Mind the gap in kidney care: translating what we know into what we do / Atenção às lacunas no cuidado renal: traduzindo o que sabemos em ações

Abstract Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Resumo Historicamente, são necessários, em média, 17 anos para que novos tratamentos passem da evidência clínica para a prática diária. Considerando os tratamentos altamente eficazes disponíveis atualmente para prevenir ou retardar o início e a progressão da doença renal, esse período é demasiadamente longo. Agora é o momento de reduzir a lacuna entre o que sabemos e aquilo que fazemos. Existem diretrizes claras para a prevenção e o manejo dos fatores de risco comuns para doenças renais, como hipertensão e diabetes, mas apenas uma fração das pessoas com essas condições é diagnosticada mundialmente, e um número ainda menor recebe tratamento adequado. Da mesma forma, a grande maioria das pessoas que sofrem de doença renal não têm conhecimento de sua condição, pois ela costuma ser silenciosa nos estágios iniciais. Mesmo entre pacientes que foram diagnosticados, muitos não recebem tratamento adequado para a doença renal. Levando em consideração as graves consequências da progressão da doença renal, insuficiência renal ou óbito, é imperativo que os tratamentos sejam iniciados precocemente e de maneira adequada. As oportunidades para diagnosticar e tratar precocemente a doença renal devem ser maximizadas, começando no nível da atenção primária. Existem muitas barreiras sistemáticas, que vão desde o paciente até o médico, passando pelos sistemas de saúde e por fatores sociais. Para preservar e melhorar a saúde renal para todos em qualquer lugar, cada uma dessas barreiras deve ser reconhecida para que soluções sustentáveis sejam desenvolvidas e implementadas sem mais demora.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database.

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Mortality risk and burden of aortic aneurysm and dissection attributable to low temperatures: A nationwide case-crossover analysis in Brazil, a predominantly tropical country.

BACKGROUND: Low temperatures are adverse contributors to cardiovascular diseases, but the associations between short-term exposure to cold and the risk of death from aortic dissection and aneurysm remain unclear, particularly in tropical regions. OBJECTIVE: This study was conducted based on 123,951 records of deaths caused by aortic dissection and aneurysms extracted from the national Mortality Information System in Brazil between 2000 and 2019. METHODS: Relative risks and 95 % confidence intervals (CI) for the aortic-related deaths associated with low ambient temperatures were estimated using the conditional logistic model combined with the distributed lag nonlinear model. Subgroup analyses were performed by age group, sex, race, education level, and residential region. Furthermore, this study calculated the number and fraction of aortic-related deaths attributed to temperatures below the temperature threshold to quantify the cold-related mortality burden of aortic diseases. RESULTS: During the study period, aortic-related deaths and mortality rates in Brazil exhibited a steady increase, rising from 4419 (2.66/100,000) in 2000 to 8152 (3.88/100,000) in 2019. Under the identified temperature threshold (26 °C), per 1 °C decrease in daily mean temperature was associated with a 4.77 % (95 % CI: 4.35, 5.19) increase in mortality risk of aortic-related diseases over lag 0-3 days. Females, individuals aged 50 years or older, Asian and Black race, and northern residents were more susceptible to low temperatures. Low temperatures were responsible for 19.10 % (95 % CI: 17.71, 20.45) of aortic-related deaths in Brazil. CONCLUSION: This study highlights that low temperatures were associated with an increased risk of aortic-related deaths, with a remarkable burden even in this predominantly tropical country.

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma.

OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

Ecological niche shift and suitable area expansion of a globally invasive species Phthorimaea operculella.

Phthorimaea operculella is a major potato pest of global importance, early warning and detection of which are of significance. In this study, we analyzed the climate niche conservation of P. operculella during its invasion by comparing the overall climate niche from three dimensions, including the differences between native range (South America) and entire invaded region (excluding South America), the differences bwtween native range (South America) and five invaded continents (North America, Oceania, Asia, Africa, and Europe), as well as the differences between native region (South America) and an invaded region (China). We constructed ecological niche models for its native range (South America) and invaded region (China). The results showed that the climatic niche of the pest has expanded to varying degrees in different regions, indicating that the pest could well adapt to new environments during the invasion. Almost all areas of South America are suitable for P. operculella. In China, its suitable area is mainly concentrated in Shandong, Hebei, Tianjin, Beijing, Henan, Hubei, Yunnan, Guizhou, Sichuan, Hainan, northern Guangxi, southern Hunan, Anhui, Guangdong, Jiangsu, southern Shanxi, and southern Shaanxi. With increasing greenhouse gas emissions and global temperature, its suitable area will decrease at low latitude and increase gradually at high latitude. Specifically, the northern boundary will extend to Liaoning, Jilin, and the southeastern region of Inner Mongolia, while the western boundary extends to Sichuan and the southeast Qinghai-Tibet Plateau. The suitable area in the southeast Yunnan-Guizhou Plateau, Hainan Island, and the south of Yangtze River, will gradually decrease. The total suitable habitat area for P. operculella in China is projected to increase under future climate condition. From 2081 to 2100, under the three greenhouse gas emissions scenarios of ssp126, ssp370, and ssp585, the suitable area is expected to increase by 27.78, 165.54, and 140.41 hm2, respectively. Therefore, it is crucial to strengtehen vigilance and implement strict measures to prevent the further expansion of P. operculella.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation.

OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Brazilin-7-acetate, a novel potential drug of Parkinson's disease, hinders the formation of α-synuclein fibril, mitigates cytotoxicity, and decreases oxidative stress.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the accumulation of α-synuclein (α-Syn) aggregates. However, there are currently no effective therapies for PD. Brazilin, an inhibitor of α-Syn aggregation, is unstable and toxic. Therefore, we have developed and synthesized derivatives of brazilin. One of these derivatives, called brazilin-7-acetate (B-7-A), has shown reduced toxicity and a stronger effect on inhibiting α-Syn aggregation. It showed that B-7-A prevented the formation of α-Syn fibers and disrupted existing fibers in a dosage-dependent manner. Additionally, B-7-A significantly reduced the cytotoxicity of α-Syn aggregates and alleviated oxidative stress in PC12 cells. The beneficial effects of B-7-A were also confirmed using the Caenorhabditis elegans model. These effects included preventing the accumulation of α-Syn clumps, improving behavior disorder, increasing lifespan, reducing oxidative stress, and protecting against lipid oxidation and loss. Finally, B-7-A showed good ADMET properties in silico. Based on these findings, B-7-A exhibits potential as a prospective treatment for PD.

High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation

SUMMARY OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma

Abstract Objective To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. Methods 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. Results GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. Conclusion GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage.

PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

Graph analysis of cortical reorganization after virtual reality-based rehabilitation following stroke: a pilot randomized study.

Introduction: Stroke is the leading cause of functional disability worldwide. With the increase of the global population, motor rehabilitation of stroke survivors is of ever-increasing importance. In the last decade, virtual reality (VR) technologies for rehabilitation have been extensively studied, to be used instead of or together with conventional treatments such as physiotherapy or occupational therapy. The aim of this work was to evaluate the GestureCollection VR-based rehabilitation tool in terms of the brain changes and clinical outcomes of the patients. Methods: Two groups of chronic patients underwent a rehabilitation treatment with (experimental) or without (control) complementation with GestureCollection. Functional magnetic resonance imaging exams and clinical assessments were performed before and after the treatment. A functional connectivity graph-based analysis was used to assess differences between the connections and in the network parameters strength and clustering coefficient. Results: Patients in both groups showed improvement in clinical scales, but there were more increases in functional connectivity in the experimental group than in the control group. Discussion: The experimental group presented changes in the connections between the frontoparietal and the somatomotor networks, associative cerebellum and basal ganglia, which are regions associated with reward-based motor learning. On the other hand, the control group also had results in the somatomotor network, in its ipsilateral connections with the thalamus and with the motor cerebellum, which are regions more related to a purely mechanical activity. Thus, the use of the GestureCollection system was successfully shown to promote neuroplasticity in several motor-related areas.

Texture-based brain networks for characterization of healthy subjects from MRI.

Brain networks have been widely used to study the relationships between brain regions based on their dynamics using, e.g. fMRI or EEG, and to characterize their real physical connections using DTI. However, few studies have investigated brain networks derived from structural properties; and those have been based on cortical thickness or gray matter volume. The main objective of this work was to investigate the feasibility of obtaining useful information from brain networks derived from structural MRI, using texture features. We also wanted to verify if texture brain networks had any relation with established functional networks. T1-MR images were segmented using AAL and texture parameters from the gray-level co-occurrence matrix were computed for each region, for 760 subjects. Individual texture networks were used to evaluate the structural connections between regions of well-established functional networks; assess possible gender differences; investigate the dependence of texture network measures with age; and single out brain regions with different texture-network characteristics. Although around 70% of texture connections between regions belonging to the default mode, attention, and visual network were greater than the mean connection value, this effect was small (only between 7 and 15% of these connections were larger than one standard deviation), implying that texture-based morphology does not seem to subside function. This differs from cortical thickness-based morphology, which has been shown to relate to functional networks. Seventy-five out of 86 evaluated regions showed significant (ANCOVA, p < 0.05) differences between genders. Forty-four out of 86 regions showed significant (ANCOVA, p < 0.05) dependence with age; however, the R2 indicates that this is not a linear relation. Thalamus and putamen showed a very unique texture-wise structure compared to other analyzed regions. Texture networks were able to provide useful information regarding gender and age-related differences, as well as for singling out specific brain regions. We did not find a morphological texture-based subsidy for the evaluated functional brain networks. In the future, this approach will be extended to neurological patients to investigate the possibility of extracting biomarkers to help monitor disease evolution or treatment effectiveness.

