Citations

Objective Cognitive impairment is prevalent in rheumatoid arthritis (RA), yet risk factors are not well understood. We explored associations between clinical characteristics and cognitive impairment in an RA cohort. Methods Data were from a longitudinal RA cohort at Veterans Affairs Puget Sound Health Care System. Cognition was evaluated using the Saint Louis University Mental Status (SLUMS) examination. Demographics and health factors, objectively measured physical function, participant‐reported symptoms, RA disease characteristics, and comorbidities were evaluated. Univariable linear regressions explored the association between clinical factors and SLUMS scores. Those with P < 0.1 in the univariable models were evaluated in separate multivariable linear regressions controlling for age, sex, and years of education. Results A total of 145 participants with RA were included, with a mean age of 64.5 (SD 11.6) years, and were predominantly male (74%). Using SLUMS, 42 participants (29%) had normal cognition, 83 (57%) had mild cognitive impairment, and 20 (14%) had dementia. Physical performance (aβ: 0.35, confidence interval [CI] 0.11 to 0.59), self‐reported exhaustion (aβ: −2.22, CI −3.44 to −0.99), pain (aβ: −0.25, CI −0.50 to −0.00), disability (aβ: −1.79, CI −3.16 to −0.42), and trouble falling asleep (aβ: −2.57, CI −4.00 to −1.14) were all independently associated with a lower SLUMS score (all P < 0.05). Conclusion Cognitive impairment was prevalent in our cohort of veterans with RA and was associated with several modifiable clinical factors. Future longitudinal studies are needed to determine the directionality of these associations and evaluate interventions for modifiable risk factors that may mitigate cognitive dysfunction. image

Abstract Psychological distress, moral injury, and burnout are prevalent among intensive care unit (ICU) professionals, impacting individual well-being, team dynamics, and patient safety. Structured peer support programmes, delivered by trained colleagues rather than mental health professionals, could be implemented as low-threshold, scalable interventions to promote psychological safety and resilience. This review outlines five foundational pillars for implementing peer support in the ICU, including formal programme design, training, inclusivity, confidentiality, and continuous evaluation. It also addresses practical strategies to overcome cultural and institutional barriers, such as stigma, time constraints, and hierarchical norms. Drawing on current evidence and recent unpublished survey data from North American critical care cardiologists, the article provides a practical framework for integrating peer support into ICU culture. Peer support represents a complementary approach to formal mental health services and offers tangible benefits for clinician well-being, retention, and quality of care.

Study Design: Retrospective cohort analysis. Objective: To determine the effect of long-segment posterior cervical decompression and fusion (PCDF) on perioperative changes in vertebral Hounsfield Units (HUs) and the impact of these changes on radiographic outcomes and fusion status. Summary of Background Data: Low preoperative CT HUs have been associated with adverse outcomes after spinal fusion, including hardware complications and reoperation. No existing studies have investigated the preoperative to postoperative change in HUs after cervical spinal fusion. Stress shielding may decrease bone quality within the fusion construct. Whereas, altered junctional loading and increased segmental mobility may precipitate bony hypertrophy in the terminal and adjacent levels. Methods: All adult patients who underwent C2-T2 PCDF for myelopathy/ myeloradiculopathy at an academic center between 2013 and 2020 were retrospectively identified. Preoperative and postoperative HUs were assessed on axial CT images in the cranial, middle, and caudal C2, C6, T2, and T3 vertebral bodies, outside of the region of instrumentation and artifact by 2 independent reviewers. Paired t test compared preoperative to postoperative changes in HUs. Preoperative and long-term postoperative cervical alignment, fusion, and revision rates were assessed. Univariate and regression analysis compared patient factors and outcomes between groups with perioperative increase versus decrease in vertebral HUs. Results: One hundred patients were included. The average preoperative to postoperative change in HUs in the C2, C6, T2, and T3 vertebral bodies were −19.80 (P=0.008), −52.63 (P<0.001), 15.15 (P=0.014), and 9.41 (P=0.346), respectively. Perioperative increase in C2 HUs was predictive of increased postoperative distal junctional angle (β=3.41, P=0.048) and increased T1–T4 kyphosis (β=6.50, P=0.003). Perioperative increase in C6 HU predicted pseudoarthrosis (fusion odds ratio: 0.19, P=0.007). Conclusions: Significant perioperative decreases in C6 HUs within a long-fused construct may demonstrate stress shielding. The significant association between greater distal kyphosis and an increase in C2 HUs may be attributed to a stress riser effect. Level of Evidence: Level III.

