Role of Non-invasive Ventilation (NIV) in Managing Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review.

Chronic obstructive pulmonary disease (COPD) is a significant global health issue that is characterized by airflow constriction and breathing difficulties. Non-invasive ventilation (NIV) is a recommended treatment for acute exacerbations of COPD (AECOPD), offering benefits over invasive mechanical ventilation (IMV). We aimed to evaluate the effectiveness, safety, and impact of NIV in managing AECOPD. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Medline, Cochrane Library, Embase, and Google Scholar for relevant studies published between 2015 and 2024. Inclusion criteria focused on studies involving AECOPD patients treated with NIV, including randomized controlled, cohort, and observational studies. We included 10 studies that fit our inclusion criteria for a thorough review. From the studies selected, NIV demonstrated significant reductions in mortality rates, intubation rates, and hospital stays compared to IMV. Albeit the need to train healthcare providers is essential, high adherence to NIV guidelines was observed. Different NIV modes showed comparable efficacy, and structured weaning protocols reduced relapse rates. NIV is a highly effective and safe treatment for patients with AECOPD than IMV. High-flow nasal therapy (HFNT) is a viable alternative for patients intolerant to NIV. Further research should standardize treatment protocols and optimize NIV use in clinical practice.

Outcomes of Non-vascularized Fibular Grafts in Proximal Humerus Aneurysmal Bone Cysts.

Introduction This study focuses on the management of primary aneurysmal bone cysts (ABCs) through comprehensive curettage, hydrogen peroxide lavage, and non-vascularized strut fibular grafting. Methods The research encompassed 20 cases, predominantly males (80%), with an average age of 11.35 years. Patient assessment involved thorough history-taking, clinical examinations, and radiological evaluations, including plain radiographs, CT scans, and MRI. The study evaluated healing, bone consolidation, and complications, with patients assessed using the Musculoskeletal Tumor Society (MSTS) upper limb score. Results and discussion The results demonstrated a mean MSTS score of 91.55%, indicating favorable outcomes compared to prior studies. The utilization of non-vascularized autogenous fibular grafts offered effective mechanical stabilization and facilitated an early return to normal function, even prior to complete cavity filling. Our research underscores the efficacy of this treatment approach for primary ABC, particularly in achieving satisfactory functional outcomes. Moreover, the findings contribute to the understanding of optimal management strategies for ABC, considering factors such as patient age, lesion location, vascularity, and size. Conclusion The study advocates for the adoption of thorough curettage, hydrogen peroxide lavage, and non-vascularized strut fibular grafting as a reliable treatment modality for primary ABC. This approach highlights its potential to enhance patient outcomes and functional recovery.

Extensive study of CCN4, VCAM-1, MMP-3, and GM-CSF as reliable markers for disease activity in rheumatoid arthritis.

Background: The involvement of Wnt-1-induced secreted protein-1 (WISP1/CCN4) in several inflammatory reaction has recently been proposed. Nevertheless, this protein's involvement in rheumatoid arthritis (RA) remains debated. Associations between poorly diagnosed RA and several classical markers derived from demography and biochemistry have been reported. Aim: We sought to investigate the reliability and effectiveness of serum concentrations of CCN4, vascular cell adhesion molecule-1 (VCAM-1), matrix melloprotenase-3 (MMP-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in monitoring and predicting RA and bone damage, and their correlation with RA disease course. Methods: The study analyzed 128 patients with RA, comprising 68 newly diagnosed and 60 previously diagnosed patients, as well as 60 controls. Biomarker levels were measured with enzyme linked immuno-sorbent assays. Routine laboratory parameters such as serological, clinical, biochemical, and hematological parameters were additionally measured. Demography, anthropometry, and clinical symptom data were collected through interviews and a questionnaire. The joint disease activity score 28 (DAS28) was used to determine disease activity. Results: Concentrations of four biomarkers were significantly higher in the RA group than the healthy controls. Elevated biomarker concentrations were also observed in patients with high, rather than moderate or low, DAS28-ESR activity status, except for monocyte count, hematocrit (%), and urea level. Furthermore, CCN4 level positively correlated with VCAM-1, MMP-3, and GM-CSF levels, DA-S28-CRP and DAS28-ESR. The levels of three predictive markers, CCN4, VCAM-1, and MMP-3, were elevated in non-treated patients, whereas GM-CSF level showed no difference. The highest area under the curve was 73.3% for CCN4, with 93.3% sensitivity and 64.7% specificity. Conclusion: Our data suggest that CCN4 can be reliably used to indicate activity and therapeutic response associated with RA, thus facilitating earlier RA diagnosis.

