Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring.

Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immune-intermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.

Intraretinal Microvascular Abnormalities in Eyes with Advanced Stages of Nonproliferative Diabetic Retinopathy: Comparison Between UWF-FFA, CFP, and OCTA-The RICHARD Study.

INTRODUCTION: This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. METHODS: The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). RESULTS: Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. CONCLUSIONS: Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05112445.

DIAGNOSTIC ACCURACY OF THE NON-INVASIVE MARKERS NFLS, NI-NASH-DS, AND FIB-4 FOR ASSESSMENT OF DIFFERENT ASPECTS OF NON-ALCOHOLIC FATTY LIVER DISEASE IN INDIVIDUALS WITH OBESITY: CROSS-SECTIONAL STUDY.

BACKGROUND: Non-invasive markers have been developed to assess the presence and severity of liver abnormalities related to non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: To analyze the diagnostic accuracy of non-invasive NAFLD markers (NAFLD liver fat score [NLFS], non-invasive non-alcoholic steatohepatitis detection score [NI-NASH-DS] and fibrosis score based on four variables [FIB-4]) in individuals with obesity undergoing bariatric surgery. METHODS: A descriptive retrospective cross-sectional study was carried out enrolling 91 individuals who underwent bariatric surgery at a tertiary-level public university hospital. Non-invasive NAFLD markers were calculated using laboratory tests, clinical and anthropometric variables and diagnostic accuracy tests were calculated comparing them in relation to the gold-standard test for this analysis (histopathological evaluation). RESULTS: A total of 85.7% of the participants were female and mean age was 39.1±9.8 years. The average body mass index was 38.4±3.6 kg/m2. At histopathological examination, 84 (92.3%) patients presented with steatosis, 82 (90.1%) with some type of fibrosis; 21 (23.1%) patients were diagnosed with NASH according to the NAFLD activity score criteria. The overall accuracy of NLFS score was 58.2% for general hepatic steatosis and 61.5% for moderate to severe steatosis. The overall accuracy of FIB-4 was 95.4% for advanced fibrosis. NI-NASH-DS had a 74.7% overall accuracy for NASH. CONCLUSION: In a population of individuals with obesity, the FIB-4 score had high overall accuracy in assessing the presence of advanced liver fibrosis, whereas the NFLS and NI-NASH-DS had moderate accuracies for the assessment of steatosis and NASH, respectively.

Effects of bariatric surgery on renal function: a retrospective cohort study comparing one-year outcomes between one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Evidence on the effect of one-anastomosis gastric bypass (OAGB) on renal function is limited. OBJECTIVE: To compare the evolution of estimated renal function observed 1 year after OAGB and Roux-en-Y gastric bypass (RYGB) in individuals with obesity. DESIGN AND SETTING: Observational, analytical, and retrospective cohort study. Tertiary-level university hospital. METHODS: This study used a prospectively collected database of individuals who consecutively underwent bariatric surgery. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR), according to the Chronic Kidney Disease Epidemiology Collaboration. The one-year variation in the eGFR was compared between the procedures. RESULTS: No significant differences in age, sex, obesity-associated conditions, or body mass index were observed among individuals who underwent either OAGB or RYGB. OAGB led to a significantly higher percentage of total (P = 0.007) and excess weight loss (P = 0.026). Both OAGB and RYGB led to significantly higher values of eGFR (103.9 ± 22 versus 116.1 ± 13.3; P = 0.007, and 102.4 ± 19 versus 113.2 ± 13.3; P < 0.001, respectively). The one-year variation in eGFR was 11 ± 16.2% after OAGB and 16.7 ± 26.3% after RYGB (P = 0.3). Younger age and lower baseline eGFR were independently associated with greater postoperative improvement in renal function (P < 0.001). CONCLUSION: Compared with RYGB, OAGB led to an equivalent improvement in renal function 1 year after the procedure, along with greater weight loss.

Patterns of Progression of Nonproliferative Diabetic Retinopathy Using Non-Invasive Imaging.

Purpose: To identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. Methods: This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Results: Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Conclusions: Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Translational Relevance: Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.

Characterization of central-involved diabetic macular edema using OCT and OCTA.

PURPOSE: To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). METHODS: In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. RESULTS: During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (ß = 7.7 ± 2.1 µm/year, p < 0.001) and in LOR values (ß = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CONCLUSIONS: CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.

