An unusual cardiac involvement in mixed connective tissue disease / Una afección cardíaca poco común en la enfermedad mixta del tejido conjuntivo

Mixed connective tissue disease is an autoimmune disorder with overlapping features of systemic lupus erythematosus, systemic sclerosis and polymyositis. Cardiac involvement is common, being pericarditis the most frequent manifestation, as also pulmonary hypertension. The authors present a case of a woman with one year of symptoms of polyarthritis and myalgia with gradual muscle weakness and weight loss, with severe impaired mobility in the last months. The initial evaluation showed an inflammatory systemic condition with an infiltrative pattern in echocardiogram, with pulmonary hypertension, that was confirmed by cardiac magnetic resonance. After an extensive study, where infiltrative cardiomyopathies were a differential diagnosis, the patient meet criteria to mixed connective disease with signs of pulmonary hypertension and an atypical cardiac involvement. Immunosuppressive treatment and rehabilitation were initiated and one year after the patient remains asymptomatic without any limitations. (AU)

La enfermedad mixta del tejido conectivo es un trastorno autoinmune con características superpuestas de lupus eritematoso sistémico, esclerosis sistémica y polimiositis. La afectación cardiaca es común, siendo la pericarditis la manifestación más frecuente, al igual que la hipertensión pulmonar. Los autores presentan el caso de una mujer con un año de síntomas de poliartritis y mialgia con debilidad muscular gradual y pérdida de peso, con grave deterioro de la movilidad en los últimos meses. La evaluación inicial mostró un cuadro inflamatorio sistémico con patrón infiltrativo en ecocardiograma, con hipertensión pulmonar, que se confirmó por resonancia magnética cardiaca. Tras un amplio estudio, en el que las miocardiopatías infiltrativas constituyeron un diagnóstico diferencial, la paciente cumplía criterios de conectivopatía mixta con signos de hipertensión pulmonar y una afectación cardiaca atípica. Se inició tratamiento inmunosupresor y rehabilitación y un año después la paciente permanece asintomática sin limitaciones. (AU)

Systolic Blood Pressure and Pulse Pressure Are Predictors of Future Cardiovascular Events in Patients with True Resistant Hypertension.

Given the increased risk of cardiovascular events associated with resistant hypertension, predictive cardiovascular prognosis is extremely important. Ambulatory blood pressure monitoring (ABPM) is mandatory for resistant hypertension diagnosis, but its use for prognosis is scarce. This observational longitudinal study included 258 patients (mean age of 60.4 ± 11.2 years; 61.2% male), who underwent 24 h ABPM in a hypertension unit from 1999 to 2019. The outcomes were global cardiovascular events (cerebrovascular, coronary, and other cardiovascular events). The mean follow-up period was 6.0 ± 5.0 years. Sixty-eight cardiovascular events (61 nonfatal) were recorded. Patients who experienced cardiovascular events were generally older, with higher rates of chronic kidney disease and prior cardiovascular events. The 24 h systolic blood pressure (hazard ratio 1.44; 95% CI 1.10-1.88), night systolic blood pressure (1.35; 95% CI 1.01-1.80), and 24 h pulse pressure (2.07; 95% CI 1.17-3.67) were independent predictors of global cardiovascular events. Multivariate Cox analysis revealed a higher risk of future cardiovascular events, particularly in patients with a 24 h daytime and nighttime pulse pressure > 60 mm Hg with respective hazard ratios of 1.95; 95% CI 1.01-3.45; 2.15; 95% CI 1.21-3.83 and 2.07; 95% CI 1.17-3.67. In conclusion, APBM is a fundamental tool not only for the diagnosis of resistant hypertension, but also for predicting future cardiovascular events.

Pott's disease (tuberculous spondylitis).

