Explore the vast range of titles available.

Calciphylaxis is a condition with unpredictable onset that predominantly affects people with kidney disease. This rare, incredibly painful condition results in necrotic skin lesions caused by calcified occlusions of the microvasculature and has an average one-year mortality rate of 50%. There is no cure for calciphylaxis, and treatment primarily focuses on symptom management. We sought to understand the lived experience of calciphylaxis. This qualitative study utilized semi-structured, phenomenological interviewing. We created a code table in which primary codes were analyzed from the biopsychosocial perspective from which overarching domains of experience were identified. Our sample consisted of 15 outpatient participants: 9 were in remission from calciphylaxis while 6 had active disease. Twelve participants were women while 3 were male. Participants ages ranged from 38 – 80 (mean 59). The calciphylaxis patient experience was characterized by severe pain, a lack of adequate pain management, limited calciphylaxis literacy among providers, and complicated interpersonal relationships with family, friends, and medical providers. Calciphylaxis is a life-altering condition characterized by severe pain and uncertainty on multiple fronts. This study demonstrates that clinical management of rare, severe illnesses, such as calciphylaxis, requires clear, honest provider-patient communication, sufficient provider and patient education, adequate symptom management, and empathy.

Dialysis patients have been shown to have low serum carnitine due to poor nutrition, deprivation of endogenous synthesis from kidneys, and removal by hemodialysis. Carnitine deficiency leads to impaired cardiac function and dialysis-related hypotension which are associated with increased mortality. Supplementing with levocarnitine among hemodialysis patients may diminish incidence of intradialytic hypotension. Data on this topic, however, lacks consensus. We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to 19th November 2021 to identify randomized controlled studies (RCTs), which examined the effects of oral or intravenous levocarnitine (L-carnitine) on dialysis-related hypotension among hemodialysis patients. The secondary outcome was muscle cramps. Study results were pooled and analyzed utilizing the random-effects model. Trial sequential analysis (TSA) was performed to assess the strength of current evidence. Eight trials with 224 participants were included in our meta-analysis. Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among hemodialysis patients (pooled OR = 0.26, 95% CI [0.10-0.72], p = 0.01, I2 = 76.0%). TSA demonstrated that the evidence was sufficient to conclude the finding. Five studies with 147 participants showed a reduction in the incidence of muscle cramps with L-carnitine group (pooled OR = 0.22, 95% CI [0.06-0.81], p = 0.02, I2 = 74.7%). However, TSA suggested that further high-quality studies were required. Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. Regarding dose and duration of L-carnitine supplementation, the dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension. Supplementing oral L-carnitine for at least three months above 4,200 mg/week helps prevent dialysis-related hypotension. L-carnitine supplementation may ameliorate muscle cramps. Further well-powered studies are required to conclude this benefit.

Abstract Context Discontinuation of denosumab leads to a rapid reversal of its therapeutic effect. However, there are no data regarding how unintended delays or missed injections of denosumab impact bone mineral density (BMD) response. Objective We examined the association of delays in injections of denosumab with BMD change. Design We used electronic medical records from two academic hospitals from 2010 to 2017. Participants Patients older than 45 years of age and used at least 2 doses of 60 mg denosumab. Denosumab adherence was evaluated by the medication coverage ratio (MCR). Good adherence corresponds to a dosing interval ≤7 months (defined by MCR ≥93%), moderate adherence corresponds to an interval of 7 to 10 months (MCR 75%–93%), and poor adherence corresponds to an interval ≥10 months (MCR ≤75%). Outcome Measures Annualized percent BMD change from baseline at the lumbar spine, total hip, and femoral neck. Results We identified 938 denosumab injections among 151 patients; the mean (SD) age was 69 (10) years, and 95% were female. Patients with good adherence had an annualized BMD increase of 3.9% at the lumbar spine, compared with patients with moderate (3.0%) or poor adherence (1.4%, P for trend .002). Patients with good adherence had an annualized BMD increase of 2.1% at the total hip, compared with patients with moderate (1.3%) or poor adherence (0.6%, P for trend .002). Conclusions A longer interval between denosumab injections is associated with suboptimal BMD response at both spine and total hip. Strategies to improve the timely administration of denosumab in real-world settings are needed.

Calciphylaxis is a rare and life-threatening disease that classically manifests with painful skin lesions. It occurs mainly in patients with end-stage renal disease (ESRD) treated with dialysis, has poor outcomes, and has no FDA-approved treatment. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. Data from 70 calciphylaxis patients who were evaluated at the Massachusetts General Hospital between January 2014 and April 2018 were collected from the institutional electronic database. The median age was 58 years (interquartile range [IQR]: 49-69 years), 60% were women, and 73% were of white race. Most (74%) patients reported severe pain at the time of calciphylaxis diagnosis with a median pain intensity score of 8/10 (IQR: 6-10) on a 0-10 pain scale. The median time from symptom onset to clinical diagnosis was 9 weeks (IQR: 6-16 weeks). The majority (87%) of patients presented with open necrotic wounds (advanced stage lesion) at the time of diagnosis. Common cutaneous clinical features included ulceration (79%), induration (57%), and erythema (41%), while common pathological features included cutaneous microvascular calcification (86%) and necrosis (73%). The presence of fibrin thrombi in skin biopsies was associated with pain severity (p = 0.04). The stage of a skin lesion positively correlated with the presence of necrosis on histological analyses (p = 0.02). These findings have implications for improving understanding of calciphylaxis origins and for developing novel treatments.

Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab. We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years. Observational cohort study using electronic medical records from two academic medical centers in the United States. The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab. Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck. Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by -2.2% (95% CI -2.9 to -1.5%) and the femoral neck by -1.1% (95% CI -2.1 to -0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years. Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.

