Lake City VA Medical Center

We assessed whether circulating adipokines are associated with incident fractures in patients with rheumatoid arthritis (RA). Three adipokines (adiponectin, leptin, and fibroblast growth factor [FGF]-21) were measured using banked enrollment serum from participants in a longitudinal RA cohort. Adipokine levels were dichotomized as high/low using median values. Incident osteoporotic fracture was defined based on published algorithms using diagnostic codes and confirmed by chart review. Cox proportional hazard models evaluated adipokines and incident fracture risk adjusting for age, sex, race, smoking status, body mass index (BMI), prednisone use, disease activity, comorbidity score, calendar year, osteoporosis history, and previous fracture. A total of 2,527 participants were included (89% male, mean age 72 years). There were 228 incident fractures over 27,540 person-years of follow-up (8.3 fractures per 1,000 person-years). After adjustment, the risk of incident fracture was increased for high levels of leptin (hazard ratio [HR] = 1.47; 95% confidence interval [CI] 1.15-1.90; P = 0.003), FGF-21 [HR = 1.39; 95% CI 1.16-1.67; P < 0.001), and adiponectin (HR = 1.21; 95% CI 0.94-1.55), with the latter not achieving significance (P = 0.13). Participants who had elevated levels of all three adipokines experienced twice the risk of fracture compared with those in whom none was elevated (HR = 2.17; 95% CI 1.27-3.70; P = 0.005). Elevations in adipokines are associated with an increased risk of fracture in patients with RA, independent of other established risk factors including BMI, smoking, and prednisone use. This supports further investigation to understand whether this association is related to altered body composition or disrupted metabolic pathways.

Introduction: The gut microbiota has emerged as a key regulator of endocrine homeostasis. Its interaction with the endocrine system defines the gut–endocrine axis, influencing metabolism, thyroid function, insulin secretion, and HPA axis regulation. Objective: To explore recent advances in understanding the gut–endocrine axis and its clinical implications. Methods: Narrative review of scientific literature from 2019 to 2025 in databases such as PubMed, Scopus, and Web of Science. Included original articles, systematic reviews, and clinical trials addressing microbiota and endocrine regulation. Results: Key communication mechanisms between microbiota and endocrine organs were identified, including SCFAs, tryptophan metabolites, and endotoxins modulating hormonal secretion. Evidence shows microbiota influences insulin resistance, thyroid dysfunction, obesity, and HPA axis. Conclusions: The gut–endocrine axis represents a novel dimension in the pathophysiology of metabolic and endocrine disorders, offering new therapeutic targets based on microbiota modulation.

The importance of codes for documenting healthcare concepts has expanded from a historical need to collect statistics to today's wide array of clinical and other secondary uses. The most deeply embedded system for coding diagnoses is the World Health Organization's (WHO) International Classification of Diseases (ICD). WHO's eleventh revision, ICD-11, was evaluated to determine how best to meet the needs of stakeholders concerned about clinical quality, healthcare decision-making, and other secondary use cases. This study explored the capability of ICD-10-CM, the standard ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS), and an enhanced ICD-11-MMS prototype (ICD-11-CCL) to represent clinical patient profiles for two natural clinical language scenarios. Systems were evaluated for granularity, comprehensiveness, accuracy, precision, relevancy, and their capability to provide user-friendly coding support. Both the standard and enhanced ICD-11-MMS produced code clusters that captured more clinical details and insight than ICD-10-CM's codes. However, ICD-11-MMS was less comprehensive than ICD-11-CCL and introduced occasional new inaccuracies. Unlike ICD-10-CM and ICD-11-MMS, ICD-11-CCL enabled clinicians to designate their clinical perspectives directly. While ICD-11-MMS produced numerous synonymous code clusters, the enhanced syntax of ICD-11-CCL resulted in a unique code cluster for each scenario. Adoption of an enhanced ICD-11-MMS such as ICD-11-CCL could provide clinically nuanced data to support important secondary data applications more effectively than standard ICD-11-MMS, while retaining ICD-11-MMS's capability to support international comparative analyses such as mortality and morbidity statistics. With automated coding tools, enhanced ICD-11-MMS could also reduce the burden on humans to select, review, memorize or decipher codes. Enhanced ICD-11-MMS represents a substantial improvement over customized modifications of ICD-10 and, with further development and testing, could be a viable option for future adoption.

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) is not fully understood. This study tested the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 yr). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after exercise and hemodynamics were assessed. MSNA was recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+15 ± 5 burst/100 bpm) and ExPECO 40% (+22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Leg vascular conductance (vasodilation) during PLM was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate elevated MSNA attenuates the vasodilatory response to PLM and the magnitude of reduction in vasodilation during PLM is graded with the degree of sympathoexcitation.

Neural drive originating in higher brain areas reaches exercising limb muscles through the corticospinal-motoneuronal pathway, which links the motor cortex and spinal motoneurones. The properties of this pathway have frequently been observed to change during fatiguing exercise in ways that could influence the development of central fatigue (i.e. the progressive reduction in voluntary muscle activation). However, based on differences in motor cortical and motoneuronal excitability between exercise modalities (e.g. single-joint vs. locomotor exercise), there is no characteristic response that allows for a categorical conclusion about the effect of these changes on functional impairments and performance limitations. Despite the lack of uniformity in findings during fatigue, there is strong evidence for marked 'inhibition' of motoneurones as a direct result of voluntary drive. Endogenous forms of neuromodulation, such as via serotonin released from neurones, can directly affect motoneuronal output and central fatigue. Exogenous forms of neuromodulation, such as brain stimulation, may achieve a similar effect, although the evidence is weak. Non-invasive transcranial direct current stimulation can cause transient or long-lasting changes in cortical excitability; however, variable results across studies cast doubt on its claimed capacity to enhance performance. Furthermore, with these studies, it is difficult to establish a cause-and-effect relationship between brain responsiveness and exercise performance. This review briefly summarizes changes in the corticomotoneuronal pathway during various types of exercise, and considers the relevance of these changes for the development of central fatigue, as well as the potential of non-invasive brain stimulation to enhance motor cortical excitability, motoneuronal output and, ultimately, exercise performance.

