Durable Improvement Research Articles

Preservation of sexual function with Optilume-a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

The Optilume benign prostatic hyperplasia (BPH) catheter system is a novel minimally invasive paclitaxel-coated dilation system that has demonstrated substantial and durable results in urinary flow and symptoms. We now assess the impact of Optilume BPH procedure on sexual function. Prior published results have described the methods of data collection during the PINNACLE study, which demonstrated durable improvement in urinary symptoms. Follow-up assessments for the current study included IIEF-EF and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Semen quality was also examined. IIEF-EF and MSHQ-EjD scores in the Optilume BPH group were not different from the sham group at 3months, 6months, or 12months. A total of 148 men were randomized to receive the procedure (100) or a sham surgical procedure (48). Subjects in both groups had similar rates of erectile dysfunction (ED) previously diagnosed at baseline (56% vs 54.2%, P = .83) and those men who were sexually active. IIEF-EF and MSHQ-EjD scores in the Optilume BPH group were not different from the sham group at 3, 6, or 12months. Change in IIEF-EF scores remained consistent across all levels of baseline ED severity after Optilume BPH procedure. No clear trend was seen after treatment with Optilume BPH for semen volume, sperm motility, progressive motility, or sperm morphology. The Optilume BPH catheter system provides patients with a durable improvement in lower urinary tract symptoms while preserving sexual function. This study uses validated questionnaires to assess patients' sexual function at baseline and regularly for 1year after the procedure. Given exclusion criteria regarding patient age and prostate size, the results may not be applicable to all BPH phenotypes. Optilume appears to provide clinical benefit with a high degree of patient satisfaction and minimal impact on sexual function.

Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.

Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials. This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36months as data inferences became limited. Participants received a single intra-articular LOR or placebo (PBO) injection at their parent-trial baseline. The primary outcome was the comparative incidence of serious adverse events (SAEs), with AEs and similar safety measures comprising secondary outcomes. A post hoc baseline-adjusted analysis of covariance (ANCOVA) compared changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function subscores and medial joint space width (JSW) between LOR 0.07mg and PBO groups in a subpopulation of participants with unilateral knee pain and widespread pain low enough to allow participants to differentiate their target knee pain. The safety analysis set for the extension study included 495 LOR-treated and 208 control participants, with 409 (82.6%) and 175 (84.1%) remaining at study close, respectively. There were 68 SAEs reported in 38 (5.4%) patients; none were considered treatment-related by investigators. The incidence of AEs was similar between groups. In the post hoc subgroup efficacy analyses, LOR 0.07mg demonstrated greater mean improvements from baseline compared with PBO in WOMAC pain and function scores out to 12months post-injection. No between-group differences in medial JSW were observed out to 18months. LOR appeared generally safe and well tolerated. Efficacy analyses on the subset of completer patients demonstrated durable symptom improvements in WOMAC pain and function for at least 12months compared to PBO after a single injection of LOR. NCT02951026.

PRP Injections for the Treatment of Knee Osteoarthritis: The Improvement Is Clinically Significant and Influenced by Platelet Concentration: A Meta-analysis of Randomized Controlled Trials

