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.

The Epidemiology and Clinical Presentation of Pancreatic Divisum: A Case Series of 57 Case Reports.

OBJECTIVES: Pancreatic divisum (PD) is the second most common congenital abnormality of the pancreatic duct, which affects 2% to 3% of the population. Most of the population remains asymptomatic, but in people who present with symptoms, it can be a cause of anguish and should be recognized. The main goal of this article was to provide a comprehensive picture of clinical and epidemiological methods of diagnosis and treatment of PD. METHODS: A total of 57 PD case reports were considered in this descriptive analysis with 51 case reports and case series published within the last 25 years. The search strategies include systemic searches using scholarly search engines such as Medscape, Scopus, Cochrane, and PubMed. RESULTS: The 57 cases we studied have an average age of presentation of 42 years, with female sex (58%) predominance. Common presenting symptoms were abdominal pain (87.72%) and radiation to the back (21.6%). Eighty-one percent of the case studies reported pancreatitis, and 63.2% had recurrent pancreatitis. At presentation, laboratory values demonstrated increased amylase, lipase, and liver enzymes. PD was diagnosed using magnetic resonance cholangiopancreatography (28.1%), endoscopic retrograde cholangiopancreatography (57.9%), endoscopic ultrasound (7%), or computed tomography (5.3%) scan of the abdomen. Of significance, biliary duct dilation was found in 70.6% of patients diagnosed as having PD. Incidental masses were found in 66.7% of the patients. The most successful treatment was sphincterotomy with or without stents (47.6%), followed by pancreatoduodenectomy (19%) and pancreaticojejunostomy (10%). CONCLUSIONS: Physicians managing pancreatitis should add PD to their differential diagnoses because it will help improve patient outcomes and avoid unfavorable consequences.

Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases.

Angelman syndrome is a neurogenetic disorder with varying clinical presentations and symptoms as the individual ages. The goal of this study was to characterize changes over time in the natural history of this syndrome in a large population. We reviewed the medical records of the 53 patients who were born prior to 2000 and seen at the Angelman Syndrome Clinic at Massachusetts General Hospital to assess neurological, sleep, behavioral, gastrointestinal, orthopedic, and ophthalmologic functioning. The average age of this cohort was 24 years. Active seizures were present in 35%, nonepileptic myoclonus in 42%, and clinically significant tremors in 55%. Anxiety was present in 57%, increasing to 71% in those ages 26-43 years. In terms of sleep, 56% reported 8 hr of sleep or more, although 43% reported frequent nocturnal awakenings. Gastrointestinal issues remain problematic with 81% having constipation and 53% gastroesophageal reflux. The majority lived in a parent's home and remained independently mobile, though scoliosis was reportedly present in 30%, and 20% had reported low bone density/osteoporosis. The results of this study suggest that the prevalence of active seizures may decrease in adulthood but that the prevalence of movement disorders such as tremor and nonepileptic myoclonus may increase. Anxiety increases significantly as individuals age while defiant behaviors appear to decrease. Sleep dysfunction typically improves as compared to childhood but remains a significant issue for many adults. Other areas that require monitoring into adulthood include gastrointestinal dysfunction, and orthopedic/mobility issues, such as reported scoliosis and bone density, and ophthalmologic disorders.

Systematic review of infant and young child complementary feeding practices in South Asian families: the Pakistan perspective.

OBJECTIVE: Suboptimal nutrition among children remains a problem among South Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly reduce this risk. Thus, we undertook a systematic review of studies assessing CF (timing, dietary diversity, meal frequency and influencing factors) in children aged <2 years in Pakistan. DESIGN: Searches between January 2000 and June 2016 in MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research on CF practices in SA children aged 0-2 years and/or their families. Search terms: 'children', 'feeding' and 'Asians' with their derivatives. Two researchers undertook study selection, data extraction and quality appraisal (EPPI-Centre Weight of Evidence). RESULTS: From 45 712 results, seventeen studies were included. Despite adopting the WHO Infant and Young Child Feeding guidelines, suboptimal CF was found in all studies. Nine of fifteen studies assessing timing recorded CF introduced between 6 and 9 months. Five of nine observed dietary diversity across four of seven food groups; and two of four, minimum meal frequency in over 50 % of participants. Influencing factors included lack of CF knowledge, low maternal education, socio-economic status and cultural beliefs. CONCLUSIONS: This is the first systematic review to evaluate CF practices in Pakistan. Campaigns to change health and nutrition behaviour are needed to meet the substantial unmet needs of these children.