Association of Histopathological and Biochemical Aspects of NAFLD With the Severity of Liver Fibrosis in Individuals With Obesity: Cross-sectional Study.

BACKGROUND: Given the importance of fibrosis in the progression of non-alcoholic fatty liver disease (NAFLD), identifying biochemical and histopathological aspects associated with its severity is important to determine the course of disease in high-risk populations. OBJECTIVES: The study aims to investigate correlations between biochemical and histopathological variables associated with the occurrence and severity of NAFLD-related liver fibrosis in individuals with obesity. METHODS: This is a cross-sectional study which enrolled 171 individuals who underwent bariatric surgery at a tertiary university hospital. Clinical, laboratory, and histopathological hepatic characteristics were analyzed. Univariate and multivariate analyses were carried out to identify factors associated with the outcomes studied (severity of fibrosis staging) through simple and multiple regression models. RESULTS: Female were 87.7%, and the mean age was 38.4 ± 9.3 years. The most common histopathological abnormalities were macrovesicular steatosis (74.9%) and hepatocellular ballooning (40.4%). In the histopathological univariate analysis, liver fibrosis significantly correlated with severities of microvesicular steatosis (p = 0.003), lobular inflammation (p = 0.001), and NAS (p < 0.001). In the multivariate analysis, the degrees of microvesicular steatosis (p < 0.001) and NAS (p < 0.001) independently correlated with fibrosis severity. In the univariate biochemical analysis, fibrosis severity significantly correlated with levels of hemoglobin A1c (p = 0.004) and glucose (p = 0.01). In the multivariate analysis, glucose levels independently correlated with liver fibrosis degree (p = 0.007). CONCLUSION: Significant and independent associations were observed between the intensities of microvesicular steatosis, NAS, and glucose levels and the severity degree of liver fibrosis in individuals with obesity.

Hereditary angioedema with normal C1-inhibitor: Clinical and genetic characterization of 15 Portuguese unrelated families.

BACKGROUND: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease with similar phenotype to HAE-C1-INH but different genetic background. Currently, 6 subtypes are recognized, based on the underlying mutations. Several aspects need further clarification. OBJECTIVE: To assess clinical features of patients with genetically characterized HAE-nC1-INH from the North of Portugal. METHODS: Retrospective assessment of clinical data from all patients with HAE-nC1-INH followed at a HAE Reference Center. RESULTS: A total of 41 patients were identified, 4 with no family history. The FXII mutation Thr328Lys (38 carriers) was the most prevalent. There were 3 new potentially disease-causing variants linked to HAE-nC1-INH identified (c.529+4A>G:FXII; Cys248*:Kininogen-1; and Arg261His:Plasminogen). The HAE-FXII cohort included 82% females and 71.8% symptomatic patients. Penetrance rate was significantly higher in females (81.3% vs 28.6%; P = .012). A hormonal influence was observed in 96.2% of the symptomatic females, although 62.5% remained symptomatic after oral estrogen withdrawal. Trauma and dental procedures were frequent triggers (82.6% and 45.5%, respectively). Main locations were facial (described by 96%), lips (82.1%), and eyelids (64.3%). One patient reported erythema marginatum as prodrome. Plasma-derived C1-INH was effective as short-term prophylaxis in all treated patients, but only in 80% as on-demand treatment. Icatibant was effectively used on demand in 9 patients, but with relapses in 5 (57%). CONCLUSION: We described a large Portuguese series of patients with HAE-nC1-INH genetically characterized. Differences with others may contribute to improve current unmet needs and raise awareness of this rare disease. We highlighted the identification of 3 new variants (additional molecular studies are ongoing) and the report of erythema marginatum in HAE-nC1-INH.

Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery.

BACKGROUND: As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. OBJECTIVE: To identify predictors of the occurrence and severity of NAFLD and NASH. METHODS: This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. RESULTS: Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. CONCLUSIONS: NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.

Fibrotic NASH in Individuals with Obesity: a Cross-sectional Analysis of the Prevalence of this Significant Milestone of Disease Progression and Accuracy of a Non-invasive Marker for its Screening.

