Testicular differentiation in 46,XX DSD: an overview of genetic causes.

In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of SRY to the X chromosome or an autosome. In the absence of SRY, other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.

Elevated plasma miR-210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development.

BACKGROUND: Differences of sex development (DSD) is a term used for conditions in which the chromosomal, gonadal or phenotypical sex is atypical. 46,XY DSD patients frequently present undervirilized external genitalia. The expression of different miRNAs in many organs of the male genital system has been reported, and these miRNAs have been associated with testicular function and its disorders, but no description has been related to DSD conditions. This study aimed to evaluate the plasma expression of miR-210 in 46,XY DSD patients who presented atypical genitalia at birth. METHODS: Eighteen 46,XY DSD patients who presented atypical genitalia (undescended testis and/or hypospadias, bifid scrotum or micropenis) at birth and 36 male control individuals were selected. Plasma levels of miR-210 and reference miR-23a were measured using RT-qPCR and the data were analysed by the 2-ΔCt method. RESULTS: MiR-210 plasma levels were significantly higher in 46,XY DSD patients with atypical genitalia than in male control subjects (p = 0.0024). A positive association between miR-210 levels and the presence of cryptorchidism and hypospadias (p = 0.0146 and p = 0.0223) was found in these patients. Significantly higher levels of miR-210 were observed in patients with 46,XY DSD and cryptorchidism than in control subjects (p = 0.0118). These results are in agreement with previous literature reports, in which increased levels of miR-210 expression were observed in human testicular tissue from adult males with undescended testes in comparison with samples of descended testes. CONCLUSION: Our study showed a positive association between the presence of atypical genitalia and plasma levels of miR-210 expression in the group of patients with 46,XY DSD of unknown aetiology studied. These findings contribute to reveal a new perspective on the role of miRNAs in the development of male external genitalia and the broad spectrum of phenotypes presented by patients with 46,XY DSD.

Red blood cell transfusions worsen the outcomes even in critically ill patients undergoing a restrictive transfusion strategy.

CONTEXT AND OBJECTIVE: Anemia and blood transfusions are common in intensive care. This study aimed to evaluate epidemiology and outcomes among critically ill patients under a restrictive transfusion strategy. DESIGN AND SETTING: Prospective observational cohort study in an intensive care unit (ICU) at a tertiary hospital. METHODS: All adults admitted to the ICU over a one-year period who remained there for more than 72 hours were included, except those with acute coronary syndrome, ischemic stroke, acute hemorrhage, prior transfusion, pregnant women and Jehovah's Witnesses. The restrictive strategy consisted of transfusion indicated when hemoglobin levels were less than or equal to 7.0 g/dl. RESULTS: The study enrolled 167 patients; the acute physiology and chronic health evaluation II (APACHE II) score was 28.9 ± 6.5. The baseline hemoglobin level was 10.6 ± 2.2 g/dl and on day 28, it was 8.2 ± 1.3 g/dl (P < 0.001). Transfusions were administered to 35% of the patients. In the transfusion group, 61.1% did not survive, versus 48.6% in the non-transfusion group (P = 0.03). Transfusion was an independent risk factor for mortality (P = 0.011; odds ratio, OR = 2.67; 95% confidence interval, CI = 1.25 to 5.69). ICU stay and hospital stay were longer in the transfusion group: 20.0 (3.0-83.0) versus 8.0 (3.0-63.0) days (P < 0,001); and 24.0 (3.0-140.0) versus 14.0 (3.0-80.0) days (P = 0.002), respectively. CONCLUSIONS: In critically ill patients, there was a reduction in hemoglobin with increasing length of ICU stay. Moreover, transfusion was associated with worse prognoses.

