Bone Mineral Density in Neurofibromatosis Type 1: A Systematic Review and Meta-Analysis.

To assess BMD in patients with neurofibromatosis type 1 (NF1) using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised terms for "Bone mineral density" and Neurofibromatosis type 1″. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined using the generic inverse variance method. A total of 1,165 articles were identified. After systematic review, 19 studies were included. The meta-analysis revealed that patients with NF1 had negative mean Z-scores for total body BMD (pooled mean Z-score -0.808; 95%CI, -1.025 to -0.591) and BMD at lumbar spine (pooled mean Z-score -1.104; 95%CI, -1.376 to -0.833), femoral neck (pooled mean Z-score -0.726; 95%CI, -0.893 to -0.560) and total hip (pooled mean Z-score -1.126; 95%CI, -2.078 to -0.173). The subgroup meta-analysis in pediatric patients aged < 18 years revealed that patients with NF1 had negative mean Z-scores for lumbar spine BMD (pooled mean Z-score -0.938; 95%CI, -1.299 to -0.577) and femoral neck BMD (pooled mean Z-score -0.585; 95%CI, -0.872 to -0.298). The current meta-analysis found that patients with NF1 had low Z-scores although the degree of low BMD may not be of clinical significance. The results do not support the role of early BMD screening in children and young adults with NF1.

Inpatient epidemiology, healthcare utilization, and association with comorbidities of Turner syndrome: A National Inpatient Sample study.

We aimed to investigate the prevalence, resource utilization, and comorbidities of patients with Turner syndrome (TS) hospitalized in the United States. We identified patients within the Nationwide Inpatient Sample database from the year 2017 to 2019. A propensity-matched cohort of non-TS patients from the same database was constructed to serve as comparators. There were 9845 TS patients, corresponding to inpatient prevalence of 10.4 per 100,000 admissions. The most common admission diagnosis was sepsis (27.9%). TS patients had higher inpatient mortality (adjusted odds ratio 2.16, 95% confidence interval 1.57-2.96) and morbidity, including shock, ICU admission, acute kidney injury, systemic inflammatory response syndrome, acute respiratory distress syndrome, and multi-organ failure. Increased risk of comorbidities, such as stroke, myocardial infarction, autoimmune diseases, and non-variceal gastrointestinal bleeding, was observed. TS patients had longer length of stay (LOS; 5.1 days vs. 4.5 days, p < 0.01) and displayed a mean additional $5382 (p < 0.01) in total hospital costs and a mean additional $20,083 (p < 0.01) in total hospitalization charges. In conclusion, hospitalization of patients with TS was associated with a significantly higher inpatient morbidity, mortality, expenditures, and longer LOS compared to non-TS patients. Patients with TS had a higher risk of cardiovascular complications, autoimmune diseases, and gastrointestinal bleeding.

Impact of the COVID-19 pandemic on medical genetics and genomics training: Perspective from clinical trainees.

We sought to understand how the coronavirus disease 2019 (COVID-19) pandemic has affected the well-being, clinical training, and medical education for clinical trainees in medical genetics and genomics residency and fellowship programs. All clinical genetics trainees in the Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs were invited to complete a survey. 31 out of 174 trainees completed the survey. With regards to well-being, 18 trainees reported increased anxiety, 10 had increased depression, 3 increased financial strain, 13 worsening work-life balance, and 13 worsening physical health. There was increased telehealth utilization in both outpatient (3% before the pandemic vs. 67% during the pandemic) and inpatient clinical encounters (0% vs. 29%). The most commonly reported challenges in telehealth use were inadequate physical examination and technical problems during visits. Twenty trainees believed that the pandemic has negatively impacted overall clinical training while none reported a positive impact. We concluded that the COVID-19 pandemic has negatively impacted most clinical genetics trainees in ACGME-accredited training programs. Telehealth has been increasingly used with some challenges. Further studies are needed on how to optimally integrate what we have learned into the training of medical genetics and genomics in the post-pandemic era.

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys).

Activating variants in the platelet-derived growth factor receptor ß gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next-generation sequencing-based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB-activating variants through literature search. The conditions caused by PDGFRB-activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant-related phenotypes are present. Whole-body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6- to 12-month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.

Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy.

More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late-onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB. Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.

SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmic disease linked to SCN5A mutations. It is controversial whether SCN5A mutation carriers possess a greater risk of major arrhythmic events (MAE). We examined the association of SCN5A mutations and MAE in BrS patients. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort and case-control studies that compared MAE in BrS patients with and without SCN5A mutations. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Seven studies from March 2002 to October 2017 were included (1,049 BrS subjects). SCN5A mutations were associated with MAE in Asian populations (RR = 2.03, 95% CI: 1.37-3.00, p = 0.0004, I2  = 0.0%), patients who were symptomatic (RR = 2.66, 95% CI: 1.62-4.36, p = 0.0001, I2  = 23.0%), and individuals with spontaneous type-1 Brugada pattern (RR = 1.84, 95% CI: 1.05-3.23, p = 0.03, I2  = 0.0%). CONCLUSIONS: SCN5A mutations in BrS increase the risk of MAE in Asian populations, symptomatic BrS patients, and individuals with spontaneous type-1 Brugada pattern. Our study suggests that SCN5A mutation status should be an important tool for risk assessment in BrS patients.

Landing a GI Fellowship: The Match and the Map.

BACKGROUND: Based on the location of training programs, internal applicants and local applicants were defined as applicants who attended the same training institution and trained in local areas (i.e., state, division, and region), respectively. While being an internal applicant does influence fellowship matching success for some specialties, gastroenterology fellowship program directors do not rank this consideration in the top half of their priority list. There is no published evidence about the frequency that internal applicants and local applicants match in US gastroenterology training program. AIM: To find the proportion of gastroenterologists who were internal applicants and local applicants during the graduation years 2010-2019. METHODS: Online search in Doximity was conducted to obtain postgraduate training information of gastroenterologists with the graduation years 2010-2019. Programs were classified into nine divisions and four regions per United States Census Bureau. We used confidence level 95% and margin of error 2% to calculate sample size. RESULTS: In total, 1489 physicians (N = 1489) were included. The proportion of internal applicants was 39.56% of the sample size. The proportions of gastroenterologists who attended IM residency programs in the same state, same division, and same region were 53.06, 60.64, and 71.93%, respectively. CONCLUSION: A large proportion of gastroenterologists were either internal applicants or local applicants. Further research is necessary to better understand the reasons behind these trends and whether the bias against external or geographically distant fellowship candidates is intended or unintended, as these data have broad implications for GI fellowship candidate residency program and geography choices.

Atypical Femoral Fracture in Hypophosphatasia: A Systematic Review.

Objective: To summarize the characteristics of all reported patients with hypophosphatasia (HPP) who sustained atypical femoral fracture (AFF) and identify all available evidence to quantify the rate of coexistence between HPP and AFF. Methods: Potentially eligible articles were identified from the MEDLINE and EMBASE databases from its inception to September 2022, using a search strategy consisting of terms related to "Hypophosphatasia" and "Atypical femoral fracture." Eligible articles must report one of the following information: (1) individual data of patients diagnosed with HPP and AFF, (2) prevalence of HPP among patients with AFF, or (3) prevalence of AFF among patients of HPP. Characteristics of patients reported in each study were extracted. Results: A total of 148 articles were identified. After the systematic review, 24 articles met the eligibility criteria. A total of 28 patients with AFF and HPP were identified. The mean ± SD age of the reported patients was 53.8 ± 12.5 years, and 22 patients (78.6%) were female. Nine patients (32.1%) received antiresorptive medication (bisphosphonate and/or denosumab), and two patients (7.1%) received teriparatide prior to the development of AFF. Seven (25.0%) and eighteen (64.3%) patients sustained unilateral and bilateral AFF, respectively (laterality not reported in three cases). Thirteen patients (46.4%) had a history of fractures at other sites. Four (14.3%) and seven (25.0%) patients received asfotase alfa and teriparatide after sustaining AFF. Two studies reported the prevalence of AFF among patients with HPP of approximately 10%. One study reported one HPP patient in a cohort of 72 patients with AFF. Conclusions: Based on the limited evidence, AFF occurred in up to 10% of patients with HPP. Based on the 28 case reports, about two-thirds did not receive antiresorptive treatment, suggesting that the HPP itself could potentially be a risk factor for AFF.