Systematic review of infant and young child complementary feeding practices in South Asian families: the India perspective.

OBJECTIVE: Suboptimal nutrition among children remains a problem among South Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly reduce this risk. Thus, we undertook a systematic review of studies assessing CF (timing, dietary diversity, meal frequency and influencing factors) in children aged <2 years in India. DESIGN: Searches between January 2000 and June 2016 in MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research on CF practices in SA children aged 0-2 years and/or their families. Search terms: 'children', 'feeding' and 'Asians' and derivatives. Two researchers undertook study selection, data extraction and quality appraisal (EPPI-Centre Weight of Evidence). RESULTS: From 45 712 abstracts screened, sixty-four cross-sectional, seven cohort, one qualitative and one case-control studies were included. Despite adopting the WHO Infant and Young Child Feeding guidelines, suboptimal CF practices were found in all studies. In twenty-nine of fifty-nine studies, CF was introduced between 6 and 9 months, with eight studies finding minimum dietary diversity was achieved in 6-33 %, and ten of seventeen studies noting minimum meal frequency in only 25-50 % of the study populations. Influencing factors included cultural influences, poor knowledge on appropriate CF practices and parental educational status. CONCLUSIONS: This is the first systematic review to evaluate CF practices in SA in India. Campaigns to change health and nutrition behaviour and revision of nationwide child health nutrition programmes are needed to meet the substantial unmet needs of these children.

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.

Sexual activity, endogenous reproductive hormones and ovulation in premenopausal women.

We investigated whether sexual activity was associated with reproductive function in the BioCycle Study, a prospective cohort study that followed 259 regularly menstruating women aged 18 to 44years for one (n=9) or two (n=250) menstrual cycles in 2005-2007. Women were not attempting pregnancy nor using hormonal contraceptives. History of ever having been sexually active was assessed at baseline and frequency of sexual activity, defined as vaginal-penile intercourse, was self-reported daily throughout the study. Serum concentrations of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and testosterone were measured up to 8times/cycle. Sporadic anovulation was identified using peak progesterone concentration. Linear mixed models were used to estimate associations between sexual activity and reproductive hormone concentrations and generalized linear models were used to estimate associations with sporadic anovulation. Models were adjusted for age, race, body mass index, perceived stress, and alcohol consumption and accounted for repeated measures within women. Elevated concentrations of estrogen (+14.6%, P<.01), luteal progesterone (+41.0%, P<.01) and mid-cycle LH (+23.4%, P<.01), but not FSH (P=.33) or testosterone (P=.37), were observed in sexually active women compared with sexually inactive women (no prior and no study-period sexual activity); sexually active women had lower odds of sporadic anovulation (adjusted odds ratio=0.34, 95% confidence interval: 0.16-0.73). Among sexually active women, frequency of sexual activity was not associated with hormones or sporadic anovulation (all P>.23). Findings from our study suggest that ever having been sexually active is associated with improved reproductive function, even after controlling for factors such as age.

A Rare Case of Cardiac Myxoma With Moyamoya Phenomenon: A Disease or Syndrome?

Moyamoya disease (MMD) is a rare, idiopathic, progressive, obstructive, vasculopathy affecting primarily the terminal portions of the intracerebral internal carotid arteries, typically at the base of the brain. It is more commonly seen in people of East Asian descent. The moyamoya phenomenon refers to the characteristic appearance of the tangle of fine blood vessels, also described as a puff of smoke. Moyamoya syndrome (MMS) refers to the constriction-induced chronic brain ischemia that is believed to cause overexpression of proangiogenic factors, creating a fragile network of collateral capillaries. MMS refers to the moyamoya phenomenon in the presence of other congenital or acquired disorders. Intracerebral hemorrhage is the leading cause of death for MMS patients. Overall, the prognosis is variable. Cardiac myxoma can cause embolization of tumor cells, plaques, and thrombus, and recurrent thromboembolism can lead to chronic brain ischemia, which can lead to the development of collaterals. There have been cases reported where the moyamoya phenomenon resolved following myxoma resection. Here, we present the case of a female who had intraventricular bleeding and was diagnosed with MMD. Eighteen months later, she presented with shortness of breath and was diagnosed with cardiac myxoma with multiple valvular regurgitations. The myxoma was surgically removed.

A Case Report of Cardiac Failure in a Patient on Teduglutide for High-Output Ileostomy Stoma.