Background: Platelet-rich plasma (PRP) has emerged as a promising therapeutic intervention for knee osteoarthritis (OA), attracting substantial clinical and research attention. However, the clinical relevance of the treatment benefit remains controversial. Purpose: To evaluate the effectiveness of PRP compared with placebo in patients with knee OA in terms of minimal clinically important difference (MCID) and to investigate the possible influence of platelet concentration on the clinical outcome. Study Design: Meta-analysis. Level of evidence 1. Methods: The search was conducted on 5 databases (PubMed, Cochrane Library, Scopus, Embase, Web of Science) using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were randomized controlled trials comparing PRP and placebo injections to treat knee OA, written in the English language, with no time limitation. The effects were quantified at 1-, 3-, 6-, and 12-month follow-up points. Visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used, with subanalyses based on platelet concentration performed using a 1,000,000 ± 20% platelets/µL cutoff. The MCID values (VAS, 1.37; WOMAC, 6.4) were used to interpret clinical improvement. The articles’ quality was assessed using the Revised Tool for Risk of Bias in Randomized Trials and the Grading of Recommendations Assessment, Development and Evaluation guidelines. Results: Among the 5499 articles retrieved, 18 randomized controlled trials (1995 patients) were included. PRP presented statistically superior improvements in VAS and WOMAC scores compared with placebo at all follow-up points, exceeding the MCID at 3- and 6-month follow-up points for VAS and at all follow-up points for WOMAC. The subanalysis based on platelet concentration showed that high-platelet PRP provided clinically significant pain relief with the improvement exceeding the MCID compared with placebo at 3-, 6-, and 12-month follow-up points. In contrast, low-platelet PRP failed to offer a clinically perceivable benefit in terms of VAS score. WOMAC results showed that both products provided a clinically significant improvement at 3 and 6 months of follow-up. This benefit was maintained up to the 12-month follow-up in the high-platelet group but not in the low-platelet group, where the improvement compared with placebo did not reach statistical significance. Conclusion: This meta-analysis showed that PRP offered clinically relevant functional improvement at 1-, 3-, 6-, and 12-month follow-up points and pain relief at 3- and 6-month follow-up points compared with placebo for the treatment of knee OA. Platelet concentration was found to influence treatment efficacy, with high-platelet PRP providing superior pain relief and more durable functional improvement compared with low-platelet PRP.

International web-based survey of patients with non-hydrocephalic symptomatic pineal cysts

ObjectivesTo report the results of an international patient-reported survey that adds to the growing body of evidence surrounding the role of surgery in the management of a subset of patients with non-hydrocephalic symptomatic pineal cyst.DesignAn international web-based survey of health outcomes in patients with nhSPC.SubjectsAll survey participants who self-reported a diagnosis of symptomatic pineal cyst without hydrocephalus after radiological imaging.MethodsThe survey was developed in collaboration with the patient group Pineal Cyst UK. It was publicised and distributed via several online platforms and social media. Data collected included demographics, cyst size, symptom frequency and severity, number of appointments with healthcare professionals, treatment options trialled, and whether patients underwent surgery.Results543 participants (mean age 38.6 years, range 1–83) were included in the analysis, of which 82 (mean age 38.9 years, range 16–72) had undergone cyst resection. After a median period of 18.3 months between date of surgery and date of questionnaire completion, 72 (90%) of the surgical cohort reported overall improvement, and all symptoms improved overall, whereas no symptoms improved overall in the non-surgical cohort. Of the non-surgical cohort (n = 461), 269 participants received some form of conservative treatment, of whom 194 (72.1%) did not experience symptom improvement on any treatment offered.ConclusionsA cohort of patients with nhSPC who participated in this international survey reports substantial and durable improvement in symptom severity and quality of life after pineal cyst resection.

Persistent Patient-Level Effect of Guselkumab at Consecutive 8-Week Dosing Visits and Over Time in Patients With Active Psoriatic Arthritis: Post Hoc Analysis of a 2-Year, Phase 3, Randomized, Controlled Study.

