Higher Proportion Of Patients Research Articles

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240).

Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1months), actuarial 12-months overall survival (OS) of 80% (median 23.1months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl). Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed. At the cut-off date (i.e., November 1st 2023), median follow-up was 23months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence). At 5years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects. NCT03048240. EudraCT number: 2016-002706-39.

Caracterización clínica y genética de leucemias pediátricas en Montería-Córdoba.

Introduction: leukemias are characterized by the infiltration of malignant cells from the hematopoietic system to the bone marrow and other tissues. 95% of childhood leukemias are acute, of which 75% are lymphoid and 25% myeloid. Although the survival rate can reach up to 90% in high-income countries, for middle- and low-income countries it can vary from 20 to 40%, depending on social and clinical factors that are determinant for survival in the pediatric age. Objective: to describe the clinical and genetic characteristics of a retrospective cohort of pediatric patients with leukemia, in a high complexity clinic in Montería-Córdoba. Methodology: Retrospective cohort study of 124 subjects aged 1-18 years. Frequencies were calculated and associated factors were identified using Ji-square in SPSS 27.0. Results: the highest proportion of patients were men (54.8%), aged 1-5 years (38.7%); 83.1% with lymphoblastic leukemia and 14.5% myeloblastic, the majority with affiliation to the subsidized regime. The clinical and genetic characteristics were not associated with sociodemographic variables. Conclusion: The main leukemias were type B ALL, a higher probability of splenomegaly was found in ALL and more advanced risk levels in AML, determining information to optimize care actions for this pathology

Everolimus Treatment for Chronic Lung Allograft Dysfunction in Lung Transplantation.

This retrospective study included LT patients in two reference LT units who started everolimus therapy to treat CLAD from October 2008 to October 2016. We assessed the variation in the maximum forced expiratory volume in the first second (FEV1) before and after the treatment. Fifty-seven patients were included in this study. The variation in the FEV1 was -102.7 (149.6) mL/month before starting everolimus compared to -44.7 (109.6) mL/month within the first three months, +1.4 (63.5) mL/month until the sixth month, and -7.4 (46.2) mL/month until the twelfth month (p < 0.05). Glomerular filtrate remained unchanged after everolimus treatment [59.1 (17.5) mL/min per 1.73 m2 at baseline and 60.9 (19.6) mL/min per 1.73 m2, 57.7 (20.5) mL/min per 1.73 m2, and 57.3 (17.8) mL/min per 1.73 m2, at 1, 3, and 6 months, respectively] (p > 0.05). Everolimus was withdrawn in 22 (38.6%) patients. The median time to withdrawal was 14.1 (5.5-25.1) months. This study showed an improvement in FEV1 decline in patients with CLAD treated with everolimus. However, the drug was withdrawn in a high proportion of patients.

Adherence and Persistence Among Risdiplam-Treated Individuals with Spinal Muscular Atrophy: A Retrospective Claims Analysis.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions and/or mutations in the survival of motor neuron1 (SMN1) gene. Risdiplam, the first and only oral SMN2 pre-mRNA splicing modifier, is US Food and Drug Administration-approved for the treatment of pediatric and adult patients with SMA. For patients with SMA, long-term adherence to and persistence with an SMA treatment may be important for achieving maximum clinical benefits. However, real-world evidence on patient adherence to and persistence with risdiplam is limited. This retrospective study examined real-worldadherence and persistence with risdiplamfrom a specialty pharmacy in patients with SMA over a 12-month period. Adherence was estimated by using proportion of days covered (PDC) and was calculated over variable (time between first and last fill) and fixed (time from first fill to study period end) intervals. Persistence was defined as no gap in supply ≥ 90days. Patients were included if the time between the index date and study observation period was ≥ 12months, if they initiated risdiplam between August 2020 and September 2022, received ≥ 2 risdiplam fills, and had an SMA diagnosis associated with a risdiplam fill. Subgroup analyses of risdiplam adherence and persistence were performed by age and primary payer type. The proportion of patients (N = 1636) adherent at 12months based on variable and fixed interval PDC was 93% and 79%, respectively. Adherence was high among patients on commercial insurance, Medicaid, or Medicare (range 86-96%). Mean persistence was 330.4days. The highest proportion of patients who were persistent were on Medicaid (81%). These findings demonstrate that patient adherence to and persistence with risdiplam treatment were high, including across all subgroups tested.

