Intermuscular adipose tissue in patients with systemic lupus erythematosus.

OBJECTIVE: Patients with SLE frequently have debilitating fatigue and reduced physical activity. Intermuscular adipose tissue (IMAT) accumulation is associated with reduced physical exercise capacity. We hypothesised that IMAT is increased in patients with SLE and associated with increased fatigue, reduced physical activity and increased inflammation. METHODS: In a cross-sectional study, 23 patients with SLE and 28 control participants were evaluated. IMAT was measured in the calf muscles using sequential T 1-weighted MRI. Patient-reported physical activity and fatigue were measured and a multiplex proteomic assay was used to measure markers and mediators of inflammation. RESULTS: IMAT accumulation (percentage of IMAT area to muscle area) was significantly higher in SLE versus control participants (7.92%, 4.51%-13.39% vs 2.65%, 1.15%-4.61%, median, IQR, p<0.001) and remained significant after adjustment for age, sex, race and body mass index (p<0.001). In patients with SLE, IMAT accumulation did not differ significantly among corticosteroid users and non-users (p=0.48). In the study cohort (patients and controls), IMAT was positively correlated with self-reported fatigue score (rho=0.52, p<0.001) and inversely correlated with self-reported walking distance (rho=-0.60, p<0.001). Several markers of inflammation were associated with IMAT accumulation in patients with SLE, and gene ontology analysis showed significant enrichment for pathways associated with macrophage migration and activation in relation to IMAT. CONCLUSION: Patients with SLE have greater IMAT accumulation than controls in the calf muscles. Increased IMAT is associated with greater fatigue and lower physical activity. Future studies should evaluate the effectiveness of interventions that improve muscle quality to alleviate fatigue in patients with SLE.

CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice.

Cytochrome P450 2D6 (CYP2D6) O-demethylates codeine to the active drug, morphine. However, the utility of testing for CYP2D6 metabolizer status in patients receiving codeine in real-world clinical practice is poorly defined. Using data from a DNA bank linked to de-identified electronic health records, we studied 157 patients with a baseline pain score higher than 4 (0-10 scale) who received codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid CYP2D6 metabolizers. Pain response was defined as a score of 4 or lower while receiving codeine. In a propensity-score adjusted model, poor/intermediate metabolizers had lower odds (OR = 0.35, p = 0.02) of achieving a pain response than normal/ultrarapid metabolizers. To discriminate between codeine responders and nonresponders, a score including CYP2D6 phenotype and clinical variables was built. The response rate was 38.5% among patients in the high, 17.3% in the intermediate, and 9.4% in the low-score groups, respectively (p = 0.001).

Ambulatory blood pressure in patients with systemic lupus erythematosus: Association with markers of immune activation.

Objectives: Ambulatory blood pressure monitoring measures 24-hour blood pressure, night-time blood pressure, and impaired dipping of nocturnal blood pressure, parameters that better predict cardiovascular risk than standard office blood pressure measurements. Systemic lupus erythematosus is characterized by immune system hyperactivity, elevated cardiovascular risk and high prevalence of hypertension; however, little is known about ambulatory blood pressure in lupus patients and its relationship to immune activation. Methods: We studied 26 patients with lupus and 26 control subjects. We obtained ambulatory 24-hour blood pressure measurements and report plasma concentrations of 77 markers of immune activation using a multiplex immunoassay and assessed their association with blood pressure measurements. Results: Despite similar office blood pressure measurements in patients with lupus and controls, lupus patients had higher 24-hour systolic [median (interquartile range) 129 (113 - 140) vs. 116 (111 - 121) mmHg, p = 0.03] and diastolic blood pressure [80 (69 - 86) vs. 72 (64 - 75) mmHg, p = 0.006] as well as less nocturnal dipping [7.8% (5.1 - 14.2%) vs. 12.0% (8.1 20.0%)] p = 0.03], compared to controls. In patients with lupus, markers of the innate (monocyte chemotactic protein-3) and adaptive immune systems [CUB domain-containing protein-1 and Interleukin-15 receptor subunit-α,] were associated with nocturnal blood pressure measurements and attenuated nocturnal dipping. In conclusion, 24-hour systolic and diastolic blood pressure was higher and nocturnal blood pressure dipping was attenuated in patients with lupus compared to control subjects. Conclusion: In patients with SLE, nocturnal blood pressure and attenuated nocturnal blood pressure dipping were significantly associated with several innate and adaptive immune system biomarkers.

A Genetic Approach to the Association Between PCSK9 and Sepsis.

