Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina.

BACKGROUND: Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center. METHODS: All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes. RESULTS: Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS. CONCLUSION: Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

The Evolving Role of Rituximab in Adult Minimal Change Glomerulopathy.

BACKGROUND: Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab. METHODS: Demographic and clinical data were collected and analyzed from all adult patients with native kidney, biopsy-proven, minimal-change glomerulopathy who were administered rituximab between 2009 and 2014 and cared for at the UNC Kidney Center. RESULTS: Ten patients with corticosteroid-resistant (n = 5) or corticosteroid-dependent (n = 5) idiopathic minimal-change glomerulopathy were treated with rituximab between 2009 and 2014. Rituximab treatment induced remission in all 10 patients with a median time to remission of 2 months. The median time from rituximab to corticosteroid discontinuation was 3.5 months. The median remission time was 29 months and follow-up time was 39.5 months. No serious adverse events attributable to rituximab were observed. CONCLUSION: Rituximab induced remission in all patients with corticosteroid-dependent or -resistant minimal-change glomerulopathy, and may hold great therapeutic potential with good efficacy and minimal toxicity. Mounting evidence implies that a well-conducted randomized controlled clinical trial using rituximab in adults with minimal-change glomerulopathy in both corticosteroid-resistant and corticosteroid-dependent patients is warranted.

Clinical Features and Outcomes of a Racially Diverse Population with Fibrillary Glomerulonephritis.

BACKGROUND: Fibrillary glomerulonephritis is characterized by randomly arranged fibrils, approximately 20 nm in diameter by electron microscopy. Patients present with proteinuria, hematuria and kidney insufficiency, and about half of the reported patients progress to end-stage kidney disease within 4 years. The dependence of patient characteristics and outcomes on race has not been explored. In this study, we describe a cohort of patients with fibrillary glomerulonephritis and compare their clinical characteristics and outcomes with those of patients previously described. METHODS: The University of North Carolina (UNC) Nephropathology Database was used to retrospectively identify patients diagnosed with fibrillary glomerulonephritis between 1985 and 2015. Of these patients, those treated at UNC were selected. Their demographic and clinical characteristics - including signs and symptoms, comorbidities, laboratory values, treatments and outcomes - were compared with those of patients described earlier. RESULTS: Among the 287 patients identified, 42 were treated at the UNC Kidney Center. When compared to earlier cohorts, a higher frequency of black race, hepatitis C virus (HCV) infection and use of hemodialysis were noted in both black and HCV-positive patients. Autoimmune diseases, infections and malignancies were frequently observed, present in over half of all cases. CONCLUSION: According to this study, fibrillary glomerulonephritis represents a secondary glomerular disease process (associated with autoimmune disease, infection or malignancy) in many cases and hence screening is essential. As the screening for comorbidities increased over time, more underlying causes were identified. We noted a high frequency of HCV among black patients, suggesting a possible causative association. Treatment of underlying disease is essential for patients for the best outcome.

Spillover transmission is mediated by the excitatory GABA receptor LGC-35 in C. elegans.

Under most circumstances, GABA activates chloride-selective channels and thereby inhibits neuronal activity. Here, we identify a GABA receptor in the nematode Caenorhabditis elegans that conducts cations and is therefore excitatory. Expression in Xenopus oocytes demonstrates that LGC-35 is a homopentameric cation-selective receptor of the cys-loop family exclusively activated by GABA. Phylogenetic analysis suggests that LGC-35 evolved from GABA-A receptors, but the pore-forming domain contains novel molecular determinants that confer cation selectivity. LGC-35 is expressed in muscles and directly mediates sphincter muscle contraction in the defecation cycle in hermaphrodites, and spicule eversion during mating in the male. In the locomotory circuit, GABA release directly activates chloride channels on the muscle to cause muscle relaxation. However, GABA spillover at these synapses activates LGC-35 on acetylcholine motor neurons, which in turn cause muscles to contract, presumably to drive wave propagation along the body. These studies demonstrate that both direct and indirect excitatory GABA signaling plays important roles in regulating neuronal circuit function and behavior in C. elegans.

