A scoring-based clinical grading model for xanthelasma palpebrarum: predicting treatment frequency and prognosis.

Xanthelasma palpebrarum is one of the most common cutaneous xanthomas in humans. Currently, there are various methods available for treating xanthelasma palpebrarum, but the high treatment frequency and recurrence rate remain significant challenges for patients. Therefore, it is necessary to establish a reasonable and effective clinical grading system to guide the diagnosis and treatment of xanthelasma palpebrarum. We developed a clinical scoring system related to local injection of pingyangmycin for the treatment of xanthelasma palpebrarum, which can be used to predict early prognosis and treatment outcomes in patients. We collected and retrospectively studied 246 outpatient cases of xanthelasma palpebrarum treated with local injection of pingyangmycin in the Department of Plastic Surgery at Shanghai East Hospital from February 2020 to August 2022. Potential independent risk factors for adverse outcomes (recurrence or non-recurrence) were considered in univariate and multivariate logistic regression models. Predictive factors were determined based on the multivariate logistic regression model and Cox model, and a scoring grading system was established. External validation was conducted on an independent cohort of 110 patients. Based on logistic regression analysis, the number, area, and color of lesions were identified as significant predictive indicators (P < 0.05), with respective AUCs of 0.710, 0.799, and 0.755. The Cox model established hazard ratios for four new severity indicators of xanthelasma palpebrarum: hyperlipidemia, number of lesions, lesion area, and lesion grayscale value. Based on these findings, a new clinical grading model was developed, which was validated to be effective in the external cohort. The new scoring-based clinical predictive model can effectively predict the number of pingyangmycin injection treatments and prognosis in patients with xanthelasma palpebrarum. It holds promise for broader application in clinical practice.

Anticoagulant Impact on Clinical Outcomes of Pulmonary Embolism Compared With Thrombolytic Therapy; Meta-Analysis.

BACKGROUND: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. OBJECTIVES: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. METHOD: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. RESULTS: For sub-massive PE, CDT plus AC significantly reduced in-hospital, 30-day, and 12-month mortality compared to AC alone, odds ratio (OR) of -0.99 (95% CI [-1.32 to -0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [-0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all-cause or in-hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. CONCLUSION: The addition of CDT to AC improves mortality outcomes for sub-massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies.

Influence of Dietary Heritage in a Restricted Geographic Area and Role of Food Additives on Risk of Recurrent Kidney Stone.

Dietary factors may be implicated in the formation of kidney stones and should be closely monitored. To achieve this aim, patients are routinely assessed by means of generic dietary recall, a tool widely used by authors in a range of extensive patient populations to record food intake; the findings obtained, however, may be skewed due to dietary variations and underestimation of the effect of food additives. Fifty Frequent Kidney Stone Formers (FKSFs, mean age: 54.3 ± 13.9 years) with normal kidney function, absence of comorbidities, and reliable compliance were selected from a total of 68 patients' resident in Sardinia, an Italian island where genetic admixtures have been relatively rare for generations. The study, conducted from 1 January 2020 to 31 December 2023, was aimed at assessing nutritional values based on the meticulous recording of food quantities, quality, and potential modifications related to food preparation. Patients were selected during an initial clinical check-up and all efforts made to ensure they were capable of reliably recording all food and drinks consumed. A seven-day food diary was provided in which food and drink intake and their impact on 24 h urine output was recorded. The following parameters were measured in both foods and urine output: citrates, oxalates, calcium, phosphorous, uric acid, proteins and nitrogen compounds, magnesium, sulfates, potassium, carbohydrates, free fatty acids. Study outcomes established the presence of hypocitraturia, hyperoxaluria, hypercalciuria, and moderately high levels of nitrogen compounds. Univariate analysis followed by multivariate analysis for further confirmation were performed and the following observations made. Citrate intake correlated with citraturia but did not promote oxaluria; calcium intake promoted onset of sulfaturia, azoturia, and ammoniuria, whilst magnesium correlated with magnesiuria but not with oxaluria, calciuria, phosphaturia, and azoturia; sulfate intake elicited onset of azoturia but not kaliuresis; potassium intake promoted oxaluria and protein intake resulted in onset of ammoniuria and azoturia. (A) The chemical composition of urine based on dietary intake is hard to predict without taking into account the presence of dietary and urinary interferents; (B) the geographic isolation of patients studied underlines the importance of epigenetics in maintaining a traditional dietary heritage. (C) Moreover, the widespread use of food additives should consistently be taken into account to ensure a correct diagnosis of FKSF and set up a valid treatment plan.

Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin.

OBJECTIVE: Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT. METHODS AND ANALYSIS: A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed. RESULTS: The patients experienced 2-7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4+CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA-CCR7- T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes. CONCLUSION: Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.

Development and evaluation of fermented milk with Lactobacillus acidophilus added to concentrated cranberry (Vaccinium macrocarpon) juice with the potential to minimize the recurrence of urinary tract infections.

Repeated urinary tract infections affect many people worldwide. A potential strategy to reduce the incidence of these infections is to consume probiotics and cranberry fruit regularly. In this context, this study aims to prepare fermented milk with Lactobacillus acidophilus La-5 added with concentrated cranberry juice in two concentrations (5 and 10 %, corresponding to C1 and C2 samples, respectively) and evaluate different technological aspects of the samples after production and during storage, and comparing with the control sample (C). The juice had pH 1.91, 70.09 % of solids, and total proanthocyanidins and A-type proanthocyanidins (PACs) values of 117.03 mg/100 g and 16.38 mg/100 g, respectively. The higher the juice content added to the product, the higher the acidity (1.4 and 2.6 g of lactic acid in 100 g, corresponding to C1 and C2 on day 1 (D1), respectively), the total proanthocyanidin content (1.96 and 4.01 mg/100 g on D1; and 1.31 and 3.05 mg/100 g on day 28 of storage (D28), corresponding to C1 and C2, respectively) and A-type proanthocyanidin (0.56 and 1.26 mg/100 g in Day 1; and 0.54 and 1.19 mg/100 g in D28, corresponding to C1 and C2, respectively), higher the values of the color parameters (L*a* and C*), and lower pH value, probiotic viability, and sensory acceptance. Furthermore, the rheological parameters demonstrated a stronger protein network due to the addition of cranberry. The new formulations, including samples C1 and C2, are alternatives as functional products, which regular consumption probably has the potential to minimize the recurrence of urinary tract infections.

Endoscopic Management of Weight Regain After Bariatric Surgery.

Weight regain, also known as recurrent weight gain, is common following bariatric surgeries. While anti-obesity medications and surgical revisions offer effective treatment options, they are not without their challenges and limitations. Over the last few decades, there have been significant advancements in endoscopic interventions to address weight regain following bariatric surgery. These procedures have demonstrated feasibility, safety, efficacy, and durability, offering minimally invasive treatment options for this patient population.

Ligation of intersphincteric fistula tract: A retrospective, single centre, individual surgeons' experience for the management of complex fistula in ano.

Objectives: To identify early treatment outcomes among patients having undergone ligation of intersphincteric fistula tract for complex fistula-in-ano in a tertiary care setting. METHODS: The single-centre retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2016 to January 2021 of adult complex fistula-in-ano patients who underwent ligation of intersphincteric fistula tract procedure. All surgeries were done by a single surgeon. Pre- and post-operative Wexner continence scores were measured, and various factors, including change in continence, complete wound healing, postoperative infection and recurrence, were assessed. Data was analysed using SPSS 23. RESULTS: Of the 20 patients, 15(75%) were females and 5(25.0%) were males. The overall mean age was 38.4±13.8 years. The median duration of surgery was 65 minutes (interquartile range: 57-99 minutes). There were 2(10%) patients who showed a change in continence after surgery to flatus alone. Complete healing was noted in 11(55%) patients. Recurrence was noted in 8(40%) patients; trans-sphincteric fistula-in-ano in 2(10%) patients, and inter-sphincteric fistula in 6(30%). Body mass index had a significant association with the change in continence (p=0.028). CONCLUSIONS: There was a comparable risk of recurrence after ligation of intersphincteric fistula tract surgery, but among those without recurrence, the post-operative outcomes were optimal and no faecal incontinence was noted.

