Johnson, A

Objective: Percutaneous needle tenotomy (PNT) and ultrasonic debridement (UD) are minimally invasive interventions for the management of chronic tendinopathy. Despite their increasing use, no standardized, evidence-based rehabilitation guidelines currently exist to direct clinicians in post-procedural management. This systematic review aimed to characterize and synthesize reported rehabilitation protocols following PNT and UD for patellar, proximal hamstring, and gluteal tendinopathies. Design: Systematic Review Results: Twenty-seven studies met inclusion criteria, with patellar tendon procedures (n=13) being the most common, followed by gluteal (n=6), proximal hamstring (n=3), and multi-tendon protocols (n=5). Of the included studies, 21 (78%) utilized percutaneous needle tenotomy (PNT) and six (22%) used ultrasound debridement or Tenex. Exercise restrictions were mandated in 19 studies (70%), while 12 (44%) provided a detailed, structured rehabilitation program, frequently emphasizing eccentric loading for patellar and hamstring tendons. Weight-bearing limitations were uncommon, appearing in only three studies (11%). Fifteen studies (56%) combined the procedure with platelet-rich plasma (PRP). Pharmacological protocols also showed high variance, with NSAID restrictions ranging from 1 to 28 days and corticosteroid avoidance lasting between 10 days and one year. Overall, substantial variability remains regarding recommended activity progression, exercise initiation, and mechanical loading strategies across current research. Conclusion: PNT and UD appear effective for managing refractory tendinopathy, yet post-procedure rehabilitation guidelines remain inconsistent and supported by limited high-quality evidence. Future research should aim to identify key variables that guide individualized rehabilitation progressions, optimizing recovery timelines, and facilitating safe and efficient return to activity following PNT and UD procedures.

Syndesmotic injuries are complex and often require a longer return to play as compared with lateral ankle sprains. As common as they are, they can be difficult to diagnose owing to the complex biomechanics of the ankle joint as well as their varying degrees of stability. A careful physical examination and dedicated imaging can assist with the diagnosis. Weightbearing ankle X-rays should be obtained to assess for fractures or gross instability with anteroposterior, lateral, and mortise views. If these are inconclusive but there is high clinical suspicion, stress views can be added. Advanced imaging also plays a role. Classification systems attempt to distinguish a stable, dynamically unstable, and unstable injury, as this guides management. Stable injuries can be treated conservatively and unstable injuries warrant surgical intervention. It is the diagnosis and treatment of unstable injuries that can be particularly challenging.

Introduction Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The M odulate O besity and relate D metabolic compl I cations F or Y ielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research ANd Development/University of California, Los Angeles (RAND/UCLA) Appropriateness Method (RUAM) consensus process. Methods and analysis We will conduct three systematic reviews and a structured evidence synthesis organised into three domains: (1) the impact of obesity on IBD outcomes, (2) the burden of cardiometabolic complications in IBD and (3) the management of overweight, obesity and cardiometabolic comorbidities in IBD. A multidisciplinary international panel of gastroenterologists, surgeons, endocrinologists, hepatologists, cardiologists and dietitians will assess each statement using the RAND/UCLA appropriateness method. Panellists will rate the appropriateness of each statement (only those that fall within their area of expertise) on a 1–9 scale (1–3=inappropriate, 4–6=uncertain and 7–9=appropriate), with medians rounded up (eg, 6.5=appropriate). Agreement will be assessed using the RAND Disagreement Index (DI<1.0=agreement). Ethics and dissemination This study will not involve direct patient participation, as it is based on evidence synthesis and expert consensus; therefore, formal research ethics committee approval will not be required. Patient representatives will contribute to the consensus process to provide contextual perspectives but no identifiable data will be collected. Findings will be disseminated through publication in peer-reviewed journals, presentation at major gastroenterology and IBD conferences and communication with professional societies. A lay summary and patient-friendly infographic will also be developed to facilitate translation of recommendations into clinical practice. PROSPERO registration numbers CRD420251178843: a systematic review of the impact of obesity on inflammatory bowel disease outcomes. CRD420251178799: a systematic review of cardiometabolic complications in inflammatory bowel disease. CRD420251174653: management of overweight, obesity and cardiometabolic comorbidities in inflammatory bowel disease: a systematic review.