Pott's disease is a vertebral infection caused by Mycobacterium tuberculosis. Indolent nature and subacute course are associated with late diagnosis. A clinical case is presented whose diagnosis was delayed by atypical presentation with progressive worsening of symptoms. Magnetic resonance imaging (MRI) of the dorsolumbar spine revealed T7-T8 angulation suggestive of secondary injury, with intracanalar extension and spinal cord compression. Gastric aspirate cultures, direct microscopy, and polymerase chain reaction (PCR) were A 79-yearold female came to the emergency department with right back pain, pleuritic, with 12 h of evolution. Anorexia and weight loss,1 month evolution. Computed tomography (CT) of the dorsal spine revealed T7-T8 lytic lesions, suggestive of secondary nature. Objectively:weight loss and pain during thoracic palpation. Annalistically: normocytic/normochromic anemia, hypercalcemia, hepatic cholestasis, C-reactive protein (CRP) 7.12 mg/dL. Chest X-ray and electrocardiogram without alterations. She was admitted in Internal Medicine service. Analytically: hypophosphatemia, parathyroid hormone elevated, CRP 6 mg/dL, Beta-2 microglobulin elevated, dyslipidemia, iron and folicacid deficiency.negative for M. tuberculosis. T8 aspiration CT guided: cultures/direct microscopy negative, PCR positive for M. tuberculosis. Introductionof antitubercular drugs. Worsening of symptomatology, with paraparesia. MRI of the dorsal spine revealed spondylodiscitis and spinal cordcompression in T7-T8. Diagnosis revealed vertebral tuberculosis with spinal cord compression. She was transferred to neurosurgery servicefor surgical treatment. There was clinical and analytical improvement. Draws attention to difficulty in diagnose a treatable disease in a patientwith a rare presentation.

Multi-Gene Panel Testing in Gastroenterology: Are We Ready for the Results?

Genetic testing aims to identify patients at risk for inherited cancer susceptibility. In the last decade, there was a significant increase in the request of broader panels of genes as multi-gene panel testing became widely available. However, physicians may be faced with genetic findings for which there is lack of management evidence, despite some progress in understanding their clinical relevance. In this short review, we discuss the advantages and the drawbacks related to multi-gene panel testing in the setting of a Gastrointestinal Familial Cancer Risk clinic. We also summarize the available recommendations on management of pathogenic variant carriers.

O estudo genético tem como objetivo identificar indivíduos em risco de cancro hereditário. Na última década, verificou-se um aumento significativo do número de genes analisados devido ao surgimento de painéis de sequenciação multi-gene. Neste sentido, os médicos podem ser confrontados com resultados genéticos para os quais não há orientações de manejo ou seguimento, apesar de progressos na compreensão da relevância clínica dessas variantes genéticas. Nesta revisão de literatura, discutimos as vantagens e desvantagens dos testes de sequenciação multi-gene e apresentamos um resumo das recomendações disponíveis relativas à orientação dos portadores de variantes genéticas patogénicas.

Familial Amyloidotic Polyneuropathy Type 1: A Hereditary Legacy.

Familial amyloidotic polyneuropathy type 1 (FAP 1) is a systemic autosomal dominant amyloidosis, associated with transthyretin mutation. It is characterised by motor, autonomic and sensory neuropathy with relentless progression that results from amyloid deposition in different tissues. The authors describe the case of a patient with family history of a nephew, who underwent liver transplantation for unknown pathology, as well as the deaths of both his mother and a brother due to stroke. He reported complaints of dizziness, asthenia and sensory changes in the lower limbs and a history of arterial hypertension, dyslipidemia and chronic kidney disease. Physical examination revealed macroglossia and pain hyposensitivity in the anterior feet. In subsequent evaluation, the presence of proteinuria, changes in cardiac electrical conduction, sensory and motor neuropathy with sympathetic and parasympathetic dysfunction in electrophysiological study raised the suspicion of a systemic disease. The patient underwent kidney biopsy, which was positive for amyloid. FAP 1 diagnosis was later confirmed by genetic testing. Family history review confirmed that patient's liver transplanted nephew and other two nieces had FAP 1, which he was initially unaware of. Key Words: Familial amyloidotic polyneuropathy, Systemic amyloidosis, Transthyretin.