A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack.

BACKGROUND AND OBJECTIVES: To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. METHODS: In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. RESULTS: A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). DISCUSSION: The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. TRIAL REGISTRATION INFORMATION: CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

TARGET based m6A methylation-related genes predict prognosis relapsed B-cell acute lymphoblastic leukemia.

PURPOSE: The current study aims to investigate the significance of N6-methyladenosine (m6A) methylationrelated genes in the clinical prognosis of childhood relapsed B-cell acute lymphoblastic leukemia (B-ALLL) patient. METHODS: Transcriptome data and corresponding clinical data on m6A methylation-related genes (including 20 genes) were obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database. RESULTS: The bone marrow (BM) samples of 134 newly diagnosed (naive) and 116 relapsed B-ALL from TARGET were enrolled in the current study. Three genes (FTO, HNRNPC, RBM15B) showed significant up-regulation in relapsed B-ALL compared with that in naive B-ALL.The three genes had a significantly worse survival (P < 0.05). The LASSO Cox regression model was used to select the most predictive genes as prognostic indicators, and YTHDC1 and FTO were identified as prognostic factors for relapsed B-ALL. Finally, the results of multivariate regression analysis showed that the risk score of m6A methylation-related genes was an independent prognostic factor in relapsed B-ALL (P < 0.05). CONCLUSION: We found that the expression levels of m6A methylation-related genes were different in naive and relapsed patients with B-ALL and correlated with survival and prognosis.This implies that m6A methylation-related genes may be promising prognostic indicators or therapeutic targets for relapsed B-ALL.

Relapse-Independent disease activity in neuromyelitis optica spectrum disorder: A systematic review.

INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a neuroinflammatory condition characterized by optic neuritis and transverse myelitis. While the current approach to NMOSD focuses on relapse-associated worsening (RAW), recent evidence indicates Relapse-Independent Disease Activity (RIDA) in patients. METHOD: Databases including Embase, PubMed, Scopus, and Web of Sciences were systematically searched up to December 2023. No restrictions were applied. Inclusion criteria focused on studies reporting evidence of RIDA in NMOSD patients. Data extraction involved details such as study title, author, participant characteristics, treatment, evaluation methods, positive findings according to RIDA, and prevalence of findings in NMOSD patients. This study is conducted following the PRISMA guidelines with a registered protocol on PROSPERO (ID = CRD42023492352). RESULT: Of 802 studies, 38 were included in the systematic review, covering 1881 NMOSD patients. AQP4-IGg status was positive in 90.6 % of the patients. Ocular findings indicative of RIDA were reported in 23 studies, including thinning of GCIPL, RNFL, GCC, and GCL layers, foveal and macular shape and volume abnormalities, vessel loss, and visual evoked potentials (VEPs) abnormalities. MRI findings supporting the RIDA were reported in 13 studies, including new lesion incidence and brain and spinal cord atrophy. Serum and CSF RIDA-supporting findings were reported in five studies, including elevation in sGFAP and sNFL. Biopsies and autopsies suggested inflammatory processes in relapse-free patients in 2 studies. The predominant manifestation of RIDA in NMOSD was identified in the visual system, suggesting the impaired retinal glial cells like Müller cells during the relapse-free period in NMOSD. INTERPRETATION: Our systematic review provides valuable insights into RIDA in NMOSD. Establishing guidelines for the diagnosis and treatment of RIDA is crucial. Further studies are needed to provide robust evidence on RIDA in NMOSD patients.

