Course Of Disease Research Articles

Updates in the Use of Targeted Therapies for Gynecologic Cancers.

Targeted therapies have changed the treatment landscape in gynecologic cancer. Studies released over the past year have led to the incorporation of immunotherapy (IO) into the treatment for all patients with endometrial and cervical cancers at some point during their disease course. Poly(ADP-ribose) polymerase (PARP) inhibitors continue to play a role in women with ovarian carcinoma, particularly in homologous repair deficient tumors. Furthermore, the benefit of PARP inhibitors in challenging subgroups continues to be elucidated. Biomarker identification has led to the approval or compendium listing of several antibody-drug conjugates (ADCs). This review will update on IO, ADCs, and PARP inhibition for the treatment of gynecologic cancers.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

The Natural Course of the Carotid Artery Atherosclerotic Disease in the Contralateral Carotid Artery After Carotid Endarterectomy

The Natural Course of the Carotid Artery Atherosclerotic Disease in the Contralateral Carotid Artery After Carotid Endarterectomy

Visceral Adipose Tissue Reduction Measured by Deep Neural Network Architecture Improved Reflux Esophagitis Endoscopic Grade.

Visceral obesity is a risk factor for reflux esophagitis (RE). We investigated the risk of RE according to visceral adipose tissue (VAT) measured by deep neural network architecture using computed tomography (CT) and evaluated the longitudinal association between abdominal adipose tissue changes and the disease course of RE. Individuals receiving health checkups who underwent esophagogastroduodenoscopy (EGD) and abdominal CT at Seoul National University Healthcare System Gangnam Center between 2015 and 2016 were included. Visceral and subcutaneous adipose tissue areas and volumes were measured using a deep neural network architecture and CT. The association between the abdominal adipose tissue area and volume and the risk of RE was evaluated. Participants who underwent follow-up EGD and abdominal CT were selected; the effects of changes in abdominal adipose tissue area and volume on RE endoscopic grade were investigated using Cox proportional hazards regression. We enrolled 6,570 patients who underwent EGD and abdominal CT on the same day. RE was associated with male sex, hypertension, diabetes, excessive alcohol intake, current smoking status, and levels of physical activity. The VAT area and volume increased the risk of RE dose-dependently. A decreasing VAT volume was significantly associated with improvement in RE endoscopic grade (hazard ratio: 3.22, 95% confidence interval: 1.82-5.71). Changes in subcutaneous adipose tissue volume and the disease course of RE were not significantly correlated. Visceral obesity is strongly associated with RE. VAT volume reduction was prospectively associated with improvement in RE endoscopic grade dose-dependently. Visceral obesity is a potential target for RE treatment.

Sentinel Enhanced Dengue Surveillance System - Puerto Rico, 2012-2022.

Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential. May 2012-December 2022. SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan. During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined. Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses. SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.

Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder.

Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths. To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator. This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023. Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy. The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes. The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use. These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders: A Systematic Review and Meta-Analysis.

Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking. To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients. MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses. Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria. Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate. A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P < .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76). This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.

Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome

Abstract The objective of this study was to evaluate the efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome (CPPS). A total of 79 female patients diagnosed with CPPS from January 2021 to December 2022 were prospectively analyzed. Every patient received 3 weeks of treatment which included myofascial release therapy combined with electrical and magnetic stimulation. The visual analog score (VAS) of pelvic floor muscle (PFM) trigger points (TrPs) and the changes in pelvic floor surface electromyography before and after treatment were compared. Multiple linear regression was used to analyze the influencing factors of each outcome index. There were significant differences in VASs of muscle TrPs before and after treatment (P &lt; 0.05). For the surface electromyography of PFMs, the differences in pre-baseline rest, post-baseline rest, isometric contractions for muscle endurance evaluation, and coefficient of variation were statistically significant (P &lt; 0.05). Linear regression analysis showed that disease course (X 1), dyspareunia (X 5), and urinary incontinence (X 6) were influencing factors for the decline of pre-baseline rest (r5 = 1.067, R 2 = 0.089), post-baseline rest (r1 = 0.055, r5 = 0.99, R 2 = 0.119), VASs of ischial spine (r5 = 0.916, R 2 = 0.102), obturator internus (r5 = 0.796, r6 = −0.703, R 2 = 0.245), and pubococcygeus (r5 = 0.885, R 2 = 0.149) after treatment in the CPPS group. This study confirmed that individualized myofascial release therapy combined with electrical and magnetic stimulation has significant efficacy for patients with CPPS. At the same time, it is more effective for CPPS patients with longer course of disease, dyspareunia, and without urinary incontinence.