Group-level analyses from the phase 3 DISCOVER-2 trial of guselkumab demonstrated robust and durable improvements across psoriatic arthritis (PsA) domains. To specifically evaluate continuous disease control in individual patients, persistence of clinically relevant improvements was assessed, both at consecutive guselkumab dosing visits and over time. Post hoc analyses included biologic-naïve patients randomized to 100 mg of guselkumab at week 0, week 4, and then every 8 weeks (Q8W). Improvements in joint (minimal clinically important improvement [MCII] in Disease Activity Index for PsA [DAPSA; ≥7.25], clinical DAPSA [cDAPSA; ≥5.7]), skin (Investigator's Global Assessment [IGA] 0/1), and overall disease activity (patient global assessment of arthritis and psoriasis [PtGA Arthritis+Psoriasis; MCII ≥ 15 mm], PsA Disease Activity Score [PASDAS; MCII ≥ 0.8]) were assessed. Proportions of patients with maintenance of DAPSA and cDAPSA MCII at consecutive Q8W guselkumab dosing visits (ie, at weeks 4 and 12, weeks 12 and 20, etc through week 52) and patient-level durability of response through week 100 (Kaplan-Meier) were determined. Among 248 patients randomized to guselkumab Q8W, 93% to 99% maintained clinical improvement in joint disease at consecutive Q8W dosing visits through week 52 across time periods. Among guselkumab patients achieving MCII by week 24, estimated probabilities of maintenance of clinical improvement 100 weeks post achievement ranged from 68% (IGA 0/1) to 89% (PASDAS MCII). Median times to loss of improvement were not reached; estimated mean weeks of maintenance of improvement were 58.6, 52.4, 75.7, 83.6, and 76.7, respectively, for DAPSA, cDAPSA, IGA, PtGA Arthritis+Psoriasis, and PASDAS. Guselkumab provided highly durable patient-level improvements, both at consecutive Q8W dosing visits for joint disease activity and over time across PsA domains according to physician- and patient-driven assessments.

Zenker’s Per-Oral Endoscopic Myotomy (Z-POEM): The Ideal First Line Therapy for Treatment of Zenker’s Diverticulum

Zenker's diverticulum is a mucosal herniation at the pharyngoesophageal junction. While open surgical myotomy is the conventional treatment, robust evidence on third-space flexible endoscopic myotomy is lacking. We assessed safety, effectiveness and patient-reported outcomes of per-oral endoscopic myotomy (Z-POEM) in the largest reported single-centre experience with this technique. Retrospective cohort study was performed of consecutive patients undergoing Z-POEM in a tertiary hospital thoracic surgery practice from 2018-2024. Data collected included demographics, comorbidities, clinical and radiographic (pre/post-operative esophagram) outcomes, and validated patient-reported quality-of-life outcomes (Dakkak and Eckardt scores). Descriptive analyses were used to describe the population, outcomes, and complications. Aggregate and individual-patient symptom trajectories were charted over time. Fifty-seven patients (57.9% female, n=33) with a mean age of 74 years underwent Z-POEM. Median diverticulum size was 2 cm (IQR 2-3). All patients reported subjective symptom improvement and showed complete resolution of obstructed barium flow on postoperative esophagrams. At median follow-up of 9 months, all Z-POEM patients reported clinically-important improvements in objective symptom scores, with symptom trajectories showing rapid and durable improvement up to 5 years postoperatively. Four patients (7%) experienced complications. Majority of the cohort (66.7%) was unsuitable for rigid stapled myotomy, mainly due to short diverticulum or limited neck/mouth movement. No patients required repeat myotomy. We demonstrate significant and sustained relief of patient-reported outcomes/symptoms following Z-POEM, including for small diverticuli, with low complication rates. Its safety and versatility has made it the new standard of care locally; Z-POEM can be adopted by third-space endoscopy-trained thoracic surgeons.

Randomized Controlled Trial of a Virtually Delivered Exercise and Stress Management Program to Improve Physical Performance of Hematopoietic Cell Transplant Survivors.

Because of advances in hematopoietic cell transplant (HCT), meeting the long-term health needs of increasing numbers of HCT survivors remains challenging. This multicenter trial aimed to assess the short- and long-term effects of an exercise and mindfulness intervention delivered by telehealth. One hundred thirty-nine participants >6 months post-HCT were randomly assigned 1:1 to a 6-week personalized exercise and mindfulness training with three motivation sessions at 3-6 months via an online meeting platform or usual care. Physical and quality-of-life (QOL) assessments were conducted online for 12 months. The primary end point was the 6-minute walk test (6-MWT) at 3 months. The median time post-HCT was 21 months (range, 7-67 months). Improvement in mean difference of 6-MWT was found in the intervention group compared with control (intention-to-treat) at 3 months (51.4 m [95% CI, 27.3 to 75.5]; P < .001; effect size [ES], 0.52) and was maintained at 12 months (59.3 m, P = .003; ES, 0.60). Sustained improvements in mean difference for sit-to-stand (STS) at 3 and 12 months were seen. There were no significant changes in hand grip strength or QOL outcomes between groups. A significant difference in serum soluble intercellular adhesion molecule-1 (sICAM-1) concentration was observed between the intervention and control groups in the exploratory study. No intervention adverse events were found. The supervised multimodal telehealth intervention provided clinically meaningful and durable improvement of physical capacity in HCT survivors. This home-based program has the potential to provide an unmet need for HCT survivors. Similar programs may benefit survivors of other cancers, organ transplants, and chronic disorders.

