Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

OBJECTIVE: Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterised the composition and function of ECM in fibrostenosing Crohn's disease (CD) and control tissues. DESIGN: Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative PCR (qPCR) and immunohistochemistry. Primary human intestinal myofibroblasts (HIMFs) treated with milk fat globule-epidermal growth factor 8 (MFGE8) were evaluated regarding the mechanism of their antifibrotic response, and the action of MFGE8 was tested in two experimental intestinal fibrosis models. RESULTS: We established and validated an optimal decellularisation protocol for intestinal IBD tissues. Matrisome analysis revealed elevated MFGE8 expression in CD strictured (CDs) tissue, which was confirmed at the mRNA and protein levels. Treatment with MFGE8 inhibited ECM production in normal control HIMF but not CDs HIMF. Next-generation sequencing uncovered functionally relevant integrin-mediated signalling pathways, and blockade of integrin αvß5 and focal adhesion kinase rendered HIMF non-responsive to MFGE8. MFGE8 prevented and reversed experimental intestinal fibrosis in vitro and in vivo. CONCLUSION: MFGE8 displays antifibrotic effects, and its administration may represent a future approach for prevention of IBD-induced intestinal strictures.

Pulmonary Adenocarcinoma Mimicking Pneumonia in a Young Adult.

Lung cancer is the third most common cancer in the United States. Lung adenocarcinoma is a subtype of non-small cell lung cancer. On computed tomography (CT) it can appear as ground glass nodules, consolidative opacity, or solid mass lesions located in the periphery. Because it can appear as a consolidation, it can sometimes be confused with an infectious process such as pneumonia. We present a case of a 27-year-old male initially diagnosed with pneumonia; however, three months later, when he presented to the hospital with worsening pleuritic chest pain, fever, and dyspnea after a bronchoscopy a week before admission, pathology was positive for adenocarcinoma.

An Interesting Case of Prostate Cancer Presenting With Colonic Metastasis.

Prostate cancer is common cancer that grows slowly and tends to metastasize to bones, lungs, and the liver. Most malignancies have established patterns in presentation, localization, and organs where they metastasize. We are presenting a case of a 60-year-old man who presented with abdominal pain and, on further investigation, was found to have polyps in the colon, a flat rectal mass with eccentric thickening of the rectum, a moderately enlarged prostate, and multiple liver masses suggestive of metastasis. It was initially thought to be colorectal cancer with metastasis but was eventually diagnosed as a stage IV prostate adenocarcinoma with metastases to the liver and rectum. It is very unusual for prostate cancer to present with distal metastasis to the liver and rectum, as in this case.

Abdominal Compartment Syndrome (ACS) With Sigmoid Volvulus (SV): Lost Hours Are Lost Lives.

Normal intra-abdominal pressure (IAP) ranges from 0 to 5, and abdominal compartment syndrome (ACS) occurs when a sustained IAP >20 mmHg causes organ dysfunction. ACS mainly occurs in patients who are critically ill. It occurs due to an injury or disease in the abdomen or pelvic area, including trauma, abdominal surgery, acute pancreatitis, pancreatic ileus, volvulus, fecal impaction, and ruptured abdominal aortic aneurysm. If not recognized early, ACS leads to multiorgan dysfunction, shock, and sepsis and has high morbidity and mortality. Our patient was brought to the emergency department (ED) following cardiac arrest and resuscitation and was diagnosed with sigmoid volvulus (SV) and ACS. SV is seen in older men, and its presentation is often insidious and leads to bowel gangrene and ACS. The patient's delay in presenting to the hospital and the severity of his condition leads to a poor outcome despite surgery. A delay in recognizing ACS can lead to a worse outcome.

Amoxicillin-Clavulanate Induced Liver Injury in a Young Female.

Amoxicillin-clavulanate (AC) is an antibiotic widely used for various infections. It has rarely been associated with drug-induced liver injury (DILI), mainly in males 55 or older with associated alcohol consumption or medications causing liver injury. Here we present an atypical case of a 22-year-old female with a past medical history of celiac disease and alopecia areata who was prescribed AC in urgent care for bilateral cervical lymphadenopathy, nausea, and chills. Her nausea and vomiting worsened after taking AC for three days, and she developed jaundice. On workup, she was found to have deranged liver functions, and pan-lobular hepatitis was confirmed on liver biopsy. She started to improve symptomatically after withdrawing AC, and her transaminases started showing a decreasing trend.