Importance: Whether the PCSK9 gene is associated with the progress from infection to sepsis is unknown to date. Objective: To test the associations between PCSK9 genetic variants, a PCSK9 genetic risk score (GRS), or genetically estimated PCSK9 expression levels and the risk of sepsis among patients admitted to a hospital with infection. Design, Setting, and Participants: This retrospective cohort study used deidentified electronic health records to identify patients admitted to Vanderbilt University Medical Center, Nashville, Tennessee, with infection. Patients were white adults, had a code indicating infection from the International Classification of Diseases, Ninth Revision, Clinical Modification, or the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification, and received an antibiotic within 1 day of hospital admission (N = 61 502). Data were collected from January 1, 1993, through December 31, 2017, and analyzed from April 1, 2018, to March 16, 2019. Exposures: Four known PCSK9 functional variants, a GRS for PCSK9, and genetically estimated PCSK9 expression. Main Outcomes and Measures: The primary outcome was sepsis; secondary outcomes included cardiovascular failure and in-hospital death. Results: Of patients with infection, genotype information was available in 10 922 white patients for PCSK9 functional variants (5628 men [51.5%]; mean [SD] age, 60.1 [15.7] years), including 7624 patients with PCSK9 GRS and 6033 patients with estimated PCSK9 expression. Of these, 3391 developed sepsis, 835 developed cardiovascular failure, and 366 died during hospitalization. None of the 4 functional PCSK9 variants were significantly associated with sepsis, cardiovascular failure, or in-hospital death, with or without adjustment for (1) age and sex or (2) age, sex, and Charlson-Deyo comorbidities (in model adjusted for age, sex, and comorbidities, odds ratios for any loss-of function variant were 0.96 [95% CI, 0.88-1.04] for sepsis, 1.05 [95% CI, 0.90-1.22] for cardiovascular failure, and 0.89 [95% CI, 0.72-1.11] for death). Similarly, neither the PCSK9 GRS nor genetically estimated PCSK9 expression were significantly associated with sepsis, cardiovascular failure, or in-hospital death in any of the analysis models. For GRS, in the full model adjusted for age, sex, and comorbidities, the odds ratios were 1.01 for sepsis (95% CI, 0.96-1.06; P = .70), 1.03 for cardiovascular failure (95% CI, 0.95-1.12; P = .48), and 1.05 for in-hospital death (95% CI, 0.92-1.19; P = .50). For genetically estimated PCSK9 expression, in the full model adjusted for age, sex, and comorbidities, the odds ratios were 1.01 for sepsis (95% CI, 0.95-1.06; P = .86), 0.96 for cardiovascular failure (95% CI, 0.88-1.05; P = .41), and 0.99 for in-hospital death (95% CI, 0.87-1.14; P = .94). Conclusions and Relevance: In this study, PCSK9 genetic variants were not significantly associated with risk of sepsis or the outcomes of sepsis in patients hospitalized with infection.

Association between urinary sodium and potassium excretion and blood pressure and inflammation in patients with rheumatoid arthritis.

Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na+) and low potassium (K+) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na+ and K+ urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na+ and K+ excretion. Estimated 24-h Na+ excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9-6.6 g]) and controls (4.9 g, [4.0-6.5 g]), p = 0.9, despite higher rates of hypertension in RA (54 vs. 39%, p = 0.03). The Na+:K+ excretion ratio was significantly higher in RA (2.0 [1.6-2.4]) vs. 1.7 [1.5-2.1]), p = 0.02] compared to controls. In RA, a lower K+ excretion was inversely correlated with diastolic blood pressure (adjusted ß = - 1.79, p = 0.04). There was no significant association between Na+ or K+ excretion and inflammatory markers. Despite a similar Na+ excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na+:K+ excretion ratio than controls, and lower K+ excretion was associated with higher diastolic blood pressure in RA.

Determining Optimal Route of Hysterectomy for Benign Indications: Clinical Decision Tree Algorithm.

OBJECTIVE: To evaluate practice change after initiation of a robotic surgery program using a clinical algorithm to determine the optimal surgical approach to benign hysterectomy. METHODS: A retrospective postrobot cohort of benign hysterectomies (2009-2013) was identified and the expected surgical route was determined from an algorithm using vaginal access and uterine size as decision tree branches. We excluded the laparoscopic hysterectomy route. A prerobot cohort (2004-2005) was used to evaluate a practice change after the addition of robotic technology (2007). Costs were estimated. RESULTS: Cohorts were similar in regard to uterine size, vaginal parity, and prior laparotomy history. In the prerobot cohort (n=473), 320 hysterectomies (67.7%) were performed vaginally and 153 (32.3%) through laparotomy with 15.1% (46/305) performed abdominally when the algorithm specified vaginal hysterectomy. In the postrobot cohort (n=1,198), 672 hysterectomies (56.1%) were vaginal; 390 (32.6%) robot-assisted; and 136 (11.4%) abdominal. Of 743 procedures, 38 (5.1%) involved laparotomy and 154 (20.7%) involved robotic technique when a vaginal approach was expected. Robotic hysterectomies had longer operations (141 compared with 59 minutes, P<.001) and higher rates of surgical site infection (4.7% compared with 0.2%, P<.001) and urinary tract infection (8.1% compared with 4.1%, P=.05) but no difference in major complications (P=.27) or readmissions (P=.27) compared with vaginal hysterectomy. Algorithm conformance would have saved an estimated $800,000 in hospital costs over 5 years. CONCLUSION: When a decision tree algorithm indicated vaginal hysterectomy as the route of choice, vaginal hysterectomy was associated with shorter operative times, lower infection rate, and lower cost. Vaginal hysterectomy should be the route of choice when feasible.