Introduction: Gulf war illness (GWI) is a multisystem disorder of unknown etiology. There is high prevalence of IBS among Veterans with GWI. There is inconsistent evidence that low grade chronic gastrointestinal (GI) inflammation may play a part in the pathogenesis of IBS and GWI. We examined the blood cytokines profile of Veterans with IBS and GW illness before and after treatment with probiotics. Methods: In a randomized double-blind placebo controlled trial we enrolled Veterans with IBS (Rome III criteria) and two or more symptoms of GWI. Veterans were randomized to receive probiotic (De Simone Formulation; formally known as VSL#3) or identical placebo. Blood was collected at enrollment and after 8-week treatment with probiotics. A multiplexed immunoassay was used to assess the serum concentration of 13 cytokines/inflammatory markers: interferon (IFN)-γ; interleukins (ILs)-1β, 2, 4, 5, 6, 8, 10, 12, 13, and 17; tumor necrosis factor (TNF-α, IL-2 receptor. The cytokine levels were compared to reference intervals established on 120 healthy controls. Results: Data was analyzed from 42 Veterans who provided baseline and 11 Veterans who provided both pre and post treatment blood samples for cytokine analysis. The serum pro- and anti-inflammatory cytokines levels were no different between IBS with GWI and healthy controls. There was no change in pro- or anti-inflammatory cytokines after treatment with probiotics (Figure). Conclusion: The level of pro- and anti-inflammatory cytokines were no different in Veterans with IBS and GWI compared with healthy controls and the levels do not alter after treatment with probiotics. The role of cytokines in pathophysiology, and as a biomarker of treatment of IBS and GWI is likely complex and remains unknown.Figure 1.: Comparison of Pre and Post treatment with probiotics cytokines (mean±SE)

IMPORTANCEPosttraumatic stress disorder (PTSD) is a prevalent and seriousmental health problem. Although there are effective psychotherapies forPTSD, there is little information about their comparative effectiveness.OBJECTIVETo compare the effectiveness of prolonged exposure (PE) vs cognitiveprocessing therapy (CPT) for treating PTSD in veterans.DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial assessed the comparativeeffectiveness of PE vs CPT among veterans with military-related PTSDrecruited from outpatient mental health clinics at 17 Department of VeteransAffairs medical centers across the US from October 31, 2014, to February 1,2018, with follow-up through February 1, 2019. The primary outcome wasassessed using centralized masking. Tested hypotheses were prespecifiedbefore trial initiation. Data were analyzed from October 5, 2020, to May 5,2021.INTERVENTIONSParticipants were randomized to 1 of 2 individualcognitive-behavioral therapies, PE or CPT, delivered according to a flexibleprotocol of 10 to 14 sessions.MAIN OUTCOMES AND MEASURESThe primary outcome was change in PTSD symptom severity on theClinician-Administered PTSD Scale for DSM-5 (CAPS-5) frombefore treatment to the mean after treatment across posttreatment and 3- and6-month follow-ups. Secondary outcomes included other symptoms, functioning,and quality of life.RESULTSAnalyses were based on all 916 randomized participants (730 [79.7%]men and 186 [20.3%] women; mean [range] age 45.2 [21–80] years), with455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95%CI, 39.1–40.7] points) and 461 participants randomized to CPT (meanCAPS-5 score at baseline, 40.3 [95% CI, 39.5–41.1] points). PTSDseverity on the CAPS-5 improved substantially in both PE (standardized meandifference [SMD], 0.99 [95% CI, 0.89–1.08]) and CPT (SMD, 0.71 [95%CI, 0.61–0.80]) groups from before to after treatment. Meanimprovement was greater in PE than CPT (least square mean, 2.42 [95% CI,0.53–4.31]; P = .01), but the difference was notclinically significant (SMD, 0.17). Results for self-reported PTSD symptomswere comparable with CAPS-5 findings. The PE group had higher odds ofresponse (odds ratio [OR], 1.32 [95% CI, 1.00–1.65];P < .001), loss of diagnosis (OR, 1.43 [95% CI,1.12–1.74]; P < .001), and remission (OR,1.62 [95% CI, 1.24–2.00]; P < .001) comparedwith the CPT group. Groups did not differ on other outcomes. Treatmentdropout was higher in PE (254 participants [55.8%]) than in CPT (215participants [46.6%]; P < .01). Three participantsin the PE group and 1 participant in the CPT group were withdrawn fromtreatment, and 3 participants in each treatment dropped out owing to seriousadverse events.CONCLUSIONS AND RELEVANCEThis randomized clinical trial found that although PE wasstatistically more effective than CPT, the difference was not clinicallysignificant, and improvements in PTSD were meaningful in both treatmentgroups. These findings highlight the importance of shared decision-making tohelp patients understand the evidence and select their preferredtreatment.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01928732