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PURPOSE Older patients with ALL receiving conventional chemotherapy have poor survival due to toxic death and relapse. We hypothesized that a chemotherapy-free, targeted regimen using the anti-CD22 antibody-calicheamicin conjugate inotuzumab ozogamicin followed by the bispecific anti-CD19/CD3 T-cell engager blinatumomab would reduce toxic death and yield high rates of prolonged remission and survival. METHODS Eligible patients were age 60 years and older with untreated, Philadelphia chromosome (Ph)–negative, CD22-positive, B-cell ALL. Patients received up to two cycles of inotuzumab ozogamicin followed by four or five cycles of blinatumomab with intrathecal methotrexate CNS prophylaxis. The primary end point was 1-year event-free survival (EFS). RESULTS The 33 eligible patients had a median age of 71 years (range, 60-84) and a median CD22 expression of 92% (range, 21%-100%). Eight (24%) had previous chemotherapy or radiation for other cancers, six for multiple myeloma. The composite complete remission rate was 85% after two cycles of inotuzumab ozogamicin and 97% by the end of two cycles of blinatumomab. At a median follow-up of 30 months, the 1-year EFS and overall survival were 75% (95% CI, 61 to 92) and 85% (95% CI, 73 to 98), respectively. EFS was shorter with lower CD22 expression or detectable measurable residual disease at any time point. CONCLUSION Inotuzumab ozogamicin then blinatumomab without maintenance chemotherapy in older patients with untreated, Ph-negative, CD22-positive, B-cell ALL yields a high remission rate and excellent EFS. Given the lack of standard, safe, and effective therapies in this population, the regimen should be considered a standard treatment option.

Objective The primary lateral sclerosis ( PLS ) consensus diagnostic criteria and functional rating scale ( PLSFRS ) were recently established to facilitate and optimize future PLS clinical trials. We examined the trajectory of the PLSFRS and other functional outcome measures and biomarkers in the PLS Natural History Study ( PLS NHS ) to understand their performance in this prospective cohort. Methods The PLS NHS is a prospective, longitudinal, multicenter study of people living with PLS in different diagnostic categories: early (disease duration <2 years); probable (2–4 years); and definite PLS (4–15 years). PLSFRS scores and other functional outcome measures were collected at baseline, 3‐, 6‐, 9‐, and 12‐month follow‐up visits. Baseline characteristics were compared between the groups. The slopes of the PLSFRS and other functional outcome measures over 12 months were examined in the overall cohort and subgroups using linear mixed‐effect models. The associations between baseline characteristics and the rate of PLSFRS decline were analyzed with linear regression models. Results A total of 76 participants were included: early (n = 6); probable (n = 26); and definite (n = 44) PLS . Baseline PLSFRS total scores were highest in the early PLS group, followed by the probable and definite PLS groups. In the overall cohort, the PLSFRS total score declined by 0.33 points/month (95% confidence interval [0.27–0.39], adjusted p < 0.05). The rate of decline was steepest in the early PLS group, followed by the probable and definite PLS groups. Baseline neurofilament light chain level was associated with the rate of PLSFRS decline over 1 year ( p = 0.001). Interpretation In PLS, the rate of functional decline, as measured by the PLSFRS total score, is faster during the early phase of the disease. Neurofilament light might serve as a prognostic biomarker in PLS. ANN NEUROL 2026;99:418–428

Background: Substance use disorders (SUDs) are highly prevalent, affecting over 48.5 million Americans. Available treatments for SUD remain insufficient, and many patients do not respond to existing interventions despite adequate adherence to treatments. While novel therapies for SUD are urgently needed, the use of psychedelic drugs for the treatment of SUDs has shown promise. Objectives: This overview of systematic reviews summarizes existing evidence on hallucinogens—serotonergic psychedelics and ketamine—for the treatment of SUD. Methods: A comprehensive search of the literature was conducted to identify relevant evidence for using serotonergic and non-serotonergic psychedelics for the treatment of SUDs. After initial screening (n = 468 studies), 62 studies were retrieved and assessed for eligibility, and a total of 16 systematic reviews were included. Conclusions: Although preliminary, evidence suggests that the use of serotonergic and non-serotonergic psychedelics for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances. Research with these drugs has faced significant challenges, though, and caution when interpreting results is warranted, given high risk of bias and several other methodological limitations from the studies to date. Furthermore, risks associated with these drugs are not negligible. For now, the use of psychedelic drugs for the treatment of SUDs remains experimental, and existing evidence is insufficient to support its use in clinical practice.