Landscape of in situ cytokine expression, soluble C-type lectin receptors, and vitamin D in patients with recurrent vulvovaginal candidiasis.

The immunopathogenesis of recurrent vulvovaginal candidiasis (RVVC) is poorly understood. Recently, it was reported that patients with RVVC present a decrease in both the fungicidal capacity of neutrophils and the proliferative capability of peripheral blood mononuclear cells in response to Candida albicans infection, suggesting an alteration in the innate and adaptive immune response. The aim of this study was to determine the in-situ expression, in the vaginal mucosa, of genes associated with the immune response, as well as the serum concentrations of dectin-1, mannose-binding lectin (MBL), and vitamin D in patients with RVVC. A study was carried out on 40 patients with a diagnosis of RVVC and 26 healthy women. Vaginal scrapings were obtained, and the expression of genes that encode cytokines and transcription factors specific for Th1, Th2, Th17, Treg, pro-inflammatory profiles, and enzymes related to oxidative/microbicidal mechanisms was evaluated by quantitiative polymerase chain reaction (qPCR). Additionally, serum levels of vitamin D and the soluble receptors dectin-1 and MBL were determined by enzyme-linked immunosorbent assay (ELISA). In patients with RVVC, a decreased expression of T-bet, RORγ-T, IL-1ß, and IL-17, and an increase in the expression of FOXP3, IL-4, IL-8, IL-10, and IL-18 were observed when compared to healthy women: moreover, decreased levels of MBL were also observed in these patients. These results confirm that patients with RVVC present in-situ alterations in both the specific and adaptive immune response against Candida spp., a fact that could be associated with the exaggerated vaginal inflammatory response.

The study concerns the immune response of women with recurrent vulvovaginal candidiasis; we observed an alteration in the expression of genes that participate in the control of infection, a fact that could be associated with the exaggerated vaginal inflammatory response observed in those patients.

Hyperkalemia burden and treatment patterns in Chinese patients on hemodialysis: final analysis of a prospective multicenter cohort study (PRECEDE-K).

OBJECTIVES: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients. METHODS: In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months). RESULTS: Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate. CONCLUSION: Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04799067.

The Arthroscopically Guided Bristow-Latarjet Procedure With Cortical Button Fixation: A Minimum 10-Year Follow-up.

BACKGROUND: Despite improved visualization, the use of arthroscopic surgery to perform the Latarjet procedure has not decreased the rates of complications and glenohumeral osteoarthritis (OA) in the long term. Many of the reported complications are related to the use of screws for bone block fixation with freehand drilling. PURPOSE: To evaluate the long-term (at a minimum 10-year follow-up) clinical and radiological outcomes of the arthroscopic Bristow-Latarjet procedure using a posterior guided drilling technique and suture button for coracoid bone graft fixation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive patients who underwent the arthroscopic Bristow-Latarjet procedure with suture button fixation between 2011 and 2013 were reviewed by 2 independent evaluators. Complications and revision surgery were recorded, and we evaluated patient-reported outcomes including subjective scores, recurrence of shoulder instability (dislocation or subluxation), range of motion limitations, and return to sports. Patients had radiographs taken at least 10 years after surgery to assess glenohumeral OA according to the Samilson-Prieto classification system and computed tomography scans to assess bone block positioning and healing. RESULTS: A total of 65 consecutive patients (68 shoulders) with a mean follow-up of 135 months (range, 120-156 months) were included. The mean age at the time of surgery was 25 ± 8 years; 7 patients had previous failed Bankart repair. At follow-up, 94% (64/68) of the shoulders had no recurrence of instability. The 4 cases of instability recurrence were traumatic and occurred at 3 weeks (a fall), 4 months, 2 years, and 7 years after surgery. No hardware failures, coracoid fractures, or neurological complications were observed. Overall, 61 patients (94%) were still participating in sports, with 44 (68%) at the same or higher level. Range of motion showed nonsignificant restrictions in external rotation with the arm at the side (7° ± 9°) and with the arm at 90° of abduction (9° ± 10°) compared with the contralateral side. Additionally, 11 shoulders (16%) had some residual anterior apprehension on clinical examination. At last follow-up, 77% (47/61) of the shoulders had no OA development or progression. Previous failed Bankart repair was a risk factor for the development of OA. Patients with OA had significantly lower Subjective Shoulder Value scores (79% vs 91%, respectively; P = .01) and decreased external rotation with the arm at the side (40° vs 65°, respectively; P = .001) compared with patients with no or little OA. CONCLUSION: The arthroscopically guided Bristow-Latarjet procedure with suture button fixation is a safe and durable surgical treatment method for recurrent anterior shoulder instability, allowing a high rate of return to sports without significant motion restrictions and no or little OA in the long term.