Efficacy and safety of ultrasound-guided pulsed radiofrequency in the treatment of the ophthalmic branch of postherpetic trigeminal neuralgia

ObjectiveTo investigate the efficacy and safety of ultrasound-guided pulsed radiofrequency (PRF) targeting the supraorbital nerve for treating the ophthalmic branch of postherpetic trigeminal neuralgia.MethodsA retrospective cohort study was conducted involving patients who presented at the Department of Pain, Affiliated Hospital of Southwest Medical University from January 2015 to January 2022. The patients were diagnosed with the first branch of postherpetic trigeminal neuralgia. In total, 63 patients were included based on the inclusion and exclusion criteria. The patients were divided into the following two groups based on the treatment method used: the nerve block (NB) group (n = 32) and the PRF + NB group (radiofrequency group, n = 31). The visual analog scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score, and pregabalin dose were compared between the two groups before treatment, 1 week after the procedure, and 1, 3, and 6 months post-procedure, and the complications, such as local infection, local hematoma, and decreased visual acuity, were monitored post-treatment.ResultsNo significant difference was found in terms of pretreatment age, sex, course of disease, preoperative VAS score, preoperative PSQI score, and preoperative pregabalin dose between the two groups (P &amp;gt; 0.05). The postoperative VAS score, PSQI score, and pregabalin dose were significantly decreased in both groups. Furthermore, significant differences were found between the two groups at each preoperative and postoperative time point (P &amp;lt; 0.05). The VAS score was lower in the radiofrequency group than in the NB group at 1, 3, and 6 months, and the difference was statistically significant (P &amp;lt; 0.05). The PSQI score was lower in the radiofrequency group than in the NB group at 1 week, 1, 3, and 6 months post-procedure, and the difference was statistically significant (P &amp;lt; 0.05). The dose of pregabalin was lower in the radiofrequency group than in the NB group at 1 week, 1, 3, and 6 months post-procedure, and the difference was statistically significant at 3 and 6 months (P &amp;lt; 0.05). After 6 months of treatment, the excellent rate of VAS score in the radiofrequency group was 70.96%, and the overall effective rate was 90.32%, which was higher than that in the NB group. The difference in the efficacy was statistically significant (P &amp;lt; 0.05).ConclusionPRF targeting the supraorbital nerve can effectively control the pain in the first branch of the trigeminal nerve after herpes, enhance sleep quality, and reduce the dose of pregabalin. Thus, this study shows that PRF is safe under ultrasound guidance and is worthy of clinical application.

Vaccination status and self-reported side effects after SARS-CoV-2 vaccination in relation to psychological and clinical variables in patients with multiple sclerosis