Observed Glycemic and Psychosocial Benefits in the Prospective Bigfoot Unity Real World Study: A Six-Month Analysis.

The Bigfoot Unity Diabetes Management System integrates Abbott FreeStyle Libre 2 continuous glucose monitoring (CGM) data into a smart pen cap and mobile app enabling clinician-directed insulin dose recommendations and real-time alerts. The objective was to analyze real world 6-month glycemic control in a prospective study for individuals using the System for multiple daily insulin injections (MDI). We conducted a 6-month analysis from the BURST study (NCT05088265) of individuals with type 1 or type 2 diabetes (T2D). Participants reported baseline demographics, adverse event and other surveys electronically. Either at-home kit or electronic medical record glycated hemoglobin A1c (HbA1c) data were collected. Of 102 participants in the per-protocol cohort, median age was 59 years, 87% had T2D, 42% used CGM previously, 62% were White non-Hispanic and 59% female. Mean HbA1c decreased from 9.1 ± 1.7% at baseline to 8.0 ± 1.2% at 6 months (mean difference -1.1%, 95% confidence interval -1.4 to -0.8, P < 0.001). At 6 months, time in range 70-180 mg/dL, time <70 mg/dL and <54 mg/dL were 56 ± 23%, 1.0 ± 1.4% and 0.04 ± 0.14%, respectively. Six severe hypoglycemia events occurred in 4 participants (none system related) and no diabetic ketoacidosis events occurred in the per-protocol cohort. In this study primarily of older adults with T2D using MDI, durable glycemic improvement occurred using the System at 6 months, with the frequency of hypoglycemia being substantially below established targets of <4% and <1% for time below 70 and 54 mg/dL, respectively.

Satisfactory Clinical Outcomes After Latissimus Dorsi Tendon Transfer for Irreparable Posterosuperior Massive Rotator Cuff Tears: A 10- to 20-Year Follow-up

Background: Latissimus dorsi tendon transfer (LDTT) leads to good clinical outcomes and recovery of function. A previous study have evaluated the outcomes of LDTT at a minimum 10-year follow-up and found durable improvements in shoulder function and pain relief but observed that shoulders with fatty infiltration of the teres minor muscle and insufficiency of the subscapularis muscle tended to have inferior results. Purpose: To evaluate the outcomes of LDTT with a minimum follow-up of 10 years in a sizeable cohort for the treatment of irreparable posterosuperior massive rotator cuff tears (mRCTs). Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent LDTT for irreparable mRCTs between 2004 and 2013, performed by the same senior surgeon, were included in this study. All intraoperative and postoperative complications, as well as whether patients required conversion to reverse shoulder arthroplasty (RSA), were noted. At a minimum follow-up of 10 years, an independent observer collected range of motion measurements and clinical scores, including those for the Constant score, the Subjective Shoulder Value, and a visual analog scale for pain; the subacromial space was also assessed. Results: A total of 143 patients (147 shoulders) that underwent LDTT, with a minimum follow-up of 10 years, were included; of these, 24 patients (24 shoulders, 16%) were lost to follow-up, 1 patient (1 shoulder, 0.7%) died 9 years after the index procedure for reasons unrelated to shoulder surgery, and 18 patients (18 shoulders, 12%) required conversion to RSA, of which 6 underwent conversion at ≥6 years after LDTT. The remaining 101 patients (104 shoulders), including 3 patients who were scheduled to undergo RSA, were assessed at a mean time of 12.3 ± 2.2 years (range, 10-20 years) after index LDTT, comprised 52 men (53 shoulders) and 49 women (51 women) and had a mean age of 61.6 ± 8.0 years (range, 39-81 years) at the time of index surgery. Complications were noted in 14 shoulders, of which 4 required a reoperation. The Constant score improved by 34.2 ± 11.7 points, the adjusted Constant score by 43.5 ± 15.3 points, and the Subjective Shoulder Value score by 50.4 ± 16.4 points. The subacromial space decreased by 0.3 ± 2.0 mm. Conclusion: At a minimum follow-up of 10 years, LDTT for the treatment of irreparable posterosuperior mRCTs led to satisfactory clinical scores. Of the 147 shoulders that underwent LDTT, 18 (12%) required conversion to RSA.