Clinical rebound after treatment with nirmatrelvir/ritonavir in COVID-19.

BACKGROUND: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes. METHODS: We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r. RESULTS: We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs. 54.5% no rebound), Black race (12.5% rebound vs. 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs. 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs. 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound. CONCLUSIONS: COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

Lipoprotein(a) in interventional cardiology: identifying patients at highest risk of recurrent cardiovascular events through early recognition - a case based review.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is linked to higher risks of atherosclerotic cardiovascular disease (ASCVD). Current guideline recommendations are quite liberal on measuring Lp(a) (Class IIa, Level C), and may lead to underuse among (interventional) cardiologists. AREAS COVERED: This case-based narrative review outlines four clinical cases of patients with elevated Lp(a) to illustrate its pathophysiological impact on coronary artery disease (CAD). The expert consensus statements from the American Heart Association (AHA) and European Atherosclerosis Society (EAS) served as the basis of this review. More recent publications, from 2023 to 2024, were accessed through the MEDLINE online library. EXPERT OPINION: We highlighted the importance of routine Lp(a) measurement in identifying patients at high risk for atherosclerosis, necessitating potent risk mitigation. Measuring Lp(a) helps clinicians identify which patients are at highest residual risk, who require potent pharmacological treatment and special attention during catheter interventions. As noninvasive and advanced intravascular imaging modalities evolve, future catheterization laboratories will integrate advanced imaging, diagnostics, and treatment, facilitating tailored patient care. Knowing Lp(a) levels is crucial in this context. While Lp(a)-lowering drugs are currently investigated in clinical trials, it is of paramount importance to know Lp(a) levels and strive toward aggressive management of other modifiable risk factors in patients with elevated Lp(a) and established symptomatic CAD being diagnosed or treated in catheterization laboratories.

The Impact of Adding a Tibial Tubercle Osteotomy to Medial Patellofemoral Ligament Reconstruction in the Treatment of Patellar Instability.

BACKGROUND: An isolated medial patellofemoral ligament (MPFL) reconstruction (MPFLR) has been demonstrated to be an effective treatment option in the prevention of patellar instability, but there is growing support for performing a tibial tubercle osteotomy (TTO) in patients with an elevated tibial tubercle-trochlear groove distance. The purpose of this study was to evaluate the impact of adding a TTO to MPFLR on patient reported outcomes. METHODS: A retrospective review of patients who underwent MPFLR with or without TTO with a minimum of 12-month follow-up was performed. Patients in both groups were matched based on age, sex, and follow-up time. Recurrent instability (including re-dislocation and subluxation), visual analog scale (VAS) for pain score, Kujala score, and satisfaction were evaluated. RESULTS: There were 59 patients who underwent MPFLR with concomitant TTO performed at our institution and met our inclusion and exclusion criteria. These patients were then matched to patients undergoing isolated MPFLR based on demographics and follow-up time. The mean age was 25.0, 76.3% were female, and the mean follow-up time was 49 months. There was a significant difference in mean tibial tubercle-trochlear groove distance (19.8 ± 3.9 vs. 14.1 ± 2.8) between groups. There was no significant difference in VAS (1.48 ± 2.0 vs. 1.49 ± 2.1, p = 0.972), satisfaction (86.1% ± 24.2% vs. 81.2% ± 27.9, p = 0.311), or revision surgeries (10.2% vs. 10.2%) between groups. CONCLUSION: There was a low complication rate, excellent patient reported outcomes, and a low rate of recurrent patellar instability following TTO and MPFLR with allograft.

