Persistence Rates Research Articles

Persistence on subcutaneous tocilizumab as monotherapy or in combination with synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients in Greece (EMBRACE study): a multicenter, post-marketing, non-interventional, observational trial

IntroductionRheumatoid arthritis (RA) is a systemic, inflammatory disease affecting multiple organs and causing physical disability over time.ObjectiveThe primary objective was to evaluate treatment persistence to subcutaneous tocilizumab (TCZ-SC). Additionally, treatment effects on persistence and their associations with clinical and patient-reported outcomes were assessed.MethodWe performed a multicenter, non-interventional, 52-week observational study on 222 patients with moderate or severe RA. Clinical outcomes were evaluated by using disease activity score for 28 joints (DAS28) and European League Against Rheumatism (EULAR) response, and patients’ perceptions were evaluated by using Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS) for pain, and patient global assessment (PtGA) of disease activity. Safety was assessed throughout the study.ResultsThe mean age of the overall cohort was 62.2 ± 12.3 years, and 83.8% were females. Persistence to TCZ-SC was 89.6% at week 24 and 85.1% at week 52 in the overall cohort with slightly increased persistence in the combination group. At week 52, changes from the baseline were − 2.68 in DAS28, − 0.76 in HAQ, − 43.21 in VAS pain, and − 41.66 in PtGA (p < 0.0001 for all). Moderate and good EULAR response was achieved in 83.2% of patients. Non-serious and serious adverse events occurred in 18.5% and 3.2% of the participants, respectively.ConclusionsThe current study confirms the favorable safety and effectiveness of TCZ-SC as well as its acceptability by RA patients in Greece, with sustained high persistence rates up to 52 weeks. TCZ-SC offers a sustainable treatment response in RA.Key Points• Based upon clinical and patient-reported outcomes, TCZ-SC is a highly effective and safe treatment modality in patients with moderate-to-severe RA.• Persistence to TCZ-SC was high throughout the study, both as monotherapy and in combination with csDMARDs.• TCZ-SC is effective both as monotherapy and when used in combination with other csDMARDs regardless of the line of treatment.

Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials

BackgroundConventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene–related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders.MethodsThis post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM).ResultsThe safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation.ConclusionsOverall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults.Trial registrationClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309).Graphical

Using historical habitat loss to predict contemporary mammal extirpations in Neotropical forests.

Understanding which species will be extirpated in the aftermath of large-scale human disturbance is critical to mitigating biodiversity loss, particularly in hyperdiverse tropical biomes. Deforestation is the strongest driver of contemporary local extinctions in tropical forests but may occur at different tempos. The 2 most extensive tropical forest biomes in South America-the Atlantic Forest and the Amazon-have experienced historically divergent pathways of habitat loss and biodiversity decay, providing a unique case study to investigate rates of local species persistence on a single continent. We quantified medium- to large-bodied mammal species persistence across these biomes to elucidate how landscape configuration affects their persistence and associated ecological functions. We collected occurrence data for 617 assemblages of medium- to large-bodied mammal species (>1kg) in the Atlantic Forest and the Amazon. Analyzing natural habitat cover based on satellite data (1985-2022), we employed descriptive statistics and generalized linear models (GLMs) to investigate ecospecies occurrence patterns in relation to habitat cover across the landscapes. The subregional erosion of Amazonian mammal assemblage diversity since the 1970s mirrors that observed since the colonial conquest of the Atlantic Forest, given that 52.8% of all Amazonian mammals are now on a similar trajectory. Four out of 5 large mammals in the Atlantic Forest were prone to extirpation, whereas 53% of Amazonian mammals were vulnerable to extirpation. Greater natural habitat cover increased the persistence likelihood of ecospecies in both biomes. These trends reflected a median local species loss 63.9% higher in the Atlantic Forest than in the Amazon, which appears to be moving toward a turning point of forest habitat loss and degradation. The contrasting trajectories of species persistence in the Amazon and Atlantic Forest domains underscore the importance of considering historical habitat loss pathways and regional biodiversity erosion in conservation strategies. By focusing on landscape configuration and identifying essential ecological functions associated with large vertebrate species, conservation planning and management practices can be better informed.