Outcome of Pediatric Gastroenterology Outpatients With Fever and Central Line.

OBJECTIVE: Although management algorithms for fever and central venous catheters (CVCs) have been implemented for pediatric oncology (PO) patients, management of pediatric outpatients with noncancer diagnoses and CVCs lacks clear protocols. The aim of the study was to assess outcomes for pediatric outpatients with gastrointestinal disorders presenting with fever and CVC. METHODS: Using a microbiology database and emergency department records, we created a database of pediatric gastroenterology (PGI) and PO outpatients with fever and a CVC who presented to our emergency department or clinics from January 2010 through December 2012. We excluded patients who had severe neutropenia (absolute neutrophil count, <500/mm). We performed chart reviews to assess demographic and clinical characteristics. RESULTS: A total of 334 episodes in 144 patients were evaluated. Fifty-three percent (95% confidence interval, 38%-68%) of PGI patients had a bloodstream infection, whereas only 9% (95% confidence interval, 5%-14%) of PO patients had a bloodstream infection (P < 0.001). Among patients with a bloodstream infection, the PGI patients were more likely than the PO patients to have polymicrobial infections (46% vs 15%), gram-negative infections (57% vs 27%), and/or infection with enteric organisms (61% vs 23%). The PGI patients had higher rates of CVC removal (19% vs 4%) but no statistical difference in intensive care unit needs (11% vs 4%). CONCLUSIONS: Pediatric gastroenterology outpatients with fever and a CVC have a high prevalence of bloodstream infection. Algorithms for management need to be subspecialty specific. Pediatric gastroenterology patients presenting to emergency departments or clinics with fever and CVC require admission for monitoring and management.

Risk factors for persistent dysphagia after anterior cervical spine surgery.

Dysphagia is a relatively common complication of anterior cervical spine surgery. Smoking has not been definitively assessed as a risk factor for dysphagia. This study examined risk factors for dysphagia, including smoking and pain severity. The authors performed a cross-sectional cohort study of 100 patients who underwent anterior cervical diskectomy and fusion (ACDF). Dysphagia was assessed with the Yoo-Bazaz questionnaire. Clinical notes were reviewed for demographic information, diagnosis, preoperative pain severity, preoperative smoking status, and operative details. The dysphagia questionnaire was administered via telephone. The rate of dysphagia at an average of 2.75 years (33 months) was 26%. Rare and mild dysphagia were reported by 2% and 7% of patients, respectively. Moderate dysphagia was reported by 12% patients, and severe dysphagia was reported by 5% of patients. Smokers were more likely to report dysphagia symptoms, and their dysphagia scores were more severe than those in nonsmokers (1.17 vs 0.54; P=.02). Patients undergoing revision surgery (n=7) had dysphagia at a rate of 71% compared with 23% of patients undergoing primary surgery (P<.004). Age, sex, diagnosis, severity of preoperative pain, and number of levels treated did not reach statistical significance. The prevalence of persistent dysphagia at an average of 33 months after ACDF was 23% in primary cases. To the authors' knowledge, the severity of dysphagia in smokers has not been reported previously. These data confirm previous reports that dysphagia symptoms persist in a significant proportion of patients more than 1 year after anterior cervical spine surgery.

Decreasing time to antibiotics in febrile patients with central lines in the emergency department.