Immunomodulators and immunosuppressants for progressive multiple sclerosis: a network meta-analysis.

BACKGROUND: In recent years a broader range of immunomodulatory and immunosuppressive treatment options have emerged for people with progressive forms of multiple sclerosis (PMS). While consensus supports these options as reducing relapses, their relative benefit and safety profiles remain unclear due to a lack of direct comparison trials. OBJECTIVES: To compare through network meta-analysis the efficacy and safety of alemtuzumab, azathioprine, cladribine, cyclophosphamide, daclizumab, dimethylfumarate, diroximel fumarate, fingolimod, fludarabine, glatiramer acetate, immunoglobulins, interferon beta 1-a and beta 1-b, interferon beta-1b (Betaferon), interferon beta-1a (Avonex, Rebif), laquinimod, leflunomide, methotrexate, minocycline, mitoxantrone, mycophenolate mofetil, natalizumab, ocrelizumab, ofatumumab, ozanimod, pegylated interferon beta-1a, ponesimod, rituximab, siponimod, corticosteroids, and teriflunomide for PMS. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase up to August 2022, as well as ClinicalTrials.gov and the WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials (RCTs) that studied one or more treatments as monotherapy, compared to placebo or to another active agent, for use in adults with PMS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We performed data synthesis by pair-wise and network meta-analysis. We assessed the certainty of the body of evidence according to GRADE. MAIN RESULTS: We included 23 studies involving a total of 10,167 participants. The most frequent (39% of studies) reason for a rating of high risk of bias was sponsor role in study authorship and data management and analysis. Other concerns were performance, attrition, and selective reporting bias, with 8.7% of studies at high risk of bias for all three of these domains. The common comparator for network analysis was placebo. Relapses over 12 months: assessed in one study (318 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 24 months: assessed in six studies (1622 participants). The number of people with clinical relapses is probably trivially reduced with rituximab (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.19 to 1.95; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 36 months: assessed in four studies (2095 participants). The number of people with clinical relapses is probably trivially reduced with interferon beta-1b (RR 0.82, 95% CI 0.73 to 0.93; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 24 months: assessed in 11 studies (5284 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 36 months: assessed in five studies (2827 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Serious adverse events: assessed in 15 studies (8019 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Discontinuation due to adverse events: assessed in 21 studies (9981 participants). The number of people who discontinued treatment due to adverse events is trivially increased with interferon beta-1a (odds ratio (OR) 2.93, 95% CI 1.64 to 5.26; high certainty evidence). The number of people who discontinued treatment due to adverse events is probably trivially increased with rituximab (OR 4.00, 95% CI 0.84 to 19.12; moderate certainty evidence); interferon beta-1b (OR 2.98, 95% CI 1.92 to 4.61; moderate certainty evidence); immunoglobulins (OR 1.95, 95% CI 0.99 to 3.84; moderate certainty evidence); glatiramer acetate (OR 3.98, 95% CI 1.48 to 10.72; moderate certainty evidence); natalizumab (OR 1.02, 95% CI 0.55 to 1.90; moderate certainty evidence); siponimod (OR 1.53, 95% CI 0.98 to 2.38; moderate certainty evidence); fingolimod (OR 2.29, 95% CI 1.46 to 3.60; moderate certainty evidence), and ocrelizumab (OR 1.24, 95% CI 0.54 to 2.86; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. AUTHORS' CONCLUSIONS: The number of people with PMS with relapses is probably slightly reduced with rituximab at two years, and interferon beta-1b at three years, compared to placebo. Both drugs are also probably associated with a slightly higher proportion of withdrawals due to adverse events, as are immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab; we have high confidence that this is the case with interferon beta-1a. We found only low or very low certainty evidence relating to disability progression for the included disease-modifying treatments compared to placebo, largely due to imprecision. We are also uncertain about the effect of interventions on serious adverse events, also because of imprecision. These findings are due in part to the short follow-up of the included RCTs, which lacked detection of less common severe adverse events. Moreover, the funding source of many included studies may have introduced bias into the results. Future research on PMS should include head-to-head rather than placebo-controlled trials, with a longer follow-up of at least three years. Given the relative rarity of PMS, controlled, non-randomised studies on large samples may usefully integrate data from pivotal RCTs. Outcomes valuable and meaningful to people with PMS should be consistently adopted and measured to permit the evaluation of relative effectiveness among treatments.