Abstract PO1-16-06: LuciA-15 - A real-world prospective study of PARP inhibitors for the treatment of Latin American patients with HER-2 negative metastatic breast cancer with mutation of BRCA1/2 genes or in the Homologous Recombination Repair genes

Abstract Background PARP inhibitors (PARPi) improves progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to physician choice of chemotherapy (CT). The AIM of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population. Methods We analyzed data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA 1 or BRCA 2 or in the Homologous Recombination Repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. From September 2019 and April 2023, we collected baseline characteristics, previous systemic treatments, type and pattern of use, treatment beyond PARPi progression, and patient predisposition. Objective responses, best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analyzed with R software and RStudio version 14.0. Results After a median follow-up of 18.07 months (CI95% 10.53 - 30.07), 51 patients were treated with PARPi. Mean age at start treatment was 47,08 years. 62.7% had ER+ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talalaparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT (PbCT) in the (neo)adjuvant/metastatic setting. 57.5% had visceral metastasis and the median number of metastatic sites were 2 (range 1-4). Median number of lines at the time to start PARPi was 2 (range 0-8), 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively. The rwORR was 47.0%, and the median rwPFS1 was 7.77 months (CI95% 5.67-14.7). There was a tendence of better rwPFS1 in patients without previous CT versus previous CT in the advance setting, 14.30 months (CI95% 6.47-NR) versus 6.37 months (CI95% 5.03-8.73), respectively (p 0.084). The median rwOS was 26.97 months (CI95% 13.50-NR) and higher in the subgroup of patients naïve for CT versus previous exposure to CT in the advance setting, the median rwOS was 32.1 months (CI95% 27.0-NR) versus 13.0 (IC95%10.1-NR), respectively (p 0.022). 23.5% of patients progressed on PARPi during the first 6 months of treatment, 32.4% with visceral compromise, 27.8% with visceral crisis, and 26.5% with ≥2 metastatic sites. CT was the treatment of choice in most patients (55.3%). The medium rwPFS2 (next treatment after PARPi failure) was 4.00 months (CI95% 3.43 – 7.13). Treatment was discontinued for adverse events in 4.0 % of patients. Conclusion This is the first Latin-American evidence that replicate the data already published in randomized clinical trials and other scanty real-world evidence studies in this field, positive results in rwORR and rwPFS, encouraging data in rwOS. Notably, high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, similar rwOS results among subgroups (TNBC versus ER+ve/HER2-ve, talazoparib versus Olaparib, etc). &amp;lt;graphic&amp;gt; Citation Format: Fernando E. Petracci, Cynthia Villarreal-Garza, Facundo Argañaraz, Gonzalo Gómez Abuin, José Peñaloza, Marcos A. Flores, Luciano Piazzoni, Cecilia Riggi, Lucía Fabiano, Lucía González, Belén Cieplinski, Sergio Rivero, Ernesto Korbenfeld, Pablo Mandó. LuciA-15 - A real-world prospective study of PARP inhibitors for the treatment of Latin American patients with HER-2 negative metastatic breast cancer with mutation of BRCA1/2 genes or in the Homologous Recombination Repair genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-06.

Abstract PO5-22-12: Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial

Abstract Background: De-escalation of axillary surgery in patients with lymph node-positive breast cancer is currently being tested in ongoing trials for patients with downstaged nodes after neoadjuvant chemotherapy (NAC). A proportion of such patients will achieve an excellent axillary node response to NAC, i.e. conversion to pathologic node-negative status after chemotherapy. Genomic prediction of tumor chemosensitivity before final surgery may identify which patients could safely undergo conservative surgical management of their regional lymph nodes. Methods: The AGO-35 (NCT0203274) is a prospective trial for patients with HER2 negative breast cancer scheduled for neoadjuvant chemotherapy that includes an anthracycline- based regimen followed by 3-4 cycles of taxanes. The LN predictor is a newly developed model for predicting the probability of pathological lymph node-positivity after NAC in triple-negative (TNBC) or hormone-receptor positive (HR+) breast cancer. To calculate the LN predictor, which is developed in microarray, we calibrated the normalized individual gene module and SET ER/PR from RNAseq to the Affymetrix U133A platform using independently combined total of 220 pairs of TNBC samples with both RNAseq and U133A microarray results. The logistic regression model is applied for the prediction of the binary outcome, pathological lymph node-positive or negative after NAC. The cut-points of LN predictor in TNBC and HR+ samples were pre-determined for each subtype of breast cancer and then, independent, blinded evaluation in the AGO-35 trial samples. Results: A total of 251 patients with HER2 negative breast treated with neoadjuvant chemotherapy were included. The LN predictor was validated on 189 qualified samples with wtRNA sequence. Statistical analysis of 181 samples is shown in Table 1. Conclusion: Preliminary results of the AGO-35 trial show that the newly developed molecular LN predictor may accurately predict chemosensitivity response to NAC, in high proportion of patients with TNBC. Supported by: Wissenschaftsfonds (FWF) KLI 406 EUBREAST study group AGO Österreich Breast Cancer Research Foundation (BCRF-0158) Table 1. Genomic prediction of chemosensitivity Citation Format: Florentia Peintinger, Thorsten Kühn, Hans-Christian Kolberg, Roland Reitsamer, Sabine Schmatloch, Elisa Sieghartsleitner, Lili Du, Andrea Berghold, W. Fraser Symmans. Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-12.