Abstract The impact of microglia antigen presentation on CNS infiltrating CD8 T cells responses during neurotropic virus infection has been difficult to define. Using Theiler’s murine encephalomyelitis virus (TMEV) infection of neurons as a model system, our laboratory has previously determined that H-2D b restricted, but not H-2K b restricted CD8 T cells are required for viral clearance, demonstrating the role of discrete MHC class I alleles. To determine the extent microglia antigen presentation impacts brain-infiltrating CD8 T cells, our laboratory generated novel single MHC class I conditional knockout mice in which H-2K b or H-2D b can be specifically deactivated in TMEM119+ microglia with tamoxifen administration. During TMEV infection, conditional knockout of H-2K b in microglia reduced antigen-specific CD8 T cell proliferation in the brain. Meanwhile, mice with deletion of D b in microglia had reduced levels of perforin in antigen-specific CD8 T cells. Furthermore, microglia specific deletion of H-2D b reduced CD8 T cell numbers in the brain and preserved blood-brain barrier (BBB) integrity. Microglial D b restricted antigen presentation was also essential for the reactivation of CD8 tissue resident memory (TRM) cells and BBB integrity during memory recall responses. These findings further our understanding of how brain infiltrating antiviral CD8 T cell responses are impacted by microglia, as well as define how this cellular interaction contributes to BBB disruption during neuroinflammation. These findings also have high significance to our understanding of how microglia impact CD8 TRM cell populations that reside in the brain long after virus infection is cleared. Graphical abstract

Abstract Background We aimed to describe the real-world durability of clinical and endoscopic outcomes of upadacitinib (UPA) in ulcerative colitis (UC). Methods We retrospectively analyzed an ongoing multi-center cohort of UC patients(pts) in the United States who were started on UPA for active disease. Primary outcome was clinical remission at 1yr assessed by partial Mayo score(pMS)(resolution of all UC related symptoms and physician global assessment). Secondary outcomes assessed at various timepoints, including after re-escalation, included clinical response(&gt;50%reduction in symptoms utilizing the pMS), endoscopic response (Mayo endoscopic score≤1or absence of erosions/ulcerations) and histological remission(defined as normal or chronic inactive). Durable secondary outcomes achieved at both 6months and at 1yr and beyond were also assessed. Descriptive statistics were performed. Adverse events(AEs) investigated included cardiovascular events and herpes zoster (HZ). Results 416pts were included(Table 1) with median values for age at initiation of36.00yrs(range27-48), disease duration7.00yrs(range3-14)and follow-up 993days(IQR,672-1103), with206(49.52%)with follow-up at 1yr or beyond. Of these, 66.1%had extensive colitis. Induction duration was8wks in 86.5%and16wks in 4.8 %(20/416). Most received an induction dose of45mg(97.1%)and maintenance dose of30mg(85.8%). Among the evaluable population at1yr and beyond, 62.5%(45/80)were in clinical remission, 75.9%(22/29)in endoscopic response with58.6%(17/29) in remission and66.6%(20/30)in histological remission. At 6months, clinical remission was51.6%(42/93), endoscopic response was 75%(24/32) of which43.75%(14/32)were in remission and histologic remission was seen in 40.8%(20/49).Durable secondary outcomes of clinical remission were seen in 71.4%(30/42), endoscopic improvement in 45.8%(11/24), and histologic remission in35%(7/20). Re-escalation to 45mg occurred in 35pts, of which48.6%(17/35)were re-escalated due to incomplete induction clinical response with all achieving response(11 in remission). The rest(18/35)were re-escalated for clinical relapse after initial remission where72.2%(13/18)were able to recapture remission. After re-escalation,54.3%(19/35)continued on 45mg daily. AEs were reported in12.7%with HZ in 7pts(2.1%). One pt aged53yrs had an episode of TIA after 1yr on UPA at 15mg, without pre-existing cardiovascular risk factors and UPA use is ongoing at the same dose. There were no reported episodes of worsening of pre-existing cardiovascular disease or DVT/PE. Conclusion UPA is durably effective and safe in a real-world clinical setting with re-escalation to 45mg capturing response in a majority of the pts. Ongoing recruitment will provide further evidence on long term effectiveness and safety. Conflict of interest: Ms. Huang, Katherine: No conflict of interest Chandnani, Arun: No conflict of interest Samaan, Sami: None Tan, Tingyi: I have no conflict of interests to declare. Ramesh, Prajith Raj: None Conlon, Caroline: No conflict of interest Klein, Jeremy: None Reddy, Nikhil: No conflict of interest Ayoub, Malek: None Cervantes Limon, Gabriela: none Myers, Melissa: None Bucaram, Martha: No conflict of interest Lieto, Stephen: No conflict of interest Scalzo, Nicholas: No conflict of interest Cohen, Benjamin: Abbvie - consulting and speaking ALPCO - consulting J & J Innovative Medicine - consulting Takeda - consulting and speaking Emmes Biopharma Services LLC - DSMB Pfizer - consulting Mohamed, Islam: nothing to declare Ciorba, Matthew: Advisory Board: Janssen, AbbVie, Pfizer, Geneoscopy Consulting: Janssen, AbbVie, Pfizer, Geneoscopy Grant contracts: Janssen, Pfizer, Incyte Shukla, Richa: Speakers bureau - Abbvie and Lilly Wright, Michael: None Xu, An Tao: No conflict of interest Chowla, Navreet: No conflict of interest Ogholikhan, Sina: Abbvie Medical Director Kujawski, Michelle: Abbvie Scientific Director Dulaney, David: Speaker bureau - Regeneron Speaker bureau - Sanofi Speaker bureau - Takeda Speaker bureau - Eli Lilly Fenster, Marc: none Benson, Caroline: No conflict of interest Alhobayb, Tamara: No conflict of interest Berinstein, Jeffrey: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.

