Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

What is the epidemiological profile of acute hand infections at a hospital in sao paulo? / Qual o perfil epidemiológico de infecções agudas na mão num hospital filantrópico de são paulo?

ABSTRACT Objective: To determine the epidemiological profile of patients treated at a philanthropic hospital specialized in Orthopedics and Traumatology, located in a significant urban center, and evaluate the efficacy of initial empirical antibiotic treatment. Methods: Patients diagnosed with hand infections from September 2020 to September 2022 were included, excluding cases related to open fractures or post-surgical infections and those with incomplete medical records. The chi-square test was performed using STATISTICA ® software to correlate various variables. Results: A total of 34 patients participated, including 24 men and 10 women, with an average age of 41.9 years. Most male patients had Diabetes Mellitus, HIV, and drug addiction, and they resided in urban areas. Half of the patients did not report any apparent trauma. The most common infectious agent was Staphylococcus aureus*. Nearly 62% of patients required a change in the initial antibiotic regimen, with Penicillin being the most frequently substituted medication. Beta-lactam antibiotics and Quinolones were the most effective. Conclusion: These results suggest the importance of carefully evaluating the epidemiological profile of patients with acute hand infections and improving initial empirical treatment to ensure appropriate and effective therapy. Level of Evidence IV, Cross-Sectional Observational Study.

RESUMO Objetivo: Determinar o perfil epidemiológico de pacientes atendidos em um hospital filantrópico referência em Ortopedia e Traumatologia localizado em um centro urbano importante, e avaliar a eficácia do tratamento antibiótico empírico inicial. Métodos: Foram incluídos pacientes com diagnóstico de infecção na mão, atendidos no período de setembro de 2020 a setembro de 2022, excluindo-se casos relacionados a fraturas expostas ou pós-cirúrgicas e aqueles com prontuários incompletos. Realizou-se o teste do qui-quadrado, utilizando o software STATISTICA ® para correlacionar diversas variáveis. Resultados: Participaram do estudo 34 pacientes, sendo 24 homens e 10 mulheres, com média de idade de 41,9 anos. A maioria era de homens, com alta incidência de diabetes mellitus, HIV e drogadição, que residiam em áreas livres. Metade não relatou trauma evidente. O agente infeccioso mais comum foi o Staphylococcus aureus. Aproximadamente 62% dos pacientes precisaram de troca do esquema inicial de antibióticos, sendo a penicilina o medicamento mais frequentemente substituído. Os antibióticos beta-lactâmicos e quinolonas foram os mais eficientes. Conclusão: Esses resultados sugerem a importância de avaliar cuidadosamente o perfil epidemiológico dos pacientes com infecções agudas na mão e aprimorar o tratamento empírico inicial para garantir uma terapia adequada e eficaz. Nível de Evidência IV, Estudo Observacional Transversal.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma

Abstract Background Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. Objectives This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. Methods The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. Results Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitations The study was retrospective, and the sample size was small. Conclusion The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

Efficacy of the hybrid closed-loop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis

ABSTRACT The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucose level was > 180 mg/dL (WMD -10.46%, 95% CI -13.99 to -6.93%) and the mean levels of glucose (WMD -16.67 mg/dL, 95% CI -22.25 to -11.09 mg/dL) and HbA1c (WMD -0.50%, 95% CI -0.68 to -0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Beckwith-Wiedemann syndrome mimicking the classical form of congenital adrenal hyperplasia in newborn screening

SUMMARY Beckwith-Wiedemann syndrome (BWS) is a common genetic congenital disease characterized by somatic overgrowth and its broad clinical spectrum includes pre- and post-natal macrosomia, macroglossia, visceromegaly, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS occurs due to genetic/epigenetic changes involving growth-regulating genes, located on region 11p15, with an important genotype-phenotype correlation. Congenital adrenal hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases presenting a variety of clinical manifestations due to a deficiency in one of the enzymes involved in cortisol secretion. Early diagnosis based on newborn screening prevents the adrenal crisis and early infant death. However, high 17-hydroxyprogesterone (17-OHP) levels can occur in newborns or premature infants without CAH, in situations of stress due to maternal or neonatal factors. Here, we report new cases of false-positive diagnosis of 21-hydroxylase deficiency during newborn screening - two girls and one boy with BWS. Methylation-specific multiplex ligation-dependent probe amplification revealed a gain of methylation in the H19 differentially methylated region. Notably, all three cases showed a complete normalization of biochemical changes, highlighting the transient nature of these hormonal findings that imitate the classical form of CAH. This report sheds light on a new cause of false-positive 21-hydroxylase deficiency diagnosis during newborn screening: Beckwith-Wiedemann syndrome.

