Serogroup B Meningococcal Disease Outbreak and Carriage Evaluation at a College - Rhode Island, 2015.

On February 2, 2015, the Rhode Island Department of Health was notified of a case of meningococcal disease in a male undergraduate student at Providence College. Three days later, a second case was reported in a male undergraduate with no contact with the first student, indicating an attack rate of 44 cases per 100,000 students, nearly 500 times higher than the national incidence of 0.15 cases per 100,000 among persons aged 17-22 years (Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC, unpublished data, 2013). Both cases were caused by a rare outbreak strain of Neisseria meningitidis serogroup B (ST-9069); neither case was fatal. In response to the outbreak, potential contacts received antibiotic chemoprophylaxis, and a mass vaccination campaign with a recently licensed serogroup B meningococcal (MenB) vaccine was implemented. In collaboration with CDC, the first phase of a meningococcal carriage evaluation was undertaken.

Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy.

Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated during ischemic and inflammatory AKI, in a sugarcane worker population in Nicaragua with high rates of MeN. Methods: Among 693 male sugarcane workers studied, we identified 45 who developed AKI during the harvest season. We matched them 1:1 based on age and job category with 2 comparison groups: (i) "no kidney injury," active sugarcane workers with serum creatinine (sCr) <1.1 mg/dl; and (ii) "CKD," individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for sCr. We measured urine metabolites using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) and compared Q/T and other metabolic features between the AKI and comparison groups. Results: Urine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median interquartile Range [IQR]: 0.104 [0.074-0.167] vs. 0.060 [0.045-0.091], P < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063-0.142], P = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups. Conclusion: Workers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, thereby providing new insights into the metabolic mechanisms of injury in this population. Therapeutic use of oral nicotinamide, which may ameliorate NAD+ biosynthetic derangement and fortify against kidney injury, should be investigated to prevent AKI in this setting.

Effects of correction rate for severe hyponatremia in the intensive care unit on patient outcomes.

PURPOSE: Limited evidence exists regarding outcomes associated with different correction rates of severe hyponatremia. MATERIALS AND METHODS: This retrospective cohort analysis employed a multi-center ICU database to identify patients with sodium ≤120 mEq/L during ICU admission. We determined correction rates over the first 24 h and categorized them as rapid (> 8 mEq/L/day) or slow (≤ 8 mEq/L/day). The primary outcome was in-hospital mortality. Secondary outcomes included hospital-free days, ICU-free days, and neurological complications. We used inverse probability weighting for confounder adjustment. RESULTS: Our cohort included 1024 patients; 451 rapid and 573 slow correctors. Rapid correction was associated with lower in-hospital mortality (absolute difference: -4.37%; 95% CI, -8.47 to -0.26%), longer hospital-free days (1.80 days; 95% CI, 0.82 to 2.79 days), and longer ICU-free days (1.16 days; 95% CI, 0.15 to 2.17 days). There was no significant difference in neurological complications (2.31%; 95% CI, -0.77 to 5.40%). CONCLUSION: Rapid correction (>8 mEq/L/day) of severe hyponatremia within the first 24 h was associated with lower in-hospital mortality and longer ICU and hospital-free days without an increase in neurological complication. Despite major limitations, including the inability to identify the chronicity of hyponatremia, the results have important implications and warrant prospective studies.

Altered consciousness mediates the effect of hypernatremia, but not hyponatremia, on mortality among patients observed in the ICU.

