Citations

Summary Objective Patient–provider communication has been found to be less patient centred, on average, with patients who are members of stigmatized or minority groups. Obesity is a stigmatized condition, and thus, people with obesity may experience less patient‐centred communication (PCC). The objective of this study was to assess the association between patient body mass index (BMI) and self‐reported quality of PCC experienced over a 12‐month period and whether that relationship differed for men and women. Methods Data collected for the National Cancer Institute's Health Information National Trends Survey were analysed. Respondents who reported a BMI ≥ 18.5 kg/m 2 and indicated having seen a healthcare provider outside of an emergency room in the last 12 months were included. PCC was measured using a validated six‐item scale. Multivariate logistic regression was used to model the odds of reporting PCC greater than the sample median. Results Compared with people with normal weight BMIs, no associations were found between overweight (odds ratio [OR] = 0.84, p = 0.17), class I & II obesity (OR = 0.94, p = 0.68) or class III obesity (OR = 0.86, p = 0.47) and PCC. There was a significant interaction ( p = 0.015) such that for men, but not women, higher BMI was associated with less PCC. Conclusion Unlike evidence that women experience more weight stigma, in the healthcare domain, men may be at elevated risk of experiencing communication influenced by weight stigma.

Abstract Given the frequent and largely incurable occurrence of multiple myeloma, identification of germline genetic mutations that predispose cells to multiple myeloma may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell (PC). Here, we identified familial and early-onset multiple myeloma kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. In addition, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in patients with multiple myeloma unselected for family history compared with controls. Both monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma cells have significantly lower KDM1A transcript levels compared with normal PCs. Transcriptome analysis of multiple myeloma cells from KDM1A mutation carriers shows enrichment of pathways and MYC target genes previously associated with myeloma pathogenesis. In mice, antigen challenge followed by pharmacologic inhibition of KDM1A promoted PC expansion, enhanced secondary immune response, elicited appearance of serum paraprotein, and mediated upregulation of MYC transcriptional targets. These changes are consistent with the development of MGUS. Collectively, our findings show that KDM1A is the first autosomal-dominant multiple myeloma germline predisposition gene providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B-cell differentiation. Significance: KDM1A is the first germline autosomal dominant predisposition gene identified in multiple myeloma and provides new insights into multiple myeloma etiology and the mechanistic role of KDM1A as a tumor suppressor during post-germinal center B-cell differentiation. Cancer Res; 78(10); 2747–59. ©2018 AACR.

ABSTRACTIntroduction: For sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers (ENFs), but then healthy subject reference values of HP thresholds are needed. Methods: Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. Results: In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. Discussion: For the studied somatotopic sites, we provide ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Muscle Nerve 58: 509–516, 2018

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

As a result of observations on 50 isolated perfused hearts of guinea pigs it was found that the vagus nerves were active in 48 instances and the average duration of response to stimulation was 108 minutes. In one heart the vagi remained responsive to stimulation for 6 hours. It has again been shown that injections of appropriate doses of l-epinephrine are capable of restoring the unresponsive or exhausted vagal nerves to renewed chronotropic effectiveness.

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

Abstract Background Adverse childhood experiences ( ACE s) are associated with adult high‐risk behaviors and diseases. There is value in screening parents for ACE s given the repercussions parental ACE s may have on parenting behaviors and child development. The primary aim of this study was to assess the feasibility of parental ACE screening in the home setting. A secondary aim was to evaluate whether or not maternal ACE s correlated with maternal mental health measures. Methods Two home visiting programs that support early childhood development and conduct parental mental health screening implemented ACE screening for parents of infants <1 year of age. Descriptive statistics were produced for population surveillance of ACE s as well as standard practice screens for depression, anxiety, substance use, and intimate partner violence. Logistic models were used to examine associations between ACE score and mental health measures. Results A total of 110 parents completed the ACE screen. All possible ACE score outcomes were represented (0–10). A trend toward association of positive prenatal maternal depression screen with ACE score was identified ( p = .05). Conclusion This novel prospective home‐based screening program for parental ACE s was feasible and identified a trend toward increasing ACE score association with positive prenatal maternal depression screen.