Is There Synergistic Effect Between Obesity and Hypoalbuminemia on Postoperative Outcomes Among Primary Total Shoulder Arthroplasty Recipients?

Background: Malnutrition and obesity are established predictors of complications following joint replacement surgery. However, the effect of obesity in the setting of albumin deficiency has not been explored in non-weight-bearing upper-extremity joint arthroplasty. Purpose: We sought to determine whether there is a synergistic effect between obesity and hypoalbuminemia among patients undergoing primary total shoulder arthroplasty (TSA) with respect to postoperative outcomes, including (1) mortality rates, (2) composite surgical complications, (3) length of hospitalization, and (4) hospital readmission. Methods: We conducted a retrospective cohort study using the National Surgical Quality Improvement Program (NSQIP) database to find patients who underwent primary TSA from January 1, 2006, to December 31, 2019. We grouped these patients as obese (body mass index [BMI] ≥ 30 kg/m2) or nonobese (BMI = 18.5-29.9 kg/m2) and by serum albumin level (hypoalbuminemia < 3.5 mg/dL or normoalbuminemia ≥ 3.5 mg/dL). We gathered data on readmission and mortality rates, and NSQIP complications were organized into 3 composite variables: wound infection, systemic infection, and cardiac/pulmonary complication. For each outcome, multivariate logistic regression analysis evaluated its association with obesity and hypoalbuminemia, as well as with the interaction of BMI and albumin, while adjusting for covariates. Results: Of 12,881 patients, 51.8% were obese and 7.0% had hypoalbuminemia; 7.6% of obese patients had hypoalbuminemia versus 6.3% of those who were not obese. Patients with hypoalbuminemia had the longest hospital stays and the highest rates of mortality and systemic infection of all subgroups. Multivariate logistic regression analysis did not show higher complication rates due to obesity or evidence of additive interaction between hypoalbuminemia and obesity. Conclusion: Unlike previous reports in weight-bearing arthroplasty, in this retrospective study of a cohort of patients who underwent TSA, we did not observe greater complications due to obesity alone, nor did we find evidence of additive interaction between obesity and hypoalbuminemia. This distinction may be due to the non-weight-bearing nature of TSA, in which excessive BMI may be less relevant for postoperative healing.

Association between Paravertebral Block and Pain Score at the Time of Hospital Discharge in Oncoplastic Breast Surgery: A Retrospective Cohort Study.

BACKGROUND: Using nonopioid analgesics may decrease the risk of patients chronically using opioids postoperatively. The authors evaluated the relationship between paravertebral block and pain score at the time of hospital discharge. METHODS: The authors performed a retrospective cohort study of 89 women with American Society of Anesthesiologists Physical Status I to III undergoing oncoplastic breast surgery with 20 to 50 percent breast tissue removal and immediate contralateral reconstruction between August of 2015 and August of 2018. The primary outcome was pain score at hospital discharge with or without paravertebral block. The secondary outcome was postoperative length of stay. Data were analyzed using the Wilcoxon rank sum test, t test, Fisher's exact test, univariable and multivariable regression, Kaplan-Meier analyses, and Cox regression. RESULTS: Median pain score at hospital discharge was lower with paravertebral block [2 (interquartile range, 0 to 2) compared to 4 (interquartile range, 3 to 5); p < 0.001]. Multivariable regression revealed that pain score at the time of hospital discharge was inversely associated with paravertebral block after adjusting for age, body mass index, American Society of Anesthesiologists class, extent of lymph node surgery, and duration of surgery (p < 0.001). Pain score at hospital discharge was also associated with total opioid consumption during the first 24 hours after surgery (p = 0.001). Patients who received paravertebral blocks had median total 24-hour postoperative opioid consumption in morphine equivalents of 7 mg (interquartile range, 3 to 10 mg) compared with 13 mg (interquartile range, 7 to 18 mg) (p < 0.001), and median length of stay of 18 hours (interquartile range, 16 to 20 hours) compared with 22 hours (interquartile range, 21 to 27 hours) (p < 0.001). CONCLUSION: Paravertebral blocks are associated with decreased pain score at the time of hospital discharge. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Asthma and Atopic Dermatitis: A Review of Targeted Inhibition of Interleukin-4 and Interleukin-13 As Therapy for Atopic Disease.