A Young Adult With Essential Thrombocythemia Presenting as Myocardial Infarction.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm involving the clonal proliferation of platelets. It is Philadelphia negative and is associated with Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations. The resultant platelets have quantitative and qualitative defects, making them more sticky and prone to thromboembolism. However, ET does not only affect platelet survival, it also has a low leukemogenic potential. It's more common in the elderly, 60 years or more, but can be seen in all age groups, including children. Patients with ET have an increased risk of vascular events like hemorrhage and thromboses like cerebrovascular events, myocardial infarction, superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism. Cardiovascular risk factors like hypertension, diabetes, and smoking can lead to increased thromboembolism and atherosclerosis. The management of ET focuses primarily on the prevention of thrombosis and hemorrhage. It involves cardiovascular risk management and antiplatelet and cytoreductive therapy according to the risk stratification. Low-risk ET patients are treated with low-dose aspirin, and high-risk ET patients are treated with cytoreductive therapy with hydroxyurea. Interferon (IFN) and anagrelide are reserved for young patients or pregnant women. This case report discusses a 40-year-old male, a known smoker presenting with myocardial infarction and left anterior descending artery (LAD) blockage without any prior history. His high platelets and the relative absence of cardiovascular risk factors helped reach the diagnosis, and bone marrow analysis and mutation analysis confirmed the diagnosis. The patient was started on hydroxyurea, which decreased the total platelet count.

A Case Report of Nodular Regenerative Hyperplasia and Non-cirrhotic Portal Hypertension Post Oxaliplatin Chemotherapy.

Oxaliplatin is widely used in chemotherapeutic regimens for colorectal carcinoma, its recurrence, and metastasis, and is associated with better outcomes. However, oxaliplatin use is associated with injury to hepatic sinusoidal endothelium and the development of nodular regenerative hyperplasia (NRH) in the liver, which can be differentiated from nodular hyperplasia of cirrhosis by the presence of diffuse micronodular transformation without a fibrous band and the lack of perinuclear collagen tissue. This causes non-cirrhotic portal hypertension (NCPH), which presents with splenomegaly and variceal bleeding and preserved synthetic liver function. Its treatment revolves around managing variceal bleeding with banding, sclerotherapy, and beta blockers. Some patients may end up requiring liver transplantation because of recurrent variceal bleeding. We present the case of a 46 years old female who presented with recurrent variceal bleeding due to NCPH and NRH six years after treatment of colon carcinoma with oxaliplatin.

A Case Report of a Prevertebral Mass in an Elderly Male Post Hodgkin's Lymphoma.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory autoimmune disease characterized by tissue infiltration by dense lymphoplasmacytic infiltrate composed of T cells, activated B-cells, and plasma cells expressing IgG4 and has varied presentations with similar histopathology. It can involve visceral organs, glands, aorta, lymph nodes, and retroperitoneal tissue. In our case, a 68-year-old male with a past history of Hodgkin's lymphoma and in remission presented for investigation of polyclonal gammopathy. Serum electrophoresis showed increased free kappa light chains, free lambda light chains, and kappa lambda ratio; immunoglobulin G (IgG) levels were also increased. A positron emission tomography (PET) scan and magnetic resonance imaging (MRI) thoracic spine suggested a hypermetabolic prevertebral soft tissue density. Biopsy of the mass suggested IgG4-related disease (IgG4-RD). He also had a compression fracture of the T7 vertebra. He was started on intravenous methylprednisolone and rituximab, following which he had a significant decrease in the size of the mass along with a decline in the levels of IgG, kappa, and lambda chains.

A Rare Presentation of Granulomatosis With Polyangiitis with Multiple Cardiac Valvular Insufficiencies.

Granulomatosis with polyangiitis (GPA), earlier known as Wegener's granulomatosis, is an autoimmune inflammatory disorder that causes necrotizing vasculitis of small- and medium-sized blood vessels. It primarily affects the upper respiratory tract, lungs, and kidneys. Most of the cardiac involvement tends to be subclinical and is often not clinically apparent with involvement of the conduction pathway; myocarditis, pericarditis, or coronary artery involvement are associated with increased morbidity and mortality. These present with the symptoms of shortness of breath, cough, bilateral pedal edema, orthopnea, syncope, and features of heart failure such as elevated jugular venous pressure. We report a rare case of heart involvement with profound valvular deformity involving all four cardiac valves along with renal impairment in a 76-year-old female with recently diagnosed granulomatosis with polyangiitis.