Arthroscopic Assessment of the Incidence of Biceps Pulley Lesions Associated With Rotator Cuff Tears: An Observational Study.

The shoulder joint houses a stabilizing structure called the biceps pulley. Biceps pulley lesions can trigger anterior shoulder pain and frequently coincide with rotator cuff tears, whose prevalence rises with age. In our study, we aim to assess the incidence of biceps pulley lesions associated with rotator cuff tears in patients undergoing arthroscopic repair, the possible associated factors, and whether MRI findings were correlated with them. This study was a prospective observational one conducted at Al-Hadra University Hospital. The patients aged 40 to 65 years were indicated for arthroscopic repair of a rotator cuff tear. We used IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. to conduct the analysis. A total of 60 patients were enrolled in the study. The mean age was 50.97 ± 6.90. The overall incidence of biceps pulley lesions was 85%. Older age was found to be significantly associated with increased incidence. On the other hand, gender, and the mode of injury (cuff tear) had no significant associations with the incidence. Also, formal MR had no significance in diagnosing biceps pulley lesions. The overall incidence of biceps pulley lesions in the current study was 85%. The older the patient with a cuff tear, the greater the incidence of finding a pulley lesion arthroscopically. Moreover, MRI did not have a significant role in diagnosing the biceps pulley lesions.

Interventional approaches to treatment resistant depression (DTR) in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent in youth. Conventional treatment paradigms primarily involve selective serotonin reuptake inhibitors (SSRIs) and psychotherapy, yet a significant proportion of this population exhibits treatment-resistant depression (TRD). In adults, interventional therapies like Electroconvulsive Therapy (ECT), repetitive Transcranial Magnetic Stimulation (rTMS), and ketamine have shown promise for TRD, but their comparative efficacy remains underexplored in Adolescent and pediatric population. This systematic review and meta-analysis aims to assess the relative effectiveness of ECT, rTMS, and ketamine in treating TRD among adolescents. METHODS: Following PRISMA guidelines, we systematically searched databases for studies of ECT, rTMS, or ketamine for treatment-resistant depression in youth ages 10-24. Three reviewers independently screened for inclusion based on predefined criteria. Included observational and randomized controlled trials reported depression symptoms with measures like HDRS and MADRS in youth treated with ECT, rTMS, or ketamine. Two reviewers extracted data on interventions, patients, and depression symptom outcomes. Chance-adjusted inter-reviewer agreement was calculated. For meta-analysis, we pooled standardized mean differences (SMDs) in depression scores using random effects models and assessed heterogeneity with I2 statistics. RESULTS: Meta-analysis of 10 observational studies examined SMD in depression scores for treatment resistant depression patients treated with ECT, ketamine, or rTMS. Patients treated with ECT had a significantly lower SMD of 1.99 (95 % CI 0.92-3.05, p < 0.001) compared to baseline. Patients treated with ketamine also had a significantly lower SMD of 1.58 (95 % CI 1.04-2.12, p < 0.001). Patients treated with rTMS had the lowest SMD of 2.79 (95 % CI 0.79-4.80, p = 0.006). There was no significant difference between the three groups overall (p > 0.05). Comparative analysis between ECT and ketamine found no significant difference in SMD (p = 0.387). Comparison of ECT versus rTMS found a significant difference in SMD favoring rTMS (p = 0.004). Comparison of ketamine versus rTMS suggested a potential difference in SMD favoring rTMS (p = 0.058). In summary, rTMS resulted in significantly larger reductions in depression scores than ECT, and potentially larger reductions than ketamine. CONCLUSIONS: This meta-analysis illustrates the ability of rTMS, ECT, and ketamine to improve depression in youth. rTMS resulted in the largest improvements, highlighting its potential as a first-line treatment for pediatric treatment-resistant depression given its favorable side effect profile compared to ECT. Further research directly comparing these modalities is needed.