BN SO30 - One hundred consecutive Laparoscopic Heller's Cardiomyotomy &amp; Fundoplication – a personal series

Abstract Background Oesophageal Achalasia (OA) is an uncommon primary oesophageal motility disorder, characterised by the loss of inhibitory neurons in the oesophageal myenteric plexus. The primary goal of treating OA is to alleviate dysphagia caused by the functional obstruction of the distal oesophagus due to the inability of the lower oesophageal sphincter (LOS) to relax appropriately after swallowing. Heller's cardiomyotomy (HCM) remains a standard treatment for OA. The aim of this study was to assess the symptomatic improvement and post-operative outcomes following HCM with fundoplication at our centre. Method All patients underwent HCM through laparoscopic blunt muscle separation technique, between January 2005 and March 2024, by a single surgeon. Retrospective review of electronic and compiled paper patient records were analysed to assess patient demographics, preoperative symptoms, operative details, length of stay (LOS), complications, post-operative symptoms, gastroscopy and pneumatic dilation (PD) as well as revisional surgery. Primary outcomes assessed were binary changes in key symptoms of weight loss, dysphagia, retrosternal pain and regurgitation. Comparison of pre and post-operative outcomes were performed using paired t-test. A p-value of &amp;lt;0.05 was considered statistically significant. Results 100 procedures involving 99 patients (average age 50 years, 43% female), 1 conversion to open and 1 revision at 3 years. ASA grades were 1 (27%), 2 (58%), and 3 (15%). Median LOS was one day, median follow-up 99 months. Post-operatively; weight loss persisted in 11% of patients from 48%, dysphagia reduced from 98% to 42%, retrosternal chest pain from 39% to 20% and regurgitation from 57% to 24% (all p&amp;lt;0.05). 2 patients required (PD) ≤30 days (CD≥3). 36 patients underwent PD at median of 13 months, 20 needed repeat PD. None of the patients developed cancer. Conclusion As demonstrated in this large series of 100 consecutive patients, HCM remains one of the best treatment modalities for OA. Key symptoms of OA significantly reduced following HCM. Our technique avoided the use of energy devices, ensured a short hospital stay and durable symptom improvement, lends support to its continued application in managing this condition.

Longitudinal email-based electrocardiogram interpretation curriculum for paediatric residents.

Electrocardiograms are frequently obtained in infants and children. Training specific to paediatric electrocardiogram interpretation is necessary given that cardiac physiology and electrocardiogram findings in children are different than adults and change throughout infancy and childhood. Distributed practice may be an effective method to improve paediatric residency electrocardiogram education efforts. A pre-survey was administered to paediatric and internal medicine/paediatrics residents to ascertain baseline comfort with electrocardiogram interpretation. Subsequently, residents were emailed a clinical vignette with an associated electrocardiogram and multiple-choice question 1-2 times monthly. After submitting their answer, residents were taken to a webpage explaining key concepts explored in the clinical vignette. After 6 and 12 months, a survey was administered asking residents to again rate their confidence in the same electrocardiogram interpretation skills. The longitudinal email-based curriculum increased exposure to electrocardiogram training. Six months of participation in the curriculum correlated with significant increases in confidence in electrocardiogram interpretation skills. While there was no further increase in confidence seen at 12 months, the improvement seen at 6 months was durable. Participation in the curriculum most significantly correlated with changes in confidence in ability to utilise a stepwise approach for electrocardiogram interpretation. The curriculum resulted in durable improvement in confidence in electrocardiogram interpretation skills for paediatric residents at our centre, suggesting that email-based distributive practice can be an effective method for skill and knowledge improvement for complex educational topics.

Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab

In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck. Least squares mean change from baseline to Week 56 in EASI score was analyzed by anatomic region (head and neck, trunk, upper extremities, or lower extremities) for patients with baseline moderate-to-severe AD in the respective anatomic region, using mixed models for repeated measures. Rocatinlimab groups were compared with placebo at Week 16. The proportion of patients achieving at least 75% reduction from baseline in EASI (EASI-75) was calculated. Probability of relapsing in EASI-75 during the off-treatment follow-up period (Weeks 36–56) was estimated using a Kaplan − Meier approach. At Week 16, decrease from baseline in mean EASI score was greater with all rocatinlimab regimens versus placebo across all anatomic regions for patients with baseline moderate-to-severe AD in the respective region (all P < 0.001). EASI scores continued to improve on treatment after Week 16 and were maintained during the off-treatment period across all regions. Among patients with baseline moderate-to-severe AD in the head and neck (n = 219; rocatinlimab, n = 174; placebo, n = 45), mean difference (rocatinlimab vs placebo) at Week 16 in LS mean percent change in head and neck EASI score ranged from − 30.4% to − 42.6% across treatment regimens. In patients who received rocatinlimab from the start of the trial, 47% − 71% achieved EASI-75 in the head and neck at Week 36. Among EASI-75 responders at Week 36, the probability of relapsing in EASI-75 in any region was low (< 25% in the head and neck) 20 weeks after treatment discontinuation until Week 56.Rocatinlimab treatment led to durable improvements in AD across multiple anatomic regions, including the sensitive head and neck region.Graphical abstract

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage. In this study, we have evaluated the effect of the pH-sensitive GluN2B-selective NMDAR inhibitor, NP10679, on neurologic impairment after SAH. This compound demonstrates a selective increase in potency at the acidic extracellular pH levels that occur in the setting of ischemia. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. Based on allometric scaling of both toxicological and efficacy data, the therapeutic margin in man should be at least 2. These results further demonstrate the utility of pH-dependent neuroprotective agents and GluN2B-selective NMDAR inhibitors as potential therapeutic strategies for the treatment of aSAH. Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication.

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

Abstract X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking. A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P&amp;lt;.001) and physical function (-14.3 ± 16.2, P=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

ID: 314835 Painful Diabetic Neuropathy: 10 kHz SCS Provides Significant, Durable Improvements in Quality of Life Metrics

ID: 314835 Painful Diabetic Neuropathy: 10 kHz SCS Provides Significant, Durable Improvements in Quality of Life Metrics

Immune checkpoint blockade effect on immunologic and virologic profile of five cancer patients living with human immunodeficiency virus (HIV) infection.

Immune checkpoint inhibitors (ICI) have changed the prognostic outlook for several malignancies. Despite the unprecedented durable responses and improvement in survival outcomes with ICIs, exclusion of oncology patients living with human immunodeficiency virus (HIV) from most ICI-related trials has limited utility of these agents. Clinical outcomes related to concomitant use of antiretroviral therapy and ICI remain unclear. We present a case series based on our institution's experience to address this unmet need of clinical outcomes with ICI in oncology patients living with HIV. Electronic medical records were queried to identify patients living with HIV who were also diagnosed with cancer and treated with ICI from May 2019 to September 2022. A total of five patients were on concurrent antiretroviral therapy and immunotherapy. From an efficacy perspective, three patients were observed to have a response (one complete response, one partial response, and one stable disease). There were three patients with known cluster of differentiation (CD4 + ) levels who had an increase in CD4 + cell count with ICI treatment. The HIV viral load remained undetected in most of the patients on ICI treatment. No confirmed immune-related adverse effects were documented for any patients in this review. Immune checkpoint inhibitors may be efficacious and tolerable for treatment of cancer in patients living with HIV. Upward trends in CD4 + cell counts observed in this case series suggest that immune checkpoint inhibitors may enhance HIV disease control. Further research is needed for this patient population to supply more robust evidence for clinical practice.

