Development and validation of a scoring system to predict response to obeticholic acid in primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N 441) and the IBER-PBC (N 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS), or also after 6 months of treatment (ORS+). Multivariable Cox's regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (ALP/ULN<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or NORMAL RANGE criteria (NR: normal ALP, ALT and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were of 0.75, 0.78 and 0.72 for POISE, ALP/ULN<1.67 and NR response, which raised to 0.83, 0.88, 0.81 with ORS+, respectively. The respective performances in validation were of 0.70, 0.72 and 0.71 for ORS, and 0.80, 0.84, 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

Asymptomatic Elevation of Pancreatic Enzymes: A Case of Gullo's Syndrome.

Benign pancreatic hyperenzymemia (BPH) or Gullo's syndrome is a benign condition consisting of an oscillating elevation of pancreatic enzymes without the identification of pancreatic disease. Its diagnosis is usually incidental and by excluding other conditions that occur with elevated pancreatic enzymes. To the best of our knowledge, there are no reports of this diagnosis to this day in Portugal. A 65-year-old female was referred to an internal medicine consultation for complaints of xerostomia, xerophthalmia, and xeroderma with one year of evolution. From the study carried out by the patient prior to the consultation, an incidental elevation of amylase stands out. The sicca symptoms were attributed to sertraline since, after excluding other causes, its discontinuation resolved the symptoms. Regarding the elevation of pancreatic enzymes, the patient underwent an extensive diagnostic study for clarification without identifying any condition. The serial measurement of amylase and lipase revealed an oscillating increase in pancreatic enzymes with temporary normalization. After one year of follow-up, the diagnosis of Gullo's syndrome was established. The identification of Gullo's syndrome is extremely important as it avoids carrying out unnecessary tests in the future and allows the patient to be reassured in the face of this benign alteration of pancreatic enzymes. A follow-up of at least one year is crucial since some pancreatic tumors course with an asymptomatic increase in pancreatic enzymes.

Severe Ascites in Common Variable Immunodeficiency.

Liver disease is one of the possible clinical manifestations of common variable immunodeficiency and can range from mild hepatomegaly and persistent elevation of liver enzymes to cirrhosis, portal hypertension, and nodular regenerative hyperplasia. The last one is the most common histologic presentation of liver involvement by common variable immunodeficiency and its clinical spectrum can range from asymptomatic to cholestasis, liver cirrhosis, or idiopathic non-cirrhotic portal hypertension, with the severe manifestations being less recognised. We present a case of a 48-year-old woman who was referred for an internal medicine consultation for evaluation of rapidly progressing (span of three months) large-volume ascites and marked asthenia. The patient had a past medical history of common variable immunodeficiency and a recent episode of severe haemolytic anaemia. Peritoneal fluid analyses identified portal hypertension as the cause of the ascites. Abdominal Doppler ultrasound and contrasted abdominal computed tomography confirmed the presence of permeable hepatic and portal veins. Liver biopsy revealed regenerative nodular hyperplasia without cirrhosis. A diagnosis of idiopathic non-cirrhotic portal hypertension secondary to common variable immunodeficiency was made. Treatment was adjusted with considerable improvement in ascites. In conclusion, idiopathic non-cirrhotic portal hypertension is a possible and often overlooked complication in patients with common variable immunodeficiency and is an exclusion diagnosis that requires a high level of suspicion, especially in patients with ascites.

Nitrofurantoin-induced agranulocytosis.

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/µL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.

Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease.

BACKGROUND: The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. OBJECTIVE: This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. METHODS: Patients with PBC as main diagnosis were included from a national multicentric patient registry-Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. RESULTS: A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti-mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow-up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02-1.54; p = 0.033) and 35% (95%CI:1.06-1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01-1.10; p = 0.013) for those with elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP). CONCLUSION: A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization.

A Case of Liver Injury after Exposure to Isopropanol: A Challenging Diagnosis.