BACKGROUND: Fibrotic non-alcoholic steatohepatitis (NASH), i.e., the concomitant presence of active inflammation and fibrosis, represents a milestone in the natural history of NAFLD and a critical time point in its progression. The purpose of this study was to analyze the diagnostic accuracy of the non-invasive Fibrotic NASH Index (FNI) in individuals with obesity undergoing bariatric surgery. METHODS: This is a cross-sectional study, enrolling individuals who underwent bariatric surgery with liver biopsy at a tertiary university hospital. FNI was calculated, and a cutoff value was determined. Its diagnostic accuracy was then calculated through comparison with the gold standard test for this analysis (histopathological examination). RESULTS: Of 128 participants, 83.6% were female, and the average age was 39.8 ± 8.7 years. The mean BMI was 38.7 ± 5.7 kg/m2. NAFLD was histologically confirmed in 76.6%, of which 81.6% had NASH. Histologically confirmed fibrotic NASH was observed in 22.7% of the general study population, 29.6% of individuals with NAFLD, and 36.3% of those with NASH. The mean FNI was 0.18 ± 0.19. An optimal cutoff point of 0.21 was determined, with an overall accuracy of 90.1%, an 82.8% sensitivity, a 90.8% specificity, a 72.6% positive predictive value, and a 94.7% negative predictive value. CONCLUSIONS: FNI provided adequate accuracy in detecting and ruling out fibrotic NASH. Considering the importance of fibrotic NASH within the natural history of NAFLD progression and the fact that this marker uses simple variables, it may be of great importance in high-risk populations, and its external validation and use should be encouraged.

CENTRAL AND PERIPHERAL INVOLVEMENT OF THE RETINA IN THE INITIAL STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery. METHODS: Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA). RESULTS: Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%. CONCLUSION: Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy.

Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison

ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

Effects of bariatric surgery on renal function: a retrospective cohort study comparing one-year outcomes between one-anastomosis gastric bypass and Roux-en-Y gastric bypass

ABSTRACT BACKGROUND: Evidence on the effect of one-anastomosis gastric bypass (OAGB) on renal function is limited. OBJECTIVE: To compare the evolution of estimated renal function observed 1 year after OAGB and Roux-en-Y gastric bypass (RYGB) in individuals with obesity. DESIGN AND SETTING: Observational, analytical, and retrospective cohort study. Tertiary-level university hospital. METHODS: This study used a prospectively collected database of individuals who consecutively underwent bariatric surgery. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR), according to the Chronic Kidney Disease Epidemiology Collaboration. The one-year variation in the eGFR was compared between the procedures. RESULTS: No significant differences in age, sex, obesity-associated conditions, or body mass index were observed among individuals who underwent either OAGB or RYGB. OAGB led to a significantly higher percentage of total (P = 0.007) and excess weight loss (P = 0.026). Both OAGB and RYGB led to significantly higher values of eGFR (103.9 ± 22 versus 116.1 ± 13.3; P = 0.007, and 102.4 ± 19 versus 113.2 ± 13.3; P < 0.001, respectively). The one-year variation in eGFR was 11 ± 16.2% after OAGB and 16.7 ± 26.3% after RYGB (P = 0.3). Younger age and lower baseline eGFR were independently associated with greater postoperative improvement in renal function (P < 0.001). CONCLUSION: Compared with RYGB, OAGB led to an equivalent improvement in renal function 1 year after the procedure, along with greater weight loss.

NI-NASH-DS e FIB-4 para avaliação de diferentes aspectos da doença hepática gordurosa não-alcoólica em indivíduos com obesidade: estudo transversal / Diagnostic accuracy of the non-invasive markers nfls, ni-nash-ds, and fib-4 for assessment of different aspects of non-alcoholic fatty liver disease in individuals with obesity: cross-sectional study

ABSTRACT Background: Non-invasive markers have been developed to assess the presence and severity of liver abnormalities related to non-alcoholic fatty liver disease (NAFLD). Objective: To analyze the diagnostic accuracy of non-invasive NAFLD markers (NAFLD liver fat score [NLFS], non-invasive non-alcoholic steatohepatitis detection score [NI-NASH-DS] and fibrosis score based on four variables [FIB-4]) in individuals with obesity undergoing bariatric surgery. Methods: A descriptive retrospective cross-sectional study was carried out enrolling 91 individuals who underwent bariatric surgery at a tertiary-level public university hospital. Non-invasive NAFLD markers were calculated using laboratory tests, clinical and anthropometric variables and diagnostic accuracy tests were calculated comparing them in relation to the gold-standard test for this analysis (histopathological evaluation). Results: A total of 85.7% of the participants were female and mean age was 39.1±9.8 years. The average body mass index was 38.4±3.6 kg/m2. At histopathological examination, 84 (92.3%) patients presented with steatosis, 82 (90.1%) with some type of fibrosis; 21 (23.1%) patients were diagnosed with NASH according to the NAFLD activity score criteria. The overall accuracy of NLFS score was 58.2% for general hepatic steatosis and 61.5% for moderate to severe steatosis. The overall accuracy of FIB-4 was 95.4% for advanced fibrosis. NI-NASH-DS had a 74.7% overall accuracy for NASH. Conclusion: In a population of individuals with obesity, the FIB-4 score had high overall accuracy in assessing the presence of advanced liver fibrosis, whereas the NFLS and NI-NASH-DS had moderate accuracies for the assessment of steatosis and NASH, respectively.