Clinical diagnoses of patients showing caloric inversion

Abstract Objectives When air irrigation is used for caloric stimulation in patients with a perforated ear, warm irrigation may elicit a nystagmus that initially beats in the opposite direction of what is expected for warm irrigations, which is referred to as "caloric inversion". This study aimed to investigate the disease group in which caloric inversion appeared in patients who underwent caloric testing and to classify the patterns of caloric inversion. Methods We conducted a retrospective review of bithermal caloric test results that were collected in our dizziness clinic between 2005 and 2022. Caloric inversion was defined when nystagmus induced by caloric stimulation appeared in the opposite direction to that expected. The incidence of caloric inversion among all patients who underwent bithermal caloric tests was calculated. To confirm the clinical diagnoses of the patients with caloric inversion, their clinical records were reviewed. Results Out of 9923 patients who underwent bithermal caloric tests, 29 patients (0.29%) showed a caloric inversion. The most common clinical diagnosis was chronic otitis media (21 of 29, 72%). Of the 21 patients with chronic otitis media, 20 patients showed a caloric inversion by warm air irrigation and one patient showed caloric inversion by cold air stimulation. Patients with clinical diagnoses other than chronic otitis media such as sudden sensorineural hearing loss, benign paroxysmal vertigo of childhood and recurrent vestibulopathy showed caloric inversion by warm air irrigation. Caloric inversion by warm water irrigation was observed in patients with lateral semicircular canal cupulopathy and recurrent vestibulopathy. Two patients (one with Meniere's disease and one with age-related dizziness) showed caloric inversion by cold water irrigation. Conclusion Caloric inversion can be observed in various diseases other than chronic otitis media with tympanic membrane perforation. Special care should be taken in the interpretation of caloric test results. Level of Evidence: Level 4.

Chronic Toxoplasma gondii infection is associated with decreased working memory performance in women / Infecção crônica por Toxoplasma gondii está associada à diminuição de desempenho da memória de trabalho em mulheres

Abstract Objective The present study sought to investigate changes in mood, inhibitory control, and working memory associated with T. gondii infection in a sample of Brazilian women. Method Twenty-eight female participants were equally distributed into two groups, according to the serology for chronic infection by T. gondii. The participants answered a Sociodemographic questionnaire, the CES-D, and performed Simon and N-Back tasks. Results Infected participants presented less accuracy and longer response time in N-Back tasks. No significant differences were found in the Simon task performance or in the depression levels. Conclusion Our findings suggest that chronic infection by T. gondii may result in impaired working memory and point out the importance of public policies aiming at preventing this infection.

Resumo Objetivo O presente estudo investigou alterações de humor, controle inibitório e memória de trabalho associadas à infecção por T. gondii em uma amostra de mulheres brasileiras. Método Vinte e oito participantes foram distribuídas igualmente em dois grupos de acordo com a sorologia para infecção crônica por T. gondii. As participantes responderam a um questionário sociodemográfico, à CES-D e realizaram as tarefas Simon e N-Back. Resultados As participantes infectadas apresentaram menor acurácia e maior tempo de resposta na tarefa N-Back. Nenhuma diferença significativa foi encontrada na tarefa Simon ou na escala de depressão. Conclusão Nossos achados sugerem que a infecção crônica por T. gondii pode resultar em comprometimento da memória de trabalho, e apontam para a importância de políticas públicas de prevenção dessa infecção.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon

ABSTRACT Objective: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. Results: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. Conclusion: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Internal carotid artery dissection associated with acute dengue virus infection: a case report / Dissecção da artéria carótida interna associada à infecção aguda pelo vírus da dengue: relato de caso

Cervical artery dissections (CAD) can occur spontaneously or as a direct result of significant trauma. Viral infections, such as SARS-CoV2, influenza, and Epstein Barr, are risk factors for spontaneous CAD. Dengue virus infections have dramatically increased in recent decades, and Brazil is one of the endemic areas. The dengue virus can cause headache and neurological complications such as encephalitis, myelitis, Guillain-Barré syndrome, and myositis. No report has yet been found in the literature of dissection of the internal carotid artery secondary to dengue infection. Our objective is to report the case of a patient with dissection of the internal carotid artery associated with acute dengue virus infection.