Red blood cell transfusions worsen the outcomes even in critically ill patients undergoing a restrictive transfusion strategy / Transfusões de concentrados de hemácias pioram os resultados mesmo em pacientes graves, submetidos a estratégia restritiva de transfusão

CONTEXT AND OBJECTIVE: Anemia and blood transfusions are common in intensive care. This study aimed to evaluate epidemiology and outcomes among critically ill patients under a restrictive transfusion strategy. DESIGN AND SETTING: Prospective observational cohort study in an intensive care unit (ICU) at a tertiary hospital. METHODS: All adults admitted to the ICU over a one-year period who remained there for more than 72 hours were included, except those with acute coronary syndrome, ischemic stroke, acute hemorrhage, prior transfusion, pregnant women and Jehovah's Witnesses. The restrictive strategy consisted of transfusion indicated when hemoglobin levels were less than or equal to 7.0 g/dl. RESULTS: The study enrolled 167 patients; the acute physiology and chronic health evaluation II (APACHE II) score was 28.9 ± 6.5. The baseline hemoglobin level was 10.6 ± 2.2 g/dl and on day 28, it was 8.2 ± 1.3 g/dl (P < 0.001). Transfusions were administered to 35% of the patients. In the transfusion group, 61.1% did not survive, versus 48.6% in the non-transfusion group (P = 0.03). Transfusion was an independent risk factor for mortality (P = 0.011; odds ratio, OR = 2.67; 95% confidence interval, CI = 1.25 to 5.69). ICU stay and hospital stay were longer in the transfusion group: 20.0 (3.0-83.0) versus 8.0 (3.0-63.0) days (P < 0,001); and 24.0 (3.0-140.0) versus 14.0 (3.0-80.0) days (P = 0.002), respectively. CONCLUSIONS: In critically ill patients, there was a reduction in hemoglobin with increasing length of ICU stay. Moreover, transfusion was associated with worse prognoses.

CONTEXTO E OBJETIVO: Anemia e transfusões sanguíneas são comuns em terapia intensiva. O objetivo deste estudo foi investigar a epidemiologia e resultados em pacientes críticos sob o regime de transfusão restritiva. TIPO DE ESTUDO E LOCAL: Estudo de coorte, prospectivo e observacional em unidade de terapia intensiva de um hospital terciário. MÉTODOS: Foram incluídos todos adultos admitidos na unidade durante um ano e que permaneceram internados por mais de 72 horas, exceto pacientes com lesão coronariana aguda, isquemia cerebral aguda, hemorragia aguda, transfusão anterior, mulheres grávidas e testemunhas de Jeová. A estratégia restritiva consiste na transfusão indicada com a hemoglobina inferior ou igual a 7.0 g/dl. RESULTADOS: Totalizando 167 pacientes incluídos, APACHE II (Acute Physiology and Chronic Health disease II) foi de 28,9 ± 6,5. O valor da hemoglobina basal foi de 10,6 ± 2.2 g/dl e no 28º dia foi de 8,2 ± 1.3 g/dl (P < 0,001). 35% dos pacientes receberam transfusões. No grupo de transfusão 61,1% não sobreviveram versus 48,6% do grupo não transfusão (P = 0,03). A transfusão foi fator de risco independente de mortalidade (P = 0,011; odds ratio, OR = 2,67; intervalo de confiança, IC 95% = 1,25-5,69). A internação na unidade de terapia intensiva e hospitalar foi maior no grupo de transfusão: 20,0 (3,0-83,0) versus 8,0 (3,0-63,0) dias (P < 0,001); e 24,0 (3,0-140,0) versus 14,0 (3,0-80,0) dias (P = 0,002). CONCLUSÕES: Em pacientes graves, observou-se redução da hemoglobina com a progressão da permanência na UTI. Além disso, a transfusão foi associada com piores prognósticos.

Cisto broncogênico simulando asma brônquica em criança / Brochongenic cyst mimicking asthma in an infant

O cisto broncogênico é a lesão cística mais comum do mediastino. Algumas de suas manifestações clínicas ocorrem por compressão das vias aéreas. Uma forma incomum de apresentação é o caráter recorrente dos sintomas obstrutivos, assemelhando-se a asma brônquica. Os autores relatam e discutem caso de cisto broncogênico simulando asma em uma criança, onde a retirada da lesão possibilitou a remissão completa dos sintomas