Increased family history documentation in internal medicine resident continuity clinic at a community hospital through resident-led structured genetic education program.

We aim to assess residents' perspectives and clinical utility of obtaining family history (FH) as well as to improve the rate of FH documentation in electronic medical record (EMR) at an internal medicine resident continuity clinic at a community hospital. The residents' perspectives were assessed with questionnaires. The study period was divided into the first 10-week Phase 1 in which genetic education interventions were delivered by residents, and the second 10-week Phase 2 with minimal intervention. FH documentation in EMR was reviewed and compared to a 4-week baseline (Phase 0). We found that time constraint was the most reported barrier. We reviewed 1197 patient visits; FH was recorded in 34% (67/200), 52% (272/522), and 50% (239/475) during Phase 0, Phase1, and Phase 2, respectively. Genetic education significantly increased the rate of FH documentation in Phase 1 from baseline, which was maintained in Phase 2 despite removal of interventions. The mean age of patients with documented FH was younger than those without documentation (48 years vs 51 years; p < 0.001). Documented FH of cancers and coronary artery disease lacked important details, such as age at diagnosis, in 62% (86/138) and 51% (41/81) of them, respectively. Out of 511 patients that had documented FH, we identified 66 patients (13%) where positive family history could alter medical management. In conclusion, resident-led structured genetic education effectively increased family history documentation in EMR in internal medicine resident continuity clinic and showed clinical utility.

Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders.

BACKGROUND: We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder. METHODS: Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays. RESULTS: We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype. CONCLUSIONS: Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.

Prevalence of thyroid diseases in familial adenomatous polyposis: a systematic review and meta-analysis.

Thyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its exact prevalence is not well established and recent studies have shown an increasing number of TC in this patient population. The prevalence of benign thyroid masses and endocrinologic thyroid disorders are also poorly described. We conducted a systematic review and meta-analysis by using a random-effects model to characterize TC and estimated the prevalence of thyroid diseases in FAP patients. Twelve studies (n = 9821) were included. Pooled prevalence of TC, benign thyroid masses, and endocrinologic thyroid disorders in FAP were 2.6% [95% confidence interval (CI) 1.3-4.8], 48.8% [95% CI 33.8-64.0], and 6.9% [95% CI 4.5-10.3] respectively. Subgroup analyses revealed higher prevalence of TC in studies with fewer participants, studies that used screening ultrasound to diagnose TC, and studies that were published after 2002. TC diagnosis preceded the diagnosis of FAP in 34% of the patients. The means age at diagnosis of FAP and TC were 29 and 31 years, respectively. 95% of the patients were female and the most common pathology was of papillary subtype (83.3%). Most mutations (79.2%) were located at the 5' end of APC gene. In summary, benign thyroid disorders are common in FAP, yet, TC is an uncommon phenomenon. Certain patient subset, such as young female with APC mutation at the 5' end, might benefit from routine surveillance ultrasound.

Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.

OBJECTIVE: The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear. METHODS: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab's effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055). RESULTS: Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m2. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88-5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, - 0.13 to 1.16) mmol/L and - 13.24 (95% CI, - 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements. CONCLUSION: Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.

C-peptide as a key risk factor for non-alcoholic fatty liver disease in the United States population.

AIM: To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease (NAFLD) in United States population. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD (e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05. RESULTS: Of 18825 participants aged ≥ 20, 3235 participants (n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2 , were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase (ALT), total protein, being Mexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level. CONCLUSION: Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.

A Chromosome 4q25 Variant is Associated with Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies suggested that variants on chromosome loci 4q25, 1q21, and 16q22 were associated with atrial fibrillation recurrence after catheter ablation. In this study, we performed a systematic review and meta-analysis to explore the association between variants on chromosome loci 4q25, 1q21, and 16q22 and atrial fibrillation recurrence after catheter ablation. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to January 2017. Included studies were published prospective or retrospective cohort and case control studies that compared the risk of atrial fibrillation recurrence after catheter ablation in AF patients with chromosome 4q25, 1q21, and 16q22 variants versus no variants. Single-nucleotide polymorphism rs1906617, rs2106261, rs7193343, rs2200733, rs10033464, rs13376333, and rs6843082 were included in this analysis. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals. RESULTS: Seven studies from January 2010 to June 2017 involving 3,322 atrial fibrillation patients were included in this meta-analysis. According to the pooled analysis, there was a strong independent association between chromosome 4q25 variant (rs2200733) and the risk of atrial fibrillation recurrence after catheter ablation (risk ratio 1.45 [95% confidence interval 1.15-1.83], P = 0.002). No association was found in other variants. CONCLUSION: Our meta-analysis demonstrates a statistically significant increased risk of atrial fibrillation recurrence after catheter ablation in 4q25 variant (only in rs2200733) but not in 1q21 or 16q22 variants.

