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BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.
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Cardiopatias Congênitas , Hipertensão Pulmonar , Complicações Cardiovasculares na Gravidez , Hipertensão Arterial Pulmonar , Gravidez , Feminino , Humanos , Masculino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Gestantes , Estudos Retrospectivos , Peptídeo Natriurético Encefálico , Complicações Cardiovasculares na Gravidez/diagnóstico , Resultado da Gravidez , Cardiopatias Congênitas/diagnósticoRESUMO
BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS. METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF. RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = - 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all). CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF.
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Hidronefrose , Urografia , Criança , Humanos , Estudos Retrospectivos , Urografia/métodos , Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cintilografia , Espectroscopia de Ressonância MagnéticaRESUMO
Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetically heterogeneous disease and characterized by incomplete or absent puberty and infertility. It is worth noting that partial IHH patients could recover reproductive endocrine function following treatment, which is termed reversal. This study aimed to investigate clinical and genetic characteristics of IHH reversal patients. A total of 141 IHH male patients were enrolled and followed up regularly. Their clinical and genetic features were collected and analysed to discover something in common in reversal cases. These IHH patients with a median age of 21 years (interquartile range: 18-24) were divided into reversal group (n = 13) and non-reversal group (n = 128). IL17RD, ERBB4, DLX5, EGFR, SEMA4D, B3GNT1 and CCKAR RSVs were demonstrated in reversal cases for the first time. Pathogenic/likely pathogenic (P/LP) RSVs consisted of 3 RSVs (one each patient, including PROKR2 p.W178S, EGFR p.G630R and CCKAR p.S291del) in reversal group. Reversal of IHH could not be ignored in clinical follow-up. Patients with high levels of basal LH and T may harbour more possibility of reversal and worthy extra attention to identify whether reversal occurs or not. Relapse after reversal also needs to be monitored.
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Hipogonadismo , Adulto , Humanos , Masculino , Adulto Jovem , China , Estudos de Coortes , Hipogonadismo/tratamento farmacológico , Hipogonadismo/genéticaRESUMO
Fibroblast growth factor receptor 1 (FGFR1) is an idiopathic hypogonadotropic hypogonadism (IHH)-associated gene, mutated in approximately 10% of the patients with this condition. Through targeted gene sequencing of 153 males with IHH and 100 healthy controls, we identified 10 mutations in FGFR1 from IHH patients with a frequency of 5.9% in the Chinese population of central China. These included nine missense mutations(NM_023110.2, p.Gly687Arg, p.Ala608Asp, p.Gly348Glu, p.Asn296Ser, p.Gly226Asp, p.Arg209Cys, p.Gly97Arg, p.Val71Met, p.Gly70Arg) and a splicing mutation c.1430 + 1G > T. in vitro and in silico analyses of FGFR1 variants were conducted to study the impact of the identified mutations. Our findings indicated that the splicing mutation dramatically affected premRNA processing, causing exon 10 and 6 nucleotides in the 3' end of exon 9 to be completely skipped. Two variants (p.Gly687Arg and p.Ala608Asp) markedly impaired tyrosine kinase activity, while the other variants had limited impact on the mitogen-activated protein kinase (MAPK) signaling pathway. However, the functional impairment of the mutant receptors was not always consistent with the phenotypes, indicating that FGFR1 mutations might cause IHH in conjunction with other mutant genes. In this study, we expanded the knowledge on the mutation spectrum of FGFR1 in IHH patients and explored the genotype-phenotype relationship.