Purpose: Dysnatremias - hypernatremia and hyponatremia - may be associated with mortality through their impact on altered consciousness. We examined the mediating effect of decreased consciousness on the relationship between dysnatremia and mortality. Methods: Among 195,568 critically ill patients in the United States contained in the eICU database, we categorized serum sodium into bands of 5mEq/L. Using causal mediation analysis, we compared bands in the hypernatremia and hyponatremia ranges to a reference band of 135-139mEq/L to determine the proportion of mortality mediated by decreased consciousness as determined by the Glasgow Coma Score (GCS). Results: Both hyponatremia (OR [95%CI] for bands: <120mEq/L: 1.58 [1.26-1.97]; 120-<125mEq/L: 1.92 [1.64-2.25]; 125-<130mEq/L: 1.76 [1.60-1.93]; 130-<135mEq/L: 1.32 [1.24-1.41]) and hypernatremia (OR [95%CI] for bands: 140-<145mEq/L: 1.12 [1.05-1.19]; 145-<150mEq/L: 1.89 [1.70-2.11]; ≥150mEq/L: 1.86 [1.57-2.19]) were significantly associated with increased mortality. GCS mediated the effect of hypernatremia on mortality risk (Proportion mediated [95%CI]: 140-144mEq/L: 0.38 [0.23 to 0.89]; 145-149mEq/L: 0.27 [0.22 to 0.34]; ≥150mEq/L: 0.53 [0.41 to 0.81]) but not hyponatremia (proportion mediated 95%CI upper bound <0.05 for all bands). Conclusion: Decreased consciousness mediates the association between increased mortality and hypernatremia, but not hyponatremia. Further studies are needed to explore neurologic mechanisms and directionality in this relationship.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.

Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19-Related Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is common in COVID-19 and associated with increased morbidity and mortality. We investigated alterations in the urine metabolome to test the hypothesis that impaired nicotinamide adenine dinucleotide (NAD+) biosynthesis and other deficiencies in energy metabolism in the kidney, previously characterized in ischemic, toxic, and inflammatory etiologies of AKI, will be present in COVID-19-associated AKI. METHODS: This is a case-control study among the following 2 independent populations of adults hospitalized with COVID-19: a critically ill population in Boston, Massachusetts, and a general population in Birmingham, Alabama. The cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes (KDIGO) criteria; the controls had no AKI. Metabolites were measured by liquid chromatography-mass spectrometry. RESULTS: A total of 14 cases and 14 controls were included from Boston and 8 cases and 10 controls from Birmingham. Increased urinary quinolinate-to-tryptophan ratio (Q/T), found with impaired NAD+ biosynthesis, was present in the cases at each location and pooled across locations (median [interquartile range]: 1.34 [0.59-2.96] in cases, 0.31 [0.13-1.63] in controls, P = 0.0013). Altered energy metabolism and purine metabolism contributed to a distinct urinary metabolomic signature that differentiated patients with and without AKI (supervised random forest class error: 2 of 28 in Boston, 0 of 18 in Birmingham). CONCLUSION: Urinary metabolites spanning multiple biochemical pathways differentiate AKI versus non-AKI in patients hospitalized with COVID-19 and suggest a conserved impairment in NAD+ biosynthesis, which may present a novel therapeutic target to mitigate COVID-19-associated AKI.

Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational Study.

Background: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT. Results: A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P=0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P=0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P=0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

Association of Chloride Ion and Sodium-Chloride Difference With Acute Kidney Injury and Mortality in Critically Ill Patients.

OBJECTIVES: Derangements of chloride ion concentration ([Cl-]) have been shown to be associated with acute kidney injury and other adverse outcomes. For a physicochemical approach, however, chloride ion concentration should be considered with sodium ion concentration. This study aimed to examine the association of chloride ion concentration and the main strong ion difference (difference between sodium ion concentration and chloride ion concentration) during the first 24 hours after admission into ICU with the development of acute kidney injury and mortality. DESIGN: Retrospective analyses using the eICU Collaborative Research Database. SETTING: ICUs in 208 hospitals across the United States between 2014 and 2015. PATIENTS: Critically ill patients who were admitted into the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 34,801 patients records were analyzed. A multivariable logistic regression analysis for the development of acute kidney injury within 7 days of ICU admission shows that, compared with main strong iron difference 32-34 mEq/as a reference, there were significantly high odds for the development of acute kidney injury in nearly all groups with main strong iron difference more than 34 mEq/L (main strong iron difference = 34-36 mEq/L, odds ratio = 1.17, p = 0.02; main strong iron difference = 38-40 mEq/L, odds ratio = 1.40, p < 0.001; main strong iron difference = 40-42 mEq/L, odds ratio = 1.46, p = 0.001; main strong iron difference > 42 mEq/L, odds ratio = 1.56, p < 0.001). With chloride ion concentration 104-106 mEq/L as a reference, the odds for acute kidney injury were significantly higher only in chloride ion concentration less than or equal to 94 mEq/L and chloride ion concentration 98-100 mEq/L groups. Analyses conducted using inverse probability weighting showed significantly greater odds for ICU mortality in all groups with main strong iron difference greater than 34mEq/L other than the 36-38mEq/L group, as well as in the less than 26-mEq/L group. CONCLUSIONS: Main strong iron difference measured on ICU presentation to the ICU predicts acute kidney injury within 7 days, with low and, in particular, high values representing increased risk. The association between the chloride levels and acute kidney injury is statistically insignificant in models incorporating main strong iron difference, suggesting main strong iron difference is a better predictive marker than chloride on ICU admission.