Abstract Nephrotic syndrome is a rare, heterogeneous kidney disorder characterized by proteinuria, hypoalbuminemia, and edema. To elucidate its genetic architecture, we conducted a large-scale, electronic health record (EHR)-linked, multi-ancestry genome-wide association study comprising 5,214 cases and 1,601,060 controls. We identified 37 distinct loci associated with disease risk, including novel associations at JAML and STPG2 , and confirmed prior signals at PLA2R1 , HMCN1 , and APOL1 . Fine-mapping of the major histocompatibility complex (MHC) revealed the strongest association at DRB103:01:01G in individuals of European ancestry (OR = 2.01, P = 1.4×10⁻²⁰), alongside nominal ancestry-specific associations in African ( DOA01:01:05 ) and Latino ( DPB1*14:01:01G ) populations. Transcriptome-wide association analysis (TWAS) identified 484 significant gene-tissue associations, including C4A in kidney cortex. Expression quantitative trait locus (eQTL) mapping revealed numerous cis-eQTLs in glomerular and tubular renal tissues, largely within the MHC region. We observed significant genetic correlation between adult and pediatric nephrotic syndrome (Rg = 0.63, P = 3.5x10 -11 ), suggesting shared genetic etiology. Pathway analyses implicated estrogen receptor signaling and histone modification. Mendelian randomization implicated APOM expression and apomorphine exposure with increased disease risk (OR = 4.93, P = 1.8x10 -19 ). These results expand the understanding of nephrotic syndrome pathogenesis and highlight ancestry-informed targets for therapeutic development.

Abstract Background: Medical education commonly utilizes the “see one, do one” two-step approach for teaching psychomotor skills; however, recent evidence suggests that Peyton’s four-step method leads to superior learning. The effect of Peyton’s four-step method on long term skill retention is less apparent and has never been assessed for Point-of-Care Ultrasound (POCUS). The purpose of this research project was to evaluate the effectiveness of Peyton’s four-step method on teaching the POCUS psychomotor skills of image acquisition to novice learners. Additionally, this research project assessed the influence of Peyton’s four-step method at three different points in time during the skill acquisition phase, in the setting of ongoing deliberate skill practice. Methods: A single-blinded, repeated measures interventional study based on experimental design was completed. PA students from one large academic medical center were randomized into a control group (using the two-step method) and intervention group (using Peyton’s four-step method). Students were taught POCUS of the aorta, bladder, heart, lungs, and kidneys. Students' POCUS skills were assessed during the immediate, intermediate, and delayed learning phases. At each assessment, an organ-specific score and a total score were obtained. Scores were compared using a Wilcoxon rank sum test. An ordinal logistic regression analysis was performed using a generalized linear mixed model with a multinomial distribution and cumulative logit link function to assess overall effect of Peyton's four-step method. Results: Students who were taught using Peyton’s method were found to have an increased likelihood of higher total scores compared to those taught using usual instruction (OR = 4.2, p = 0.003). Peyton’s method was found to have increased likelihood of higher scores for cardiac (OR = 2.3, p = 0.032), lung (OR = 2.5, p = 0.034), and kidney (OR = 3.0, p = 0.015). Student performance statistically improved with Peyton’s four-step method during the immediate (p = 0.031) and delayed (p = 0.011) skill acquisition phases, but not in the intermediate phase. Conclusion: Peyton’s four-step method improves overall psychomotor skill acquisition for POCUS. Peyton’s four-step method specifically improved psychomotor skills in the immediate skill acquisition phase and the delayed skill acquisition phase. The benefit of Peyton’s four-step method was more prominent in higher complexity POCUS applications.

Abstract Importance The addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy. Objective To determine the safety and efficacy of palbociclib combined with cisplatin (cis) or carboplatin (carbo) in advanced solid malignancies Design Enrollment on dose escalation (part I) proceeded using the Bayesian adaptive design Escalation with Overdose Control (EWOC). Setting Single institution investigator initiated trial. Participants Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract cancers. Intervention Escalating doses of palbociclib in combination with different doses of cisplatin or carboplatin. Main Outcomes and Measures Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS). Results We enrolled 39 patients on dose escalation (part I) and 32 additional patients on dose expansion (part II). RP2D of palbociclib 100 mg on Day 2-22 + Cisplatin (cis) 60 mg/m2 IV on Day 1 Q4W (Arm A); and palbociclib 75 mg on Day 2-22 + Carboplatin (carbo) AUC 6 IV on Day 1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 months, respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4), and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment-related adverse events (TRAEs—all grade %): Arm A—neutropenia (66%), thrombocytopenia (26%), nausea, fatigue, and anemia (20% each); Arm B—neutropenia (64.7%), thrombocytopenia (53%), and anemia (29%). There were no grade 4-5 TRAEs. Conclusions and Relevance The combination of palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial registration number: NCT02897375

ABSTRACT Objective The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. Methods Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post‐contrast gadolinium enhancement resolution at 6 months post‐treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow‐up. Results Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39–55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2–3) and 4 (IQR 2.5–6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A 1 ), 36 (17.8%) received corticosteroids < 4 weeks (B 1 ), 21 (10.4%) received corticosteroids plus sarcoidosis‐directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non‐sarcoidosis‐directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A 1 27/106 (25.5%), B 1 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal–Wallis p = 0.69 and 0.63, respectively) after median follow‐up of 46.5 months (IQR 18–91.3). Interpretation Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.