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Processamento Alternativo/genética , Estudos de Associação Genética , Hipogonadismo/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Adulto , Pré-Escolar , Simulação por Computador , Éxons/genética , Genótipo , Humanos , Hipogonadismo/patologia , Lactente , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo , Adulto JovemRESUMO
BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder characterized by absent or incomplete puberty and infertility, and heterogeneous responses are often observed during treatment. AIM: To investigate the role of CHH-associated variants in patients with CHH with poor responses to human chorionic gonadotropin (hCG). METHODS: This retrospective study investigated 110 Chinese male patients with CHH undergoing genetic analysis and hCG treatment. CHH-associated rare sequence variants (RSVs) were identified by using a tailored next-generation sequencing panel and were interpreted in accordance with the American College of Medical Genetics and Genomics criteria. Clinical characteristics were recorded, and Kyoto Encyclopedia of Genes and Genomes analysis was conducted to assess pathways enriched in protein networks implicated in poor responses. OUTCOMES: The outcomes include testicular volume, serum hormonal profiles, parameters of semen analysis, pathogenicity classification, and pathway enrichment. RESULTS: Among the 110 patients, 94.55% achieved normal serum testosterone and 54.55% achieved seminal spermatozoa appearance (SSA). PLXNB1, ROBO3, LHB, NRP2, CHD7, and PLXNA1 RSVs were identified in patients who had an abnormal serum testosterone level during treatment. In spermatogenesis, the number of CHH-associated RSVs was not significantly strongly associated with delayed SSA. After pathogenicity classification, pathogenic/likely pathogenic (P/LP) RSVs were identified in 30% (33/110) of patients. Patients with P/LP RSVs showed delayed SSA compared with noncarriers, and P/LP PROKR2 RSVs showed the strongest association (48, 95% CI: 34.1-61.9 months, P = .043). Enriched pathways implicated in delayed SSA included neuroactive ligand-receptor interaction; Rap1, MAPK, PI3K-Akt signaling; and regulation of actin cytoskeleton. CLINICAL IMPLICATIONS: Male patients with CHH harboring P/LP PROKR2 RSVs should be aware of a high probability of poor responses to hCG; If these patients desire fertility, it might be better to recommend hCG/human menopausal gonadotropin, hCG/recombinant follicle-stimulating hormone, or pulsatile GnRH administration before treatments start or as early as possible. STRENGTHS & LIMITATIONS: Strengths are the standardized regimen and extensive follow-up (median time of 40 months). However, included patients in the study voluntarily chose hCG treatment because of the burden of drug cost and/or little fertility desire. Therefore, human menopausal gonadotropin or follicle-stimulating hormone was not added to this cohort. Our observed correlations should be further verified in patients with CHH undergoing other treatments. CONCLUSION: Among all P/LP RSVs, P/LP PROKR2 RSVs might correlate with poor responses in CHH under hCG treatment; our study supports the pathogenicity assessment of American College of Medical Genetics and Genomics criteria in genetic counseling, to improve management of patients with CHH. Chen Y, Sun T, Niu Y, et al. Correlations AmongGenotype and Outcome in Chinese Male Patients WithCongenital Hypogonadotropic Hypogonadism Under HCG Treatment. J Sex Med 2020;17:645-657.
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Gonadotropina Coriônica/administração & dosagem , Hipogonadismo/tratamento farmacológico , Espermatogênese , Adolescente , Adulto , Estudos de Coortes , Genótipo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade/etiologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
Varicocele is the most common cause of male infertility. Varicoceles are classified into two types: clinical and subclinical varicoceles. Some researchers reported right subclinical varicoceles are often accompanied with left clinical varicoceles. However, the treatment is controversial. Our aim was to compare the clinical outcome of unilateral varicocelectomy (UV) and bilateral varicocelectomy (BV) in infertile males with left clinical and right subclinical varicocele. A total of four randomised controlled trials (RCT) were enrolled in this study, including 637 cases with left clinical and right subclinical varicocele (318 cases in the BV group and 319 cases in the UV group). The fixed effects model combined difference in progressive sperm motility between the two groups was 6.42% (95% CI: 5.09, 7.75). The random effects model combined difference in normal sperm morphology between the two groups was 2.04% (95% CI: 0.60, 3.48). The odds ratio shown by the fixed effects model in spontaneous pregnancy rate was 1.73 (95% CI: 1.24, 2.43). No statistically significant difference between the two groups was found in sperm concentration and sperm motility. Thus, BV may be superior to UV for infertile male patients with left clinical and right subclinical varicocele. However, more properly conducted RCTs are still needed.