Drug-induced liver injury is hardly diagnosed, considering not only the wide range of hepatotoxic substances but also the diversity of associated phenotypes and the absence of specific biomarkers. Symptom chronology, drug or toxic exposure, and temporal association help to establish the diagnosis. Exposure to isopropanol has known but rare toxic effects. We report the clinical case of a 33-year-old female hairdresser admitted to the hospital with fatigue, epigastric pain, and jaundice. She presented the following values: aspartate aminotransferase, 485 U/L; alanine transaminase, 908 U/L; ALP, 240 U/L; GGT, 370 U/L; total bilirubin, 3.5 mg/dL; and direct bilirubin, 2.1 mg/dL. Albumin, platelet, and INR values were normal. Structural, infectious, immune, and vascular causes were excluded. Liver biopsy was suggestive of toxic hepatitis. A possible association with ibuprofen intake was considered. The patient resumed professional activity, with fatigue and jaundice relapse, as well as a new liver enzyme increase, despite ibuprofen withdrawal. It was concluded that a new hair product containing isopropanol had recently been introduced. As soon as its professional use was discontinued, there was no recurrence of the symptoms. Given the temporal association between the development of acute hepatitis and the use of an isopropanol-containing product, liver toxicity by exposure to isopropanol was assumed. This substance is metabolized in the liver and toxicity may occur by ingestion, skin exposure, or inhalation, and it is described in cases of occupational or accidental exposure. The treatment is symptomatic and comprises toxic suspension.

A lesão hepática induzida por tóxicos é um dos distúrbios de mais difícil diagnóstico, quer pela existência de múltiplos hepatotóxicos, quer pela diversidade de fenótipos associados e ausência de biomarcadores específicos. A cronologia dos sintomas, exposição a fármacos ou tóxicos e associação temporal auxilia o diagnóstico. A exposição a isopropanol tem efeitos tóxicos conhecidos e raros. Descrevemos o caso clínico de uma mulher de 33 anos, cabeleireira, admitida por fadiga, epigastralgias e icterícia. Apresentava AST 485 U/L, ALT 908 U/L, FA 240 U/L, GGT 370 U/L, bilirrubina total 3,5 mg/dL e bilirrubina direta 2,1 mg/dL; o doseamento sérico de albumina, plaquetas e o valor de INR eram normais. Foram excluídas lesões estruturais, causas infeciosas, imunes e vasculares. Biópsia hepática sugestiva de hepatite tóxica. Considerada possível associação a toma de ibuprofeno. Retomou atividade profissional, com recorrência de fadiga e icterícia, bem como elevação das enzimas hepáticas novamente, apesar de suspensão de ibuprofeno. Apurada exposição a tóxicos profissionais, percebendo-se que o quadro coincidiu com início da utilização de novo produto capilar contendo isopropanol. A doente retomou atividade profissional, não utilizando o produto, sem recorrência. Dada a relação temporal entre o desenvolvimento de hepatite aguda e a utilização de produtos contendo isopropanol, assumiu-se hepatotoxicidade por exposição profissional ao isopropanol. Esta substância é metabolizada no fígado e a toxicidade pode ocorrer por ingestão, exposição cutânea ou inalação, estando descrita em casos de exposição ocupacional ou acidental. O tratamento é sintomático e inclui a suspensão do tóxico.

Hypercalcemia-Leukocytosis syndrome and adenosquamous lung carcinoma: An overlooked conjugation.