An unusual presentation of pacifier thumb duplication with VACTERL association: Case report and review of literature.

INTRODUCTION AND IMPORTANCE: Polydactyly of the hand is a common anomaly among pediatrics, which can present in conjugation with other syndromes or on its own. Various types can be seen, ranging from the involvement of skin only to a completely formed digit. We report the first case of pacifier type thumb duplication presenting with VACTERL association. Herein, we also summarize the existing literature of the distinctive features and management of pacifier polydactyly. CASE PRESENTATION: A premature male infant with intrauterine growth restriction due to maternal type II diabetes was referred for a soft tissue attachment to the left hand. The infant showed VACTERL association signs, including a single kidney, small atrial septal defect, and ventricular septal defect. Examination revealed preaxial polydactyly with a cystic swelling connected to the palm. CLINICAL DISCUSSION: Preaxial polydactyly is the second most common congenital hand anomaly, and its pathology is thought to involve the disruption of apoptosis during embryonic development. Pacifier-type polydactyly is a unique variation characterized by severe edema of the soft tissue digit, believed to be caused by physical damage in utero. The case presented did not require surgical intervention as the duplicated thumb underwent spontaneous autoamputation as opposed to other cases in the literature. CONCLUSION: This is the first reported case of pacifier-type thumb duplication in a patient with VACTERL association. The presentation of this condition adds to the existing body of literature on VACTERL association. Surgical removal is the treatment of choice for pacifier polydactyly, but spontaneous resolution can occur.

An Investigation on the Potential of Utilizing Aluminum Alloys in the Production and Storage of Hydrogen Gas.

The interest in hydrogen is rapidly expanding because of rising greenhouse gas emissions and the depletion of fossil resources. The current work focuses on employing affordable Al alloys for hydrogen production and storage to identify the most efficient alloy that performs best in each situation. In the first part of this work, hydrogen was generated from water electrolysis. The Al alloys that are being examined as electrodes in a water electrolyzer are 1050-T0, 5052-T0, 6061-T0, 6061-T6, 7075-T0, 7075-T6, and 7075-T7. The flow rate of hydrogen produced, energy consumption, and electrolyzer efficiency were measured at a constant voltage of 9 volts to identify the Al alloy that produces a greater hydrogen flow rate at higher process efficiency. The influence of the electrode surface area and water electrolysis temperature were also studied. The second part of this study examines these Al alloys' resistance to hydrogen embrittlement for applications involving compressed hydrogen gas storage, whether they are utilized as the primary vessel in Type 1 pressure vessels or as liners in Type 2 or Type 3 pressure vessels. Al alloys underwent electrochemical charging by hydrogen and Charpy impact testing, after which a scanning electron microscope (SEM) was used to investigate the fracture surfaces of both uncharged and H-charged specimens. The structural constituents of the studied alloys were examined using X-ray diffraction analysis and were correlated to the alloys' performance. Sensitivity analysis revealed that the water electrolysis temperature, electrode surface area, and electrode material type ranked from the highest to lowest in terms of their influence on improving the efficiency of the hydrogen production process. The 6061-T0 Al alloy demonstrated the best performance in both hydrogen production and storage applications at a reasonable material cost.

Treatment Outcomes in Vertical Shear Pelvic Fractures: A Comparative Study.