Effect of chair types on work-related musculoskeletal discomfort during vaginal surgery.

BACKGROUND: Evidence supports that surgeons are at high risk for work-related musculoskeletal disorders. OBJECTIVE: The objective of the study was to compare the effect of different chairs on work-related musculoskeletal discomfort for surgeons during vaginal operations. STUDY DESIGN: This crossover study randomly assigned 4 surgeons to 4 chair types using a 4 × 4 Latin square model: a conventional round stool, a round stool with a backrest, a saddle chair with a backrest, and a Capisco chair. Subjective assessments of surgeon discomfort were performed with a validated body discomfort survey, and workload was assessed with the surgical task load index. The objective postural load was quantified with inertial measurement units of the modified rapid upper limb assessment limits. Subjective and objective assessments of chair comfort were performed with an 11 point scale and seat interface pressure-mapped distributions, respectively. The primary outcome was the difference in body discomfort scores between pre- and postsurgery measurements. Secondary outcomes were the differences in chair comfort scores, postural load, and seating interface pressure-mapped distribution. For each outcome, comparisons among the chair types were based on fitting a linear mixed model that handled the surgeon as a random effect and the chair type as a fixed effect. RESULTS: Data were collected for 48 vaginal procedures performed for pelvic organ prolapse. Mean (SD) duration of surgery was 122.3 (25.1) minutes. Surgeons reported body discomfort during 31 procedures (67.4%). Subjective increase in discomfort from the preoperative state was noted most commonly in the lower back (n = 14, 30.4%), followed by right shoulder (n = 12, 26.1%), upper back (n = 8, 17.4%), hips and buttocks (n = 7, 15.2%), left shoulder (n = 6, 13.0%), right or left thigh (n = 6, 13.0%), and neck (n = 6, 13.0%). Pre- and postsurgery body discomfort scores did not differ with respect to chair type. Chair discomfort scores for the round stool and the saddle chair were significantly higher than the round stool with backrest and the Capisco chair (P < .001). Although the average modified rapid upper limb assessment postural scores showed moderate to high musculoskeletal risk of neck and shoulder discomfort across the 4 surgeons; chair type did not affect postural scores. The saddle chair had significantly reduced dispersion of seated pressure vs the round stool with backrest (P ≤ .001), depicted by the number of cells with pressure values >5 mm Hg. An increased dispersion of pressure across the chair surface was associated with increased comfort (Spearman correlation, 0.40, P = .006). CONCLUSION: Musculoskeletal strain and associated discomfort for surgeons are very high during vaginal operations. Chair type can affect comfort, and chairs with more uniform distribution and fewer pressure points are more comfortable. However, the chair type used in surgery did not influence the musculoskeletal postural load findings.

Predictors of vaginal mesh exposure after midurethral sling placement: a case-control study.

INTRODUCTION AND HYPOTHESIS: Female stress urinary incontinence is highly prevalent, and synthetic midurethral sling placement is the most common type of anti-incontinence surgery performed in the USA. We aimed to identify risk factors associated with surgery used to treated vaginal mesh exposure after midurethral sling placement for stress urinary incontinence. METHODS: We identified women who underwent anti-incontinence procedures from January 2002 through December 2012. Patients with vaginal mesh exposure undergoing surgical repair after midurethral sling placement were compared with a control group without mesh exposure in a 1:3 ratio. Patients with ObTape sling placement (Mentor Corporation) were excluded. Logistic regression models were used to evaluate associations between clinical risk factors and vaginal mesh exposure. RESULTS: Overall, 2,123 patients underwent primary sling placement, with 27 (1.3 %) having vaginal mesh exposure necessitating surgical repair. Patients with mesh exposure were more likely to have undergone previous bariatric surgery (P = 0.008), hemoglobin <13 g/dL (P = 0.006), premenopausal status (P = 0.008), age <50 years (P = 0.001), and the retropubic approach to sling placement (P = 0.03). Multivariate analysis identified these risk factors: previous bariatric surgery (odds ratio [OR], 7.0; 95 % CI, 1.1-61.4), retropubic approach (OR, 5.7; 95 % CI, 1.1-107.0), preoperative hemoglobin <13 g/dL (OR, 2.8; 95 % CI, 1.1-7.5), and premenopausal status (OR, 2.6; 95 % CI, 1.0-7.3). Among postmenopausal patients, those with mesh exposure were significantly more likely to receive preoperative estrogen therapy (OR, 12.4; 95 % CI, 2.7-57.8). CONCLUSIONS: Previous bariatric surgery, retropubic approach, premenopausal status, and lower preoperative hemoglobin were associated with a significantly increased risk of surgery for vaginal mesh exposure after midurethral sling placement. Recognizing these factors can improve preoperative patient counseling.