RESUMO Contexto: Marcadores não-invasivos foram desenvolvidos para avaliar a presença e a gravidade de anormalidades hepáticas relacionadas à doença hepática gordurosa não-alcoólica (DHGNA). Objetivo: Analisar a acurácia diagnóstica de marcadores não-invasivos de DHGNA (escore de gordura hepática da DHGNA [NLFS], escore não-invasivo de detecção de esteato-hepatite não-alcoólica [NI-NASH-DS] e escore de fibrose de 4 variáveis [FIB-4]) em indivíduos obesos submetidos à cirurgia bariátrica. Métodos: Foi realizado um estudo descritivo retrospectivo transversal com 91 indivíduos submetidos à cirurgia bariátrica em um hospital universitário público de nível terciário. Marcadores não-invasivos de DHGNA foram calculados por meio de exames laboratoriais, variáveis clínicas e antropométricas; testes de acurácia diagnóstica foram calculados comparando-os em relação ao exame padrão-ouro para essa análise (avaliação histopatológica). Resultados: Um total de 85,7% dos participantes eram do sexo feminino e a média de idade foi de 39,1±9,8 anos. O índice de massa corporal médio foi de 38,4±3,6 kg/m2. Ao exame histopatológico, 84 (92,3%) pacientes apresentavam esteatose, 82 (90,1%) com algum grau de fibrose; 21 (23,1%) pacientes foram diagnosticados com esteato-hepatite não-alcoólica (EHNA) de acordo com os critérios do escore de atividade da DHGNA. A acurácia global do escore NLFS foi de 58,2% para esteatose hepática e 61,5% para esteatose moderada a grave. A acurácia global do FIB-4 foi de 95,4% para fibrose avançada. NI-NASH-DS apresentou uma acurácia global de 74,7% para EHNA. Conclusão: Em uma população de indivíduos com obesidade, o escore FIB-4 teve alta acurácia global para avaliar a presença de fibrose hepática avançada, enquanto o NFLS e o NI-NASH-DS tiveram acurácias moderadas para avaliar a esteatose e EHNA, respectivamente.

Retinal Capillary Nonperfusion in Preclinical Diabetic Retinopathy.

INTRODUCTION: The aim of the study was to identify retinal microvascular changes using optical coherence tomography angiography (OCTA) in type 2 diabetes (T2D) patients with preclinical retinopathy identified by ultra-widefield fundus photography (UWF-FP). METHODS: This is a cross-sectional observational study. All patients underwent UWF-FP 200° examinations with OPTOS California (Optos, Dunfermline, UK) and Cirrus AngioPlex® spectral-domain (SD)-OCTA 3 × 3 mm acquisitions (ZEISS, Dublin, CA, USA). The absence of visible lesions was identified using UWF-FP. RESULTS: One hundred and ninety three eyes of individuals with T2D with no visible lesions in the fundus and identified in a screening setting were included in the study. Skeletonized vessel density (SVD), perfusion density (PD), and areas of capillary nonperfusion (CNP) values on SD-OCTA were significantly decreased when compared with healthy population (p < 0.001). SVD and CNP values of the superficial capillary plexus (SCP) were more frequently decreased (35% and 45%, respectively) than SVD values of the deep capillary plexus (DCP) (9% and 15%, respectively), demonstrating that diabetic microvascular changes occur earlier in the SCP than in the DCP. The ischemic phenotype, identified by a definite decrease in SVD or CNP in the SCP may, therefore, be identified in the preclinical stage of diabetic retinal disease. CONCLUSIONS: Retinal capillary nonperfusion detected by OCTA metrics of SVD and CNP can be identified in the central retina in eyes with T2D before development of visible lesions in the retina. Our findings confirm the relevance of OCTA to identify macular microvascular changes in the initial stages of diabetic retinopathy, allowing the identification of its ischemic phenotype very early in the disease process.

