Citations

Background: We aimed to describe the incidence of hospital-acquired dyschloremia and its association with in-hospital mortality in general hospitalized patients. Methods: All hospitalized patients from 2009 to 2013 who had normal admission serum chloride and at least two serum chloride measurements in the hospital were studied. The normal range of serum chloride was defined as 100–108 mmol/L. Hospital serum chloride levels were grouped based on the occurrence of hospital-acquired hypochloremia and hyperchloremia. The association of hospital-acquired hypochloremia and hyperchloremia with in-hospital mortality was analyzed using logistic regression. Results: Among the total of 39,298 hospitalized patients, 59% had persistently normal hospital serum chloride levels, 21% had hospital-acquired hypochloremia only, 15% had hospital-acquired hyperchloremia only, and 5% had both hypochloremia and hyperchloremia. Compared with patients with persistently normal hospital serum chloride levels, hospital-acquired hyperchloremia only (odds ratio or OR 2.84; p < 0.001) and both hospital-acquired hypochloremia and hyperchloremia (OR 1.72; p = 0.004) were associated with increased in-hospital mortality, whereas hospital-acquired hypochloremia only was not (OR 0.91; p = 0.54). Conclusions: Approximately 40% of hospitalized patients developed serum chloride derangements. Hospital-acquired hyperchloremia, but not hypochloremia, was associated with increased in-hospital mortality.

AbstractObjectiveData on the presentations and outcomes of patients with adrenal gland metastases are limited. Our objectives were to characterize the prevalence of adrenal metastases subtypes and investigate how varying clinical presentations affect disease progression, development of primary adrenal insufficiency (PAI) and mortality.DesignSingle institution tertiary centre, retrospective cohort study from 1997 to 2020.Patients and MeasurementsAdult patients with adrenal metastases. Clinical, radiologic and biochemical presentations and outcomes were reviewed.ResultsOf 579 patients (62.3% men, median age 67 years [range 25‐92]) with adrenal metastases (median tumour size of 30 mm [range 5‐200]), 339 (58.5%) were discovered during cancer staging, 210 (36.3%) were found incidentally, and 29 (5.0%) based on symptoms. Tumours originated from the lung (226, 39.0%), genitourinary (GU) (160, 27.6%), gastrointestinal (GI) (79, 13.6%) and other (114, 19.7%) organ systems. Bilateral metastases were found in 140 (24.2%) patients at the time of initial diagnosis, and 249 (43.0%) had bilateral disease throughout the study course. PAI developed in 12.4% of patients with bilateral disease and was associated with larger tumour size. Median follow‐up time was 14 months (range 0‐232), and 442 (76.3%) patients died. Higher mortality was independently associated with older age, adrenal metastases originating from the lung, bilateral disease, and the absence of adrenalectomy.ConclusionsAdrenal gland metastases originated most commonly from lung, GU and GI malignancies. Bilateral adrenal metastases occurred in 43% of patients, and PAI occurred in 12.4% of those with bilateral disease, warranting further case detection strategies.

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = −234.50 pg/mL (five studies; 95% CI −444.84 to −24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of −232.24 pg/mL (three studies; 95% CI –299.41 to −165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = −110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = −92.41 pg/mL (two studies; 95% CI −180.53 to −4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.

PURPOSE Intrahepatic cholangiocarcinoma (IHCCA), a global health problem, is increasing in incidence and has differing etiologies worldwide. Next-generation sequencing (NGS) is rapidly being incorporated into the clinical management of biliary cancers. IHCCA is enriched with actionable mutations, and there are several promising targeted therapies under development. NGS data from Asia, where IHCCA is most prevalent, are limited. METHODS Comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 164 Asian and 283 Western patients with IHCCA was performed using NGS. We measured the distribution of DNA repair genetic aberrations (GAs) in IHCCA, along with actionable mutations. Also, we evaluated the association between DNA repair GAs and tumor mutation burden (TMB). Based on the TMB status, patients were distinguished into 3 levels: low (< 6 mut/Mb), intermediate (6-10 mut/Mb), and high (TMB-H; ≥ 10 mut/Mb). RESULTS Seventy-two percent of Asian patients had ≥ 1 actionable GA, with a significantly higher frequency in KMT2C , BRCA1/2, and DDR2 compared with Western patients ( P = .02, .003, and .003, respectively); 60.9% of Western patients had ≥ 1 actionable GA and higher frequency of CDKN2A/B and IDH1/2 GAs ( P = .0004 and < .001, respectively). GAs in nuclear factor kappa B pathway regulators and DNA repair genes occurred more frequently in Asian patients ( P = .006 and .001, respectively). There was a higher frequency of TMB-H in Asian compared with the Western cohort (12.2% v 5.9%; P = .07). CONCLUSION A higher burden of DNA repair mutations and frequency of patients with TMB-H in the Asian IHCCA cohort compared with the Western patients suggests a potential role for DNA repair and immune checkpoint inhibitors in the Asian population. Future clinical trials should account for this genetic heterogeneity.

