Citations

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Background: The NanoScope, given its smaller size, may be further from critical structures when establishing volar wrist arthroscopy portals compared to the traditional 2.7-mm arthroscope. Methods: Ten fresh-frozen latex-injected cadaver specimens were utilized. The volar radial (VR) and volar ulnar (VU) portals were created using an inside-out approach. The volar radial midcarpal (VR-MC) and volar ulnar midcarpal (VU-MC) portals were created using an inside-out approach. The arm was then dissected under 3.5-mm loupe magnification. Digital calipers were used to measure the distance between the portals and the surrounding anatomic structures by two fellowship-trained hand surgeons. Results: The median nerve was on average 1.6, 7.2, 1.8, and 5.6 mm away from the trochar for the VR, VU, VR-MC, and VU-MC, respectively. The median nerve fascia was pierced by the VR portal in one specimen. The radial artery, ulnar artery, and ulnar nerve were not pierced in any specimen. Compared to historical controls, for the VR-MC portal, the NanoScope was further from all critical structures, aside from the radial artery, and did not pierce any neurovascular structures. For the VU-MC portal, the NanoScope was further from the ulnar artery and median nerve and did not pierce any neurovascular structures. Conclusion: In developing volar portals, after placing the cannula through the volar capsule from an inside-out approach, we recommend making a volar incision and dissecting the local anatomic structures to guard against injury. Compared to historical controls, the NanoScope was typically further from neurovascular structures.

Abstract Background Nanoscope, given its smaller size, may be safer when establishing dorsal wrist arthroscopy portals compared with the traditional 2.7 mm arthroscope. Case Description Ten fresh frozen cadaver specimens were utilized. Dorsal radiocarpal portals were established with the Nanoscope and calipers were used to measure the distance between the portals and the surrounding anatomical structures. The only structure that was pierced during portal placement was the dorsal sensory branch of the ulnar nerve (DSUN) in one specimen when establishing the 6U portal. Our study did not note any tendon injuries. Literature Review Traditional wrist arthroscopy may be performed with a 2.7 mm arthroscope. With its larger outer sheath cannula, this may place adjacent anatomical structures at risk of injury. Clinical Relevance During wrist arthroscopy, the Nanoscope may be safer when creating portals to underlying structures. Level of Evidence This is a Level IV study.

Background: When treating upper-extremity infections, clinicians frequently must decide whether to initiate antibiotics or delay them with the goal of optimizing culture yield at the time of surgical debridement. The purpose of this study was to determine whether the administration of preoperative antibiotics affects intraoperative culture yield and whether there is a “safe” interval prior to culture acquisition within which antibiotics can be administered without affecting culture yield. Methods: We conducted a retrospective review of 470 consecutive patients who underwent debridement for a presumed acute infection of the hand, wrist, or forearm at a single tertiary care center between January 2015 and May 2020. Data including patient demographics, mechanism of infection and affected body part(s), and details of antibiotic administration, including type and timing with respect to culture acquisition, were collected. Results: Three hundred and forty-one patients (73%) received preoperative antibiotics prior to debridement and culture acquisition. The rate of positive cultures among patients who received preoperative antibiotics was 81% compared with 95% among patients who did not receive preoperative antibiotics (p < 0.01; odds ratio, 4.73). Even a single dose of antibiotics imparted a significantly increased risk of obtaining negative intraoperative cultures, and an incremental increase in the likelihood of obtaining negative cultures was seen with each preoperative dose given up to 7 doses. We did not identify a “safe” interval of time between antibiotic administration and culture acquisition such that culture yield was not affected. Conclusions: Patients who received preoperative antibiotics for the treatment of upper-extremity infections were approximately 5 times more likely to have negative cultures at the time of debridement than those who did not receive preoperative antibiotics. This effect persisted regardless of the number of doses given or the interval between antibiotic administration and culture acquisition. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Backgroud: The purpose of this study was to compare the 1,2 with a novel 2R portal in terms of proximity to critical structures. Methods: Wrist arthroscopy was performed on 8 fresh frozen cadavers via the 1,2 and 2R portals. External anatomy was then dissected under loupe magnification. The closest distance between the portals and surrounding anatomical structures was measured in millimeters using digital calipers. Results: The 1,2 portal was significantly closer to radial artery and first extensor compartment tendons than the 2R portal. The radial artery was on average 1.32 mm from the 1-2 portal and 14.25 mm from the 2R portal. The 2R portal was significantly closer to the second and third extensor compartment tendons. The closest branch of the superficial branch of the radial nerve (SBRN) was on average 2.04 mm from the 1-2 portal and 7.59 mm from the 2R portal, but this was not statistically significant. Conclusions: We advocate using the 2R portal preferentially to the 1,2 portal when treating radial sided wrist pathology to decrease the risk of iatrogenic radial artery and SBRN injury.