Type 2 helper T cell (Th2)-mediated inflammation plays a critical role in the pathogenesis of allergic asthma and atopic dermatitis (AD). Recent research focusing on the suppression of the Th2 axis with targeted inhibitors in atopic disease is showing promising early results. In particular, the simultaneous blockage of interleukin (IL)-4 and IL-13 has successfully mitigated symptoms of allergic asthma and AD in preliminary clinical trials. Given the current therapeutic challenges of treating these chronic and severe diseases, this review brings to light new data demonstrating that agents targeting IL-4 and IL-13 are relatively safe and effective medications in blocking the inflammatory cascade responsible for allergic asthma and atopic dermatitis.

Clearance of psoriasis: the impact of private versus public insurance.

BACKGROUND: Psoriasis treatments and therapeutic response as they relate to private versus public patient insurance in the United States have not yet been reviewed. Improved understanding could clarify factors challenging optimal psoriasis management and offer insight for dermatologists treating psoriasis within our healthcare system. METHODS: 258 subjects were included from a database of psoriasis patients seen at Tufts Medical Center (Boston, MA) during 2008-2014. Insurance was classified as primarily private or public (Medicare or MassHealth/Medicaid). Patients required a minimum of two consecutive visits per treatment and at least 8 weeks within one of four treatment categories: biologics, oral systemics/ phototherapy, combined biologics and oral systemics/phototherapy, or topicals only. Primary endpoint was the Simple-Measure for Assessing Psoriasis Activity (S-MAPA) calculated by multiplying Physician Global Assessment by Body Surface Area. S-MAPA<3 constituted absolute clearance. Insurance type was evaluated as a predictor of prescribed treatment categories, maximum S-MAPA improvement from baseline, and total drugs used per treatment course ("drug-switching"). RESULTS: 80.2% (n=207) and 19.8% (n=51) had primarily private and public insurance, respectively. 69.6% with private insurance were prescribed biologics versus 66.7% (public insurance) (P=0.689). 54% (private) versus 49% (public) achieved clearance (P=0.514). However, S-MAPA decreased 78.35% from baseline in those with private insurance compared to 61.48% (public) (P=0.036). On average, privately insured patients used at least twice as many same-category treatments, most commonly biologics, than publicly insured individuals (P=0.003). Drug-switching was significantly associated with clearance (P=0.024). Multivariate analysis demonstrated no significant differences in prescribed treatment categories, drug efficacy, clearance, S-MAPA, or drugswitching with respect to patient age. CONCLUSIONS: Treatment categories were comparably prescribed between insurance subgroups. However, privately insured patients achieved significantly greater degrees of clearance and switched between more medications within biologic and systemic categories, potentially explaining their overall improved therapeutic response. Further studies including cost-analysis could clarify any difference in the effectiveness of prescribed therapy for these two patient populations.

Prevalence of the metabolic syndrome in children with psoriatic disease.

Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality.

Explanatory models of female pubertal timing: discordances between cultural models of maturation and the recollection and interpretation of personal developmental experiences.