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Infertilidade Masculina/cirurgia , Varicocele/cirurgia , Feminino , Humanos , Infertilidade Masculina/etiologia , Masculino , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Motilidade dos Espermatozoides , Varicocele/complicaçõesRESUMO
Varicocele is one of the common correctable causes of male infertility. Recent studies have demonstrated varicocelectomy in males with abnormal semen parameters was associated with better fertility outcome, but the effect of adjuvant drug therapy after varicocelectomy on fertility outcome in patients with varicocele-associated infertility remains undefined. Hence, the present meta-analysis was performed to assess the efficacy of adjuvant drug therapy after varicocelectomy. The protocol was registered with PROSPERO (No. CRD42018093749). Ten randomised controlled trails containing 533 patients with adjuvant drug therapy after varicocelectomy and 368 patients with no medical treatment after varicocelectomy were included. Our analysis revealed that the improvement in pregnancy rate after adjuvant drug therapy was insignificant. (OR = 1.70, 95%CI = 0.99-2.91), but resulted in significant improvements in sperm concentration (MD = 13.71, 95%CI = 5.80-21.63) and motility (MD = 4.77, 95%CI = 3.98-5.56) at 3 months, sperm DNA integrity (SMD = 3.13, 95%CI = 1.50-4.75) and serum FSH level (MD = -1.02, 95%CI = -1.79 to -0.24). Therefore, compared to no medical treatment, the adjuvant drug therapy, especially the use of antioxidants seems to be associated with better fertility outcome. However, more evidences with high-quality studies are necessary to conform its benefits.
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Infertilidade Masculina/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Varicocele/cirurgia , Procedimentos Cirúrgicos Vasculares , Quimioterapia Adjuvante/métodos , Humanos , Infertilidade Masculina/etiologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Resultado do Tratamento , Agentes Urológicos/farmacologia , Varicocele/complicaçõesRESUMO
BACKGROUND Persistent truncus arteriosus is a rare congenital cyanotic heart defect characterized by a single ventricular outflow tract. Without surgical intervention, it has a poor prognosis in infancy. Here, we report an adult female patient with uncorrected truncus arteriosus type I, who presented with acute-onset abdominal pain due to torsion of a small bowel gastrointestinal stromal tumor (GIST). CASE REPORT A 41-year-old woman came to our Emergency Department with acute-onset lower abdominal pain for 2 days. Congenital heart disease, truncus arteriosus, had been diagnosed at birth, and there had been no surgical intervention. Abdominal computed tomography revealed a 10×9×12-cm mixed-density mass in the pelvic capacity. Transthoracic echocardiography revealed a 33-mm ventricular septal defect. The ascending aorta originated mainly from the right ventricle, and the pulmonary artery originated from the beginning of the aorta (type I truncus arteriosus, according to Collett and Edwards classification). After a quick and detailed preoperative workup, the patient underwent tumor resection by open surgery with general anesthesia. CONCLUSIONS This is the first case to report emergency surgery for a patient with uncorrected persistent truncus arteriosus due to torsion of a small bowel GIST. A multidisciplinary team with deep understanding of the disease entity was crucial. By considering the fixed hemodynamic and respiratory physiology, overtreatment and unrealistic goals were avoided. Eventually, the patient was discharged after being hospitalized for 2 weeks.
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Tumores do Estroma Gastrointestinal , Humanos , Feminino , Adulto , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/cirurgia , Anormalidade Torcional/cirurgia , Anormalidade Torcional/diagnóstico , Persistência do Tronco Arterial/cirurgia , Persistência do Tronco Arterial/complicações , Intestino Delgado/anormalidadesRESUMO
Magnetic resonance imaging (MRI) has been proven to be an indispensable imaging method in bladder cancer, and it can accurately identify muscular invasion of bladder cancer. Multiparameter MRI is a promising tool widely used for preoperative staging evaluation of bladder cancer. Vesical Imaging-Reporting and Data System (VI-RADS) scoring has proven to be a reliable tool for local staging of bladder cancer with high accuracy in preoperative staging, but VI-RADS still faces challenges and needs further improvement. Artificial intelligence (AI) holds great promise in improving the accuracy of diagnosis and predicting the prognosis of bladder cancer. Automated machine learning techniques based on radiomics features derived from MRI have been utilized in bladder cancer diagnosis and have demonstrated promising potential for practical implementation. Future work should focus on conducting more prospective, multicenter studies to validate the additional value of quantitative studies and optimize prediction models by combining other biomarkers, such as urine and serum biomarkers. This review assesses the value of multiparameter MRI in the accurate evaluation of muscular invasion of bladder cancer, as well as the current status and progress of its application in the evaluation of efficacy and prognosis.