Is low-intensity shockwave therapy for erectile dysfunction a durable treatment option?-long-term outcomes of a randomized sham-controlled trial.

Low-intensity shockwave therapy (LiSWT) is an emerging non-invasive and restorative therapy for erectile dysfunction (ED) with demonstrated efficacy and few adverse events. Although LiSWT has been shown to improve erectile function amongst men with ED, few studies have examined its long-term durability. We present the long-term results of a randomized controlled trial (RCT) assessing erectile function after LiSWT. A total of 30 patients with baseline ED seen at the University of Virginia were randomized to LiSWT or sham treatment. Patients in the sham group crossed over at 1 month and were unblinded. After initial trial completion, patients enrolled in the long-term outcome study were considered one combined cohort. Patients were treated twice weekly for 3 consecutive weeks with a Storz® Duolith™ device delivering 3,000 shockwaves at 0.1 mJ/mm2 to the distal penis, the base of the penis, and the crura. Primary outcomes were changes in Sexual Health Inventory for Men (SHIM) and Erection Hardness Score (EHS) from baseline (3 months pre-treatment) up to 36 months post-treatment. Changes in SHIM and EHS scores were evaluated using linear mixed effects models. Patient satisfaction was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index. The mean baseline SHIM score was 10.8±0.94. At 12-, 24-, and 36-month assessment following treatment, the mean SHIM scores were 15.6±1.27 (P<0.001), 15.0±1.14 (P<0.001), and 12.2±1.43 (P=0.31). The mean baseline EHS score was 1.87±0.17. At 12-, 24-, and 36-month assessment following treatment, the mean EHSs were 2.70±0.24 (P<0.001), 2.66±0.21 (P<0.001), and 2.29±0.26 (P=0.10). The median [interquartile range (IQR)] EDITS score was 48.9 (22.7, 74.4), indicating moderate satisfaction with LiSWT. There were no adverse events recorded. Our analysis demonstrates sustained long-term improvement in erectile function after LiSWT for a heterogeneous cohort. While limited by population size, the results suggest durable improvement in erectile function for the first 2 years with a peak treatment effect at 1 year. Treatment effect appears to decline between 2 and 3 years. ClinicalTrials.gov, NCT04434352.

Secondary Contouring for the Butterfly Graft: Improving Form and Preserving Function.

The butterfly graft (BFG) secondary contouring procedure addresses external nasal irregularities following the primary BFG surgery. We explore demographic factors associated with the desire for secondary contouring and assess patient-reported outcomes following the procedure. A retrospective analysis of 374 patients undergoing BFG between April 2020 and April 2023 identified 10 individuals electing for secondary contouring. Demographics, Nasal Obstruction Symptoms Evaluation (NOSE) scores, Rhinosinusitis Disability Index (RSDI), and decision regret scale (DRS) were collected and reported. Secondary contouring rate was 2.7% of total cases. The majority of patients desiring BFG secondary contouring were white females (90%). NOSE scores significantly improved post-primary surgery (mean change: 51.7, SD: 14.01, p-value: <0.05). Although overall NOSE scores remained improved after secondary contouring (mean change: 47.2, SD: 18.84, p-value: <0.05) compared with their preoperative NOSE scores, one patient (10%) reported worse score after secondary contouring. Four patients (40%) reported worsening after secondary contouring compared with after initial BFG surgery. DRS indicated minimal regret from patients. BFG secondary contouring is a valuable option for patients with external nasal complaints, providing improvements in nasal appearance and durable improvement in breathing outcomes. We emphasize the importance of patient counseling and appropriate patient selection. Our results suggest that patients should expect a slight worsening of NOSE scores following secondary contouring, but that significant worsening is a low risk. Level 4: Case series Laryngoscope, 2024.

