Severe Acute Liver Injury due to Secondary Hemophagocytic Lymphohistiocytosis: A Case Report.

Severe acute liver injury (ALI) is mostly triggered by viral infections and hepatotoxic drugs; however, it can also be seen in systemic diseases. Hemophagocytic lymphohistiocytosis (HLH) is a rare, immune-mediated syndrome that presents as a life-threatening inflammatory disorder affecting multiple organs. Secondary causes occur mainly in the set of malignancy, infection, and autoimmune disease, and are seldom triggered by vaccination. Although liver involvement is common, presentation as severe ALI is rare. We describe a case of a 65-year-old male with history of low-risk chronic lymphocytic leukemia and rheumatoid arthritis treated with prednisolone who presented with persistent fever and jaundice 1 week after COVID-19 vaccination. The diagnosis was challenging given the predominant liver impairment, characterized by hyperbilirubinemia, transaminases over 1,000 U/L, and prolonged INR, which prompted an extensive investigation and exclusion of autoimmune, toxic, and viral causes of hepatitis. Laboratory workup revealed bicytopenia, hyperferritinemia, which together with organ failure and evidence of hemophagocytosis in bone marrow suggested the diagnosis of HLH. After excluding infectious etiologies, flare of rheumatological disease, and the progression of hematological disease, HLH was diagnosed. He was successfully treated with etoposide and corticosteroids, with dramatic improvement of liver tests. After exclusion of other causes of secondary HLH, the recent vaccination for COVID-19 was the likely trigger. We report a case of double rarity of HLH, as it presented with severe liver dysfunction which was probably triggered by vaccination. In this case, the predominant liver involvement urged extensive investigation of liver disease, so a high index of suspicion was required to make an early diagnosis. Clinicians should consider HLH in patients with unexplained signs and symptoms of systemic inflammatory response and multiorgan involvement, including severe liver involvement as the first presentation.

A lesão hepática aguda (LHA) grave é desencadeada principalmente por infeções virais e hepatotóxicos; contudo, pode ocorrer em condições com envolvimento sistémico. A linfohistiocitose hemofagocítica (LHH) é uma síndrome inflamatória, rara, imunomediada, potencialmente fatal, que pode afetar múltiplos órgãos. A LHH secundária ocorre em contexto de neoplasias, infeções e doenças autoimunes, podendo raramente ser precipitada pela vacinação. Embora seja frequente o envolvimento hepático na LHH, a apresentação como LHA grave é rara. Os autores descrevem o caso de um homem de 65 anos com história de leucemia linfocítica crónica de baixo risco e artrite reumatóide sob prednisolona de 65 anos, que se apresentou com febre persistente e icterícia uma semana após a primeira dose da vacina COVID-19. O diagnóstico constituiu um desafio dado o envolvimento hepático predominante, caracterizado por hiperbilirrubinemia, transaminases acima de 1000 U/L e INR prolongado, o que condicionou uma extensa investigação e exclusão das causas autoimunes, tóxicas, e virais de doença hepática. A presença de bicitopenia e hiperferritinemia, conjuntamente com o desenvolvimento de falências de órgão e evidência de hemofagocitose na medula óssea sugeriram o diagnóstico de LHH. Após exclusão infeções, agudização da doença reumatológica e progressão da doença hematológica, foi feito o diagnóstico de LHH.O doente foi tratado com etoposido e corticosteróides com sucesso, verificando-se uma melhoria dramática das provas hepáticas. Após a exclusão de outras causas de LHH secundária, a recente vacinação foi assumida como provável fator desencadeante. Relatamos um caso raro de LHH, quer pela apresentação com lesão hepática grave, quer pela vacinação como presumível desencadeante. Neste caso, o envolvimento hepático predominante promoveu a uma investigação extensa da doença hepática, tendo sido necessário um elevado índice de suspeição para um diagnóstico atempado. Os médicos devem considerar o diagnóstico de LHH em doentes com sinais e sintomas de resposta inflamatória sistémica, inexplicados que se acompanham por disfunção multiorgânica, nomeadamente disfunção hepática grave como apresentação clínica.

Severe Hypercholesterolemia Mediated by Lipoprotein X in an Immunosuppressed Patient: A Case Report.