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[This corrects the article DOI: 10.1016/j.gendis.2022.05.030.].
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OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.
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Ciclo-Oxigenase 2 , Enterocolite , Doença de Hirschsprung , Macrófagos , Transplante de Células-Tronco Mesenquimais , Doença de Hirschsprung/terapia , Doença de Hirschsprung/patologia , Animais , Enterocolite/etiologia , Transplante de Células-Tronco Mesenquimais/métodos , Macrófagos/metabolismo , Camundongos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Humanos , Masculino , Modelos Animais de Doenças , Feminino , Camundongos Knockout , Células-Tronco Mesenquimais , Receptor de Endotelina BRESUMO
The aim of this study is to determine the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) for diagnosis of small (≤ 2 cm in diameter) hepatocellular carcinoma (HCC) through a meta-analysis of published studies. A comprehensive literature search of PubMed, Embase, Web of Science, and China BioMedicine databases was conducted on articles published before 1 March 2013. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analyses were performed using Meta-Disc version 1.4 and STATA version 12.0 softwares. Fifteen studies were included with a total of 908 cirrhotic patients with 1,032 small hepatic nodules. All lesions were histologically confirmed through liver biopsies after CEUS. The pooled sensitivity was 0.81 (95% CI = 0.78-0.85); the pooled specificity was 0.86 (95% CI = 0.82-0.89). The pooled positive LR was 5.90 (95% CI = 3.90-8.94); the pooled negative LR was 0.20 (95% CI = 0.14-0.29). The pooled DOR was 37.07 (95% CI = 24.79-55.44). The area under the SROC curve was 0.93 (SE = 0.01). Meta-regression analysis showed that the number of lesions may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. This meta-analysis indicates that CEUS is a useful diagnostic tool with high sensitivity and specificity for identifying small HCC.
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Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fígado/diagnóstico por imagem , Ultrassonografia/métodos , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Análise de Regressão , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Renal tumors are very common in the urinary system, and the preoperative differential diagnosis of homogeneous renal tumors remains a challenge. This study aimed to evaluate the feasibility of the whole-lesion CT texture analysis for the identification of homogeneous renal tumors including clear cell renal cell carcinoma (ccRCC), chromophobe RCC (chRCC), and renal oncocytoma (RO). This retrospective study was approved by our local IRB. Contrast-enhanced CT examination was performed in 128 patients and histopathologically confirmed ccRCC, chRCC, and RO. The one-way ANOVA test with Bonferroni corrections was used to compare the differences, and the receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic efficiency. The whole-lesion CT histogram analysis was used to demonstrate significant differences between ccRCC and chRCC in both arterial and venous phases, and the entropy demonstrated excellent performance in discriminating these two types of tumors (AUCs = 0.95, 0.91). The inhomogeneity of ccRCC was significantly higher than that of RO both in arterial and venous phases. The entropy of chRCC was significantly lower than that of RO, and the kurtosis and entropy yielded high sensitivity (91%) and moderate specificity (74%) in the arterial phase. The whole-lesion CT histogram analysis could be useful for the differential diagnosis of homogeneous ccRCC, chRCC, and RO.