A high volume of ileostomy output in patients with extensive bowel resection can be hard to manage. This leads to extensive loss of fluids and electrolytes along with malabsorption. Medications have traditionally controlled it by delaying intestinal transit and decreasing intestinal and gastric secretion using opiates, loperamide, diphenoxylate, omeprazole, somatostatin, and octreotide. However, many patients depend on parenteral nutrition and fluid and electrolyte infusions, even with optimal drug therapy. Despite the best possible care, they may develop renal failure. Teduglutide is a glucagon-like peptide-2 (GLP-2) analog given as a daily subcutaneous injection, and it has been promising in managing short bowel syndrome. It has been effective in decreasing the dependence on parenteral nutrition. However, improving fluid and electrolyte balance can precipitate cardiac failure in some patients, especially those with borderline cardiac functions, hypertension, and thyroid disorders. This usually presents in the first few months of the initiation of teduglutide therapy and may require stopping the medication. We present the case report of an elderly female with a high-output stoma on parenteral nutrition on teduglutide. There was a significant decrease in stoma output, and parenteral nutritional support could be stopped. However, she presented with worsening dyspnea and was diagnosed with cardiac failure with an ejection fraction of 16%-20%. The baseline ejection fraction was 45%, done six months before this. Coronary angiography showed no stenosis in any vessels, and the decline in left ventricular ejection fraction and fluid overload was attributed to teduglutide therapy.

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.

Correction: A Case Report of Takotsubo Cardiomyopathy With Myxedema Coma.

[This corrects the article DOI: 10.7759/cureus.32652.].

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.

A Case Report of Successful Management of Refractory Polyarticular Gout With Pegloticase.

Gout is inflammatory arthritis and is easily recognizable by healthcare providers by its typical clinical presentation of acute gout flare or by the presence of chronic tophaceous deposits. However, chronic gouty arthropathy can be more challenging to diagnose in some cases, especially in the absence of a previous history of gout and other characteristic findings on exam. We present a case of chronic gouty arthropathy with features mimicking rheumatoid arthritis involving multiple small joints of hands and feet and other large joints. He had high serum uric acids and a dual-energy CT (DECT) scan of the feet and ankles was obtained which showed polyarticular gout. He was started on pegloticase in view of joint erosions, and severe limitations in activity which resulted in a lowering of monosodium urate crystals and symptomatic improvement.

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.

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 Severe Posterior Reversible Encephalopathy Syndrome Due to Accelerated Hypertension in a Young Patient.

Posterior reversible encephalopathy syndrome (PRES) refers to white matter vasogenic edema primarily affecting the brain's posterior occipital and parietal lobes, causing acute neurological symptoms like headaches, visual symptoms, seizures, and altered mental status. We present the case of a 32-year-old male with uncontrolled hypertension, altered mental status, and left-sided weakness. He had a rapid neurological decline, and a computed tomography (CT) head showed blurring of gray-white matter interfaces in the right posterior parietal lobe, suggesting infarction or PRES. Magnetic resonance imaging (MRI) of the brain suggested worsening with acute-early subacute infarction involving the right temporal, parietal, and occipital lobes and diffuse cerebral edema causing compression of the right ventricle with diffuse sulcal effacement and central downward herniation. There were flair hyperintensities in the bifrontal, pons, and cerebellum. Given the history of uncontrolled hypertension, the right hemispheric infarction and edema were thought to be due to secondary complications of severe PRES. He underwent urgent bilateral craniectomies with dural augmentation and external ventricular drain placement to control the intracranial pressure the next day. His mental status, as well as neurologic function, showed gradual improvement in the next few months. A high index of suspicion and rapid treatment can pave the way for a quick recovery and help reduce morbidity and death.

Dexmedetomidine-Induced Fever in a 66-Year-Old Male With Pneumonia and Pleural Effusion.

Drug-induced fever is a significant adverse effect as many commonly used medications can cause this. The incidence of drug fever is even higher in critical care settings because multiple medications are being administered simultaneously. This poses a serious problem in critical care settings as any new fever in these settings also implies any new infection or worsening of preexisting conditions. This may lead to a detailed investigation for the cause of fever, which can be time-consuming, invasive, costly, and may also increase the duration of stay along with an associated increase in morbidity and mortality. We want to highlight an adverse drug event through a documented case of Dexmedetomidine-induced fever in a critical care patient with multiple pathologies.