As dissecções da artéria cervical (DAC) podem ocorrer espontaneamente ou como resultado direto de trauma significativo. Infecções virais, como SARS-CoV2, influenza e Epstein Barr, são fatores de risco para DAC espontânea. As infecções pelo vírus da dengue aumentaram dramaticamente nas últimas décadas, e o Brasil é uma das áreas endêmicas. O vírus da dengue pode causar dor de cabeça e complicações neurológicas como encefalite, mielite, síndrome de Guillain-Barré e miosite. Ainda não foi encontrado na literatura nenhum relato de dissecção da artéria carótida interna secundária à infecção por dengue. Nosso objetivo é relatar o caso de um paciente com dissecção da artéria carótida interna associada à infecção aguda pelo vírus da dengue.

Bilateral tonic pupil during a migraine attack: a case report / Pupila tônica bilateral durante crise de enxaqueca: relato de caso

INTRODUCTION:Tonic pupil or Adie's pupil occurs due to parasympathetic denervation, and it is characterized by mydriasis with little or no response to light, with pupillary contraction to accommodation. It is caused by eye pathologies, such as infections, trauma, neoplasms, inflammatory diseases, and systemic diseases with autonomic dysfunction. Few cases have been reported of bilateral tonic pupils associated with migraine attacks. CASE REPORT: Our aimed to describe the case of a young female patient with a history of chronic migraine without aura, who presented acutely with bilateral pupillary mydriasis during a migraine attack, characterized as tonic pupil, and to discuss the possible causes of mydriasis during a migraine attack.

INTRODUÇÃO: A pupila tônica ou pupila de Adie ocorre devido à denervação parassimpática e é caracterizada por midríase com pouca ou nenhuma resposta à luz, com contração pupilar à acomodação. É causada por patologias oculares, como infecções, traumas, neoplasias, doenças inflamatórias e doenças sistêmicas com disfunção autonômica. Poucos casos foram relatados de pupilas tônicas bilaterais associadas a crises de enxaqueca. RELATO DE CASO: Nosso objetivo foi descrever o caso de uma paciente jovem, com história de enxaqueca crônica sem aura, que apresentou agudamente midríase pupilar bilateral durante uma crise de enxaqueca, caracterizada como pupila tônica, e discutir as possíveis causas da midríase durante uma crise de enxaqueca. ataque de enxaqueca.

Contemporary slave labor and subjectivity: psychosocial perspectives on the enslaved's narratives / Trabalho escravo contemporâneo e subjetividade: considerações psicossociais sobre narrativas de escravizado(a)s / Trabajo esclavo contemporáneo y subjetividad: consideraciones psicosociales sobre narrativas de personas esclavizadas

This study addresses the relation between subjectivity and contemporary enslaved labor from the enslaved workers' narratives in Brazil. A qualitative social research was carried out based on a constructionist perspective. We sought interaction with rescued workers and used (a) participant observation of workers' routine in an institutional project that supports them and a field diary, (b) semi-structured and open individual interviews with workers and a member of the team project. The fieldwork lasted a year and a half and the analysis followed Content Analysis. Freudian theory and Foucault's thought were used for interpretation, which managed to understand aspects of workers' experiences, exploitation characteristics, parental abandonment, as well as the tensions in self-classification as enslaved. The narratives pointed to a dramatic reality manifested in body exploitation, authoritarian abuses, violence, and negligence. At the same time, these narratives showed forms of worker resistance that calls for further investigations to increase knowledge on the subjective experiences of those who were enslaved.(AU)

O artigo aborda as relações entre subjetividade e trabalho escravo contemporâneo a partir da narrativa de trabalhadores(as) escravazados(as). Foi realizada uma pesquisa social qualitativa em uma perspectiva construcionista. Buscamos a interação com trabalhadores resgatados e realizamos a observação participante da rotina de trabalhadores atendidos em um projeto institucional, com diário de campo, e entrevistas individuais (semiestruturadas e abertas) com trabalhadores(as) e equipe do projeto institucional. O trabalho de campo durou um ano e meio, e a pesquisa foi realizada com o suporte da Análise de Conteúdo. Para a interpretação utilizamos aportes da teoria freudiana e do pensamento de Foucault, com os quais foi possível compreender aspectos das vivências dos trabalhadores, características da exploração, abandonos parentais e tensões em torno da autoclassificação como "escravo". As narrativas apontaram uma realidade dramática manifesta na exploração do corpo, em abusos autoritários, na violência e negligência. Ao mesmo tempo, as narrativas evidenciaram formas de resistência dos trabalhadores que convocam mais investigações para adensar o conhecimento sobre as experiências subjetivas desses que estão num lugar de escravizado(a).(AU)