Evaluation of concordance between loop electrosurgical excisional procedure and cervical colposcopic biopsy results

To evaluate the results of loop electrosurgical excisional procedures (LEEP) with colposcopic biopsy results of patients who presented to our hospital for vaginal smears. The LEEP reports of patients who presented to our gynecology clinic between January 2015 and December 2020 were retrospectively evaluated. The data were obtained from electronic patient records and the department of medical pathology archives. A total of 579 patients were evaluated with a mean age of 38.05±6.17 years. Colposcopy-guided biopsy was not taken from 102 patients. The results of the remaining 477 (82.4%) patients were: no dysplasia (n=12; 2.1%), Cervical intraepithelial neoplasia-I (CIN-I) (n=99; 17.1%), CIN-II (n=111; 19.2%), CIN-III (n=248; 42.8%), and cancer (n=7; 1.2%). Completed excision was performed in 87.0% of the patients using LEEP, the lesion was positive at the surgical margins in 10.9%, and the lesion could not be completely excised in 2.1%. The complication rate after LEEP was 3.1% including pelvic pain (n=5; 0.9%) and bleeding (n=13; 2%). The histopathologic results of LEEP were: benign (n=50; 8.6%), CIN-I (n=110; 19.0%), CIN-II (n=89; 15.4%), CIN-III (n=280; 48.4%), cancer (n=7; 1.2%), and metaplasia (n=37; 6.4%). The concordance between colposcopic biopsy and LEEP results was 85.9% for CIN-I, 71.2% for CIN-II, 98.4% for CIN-III, and 85.7% for cancer diagnoses. LEEP is a simple minimally invasive method used in the treatment of CIN, with low persistence, recurrence, and complication rates and increased human papillomavirus clearance in most patients. Our results support the consistency of cervical colposcopic biopsy and LEEP results.

Two-year treatment persistence with subcutaneous abatacept in rheumatoid arthritis: results from the French cohort of the ASCORE study.

While multiple studies have investigated treatment persistence rates with intravenous abatacept, limited information is available about real-world treatment continuation with the subcutaneous form. The international ASCORE study described the characteristics and treatment persistence of real-world patients with rheumatoid arthritis (RA) receiving subcutaneous abatacept. This article presents the findings of the French cohort. This was an observational study in French RA patients who initiated subcutaneous abatacept between August 2014 and January 2017. The primary endpoint was treatment maintenance at 2 years, analysed according to the number of previous biologic therapies. Of 546 evaluable patients, 281 (51.5%) were biologic-naive, 265 (48.5%) had experienced failure with 1 (n=134; 24.5%) or ≥2 (n=131; 24.0%) biologic therapies. At enrolment, patients who had experienced failure with ≥1 biologic therapy had more erosions and a longer duration of RA compared with biologic-naive patients, but had comparable mean disease activity scores. Overall, 43.0% of patients (95% confidence interval 38.6-47.2) were still taking subcutaneous abatacept at 2 years, which was comparable with that in other countries participating in ASCORE. The abatacept persistence rate was higher in biologic-naive patients (48.8%) than in those with 1 (40.9%) or ≥2 (32.8%) biologic therapy failures. The main reason for discontinuing abatacept was lack of efficacy (46.6%). In current practice in France, the rate of subcutaneous abatacept persistence at 2 years was comparable with that of the intravenous form. Treatment persistence was higher when abatacept was used as first-line versus later-line biologic therapy.

Characterization of the agonistic behavior of the weakly electric fish Gymnotus sylvius

AbstractElectric fish are good models in neuroethology as any behavior in electric fish involves both locomotor and electrical displays, which are experimentally accessible and controlled by well‐known neural circuits. The agonistic behavior within the genus Gymnotus has been evaluated in Gymnotus carapo and Gymnotus omarorum, providing an advantageous model system to address comparative analyses. Gymnotus sylvius is a weakly electric fish which occurs in sympatry with G. omarorum in freshwater environments of Argentina. Here, we describe the agonistic behavior of G. sylvius in laboratory conditions. All dyads engaged in intense fights, with a latency to the first attack of 8 ± 7.8 s and a contest phase of 42.71 ± 31.7 s. Individual initiative in the first attack predicted contest outcome with no apparent influence of body weight asymmetry between contenders. Contenders did not escalate in their aggression during the short contest; in turn, subordinates tended to retreat in response to dominants' attacks. Submission and dominance were expressed by electric signals: dominants increased their basal electric organ discharge (EOD) rate after contest resolution, resulting in a persistent EOD rate rank. Subordinates also emitted chirps and offs during the contest and post‐resolution phases without a clear temporal pattern. The agonistic behavior of G. sylvius presents some similarities with other species of the genus Gymnotus: EOD rank between dominants and subordinates, electric signals of submission, and the presence of attacks in the post‐resolution phase. On the other hand, it also presents differences: a shorter evaluation phase in G. sylvius, initiative as a determinant of outcome, a higher attack rate of dominants in G. sylvius, a different temporal pattern of chirps, and different mechanisms to separate EOD rate of dominants and subordinates. These facts open a promising road to analyze the evolution of different neuroendocrine strategies, operating on homologous neural pathways, to command the same behavior.

Targeted Coaching to Improve Osteoporosis Therapy Adherence: A Single Arm Variation of the C-STOP Study.

