that intra-abdominal pathology should always be suspected in patients with referred hip pain and Crohn's disease. A thorough physical examination including maneuvers for assessment of possible iliopsoas inflammation should be effectively performed at the bedside to determine the likelihood of the condition and proper imaging should follow to confirm the diagnosis.

E-cigarette or vaping induced lung injury: A case series and literature review.

INTRODUCTION: Recently, a rapidly increasing number of e-cigarette or vaping induced lung injury (EVALI) has been reported across the nation. Given the ongoing epidemic, it has been suggested that specific chemical substances used as additives in e-cigarettes could be highly related to EVALI. A history of vaping with positive radiographic changes and low suspicion for active infection are requirements for diagnosis but it still remains a diagnosis of exclusion. The course of the disease, mechanism of lung injury and the optimal management options need to be better understood. Here we aimed to discuss the clinical characteristics recognized in a case series of ten hospitalized EVALI patients with radiological findings of lung injury and provide an up today summary of the known literature of EVALI-induced lung injury. METHODS: A retrospective chart review was conducted on ten patients who presented to Saint Peter's University Hospital in New Brunswick, NJ from July 2019 to February 2020, with a mean hospital stay of five days. According to the CDC recommended definition of the disease, our cases met the current working definition of confirmed or probable cases of EVALI. RESULTS: Ten patients, with mean age 30.8 years (50 % male) and average years of vaping 1.708 with 60 % endorsing a simultaneous history of cannabis-related products use, went under a retrospective review. 3/10 (30 %) had documented medically-managed pulmonary disease history, 8/10 (80 %) presented with the respiratory-related chief complaint, 6/10 (60 %) presented with gastrointestinal symptoms and 7/10 (70 %) had constitutional symptoms. All patients (100 %) were found to have bilateral ground-glass opacities on chest imaging. 9/10 were admitted, 6/10 (60 %) had an oxygen saturation of <95 % requiring oxygen supplementation with 4/10 managed in the intensive care unit. CONCLUSION: EVALI patients with radiological findings of lung injury, although mainly present respiratory symptoms, may very often appear with constitutional and gastrointestinal symptoms. Based on the existing literature and our data it is argued that EVALI may be misdiagnosed and that closer monitoring is required to determine optimal diagnostic and therapeutic management of this condition. Our data and the existing literature suggest that laboratory and epidemiologic findings can be contributory for the diagnosis of the disease.

The temporal effects of topical NF-κB inhibition, in the in vivo prevention of bile-related oncogenic mRNA and miRNA phenotypes in murine hypopharyngeal mucosa: a preclinical model.

Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-κB-related pathway. We hypothesize that topical pre- or post-application of pharmacologic NF-κB inhibitor, BAY 11-7082 (0.25 µmol), on murine (C57BL/6J) HM (twice a day for 10 days) can effectively inhibit acidic bile (10 mmol/l; pH 3.0) induced oncogenic molecular events, similar to prior in vitro findings. We demonstrate that the administration of BAY 11-7082, either before or after acidic bile, eliminates NF-κB activation, prevents overexpression of Bcl2, Rela, Stat3, Egfr, Tnf, Wnt5a, and deregulations of miR-192, miR-504, linked to bile reflux-related hypopharyngeal cancer. Pre- but not post-application of NF-κB inhibitor, significantly blocks overexpression of Il6 and prostaglandin H synthases 2 (Ptgs2), and reverses miR-21, miR-155, miR-99a phenotypes, supporting its early bile-induced pro-inflammatory effect. We thus provide novel evidence that topical administration of a pharmacological NF-κB inhibitor, either before or after acidic bile exposure can successfully prevent its oncogenic mRNA and miRNA phenotypes in HM, supporting the observation that co-administration of NF-κB inhibitor may not be essential in preventing early bile-related oncogenic events and encouraging a capacity for further translational exploration.