Cholestatic liver diseases may be associated with increased plasmatic cholesterol due to an abnormal lipoprotein - lipoprotein X (LpX). Correcting the underlying cause of cholestasis is the critical treatment of LpX-associated hypercholesterolemia without any proven benefit from conventional lipid-lowering agents. In some situations, plasma exchange may apply to prevent associated complications, such as hyperviscosity syndrome. The authors present the case of a 44-year-old man with orbital inflammatory pseudotumor on prednisolone, admitted due to hepatocellular and cholestatic lesion and severe hypercholesterolemia. Laboratory investigation established that hepatitis E virus was responsible for liver injury and showed that LpX mediated the severe hypercholesterolemia. Reduction of the immunosuppressive load contributed to virus clearance. The consequent resolution of cholestasis and cholesterol removal by plasmapheresis allowed lipid profile normalization. The authors report the first case of LpX-associated hypercholesterolemia in a patient with hepatitis E-induced cholestasis and revisit the role of the liver in lipid metabolism.

As doenças hepáticas colestáticas podem associar-se a um aumento do colesterol à custa de uma lipoproteína anómala, a lipoproteína X (LpX). Os agentes hipolipemiantes convencionais não apresentam benefício nesta entidade, pelo que o tratamento da hipercolesterolemia associada de LpX baseia-se na correção da causa subjacente da colestase. A plasmaferese pode ser necessária para evitar complicações, como a síndrome de hiperviscosidade. Os autores apresentam o caso de um homem de 44 anos com antecedentes de pseudotumor inflamatório da órbita sob prednisolona, admitido por lesão hepatocelular e colestática e hipercolesterolemia grave. A investigação laboratorial permitiu estabelecer a hepatite E aguda como responsável da lesão hepática e mostrou que a hipercolesterolemia grave foi mediada pela LpX. A redução da carga imunossupressora facilitou a eliminação do vírus da hepatite E. A consequente resolução da colestase coadjuvada pela remoção de colesterol por plasmaferese, permitiu a normalização mantida do perfil lipídico. Os autores relatam o primeiro caso de hipercolesterolemia associada a LpX em contexto de colestase induzida pelo vírus da hepatite E, e revisitam a importância do fígado no metabolismo dos lípidos.

Inflammatory myofibroblastic tumor presenting as a subepithelial lesion of the colon.

We present the case of a 42-year-old male admitted to the emergency department for a 15-day history of diarrhea, with bloody stools in the past 7 days. The patient denied abdominal pain or distension as well as any constitutional symptoms. On physical examination he presented good general health condition, with abdomen slightly tender in the lower quadrants; digital rectal examination was remarkable for the presence of dark blood. Laboratory evaluation revealed new onset normocytic anemia (Hb 10.8 g/dL, MCV 89 fL) and RCP of 3.3 mg/dL. Colonoscopy was performed, which showed a large cecal subepithelial lesion, with surface ulcerations. Histology reported mixed inflammatory infiltrate but no malignancy. Further investigation was carried out with an abdominal and pelvic computerized tomography that, other than the cecal mass, showed multiple infracentimetric mesenteric lymph nodes. A right laparoscopic hemicolectomy was performed. Pathological analysis led to the unusual diagnosis of inflammatory myofibroblastic tumor (IMT) of the colon. There was no sign of recurrence after 6 months of follow-up.

Primary gastric leiomyosarcoma presenting as a giant polyp.

We present the case of a 35-year-old woman with previous hereditary retinoblastoma treated with radiotherapy, admitted due to severe iron deficiency anemia. Upper endoscopy and endoscopic ultrasound revealed a 5-cm polypoid lesion in the fundus arising from muscularis mucosa. Histological findings favored a sarcoma with muscular differentiation. After exclusion of metastatic disease, the patient underwent surgery and diagnosis of primary gastric leiomyosarcoma was confirmed. We report a case of double rarity of gastric leiomyosarcoma, as she presented with severe anaemia from a polypoid lesion of the gastric fundus.

Intestinal and perianal tuberculosis: an uncommon clinical presentation and challenging diagnosis.