HLA-A23/HLA-A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasma.

MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma-derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/pre-dementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA-A23/A24 and dementia. HLA-A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA-A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA-A23/HLA-A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers.

Osteomyelitis caused by Aspergillus terreus complex in a dog: a case report.

BACKGROUND: In dogs, the most frequently reported mycosis associated with Aspergillus spp. are respiratory infections. Systemic aspergillosis is uncommon, with reported cases been associated with several Aspergillus species. Aspergillus terreus species complex are ubiquitous organisms, unfrequently associated with local or systemic disease in animals and humans, and treatment of osteomyelitis caused by this species is usually unfavorable. CASE PRESENTATION: This case report describes the case of a 5-year-old dog, referred to the Veterinary Hospital of the Faculty of Veterinary Medicine of the University of Lisbon, Portugal, with a history of lameness of the right thoracic limb. Radiographs and CT scan revealed two different lesions on right humerus and radio, which were biopsied. The samples collected were submitted to cytological and histopathological evaluation and bacterial and mycological culture. Environmental samples, including of the surgery room and of the biopsy needle were also evaluated for the presence of fungi. Regarding biopsy samples, bacterial culture was negative, but mycological analysis originated a pure culture of a fungal species later identified as Aspergillus terreus by Sanger sequencing. Results were compatible with histopathologic examination, which revealed periosteal reaction and invasion of hyphae elements. Also, mycological analysis of both environmental samples evaluated were negative. The virulence profile of the fungal isolate was phenotypically characterized using specific media, allowing to reveal its ability to produce several enzymes involved in its pathogenicity, namely lipase, hemolysin and DNAse, corresponding to a Virulence Index (V. Index.) of 0.43. The patient was submitted to itraconazole therapy for 8 weeks. After 3 weeks, the patient showed significant clinical improvement, and after 6 weeks no radiographic signs were observed. CONCLUSIONS: Antifungal therapy with itraconazole can contribute to the remission of canine infections promoted by Aspergillus terreus complex with a relevant V. Index.

DO HELICOBACTER PYLORI INFECTION AND ERADICATION THERAPY STATUS INFLUENCE WEIGHT LOSS OUTCOMES AND ENDOSCOPIC FINDINGS AFTER ROUX-EN-Y GASTRIC BYPASS?A HISTORICAL COHORT STUDY.

BACKGROUND: Currently, there is conflicting evidence linking Helicobacter pylori (HP) infection with weight loss and endoscopic findings after Roux-en-Y gastric bypass (RYGB). OBJECTIVE: To identify correlations between HP infection and its eradication with weight loss and endoscopic findings after RYGB. METHODS: This is an observational retrospective cohort study based on a prospectively collected database of individuals who underwent RYGB from 2018-2019 at a tertiary university hospital. HP infection and the HP eradication therapy outcomes were correlated with post-operative weight loss and endoscopic findings. Individuals were classified according to the status of HP infection into four groups: no infection; successful eradication; refractory infection; and new-onset infection. RESULTS: Of 65 individuals, 87% were female and the mean age was 39±11.2 years. Body mass index significantly decreased from 36.2±3.6 to 26.7±3.3 kg/m2 one year after RYGB (P<0.0001). The percentage of total weight loss (%TWL) was 25.9±7.2% and the percentage of excess weight loss was 89.4±31.7%. HP infection prevalence decreased from 55.4% to 27.7% (p=0.001); 33.8% never had HP infection, 38.5% were successfully treated, 16.9% had refractory infection and 10.8 % had new-onset HP infection. %TWL was 27.3±7.5% in individuals who never had HP, 25.4±8.1% in the successfully treated, 25.7±5.2% in those with refractory infection, and 23.4±6.4% in the new-onset HP infection group; there were no significant differences among the four groups (P=0.6). Pre-operative HP infection significantly associated with gastritis (P=0.048). New-onset HP infections significantly associated with a lower frequency of jejunal erosions after surgery (P=0.048). CONCLUSION: No effects of the HP infection on weight loss were identified in individuals undergoing RYGB. A higher prevalence of gastritis was observed in individuals with HP infection before RYGB. New-onset HP infection after RYGB was a protective factor for jejunal erosions.