Clinical Utility of Rilonacept for the Treatment of Recurrent Pericarditis: Design, Development, and Place in Therapy.

Recurrent pericarditis (RP) has been traditionally regarded as a "nightmare" for both clinicians and patients. Until approximately a decade ago, available treatments were thin on the ground with non-steroidal anti-inflammatory medications, glucocorticoids, colchicine, and classical immunosuppressants being the only options. The first important step in the tale of RP was the advent of colchicine in clinical practice, which has been shown to halve the rate of first and subsequent pericarditis recurrences. The second major breakthrough advance in this setting was the introduction of interleukin-1 inhibitors based on the recently unveiled autoinflammatory nature of pericarditis. At present, anti-interleukin-1 inhibitors available for clinical use in patients with refractory RP include anakinra and rilonacept, with the latter having obtained FDA approval for this indication. Apart from the remarkable efficacy and good safety profile which is a common feature of all anti-interleukin-1 compounds, rilonacept has the advantage of weekly administration (instead of daily compared to anakinra) which is important in terms of adherence to treatment and improved quality of life albeit at the expense of a higher cost. This review aims to summarize the available evidence on the role of rilonacept in the treatment of RP and the reduction of the recurrences risk.

Update on the diagnosis of recurrence of lower limb deep vein thrombosis. A Consensus statement of the French Society for Vascular Medicine (SFMV).

An accurate diagnosis of lower limb deep vein thrombosis (DVT) recurrence is mandatory. The diagnosis is difficult and has not been well investigated. Our objective was to define the role of clinical probability assessment, D-dimer assay, venous ultrasound and other imaging methods in the diagnosis of this condition based on a review of published data. Our review did not find any clinical prediction rule (CPR) specific to the diagnosis of DVT recurrence. D-dimer assays have not been sufficiently validated or proved effective either alone or when combined with the assessment of clinical probability or with ultrasound. The only validated ultrasound criteria are a new non-compressible vein segment and a≥2mm or>4mm increase in diameter of the common femoral or popliteal vein under compression in the transverse plane between two examinations. Limitations of these criteria include poor inter-observer agreement, non-availability of previous ultrasound reports and measurements, a high percentage of non-diagnostic ultrasound results, lack of power in diagnostic accuracy and diagnostic management studies, and lack of external validation. The analysis of venous obstruction, thrombus appearance, vein diameter and blood flow based on colour Doppler ultrasound criteria has not yet been validated in studies. Magnetic resonance direct thrombus imaging (MRDTI) is a new promising diagnostic imaging method, but is hardly accessible, costly and needs large scale validation studies. Based on this review, an update of the guidance for clinical practice is proposed for the diagnostic management of patients with clinically suspected lower limb DVT recurrence.