We present the case of a 40-year-old immunocompetent man with complaints of perianal abscess, diarrhea, and weight loss for 3 months. He denied respiratory symptoms. Colonoscopy revealed ulcers and histopathology showed non-necrotizing granulomas and excluded acid-fast bacilli. Initially, the clinical and histological findings favored the diagnosis of Crohn's disease, however, further investigation by performing chest radiography in the context of a pre-immunomodulatory checklist, revealed pulmonary cavitations confirmed on computed tomography scan. Further mycobacteriological studies suggested the diagnosis of active pulmonary tuberculosis. Demonstration of the presence of Mycobacterium tuberculosis in the colon was possible by RT-PCR. Complete resolution of intestinal and perianal symptoms was achieved 2 weeks after treatment with anti-bacillary agents.

Gastroduodenal artery pseudoaneurysm presenting with hyperamylasemia.

We present the case of a 75-year-old male admitted due to severe epigastric pain. His medical history was remarkable for chronic alcohol abuse, diabetes mellitus type 2, arterial hypertension, dyslipidemia. At admission he was hemodynamically stable. The initial workup showed elevated amylase, and the abdominal ultrasound excluded gallstone disease, so the diagnosis of acute pancreatitis was assumed. Despite appropriate fluid therapy, the patient developed hemodynamic instability. No signs of GIB were detected. An urgent laboratory workup revealed a new onset anemia and liver tests, including hyperbilirrubinemia. He underwent an urgent abdominal computed tomography with contrast, which showed a bleeding gastroduodenal artery (pseudoaneurysm and a hematoma adjacent to the second part of the duodenum. The patient underwent coil embolization achieving hemostasis without complications. GAD (pseudo)aneurysm is rare, accounting for 1.5% of all visceral artery aneurysms. Our patient presented with elevated pancreatic and liver enzymes, a more unique and challenging presentation since another more common differential diagnosis should be considered. The aneurysm can cause extrinsic common bile duct and main pancreatic duct pressure, which could explain the raised liver tests. Gastroenterologists should be aware of this rare and life-threatening entity, especially among patients presenting with common findings such as elevated amylase, jaundice, or altered liver tests. Hemodynamic instability is the main clue unmasking this diagnosis.

Henoch-Schönlein purpura masquerading as Crohn's disease flare.

We describe the case of a 69-year-old male with Crohn's disease (CD), treated with infliximab and undergoing intestinal resection. The surgery and postoperative period were unremarkable, with no CD-related symptoms. Two months after surgery and two weeks after the introduction of infliximab, he was admitted due to acute onset diffuse abdominal pain, hematochezia and arthralgia. On physical observation on admission, he showed signs of arthritis of the left knee. Laboratory tests revealed renal failure with nephrotic proteinuria, slightly low complement (C3) and IgA elevation. Remaining autoimmunity and viral panel were negative. Abdominal examination showed duodenum and thickening of the proximal wall of the jejunum. Biopsies excluded active CD. Colon and ileum mucosa were normal. The patient met EULAR criteria for Henoch-Schönlein purpura and was started on prednisolone with response. Although no clear trigger was pointed out, we switched anti-TNF to ustekinumab. We present this case given its endoscopic exuberance, and because of the high index of suspicion to make the diagnosis in adult patients with previous inflammatory bowel disease. The distinction between this vasculitis and CD is of utmost importance, given the therapeutic implications.

Isolated Jejunal Crohn's Disease: a challenging diagnosis.

A 27-year-old Nepalese male presented with recurrent abdominal pain accompanied by a lower stool consistency over the past 2 years. These episodes occurred several times a year, lasting 1 to 2 weeks, and resolved spontaneously, after adjustment of diet and/or medication for symptomatic control (e.g., antispasmodics, probiotics). Over the last year, the patient had undergone an extensive diagnostic investigation, which revealed no alterations in the laboratory workup, abdominal scan, esophagogastroduodenoscopy, and colonoscopy, including biopsies of the duodenum, and colon, so the symptoms have been attributed to irritable bowel syndrome. However, the symptoms had become more frequent, so the patient was referred to our gastroenterology department. We repeated and extended the work-up. Laboratory investigations showed an elevated erythrocyte sedimentation rate and faecal calprotectin. The remaining laboratory as well an extensive stool workup for infection were unremarkable. Esophagogastroduodenoscopy and ileocolonoscopy were normal. Small bowel capsule endoscopy revealed jejunal mucosa with lymphangiectasias, pseudopolypoids formations and superficial longitudinal ulcers, these findings were corroborated by the double-balloon enteroscopy, and biopsies showed marked architectural distortion, chronic inflammatory infiltrate, and an epithelioid granuloma. The clinical, endoscopic, biochemical, and histological findings were consistent with isolated jejunal Crohn's disease. The patient started adalimumab with complete remission after one year. We present this case given its exuberant endoscopic findings and due to the difficulty in making the diagnosis due to its rarity, location, and unspecific presentation.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Inflammatory myofibroblastic tumor presenting as a subepithelial lesion of the colon