Objectives: To evaluate return-to-sport (RTS) rates and patient reported outcome measures (PROMs) following hip arthroscopy for femoroacetabular impingement (FAI) in active football players with a minimum of 5-years follow-up. Methods: All active football players who underwent hip arthroscopy for FAI from 2010-2019 were identified. Preoperative radiographic measures including lateral center edge angle, Tönnis angle, alpha angle, and acetabular depth were obtained. Patients were evaluated for post-operative RTS and revision surgery data at final follow-up. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), HOS Activities of Daily Living (HOS-ADL), HOS Sports Specific Subscale (HOS-Sports), Tegner Activity Scores, Visual Analogue Scale (VAS) for pain, and surgery satisfaction were collected at a minimum 5-year follow-up. Descriptive and comparative statistical analysis was performed using R software (version 4.4.1). Results: Sixty-six hips from 53 male patients were included. The mean age was 20.4 ± 6.4 years and mean BMI was 27.3 ± 6.6 kg/m² (Table 1). Mean follow-up was 8.7 ± 2.8 years. The majority (60%) were high school players and 19% were college players. Figure 1 displays the most commonly affected positions which included wide receiver (32%), defensive lineman (26%), and tight end or offensive lineman (16%). There were 11 bilateral cases and 2 revisions. The mean lateral center edge angle was 31.6º ± 6.4, the mean Tönnis angle was 5.0º ± 5, and the mean alpha angle was 63.2º ± 12.7. There was significant improvement in all PROMs from baseline to a minimum 5-year follow-up (p<0.04). Fifty-four percent of athletes returned to football postoperatively and the average overall surgery satisfaction rating was 8.1/10. Among those who didn’t return, 14% cited hip-related reasons, while 67% cited non-hip related reasons such as priorities changing or graduating (Figure 2). Athletes who returned to football had significantly higher mean HOS-ADL (p=0.049), HOS-Sport (p=0.042), and Tegner level before surgery (p=0.023) compared to those who did not return (Table 2). Conclusions: Football players undergoing hip arthroscopy for FAI demonstrate significant improvements in outcome scores at a minimum 5-year follow-up with a moderate return-to-sport rate. Athletes who are able to return to football report higher patient reported outcomes compared to those who do not. Player position may also influence incidence and outcomes. Although football players demonstrate significant improvements following hip arthroscopy, the moderate RTS rates highlights the demanding nature of the sport and need for improved perioperative counseling.

Objectives: Periacetabular osteotomy (PAO) is utilized for the treatment of hip dysplasia, with a growing trend towards hip arthroscopy at the time of PAO or in a planned, staged manner prior to PAO in order to address intra-articular pathology such as labral tears. For patients with persistent or new pain following isolated PAO, a subset undergo unplanned, primary hip arthroscopy. To date, there is a paucity of available evidence regarding the risk factors for and outcomes of unplanned hip arthroscopy for persistent or new pain after PAO. The purpose of this study was to determine demographic and radiographic characteristics of patients undergoing hip arthroscopy for persistent pain after PAO and also to compare radiographic parameters, surgical characteristics, and postoperative PROMs between patients that underwent hip arthroscopy following PAO and a demographically similar group of controls without acetabular dysplasia that underwent primary hip arthroscopy. Methods: An institutional database of 3014 hip arthroscopies performed between 1988 and 2022 was reviewed for patients having undergone unplanned (i.e. non-staged) first-time hip arthroscopy after PAO. These patients were propensity-matched on a 1:2 ratio with demographically similar, non-dysplastic patients undergoing primary hip arthroscopy with labral repair. All patients were contacted at final-follow-up to collect outcomes including subsequent procedures, progression to THA, and patient-reported outcome measures (PROMs), including modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT), Tegner Activity Scores, Visual Analogue Scale (VAS) for pain, and surgery satisfaction. Demographics, radiographic characteristics, and postoperative outcomes were compared. All statistical analysis and Kaplan-Meier survival curve analysis was performed using R software (version 4.4.1). Results: We identified 22 hips in 21 patients (17 female, 4 male; age: 24.6 ± 8.5 years; BMI: 29.3 ± 7.4 kg/m²) who underwent first-time arthroscopy after ipsilateral PAO and were followed for a mean of 7.2 ± 2.8 years (Table 1). The median post-PAO LCEA was 28° (IQR: 24.6 – 31.7) and the mean Tönnis angle was 4.2° ± 5.9. The median time from the date of PAO to date of subsequent hip arthroscopy was 1.6 years (IQR: 1.1 - 3.4). Compared to the control group, there was a significantly lower rate of femoral osteochondroplasty (50% vs, 86%, p < 0.01), as well as trends towards lower rate of labral repair (77% vs. 95% p = 0.11), and higher rate of capsular repair (64% vs. 75%, p = 0.34). No differences were found between the PAO and control groups in any of the postoperative PROMs (Table 2). Among the PAO patients, 3 (20%) progressed to total hip arthroplasty (THA) compared to 1 (9%) in the control group (p=0.62). Conclusions: Hip arthroscopy after prior PAO was associated with postoperative improvements in pain and moderate rates of conversion to THA. When patients undergoing hip arthroscopy following PAO were compared to a demographically similar matched cohort of nondysplastic hips who underwent primary hip arthroscopy without a prior PAO, similar postoperative outcome scores were observed. This data provides valuable counselling information for clinicians discussing hip arthroscopy in the setting of patients with persistent pain following PAO.