Immunologic biomarkers, morbidity and mortality among HIV patients hospitalised in a Tertiary Care Hospital in the Brazilian Amazon.

BACKGROUND: The irregular use of antiretroviral therapy (ART) and late diagnosis still account for a large part of HIV-associated mortality in people living with HIV (PLHIV). Herein, we describe HIV-associated morbidity among hospitalised HIV/AIDS patients with advanced immunosuppression and assess the comorbidities, laboratory parameters, and immunological markers associated with mortality. METHODS: The cross-sectional study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil. In all, 83 participants aged between 12 and 70 years were enrolled by convenience within 72 h of their hospitalisation. Clinical and laboratory data were obtained from electronic medical records. We prospectively measured the cytokines Th1/Th2/Th17 and inflammatory cytokines IL-8, IL-1ß, and IL-12 using cytometric bead array, and the soluble CD14 using in-house enzyme-linked immunosorbent assay. RESULTS: The HIV/AIDS inpatients presented a scenario of respiratory syndromes as the most prevalent comorbidity. Almost all patients had CD4 T counts below 350 cells/mL and the mortality rate was 20.5%. Pulmonary tuberculosis, neurotoxoplasmosis and oropharyngeal-esophageal candidiasis were the most prevalent opportunistic infections. TB and weight loss were more prevalent in HIV/AIDS inpatients who died. The Mann Whitney analysis showed that those who died had higher platelet distribution width (PDW) on admission, which is suggestive for platelet activation. The Poisson multivariate analysis showed the prevalence of TB, digestive syndrome and increases in IL-8 and lactate dehydrogenase (LDH) associated to death. CONCLUSIONS: The advanced immunosuppression characterized by the opportunistic infections presented in these HIV/AIDS inpatients was the major factor of mortality. The role of platelet activation in worse outcomes of hospitalisation and the IL-8 associated with the context of advanced immunosuppression may be promising markers in the prediction of mortality in HIV/AIDS patients.

High Detection Rate of HIV Drug Resistance Mutations among Patients Who Fail Combined Antiretroviral Therapy in Manaus, Brazil.

Virologic failure may occur because of poor treatment adherence and/or viral drug resistance mutations (DRM). In Brazil, the northern region exhibits the worst epidemiological scenarios for the human immunodeficiency virus (HIV). Thus, this study is aimed at investigating the genetic diversity of HIV-1 and DRM in Manaus. The cross-sectional study included people living with HIV on combined antiretroviral therapy and who had experienced virological failure during 2018-2019. Sequencing of the protease/reverse transcriptase (PR/RT) and C2V3 of the viral envelope gp120 (Env) regions was analyzed to determine subtypes/variants of HIV-1, DRMs, and tropism. Ninety-two individuals were analyzed in the study. Approximately 72% of them were male and 74% self-declared as heterosexual. Phylogenetic inference (PR/RT-Env) showed that most sequences were B subtype, followed by BF1 or BC mosaic genomes and few F1 and C sequences. Among the variants of subtype B at PR/RT, 84.3% were pandemic (B PAN), and 15.7% were Caribbean (B CAR). The DRMs most frequent were M184I/V (82.9%) for nucleoside reverse transcriptase inhibitors (NRTI), K103N/S (63.4%) for nonnucleoside reverse transcriptase inhibitor (NNRTI), and V82A/L/M (7.3%) for protease inhibitors (PI). DRM analysis depicted high levels of resistance for lamivudine and efavirenz in over 82.9% of individuals; although, low (7.7%) cross-resistance to etravirine was observed. A low level of resistance to protease inhibitors was found and included patients that take atazanavir/ritonavir (16.6%) and lopinavir (11.1%), which confirms that these antiretrovirals can be used-for most individuals. The thymidine analog mutations-2 (TAM-2) resistance pathway was higher in B CAR than in B PAN. Similar results from other Brazilian studies regarding HIV drug resistance were observed; however, we underscore a need for additional studies regarding subtype B CAR variants. Molecular epidemiology studies are an important tool for monitoring the prevalence of HIV drug resistance and can influence the public health policies.

