Body composition and body mass index are independently associated with widespread pain and experimental pain sensitivity in older adults: a pilot investigation.

Introduction: Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group. Methods: Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain. Results: Significant positive associations were found between number of pain sites and BMI (b = 0.37) and total fat mass (b = 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (b = 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity. Discussion: The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.

Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy.

BACKGROUND: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks. OBJECTIVE: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy. STUDY DESIGN: Hospitalized patients with hypertensive disorders of pregnancy between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to January 2024 after the implementation of serum soluble fms-like tyrosine kinase-1/placental growth factor testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (placental growth factor and soluble fms-like tyrosine kinase-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines on the basis of biomarkers but made pragmatic management decisions independently. Results of soluble fms-like tyrosine kinase-1/placental growth factor tests were available to clinicians within 24 hours of venipuncture. The association between soluble fms-like tyrosine kinase-1/placental growth factor ≥40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. RESULTS: Of the 65 patient encounters, 36 had a soluble fms-like tyrosine kinase-1/placental growth factor <40 (55.4%). The rate of delivery for indications related to hypertensive disorders of pregnancy within 2 weeks was significantly lower among encounters with a low ratio vs high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted hazard ratio, 7.52; 95% confidence interval, 3.05-18.54; P<.001). A diagnosis of preeclampsia with severe features within 2 weeks of testing was also less likely among the encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 when compared with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (2/36 [5.6%] vs 23/29 [79.3%], P<.001; positive predictive value of 79% [95% confidence interval, 0.65-0.94] and negative predictive value of 0.94 [95% confidence interval, 0.87-1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within 2 weeks of testing were 6.13 and 0.09, respectively. Encounters with a soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 were less likely to experience a maternal or fetal adverse event as compared with encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], P=.01). Among 36 encounters involving low soluble fms-like tyrosine kinase-1/placental growth factor values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed on the basis of biomarkers, and none developed preeclampsia with severe features or adverse outcomes at 2 weeks. The median latency defined as days between biomarker measurement and delivery in patients with a low biomarker ratio was 33 (interquartile ratio, 23-47) vs 7 (interquartile ratio, 4-14) days among patients with a high ratio (P<.001). Corticosteroid use within 2 weeks was also significantly reduced in the low biomarker group when compared with the high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], P<.001). CONCLUSION: In this study, the incorporation of soluble fms-like tyrosine kinase-1/placental growth factor ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with hypertensive disorders of pregnancy in the United States. Among patients with a low ratio, pregnancy may be prolonged, which results in better neonatal outcomes without harm to the mother.

Atypia Involving Fibroadenomas: Outcomes and Upgrade Rates.

OBJECTIVE: Fibroadenomas (FAs) involved by atypia are rare. Consensus guidelines for management of FAs involved by atypia when diagnosed on image-guided biopsy do not exist because of limited data reporting surgical upgrade rates to ductal carcinoma in situ (DCIS) or invasive malignancy. Therefore, these lesions commonly undergo surgical excision. METHODS: This single-institution retrospective study identified cases of FAs involved by atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) diagnosed on image-guided biopsy between January 2014 and April 2023 to determine upgrade rates. Cases with incidental atypia adjacent to but not involving FAs were excluded. RESULTS: Among 1736 FAs diagnosed on image-guided biopsy, 32 cases (1.8%) were FAs involved by atypia including 43.8% (14/32) ALH, 28.1% (9/32) ADH, 18.8% (6/32) LCIS, 6.3% (2/32) LCIS + ALH, and 3.1% (1/32) unspecified atypia. The most common imaging finding was a mass. Most cases, 81.3% (26/32), underwent subsequent surgical excisional biopsy. A single case of ADH involving and adjacent to an FA was upgraded to FA involved by low-grade DCIS on excision for an overall surgical upgrade rate of 3.8%. There were no cases upgraded to invasive malignancy. For those omitting surgical excision, there was no subsequent malignancy diagnosis at the FA biopsy site over a mean follow-up of 73 months. CONCLUSION: Cases of radiologic-pathologic concordant FAs involved by atypia have a low upgrade rate of 3.8% and should undergo multidisciplinary review. Larger multi-institutional analysis is needed to determine whether guidelines for excision of atypia should apply to atypia involving FAs.

