Citations

Multiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study. An international consensus process was conducted using validated Delphi methodology in line with British Journal of Sports Medicine guidelines. A multidisciplinary panel of 39 members from 14 countries, completed 3 rounds of online surveys exploring aspects of nomenclature, diagnosis, treatment, rehabilitation and future research priorities. Levels of agreement (LoA) with each statement were rated anonymously on a 5-point Likert scale, with experts encouraged to suggest modifications or additional statements. LoA for consensus in the final round were defined ‘a priori’ if >75% of respondents agreed and fewer than 10% disagreed, and dissenting viewpoints were recorded and discussed. After three Delphi rounds, 50 items (92.6%) reached consensus. Key statements that reached consensus within nomenclature included a clear definition for MLKI (LoA 97.4%) and the need for an updated MLKI classification system that classifies injury mechanism, extent of non-ligamentous structures injured and the presence or absence of dislocation. Within diagnosis, consensus was reached that there should be a low threshold for assessment with CT angiography for MLKI within a high-energy context and for certain injury patterns including bicruciate and PLC injuries (LoA 89.7%). The value of stress radiography or intraoperative fluoroscopy also reached consensus (LoA 89.7%). Within treatment, it was generally agreed that existing literature generally favours operative management of MLKI, particularly for young patients (LoA 100%), and that single-stage surgery should be performed whenever possible (LoA 92.3%). This consensus statement will facilitate clinical communication in MLKI, the care of these patients and future research within MLKI.

Abstract Background GERD is a common cause of chronic cough. Although barrier therapy with laparoscopic fundoplication is highly effective for typical GERD symptoms, the response rates are variable for chronic cough. We hypothesized that transoral incisionless fundoplication (TIF) or TIF with hiatal hernia repair (cTIF) may be a suitable alternative for medically refractory cough associated with GERD. Aim We prospectively s studied the effectiveness and safety of TIF/cTIF in patients with chronic cough and proven GERD. Methods Patients with GERD and extra-esophageal symptoms from 10 academic and community medical centers (TIF Registry), elevated GERD-HRQL score +/- Reflux Symptom Index (RSI) >13 and pathologic reflux by esophageal pH-metry, or erosive esophagitis/Barrett’s esophagus were evaluated before and after a minimum 6 months post TIF/cTIF performed by gastroenterologists and surgeons. Patients with history of prior foregut/bariatric surgery, chronic obstructive or interstitial lung disease, or prior lung transplant were excluded. The primary outcome was improvement in RSI score at last follow-up compared to baseline. Secondary outcomes were: 1) normalization of RSI (<13), 2) improvement in cough sub-scores of RSI (decrease ≥ 2 points or to 0 on a 5-point scale), 3) GERD symptom improvement (>50% decrease in GERD-HRQL, or < 2 in all sub-scores) 4) discontinuation of proton pump inhibitor (PPI), and 5) overall patient satisfaction. We further analyzed response in patients with cough-predominant phenotype (chief complaint of cough and RSI troublesome cough subscore ≥2). Results 198 patients with cough and GERD successfully underwent TIF/cTIF (Table 1) without serious adverse events. Greater than 6-month follow-up was available for 177 patients at a median of 12 months [IQR 6,12]. Median RSI score decreased from 18 [IQR 13, 27] to 5 [IQR 2, 11] (p < 0.0001), median change 11 [IQR5,11]. 83% of patients with elevated baseline RSI normalized their scores. 75% of patients had improvement of cough when lying down (median: 1 point [IQR 0,3]), and 72% of patients had improvement of troublesome cough (median: 1 point [IQR 1,3]). 83% of patients successfully discontinued or decreased PPI to occasional use. Patient satisfaction improved from a baseline of 5.6% to 68.8% (p <0.0001). Compared to patients without cough-predominant symptoms, cough-predominant patients (n=108) experienced an additional 4.2-point decrease in in RSI score (p = 0.01) and 1.5-point decrease in troublesome cough sub-scores (p<0.0001). Patients with regurgitation phenotype were more likely to have a favorable cough response at 6 months (p<0.0001). In appropriately selected patients, cTIF and TIF were comparable for cough, GERD-HRQL, RSI, and PPI responses. Conclusion TIF/cTIF are effective and safe alternative barrier therapies for patients with pH-positive cough-predominant GERD.

Abstract Background New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS). Methods Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2). Results There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit. Conclusions The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay.

Abstract Objective To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications. Background Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial‐and‐error approach is inefficient. Methods In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow‐up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta‐blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre‐trained a deep neural network, “TabNet,” using 145 variables, then employed TabNet‐embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non‐responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held‐out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance. Results Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta‐blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta‐blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin. Conclusion We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine‐specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible.

Arthroplasty of the proximal interphalangeal joint (PIPJ) has evolved since its inception over 60 years ago. This review examines the indications for surgery, highlights the differences in current arthroplasty designs, variances in surgical techniques, clinical controversies, current implant outcomes data and salvage options for the failed implant. Overall, PIPJ implant arthroplasty is a good and reliable option for symptomatic PIPJ degenerative, post-traumatic or inflammatory arthritis given the proper clinical setting. If current techniques for implantation and rehabilitation are followed, predictable pain relief and satisfactory function can be anticipated. The purpose of this review article is to examine the current evidence-based indications for PIPJ arthroplasty and examine the reported, implant-specific outcomes of this procedure. Various techniques and rehabilitation strategies will also be outlined.

Abstract Purpose: Early detection of neurofibromatosis type 1 (NF1)–associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. Experimental Design: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. Results: The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration–based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Conclusions: Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.

Abstract Transition services—programs that support adolescents and young adults (AYAs) as they move from a child‐centered to a more autonomous, adult‐orientated healthcare system—have been associated with improved short‐ and long‐term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders. The AYAs addressed herein are those who have: (a) a ROME positive disorder of gut–brain interaction (DGBI), (b) a primary or secondary motility disorder (including those with motility disorders that have been surgically managed), or (c) an artificial feeding requirement (parenteral or enteral tube feeding) to manage malnutrition secondary to categories (a) or (b). The issues explored in this position paper include the specific physical and psychological healthcare needs of patients with NGM disorders; key healthcare professionals who should form part of a secondary care NGM transition service; the triadic relationship between healthcare professionals, caregivers, and patients; approaches to selecting patients who may benefit most from transition care; methods to assess transition readiness; and strategies with which to facilitate transfer of care between healthcare professionals. Key areas for future research are also addressed, including the construction of NGM‐specific transition readiness questionnaires, tools to assess post‐transfer healthcare outcomes, and educational programs to train healthcare professionals about transition care in NGM.

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN‐dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN‐predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN‐predominant MND. We reviewed 24 patients with UMN‐predominant MND with TDP‐43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically‐confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically‐confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN‐predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN‐predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN‐predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN‐predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met.