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.

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.

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.

A rare case of diarrhea and ascites.

BACKGROUND: Eosinophilic enterocolitis is a rare condition included in the spectrum of the eosinophilic gastrointestinal disorders. Diagnosis is based on clinical presentation combined with an increase infiltration of eosinophils in the gastrointestinal tract, in the absence of other secondary causes of eosinophilic infiltration. CASE PRESENTATION: We report a case of a 22-year-old male with eosinophilic enterocolitis presenting with malabsorption syndrome (diarrhea, vomiting, weight loss), bowel wall thickening, and ascites. Secondary causes of intestinal eosinophilia were excluded, and diagnosis was established in a timely manner. Treatment plan included a 6-food elimination diet and corticosteroid therapy, with clinical remission after 2 weeks of therapy. The patient remains asymptomatic after 12 months of follow-up, with no relapse.

Misplacement of a nasogastric feeding tube: a case report.

Nasogastric tube (NGT) insertion is widely used for enteral feeding. After blind insertion of a NGT, confirmation of correct placement prior to feeding using reliable methods is mandatory. NGT misplacement in the respiratory tract can lead to serious complications. We report a case of a patient with dysphagia and malnutrition that needed enteral feeding as nutritional support. A NGT was blindly inserted, and its gastric position was confirmed through air insufflation and epigastric auscultation. Enteral feeding was initiated. Few hours later, the patient presented with respiratory distress. An urgent thoracic computed tomography was requested due to suspiction of pulmonary embolism, which revealed the NGT in the respiratory tree and a pneumonia in the lower lobe of the right lung. The NGT was removed, a new insertion was attempted and its gastric position was confirmed by radiography. Enteral feeding was initiated uneventfully. This case highlights the need for use of reliable methods of confirming tube location in order to avoid complications of misplacement.

Black stomach: acute gastric wall ischemia due to polycythemia of an unknown origin.

Acute ischemia of the gastric mucosa, resulting in a black stomach, is a very rare event given the blood supply of the stomach, with a rich collateral blood flow system. We present the case of a 65-year-old man, with polycythemia of unknown origin under investigation, presented to the emergency department with a history of diffuse abdominal pain and hematemesis. Blood tests revealed a hemoglobin level of 22 g/dL.Upper endoscopy revealed a black ulcerated gastric mucosa compatible with acute necrosis of the corpus and antrum of the stomach . Despite few cases described in the literature, many etiologic factors have been suggested. In this particular case, given the severe polycythemia and associated hyperviscosity, vascular compromise of the gastric blood vessels might have played a major role in the pathogenesis of the ischemic process.

Use of MALDI-TOF mass spectrometry to analyze the molecular profile of Pseudomonas aeruginosa biofilms grown on glass and plastic surfaces.

Biofilms are microbial sessile communities attached to surfaces that are known for causing many medical problems. A bacterial biofilm of clinical relevance is formed by the gram-negative bacteria Pseudomonas aeruginosa. During the formation of a biofilm, the initial adhesion of the cells is of crucial importance, and the characteristics of the contact surface have great influence on this step. In the present study, we aimed to use matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling as a new methodology to monitor P. aeruginosa biofilm development. Biofilms were grown within polypropylene tubes containing a glass slide, and were harvested after 3, 5, 7, 9, or 12 days of inoculation. Planktonic cells were obtained separately by centrifugation as control. Two independent MALDI-TOF experiments were performed, one by collecting biofilms from both the glass slide and the polypropylene tube internal surface, and the other by acquiring biofilms from these surfaces separately. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to evaluate the morphological progression of the biofilm. The molecular results showed that MALDI profiling is able not only to distinguish between different biofilm stages, but it is also appropriate to indicate when the biofilm cells are released at the dispersion stage, which occurred first on polypropylene surface. Finally, the present study pointed out that MALDI profiling may emerge as a promising tool for the clinical diagnostic and prognostic workup of biofilms formation and control.

Preeclampsia is associated with increased maternal body weight in a northeastern Brazilian population.

BACKGROUND: Preeclampsia is a disease with great variability in incidence across the world. The mortality is higher in lower income countries, where it is the leading cause of maternal mortality. This study aimed to determine the frequency of and risk factors for preeclampsia in a low income population from an urban area of Brazil. METHODS: A prospective case control study of 242 women of which 30 developed preeclampsia, 4 had gestational hypertension, 2 had superimposed hypertension, 11 had spontaneous abortion, 13 were lost to follow up and 192 had normal pregnancy. This latter group was considered the normotensive controls. The rate of preeclampsia and the risk of cardiovascular disease, after onset of preeclampsia, were determined. RESULTS: Of the 218 women who completed the study, the frequency of hypertensive disorder of pregnancy was 16.5% (36 of 218) and of preeclampsia was 13.8% (30 of 218). Women with preeclampsia had a higher body mass index (BMI), mean of 25.3 ± 4.8 compared to 23.5 ± 3.7 for the normotensive controls, p = 0.02. The risk of preeclampsia increased with BMI [Odds ratio (OR) 1.12, 95% Confidence Interval (CI = 1.02;1.24, p-value = 0.023)]. Women with preeclampsia developed chronic hypertension more often than normotensive controls (p = 0.043) and their systolic and ambulatory blood pressure monitoring was elevated (p = 0.034). Women with preeclampsia had higher BMI even 5 years post-pregnancy (p = 0.008). CONCLUSIONS: Women who are overweight or older have an increased risk of preeclampsia. Previous history of preeclampsia increases the risk of early onset of chronic hypertension. Therefore, effective preventive measures are needed, particularly women at lower social economic stratum who have less access to proper medical care and adequate nutrition.

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.

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.

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.