Delayed-Onset Muscle Soreness Alters Mechanical Sensitivity, but Not Thermal Sensitivity or Pain Modulatory Function.

Introduction: Many clinical musculoskeletal pain conditions are characterized by chronic inflammation that sensitizes nociceptors. An unresolved issue is whether inflammation affects all nociceptors in a similar manner. Exercise-induced muscle damage (EIMD) has been proposed as a model for simulating clinical inflammatory pain in healthy samples. We sought to test the effect of EIMD on various painful stimuli (pressure and thermal), central pain processing (via the nociceptive flexion reflex) and endogenous pain modulation via conditioned pain modulation and exercise-induced hypoalgesia. Methods: Eighteen participants (9F, age: 24.6 ± 3.3) were recruited for repeated measures testing and each completed pain sensitivity testing prior to and 48 hours after an eccentric exercise protocol. The participants performed a minimum of 6 rounds of 10 eccentric knee extension exercises to induce muscle damage and localized inflammation in the right quadriceps. Force decrements, knee range-of-motion, and delayed onset muscle soreness (DOMS) were used to quantify EIMD. Results: There was a significant main effect of time for pressure pain (%diff; -58.9 ± 23.1; p = 0.02, ηp2 = 0.28) but no significant main effect was observed for limb (%diff; -15.5 ± 23.9; p = 0.53, ηp2 = 0.02). In contrast, there was a significant interaction between time and limb (p < 0.001, ηp2 = 0.47) whereby participants had lower pressure pain sensitivity in the right leg only after the damage protocol (%diff; -105.9 ± 29.2; p = 0.002). Discussion: Individuals with chronic inflammatory pain usually have an increased sensitivity to pressure, thermal, and electrical stimuli, however, our sample, following muscle damage to induce acute inflammation only had sensitivity to mechanical pain. Exercise induced inflammation may reflect a peripheral sensitivity localized to the damaged muscle rather than a global sensitivity like those with chronic pain display.

The Impact of Closed-Loop Imaging on Actionable CT-Detected Breast Findings.

PURPOSE: Closed-loop imaging programs (CLIPs) are designed to ensure that patients receive appropriate follow-up, but a review of incidental CT-detected breast findings in the setting of CLIPs has not been performed. METHODS: A retrospective review was conducted of CT reports at a single academic institution from July 1, 2020, to January 31, 2022, to identify reports with recommendations for breast imaging follow-up. Medical records were reviewed to evaluate patient adherence to follow-up, CLIP intervention, subsequent BI-RADS assessment, and diagnosis. Adherence was defined as diagnostic breast imaging performed within 6 months of the CT recommendation. RESULTS: Follow-up recommendations for breast imaging were included in CT report impressions for 311 patients. Almost half of patients (47.3% [147 of 311]) underwent follow-up breast imaging within 6 months, yielding breast cancer diagnoses in 12.9% (19 of 147) and a biopsy-proven positive predictive value of 65.5% (19 of 29). Most patients who returned for follow-up within 6 months did so without CLIP intervention. The majority of CT report impressions in the follow-up group (85.0% [125 of 147]) contained specific recommendations for "diagnostic breast imaging." For patients who did not receive follow-up, the CLIP team tracked all cases and intervened in 19.1% (28 of 147). The most common intervention was a phone call and/or fax to the primary care provider. Outpatient CT examination setting and specific recommendation for diagnostic breast imaging were significantly associated with higher follow-up adherence (P < .0001). CONCLUSIONS: Actionable CT-detected breast findings require follow-up diagnostic breast imaging because of a relevant cancer detection rate of 12.9%. Although many patients return for breast imaging without intervention, almost half of patients did not receive follow-up and may account for a significant number of missed cancer diagnoses. Specific CT recommendation verbiage is associated with higher follow-up adherence, which can be addressed across settings even without CLIPs.