Background Vertical shear (VS) pelvic ring injuries present a unique challenge due to their inherent vertical and rotational instability and the risk of massive bleeding. VS injuries may result from either bony or ligamentous injury. The goal in the treatment of VS fractures of the pelvis is to achieve and maintain an accurate reduction of the displaced hemipelvis. Aim of the study This study aimed to compare the results of the treatment of VS fractures pelvis by using iliosacral (IS) screws versus lumbopelvic fixation (LPF). Methodology This retrospective study was carried out on 40 patients with VS fracture pelvis injuries at El Hadara University Hospital, Alexandria, Egypt, from January 2020 to December 2020. Twenty of them were treated by an IS screw, and the other 20 were treated by LPF. Then, both groups were followed up for six months with regard to union rate, metal failure, and clinical outcomes. Results The EQ-5D showed a significant improvement in LPF more than the IS screw group in the five items of the score. Moreover, the total EQ-5D index showed a significant increase in the LPF group more than the IS screw group (p < 0.05). The incidence of neurological complication was found in four cases in the IS screw group, while no cases were found in the LPF group. The infection was found in six patients in the IS screw group and only three cases in the LPF group. The malunion was found in two cases in the IS screw group and no cases in the LPF group. The neurological change and the incidence of infection were significantly higher in the IS screw group than in the LPF group (p < 0.05). Conclusion Our results demonstrate reliable maintenance of reduction and acceptable complication rates with a minimally invasive LPF for VS fractured pelvis. The benefits of minimally invasive LPF may be offset by increased elective reoperations for the removal of instrumentation.

Pattern of Cleft Lip and Palate Clefts at a Tertiary Care Hospital in Saudi Arabia.

BACKGROUND: Clefts of the lip and palate (CL/P) and cleft palate (CP) are the most common craniofacial congenital anomalies. Clefts are classified as syndromic and nonsyndromic. Nonsyndromic clefts have no known genetic causes. OBJECTIVES: This study combines prospective and retrospective studies to review the patterns of CL/P and CP and associated syndromes and conditions in patients registered for CL/P surgery at a tertiary care pediatric center in our tertiary care hospital in Saudi Arabia. METHODS: It included patient data from May 2015 through April 2023. Patient record forms and SPSS (IBM version 20.0) were used to collect and analyze data. A significance level of 5% was used, with p ≤ 0.05 considered statistically significant. RESULTS: Of the 319 patients who met our inclusion criteria, 175 were male. Of the total, 99 had a left unilateral isolated cleft lip, 61 had a right unilateral isolated cleft lip, 69 had a bilateral cleft lip, and 90 had an isolated CP. Of the total, 140 had CL/P. Around 242 were nonsyndromic. The Chi-square test revealed a significant association between the prevalence of isolated CP and CLP and gender. The prevalence of left unilateral isolated cleft lip and bilateral and isolated CP was significantly associated with syndromic and nonsyndromic cases. CONCLUSION: Males are more likely to be affected by orofacial clefts, which is consistent with the global trend. Isolated CP was the most common orofacial cleft. Within the sample, syndromes' association with orofacial clefts was significantly weaker than that of isolated and bilateral clefts.

A Comparison of the Results of Platelet-Rich Plasma Injection Versus the Results of Corticosteroid Injections in De-Quervain Tenosynovitis.