Abstract Background A subset of risankizumab (RZB)-treated patients experience suboptimal or secondary loss of response to standard dosing. We explored factors associated with future RZB dose-optimization, and outcomes of optimization in a multicenter consortium of adults with Crohn’s Disease (CD). Methods Baseline characteristics at time of RZB initiation and subsequent clinical, endoscopic, and biochemical outcomes were collected in a multi-center cohort. Outcomes for dose-optimized RZB were reported as clinical response and remission (based on HBI or PGA when HBI unavailable), endoscopic remission (based on SEMA-CD or absence of ulcers when SEMA-CD not available), and biochemical response. Characteristics were compared between standard and dose-optimized groups using chi-square and two-sample t-tests. Additional models adjusting for age and sex assessed predictors of dose optimization. Results We identified 309 patients treated with standard dose and 58 for whom dose-optimized RZB was recommended. Of the 58, 29 were excluded from outcomes analysis due to lack of follow-up (n = 19) or insurance denial of dose optimization (n = 10). Demographic information is outlined in Table 1. Baseline characteristics associated with future dose optimization included number of prior advanced therapies (ATs) (OR, 1.29, p &lt; 0.001), prior anti-TNF (OR,4.06; p = 0.022), and prior ustekinumab (UST) use (OR,1.82; p = 0.053) (Table 2). The 29 patients included in the outcome analysis received dose-optimized RZB for primary non-response (n = 2), partial response (n = 23), or secondary loss of response (n = 4) after a median of 321 days (IQR, 234-440) from index RZB start. Median follow-up after dose optimization was 217 days (IQR, 147-331). All patients were AT-exposed (Table 1). Baseline clinical symptoms were present in 27 patients (93.1%), with median HBI of 6.5 (IQR, 6.0-8.0). Active endoscopic disease was observed in 11/12 patients (91.7%) who had baseline endoscopy. Dosing was every 4 weeks in 19 (65.5%), every 6 weeks in 9 (31.0%), and combined IV re-induction plus every 4-weeks in 1 (3.4%) patient. Clinical response and remission was seen in 16 (55.2%) and 12 (41.4%) patients, respectively. A ≥ 50% CRP reduction was seen in 5/12 (41.7%) patients with baseline elevated CRP. Among 7 patients with baseline active endoscopic disease with available follow-up, 3 (42.9%) achieved endoscopic remission. No adverse events were reported. Conclusion In this multi-center retrospective cohort, prior AT-exposure (especially anti-TNF) was associated with need for RZB dose-optimization. Dose optimization successfully captured clinical response in a significant proportion of patients who experienced partial response or loss of response to RZB. Conflict of interest: Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Ramesh, Prajith Raj: None Said, Hyder: No conflict of interest Huang, Katherine: No conflict of interest Devi, Jalpa: none Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Alhobayb, Tamara: No conflict of interest Bassmeyer, Blake: No conflict of interest Mohamed, Mouhand: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Rathi, Jaya: No conflict of interest Luu, Bryan: No conflict of interest Khan, Abdul: No conflict of interest Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB. Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Shukla, Richa: Speakers bureau - Abbvie and Lilly Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.