Syphilitic hepatitis; a rare manifestation of a common disease.

Syphilis is a sexual transmitted disease caused by Treponema pallidum and an underdiagnosed and underreported cause of acute hepatitis. In recent years, reported cases of primary and secondary syphilis have been increasing, mostly in men who have sex with men. Clinical manifestations of syphilis are diverse, earning the name of "the great imitator" which can affect virtually any organ. Nonetheless, hepatic involvement is rare, but it can occur at any stage of the disease. We present the case of a 41-year-old immunocompetent male, that presents to us with a cholestatic hepatitis and a diffuse erythematous rash with palmo-plantar affection. The patient had no history of primary syphilis. After throughout aetiologic study, he was diagnosed with syphilitic hepatitis and treated with intramuscular Benzathine benzylpenicillin, with the disappearance of the rash and normalization of liver enzymes after 3 months. We would like to highlight that this aetiology should be considered in patients with unexplained elevation of liver enzymes (mainly cholestatic enzymes) and an epidemiologic context of unsafe sexual exposure.

Immune Thrombocytopenia: A Rare Presentation of Pulmonary Sarcoidosis.

Thrombocytopenia may be the initial presentation of sarcoidosis, which is a systemic granulomatous disorder. Various pathophysiological mechanisms have been identified. Immune thrombocytopenia often has a severe presentation but may respond favourably to immunosuppressive therapy. There are no guidelines for the treatment of thrombocytopenia in sarcoidosis. However, in emergency situations with major bleeding, it seems reasonable to apply the current guidelines recommended for immune thrombocytopenia. The authors report a case of sarcoidosis presenting with severe thrombocytopenia, petechial rash, and nasal and gingival bleeding. LEARNING POINTS: The association of thrombocytopenia with sarcoidosis has been well described and fully documented.Immune thrombocytopenia in sarcoidosis is usually severe and symptomatic at presentation but generally has a favourable course because of modern therapeutic management.Steroids may be administered as first-line treatment for sarcoidosis, but in emergency situations with a severe bleeding risk, it seems reasonable to apply the current guidelines for immune thrombocytopenia, namely methylprednisolone (1 g/day for 2 days) and/or intravenous immunoglobulin (1 g/kg/day for 3 days).

Hepatic osteodystrophy in cirrhosis due to alcohol-related liver disease.

INTRODUCTION: hepatic osteodystrophy, including osteoporosis, is an abnormal bone metabolism related with chronic liver diseases. Osteoporosis is associated with an increased risk of bone fractures, with a significant impact on morbidity, mortality and healthcare costs. Nevertheless, bone disorders tend to be undervalued in cirrhosis due to alcohol-related liver disease (ALD cirrhosis). This study aimed to assess the prevalence of hepatic osteodystrophy and osteoporosis in ALD cirrhosis. METHODS: a prospective observational study was performed that included patients with ALD cirrhosis, between September 2017 and December 2018. Bone mineral density was determined by dual energy X-ray absorptiometry at the lumbar spine and the femoral neck. Hepatic osteodystrophy was defined as a T-score below -1 SD and osteoporosis as a T-score below -2.5 SD. RESULTS: ninety-four patients were included; 24.5 % (n = 23) had prior fragility fractures and ten patients suffered new osteoporotic fractures during the study period. Hepatic osteodystrophy was diagnosed in 79.8 % (n = 75) and osteoporosis in 21.3 % (n = 20) of cases. Patients with hepatic osteodystrophy presented significantly worse Child-Turcotte-Pugh (p < 0.05) and Model for End-Stage Liver Disease (MELD-sodium) scores (p = 0.01). According to the multivariate analysis, lower body mass index (BMI) (OR = 0.787, 95 % CI: 0.688-0.901, p = 0.001) and vitamin D deficiency (OR = 6.798, 95 % CI: 1.775-26.038, p = 0.005) were significantly and independently associated with hepatic osteodystrophy. Patients with osteoporosis also had a lower BMI (p = 0.01). Female patients and those with prior fragility fractures were more likely to suffer from osteoporosis (p < 0.05). CONCLUSION: our study revealed a high prevalence of hepatic osteodystrophy and osteoporosis in patients with ALD cirrhosis (particularly in those with a lower BMI) and a concerning high rate of fragility fractures. Bone mineral density should be assessed in order to allow for an early diagnosis and the implementation of preventive measures.