A case of tracheobronchomegaly.

Tracheobronchomegaly (Mounier-Kuhn syndrome) is a rare condition characterized by an abnormally enlarged trachea and main bronchi. Herein, we present a case of 79-year-old male with idiopathic pulmonary fibrosis and acute hypoxemic respiratory failure due to multilobar pneumonia. Computed tomography of the chest demonstrated a markedly dilated trachea, with the transverse diameter of 31mm and the sagittal diameter of 30mm. The clinical manifestations as well as its diagnosis, classification, and treatment are discussed.

Increased arterial stiffness in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Arterial function is a marker of early atherosclerotic changes and cardiovascular disease. Several studies have suggested the possible association between nonalcoholic fatty liver disease (NAFLD) and increased arterial stiffness. Thus, we conducted a systematic review and meta-analysis to better characterize this association. PATIENTS AND METHODS: A comprehensive search of the databases of the MEDLINE and EMBASE was carried out from inception through September 2016. All observational studies that compared arterial stiffness between NAFLD patients and healthy controls were included. Arterial stiffness was measured by pulse wave velocity (PWV) and augmentation index. We calculated pooled mean difference (MD) with 95% confidence intervals (CIs) using the random-effects model. RESULTS: Data were extracted from 12 studies involving 9351 NAFLD patients and 17 684 controls. NAFLD is significantly associated with increased arterial stiffness as determined by carotid-femoral PWV (MD=0.75 m/s, 95% CI: 0.43-1.07, I=88%), brachial-ankle PWV (MD=0.82 m/s, 95% CI: 0.57-1.07, I=92%), and augmentation index (pooled MD=2.54%, 95% CI: 0.07-5.01, I=73%) compared with healthy controls. CONCLUSION: In conclusion, our study demonstrated a higher degree of arterial stiffness in NAFLD patients compared with controls. However, this association might be related to the higher prevalence of cardiometabolic risk factors in NAFLD patients. Further studies are needed to determine an independent association between NAFLD and arterial stiffness adjusting to cardiometabolic risks.

Dialysis Therapy and Conservative Management of Advanced Chronic Kidney Disease in the Elderly: A Systematic Review.

BACKGROUND: Dialysis in older adults with chronic kidney disease (CKD) and comorbidities may not be associated with improved life expectancy compared to conservative management. To inform clinical practice, we performed a systematic review of all available studies examining this hypothesis. METHODS: We performed a systematic review of retrospective and prospective cohort studies of older adults with stage-5 CKD who chose dialysis (hemodialysis or peritoneal dialysis) or opted for conservative management (including management of complications of CKD and palliative care). Outcomes of interest included hospitalizations and mortality. RESULTS: Twelve cohort studies (11,515 patients) were identified with most of them focusing on older adults. Patients choosing dialysis were younger compared to those opting for conservative management and were less functionally impaired. Patients opting for conservative management received care in a multidisciplinary setting focusing on palliative care and management of complications of CKD. Patients choosing dialysis and conservative management had a median survival time of 8-67 and 6-30 months, respectively. In a subset of studies of patients 65 years and older with an estimated glomerular filtration rate <15 mL/min/1.73 m2, and where the multivariable analyses included age and comorbidities, by meta-analysis, patients choosing dialysis had a pooled adjusted hazard ratio for mortality of 0.53 (95% CI 0.30-0.91, p = 0.02) relative to those opting for conservative management; however, significant heterogeneity precluded definitive conclusions. CONCLUSIONS: When caring for older adults with advanced CKD who are contemplating dialysis therapy vs. conservative management, efforts must focus on promoting patient values and preferences, shared decision-making, and symptom burden alleviation.