Abstract Background: Young women with breast cancer need highly effective contraception given the potential implications of unplanned pregnancy for optimal treatment, and the teratogenic risks. We sought to determine the contraceptive methods used by young women after diagnosis (dx) of breast cancer and factors associated with use of less effective methods or no contraceptive method, which confers a 6-90% annual risk of pregnancy in sexually active women in contrast to highly effective methods (risk &lt;1%). Methods: As part of a randomized trial conducted in 54 sites to test an education and support intervention for young women with breast cancer and their oncologists, we surveyed women about their pre-dx, current, and planned contraceptive use, and about communication with their providers regarding contraception. Women enrolled within 3 months of dx; contraception items were included on 3- and 12-month post-enrollment surveys. Intrauterine device (IUD) use, tubal sterilization, hysterectomy or bilateral salpingo-oophorectomy (hyst/BSO) after dx, or male partner vasectomy were classified as highly effective methods; all other methods and non-use were categorized as less effective. We excluded women not at risk of pregnancy: hyst/BSO prior to dx, or no indication for contraception. We used logistic regression to explore factors associated with use of less effective methods. Results: Of 424 women who completed the 3-month post-enrollment survey, median age at dx was 39 (range 22-45). 312 women at risk of pregnancy were included in this analysis, including 291 reporting sexual activity with a male partner within the last 6 months, and 21 reporting no recent sexual activity but reporting use of birth control. 123 women (39%) used highly effective contraceptive methods prior to dx; after dx, 161 (52%) reported current use of or a plan to use a highly effective method. 19 women (6%) reported use of a hormonal birth control method since dx; 7 (2%) reported withdrawal as their only contraceptive method; 25 (8%) reported no contraception. 30% of women did not recall a discussion of avoiding pregnancy or need for contraception during treatment with their providers. In multivariable analyses (N=310), desire for additional biologic children (OR 7.54, 95% CI 3.88-14.66) and provider discussion of contraception and pregnancy (OR 2.13 95% CI 1.20-3.78) were associated with use of less effective contraception. Age, race/ethnicity, disease stage, and partner status were not significantly associated with use of less effective methods. Conclusion: About half of women who are at risk of pregnancy reported use or planned use of less effective contraceptive methods or no method of contraception following dx of breast cancer. Women with breast cancer and their providers may benefit from targeted education on contraceptive options and method effectiveness. Citation Format: Rosenberg SM, Dutton CR, Ligibel J, Barry W, Ruddy KJ, Sprunck-Harrild K, Emmons KM, Partridge AH. Contraception use in young women with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-18.

Although the autoantigen involved in Graves’ hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves’ ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens.GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals’ cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens.These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

Abstract The induced pluripotent stem cell (iPSC) technology enables derivation of patient-specific pluripotent stem cells from adult somatic cells without using an embryonic cell source. Redifferentiation of iPSCs from diabetic patients into pancreatic islets will allow patient-specific disease modeling and autologous cell replacement therapy for failing islets. To date, diabetes-specific iPSCs have been generated from patients with type 1 diabetes using integrating retroviral vectors. However, vector integration into the host genome could compromise the biosafety and differentiation propensities of derived iPSCs. Although various integration-free reprogramming systems have been described, their utility to reprogram somatic cells from patients remains largely undetermined. Here, we used nonintegrating Sendai viral vectors to reprogram cells from patients with type 1 and type 2 diabetes (T2D). Sendai vector infection led to reproducible generation of genomic modification-free iPSCs (SV-iPSCs) from patients with diabetes, including an 85-year-old individual with T2D. SV-iPSCs lost the Sendai viral genome and antigens within 8–12 passages while maintaining pluripotency. Genome-wide transcriptome analysis of SV-iPSCs revealed induction of endogenous pluripotency genes and downregulation of genes involved in the oxidative stress response and the INK4/ARF pathways, including p16INK4a, p15INK4b, and p21CIP1. SV-iPSCs and iPSCs made with integrating lentiviral vectors demonstrated remarkable similarities in global gene expression profiles. Thus, the Sendai vector system facilitates reliable reprogramming of patient cells into transgene-free iPSCs, providing a pluripotent platform for personalized diagnostic and therapeutic approaches for diabetes and diabetes-associated complications.

Abstract Purpose: Increased levels of matrix metalloproteinase 1 (MMP-1) expression have been associated with poor outcome in chondrosarcoma. The existence of a single nucleotide polymorphism creating an Ets-binding site in the MMP-1 promoter may be one mechanism for elevated MMP-1 transcription. The aim of our study was to identify the prevalence of this single nucleotide polymorphism (SNP) in chondrosarcoma patients, to determine its correlation with disease outcome, and to discern whether it could serve as a prognostic marker in patients with chondrosarcoma. Experimental Design: Sixty-seven chondrosarcoma specimens were selected sequentially from an established tumor bank with a median duration of 47 months follow-up (range, 24 to 179 months). DNA was extracted, amplified with PCR, and sequenced to determine presence (GG) or absence of the Ets-binding site created by the SNP. Results: Eighteen (27%) samples were homozygous for the absence of the Ets site, 34 (51%) were heterozygous for the SNP, and 15 (22%) were homozygous for the SNP. The 5-year overall survival rate for patients was 78, 80, and 84%, respectively (P = 0.5527). The disease-free survival rate was 16, 63, and 76%, respectively (P = 0.0801). The 5-year disease-free survival rate for patients with the homozygous G/G genotype was 16%, compared with 71% for patients who were either homozygous or heterozygous for the GG allele (P = 0.0444). Conclusions: Despite a statistical correlation between MMP-1 gene expression and outcome in chondrosarcoma, this study demonstrates an absence of a correlation between the presence of the SNP and prognosis in patients with chondrosarcoma.