BACKGROUND:  De Quervain tenosynovitis (DQT) is a condition that affects the first extensor compartment of the wrist, resulting in stenosing tenosynovitis. This work aimed to evaluate the effects of platelet-rich plasma (PRP) injection in the treatment of DQT in comparison with corticosteroid (CS) injections. METHODS:  This study was carried out on 40 DQT patients aged above 18 years old of both sexes, based on a combination of clinical symptoms and signs including persistent tenderness on the radial styloid, swelling on the radial styloid, positive provocative tests such as the Finkelstein test, and patients with failed medical treatment. Patients were divided into two equal groups: group I and group II. Group I was injected with PRP, and group II was injected with CS. Follow-ups were conducted at two weeks and six months. RESULTS:  There were statistically significant differences among both groups regarding the visual analog scale (VAS), and Disabilities of Arm, Shoulder, and Hand (QuickDASH-9) score. However, complications were statistically insignificant between both groups. After injection, CS was better than PRP after two weeks, but PRP was superior to CS after six months concerning QuickDASH-9 and VAS. These differences were statistically significant. CONCLUSIONS:  CS is more effective than PRP in the short term (two weeks) and PRP is more effective in the intermediate term (six months). Both modalities are safe; however, PRP is relatively safer than CS.

Value of Optic Nerve MRI in Multiple Sclerosis Clinical Management: A MAGNIMS Position Paper and Future Perspectives.

The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS. In this article, evidence related to these 3 aspects will be summarized and gaps in knowledge will be highlighted, including (1) the acquisition challenges and novel sequences that assess pathologic changes within the anterior visual pathways; (2) the clinical implications of quantitative magnetic resonance studies of the optic nerve, focusing on atrophy measures, magnetization transfer, and diffusion tensor imaging; and (3) the relevant clinical studies performed to date. Finally, an algorithm for the application of optic nerve MRI will be proposed to guide future studies aimed at addressing our knowledge gaps.

Improving criteria for dissemination in space in multiple sclerosis by including additional regions.

OBJECTIVE: We investigated the effects of adding regions to current dissemination in space (DIS) criteria for multiple sclerosis (MS). METHODS: Participants underwent brain, optic nerve, and spinal cord MRI. Baseline DIS was assessed by 2017 McDonald criteria and versions including optic nerve, temporal lobe, or corpus callosum as a fifth region (requiring 2/5), a version with all regions (requiring 3/7) and optic nerve variations requiring 3/5 and 4/5 regions. Performance was evaluated against MS diagnosis (2017 McDonald criteria) during follow-up. RESULTS: Eighty-four participants were recruited (53F, 32.8 ± 7.1 years). 2017 McDonald DIS criteria were 87% sensitive (95% CI: 76-94), 73% specific (50-89), and 83% accurate (74-91) in identifying MS. Modified criteria with optic nerve improved sensitivity to 98% (91-100), with specificity 33% (13-59) and accuracy 84% (74-91). Criteria including temporal lobe showed sensitivity 94% (84-98), specificity 50% (28-72), and accuracy 82% (72-90); criteria including corpus callosum showed sensitivity 90% (80-96), specificity 68% (45-86), and accuracy 85% (75-91). Criteria adding all three regions (3/7 required) had sensitivity 95% (87-99), specificity 55% (32-76), and accuracy 85% (75-91). When requiring 3/5 regions (optic nerve as the fifth), sensitivity was 82% (70-91), specificity 77% (55-92), and accuracy 81% (71-89); with 4/5 regions, sensitivity was 56% (43-69), specificity 95% (77-100), and accuracy 67% (56-77). INTERPRETATION: Optic nerve inclusion increased sensitivity while lowering specificity. Increasing required regions in optic nerve criteria increased specificity and decreased sensitivity. Results suggest considering the optic nerve for DIS. An option of 3/5 or 4/5 regions preserved specificity, and criteria adding all three regions had highest accuracy.

The effect of preoperative hormonal stimulation on the urethral plate; A histologic and histochemical study.