BACKGROUND AND OBJECTIVE: Rapid antibiotic administration is essential for the successful management of patients who have central lines and present with fever. We conducted an emergency department (ED) improvement initiative to deliver antibiotics to 90% of patients within 60 minutes and to minimize process variation. METHODS: Our setting was an academic ED. We assembled a multidisciplinary team, identified contributing factors to the care delivery problem, determined key drivers and intervention steps, implemented changes, and used strategies to engage ED staff and promote sustainability. Outcomes were analyzed by using a time series design with baseline data and continuous postintervention monitoring. Outcomes included percentage of patients receiving antibiotics within 60 minutes, time to antibiotic administration, and accuracy for triage acuity and chief complaint. RESULTS: An 8-month baseline period revealed that 63% of patients received antibiotics within 60 minutes of arrival, with a mean time to antibiotics of 65 minutes. Multiple Plan-Do-Study-Act (PDSA) cycles were used to improve patient identification and initial management processes. The percentage of patients receiving antibiotics within 60 minutes of arrival was increased to 99% (297 of 301), and mean time to administration decreased to 30 minutes (95% confidence interval: 28-32). These gains were sustained for 24 months. Subanalysis identified a racial discrepancy, with African American patients experiencing significantly longer delays than patients of other races (95 vs 61 minutes; P < .05); this discrepancy was eliminated with our initiative. CONCLUSIONS: Our initiative exceeded our goal of 90% antibiotic delivery within 60 minutes for a sustained period of at least 24 months, decreased process variation and mean time to antibiotic administration, and eliminated race-based discrepancies in care.

Clinical Features of Reported Ethylene Glycol Exposures in the United States.

BACKGROUND: Ethylene glycol is highly toxic and represents an important cause of poisonings worldwide. Toxicity can result in central nervous system dysfunction, cardiovascular compromise, elevated anion gap metabolic acidosis and acute kidney injury. Many states have passed laws requiring addition of the bittering agent, denatonium benzoate, to ethylene glycol solutions to reduce severity of exposures. The objectives of this study were to identify differences between unintentional and intentional exposures and to evaluate the utility of denatonium benzoate as a deterrent. METHODS AND FINDINGS: Using the National Poison Data System, we performed a retrospective analysis of reported cases of ethylene glycol exposures from January 2006 to December 2013. Outcome classification was summed for intentionality and used as a basis for comparison of effect groups. There were 45,097 cases of ethylene glycol exposures resulting in 154 deaths. Individuals more likely to experience major effects or death were older, male, and presented with more severe symptoms requiring higher levels of care. Latitude and season did not correlate with increased exposures; however, there were more exposures in rural areas. Denatonium benzoate use appeared to have no effect on exposure severity or number. CONCLUSION: Deaths due to ethylene glycol exposure were uncommon; however, there were major clinical effects and more exposures in rural areas. Addition of denatonium benzoate was not associated with a reduction in exposures. Alternative means to deter ingestion are needed. These findings suggest the need to consider replacing ethylene glycol with alternative and less toxic agents.

Transgenerational Effects of Early Life Starvation on Growth, Reproduction, and Stress Resistance in Caenorhabditis elegans.

Starvation during early development can have lasting effects that influence organismal fitness and disease risk. We characterized the long-term phenotypic consequences of starvation during early larval development in Caenorhabditis elegans to determine potential fitness effects and develop it as a model for mechanistic studies. We varied the amount of time that larvae were developmentally arrested by starvation after hatching ("L1 arrest"). Worms recovering from extended starvation grew slowly, taking longer to become reproductive, and were smaller as adults. Fecundity was also reduced, with the smallest individuals most severely affected. Feeding behavior was impaired, possibly contributing to deficits in growth and reproduction. Previously starved larvae were more sensitive to subsequent starvation, suggesting decreased fitness even in poor conditions. We discovered that smaller larvae are more resistant to heat, but this correlation does not require passage through L1 arrest. The progeny of starved animals were also adversely affected: Embryo quality was diminished, incidence of males was increased, progeny were smaller, and their brood size was reduced. However, the progeny and grandprogeny of starved larvae were more resistant to starvation. In addition, the progeny, grandprogeny, and great-grandprogeny were more resistant to heat, suggesting epigenetic inheritance of acquired resistance to starvation and heat. Notably, such resistance was inherited exclusively from individuals most severely affected by starvation in the first generation, suggesting an evolutionary bet-hedging strategy. In summary, our results demonstrate that starvation affects a variety of life-history traits in the exposed animals and their descendants, some presumably reflecting fitness costs but others potentially adaptive.