Ischemic stroke related to HIV and SARS-COV-2 co-infection: a case report.

A 56-year-old male with human immunodeficiency virus required hospitalization due to the onset of both dyspnea and asthenia. A computed tomography of the chest exam showed the radiological pattern of coronavirus SARS-CoV-2 pulmonary involvement. Based on immunochromatographic analysis, the patient evolved as a reagent for immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-SARS-CoV-2 antibodies. The individual developed complete hemiparesis with a predominance in the right arm and conduction aphasia. T1-weighted magnetic resonance sequence of the brain showed an area of hypointensity with a high intrinsic cortical signal and hyperintensity in the T2-sequence. A Doppler velocimetric examination showed total/critical sub occlusion, suggesting an ischemic stroke.

Intestinal intussusception associated to diabetes / Intususcepción intestinal asociada a diabetes

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Isolated testicular tuberculosis with ethambutol cutaneous toxicity: A combination of two rare entities.

Tuberculosis (TB) is an infection that can affect any organ, affecting mainly the lungs. Isolated testicular TB is very rare. Six months of a multiple drug scheme is the mainstay of TB treatment. Adverse reaction to anti-TB chemotherapy is frequent and affects the course of the therapy, leading sometimes to discontinuation of drugs. Ethambutol optic nerve toxicity is frequent. However, severe cutaneous and anaphylactic reactions associated to ethambutol are very rare. We present the case of an immunocompetent patient presenting with isolated testicular TB that exhibited a severe cutaneous and anaphylactic reaction to ethambutol during the consolidation treatment phase. This led to exhaustive etiologic study and treatment modification.

Should patients with symptomatic cholelithiasis before 30 years of age be tested for ABCB4 gene mutations?

BACKGROUND AND AIMS: Low phospholipid-associated cholelithiasis syndrome (LPAC) is characterized by recurrent symptomatic cholelithiasis in young adults associated with ABCB4 gene mutations. Current diagnosing criteria are complex and heterogeneous, making this a largely underdiagnosed entity. Also, although recommended, genetic testing is not necessary for the diagnosis and its real advantages are not clear. The aim of our study was to explore the prevalence of ABCB4 mutations in symptomatic patients with cholelithiasis before the age of 30. METHODS: We conducted a multicentric prospective cohort study including patients with symptomatic cholelithiasis presenting before 30 years of age in 4 Portuguese centres between January 2017 and December 2019. ABCB4 gene was analyzed by next generation sequencing (NGS) including all exons and flanking regions. In 17/32 patients ABCB11 and ATP8B1 variants were also analyzed by NGS. RESULTS: Thirty-two patients were included (75% females, median age of symptom onset was 23 ± 5 years). We found that 8/32 (25%) patients had mutations in ABCB4 gene, 3/17 (18%) in ATP8B1 gene and 1/17 (6%) in ABCB11 gene. 44% (8/18) of patients with LPAC syndrome criteria had identified variants, while the prevalence of mutations in patients with symptoms onset before 30 as sole criteria was 29%. CONCLUSION: Our results suggest that LPAC should be systematically suspected and investigated in patients with symptomatic cholelithiasis before age of thirty, but genetic testing should only be attempted in patients complying with the more stringent LPAC criteria.

Metastasis of lobular breast carcinoma in the bowel / Metástasis de carcinoma lobular de mama en el intestino

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