Background Abnormal circadian blood pressure ( BP ) variations during sleep, specifically the non‐dipping (<10% fall in nocturnal BP ) and reverse‐dipping patterns (rise in nocturnal BP ), have been associated with an increased risk of cardiovascular events and target organ damage. However, the relationship between abnormal sleep BP variations and cerebral small vessel disease markers is poorly established. This study aims to assess the association between non‐dipping and reverse‐dipping BP patterns with markers of silent cerebral small vessel disease. Methods and Results MEDLINE , Embase, and Cochrane Databases were searched from inception through November 2019. Studies that reported the odds ratios (ORs) for cerebral small vessel disease markers in patients with non‐dipping or reverse‐dipping BP patterns were included. Effect estimates from the individual studies were extracted and combined using the random‐effect, generic inverse variance method of DerSimonian and Laird. Twelve observational studies composed of 3497 patients were included in this analysis. The reverse‐dipping compared with normal dipping BP pattern was associated with a higher prevalence of white matter hyperintensity with a pooled adjusted OR of 2.00 (95% CI , 1.13–2.37; I 2 =36%). Non‐dipping BP pattern compared with normal dipping BP pattern was associated with higher prevalence of white matter hyperintensity and asymptomatic lacunar infarction, with pooled OR s of 1.38 (95% CI , 0.95–2.02; I 2 =52%) and 2.33 (95% CI , 1.30–4.18; I 2 =73%), respectively. Limiting to only studies with confounder‐adjusted analysis resulted in a pooled OR of 1.38 (95% CI , 0.95–2.02; I 2 =52%) for white matter hyperintensity and 1.44 (95% CI , 0.97–2.13; I 2 =0%) for asymptomatic lacunar infarction. Conclusions The non‐dipping and reverse‐dipping BP patterns are associated with neuroimaging cerebral small vessel disease markers.

Abstract Objective The objective of this meta‐analysis of observational studies was to evaluate the association between simple renal cysts (SRC) and presence of aortic pathology such as aortic aneurysms and dissection. Methods We conducted searches in Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1960 to August 2019 to identify observational studies that examined the association between SRCs and any aortic diseases, including aortic aneurysms and dissection. Two reviewers independently extracted the data and assessed the risk of bias. The meta‐analysis was performed by STATA 14.1. Results In total, 11 observational studies with 19 719 participants were included in this meta‐analysis. Compared to individuals without SRCs, patients with SRCs had higher odds of abdominal aortic aneurysm (AAA) (adjusted OR = 2.61, 95% CI 2.34‐2.91, P < 0.001, I 2 = 0%), ascending thoracic aortic aneurysm (TAA) (adjusted OR = 1.98, 95% CI 1.09‐3.63, P = 0.03, I 2 = 90.1%), descending TAA (adjusted OR = 3.44, 95% CI, 2.67‐4.43, P < 0.001, I 2 = 0%), type A aortic dissection (AD) (adjusted OR = 1.98, 95% CI 1.32‐2.96, P = 0.001, I 2 = 12.9%), and type B AD (adjusted OR = 2.55, 95% CI, 1.31‐4.96, P = 0.006, I 2 = 76.2%). There was a higher average in the sum of diameter of SRCs among AAA compared to patients without AAA (WMD = 19.80 mm, 95% CI 13.92‐25.67, P < 0.001, I 2 = 63.8%). Conclusion SRC is associated with higher odds of aortic diseases including AAA, ascending and descending TAA, type A and type B dissection even after adjusting for confounders.