Distributional Characteristics Analysis of Allergens in Patients with Allergic Rhinitis in Southern Fujian Province, China.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China. A skin prick test (SPT) was performed and eight common allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dpt), weeds, animal dander, molds, cockroaches, and mangoes were chosen. The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to Df and Dpt had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to Df and Dpt were both correlated with the season. Positive reactions to Df, Dpt, cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons. This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients.

EFFECT OF HIGH DOSE APROCITENTAN IN PATIENTS WITH RESISTANT HYPERTENSION NOT CONTROLLED BY LOW DOSE

Objective: The phase 3 PRECISION study in patients with resistant hypertension tested 12.5 mg and 25 mg aprocitentan during the 4-week DB placebo-controlled part, in addition to a fixed-dose combination of amlodipine, valsartan, hydrochlorothiazide. No differences in primary endpoint (SiSBP) were observed between the two doses. This post-hoc exploratory analysis evaluates the observed long-term benefit of increasing to a higher dose (25 mg) in patients not achieving a blood pressure control after 4 weeks on the lower dose (12.5 mg). Design and method: In PRECISION, after completion of the 4-week DB part 1, all randomized patients received 25 mg aprocitentan during the 32-week SB part 2. This subgroup analysis includes 93 subjects who were still uncontrolled at week 4 (SiSBP &gt; 140 mm/Hg) in the 12.5 mg aprocitentan group (n=223). The % of patients achieving control (&lt;140 or &lt; 130 for SiSBP and &lt; 90 or &lt; 85 mm/Hg for SiDBP) or showing a response of &gt;/= -10 or &gt;/= -15 mmHg in SiSBP or &gt;/= -5 or &gt;/= -10 mm/Hg in SiDBP vs week 4 at week 6, 12 and 36 (i.e., after 2 to 32 weeks of treatment with 25 mg) were calculated. Results: Among the patients in the aprocitentan 12.5 mg group with uncontrolled SiSBP at 4 weeks, after 2 weeks of treatment with 25 mg (at study Week 6), 39.8% (37/93) of subjects achieved SiSBP &lt; 140 mmHg. This increased to 49.3% (37/73) after 32 weeks of aprocitentan 25 mg treatment, at study week 36. The control rate set at the 130 mm Hg threshold and the response rates also increased over time. Also, for SiDBP the increase in the dose of aprocitentan resulted in a high proportion of patients being controlled (45% to 68% depending on the threshold) and responders (45 to 68%) after 32 weeks of treatment. Conclusions: These additional exploratory analyses show that switching from 12.5 mg to 25 mg aprocitentan can achieve further BP control or response not obtained with the lower dose.

The prevalence and pattern of comorbid long-term conditions with low back pain and osteoarthritis in low- and middle-income countries: a systematic review and meta-analysis