Preliminary validation of the virtual bariatric endoscopic simulator

Background and AimsObesity is a global health concern. Bariatric surgery offers reliably effective and durable weight loss and improvements of other comorbid conditions. However, the accessibility of bariatric surgery remains limited. Minimally invasive techniques, including endoscopic sleeve gastroplasty (ESG), have emerged to bridge this gap. To effectively complete the ESG procedure, one requires skill in multiple complex interventional endoscopic maneuvers. This requisite expertise poses challenges for training in this burgeoning field. MethodsWe designed the Virtual Bariatric Endoscopic (ViBE) simulator software to mimic the ESG procedure accurately. It features a detailed simulation of an endoscope equipped with an endoscopic suturing system and a high-resolution stomach, enhancing the visualization of the procedural details. Furthermore, it incorporates performance metrics utilizing a reverse scoring system to evaluate users’ proficiency in tasks such as argon plasma coagulation (APC) marking, suturing, and cinching. To validate the simulator, we conducted a study involving experts and novices at the Indiana University School of Medicine, where participants engaged with the simulation environment in a series of training tasks. ResultsTwelve participants, comprising five experts and seven novices, participated in the study. They were asked to complete a post-questionnaire featuring seven items, rating each on a Likert scale. The APC task realism received the highest score, averaging 3.83. The usefulness of improving endoscopic technical skills averaged 3.08, with the realism of cinching the knot and suturing tasks receiving scores of 3.17 and 3.25, respectively, suggesting a generally positive reception. Automated performance metrics indicated that, on average, experts outperformed novices by 10.83 points. ConclusionThe ViBE simulation strives to replicate the steps of the ESG within a virtual environment. Our primary objective in developing this simulator is to enhance the learning curve for endoscopic suturing and ESG techniques, thereby safely extending these skills to a broader patient base.

Ten-Year Outcomes in Patients Aged 40 Years and Older After Primary Arthroscopic Treatment of Femoroacetabular Impingement With Labral Repair

Background: Arthroscopic labral repair has been shown to result in favorable short- and midterm outcomes; however, the durability of outcomes specifically in older patients remains underreported. Purpose: To (1) report prospectively collected hip preservation rates and patient-reported outcome measures (PROMs) at a minimum 10-year follow-up in patients aged ≥40 years after primary hip arthroscopy with labral repair and (2) perform a matched analysis comparing patients aged ≥40 years with patients aged <40 years. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed on all patients who underwent primary hip arthroscopy between February 2008 and December 2011. Patients aged ≥40 years who underwent labral repair were included. Preoperative and minimum 10-year follow-up scores were collected for multiple PROMs. Propensity score matching was utilized to compare these patients with a cohort of patients <40 years. Results: Of the 113 hips eligible, 91 hips (80.5%) on 85 patients (6 bilateral) had a minimum 10-year follow-up. There were 58 women (68%) and 27 men (32%) with a mean age and body mass index of 47.8 years and 25.8, respectively. The hip preservation rate for patients aged ≥40 years was 78%, with 20 patients requiring arthroplasty during the study period. There was significant improvement in all PROMs from baseline to minimum 10-year follow-up with high rates of achieving the minimal clinically important difference and Patient Acceptable Symptom State clinical outcome thresholds. In total, 69 patients aged ≥40 years were propensity matched to 107 patients <40 years. Patients ≥40 tended to have a lower hip preservation rate (81.2% vs 91.6%; P = .06), while patients in the younger cohort had significantly higher rates of secondary hip arthroscopy (14% vs 3%; P = .02). Improvement in PROMs was comparable between the groups. Conclusion: Patients ≥40 years who underwent primary hip arthroscopy with labral repair demonstrated a hip preservation rate of 78%, significant and durable improvement in PROMs, and high rates of satisfaction at a minimum 10-year follow-up. Matched analysis with patients <40 years revealed comparable improvement in patient-reported outcomes between the 2 groups, with a tendency to a higher level of arthroplasty in patients ≥40 years.