Given the ambiguity surrounding the source of the continuing trend toward earlier menarche observed in Westernized nations, several competing explanatory models have emerged regarding variation in pubertal timing. While a biomedical model proposes that predominantly constitutional characteristics shape the maturation timetable, an alternative framework derived from Life History Theory (LHT) evolutionary principles emphasizes the influence of psychosocial factors on development. Working with a sample of women 19-25 years of age (N = 103) drawn from two Southeastern U.S. colleges, we combined cultural consensus analysis with retrospective self-report regarding childhood stress and menarcheal timing to investigate whether reported developmental experiences align with cultural models regarding factors that should drive pubertal timing. Results suggest a robust cultural model consistent with a biomedical framework concentrating principally on constitutional characteristics. However, participants' personal developmental recollections support an association between higher childhood stress and earlier menarche. These findings support LHT predictions that early reproductive maturation is an evolutionary adaptive response to chronic childhood stress as well as clarify the extent to which cultural models of factors contributing to puberty concord with developmental experiences.

Bone marrow changes in adolescent girls with anorexia nervosa.

Early osteoporosis is common among adolescent girls with anorexia nervosa (AN) and may result from premature conversion of red (RM) to yellow bone marrow. We performed right knee magnetic resonance imaging (MRI) on a 1.0 T extremity scanner in 20 patients and 20 healthy controls, aged 16.2 +/- 1.6 years (mean +/- SD). Coronal T(1)-weighted (T(1)W) images and T(1) maps were generated from T(1) relaxometry images. Blinded radiologists visually assessed RM in the distal femoral and proximal tibial metaphyses in T(1)W images using a scale of signal intensity from 0 (homogeneous hyperintensity, no RM) to 4 (all dark, complete RM). Subjects with AN exhibited nearly twofold lower metaphyseal RM scores in both the femur (0.64 versus 1.22, p = .03) and tibia (0.54 versus 0.96, p = .08). In relaxometric measurements of four selected regions (femur and tibia amd epiphysis and metaphysis), subjects with AN showed higher mean epiphyseal but lower metaphyseal T(1). The net AN-control difference between epiphysis and metaphysis was 70 ms in the femur (+31 versus -35 ms, p = .02) and of smaller magnitude in the tibia. In relaxometry data from the full width of the femur adjacent to the growth plate, AN subjects showed mean T(1) consistently lower than in controls by 30 to 50 ms in virtually every part of the sampling region. These findings suggest that adolescents with AN exhibit premature conversion of hematopoietic to fat cells in the marrow of the peripheral skeleton potentially owing to adipocyte over osteoblast differentiation in the mesenchymal stem cell pool.

Dynamic alterations in chemokine gradients induce transendothelial shuttling of human T cells under physiologic shear conditions.

The active movement of cells from subendothelial compartments into the bloodstream (intravasation) has been recognized for several decades by histologic and physiologic studies, yet the molecular effectors of this process are relatively uncharacterized. For extravasation, studies based predominantly on static transwell assays support a general model, whereby transendothelial migration (TEM) occurs via chemoattraction toward increasing chemokine concentrations. However, this model of chemotaxis cannot readily reconcile how chemokines influence intravasation, as shear forces of blood flow would likely abrogate luminal chemokine gradient(s). Thus, to analyze how T cells integrate perivascular chemokine signals under physiologic flow, we developed a novel transwell-based flow chamber allowing for real-time modulation of chemokine levels above (luminal/apical compartment) and below (abluminal/subendothelial compartment) HUVEC monolayers. We routinely observed human T cell TEM across HUVEC monolayers with the combination of luminal CXCL12 and abluminal CCL5. With increasing concentrations of CXCL12 in the luminal compartment, transmigrated T cells did not undergo retrograde transendothelial migration (retro-TEM). However, when exposedto abluminal CXCL12, transmigrated T cells underwent striking retro-TEM and re-entered the flow stream [corrected]. This CXCL12 fugetactic (chemorepellant) effect was concentration-dependent, augmented by apical flow, blocked by antibodies to integrins, and reduced by AMD3100 in a dose-dependent manner. Moreover, CXCL12-induced retro-TEM was inhibited by PI3K antagonism and cAMP agonism. These findings broaden our understanding of chemokine biology and support a novel paradigm by which temporospatial modulations in subendothelial chemokine display drive cell migration from interstitial compartments into the bloodstream.