Association Between ICU-Acquired Hypernatremia and In-Hospital Mortality: Data From the Medical Information Mart for Intensive Care III and the Electronic ICU Collaborative Research Database.

OBJECTIVES: Describe the relationship between ICU-acquired hypernatremia and in-hospital mortality and investigate the optimal hypernatremia correction rate. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: Observational study including two individual ICU cohorts. We used the Medical Information Mart for Intensive Care III v. 1.4 database consists of all ICU patients admitted to the Beth Israel Deaconess Medical Center in Boston from 2001 to 2012 (n = 46,476). The electronic ICU v. 2.0 database consists of all ICU patients admitted to 208 distinct hospitals across the United States from 2014 to 2015 (n = 200,859). We included all adult patients admitted to an ICU with two consecutive sodium samples within normal range (135-145 mmol/L) and without two consecutive hyponatremic samples (< 135 mmol/L) during the ICU stay. RESULTS: Of 23,445 patients identified in Medical Information Mart for Intensive Care III, 9% (n = 2,172) developed hypernatremia during their ICU stay. In electronic ICU, 88,160 patients were identified and 7% (n = 5,790) developed hypernatremia. In both cohorts, patients with hypernatremia had a higher mortality (Medical Information Mart for Intensive Care III: 20% vs 42%; p < 0.01 and electronic ICU: 6% vs 22%; p < 0.01), with hypernatremia increasing the risk of in-hospital mortality (Medical Information Mart for Intensive Care III: odds ratio, 1.15; 95% CI, 1.13-1.17 and electronic ICU: odds ratio, 1.11; 95% CI, 1.10-1.12) and over time using a Cox regression. Rapid sodium correction rate (> 0.5 mmol/L/hr) was associated with an increased in-hospital mortality in both cohorts (Medical Information Mart for Intensive Care III: odds ratio, 1.08; 95% CI, 1.03-1.13 and electronic ICU: odds ratio, 1.10; 95% CI, 1.06-1.13). In the electronic ICU cohort, rapid correction rates were associated with a significant difference in in-hospital mortality, but there was no statistically significant association in the Medical Information Mart for Intensive Care III cohort. CONCLUSIONS: ICU-acquired hypernatremia is associated with increased in-hospital mortality. Furthermore, a rapid sodium correction rates may be harmful. This suggests it is important to both prevent ICU-acquired hypernatremia and to avoid rapid correction rates if a patient becomes hypernatremic.

Hemorrhage from Extra-Antral Gastric Antral Vascular Ectasia in a Patient with Duodenal Heterotopic Gastric Mucosa.

Gastric antral vascular ectasias (GAVE) have been increasingly recognized as an uncommon cause of chronic gastrointestinal bleeding and anemia, although their underlying pathogenesis is not completely well understood. Heterotopic gastric mucosa (HGM) has been reported to occur at various sites along the gastrointestinal tract and although relatively common, it is often asymptomatic. We report a case of a 60-year-old woman with a prior history of GAVE who developed melena and symptomatic anemia during her hospitalization following cardiac catheterization. Initial EGD demonstrated nonbleeding antral GAVE and a newly discovered duodenal mass. Duodenal mass biopsies were ultimately notable for HGM along with histologic features of extra-antral GAVE. The patient required blood transfusions and consequently had a small bowel endoscopy notable for fresh blood in the proximal small bowel. The patient underwent a small bowel push enteroscopy which demonstrated active bleeding of the duodenal mass and overlying oozing GAVE, which was cauterized with Argon-Plasma Coagulation with adequate hemostasis. We present for the first time a novel association between GAVE and HGM. Our case illustrates that extra-antral GAVE may occur with HGM in the duodenum. We explore potential mechanisms by which HGM may be involved in the pathogenesis of GAVE.