Background and Objectives: The optimal range of serum potassium at hospital discharge is unclear. The aim of this study was to assess the relationship between discharge serum potassium levels and one-year mortality in hospitalized patients. Materials and Methods: All adult hospital survivors between 2011 and 2013 at a tertiary referral hospital, who had available admission and discharge serum potassium data, were enrolled. End-stage kidney disease patients were excluded. Discharge serum potassium was defined as the last serum potassium level measured within 48 h prior to hospital discharge and categorized into ≤2.9, 3.0–3.4, 3.5–3.9, 4.0–4.4, 4.5–4.9, 5.0–5.4 and ≥5.5 mEq/L. A Cox proportional hazards analysis was performed to assess the independent association between discharge serum potassium and one-year mortality after hospital discharge, using the discharge potassium range of 4.0–4.4 mEq/L as the reference group. Results: Of 57,874 eligible patients, with a mean discharge serum potassium of 4.1 ± 0.4 mEq/L, the estimated one-year mortality rate after discharge was 13.2%. A U-shaped association was observed between discharge serum potassium and one-year mortality, with the nadir mortality in the discharge serum potassium range of 4.0–4.4 mEq/L. After adjusting for clinical characteristics, including admission serum potassium, both discharge serum potassium ≤3.9 mEq/L and ≥4.5 mEq/L were significantly associated with increased one-year mortality, compared with the discharge serum potassium of 4.0–4.4 mEq/L. Stratified analysis based on admission serum potassium showed similar results, except that there was no increased risk of one-year mortality when discharge serum potassium was ≤3.9 mEq/L in patients with an admission serum potassium of ≥5.0 mEq/L. Conclusion: The association between discharge serum potassium and one-year mortality after hospital discharge had a U-shaped distribution and was independent of admission serum potassium. Favorable survival outcomes occurred when discharge serum potassium was strictly within the range of 4.0–4.4 mEq/L.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0–10%, 11–20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0–10% GS (58.0%), 11–20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0–10% GS, 68.9% in 11–20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0–10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11–20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0–10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

Abstract Background: Adrenal metastases occur in 1–8% of patients with an adrenal mass. Recognizing patterns in the presentation of adrenal metastases is critical in dictating management. Objective: To describe the presentation of patients with adrenal metastases and identify baseline characteristics predicting the etiology. Methods: A retrospective analysis of adult patients diagnosed with adrenal metastases between 2000–2019 at a single institution tertiary center was performed. Partial cohort analysis is presented. Results: In 327 patients (127 (39%) women, median age at diagnosis of 67 years (range 25–92)), median tumor size was 2.7 cm (range 0.5–15), and 99 (30%) had bilateral tumors. While most patients (188, 57%) were found to have an adrenal mass during cancer staging, 117 (36%) were found incidentally and 22 (7%) based on symptoms. Adrenal metastases originated from the lung (118, 36%), genitourinary (GU) (100, 31%), gastrointestinal (GI) (47, 14%), and other (43, 13%) organ systems. Unknown primary malignancies were diagnosed in 19 (5.8%) patients. Male predominance was observed in GU (72%) and lung (62%) metastases, but equal gender distributions were noted for all other metastases, p=0.01. Patients with GI and lung metastases were diagnosed with smaller tumors (median 2.1 and 2.6 cm, respectively) compared to those with GU (median 3.5 cm) and other (median 4 cm) metastases, p=0.0008. Bilateral metastases were more frequently found in patients with lung (37%) and other (38%) metastases compared to those with GI (17%) and GU (24%) metastases, p=0.01. Of 99 (30%) patients with bilateral metastases, 23% developed primary adrenal insufficiency (PAI), most commonly in those with lung (36%) and GU (30%) malignancies. Only 123 (38%) patients were evaluated by an endocrinologist. Pheochromocytoma work-up was more often pursued if seen by an endocrinologist (71% vs. 15%, p&lt;0.0001) in 118 (36%) patients. Adrenalectomy was performed in 94 (29%) patients, most frequently in those with GU metastases (57%), compared to only 10% of those with lung metastases. Patients were followed for a median time of 14 months (range 0.1–181), and 222 (68%) died. GU metastases carried the best prognosis with a mortality rate (MR) of 43%, as opposed to a MR of &gt;70% in all other metastases, with lung metastases carrying the worst prognosis (MR of 85%). Multivariate analysis revealed that mortality was associated with increasing age (OR 1.3 (95% CI 1.04–1.6) for each decade) and metastasis subgroup (lung vs. GU: OR 7.2 (95% CI 3.7–14)). Conclusion: Adrenal metastases most commonly originated from lung, GU and GI malignancies, with a third of patients discovered incidentally. Bilateral metastases occurred in 30% of patients, where 1 in 4 developed PAI. Only a minority were evaluated by an endocrinologist or had work up for pheochromocytoma. Mortality was highest in those with adrenal metastases originating from the lung.