Hypercalcaemia and leukocytosis are two paraneoplastic conditions associated with poor prognosis. Adenosquamous carcinoma is a rare and aggressive histological subtype of lung cancer consisting of adenocarcinoma and squamous cell components. We report the case of a 57-year-old male smoker who was admitted to the Emergency Room with skull and neck tumefactions, confusion and deteriorated general condition. The complementary study in the ER revealed severe hypercalcaemia (19.8 mg/dL), leukocytosis (18.7 × 109/L) and extensive osteolytic lesions of the skull on cranioencephalic computer tomography (CT). The patient was stabilized and admitted. Thoracoabdominopelvic CT showed lung parenchyma consolidation with necrotic areas, supra and infradiaphragmatic adenopathies and scattered osteolytic lesions. Percutaneous lymph node biopsy was consistent with metastasis of adenosquamous lung carcinoma. The patients' clinical situation evolved unfavourably after hospital-acquired infection. This case is characterized by a rare presentation of advanced stage adenosquamous lung carcinoma with scattered osteolytic lesions and severe hypercalcaemia-leukocytosis syndrome, an underrecognized marker of poor prognosis.

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.

A Case of Severe Cholestasis due to Hepatic AL Amyloidosis.

INTRODUCTION: Immunoglobulin light chain-associated amyloidosis results from extracellular tissue deposition of fibril-forming monoclonal immunoglobulin light chains, secreted by a clone of plasma cells. Although the liver is often involved histologically, most cases are clinically asymptomatic, and severe intrahepatic cholestasis as the primary manifestation of the disease is rare. CLINICAL CASE: We report an unusual case of primary amyloidosis in a 71-year-old man, presenting with rapidly progressive cholestasis, associated with hepatomegaly. There are a few reported cases in the literature of cholestasis and acute liver failure as the first manifestations of AL amyloidosis. CONCLUSION: Infiltrative diseases, such as amyloidosis, must be considered when a patient presents with cholestatic hepatitis. A liver biopsy is essential for the diagnosis of amyloidosis when liver test abnormalities dominate the initial clinical presentation. Liver involvement in patients with amyloidosis is often an indicator of poor prognosis.

Acute airway obstruction due to benign multinodular goitre.

Benign multinodular goitre is a common illness. When accompanied by obstructive symptoms, such as dyspnoea, it carries an indication for surgery. Benign multinodular goitres rarely cause acute airway obstruction. We report the case of a 88-year-old woman who presented with acute shortness of breath and stridor. A chest CT revealed marked enlargement of the thyroid gland, with an extensive intrathoracic component. She was proposed for total thyroidectomy. Her intraoperative course was unremarkable, but the patient passed away in postoperative period from ventricular fibrillation. Recognition of these cases is important, as they constitute a preventable cause of mortality if timely diagnosed and treated.

Enterococcus gallinarum Causing Native Valve Endocarditis.

Endocarditis due to Enterococcus gallinarum is a rare condition, usually affecting older patients. The most frequent source of infection is the gastrointestinal or genitourinary tracts; it frequently involves the aortic valve and tends to produce heart failure. We present a case of Enterococcus gallinarum endocarditis developing on a normal native heart valve. Enterococcus gallinarum is intrinsically resistant to vancomycin. Antibiotic susceptibility patterns indicate that most isolates are penicillin and ampicillin-susceptible. LEARNING POINTS: Endocarditis due to Enterococcus gallinarum is rare.Enterococcus gallinarum is intrinsically resistant to vancomycin.Most isolates are penicillin and ampicillin-susceptible.

Recurrent mesalazine-induced myopericarditis in a patient with ulcerative colitis.

Mesalazine is a common treatment for inflammatory bowel disease and can be rarely associated with myopericarditis. We report a case of a 19-year-old man recently diagnosed with ulcerative colitis and started on mesalazine, who presented with chest pain 2 weeks after beginning this therapy. Blood tests demonstrated elevated troponin I. ECG and echocardiographic changes were consistent with myopericarditis. When mesalazine was reintroduced 2 weeks after discharge, he suffered from myopericarditis again. On cessation of the drug, the cardiac symptoms resolved in combination with anti-inflammatory therapy. The onset of symptoms after mesalazine, and improvement of chest pain and cardiac biomarkers after discontinuing the drug, suggest that our patient suffered from a rare drug-hypersensitivity reaction to mesalazine.