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Background: Preoperative evaluation of the dysganglionic bowel segment is critical for establishing the optimal resection strategy for Hirschsprung's disease (HSCR), which facilitates patient outcomes. Objective: We set out to determine the utility of the 24-h delayed film of barium retention in predicting the length of dysganglionic bowel segment in HSCR. Materials and methods: A retrospective study of patients with clinically suspicious HSCR who underwent a preoperative 24-h delayed film of barium enema and were surgically treated from January 2015 to December 2019 was conducted. Results: Two hundred and 58 patients were enrolled in this study. The sensitivity, specificity, positive and negative predictive values (NPVs) of the 24-h delayed film of barium enema to predict the neuropathological segment were 89.1, 91.5, 91.3, and 89.4%, respectively. The Youden index was 80.6%, with a kappa value of 0.806 (P < 0.001). The correlation rate between barium retention level and pathological results was 72.7% (16/22) when aganglionosis was restricted within the mid-distal rectum (short-segment type), increasing to 92.0% (46/50) and 93.5% (174/186) for patients that had aganglionosis extended beyond the mid-distal rectum (classical type) and sigmoid colon (long-segment type), respectively. Lastly, patients younger than 3 months showed a lower correlation rate (72.2%) compared to patients aged 3-12 months (91.0%) and > 12 months (92.6%). Conclusions: Our investigation of the 24-h delayed film of barium enema performed for patients suspected of having HSCR indicated that the barium retention level remains crucial in predicting dysganglionic bowel segment, which contributes to the decision-making for surgical physicians.
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Background: Hormonal therapy is a reasonable treatment for cryptorchidism caused by idiopathic hypogonadotropic hypogonadism (IHH). However, the clinical evidence on whether it is effective and safe for the treatment of cryptorchidism caused by IHH is lacking. Aim: To evaluate the effect of hormonal therapy in testicular descent, puberty development, and spermatogenesis in adult males with cryptorchidism caused by IHH. Methods: This retrospective study included 51 patients with cryptorchidism caused by IHH from the Andrology Clinic of University affiliated teaching hospital. Patients were divided into two groups: group A patients received hormonal therapy; group B patients received surgical treatment for cryptorchidism followed by hormonal therapy. Results: The rate of successful testicular descent following hormonal therapy (19/32 in group A) or surgical treatment (11/19 in group B) shows no statistically significant difference. There was also no statistically significant difference in penile length, Tanner stage of pubic hair, testicular volume, and success rate of spermatogenesis between the two groups. Testicular atrophy was seen in a single patient in group B. Conclusions: Hormone therapy in adult males with cryptorchidism caused by IHH is effective and safe regarding testicular descent, puberty development, and spermatogenesis. This study provides new insight into the treatment of cryptorchidism caused by IHH and highlights that hormonal therapy could be an effective, safe, and economic treatment option for cryptorchidism in males caused by IHH.
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Criptorquidismo , Hipogonadismo , Masculino , Humanos , Adulto , Criptorquidismo/tratamento farmacológico , Estudos Retrospectivos , Hipogonadismo/tratamento farmacológicoRESUMO
BACKGROUND AND AIM: We evaluated the clinical features of neonatal Hirschsprung's disease (HD)-associated bowel perforation (perforated HD) and investigated risk factors related to it. METHODS: We retrospectively collected clinical data of neonates (<1 month of age) with perforated HD from multicenters in China from January 2006 to December 2019. A total of 142 patients (6.7%) with perforated HD were enrolled in the study. A 1:2 matching method was used to compare the clinical information of HD patients with and without bowel perforation during the neonatal period. The risk factors for bowel perforation were identified using univariate and multivariate logistic risk regression analyses. RESULTS: Perforation site was present in the proximal ganglionic bowel in 101 (71.1%) cases and the distal aganglionosis segment in 41 (28.9%) cases. Adjacent marginal tissue from the perforated intestine revealed varying degrees of inflammatory cell infiltration, and the severity of enterocolitis was higher in the proximal ganglionic bowel than in the distal aganglionosis segment (p < 0.05). In the univariable and multivariable logistic analyses, clinical symptoms, such as vomiting (adjusted OR = 2.06, 95% CI: 2.01-2.88, p < 0.05), and inflammation index in hematologic tests, such as neutrophil proportion (adjusted OR = 1.09, 95% CI: 1.05-1.33, p < 0.05) and CRP (adjusted OR = 2.13, 95% CI: 1.01-3.27, p < 0.05) were associated with increased risk for perforated HD. CONCLUSION: Clinical Hirschsprung disease-associated enterocolitis (HAEC) highly correlated with perforated HD. Timely treatment of HAEC should be appropriate therapeutic approaches to prevent perforated HD.