Este artículo aborda la relación entre la subjetividad y el trabajo esclavo contemporáneo desde la narrativa de trabajadores esclavizados. Se realizó una investigación social cualitativa desde una perspectiva construccionista. Buscamos la interacción con los trabajadores liberados y utilizamos la observación participante de la rutina de los trabajadores atendidos en un proyecto institucional, diario de campo y entrevistas individuales (semiestructuradas y abiertas) con trabajadores y miembros del equipo del proyecto institucional. El trabajo de campo duró un año y medio, y se utilizó como apoyo el análisis de contenido. Para la interpretación se utilizaron aportes de la teoría freudiana y el pensamiento de Foucault, con lo que fue posible comprender aspectos de las vivencias de los trabajadores, características del escenario de explotación, abandono parental y las tensiones relacionadas con la autoclasificación "esclavo". Las narrativas apuntan a una realidad dramática manifestada en la explotación del cuerpo, abuso autoritario, violencia y abandono. Al mismo tiempo, evidenciaron formas de resistencia por parte de los trabajadores, que reclaman más investigaciones para profundizar en el conocimiento sobre las vivencias subjetivas de quienes se encuentran en esclavitud.(AU)

Multiple copy number variation in a patient with Kleefstra syndrome / Múltiplas variações de número de cópias em paciente com síndrome de Kleefstra

ABSTRACT Objective: To report a rare case of a patient with a molecular diagnosis of Kleefstra syndrome (KS) who has four other chromosomal alterations involving pathogenic variants. Case description: Male patient, two years old, with global delay, including in neuropsychomotor development, ocular hypertelorism, broad forehead, brachycephaly, hypotonia, ligament laxity, unilateral single palmar crease and arachnoid cyst. The microarray-based comparative genomic hybridization (a-CGH) identified copy number variations (CNVs) in five regions: 9q34.3, 6p22.1, Yq11.223, Yp11.23, and 2q24.1. The heterozygous microdeletion in 9q34.3 involving the EHMT1 gene confirms the diagnosis of KS. Comments: The presence of pathogenic CNVs and/or those of uncertain significance, located on chromosomes 2, 6 and Y, may be contributing to a variability in the patient's clinical condition (arachnoid cyst, single palmar fold and ligament laxity), compared to other individuals with only KS genetic alteration, making the dignosis of the disease harder.

RESUMO Objetivo: Relatar um caso raro de paciente com diagnóstico molecular de síndrome de Kleefstra (SK) que apresenta quatro outras alterações cromossômicas envolvendo variantes patogênicas. Descrição do caso: Paciente masculino, dois anos de idade, com atraso global de desenvolvimento neuropsicomotor, hipertelorismo ocular, fronte ampla, braquicefalia, hipotonia, frouxidão ligamentar, prega palmar única unilateral e cisto aracnoide. Exame de hibridização genômica comparativa (a-CGH) identificou variações de número de cópias (CNV) em cinco regiões: 9q34.3, 6p22.1, Yq11.223, Yp11.23 e 2q24.1. A microdeleção heterozigótica em 9q34.3 confirma o diagnóstico de síndrome de Kleefstra. Comentários: A presença das CNV patogênicas e/ou de significado incerto, localizadas nos cromossomos 2, 6 e Y, pode estar contribuindo para uma variabilidade no quadro clínico do paciente (cisto aracnoide, prega palmar única e frouxidão ligamentar) em relação a outros indivíduos somente com alteração genética da SK, dificultando o diagnóstico da doença.

Results of office-based fluid-air exchange for postvitrectomy hemorrhage in diabetic retinopathy

ABSTRACT Purpose: This study aimed to evaluate the efficacy and clinical outcomes of a one-way fluid-air exchange procedure for the treatment of postvitrectomy diabetic vitreous hemorrhage in patients with proliferative diabetic retinopathy. Methods: This retrospective study included 233 patients with proliferative diabetic retinopathy, who underwent vitrectomy. A one-way fluid-air exchange procedure was performed in 24 eyes of 24 (10.30%) patients with persistent vitreous cavity rebleeding after the operation. Preprocedural and postprocedural best-corrected visual acuity values were achieved. Complications occurring during and after the procedure were analyzed. Results: Significant visual improvement was observed 1 month after the one-way fluid-air exchange procedure (2.62 ± 0.60 LogMAR at baseline vs. 0.85 ± 0.94 LogMAR at postprocedure, p<0.0001). Moreover, 19 (79.17%) eyes needed the procedure once, and 5 (20.83%) eyed had the procedure more than twice. In 3 (12.50%) eyes, reoperation was eventually required because of persistent rebleeding despite several fluid-air exchanges. No complication was observed during the follow-up. Conclusions: The one-way fluid-air exchange procedure can be an excellent alternative to re-vitrectomy for patients with proliferative diabetic retinopathy suffering from postvitrectomy diabetic vitreous hemorrhage by removing the hemorrhagic contents directly and achieving fast recovery of visual function without apparent complications.