The recent SARS-CoV-2 pandemic and the vaccination campaign posed a challenge to patients with autoimmune disease, such as multiple sclerosis (MS). We aimed for investigating whether psychological/sociodemographic/clinical characteristics of MS patients are associated with SARS-CoV-2 vaccination status and self-reported vaccination side effects (SEs). We have asked patients with MS about their willingness to receive recommended standard vaccinations pre-pandemically since June 2019. Between 10/2021 and 01/2022, we surveyed 193 of these MS patients about their current SARS-CoV-2 vaccination status, their perception of vaccination-related SEs, and reasons for and against SARS-CoV-2 vaccination. 75.6% of the patients declared their willingness to receive standard vaccinations before the pandemic. 84.5%, 78.2%, and 13.0% of the patients had received the first, second, and third SARS-CoV-2 vaccination, respectively, until the follow-up survey. The most common reason for not getting vaccinated against SARS-CoV-2 was concern about possible side effects (82.1%), followed by the belief that the vaccines had not been adequately tested (64.3%). Vaccination-related SEs were reported by 52.8% of the patients. Younger age, higher education, lower degree of disability, relapsing disease course, shorter disease duration, not receiving a disease-modifying therapy and higher anxiety and depression levels were associated with the occurrence of certain vaccination-related SEs. Concerns about novel vaccines are widespread among MS patients and necessitate targeted education of the patients, especially to those with more severe psychopathological symptoms (anxiety or depression) and those who are generally skeptical of vaccination.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis

BackgroundRefractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0–2) at last follow-up.ResultsA total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = &amp;lt;0.0001). Older age at SE (OR = 1.384[1.046–1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362–1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069–0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168–2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323–10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0–2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified.ConclusionOur findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

Cardioprotective Effects of Exercise: The Role of Irisin and Exosome.

Exercise is an effective measure for preventing and treating cardiovascular diseases, although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore, it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review, the potential synergistic interactions between irisin and exosomes are examined, as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway, the TGFβ1/Smad2/3 pathway, the PI3K/AKT/VEGF pathway, and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin, miR-486-5p and miR-342-5p from skeletal muscles, which results in the activation protective networks in the cardiovascular system. Moreover, the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.

Establishment of a Clinical Prediction Model Based on the Study of Risk Factors for Pain Recurrence after Percutaneous Radiofrequency Thermocoagulation in Patients with Primary Trigeminal Neuralgia

Objectives: This study aimed to investigate the follow-up outcomes and risk factors associated with pain recurrence after percutaneous radiofrequency thermocoagulation (PRT) among patients with primary trigeminal neuralgia (PTN) and to establish a clinical prediction model based on these risk factors. Methods: The data of PTN patients who underwent PRT were collected in our study. All subjects were randomly divided at a 7:3 ratio into a training group (T Group) and a test group (C Group) to select risk factors. According to the follow-up results, the patients were divided into a recurrence group (F Group) and a nonrecurrence group (NF Group). Predictive factors were selected through LASSO regression analysis based on T Group. The identified variables were subjected to multivariate logistic regression analysis to construct a nomogram. Receiver operating characteristic (ROC) curves and calibration curves were uesd to evaluate discrimination and calibration ability separately. Results: A total of 884 patients were initially included, 857 patients achieved satisfactory results, and the pain relief rate at discharge was 96.95%. A total of 529 subjects were included after screening, and the recurrence rate was 27.22% after 1 year. Six non-zero variables were selected through LASSO regression analysis: the disease course, atypical pain, previous surgery, facial numbness before PRT, neurovascular contact (NVC), and operation duration. Six variables were included in the multivariate logistic regression analysis, and the results showed that they were independent risk factors (P&lt;0.05). The predictive model is represented by a nomogram. The area under the curves (AUC) of the ROC curves were 0.868 (0.826~0.909) and 0.874 (0.802~0.950) for T Group and C Group, respectively. The prediction curves for T Group (P=0.784) and C Group (P=0.293) fit the ideal prediction curve, and the Brier scores were 0.120 and 0.099 for T Group and C Group, which indicates that the probability predicted by the model is consistent with the actual occurrence. Conclusion: The Pain relief rate at discharge was 96.95% for PTN patients after PRT, and the recurrence rate was 27.22% after 1 year. The disease course, atypical pain, previous surgery, facial numbness before PRT, NVC, and operation duration are independent risk factors for the recurrence of pain. A nomogram model for pain recurrence was established, which has good predictive ability.

