How Does ADPKD Severity Differ Between Family Members?

Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability in phenotype and risk of subsequent kidney failure. Despite an established genotype-phenotype correlation in cystic kidney diseases, incomplete penetrance and variable disease expressivity are present as is the case in all monogenic diseases. In family members with autosomal dominant polycystic kidney disease (ADPKD), the same causal variant is responsible in all affected family members; however, there can still be striking discordance in phenotype severity. This narrative review explores contributors to within-family discordance in ADPKD severity. Cases of biallelic and digenic inheritance, where 2 rare pathogenic variants in cystogenic genes are coexistent in one family, account for a small proportion of within-family discordance. Genetic background, including cis and trans factors and the polygenic propensity for comorbid disease, also plays a role but has not yet been exhaustively quantified. Environmental exposures, including diet; smoking; alcohol, salt, and protein intake, and comorbid diseases, including obesity, diabetes, hypertension, kidney stones, dyslipidemia, and additional coexistent kidney diseases all contribute to ADPKD phenotypic variability among family members. Given that many of the factors contributing to phenotype variability are preventable, modifiable, or treatable, health care providers and patients need to be aware of these factors and address them in the treatment of ADPKD.

Risk and protective factors in predicting pediatric acute postsurgical pain: A systematic review and meta-analysis.

OBJECTIVE: Acute postsurgical pain (APSP), defined as pain within 3 months after surgery, is reported in most surgical pediatric patients, and a significant number of patients experience pain interfering with their daily life activities. We aimed to identify perioperative and psychosocial factors associated with APSP severity in pediatric patients undergoing surgery. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and CENTRAL were searched from database inception to October 2021. Studies that reported an association between risk or protective factors and acute pain in children were included. The primary outcome was the magnitude of association between identified factors and APSP, as measured by standardized effect sizes. RESULTS: Thirty-eight studies (7,936 participants aged 1-18 years) were included. Meta-analysis of 12 studies (1,192 participants) revealed child preoperative pain, pain immediately after surgery, anticipated pain, temperament, pain catastrophizing, age, preoperative anxiety, parent pain catastrophizing, and parent preoperative anxiety were positively associated with APSP. Child pain coping efficacy was protective against APSP. We identified several modifiable child and parent psychosocial factors as predictors of APSP severity. CONCLUSION: Given the small degree of association between identified factors and postsurgical pain, there is value in pursuing other factors that may better explain the variability in pain. Recognizing patients at risk for moderate to severe APSP enables early implementation of interventions to minimize pain burden. Interventions to enhance coping, an adaptive characteristic, may also help to reduce APSP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

How to use low-molecular-weight heparin to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis due to risk factors such as catheter instrumentation, an evolving coagulation system and congenital heart disease. Low-molecular-weight heparins (LMWHs) are the most commonly used anticoagulants in neonates. Published guidelines delineate dosing and monitoring protocols for LMWH therapy in newborns. However, challenging clinical situations frequently present that warrant healthcare providers to think critically beyond the range of guidelines, and judiciously resolve specific problems. This review describes the use of LMWH in the neonatal population, including practical aspects such as route and site of administration, preparation from concentrated formulations and methods to minimize pain of subcutaneous injection. It is followed by a discussion on dosing, monitoring and outcomes of LMWH therapy in neonates. The risk of recurrence of thrombosis in neonates after LMWH therapy is approximately 3% based on a pooled analysis of studies reporting this outcome over the last 24 years. The article concludes with an overview of the side-effects of LMWH, including the risk of bleeding which is around 4% based on pooled analyses of more than 30 studies.