Directrices para presentación de informes de ensayos clínicos sobre intervenciones con inteligencia artificial: extensión CONSORT-AI / Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension / Diretrizes para relatórios de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão CONSORT-AI

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ABSTRACT The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.

RESUMO A declaração CONSORT 2010 apresenta diretrizes mínimas para relatórios de ensaios clínicos randomizados. Seu uso generalizado tem sido fundamental para garantir a transparência na avaliação de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence) é uma nova diretriz para relatórios de ensaios clínicos que avaliam intervenções com um componente de IA. Ela foi desenvolvida em paralelo à sua declaração complementar para protocolos de ensaios clínicos, a SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 29 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão CONSORT-AI inclui 14 itens novos que, devido à sua importância para as intervenções de IA, devem ser informados rotineiramente juntamente com os itens básicos da CONSORT 2010. A CONSORT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA está inserida, considerações sobre o manuseio dos dados de entrada e saída da intervenção de IA, a interação humano-IA e uma análise dos casos de erro. A CONSORT-AI ajudará a promover a transparência e a integralidade nos relatórios de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente a qualidade do desenho do ensaio clínico e o risco de viés nos resultados relatados.

Directrices para los protocolos de ensayos clínicos de intervenciones con inteligencia artificial: la extensión SPIRIT-AI / Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension / Diretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI

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ABSTRACT The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

RESUMO A declaração SPIRIT 2013 tem como objetivo melhorar a integralidade dos relatórios dos protocolos de ensaios clínicos, fornecendo recomendações baseadas em evidências para o conjunto mínimo de itens que devem ser abordados. Essas orientações têm sido fundamentais para promover uma avaliação transparente de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence) é uma nova diretriz de relatório para protocolos de ensaios clínicos que avaliam intervenções com um componente de IA. Essa diretriz foi desenvolvida em paralelo à sua declaração complementar para relatórios de ensaios clínicos, CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 26 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão SPIRIT-AI inclui 15 itens novos que foram considerados suficientemente importantes para os protocolos de ensaios clínicos com intervenções que utilizam IA. Esses itens novos devem constar dos relatórios de rotina, juntamente com os itens básicos da SPIRIT 2013. A SPIRIT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA será integrada, considerações sobre o manuseio dos dados de entrada e saída, a interação humano-IA e a análise de casos de erro. A SPIRIT-AI ajudará a promover a transparência e a integralidade nos protocolos de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente o delineamento e o risco de viés de um futuro estudo clínico.

Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease

BACKGROUND@#Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.@*METHOD@#In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.@*RESULTS@#A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.@*CONCLUSION@#Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.

Effect of Garcinia binucao crude leaf extract supplementation on lifespan of Drosophila melanogaster chronically exposed to alcohol

Background@#Consumption and abuse of alcohol remains a significant cause of concern worldwide. Furthermore, there is evidence of the association between chronic alcohol use and reduced life expectancy. @*Objectives@#To study the effects of Garcinia binucao extract (GBE) supplementation on lifespan of Drosophila melanogaster, in the presence or absence of chronic alcohol exposure.@*Methods@#D. melanogaster was mass cultured and given GBE supplementation in high (1 mg/mL) and low (200 µg/mL) sublethal doses. D. melanogaster flies were divided into groups - with and without chronic alcohol exposure, and their respective lifespans were monitored. @*Results@#In D. melanogaster without alcohol exposure, mean lifespan was highest in the control flies (38.15 days), followed by high-dose GBE (34.42 days), low-dose GBE (33.24 days), and DMSO (22.29 days). In D. melanogaster chronically exposed to alcohol, the longest mean lifespan was observed in flies treated with high-dose GBE (33.80 days), followed by low-dose GBE (33.63 days), the DMSO group (30.30), and the control group (29.65 days), but the differences were not statistically significant. Comparing groups with and without chronic alcohol exposure, the mean lifespan of the control group chronically exposed to alcohol significantly decreased by 9.51 days (p < 0.05). In GBE treatment groups, mean lifespan significantly decreased by 0.82 days in high-dose set-up (p < 0.05), and significantly increased by 0.39 days in the low-dose set-up (p < 0.05) upon chronic alcohol exposure. @*Conclusion@#Garcinia binucao extract supplementation ameliorated the observed reduction in lifespan of Drosophila melanogaster chronically exposed to alcohol.

Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.