Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.

Interactions with alloparents are associated with the diversity of infant skin and fecal bacterial communities in Chicago, United States.

INTRODUCTION: Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin. METHODS: To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States. RESULTS: Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status. CONCLUSION: This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.

Infant Age Moderates Associations between Infant Temperament and Maternal Technology Use during Infant Feeding and Care.

Previous research illustrated that infants' temperamental traits shape parents' behaviors, but parents' behaviors can also elicit or intensify infants' behaviors in ways that shape temperament. One understudied aspect of parenting that may exhibit bidirectional influences with temperament is parent technology use (e.g., use of mobile devices) within family contexts. To date, few studies have examined whether maternal technology use is associated with infant temperament and whether age-related differences in these associations exist. The present study was a secondary analysis of pooled data from three infant feeding studies. Mothers (n = 374) of young infants (age 16.2 ± 6.2 weeks) completed measures of maternal technology use during infant feeding and care interactions, infant temperament, and family demographics. Maternal technology use was positively associated with negative affectivity and negatively associated with orienting/regulatory capacity but was not associated with positive affectivity/surgency. The association between maternal technology use and negative affectivity was stronger for younger infants than older infants, while the association between maternal technology use and orienting/regulatory capacity was not significant for younger infants but was for older infants. Findings suggest maternal technology use is associated with infant negative affectivity and orienting/regulatory capacity, but the strength of these associations may change with infant age. Further longitudinal research is needed to verify this interpretation and understand mechanisms underlying these associations.

Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study.

BACKGROUND: Prevalence estimates for monoclonal gammopathy of undetermined significance (MGUS) are based on predominantly White study populations screened by serum protein electrophoresis supplemented with immunofixation electrophoresis. A prevalence of 3% is reported for MGUS in the general population of European ancestry aged 50 years or older. MGUS prevalence is two times higher in individuals of African descent or with a family history of conditions related to multiple myeloma. We aimed to evaluate the prevalence and clinical implications of monoclonal gammopathies in a high-risk US population screened by quantitative mass spectrometry. METHODS: We used quantitative matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry and EXENT-iQ software to screen for and quantify monoclonal gammopathies in serum from 7622 individuals who consented to the PROMISE screening study between Feb 26, 2019, and Nov 4, 2021, and the Mass General Brigham Biobank (MGBB) between July 28, 2010, and July 1, 2021. M-protein concentrations at the monoclonal gammopathy of indeterminate potential (MGIP) level were confirmed by liquid chromatography mass spectrometry testing. 6305 (83%; 2211 from PROMISE, 4094 from MGBB) of 7622 participants in the cohorts were at high risk for developing a monoclonal gammopathy on the basis of Black race or a family history of haematological malignancies and fell within the eligible high-risk age range (30 years or older for PROMISE cohort and 18 years or older for MGBB cohort); those over 18 years were also eligible if they had two or more family members with a blood cancer (PROMISE cohort). Participants with a plasma cell malignancy diagnosed before screening were excluded. Longitudinal clinical data were available for MGBB participants with a median follow-up time from serum sample screening of 4·5 years (IQR 2·4-6·7). The PROMISE study is registered with ClinicalTrials.gov, NCT03689595. FINDINGS: The median age at time of screening was 56·0 years (IQR 46·8-64·1). 5013 (66%) of 7622 participants were female, 2570 (34%) male, and 39 (<1%) unknown. 2439 (32%) self-identified as Black, 4986 (65%) as White, 119 (2%) as other, and 78 (1%) unknown. Using serum protein electrophoresis with immunofixation electrophoresis, the MGUS prevalence was 6% (101 of 1714) in high-risk individuals aged 50 years or older. Using mass spectrometry, we observed a total prevalence of monoclonal gammopathies of 43% (1788 of 4207) in this group. We termed monoclonal gammopathies below the clinical immunofixation electrophoresis detection level (<0·2 g/L) MGIPs, to differentiate them from those with higher concentrations, termed mass-spectrometry MGUS, which had a 13% (592 of 4207) prevalence by mass spectrometry in high-risk individuals aged 50 years or older. MGIP was predominantly of immunoglobulin M isotype, and its prevalence increased with age (19% [488 of 2564] for individuals aged <50 years, 29% [1464 of 5058] for those aged ≥50 years, and 37% [347 of 946] for those aged ≥70 years). Mass-spectrometry MGUS prevalence increased with age (5% [127 of 2564] for individuals aged <50 years, 13% [678 of 5058] for those aged ≥50 years, and 18% [173 of 946] for those aged ≥70 years) and was higher in men (314 [12%] of 2570) compared with women (485 [10%] 5013; p=0·0002), whereas MGIP prevalence did not differ significantly by gender. In those aged 50 years or older, the prevalence of mass spectrometry was significantly higher in Black participants (224 [17%] of 1356) compared with the controls (p=0·0012) but not in those with family history (368 [13%] of 2851) compared with the controls (p=0·1008). Screen-detected monoclonal gammopathies correlated with increased all-cause mortality in MGBB participants (hazard ratio 1·55, 95% CI 1·16-2·08; p=0·0035). All monoclonal gammopathies were associated with an increased likelihood of comorbidities, including myocardial infarction (odds ratio 1·60, 95% CI 1·26-2·02; p=0·00016 for MGIP-high and 1·39, 1·07-1·80; p=0·015 for mass-spectrometry MGUS). INTERPRETATION: We detected a high prevalence of monoclonal gammopathies, including age-associated MGIP, and made more precise estimates of mass-spectrometry MGUS compared with conventional gel-based methods. The use of mass spectrometry also highlighted the potential hidden clinical significance of MGIP. Our study suggests the association of monoclonal gammopathies with a variety of clinical phenotypes and decreased overall survival. FUNDING: Stand Up To Cancer Dream Team, the Multiple Myeloma Research Foundation, and National Institutes of Health.

Direct-acting antiviral therapy slows kidney function decline in patients with Hepatitis C virus infection and chronic kidney disease.

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre- and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m2, the annual decline in eGFR in the three years prior to treatment was -5.98 ml/min per year (95% confidence interval -7.30 to -4.67) and improved to -1.32 ml/min per year (95% confidence interval -4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m2 the annual decline in eGFR in the three years prior to treatment was -1.43 ml/min per year (95% confidence interval -1.78 to -1.08) and after DAA therapy was -2.32 ml/min per year (95% confidence interval -3.36 to -1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression.

When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Hepatitis C virus (HCV) infection, a major cause of end-stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin-based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon-free direct-acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients. A recently approved, pan-genotypic, direct-acting antiviral regimen, glecaprevir and pibrentasvir, may simplify prescribing. The simplicity of these new therapies, with few side effects, makes it possible for nephrologists to treat HCV infection in their patients on dialysis. We review the workflow and motivation behind nephrology-led management of HCV infection. We highlight the importance of identifying which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist. Nephrologist involvement would lead to improved access to treatment and ensure that appropriate patients are referred for HCV treatment. In this paper, we review the background of HCV infection, its effect on dialysis patients, and impact on kidney transplantation. In addition, we outline the therapy options for each genotype of HCV, and we discuss the benefits and barriers to nephrology-led HCV treatment.