ABSTRACT Chronic musculoskeletal (MSK) pain, specifically low back pain (LBP) and osteoarthritis (OA), are a major cause of global disability, reduced quality of life and high socioeconomic burden. Research in high income countries suggests MSK pain is often comorbid with other long-term conditions / non-communicable diseases (NCDs) including diabetes, hypertension, and cardiovascular disease. However, the epidemiology of comorbid NCDs and MSK pain in low- and middle-income countries (LMICs) is unclear. This systematic review aims to describe the prevalence and pattern of comorbid NCDs in adults with MSK pain in LMICs. Nine databases were searched for epidemiological studies in LMICs (World Bank categories). Paired researchers independently identified studies, extracted data, and completed critical appraisal using Hoy risk of bias tool. Random-effect meta-analysis was used to estimate prevalence of NCDs comorbid with MSK pain. From 2112 citations; 14 studies (n=6093 adults with MSK pain, mean age=46.9years) were included. Overall prevalence of MSK pain with comorbid NCDs was 46.1% (95%CI 32.3 - 59.9). Systemic hypertension had the highest comorbid prevalence with MSK pain (42.6%, 95%CI 25.6-59.6), followed by diabetes (26.7%, 95%CI 16.1-37.3) and mental health conditions (anxiety/depression; 24.9% 95%CI 11.5-38.4). A high proportion of patients with MSK pain in LMICs experience comorbid NCDs. Variable data/population samples, and under-reporting limit accurate capture of prevalence estimates. Understanding the true burden of MSK pain (specifically lower back pain and hip/knee osteoarthritis) and comorbid NCDs is critical to informing effective treatment strategies. The health systems implications of these findings are imperative towards person-centred care, organisation of care and efficient resource utilisation in LMICs.

Unraveling the characteristics of Parkinson's Disease through neuroimaging: Insights and future directions

Parkinson's disease (PD) is a neurodegenerative disease with a high degree of patient heterogeneity, and as of 2016 there are approximately 6.1 million PD patients worldwide. PD has a high proportion of patients with intermediate to advanced disease and a high rate of disability, and clinical diagnosis and treatment are difficult due to the lack of neuromarkers to identify disease states and the inability to quantify the effects of treatment in PD. In recent years, many researchers have explored specific changes in brain activity in PD based on electrophysiological and neuroimaging data. Electroencephalography, with its high temporal resolution and rich frequency domain information, and functional magnetic resonance imaging, with its high spatial resolution, have become the main tools to characterize the state of brain activity in PD in recent years. This paper analyses some of the available data on the characteristics of PD through two neuroimaging techniques commonly used in the disease. It concludes with the prospect of being able to establish uniform criteria for determining PD.

Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.

Health Perceptions, Multimorbidity, and New Fractures and Mortality Among Patients With a Fracture

A high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored. To examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture. This prospective cohort study included participants from New South Wales, Australia, in the Sax Institute's 45 and Up Study (n = 267 357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023. Charlson Comorbidity Index (CCI) score and self-rated health (SRH). The main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males. Of 25 280 adults who sustained incident fractures, 16 191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher. In this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.

OA05 Potential impact of European Medicines Agency measures to minimise risk of serious side effects on those using JAK inhibitors in the UK

Abstract Background/Aims Janus kinase inhibitors (JAKi) are effective therapies for rheumatoid arthritis (RA). However, concerns about their safety in certain 'at-risk' populations have resulted in risk minimisation measures introduced by European Medicines Agency (EMA) in January 2023, which limits JAKi prescription to certain patient subgroups unless no suitable alternative is available. The potential impact on current and future JAKi use in the UK is unknown. Using a national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion meeting ≥1 of these criteria and therefore may be impacted by these changes. Methods RA patients starting their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the British Society for Rheumatology RA Biologics Register (BSRBR-RA) before 31st May 2022 (pre-EMA warning) were included. Patients with missing data in any EMA criteria related variables were excluded. Descriptive statistics were used to present patients' characteristics at the start of JAKi. This analysis defined four at-risk criteria assessed at the treatment start: 1) aged ≥65; 2) increased risk of major cardiovascular issues (history of hypertension, hyperlipidaemia, diabetes, ischaemic heart disease, or stroke); 3) current or past smokers; 4) increased risk of cancer (defined as prior cancer). The previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes was described among those who met the criteria. Results A total of 1,362 patients starting their first JAKi were included, most commonly baricitinib (76%), followed by tofacitinib (16%; see Table). The cohort was 78% female, with an average age of 60. Among them, 28% of patients had received ≥3 prior bDMARDs classes. 80% percent of patients (1,090) met ≥1 EMA risk criterion, with the most common individual criterion current/past smoker (54%). Of those who met ≥1 risk criteria, 645 (59%) met ≥1 EMA risk criterion and 29% had already received ≥3 prior bDMARDs classes. Conclusion A very high proportion of patients, four-in-five, initiating JAKi in UK before the EMA advisory would have fallen into the ‘high-risk' category for whom prescribing would only be advised if no suitable alternatives were available. Whilst almost a third of them had previously received ≥3 different bDMARDs classes, it’s likely that many of them would have suitable alternatives. These data highlight the enormous impact of the recent licensing updates for JAKi class. Disclosure Z. Tian: None. L. Kearsley-fleet: None. J. Galloway: Honoraria; Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Vifor. Grants/research support; Abbvie, Galapagos, GSK, Janssen, Pfizer. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