We present the case of a 42-year-old male admitted to the emergency department for a 15-day history of diarrhea, with bloody stools in the past 7 days. The patient denied abdominal pain or distension as well as any constitutional symptoms. On physical examination he presented good general health condition, with abdomen slightly tender in the lower quadrants; digital rectal examination was remarkable for the presence of dark blood. Laboratory evaluation revealed new onset normocytic anemia (Hb 10.8 g/dL, MCV 89 fL) and RCP of 3.3 mg/dL. Colonoscopy was performed, which showed a large cecal subepithelial lesion, with surface ulcerations. Histology reported mixed inflammatory infiltrate but no malignancy. Further investigation was carried out with an abdominal and pelvic computerized tomography that, other than the cecal mass, showed multiple infracentimetric mesenteric lymph nodes. A right laparoscopic hemicolectomy was performed. Pathological analysis led to the unusual diagnosis of inflammatory myofibroblastic tumor (IMT) of the colon. There was no sign of recurrence after 6 months of follow-up (AU)

Hepatocellular Carcinoma with Atrial Extension: A Case Report.

Hepatocellular carcinoma is a common malignancy usually associated with cirrhosis. Despite being a highly aggressive tumor with several cases of vascular invasion, metastatic disease to the heart is a rare condition. A 65-year-old male cirrhotic patient was admitted with dyspnea, ascites, and lower extremity edema. A transthoracic echocardiogram showed a large mass in the right atrium. Further imaging studies revealed the presence of hepatocellular carcinoma extending from the liver to the right atrium through the inferior vena cava. The cardiac mass was surgically removed to treat the symptoms of right heart failure, but unfortunately the patient died on the 30th day after surgery due to septic shock.

O carcinoma hepatocelular é uma neoplasia comum, maioritariamente associada à cirrose hepática. Apesar de se tratar de uma entidade clínica agressiva com predisposição à invasão vascular, a doença metastática com envolvimento cardíaco é rara. Os autores reportam o caso de um homem de 65 anos com cirrose hepática que recorreu ao serviço de urgência por um quadro clínico de dispneia, ascite e edema periférico. Foi realização ecocardiograma transtorácico à admissão, que revelou presença de uma massa a nivel da aurícula direita. A investigação clínica, laboratorial e imagiológica realizada permitiu o diagnóstico de carcinoma hepatocelular com extensão desde o fígado até à aurícula direita através da veia cava inferior. A massa intracardíaca foi removida cirurgicamente para alivio sintomático, no entanto o doente faleceu no 30° dia de pós-operatório devido a choque séptico.

Lower Gastrointestinal Bleeding Associated With Sodium Polystyrene Sulfonate Use.

Sodium polystyrene sulfonate (kayexalate) is a cation-exchange resin widely used in the management of hyperkalemia. Gastrointestinal adverse events are uncommon; symptoms are nonspecific, and mucosal injury can range from mild ulceration to bowel perforation. An 81-year-old man was admitted because of decompensation of cirrhosis with acute kidney injury and hyperkalemia, treated with sodium polystyrene sulfonate. During admission, he presented multiple episodes of hematochezia, accompanied by tachycardia and hemoglobin drop. Colonoscopy revealed colonic ulceration, and histopathological findings were compatible with ulceration due to kayexalate injury. Despite rare, the widespread use of sodium polystyrene sulfonate puts a large population at risk of serious complications related to its use.

Primary hepatic lymphoma in a patient with cirrhosis: a case report.