Macrophagic myofasciitis: a challenging diagnosis.

A 25-year-old man admitted for generalised muscle pain with an insidious onset 3 years ago. He had exercise intolerance and decrease in muscle strength, requiring gait support. He was previously healthy, with no chronic medication or recent history of drugs or toxics. National vaccination plan actualised with hepatitis B and tetanus vaccines administered 10 and 2 years, respectively, before symptom onset. No analytical, imaging or electromyography changes were found. Muscle biopsy revealed an inflammatory infiltrate predominantly macrophagic with aluminium deposits suggestive of macrophagic myofasciitis (MMF). It is probably associated with vaccines previously administered. MMF lesion can be regarded as pathological only if detected at least 18 months after last aluminic immunisation, as our case illustrates.

Syphilitic Aortitis Diagnosis in Clinical Setting.

INTRODUCTION: Cardiovascular syphilis can manifest as aortic aneurysms, aortic regurgitation and coronary ostial stenosis. Tertiary syphilis was the most commom reported cause of thoracic aortic aneurysm in the pre-antibiotic era, contributing to 5- 10% of cardiovascular deaths. However, in the 21st century, it has virtually disappered from the devoloping nations. Tertiay syphilis may develop in about one third of cases of untreated syphilis. In the pre-penicilin era, it was calculated that cardiovascular syphilis was responsible for 10-15% of clinical syphilis. METHODS: We present a rare case of syphilitic aortitis in a era of highly effective antibiotics. RESULTS: A 48-year-old man with no known clinical cardiac pathology went to emergency with an episode of chest pain of short duration and great intensity, being hospitalized with a differential diagnosis of coronary disease, ascending aortic aneurysm and aortic valve regurgitation. Two segments of the aorta, 5cm and 9.5cm length were observed, both had thickened wall (1cm), and firm plaques with diferent shapes and sizes. The intima of the aorta appeared rough and pitted, with the appearance of tree bark. There were heterogeneous lesions of the tunica media: hyalinization and calcification, macrophages aggregates, areas of hemorrhage and lymphoplasmacytic infiltrate forming vascular sheaths. Adventitia exhibited hyperplasia of nerve pathways with surrounding lymphoplasmocytic infiltrate. The diagnosis of syphilitic aortitis was purposed and serological analysis revealed positivity for Treponema pallidum. Patient underwent surgical correction of an aortic aneurysm. CONCLUSION: The serological positivity for Treponema pallidum and the histopathological study allowed the currently rare diagnosis of Ascending Aortic Aneurysm by Tertiary Syphilis. In the present scenario with early and widespread use of antibiotics, it is considered a very rare disease.

Prevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study.

AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals. METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed. RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files. CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.

Miliary tuberculosis and Q fever in an immunocompetent patient.

Miliary tuberculosis is a progressive disease resulting from the massive hematogeneous dissemination of Mycobacterium tuberculosis. Immunocompromised and elderly patients are the most affected. A case of an immunocompetent 45 year old man, with miliary tuberculosis and a simultaneous infection by Coxiella burnetti is presented. The clinical presentation demands a high awareness for the presence of tuberculosis. The rarity of this association, only one case reported in literature, appears to be a fortuity coincidence.

Rendimiento y deserción del escolar dominicano a nivel primario y secundario y su potencial relación con su salud y nutrición / Dominican student's performance and desertion at elementary and secundary schools and its relationship with health and nutrition

Puntualiza las siguientes consideraciones: Ningún antecedente de estudios que relacione las variables de rendimiento y deserción escolar con la nutrición y la salud, la repetición y la deserción reflejan en la mayoría de los casos problemas de tipo nutricional y de índole de salud. El problema de alimentación escolar no ha sido una respuesta ante una dimensión generalizada que demanda mayor cobertura; el problema de la nutrición no escapa de la dimensión social del pueblo dominicano