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BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease attributed to the disorder of hypothalamic-pituitary-gonadal axis. Mutations in the GNRHR gene are one of the most common genetic causes of IHH. Herein, we aimed to investigate GNRHR variants in a Chinese cohort with IHH, and to characterize them at the molecular level. METHODS: A total of 153 IHH patients were recruited, and variants were detected using a tailored next-generation sequencing panel. GNRHR rare sequencing variant (RSV) was verified using Sanger sequencing. Phenotypic features and therapeutic outcomes of patients were followed up. In order to examine the pathogenicity of the GNRHR RSV, we performed conservative analysis, crystal structure prediction, expression analysis as well as the assessment of ERK1/2 activation and IP3/Ca2+ response. RESULTS: The same heterozygous RSV (p.R240Q) in GNRHR was identified in four sporadic IHH patients. These patients exhibited different severity of testicular development and hormone profile. hCG treatment was effective in improving gonadal development, serum testosterone, and semen quality. The GNRHR RSV has no effect on the expression of mRNA and protein, whereas damaged ERK1/2 activation and inositol triphosphate/calcium signaling. CONCLUSIONS: The study expands GNRHR mutation spectrum in IHH patients, and reveals that the GNRHR RSV is a partial loss-of-function mutation. Although this heterozygous RSV may not have a significant influence on the pathogenesis of IHH, but its homozygous/ compound status should be paid attention in this research field.
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Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undecanoate (TU) supplementation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) months in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.
Assuntos
Gonadotropina Coriônica/farmacologia , Hipogonadismo/tratamento farmacológico , Espermatogênese/efeitos dos fármacos , Testosterona/análogos & derivados , Adolescente , Adulto , Gonadotropina Coriônica/uso terapêutico , Quimioterapia Combinada , Hormônio Foliculoestimulante/sangue , Humanos , Hipogonadismo/sangue , Hormônio Luteinizante/sangue , Masculino , Estudos Retrospectivos , Testosterona/sangue , Testosterona/farmacologia , Testosterona/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism (IHH) and discover new pathogenic genes that cause IHH. DESIGN: A gene panel, including 31 known IHH genes and 52 candidate genes, was used to perform semiconductor next-generation sequencing. SETTING: University hospital. PATIENTS: One hundred thirty-eight sporadic male IHH patients and 10 IHH families; 100 healthy men with normal fertility served as control subjects. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Targeted next-generation sequencing, polymerase chain reaction and sequencing, pedigree analysis, and bioinformatics analysis. RESULT(S): Variants were distributed uniformly throughout 52 genes (52/83, 62.65%), including 16 (16/31, 51.61%) causal genes and 36 (36/52, 69.23%) candidate genes. Six new pathogenic variants and 52 likely pathogenic variants were identified in 16 genes known to cause nIHH/KS (normosmic IHH/Kallmann syndrome). In the 148 probands, PROKR2 (22/148, 14.86%), CHD7, FGFR1, and KAL1 had high mutation rates, and 8.78% (13/148) of the patients carried at least two variants in known genes. In addition, variants were identified in 36 candidate genes, and EGFR, ERBB4, PAX6, IGF1, SEMA4D, and SEMA7A should be prioritized for further research and genetic testing in IHH. CONCLUSION(S): The mutation frequency of IHH-causal genes in Chinese HAN males was different from the data reported in white populations. Oligogenic inheritance was a common phenomenon in IHH. Our study expands the mutation profile for IHH, and the new likely pathogenic genes identified in our study warrant further research in GnRH neuronal networks.