Percutaneous pedicle screw anchored vertebral augmentation for the treatment of Kümmell disease without neurological symptoms

To explore the clinical effect of percutaneous pedicle screw anchored vertebral augmentation(PPSAVA) in the treatment of asymptomatic Kümmell disease without neurological symptoms. The clinical data of 20 patients with Kümmell disease without neurological symptoms treated with PPSAVA in our hospital from January 2019 to December 2021 were analyzed retrospectively, including 5 males and 15 females, aged 56 to 88 (74.95±9.93) years old. and the course of disease was 7 to 60 days with an average of (21.35±14.46) days. All patients were treated with PPSAVA. The time of operation, the amount of bone cement injected and the leakage of bone cement were recorded. The visual analogue scale(VAS), Oswestry disability index(ODI), vertebral body angle(VBA), anterior edge height and midline height of vertebral body were compared among the before operation, 3 days after operation and during the final follow-up. The loosening and displacement of bone cement were observed during the final follow-up. All the 20 patients completed the operation successfully. The operation time was 30 to 56 min with an average of (41.15±7.65) min, and the amount of bone cement injection was 6.0 to 12.0 ml with an average of (9.30±1.49) ml. Bone cement leakage occurred in 6 cases and there were no obvious clinical symptoms. The follow-up time was 6 to 12 months with an average of (8.43±2.82) months. The VBA, anterior edge height and midline height of of injured vertebral body were significantly improved 3 days after operation and the final follow-up(P<0.05), and the VBA, anterior edge height and midline height of of injured vertebral body were lost in different degrees at the final follow-up (P<0.05). The VAS and ODI at 3 days after operation and at the final follow-up were significantly lower than those at preoperatively(P<0.05), but the VAS score and ODI at the final follow-up were not significantly different from those at 3 d after operation(P>0.05). At the last follow-up, no patients showed loosening or displacement of bone cement. PPSAVA is highly effective in treating Kümmell disease without neurological symptoms, improving patients' pain and functional impairment, and reducing the risk of cement loosening and displacement postoperatively.

P.100 Plasma extracellular vesicle sampling from high grade gliomas demonstrates a small RNA signature indicative of disease and identifies lncRNA RPPH1 as a novel biomarker

Background: High grade gliomas (HGGs) and cells of the tumour microenvironment secrete extracellular vesicles (EVs) into the plasma that contain genetic and protein cargo which function in paracrine signalling. Isolation of these EVs and their cargo could lead to an important tool that can inform on diagnosis and disease-course of HGGs. Methods: EVs were isolated using Vn96 capture from plasma obtained longitudinally from HGG patients. sRNA was enriched from the EVs, followed by next-generation sequencing, multidimensional scaling, differential expression, and in silico functional enrichment analyses. Results: Over 750 differentially expressed sRNA were identified between HGG and controls. Pathway analysis revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from HGG. Other sRNA included several novel HGG plasma-EV biomarkers including lncRNA RPPH1, RNY4, and RNY5. Furthermore, in paired longitudinal patient sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly increased again with clinically defined progression. TCGA analysis demonstrated increased expression of RPPH1 in HGG tissue and additionally, higher expression of RPPH1 was associated with a worse disease-specific prognosis. Conclusions: The present study supports the role of plasma-EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG disease course surveillance.

#163 Multiome-seq and spatial transcriptomics of refractory PLA2RAb(+) membranous nephropathy reveals importance of immunomodulatory function of B cells

