Citations

Objective: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary rectal cancer (LARC) and locally recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. Background: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. Methods: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. Results: Seven hundred sixty-three patients underwent PE, of which 464 patients (61%) had LARCs and 299 (39%) had LRRCs. Five hundred forty-four patients (71%) who met predefined lower-risk criteria formed the benchmark cohort. For patients with LARC, the calculated benchmark threshold for major complication rate was ≤44%; Comprehensive Complication Index: ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For patients with LRRC, the calculated benchmark threshold for major complication rate was ≤53%; Comprehensive Complication Index: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. Conclusions: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

AbstractBackgroundDespite the overall safety and efficacy of COVID‐19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post‐vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post‐vaccination.MethodsA cross‐sectional study was conducted among participants with self‐reported new‐onset SAIDs using the COVID‐19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset—a validated, patient‐reported e‐survey—to analyze the long‐term safety of COVID‐19 vaccines. Baseline characteristics of patients with new‐onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.ResultsOf 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new‐onset SAID post‐vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new‐onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9–9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3–5.3; p = .004). New‐onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1–1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3–1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2–4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4–0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.ConclusionThis study reports a low occurrence of new‐onset SAIDs following COVID‐19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre‐existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID‐19 vaccination in the general population. However, long‐term studies are needed to understand the autoimmune phenomena arising post‐vaccination.

Abstract Introduction Skull base neuroanatomy is traditionally learned through two-dimensional anatomical atlases, which while are of unquestionable value, lack the nuanced association of three-dimensional relationships between fundamental anatomical structures relevant to surgical approaches. Surgically focused step-by-step anatomical dissections can augment trainee learning of complex skull base techniques, particularly multistep and nuanced techniques such as translabyrinthine and transcochlear approaches. Methods Translabyrinthine and transcochlear approaches were performed on six sides of three formalin-fixed latex-injected specimens. The study objective was the completion and photo documentation of the steps involved in the approach in order to provide a comprehensive, intelligible, and anatomically oriented resource for multilevel trainees. Illustrative case examples were prepared to supplement approach dissections. Results The translabyrinthine and transcochlear approaches offer unique lateral windows through the temporal bone into the posterior fossa, providing excellent access to pathology at the petrous apex, internal auditory canal, Meckel's cave, and anterolateral brainstem. The transcochlear approach, which is an anterior extension of the translabyrinthine, particularly provides excellent exposure of the prepontine region and clivus. Important surgical considerations include patient position, temporal bone drilling and identification of critical landmarks, dural opening and identification of neurovascular structures, and reconstruction/closure techniques. Conclusion The translabyrinthine and transcochlear approaches are fundamental techniques for lateral skull base and posterior fossa pathologies. Both approaches are hearing-sacrificing but often require minimal to no cerebellar retraction and deliver unique visualization of prepontine neurovascular structures. This step-by-step approach guide provides a unique practical and high-yield surgically oriented learning resource for neurosurgery and otolaryngology trainees.

Abstract Background Despite advances in medical therapy, many children and adults with ileal Crohn’s disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. Methods This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Results Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). Conclusion After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.

Background: Restoration of hand function after traumatic brachial plexus injury (BPI) remains a formidable challenge. Traditional methods such as nerve or free muscle transfers yield suboptimal results. Advancements in myoelectric prostheses, characterized by novel signal acquisition and improved material technology, show promise in restoring functional grasp. This study evaluated the ability of adults with a BPI injury to control an externally powered prosthetic hand using nonintuitive signals, simulating the restoration of grasp with a myoelectric prosthesis. It also assessed the effectiveness of a comprehensive multidisciplinary evaluation in guiding treatment decisions. Methods: A multidisciplinary brachial plexus team assessed adults with compromised hand function due to BPI. The feasibility of amputation coupled with fitting of a myoelectric prosthesis for grasp reconstruction was evaluated. Participants' ability to control a virtual or model prosthetic hand using surface electromyography (EMG) as well as with contralateral shoulder motion-activated linear transducer signals was tested. The patient’s input and injury type, along with the information from the prosthetic evaluation, were used to determine the reconstructive plan. The study also reviewed the number of participants opting for amputation and a myoelectric prosthetic hand for grasp restoration, and a follow-up survey was conducted to assess the impact of the initial evaluation on decision-making. Results: Of 58 subjects evaluated, 47 (81%) had pan-plexus BPI and 42 (72%) received their initial assessment within 1 year post-injury. Forty-seven patients (81%) could control the virtual or model prosthetic hand using nonintuitive surface EMG signals, and all 58 could control it with contralateral uniscapular motion via a linear transducer and harness. Thirty patients (52%) chose and pursued amputation, and 20 (34%) actively used a myoelectric prosthesis for grasp. The initial evaluation was informative and beneficial for the majority of the patients, especially in demonstrating the functionality of the myoelectric prosthesis. Conclusions: The study indicates that adults with traumatic BPI can effectively operate a virtual or model myoelectric prosthesis using nonintuitive control signals. The simulation and multidisciplinary evaluation influenced informed treatment choices, with a high percentage of patients continuing to use the myoelectric prostheses post-amputation, highlighting its long-term acceptance and viability. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AbstractIntroductionAlthough prior studies indicate that a QTc > 500 ms on a single baseline 12‐lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS.MethodsWe performed a retrospective analysis of 433 patients with LQTS evaluated, risk‐stratified, and undergoing active guideline‐based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF‐terminating ICD shock, and sudden cardiac death (SCD).ResultsDuring the median follow‐up of 5.5 years (interquartile range [IQR] = 3–9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c‐statistic = 0.93–0.95). Patients in the high‐risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%–81%) when compared to patients in both medium‐risk (93%–97%) and low‐risk (98%–99%) groups.ConclusionsThe risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12‐lead ECGs are at the highest risk of BCE while on guideline‐directed medical therapy.

Abstract Background Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments. Objectives To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids. Methods PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator’s Global Assessment (IGA) score ≤ 2 at week 16. Results Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3–57.2] vs. 23.1% (95% Crl 6.5–49.2)} and LPP cohorts [37.5% (95% Crl 20.2–57.3) vs. 30.8% (95% Crl 10.8–57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. Conclusions PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.

AbstractBackgroundThe pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy.ObjectivesThe COVID‐19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self‐reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown.MethodsLeveraging social media as a research tool, COVAD collected data using validated patient‐reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot‐tested, validated survey, featuring questions regarding COVID‐19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs).DiscussionWe present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them.ConclusionCollaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large‐scale, patient‐focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.