Urinary and blood cadmium and lead and kidney function: NHANES 2007-2012.

BACKGROUND: Cadmium (Cd) and lead (Pb) are widespread environmental contaminants that are known nephrotoxins. However, their nephrotoxic effects at low-environmental exposure levels are debated. OBJECTIVE: We examined the association of blood Pb (B-Pb), blood Cd (B-Cd), urinary Pb (U-Pb) and urinary Cd (U-Cd) with estimated glomerular filtration rate (eGFR) and urinary albumin (ALB). METHODS: We used multivariate linear regression to analyze the association between B-Pb, B-Cd, U-Pb, and U-Cd with eGFR and ALB in adult participants (≥20 years of age) in NHANES 2007-2012. The dataset was limited to NHANES individuals with both blood and urinary metal measurements. RESULTS: We found a statistically significant inverse association between eGFR and B-Cd and statistically significant positive associations between eGFR and both U-Cd and U-Pb, as well as statistically significant associations between ALB and the 3rd and 4th quartiles of U-Cd. CONCLUSIONS: The inverse association between eGFR and B-Cd, in conjunction with positive associations between eGFR and ALB with U-Cd, suggest that U-Cd measurement at low levels of exposure may result from changes in renal excretion of Cd due to kidney function and protein excretion. However, renal effects such as hyperfiltration from Cd-mediated kidney damage or creatinine-specific Cd effects cannot be excluded with this cross-sectional design.

Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy.

INTRODUCTION: Mesoamerican nephropathy, also known as chronic kidney disease of unknown etiology, is widespread in Pacific coastal Central America. The cause of the epidemic is unknown, but the disease may be linked to multiple factors, including diet as well as environmental and occupational exposures. As many as 50% of men in some communities have Mesoamerican nephropathy. OBJECTIVE: Describe prevalence of reduced glomerular filtration rate in a region of Nicaragua suspected to harbor high rates of Mesoamerican nephropathy; and investigate potential risk factors for such reduction associated with agricultural work (such as pesticide exposure and specific agricultural tasks associated with increased heat stress); sugar consumption; and traditional factors such as age, sex, diabetes, hypertension and nephrotoxic medication use. METHODS: This study uses a cross-sectional design with nested case-control analysis. Cases were individuals with estimated glomerular filtration rates of <60mL/min/1.73m2 and controls were individuals with those >90mL/min/1.73m2, estimated using serum creatinine. Data on nutrition, past medical history, medication and substance use, and agricultural behaviors and exposures were collected using medical questionnaires from June through August, 2012. Venous blood and urine samples were collected to assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and blood pressure measurements were made using standard techniques. Analyses were conducted using chi square, and univariate and multiple logistic regression. RESULTS: Of 424 individuals in the study, 151 had an occupational history in agriculture. Prevalence of glomerular filtration rate <60mL/min/1.73m2 was 9.8% among women and 41.9% among men (male to female ratio = 4.3, p<0.0001). Proteinuria =300 mg/dL was observed in <10% of participants with decreased glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated with decreased glomerular filtration rate. Although systolic and diastolic blood pressure was higher among participants with decreased glomerular filtration rate (p <0.001), hypertension was uncommon. Significant agricultural risk factors for reduced glomerular filtration rate included increased lifetime days cutting sugarcane during the dry season (OR 5.86, 95% CI 2.45-14.01), nondeliberate pesticide inhalation (OR 3.31, 95% CI 1.32-8.31), and sugarcane chewing (OR 3.24, 95% CI 1.39-7.58). CONCLUSIONS: Our findings demonstrate a high prevalence of chronic kidney disease not linked to traditional risk factors, and suggest it may be associated instead with occupational exposure to heat stress in conjunction with pesticide inhalation, sugarcane chewing and sugar intake during the workday.