An Interesting Case of Mixed Dust Pneumoconiosis With Progressive Massive Fibrosis and Cor Pulmonale in a South American Farmer.

Pneumoconiosis is an occupational disease found in workers with environmental exposure to organic and inorganic dust, as in mining, sandblasting, pottery, stone masonry, and farming. The inflammatory response of the lung to respirable dust causes the formation of macules, nodules, and fibrosis, and higher silica content in inhaled dust is associated with increased fibrosis. Mixed dust pneumoconiosis (MDP) is characterized by exposure to dust containing 10-20% silica, and its lung imaging show irregular opacities. Histopathology plays a vital role in the diagnosis of MDP. Though it has a favorable outcome, it evolves slowly over many years of constant exposure and is characterized by worsening dyspnea and cough gradually progressing to cor pulmonale. The only effective treatment is removing exposure, which makes it essential to recognize the disease early for a favorable outcome. We present a case of mixed dust pneumoconiosis in a farmer from South America who had asthma. He presented with worsening dyspnea and multiple nodules in both lungs on imaging and cor pulmonale. An extensive workup was done, and it ruled out any malignancy and tuberculosis. Analysis of video-assisted thoracoscopic surgery (VATS) biopsy samples confirmed the diagnosis of mixed dust pneumoconiosis. He had a confluence of irregular nodes in the upper lobes of the lungs, and the largest was 2.1 cm. This fits the International Labour Organization (ILO) definition of progressive massive fibrosis. This, along with cor pulmonale present in him, gives it a poor prognosis even after he is removed from dust exposure. He received steroids, which led to symptomatic improvement, and he was discharged to follow up with the pulmonologist.

A Rare Case of Horseshoe Kidney With Multiple Atrial Myxomas Presenting as Cerebrovascular Accident.

Myxomas are benign tumors of mesenchymal origin, containing a few pluripotent cells in the myxomatous stroma. They usually present at 30-40 years of age and are more common in females than males. These tumors mostly arise in the atria and protrude into the atrial lumen. They cause constitutional symptoms like fever and weight loss and obstructive symptoms related to outflow obstruction in the heart. Some tumors are more fragile and cause embolism and may present as stroke. Mostly sporadic but familial cases and myxomas associated with Carney syndrome (CNC) tend to be multiple. Here, we report a case of a 40-year-old female with a stroke due to embolization from multiple myxomas. She had no family history of myxoma and had no skin findings or other tumors associated with CNC. She also had an atrophied horseshoe kidney with renal failure. The association of a horseshoe kidney with myxoma is rarely reported. In an extensive literature search, we could only find only one other case. Atrial myxomas were detected while investigating the cause of stroke. Our patient gradually improved and was advised surgical removal of the myxomas, which is the treatment of choice.

Yersinia Enterocolitica Sepsis in an Elderly Male With No Iron Overload: A Case Report From the Northeastern United States.

Yersinia enterocolitica (YE) is a facultative anaerobic gram-negative coccobacillus of the genus Yersinia (the most common ones are YE serogroups O:3; O:5,27; O:8; and O:9). Its incubation period is typically 1-14 days. The symptoms of YE infection include fever, abdominal pain (which may mimic appendicitis), and diarrhea (which may be bloody and can persist for several weeks). It is most commonly reported in infants and children due to cross-contamination of their feeds and pacifiers by people handling pork products, especially while cooking chitterlings. Necrotizing enterocolitis has been described in infants following YE infections. Adults who are immunocompromised or in an iron-overload state can develop sepsis with YE infection, which has a high fatality rate. Post-infectious sequelae like reactive arthritis and erythema nodosum can occur in certain HLA types. The diagnosis is made by isolating the organism from the body fluids, stool. The gastrointestinal (GI) pathogen panel by polymerase chain reaction (PCR) is helpful in making an early diagnosis. In this report, we discuss a case of an elderly male from a nursing facility who presented with abdominal pain, vomiting, GI bleeding, and sepsis. He required a brief ICU stay and pressor support. GI pathogen panel was instrumental in the early diagnosis of YE. This condition is not often reported in the Northeastern US. Using GI pathogen PCR testing will lead to the detection of more cases of YE in geographical regions where it was not considered prevalent.