AIM OF THE WORK: Preoperative hormone stimulation (PHS) is used to increase the glans size and may improve the cosmetic appearance after hypospadias surgery. The exact effect of PHS on different penile tissues remains unclear and controversial. Previous studies showed that PHS increased vessel density in the foreskin. However, the effect of PHS on the urethral has never been studied before. In this study we examine the PHS effects on the urethral plate. MATERIALS AND METHODS: Specimens of the urethral plate and the underlying tissue were excised to correct severe chordee in 16 children with proximal and perineal hypospadias with severe chordee in 2 groups. Group A consisted of 8 children received PHS prior to surgery. Group B included 8 children with proximal and perineal hypospadias with severe chordee who did not receive PHS and served as a control group. Specimens were examined blindly using hematoxylin-eosin and elastic van-Gieson stain as well as factor 8 and SMA antibodies. RESULTS: The median age of Group A was 13 (range 10-20) months. The median age of Group B (without prior PHS) was 17 (range 14-29) months (p = 0,03). The median vessel-density in group A (82 vessels per mm2) was significantly higher than in Group B (65 per mm2), (p < 0.05). The median vessel diameter was also significantly higher in Group A (13 µm) than in Group B (11 µm), (p < 0.05). The median epithelial layer thickness in Group A was 110 µm and in Group B 98 µm, but showed no statistical significance (p = 0,16). There was no significant change in dartos fascia layer thickness or androgen receptor expression. There was no visual change in the organization of elastic fibers. CONCLUSION: This study is the first study to document the effect of PHS on the urethral plate in hypospadias with severe chordee. PHS significantly increased the median vessel-density as well as median vessel diameter as compared to a matching control group. The findings of the study may justify PHS administration before the first operation to improve the vascularity and may reduce the severity of chordee.

Prevalence of Gastroesophageal Reflux Disease and Its Impact on the Quality of Life Among Obese Individuals in Al-Baha Region, Saudi Arabia.

Background Gastroesophageal reflux disease (GERD) is a global gastrointestinal disorder, and obesity is a particular risk factor. Symptoms of GERD, such as heartburn and acid reflux, are caused by abnormal relaxation in the lower esophagus, causing gastric acid reflux. Persistent symptoms can affect the patient's quality of life (QOL) and can cause complications, such as esophageal adenocarcinoma. Management of GERD includes lifestyle changes, antacids, and anti-reflux surgery. Even though GERD is a common disease, few research has been carried out on it in Saudi Arabia. Aim This study aimed to estimate the prevalence of GERD and its associated risk factors among obese individuals in the Al-Baha region population and the effect of GERD on their QOL. Methods A cross-sectional study included 314 obese participants from the Al-Baha region. A questionnaire was filled out to measure the prevalence of GERD, risk factors, and effects on the QOL of the participants. Data were analyzed by the IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Descriptive statistics and the chi-squared test were applied. Logistic regression analysis was used to determine the factors associated with the incidence of GERD. A p-value of <0.05 was considered statistically significant. Results A total of 314 patients who met our inclusion criteria completed the survey; 42% of them were women, the mean age of all patients was 35.3 ± 12.9 years, and 38.2% of the patients were diagnosed with GERD. Epigastric pain and burning sensation were the most common symptoms (44.9%). Five out of six domains in the QOL questionnaire showed more effects among GERD participants than non-GERD participants, and the results were statistically significant (p = 0.001). Logistic regression analysis showed that men are 1.8 times more likely than women to be diagnosed with GERD, and smokers have 2.6 times the risk of being diagnosed with GERD than non-smokers. Conclusion The present study showed a high prevalence of GERD among obese patients in the Al-Baha region, negatively affecting their QOL. Major risk factors included gender, smoking, dyslipidemia, and hypertension. Public health programs to raise awareness of these risk factors and lifestyle habits are necessary to improve QOL and prevent complications.

Validation of the 2023 International Diagnostic Criteria for MOGAD in a Selected Cohort of Adults and Children.