Spontaneous hemoperitoneum during pregnancy: three case reports and literature review.

OBJECTIVES: This case report presented cases with spontaneous hemoperitoneum during pregnancy. CASE REPORT: Case 1 presented with acute abdominal pain with signs of shock. Cases 2 and 3 both presented with stable vital signs and the sudden decline of fetal heart rate. Cesarean section was performed at 27, 36+4, and 34 gestational weeks, respectively. Bleeding sites were founded on the surface of the uterus or the parametrium. The perinatal outcome was stillbirth, live birth, and neonatal severe asphyxia. CONCLUSION: Careful physical examination, strict monitoring of vital signs, and timely surgical intervention are critical for improving the prognosis.

OBJETIVO: Este caso clínico presentó casos con hemoperitoneo espontáneo durante el embarazo. REPORTE DEL CASO: El caso 1 presentó dolor abdominal agudo con signos de shock, los casos 2 y 3 se presentaron ambos con signos vitales estables y la disminución repentina de la frecuencia cardíaca fetal. La cesárea se realizó a las 27, 36 + 4 y 34 semanas de gestación, respectivamente. Los sitios de sangrado se encontraron en la superficie del útero o el parametrio. CONCLUSIÓN: Un control estricto de los signos vitales y una intervención quirúrgica oportuna son fundamentales para mejorar el pronóstico.

miRNAs signature as potential biomarkers for cervical precancerous lesions in human papillomavirus positive women.

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women.

Multi-Omic Signatures of Sarcoidosis and Progression in Bronchoalveolar Lavage Cells.

Introduction: Sarcoidosis is a heterogeneous, granulomatous disease that can prove difficult to diagnose, with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential genomic biomarkers. Methods: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of diagnosis and phenotype, adjusting for age, sex, and smoking. We built a supervised multi-omics model using a subset of features from each dataset. Results: We identified 46,812 CpGs, 1,842 mRNAs, and 5 miRNAs associated with sarcoidosis versus controls and 1 mRNA, SEPP1 - a protein that supplies selenium to cells, associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway in sarcoidosis, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. Conclusions: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing will be required for confirmation.

Analysis of angiogenesis-related subtypes of hepatocellular carcinoma and tumor microenvironment infiltration feature in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is a highly vascularized tumor, and angiogenesis plays an important role in its progression. However, the role of angiogenesis in cell infiltration in the tumor microenvironment (TME) remains unclear. METHODS: We evaluated the associations of 35 angiogenesis-related genes (ARGs) with the clinicopathological features of 816 HCC patients. In addition, we assessed the associations between the ARGs and TME cell infiltration. A nomogram was constructed to determine the prognostic value of ARGs for HCC. The ARG score was used to distinguish angiogenic subtypes of HCC, and its usefulness for predicting the prognosis and treatment response of HCC patients was evaluated. RESULTS: We distinguished three ARG clusters differing in terms of TME cell infiltration, immune cell activation status, clinicopathological features, and clinical outcomes. There were significant associations of ARG expression with tumor immunity, the epithelial-mesenchymal transition (EMT), and transforming growth factor-ß expression. An ARG score model was constructed to generate a risk score for each patient based on differentially expressed genes between clusters. Furthermore, a high ARG score was associated with high expression of CTLA-4 and PD-L1/PD-1, and a low Tumor Immune Dysfunction and Exclusion score, indicating the usefulness of the ARG score for selecting patients for immunotherapy. Considering the relationship between ARGs and tumor immunity, immunotherapy combined with vascular-targeted therapy may be the best treatment for HCC. CONCLUSIONS: ARGs play an important role in TME diversity and complexity in HCC patients. The ARG score of HCC predicts TME invasion and can guide immunotherapy.