In this pre-planned variation of the Comparing Strategies Targeting Osteoporosis to Prevent Fractures After an Upper Extremity Fracture (C-STOP) trial, we investigated whether adherence-specific coaching by the case manager (CM) further improved the adherence and persistence rates compared to those seen in the C-STOP trial. We conducted a prospective observational cohort study of community-dwelling adults 50 years or older who suffered an upper-extremity fracture and were not previously treated with osteoporosis medications, to assess whether a well-trained CM can partner with patients to improve adherence to and persistence with oral bisphosphonate intake. The primary outcome was adherence (taking > 80% of prescribed doses) to oral bisphosphonate intake at 12 months after study enrollment. Secondary outcomes included primary adherence to and 12-month persistence with oral bisphosphonate and calcium and vitamin D supplement intake at 12 months. The study cohort consisted of 84 participants, of which 30 were prescribed an oral bisphosphonate. Twenty-two (73.3%) started treatment within 3 months. The adherence rate at 12 months was 77.3%. The persistence rate at 12 months was 95.5%. Of those not prescribed an oral bisphosphonate, 62.8% were taking supplemental calcium and 93.0% were taking supplemental vitamin D at 12 months. Depression was a significant predictor of 12-month non-adherence (adjusted odds ratio, 9.8; 95% confidence interval, 1.2-81.5). Adherence-specific coaching by a CM did not further improve the level of medication adherence achieved in the original C-STOP study. Importantly, these results can inform adherence in future intervention studies.

The Vaginal Microbiota, Human Papillomavirus Infection, and Cervical Carcinogenesis: A Systematic Review in the Latina Population

BackgroundLatina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial–ethnic groups. This systematic review explores the relationship between the cervicovaginal microbiome and human papillomavirus infection, cervical dysplasia, and cervical cancer in Latinas.MethodsThe review abides by the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, EMBASE, and Scopus databases were searched from January 2000 through November 11, 2022. The review included observational studies reporting on the cervicovaginal microbiota in premenopausal Latina women with human papillomavirus infection, cervical dysplasia, and cervical cancer.ResultsTwenty-five articles were eligible for final inclusion (N = 131,183). Forty-two unique bacteria were reported in the cervicovaginal microbiome of Latinas. Seven bacteria: Lactobacillus crispatus, Lactobacillus iners, Chlamydia trachomatis, Prevotella spp., Prevotella amnii, Fusobacterium spp. and Sneathia spp. were enriched across multiple stages of cervical carcinogenesis in Latinas. Therefore, the total number of reported bacteria includes four bacteria associated with the healthy state, 16 bacteria enriched in human papillomavirus outcomes, 24 unique bacteria associated with abnormal cytology/dysplasia, and five bacteria associated with cervical cancer. Furthermore, three studies reported significantly higher alpha and beta diversity in Latinas with cervical dysplasia and cancer compared to controls. Lactobacillus depletion and an increased abundance of L. iners in Latinas compared to non-Latinas, regardless of human papillomavirus status or lesions, were observed.ConclusionsThe identification of 42 unique bacteria and their enrichment in cervical carcinogenesis can guide future cervicovaginal microbiome research to better inform cervical cancer prevention strategies in Latinas.

Deciphering differential exhumation in the Gangdese orogen in southern Tibet using exposed porphyry alteration systems and geomorphic analysis

Topography and exhumation vary strongly in the Tibetan Plateau, reflecting different geodynamics and surface processes. The Gangdese orogen in southern Tibet is characterized by west-to-east variations in topography and occurrences of the Miocene porphyry copper deposits. We integrated remote sensing based hydrothermal alteration mapping and geomorphological analysis to detect patterns of differential exhumation since the Miocene. High abundances of propylitic and potassic alteration of the eastern Miocene granitoids are identified, indicating &amp;gt;2 km of exhumation since the Miocene. The western Gangdese has intensive phyllic and argillic alteration representing ∼1 km of exhumation. Geomorphic analyses also show E-W changes that most likely resulted from differential rock uplift histories. Channel steepness index values indicate the eastern Gangdese has channel gradients between 211 m1.02 and 457 m1.02, compared to values between 30 m1.02 and 160 m1.02 in the west. Linear inversion of tributaries of the Yarlung river shows a pulse of rock uplift between 25 Ma and 7 Ma with a maximum rate of 110 m/ m.y. in the east. In contrast, the western Gangdese exhibits slower and persistent rock uplift rates between 20 m/m.y. and 40 m/m.y. since 20 Ma. The integrated results record differential exhumation and rock uplift since the Miocene. We invoke the geometric variations of the subducted Indian lithosphere to interpret the E-W differential exhumation since the Miocene. Steeper subduction of the Indian lithosphere beneath the eastern Gangdese induced mantle upwelling, triggering rapid rock uplift and deep exhumation. Conversely, the shallower subduction of the Indian slab in the west generated slow and prolonged rock uplift with less exhumation. Our study refines the exhumation process of the Gangdese since the Miocene.