Calciphylaxis is a life-threatening disorder characterized by occlusion of microvessels in the subcutaneous adipose tissue and dermis. The authors outline the current understanding of calciphylaxis and provide a framework for interdisciplinary management.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Background Patient reported outcome (PRO) instruments are important for assessing the effects of new therapeutics; however, no PRO measures have been specifically developed for use in Nephrotic Syndrome (NS) with documented evidence of content validity. Methodology The Nephrotic Syndrome Symptom and Impact Patient Reported Outcome (NephroSSI-PRO) tool was developed following a literature review, concept elicitation (CE) interviews with patients with NS and clinicians, item generation, and cognitive debriefing (CD) interviews with patients with NS. The CE interviews were conducted with four nephrologists and among adults (aged ≥ 18 years) and adolescents (aged 12–17 years) diagnosed with NS. Results In total, 45 adult and adolescent patients were interviewed across all CE and CD interviews. In the adult CE interviews, the most frequently reported symptoms were swelling in the feet/legs ( n  = 14/16), general tiredness ( n  = 13/16), change in appetite ( n  = 13/16), foamy urine ( n  = 12/16), and shortness of breath ( n  = 12/16); impacts included emotional health, physical function limitations, sleep difficulties, and social/lifestyle limitations ( n  = 13/16). In adolescents, the most frequently reported symptoms were tiredness/fatigue ( n  = 13/15), stomachache ( n  = 11/15), headache ( n  = 8/15), foamy/frothy urine ( n  = 7/15), swelling in face/eyes ( n  = 6/15), swelling in legs/ankles ( n  = 5/15), and change in appetite ( n  = 5/15), while the most common impacts were impact on schooling ( n  = 10/15), reduced ability to practice sports ( n  = 7/15), and impact on friendship ( n  = 7/15). A conceptual model was developed and used to inform item generation for the NephroSSI-PRO. During CD interviews, there were no challenges in understanding and relating to instrument instructions, items, and response options. Conclusions We have developed a PRO instrument to evaluate the symptoms and impacts of NS in adult and adolescent patients. In this study, the evidence from a literature review, and direct patient input from CE and CD support its content validity. Further work supporting the instrument’s validity will be performed in a future clinical trial.

Background Hyponatremia (serum sodium concentration < 135 mmol/L) is the most common electrolyte abnormality and is a predictor of the mortality of hospitalized patients in Western countries. However, hyponatremia data are lacking in Asian countries. Here we evaluate the epidemiology and mortality of hyponatremia in general medical hospitalized patients in China. Methods This is a cohort study of 154,378 adults who were hospitalized between 2008 and 2012 at a teaching hospital in Beijing. We identified hospital patients with hyponatremia and calculated the prevalence and in-hospital mortality of hyponatremia. We also conducted a comprehensive retrospective review of the medical records of patients who had severe hyponatremia (serum sodium <120 mmol/L) during hospitalization in 2012. Results The overall prevalence of hyponatremia at some point during hospitalization was 17.5% (26,990 patients), but only 0.26% (394 patients) of cases were identified with the diagnostic code of hyponatremia. Hyponatremia was more common in patients with infectious disease, cancer, or cardiovascular disease as the primary reason for hospitalization based on discharge diagnosis, with prevalences of 33.0, 25.9 and 24.9%, respectively. The in-hospital mortality was 0.48% amongst patients without hyponatremia compared to 3.57 and 20.23% in patients with serum sodium levels of 130–134 and <120 mmol/L, resulting in multivariable adjusted odds ratios (ORs) of 4.8 (95% CI 4.3–5.4) and 32.9 (95% CI 25.2–42.3), respectively. The mortality risk increased with increasing severity of hyponatremia in all diagnostic groups. After the multivariate adjustment, only the Charlson Comorbidity Index and age were independently associated with death risk (OR 1.36, 95% CI 1.14–1.64 and OR 1.04, 95% CI 1.00–1.09, respectively) in the patients with severe hyponatremia. Conclusions Hyponatremia is highly prevalent among Chinese hospitalized patients and is associated with increased in-hospital mortality risk. Physicians should raise awareness to improve the prognosis of hyponatremia.

The purpose of this study was to evaluate the impact of hemodialysis on the concentrations of sodium and potassium in the blood when a 25 g dose of sodium thiosulfate injection is infused over 60 minutes in combination with hemodialysis. Sodium thiosulfate (25 g) was prepared by diluting 100 mL of 250 mg/mL Sodium Thiosulfate Injection with 800 mL of 5% dextrose. This was added to the circulating blood surrogate solution at a rate of 15 mL/minute using an infusion pump of an in vitro model of dialysis machine. Serial samples were collected before the administration of the sodium thiosulfate solution, after 15 minutes, 30 minutes, and 60 minutes of infusion from pre-and post-dialyzer ports in both the dialysate circuit and the extracorporeal circuit. The concentration of sodium thiosulfate in pre-dialyzer and post-dialyzer samples of the circulating blood surrogate solution peaked at 30 minutes and 15 minutes, respectively and then remained relatively unchanged during the remainder of the infusion. Mean sodium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 103.2 ± 12.2, 114.2 ± 18.8, 117.2 ± 7.5, 93.5 ± 5.9 at 0, 15, 30, and 60 minutes, respectively (p = 0.248). Mean potassium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 1.4 ± 0.3, 1.6 ± 0.3, 1.5 ± 0.1, 1.2 ± 0.1 at 0, 15, 30, and 60 minutes, respectively (p = 0.365). Sodium and potassium concentrations in dialysate increased marginally after exposure to the dialyzer. Our study demonstrates that neither potassium nor sodium accumulated in circulating blood surrogate solution when a dose of sodium thiosulfate was infused in conjunction with hemodialysis.