BACKGROUND: Primary hepatic lymphoma is a very uncommon disease. Due to its nonspecific clinical, laboratory, and imaging findings, it is often misdiagnosed. Liver biopsy is required to make a final diagnosis. Chemotherapy is the current gold standard of treatment. CASE PRESENTATION: An asymptomatic 65-year-old Caucasian man with Child-Pugh class A cirrhosis presented to our hospital with a nodular lesion seen on a routine surveillance abdominal ultrasound. His physical examination revealed hepatomegaly and no other significant findings. Magnetic resonance imaging of the abdomen showed a voluminous nodule on the left lobe with heterogeneous contrast enhancement. His liver biopsy was compatible with diffuse large B-cell lymphoma. Systemic staging showed no evidence of nodal or bone marrow involvement, confirming the diagnosis of primary hepatic lymphoma. He was treated with chemotherapy. However, he developed febrile neutropenia after one of the cycles and died. CONCLUSIONS: In this article, we report a rare presentation of non-Hodgkin lymphoma and review the current literature on clinical features, diagnosis, and management.

O que facilita e dificulta a aprendizagem? a perspetiva de adolescentes / ¿qué facilita y dificulta el aprendizaje? la perspectiva de los adolescentes / What makes learning easier and more difficult? the perspective of teenagers

RESUMO Este estudo qualitativo teve como objetivo analisar as perceções de alunos adolescentes acerca dos aspetos que facilitam e dificultam a sua aprendizagem. O conhecimento das perceções dos alunos sobre a sua aprendizagem permite melhorar a qualidade dos processos de ensino-aprendizagem. A partir de um guião semiestruturado, foram realizados cinco grupos focais, em cinco escolas privadas do Norte de Portugal, tendo participado 32 alunos selecionados aleatoriamente. Os participantes eram alunos do 3º ciclo do Ensino Básico (7º, 8º e 9º anos), com idades compreendidas entre os 12 e os 15 anos. A análise dos dados seguiu um processo semi-indutivo de codificação descritiva. Os resultados realçam o papel fundamental do professor na aprendizagem; a importância da ação vs passividade dos alunos na sala de aula; a relevância da dimensão emocional e relacional para o envolvimento do aluno; e a relevância das estratégias de autorregulação da aprendizagem. Como implicações sugere-se a concretização de ações junto de professores e alunos assente nos dados recolhidos e analisados, que sejam promotoras da metacognição de ambos.

RESUMEN Este estudio cualitativo tuvo como objetivo analizar las percepciones de alumnos adolescentes acerca de los aspectos que facilitan y dificultan su aprendizaje. El conocimiento de las percepciones de los alumnos sobre su aprendizaje permite mejorar la calidad de los procesos de enseñanza-aprendizaje. A partir de un guión semiestructurado, cinco discusiones en grupos focales se llevaron a cabo en cinco escuelas privadas en el Norte de Portugal, que han participado 32 estudiantes seleccionados aleatoriamente. Los participantes eran alumnos del 3º ciclo de la Enseñanza Básica (7º, 8º y 9º años), con edades comprendidas entre los 12 y los 15 años. El análisis de los datos siguió un proceso semi-inductivo de codificación descriptiva. Los resultados subrayan el papel fundamental del profesor para el aprendizaje; la importancia de la acción de los alumnos en el aula versus pasividad; la relevancia de la dimensión emocional y relacional para la participación del alumno y de las estrategias de autorregulación del aprendizaje. Como implicaciones se sugiere la concreción de acciones junto a profesores y alumnos acerca de los datos recogidos y analizados, que sean promotores de la metacognición de ambos.

ABSTRACT This qualitative study aimed to understand the perceptions of adolescent students about what facilitates and hinders their learning. The knowledge of students' perceptions about their learning allows to improve the quality of the learning processes quality. Five focus groups were conducted, with a semi-structured script, in five different private schools from the North of Portugal, having participated in 32 students randomly selected. Participants were students from 7th, 8th and 9th grades, with ages between 12 and 15 years old. The data analysis followed a semi-inductive process and descriptive coding of data. The results highlighted the key role of teachers in students' learning; the importance of students action versus passivity in the classroom; the relevance of emotional and relational dimension to enhance students' engagement, and the relevance of learning self-regulation strategies. As for implications, it is suggested that actions be carried out with teachers and students based on the data collected and analyzed, in order to promote metacognition of both.