Abstract Background and Aims PLA2RAb-associated membranous nephropathy (MN) is a glomerulonephritis that may require immunosuppression to achieve proteinuria remission. However, the disease course is heterogeneous, and some patients exhibit refractory or relapsing nephrotic-range proteinuria. Additional biomarker studies are necessary to dissect the molecular profiles that reflect substantial differences in treatment response and clinical courses. Multiome-seq includes the investigation of gene expression profiles and ATAC-sequencing for open-chromatin regions, which may reveal pathophysiologic gene expression biomarkers and pathways. Method We performed multiome-sequencing of peripheral blood mononuclear cells (PBMCs) from 6 refractory or relapsing primary PLA2RAb-associated MN cases, 7 PLA2RAb-associated MN cases that reached complete remission, and disease controls including 6 minimal change disease and 6 diabetic kidney disease cases. We also collected PBMCs from 7 healthy controls. Cell type clustering, comparison of cell type proportions, and differential gene expression analysis were performed. Additionally, we conducted ATAC-sequencing analysis and identified open-chromatin profiles specific to the refractory or relapsing MN group. Lastly, we investigated the glomerular spatial transcriptome using GeoMx digital spatial profiling to determine whether transcriptomic profiles differ based on the disease courses of MN in the initial kidney tissue. Results We successfully identified diverse PBMCs in the multiome-seq data. In the DEG analysis, we identified a number of cell-type-specific DEGs in the refractory or relapsing MN cases. Of these, CD83 was the top gene that was lowly expressed in the B cells of refractory/relapsing MN compared to the remission cases. In the ATAC data, among the number of differentially expressed peaks, NFKB2 was the region that consistently showed a low open chromatin profile in the B cells of CD83. When comparing the cell subtype proportions, refractory or relapsing MN cases showed low regulatory T cells in the peripheral blood. Lastly, in the kidney tissue spatial transcriptomic profiling, there were no significant DEGs between the refractory/relapsing MN and MN with remission in the glomerulus. Conclusion The clinical course or risk of remission of PLA2RAb-associated MN was more likely a result of differences in systemic immunity rather than differences in the glomerular transcriptome at the initial diagnosis. Both CD83 and NFκB2 are well-known biomarkers of activated B cells that may have immunomodulatory roles leading to the enrichment of regulatory T cells. Such a deficient immunomodulatory status in refractory/relapsing PLA2RAb-associated MN may explain the disease course.

#901 Natural history of idiopathic nephrotic syndrome: the UK National RaDaR Idiopathic Nephrotic Syndrome Cohort

Abstract Background and Aims Idiopathic nephrotic syndrome (INS) is an important class of proteinuric renal disease leading to kidney failure (KF). Here we describe the natural history of INS and congenital nephrotic syndrome (NS) using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4610 patients with NS not attributable to glomerulonephritis or systemic disorders recruited from 107 adult and paediatric kidney units across the UK since 2010. Method Participant eligibility of RaDaR-INS Cohort patients included ≥12 months observation from disease onset and no KF (CKD stage 5 or on renal replacement therapy) at or prior to disease onset. Disease onset date was defined as first database occurrence of kidney biopsy, primary diagnosis or protein-creatinine ratio (PCR) ≥1.5 g/g. Participants were sub-categorized into those with a genetic diagnosis (INS-genetic), biopsy-proven FSGS (FSGS-biopsy), biopsy–proven minimal change disease (MCD-biopsy) and those with no genetic or biopsy-proven diagnosis (INS-no genetic or biopsy diagnosis). Participants with a biopsy-proven MCD diagnosis and a subsequent biopsy proven FSGS diagnosis were included in both MCD-biopsy and FSGS-biopsy categories and formed a category of their own (MCD progressing to FSGS). Longitudinal proteinuria, assessed as time-average protein-to-creatinine ratio (TA-PCR), and eGFR slope were calculated over the full duration of follow-up or until KF. Kidney survival was calculated from disease onset to event (KF or death) and censored at last follow-up. Results Of the 4066 patients meeting eligibility, median age at disease onset was 28 years (IQR 6-51), with children (&amp;lt;18 yrs) representing 39% of the study population. Median proteinuria was 6.4 g/g (IQR 3.1-10.8; n = 923), while mean eGFR was 118 mL/min/1.73 m2 (SD 49; n = 240) and 69 mL/min/1.73 m2 (SD 34; n = 906) for children and adults, respectively. Median follow-up duration was 8.2 yrs (IQR 4.3-13.1) with KF/death events occurring in 30% of patients. Mean TA-PCR was greater in children than adults (5.0 g/g (SD 13.9) vs. 1.9 g/g (SD 2.5), as was annual rate of loss of eGFR (−7.4 mL/min/1.73 m2 (SD 21.8) vs. −3.1 mL/min/1.73 m2 (SD 10.2)). Characteristics at disease onset and clinical outcomes of the INS cohort sub-categories are presented in Fig. 1. Kaplan Meier survival plots of each sub-category, and further divided into children and adults, illustrate the poor survival probability for patients with FSGS, particularly INS-genetic patients who are predominantly diagnosed in childhood (Fig. 2). While INS with no genetic or biopsy diagnosis presenting in childhood exhibits disease course and outcomes similar to MCD-biopsy patients, those diagnosed in adulthood have a more rapid disease course similar to FSGS-biopsy patients. Conclusion The RaDaR-INS cohort represents a large study population with lengthy follow-up data. These analyses illustrate the difference in disease progression and survival rates for INS patients with different causes or histological descriptions, highlighting in particular an unmet need for effective treatments for patients with nephrotic syndrome and FSGS.