Clinical phenotypes of comorbidities in end-stage knee osteoarthritis: a cluster analysis

ObjectivesComorbidities, as components of these heterogeneous features, often coexist with knee osteoarthritis, and are particularly prevalent in end-stage knee osteoarthritis. Here, we attempted to identify the different clinical phenotypes of comorbidities in patients with end-stage knee osteoarthritis by cluster analysis.MethodsA total of 421 inpatients diagnosed with end-stage knee osteoarthritis who underwent inpatient surgery were included in this cross-sectional study. 23 demographic, comorbidity, inflammatory immune and evaluation scale variables were collected. Systematic clustering after factor analysis and separate two-step cluster analysis were performed for individual comorbidity variables and all variables, respectively, to objectively identify the different clinical phenotypes of the study patients.ResultsFour clusters were finally identified. Cluster 1 had the largest proportion of obese patients (93.8%) and hypertension was common (71.2%). Almost all patients in cluster 2 were depressed (95.8%) and anxiety disorders (94.7%). Cluster 3 combined patients with isolated end-stage knee osteoarthritis and a few comorbidities. Cluster 4 had the highest proportion of patients with rheumatoid arthritis (58.8%).ConclusionsPatients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: "isolated end-stage knee osteoarthritis"; "obesity + hypertension"; "depression + anxiety"; and "rheumatoid arthritis", which may help guide individualized patient care and treatment strategies.

Inborn errors of immunity: features of epidemiology and continuity of medical care in the Republic of Tatarstan

BACKGROUND: Currently, inborn errors of immunity represent one of the most interesting problems in clinical immunology. The data obtained in the field of studying pathogenetic mechanisms and clinical manifestations, expanding diagnostic capabilities, including molecular genetic methods, formed the basis for revising the classification and introducing new modern treatment methods. The study of regional characteristics of inborn errors of immunity is important because it allows us to determine epidemiological indicators, clinical features of diseases and evaluate the therapy being carried out.&#x0D; AIM: To assess the effectiveness and level of continuity of medical care in the Republic of Tatarstan based on an epidemiological analysis of a group of patients diagnosed with primary immunodeficiency.&#x0D; MATERIALS AND METHODS: analysis of the register of patients living in the Republic of Tatarstan with an established diagnosis of primary immunodeficiency, observed from 1994 to 2023. A total of 240 patients were included in the study.&#x0D; RESULTS: An epidemiological analysis of inborn errors of immunity in the Republic of Tatarstan revealed an overall prevalence of 6.0 per 100,000 population, with the status "alive" ― 4.98 per 100,000 population, excluding patients with selective IgA deficiency ― 5.3 and 4.4 per 100,000 population, respectively, with a high proportion of patients over 18 years of age (53%), with the largest group of patients having defects in antibody production (42%).&#x0D; CONCLUSION: The increasing relevance of the problem of primary immunodeficiency requires special attention to the organization of medical care for patients with primary immunodeficiency, increasing continuity between specialized pediatric services and the adult network, as well as developing issues of interdisciplinary interaction.

Vestibular migraine: an update.

We performed a narrative review of the recent findings in epidemiology, clinical presentation, mechanisms and treatment of vestibular migraine. Vestibular migraine is an underdiagnosed condition that has a high prevalence among general, headache and neuro-otology clinics. Vestibular migraine has a bimodal presentation probably associated with a hormonal component in women. These patients could have a complex clinical phenotype including concomitant autonomic, inflammatory or connective tissue conditions that have a higher prevalence of psychological symptoms, which may mistakenly lead to a diagnosis of a functional neurological disorder. A high proportion of patients with postural perceptual persistent dizziness have a migraine phenotype. Independently of the clinical presentation and past medical history, patients with the vestibular migraine phenotype can respond to regular migraine preventive treatments, including those targeting the calcitonin gene-related peptide pathways. Vestibular migraine is an underdiagnosed migraine phenotype that shares the pathophysiological mechanisms of migraine, with growing interest in recent years. A thorough anamnesis is essential to increase sensitivity in patients with unknown cause of dizziness and migraine treatment should be considered (see supplemental video-abstract).