BACKGROUND AND OBJECTIVES: To test the performance of the 2023 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) criteria in adults and children with inflammatory demyelinating conditions who were tested for MOG antibodies (Abs). METHODS: This was a retrospective study of patients tested for MOG-Abs from 2018 to 2022 in 2 specialist hospitals. The inclusion criteria comprised ≥1 attendance in an adult or pediatric demyelinating disease clinic and complete clinical and MRI records. The final clinical diagnosis of MOGAD, made by the treating neurologist, was taken as the benchmark against which the new criteria were tested. The international MOGAD diagnostic criteria were applied retrospectively; they stipulate at least 1 clinical or MRI supporting feature for MOGAD diagnosis in positive fixed MOG cell-based assay without a titer. The performance MOG-Ab testing alone for MOGAD diagnosis was also assessed and compared with that of MOGAD criteria using the McNemar test. RESULTS: Of the 1,879 patients tested for MOG-Abs, 539 (135 pediatric and 404 adults) met the inclusion criteria. A clinical diagnosis of MOGAD was made in 86/539 (16%) patients (37 adults, 49 children), with a median follow-up of 3.6 years. The MOGAD diagnostic criteria had sensitivity of 96.5% (adults 91.9%, children 100%), specificity of 98.9% (adults 98.8%, children 98.9%), positive predictive value of 94.3% (adults 89.4%, children 98%), negative predictive value of 99.3% (adults 99.2%, children 100%), and accuracy of 98.5% (adults 98.3%, children 99.2%). When compared with MOG-Ab testing alone, a difference was seen only in adults: a significantly higher specificity (98.9% vs 95.6%, p = 0.0005) and nonstatistically significant lower sensitivity (91.9% vs 100%, p = 0.08). DISCUSSION: The international MOGAD diagnostic criteria exhibit high performance in selected patients with inflammatory demyelinating diseases (who had a high pretest probability of having MOGAD) compared with best clinical judgment; their performance was better in children than in adults. In adults, the MOGAD criteria led to an improvement in specificity and positive predictive value when compared with MOG-Ab testing alone, suggesting that the requirement of at least 1 clinical or MRI supporting feature is important. Future work should address the generalizability of the diagnostic criteria to cohorts of greater clinical diversity seen within neurologic settings.

Using the Progression Independent of Relapse Activity Framework to Unveil the Pathobiological Foundations of Multiple Sclerosis.

Progression independent of relapse activity (PIRA), a recent concept to formalize disability accrual in multiple sclerosis (MS) independent of relapses, has gained popularity as a potential clinical trial outcome. We discuss its shortcomings and appraise the challenges of implementing it in clinical settings, experimental trials, and research. The current definition of PIRA assumes that acute inflammation, which can manifest as a relapse, and neurodegeneration, manifesting as progressive disability accrual, can be disentangled by introducing specific time windows between the onset of relapses and the observed increase in disability. The term PIRMA (progression independent of relapse and MRI activity) was recently introduced to indicate disability accrual in the absence of both clinical relapses and new brain and spinal cord MRI lesions. Assessing PIRMA in clinical practice is highly challenging because it necessitates frequent clinical assessments and brain and spinal cord MRI scans. PIRA is commonly assessed using Expanded Disability Status Scale, a scale heavily weighted toward motor disability, whereas a more granular assessment of disability deterioration, including cognitive decline, using composite measures or other tools, such as digital tools, would possess greater utility. Similarly, using PIRA as an outcome measure in randomized clinical trials is also challenging and requires methodological considerations. The underpinning pathobiology of disability accumulation, that is not associated with relapses, may encompass chronic active lesions (slowly expanding lesions and paramagnetic rim lesions), cortical lesions, brain and spinal cord atrophy, particularly in the gray matter, diffuse and focal microglial activation, persistent leptomeningeal enhancement, and white matter tract damage. We propose to use PIRA to understand the main determinant of disability accrual in observational, cohort studies, where regular MRI scans are not included, and introduce the term of "advanced-PIRMA" to investigate the contributions to disability accrual of the abovementioned processes, using conventional and advanced imaging. This is supported by the knowledge that MRI reflects the MS pathogenic mechanisms better than purely clinical descriptors. Any residual disability accrual, which remains unexplained after considering all these mechanisms with imaging, will highlight future research priorities to help complete our understanding of MS pathogenesis.