Correction: A Young Adult With Essential Thrombocythemia Presenting as Myocardial Infarction.

[This corrects the article DOI: 10.7759/cureus.28883.].

COVID-19, HHV6 and MOG antibody: A perfect storm.

BACKGROUND: Serious neurological complications of SARS-CoV-2 are increasingly being recognized. CASE: We report a novel case of HHV6 myelitis with parainfectious MOG-IgG in the setting of COVID-19-induced lymphopenia and hypogammaglobulinemia. The patient experienced complete neurological recovery with gancyclovir, high dose corticosteroids, and plasma exchange. To our knowledge, this is the first case of HHV6 reactivation in the central nervous system in the setting of COVID19 infection and the first case of MOG-IgG myelitis in the setting of SARS-CoV-2 and HHV6 coinfection. CONCLUSION: Patients with neurological manifestations in the setting of COVID19-related immunodeficiency should be tested for opportunistic infections including HHV6. Viral infection is a known trigger for MOG-IgG and therefore this antibody should be checked in patients with SARS-CoV-2 associated demyelination.

Perceived stress, reproductive hormones, and ovulatory function: a prospective cohort study.

BACKGROUND: Stress has been shown to suppress ovulation in experimental models, but its effect on human reproduction at the population level is unclear. METHODS: Healthy women (n = 259), aged 18-44 years from Western New York, were followed for 2 menstrual cycles (2005-2007). Women completed daily perceived stress assessments, a 4-item Perceived Stress Scale (PSS-4) up to 4 times each cycle, and a 14-item PSS at baseline. Mixed model analyses were used to assess effects of stress on log reproductive hormone concentrations and sporadic anovulation. RESULTS: High versus low daily stress was associated with lower estradiol (-9.5% [95% confidence interval (CI) = -15.6% to -3.0%]), free estradiol (-10.4% [-16.5% to -3.9%]), and luteinizing hormone (-14.8% [-21.3% to -7.7%]) and higher follicle-stimulating hormone (6.2% [95% CI = 2.0% to 10.5%]) after adjusting for age, race, percent body fat, depression score, and time-varying hormones and vigorous exercise. High versus low daily stress was also associated with lower luteal progesterone (-10.4% [95% CI = -19.7% to -0.10%]) and higher odds of anovulation (adjusted odds ratio = 2.2 [95% CI = 1.0 to 4.7]). For each unit increase in daily stress level, women had a 70% higher odds of an anovulatory episode (odds ratio = 1.7 [1.1 to 2.4]). Similar but attenuated results were found for the association between the PSS-4 and reproductive hormones, while null findings were found for the baseline PSS. CONCLUSION: Daily perceived stress does appear to interfere with menstrual cycle function among women with no known reproductive disorders, warranting further research to explore potential population-level impacts and causal biologic mechanisms.

Depressive symptoms and their relationship with endogenous reproductive hormones and sporadic anovulation in premenopausal women.

PURPOSE: To determine whether depressive symptoms are associated with ovulation or reproductive hormone concentrations in eumenorrheic women without a reported diagnosis of clinical depression. METHODS: A prospective cohort of 248 regularly menstruating women, aged 18 to 44 years (27.3 ± 8.2) were evaluated for depressive symptoms at baseline using the 20-item Center for Epidemiological Studies Depression (CES-D) scale and categorized dichotomously (<16, no depressive symptoms [92%] vs. ≥ 16, depressive symptoms [8%]). Serum concentrations of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to eight times per cycle for up to two menstrual cycles. Linear mixed models estimated associations between depressive symptoms and hormone concentrations, whereas generalized linear mixed models assessed their relationship with sporadic anovulation. RESULTS: No significant associations were identified between depressive symptoms and reproductive hormone levels (all P > .05) or the odds of sporadic anovulation (adjusted odds ratio, 1.1; 95% confidence interval, [0.02-5.0]), after adjusting for age, race, body mass index, perceived stress level, and alcohol consumption. CONCLUSIONS: Despite reported associations between mental health and menstrual cycle dysfunction, depressive symptoms were not associated with reproductive hormone concentrations or sporadic anovulation in this cohort of regularly menstruating women with no recent (within 1 year) self-reported history of clinical depression.