Objectives: The role of femoral version (FV[MOU1] ) in the pre-arthritic hip pain remains increasingly recognized, including in femoroacetabular impingement (FAI). Increased femoral version or decreased femoral version may play a role in hip biomechanics contributing to hip instability or impingement, respectively. The purpose of this study was to compare the outcomes of hip arthroscopy for FAI across different femoral version groups in a multicenter prospective cohort study. Methods: A prospective multicenter cohort study of 677 FAI patients undergoing primary hip arthroscopy was performed. The current study included 603 patients with low-dose CT performed preoperatively for measurement of femoral version from the larger cohort. Inclusion criteria were patients aged 14-45 years with idiopathic FAI. Exclusion criteria were previous ipsilateral hip procedures, associated disorders, or Tönnis 2 or greater osteoarthritis. Femoral version was measured on low-dose computed tomography (CT) utilizing the Yoshioka oblique method and was broken into five subgroups: <5° (decreased FV), 6-15° (normal FV), 16-25° (mildly increased FV), 26-35° (moderately increased FV), 35°+ (severely increased FV). Patient-reported outcomes (PROs) were measured at a minimum one-year follow-up. The modified Harris hip score (mHHS) was assessed relative to the minimal clinically important difference (MCID) of 8 and patient acceptable symptom state (PASS) of 74. Additional PROs included the HOOS Pain and Sports/Recreation subscores and the iHOT-12 score. Composite failure was defined as a reoperation for persistent symptoms or a failure to achieve either the mHHS MCID or PASS. Independent t-test (Mann-Whitney U) and ANOVA were utilized to compare groups. Results: Males had statistically lower femoral version than females (14.0° vs 18.0°; p<0.001). In females, 38.0% had mildly increased FV, 17.9% had moderately increased FV, and 3.6% had severely elevated FV. This is compared to 27.6%, 9.2%, and 1.8% in males, respectively (all p<0.001). Decreased FV was present in 7.1% of males, compared to 5.9% of females. Increased or decreased femoral versions appear to have similar outcomes to normal version when evaluated by PROs or outcome states. In fact, mildly increased and moderate increased FV group demonstrated the best outcomes. Changes in HOOS pain and sports subscores were significantly higher for these groups. Severely increased FV, >35°, was only present in 2.8% of patients but did demonstrate a higher rate of composite failure (15.4%) compared to moderately increased FV (3.1%). The decreased FV group had a composite failure of 10.4% compared to normal femoral version, 16-25° (10.2%). Conclusions: In a patient cohort undergoing hip arthroscopy for FAI, significant differences in FV between males and females were present. Overall, in a multicenter prospective cohort study, the outcomes of hip arthroscopy for FAI did not seem to differ between increased or decreased femoral versions but were superior in mild to moderately increased FV. Future research with longer-term follow-up is still needed to definitively establish the longevity of outcomes of hip arthroscopy relative to FV.