Percutaneous intramedullary screw or rush pin fixation of unstable ankle fractures in patients with fragile soft tissue – retrospective study of 80 cases

IntroductionThe standard surgical procedure for unstable ankle fractures is fixation of the lateral malleolus with a plate and screws. This method has a high risk of complications, especially among patients with fragile skin conditions. The aim of this study was to estimate the re-operation rates and identify complications in patients with an unstable ankle fracture, surgically treated with an intramedullary screw or rush pin.Materials and methodsWe identified all patients who were surgically treated with either a 3.5-mm screw or rush pin at Aarhus University Hospital, Denmark, from 2012 to 2018. Major complications were re-operations within three months. We included 80 patients, of which 55 (69%) were treated with a 3.5-mm intramedullary screw and 25 (31%) with a rush pin. The majority of the study population was female (59) and the mean age was 75 (range 24 to 100) years. Of the 80 patients included, 41 patients had more than 2 comorbidities.ResultsThree patients underwent re-operation within three months due to either fracture displacement or hardware cutout. Radiographs obtained after six weeks showed that nine patients had loss of reduction. Additionally, four patients had superficial wound infections and six patients had delayed wound healing.ConclusionsIntramedullary fixation of distal fibula fractures with either a screw or rush pin has low re-operation rates. However, the high proportion of patients with radiological loss of reduction is concerning.

Correlation of the Endoscopic Gastroesophageal Flap Valve with Pathologic Reflux.

The Hill classification characterizes the geometry of gastroesophageal junction and Hill grades (HGs) III and IV have a high association with pathologic reflux. This study aimed to understand the use of the Hill classification and correlate the prevalence of pathologic reflux across different HGs. A retrospective review of 477 patients who underwent upper endoscopy and BRAVO pH monitoring between August 2018 and October 2021 was performed. These charts were reviewed for endoscopic findings for hiatal hernia and association of HGs with pathologic reflux, defined as an abnormal esophageal acid exposure time (AET) of ≥4.9%. Of 477 patients, 252 (52.8%) had an HG documented on the endoscopy report. Of the 252 patients, 61 had HG I (24.2%), 100 had HG II (39.7%), 61 had HG III (24.2%), and 30 had HG IV (11.9%). The proportion of patients with abnormal AET increases with increasing HGs (p < 0.001) as follows: I (39.3%), II (52.5%), III (67.2%), and IV (79.3%). The mean overall AET is as follows: HG I (5.5 ± 6%), HG II (7.0 ± 5.9%), HG III (10.2 ± 10.3%), and HG IV (9.5 ± 5.5%). The proportion of patients with hiatal hernia was 18% for HG I, 28% for HG II, 39.3% for HG III, and 80% for HG IV. Use of the Hill classification in clinical practice is low. There is an association of increasing HGs with increasing proportion of patients with abnormal AET. There is a high proportion of patients within HGs I and II with documented pathologic reflux and the presence of a hiatal hernia as observed on endoscopic examination. Our study suggests that endoscopic grading of the gastroesophageal junction may not adequately differentiate between normal vs abnormal reflux status, particularly for HGs I and II.

Comparison of hysterectomy cases performed by transvaginal natural orifice transluminal endoscopic surgery: A paired sample cross-sectional study.

This study aimed to investigate the feasibility, indications, and benefits of transvaginal natural orifice transluminal endoscopic surgery (v-NOTES) hysterectomy for nonmalignant gynecological diseases. The clinical data, including the baseline information and surgical conditions of 81 patients who underwent v-NOTES hysterectomy for nonmalignant gynecological diseases in a tertiary university hospital from October 2018 to August 2022, were retrospectively analyzed and compared with the total laparoscopic hysterectomy group (200 cases) and the transumbilical laparoendoscopic Single Site Surgery group (150 cases). In comparison with the other 2 groups, the highest proportion of patients in the v-NOTES group had cervical intraepithelial neoplasia. Accordingly, mean preoperative uterine volume measured by sonography was significantly smaller in the v-notes group. In the v-NOTES group, the mean number of vaginal deliveries and age were significantly higher, while the mean number of previous abdominal surgeries was lower compared to the other 2 groups. The V-NOTES group had a shorter operation time, shorter postoperative urinary catheter insertion time, earlier intestinal recovery days, shorter hospital stay, and lower visual analogue scale scores after surgery, and the differences were statistically significant. When indicated appropriately, v-NOTES hysterectomy can be a feasible and advantageous surgical modality. In particular, in comparison to the laparoendoscopic Single Site Surgery and total laparoscopic hysterectomy groups, the v-NOTES group had advantages in postoperative recovery and had more aesthetic surgical results.