#511 Inadequate diagnostic investigations and low treatment rates in CKD anemia: an inertia that can only change with long-term follow-up

Abstract Background and Aims Anemia is observed from the early stages in the course of chronic kidney disease (CKD), and as the stage progresses, the severity of anemia and its impact on quality of life increase. Early diagnosis of anemia in chronic kidney disease, assessments related to its etiology, and treatment are therefore crucial. There is no comprehensive and long-term study in Turkey addressing the diagnostic and therapeutic management of anemia seen in the course of chronic kidney disease. The aim of this study is to investigate the frequency of anemia in different stages of CKD in patients diagnosed with Stage 3 and more advanced stages, to evaluate the effectiveness of diagnostic approaches, and management of iron parameters and anemia, and to investigate the effect of anemia on patient survival. We aim to present “real-life” data from this study to guide clinical practice and correct errors or deficiencies in anemia management. Method This study is a single-center, observational-descriptive retrospective study. 1321 outpatients with Stage 3A and advanced CKD and anemia who admitted to Hacettepe University Faculty of Medicine Nephrology Clinic between 2014 and 2018 were included in the study. Data for demographics, CKD etiologies and stages, anemia severities, comorbid diseases were collected from electronic health system (Table 1). Diagnostic investigations for anemia evaluation and therapeutic interventions such as administration of iron, folic acid, vitamin B12, erythropoiesis stimulating agents (ESA) were assessed. The long-term yield of diagnostic and therapeutic approaches and their effects on survival were also evaluated. The study investigated whether the severity of anemia and improvement in anemia had an effect on survival. Results Ferritin is the most commonly performed test for the etiology of anemia (76.4%). Request rates for tests such as B12, folic acid, transferrin saturation and reticulocyte are below 20%. More than half of the patients with anemia (59.4%) have not received any form of anemia treatment. Even among those whose ferritin test was checked and the value was &amp;lt;100 µg/dL, only 41.4% were given iron treatment. As the clinical follow-up period of the patients increased, it was observed that anemia treatment was applied better and target values were reached more frequently (p &amp;lt; 0.001). More than one third of the patients (34.8%) died during follow-up. The overall survival in patients whose anemia improved was 79.8%, and it was 62.8% in patients whose anemia did not improve the overall survival was (p = 0.002) (Fig. 1). When examining the relationship between survival status and anemia severity for the non-dialysis-dependent CKD Stage 3-5 group, there was a statistically significant survival difference between the Hb group of 10-11.9 g/dL to Hb group of &amp;lt;10 g/dL (p = 0.004). Conclusion This study has shown that diagnostic tests for etiology of anemia were insufficiently ordered. It was also found that a significant majority of anemic patients who underwent etiological evaluation were not even adequately treated. Long-term follow up improved anemia treatment, and patients with improved anemia had better survival. In conclusion, we recommend an optimal evaluation of CKD patients with anemia and initiating treatment as early as possible.

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.