ABSTRACT Objectives Patients requiring long‐term enteral nutrition or continuous infusion of carbidopa/levodopa can benefit from jejunostomy tube placement. Recently, directly placed percutaneous transgastric jejunal tubes (TGJs) have been used instead of gastrostomy tubes with jejunal extensions (PEG‐Js) for enteral access. We aim to compare patient characteristics and outcomes after placement of TGJs placed via the introducer technique compared to PEG‐Js. Methods We performed a retrospective study of 141 patients (TGJ = 58, PEG‐J = 83) assessed at Mayo Clinic between 2010 and 2024. Patients were identified using a prospectively maintained procedure data registry. Demographic data, patient characteristics, procedural indications, complications, and first‐replacement date were gathered. Statistical analysis included the Wilcoxon rank sum test, chi‐square test, Fisher's exact test, and Kaplan‐Meier estimates. Patients receiving carbidopa/levodopa were excluded from complications analysis due to the carbidopa/levodopa tube's proprietary structure. A p ‐value of <0.05 was set as a threshold for significance. Results Our results demonstrated no difference in cumulative incidence of complications within 1 year for TGJs and PEG‐Js, p ‐value 0.48. Regarding time to first replacement, treating death as a competing risk factor, there was no statistically significant difference in cumulative incidence of replacement within 1 year for TGJs and PEG‐Js, p ‐value 0.389. Conclusions Our study demonstrates that both direct TGJs and PEG‐Js are safe options for long‐term jejunal feeding. More studies are needed to compare endoscopic to radiologically placed percutaneous transgastric jejunal feeding tubes.

Abstract Diffuse large B-cell lymphoma (DLBCL) poses a challenge in hematology given its varied symptoms, and the complex interplay between disease and treatment effects on health-related quality of life (HRQoL). The phase 3 POLARIX study demonstrated superior progression-free survival and a similar safety profile with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with previously untreated DLBCL. Here, we evaluate HRQoL through patient-reported outcome (PRO) instruments to fully characterize the patient experience in the POLARIX study. Changes from baseline in HRQoL, lymphoma symptoms, and gastrointestinal (GI) symptoms were assessed, as well as incidence and severity of common symptoms by PROs vs clinician-reported adverse events (AEs). Baseline characteristics of PRO-evaluable patients (N = 874) were consistent. Comparison between PROs and clinician-reported AEs revealed a notable discordance; patients generally reported a higher incidence of symptoms than clinicians, emphasizing the need for patient-centric tools to accurately capture the patient experience. Both treatments exhibited rapid and sustained improvements in HRQoL and lymphoma symptoms, with the most substantial improvements seen in global health status/QoL, lymphoma symptoms, fatigue, role, emotional, and social functioning. GI symptoms (diarrhea, constipation, nausea, and vomiting) were generally similar between treatment arms and returned to baseline levels after treatment completion. These HRQoL data underscore the complementarity of PROs, as an adjunct to clinician-reported AEs, in evaluating the efficacy and tolerability of new treatments, including Pola-R-CHP, which may represent a new benchmark for patient-reported HRQoL in previously untreated DLBCL. This trial was registered at www.clinicaltrials.gov as NCT03274492.

When encountering diseases of the anterior vitreous and peripheral retina (ie, the “middle segment” of the eye), vitreoretinal (VR) surgeons are specifically trained in surgical techniques for managing the vitreous and visualizing the peripheral retina during anterior vitrectomy, and therefore, they are well equipped to address the complications of surgery involving the anterior vitreous space. This clinical update reviews and compares the current literature discussing techniques and patient outcomes related to complete pars plana vitrectomy versus incomplete, subtotal pars plana vitrectomy, and addresses the proposition of developing an abridged training curriculum for non-VR surgeons to acquire the knowledge and skills required to perform these procedures. Recent studies confirmed that operating in the anterior vitreous carries potential risk of retinal tear, retinal detachment, and other adverse events that may cause vision loss. To mitigate these risks, studies suggest that the use of dedicated visualization equipment and illumination instruments is necessary for surgeons to safely perform anterior vitrectomy and recognize complications, should any occur. Performing VR surgery in the absence of wide-angle viewing systems, endoillumination, careful peripheral examinations, modern vitrectomy platforms, and appropriate training may lead to outcomes that are detrimental to patient safety.

Abstract Invariant Natural Killer T (iNKT) cells recognize glycolipid antigens presented on CD1d and rapidily respond to direct immune responses. iNKT cells develop in the thymus and migrate to peripheral tissues in what has been presumed to be differentiated/committed states. Accordingly, colonic iNKT cells are established in early life, considered to remain ‘fixed’ post-weaning, and determine life-long colitis susceptibility. Using single cell RNA sequencing (scRNA-seq), we demonstrate that humans and mice contain colonic iNKT populations transcriptionally resembling immature and intermediate thymic iNKT precursors. Contrary to prevailing paradigms, we demonstrate colonic iNKT cell populations expand in adult mice when CD1d expressing colonic goblet cells form goblet cell-associated antigen passages. Expansion preferentially affected intermediate iNKT cells, was durable, and protective in a colitis model. These studies reveal that the adult colon harbors iNKT cells with retained plasticity and uncover a novel role for goblet cells as unconventional antigen presenting cells regulating this axis.