Laparoscopic Treatment of Perforated Peptic Ulcer: A Propensity Score-Matched Comparison of Interrupted Stitches Repair versus Knotless Barbed Suture.

Background: Peptic ulcers result from imbalanced acid production, and in recent decades, proton pump inhibitors have proven effective in treating them. However, perforated peptic ulcers (PPU) continue to occur with a persistent high mortality rate when not managed properly. The advantages of the laparoscopic approach have been widely acknowledged. Nevertheless, concerning certain technical aspects of this method, such as the best gastrorrhaphy technique, the consensus remains elusive. Consequently, the choice tends to rely on individual surgical experiences. Our study aimed to compare interrupted stitches versus running barbed suture for laparoscopic PPU repair. Methods: We conducted a retrospective study utilizing propensity score matching analysis on patients who underwent laparoscopic PPU repair. Patients were categorised into two groups: Interrupted Stitches Suture (IStiS) and Knotless Suture (KnotS). We then compared the clinical and pathological characteristics of patients in both groups. Results: A total of 265 patients underwent laparoscopic PPU repair: 198 patients with interrupted stitches technique and 67 with barbed knotless suture. Following propensity score matching, each group (IStiS and KnotS) comprised 56 patients. The analysis revealed that operative time did not differ between groups: 87.9 ± 39.7 vs. 92.8 ± 42.6 min (p = 0.537). Postoperative morbidity (24.0% vs. 32.7%, p = 0.331) and Clavien-Dindo III (10.7% vs. 5.4%, p = 0.489) were more frequently observed in the KnotS group, without any significant difference. In contrast, we found a slightly higher mortality rate in the IStiS group (10.7% vs. 7.1%, p = 0.742). Concerning leaks, no differences emerged between groups (3.6% vs. 5.4%, p = 1.000). Conclusions: Laparoscopic PPU repair with knotless barbed sutures is a non-inferior alternative to interrupted stitches repair. Nevertheless, further research such as randomised trials, with a standardised treatment protocol according to ulcer size, are required to identify the best gastrorraphy technique.

The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3.

A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.

Current management of SARS-CoV-2 infection in solid organ transplant recipients: Experience derived from an ESGICH-ESOT survey.

Solid organ transplant (SOT) recipients have a poorer SARS-CoV-2 vaccine response and higher risk for COVID-19-associated complications. However, there is no consensus on the current management of COVID-19 and data on persistent COVID-19 rates in SOT recipients are lacking. An electronic survey concerning the management of COVID-19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID-19, late COVID-19, and persistent COVID-19. We developed a structured questionnaire including eight multiple-choice questions with branching logic in case of positive answers and three open-ended questions related to clinical practice. Questions were asked separately for lung and non-lung transplantation. Thirty-two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non-lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID-19, and particularly noticeable when considering lung and non-lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID-19, the use of immunomodulatory drugs other than steroids for late COVID-19, and the need for treating asymptomatic viral shedding in persistent COVID-19. There was more similarity in terms of prophylaxis recommendations. Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS-CoV-2 infections in SOT recipients.

Once-Weekly Somapacitan as an Alternative Management of Growth Hormone Deficiency in Prepubertal Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily growth hormone injection regimen, leading to low adherence and persistence rates. Once-weekly Somapacitan is a potential alternative for treating children with GHD. This study aimed to evaluate the efficacy, safety, and adherence of once-weekly subcutaneous Somapacitan compared to daily growth hormone injection in prepubertal children with GHD. A search for the published records was carried out on 17 October 2023 utilizing the searching feature available on PubMed, Embase, and Scopus. Primary study outcomes included (1) efficacy, measured by height velocity (HV), standard deviation score (SDs), height SDs, insulin-like growth factor-SDs (IGF-I SDs), and bone age vs. chronological age ratio (BA vs. CA); (2) safety, assessed through adverse events and injection site reactions; and (3) adherence, determined by the percentage of the sample completing treatments. Secondary outcomes evaluated disease burden scores, divided into three subgroup domains: emotional well-being, physical functional, and social well-being scores. We retrieved 6 studies that were eligible for the systematic review (417 versus 186 for intervention and control, respectively). Only 2 of the total included studies were eligible for pooled analysis (175 versus 82 for intervention and control, respectively). The efficacy profile of Somapacitan was similar to daily growth hormones, indicated by HV (mean difference (MD = 0.04; p = 0.96), HV SDs (MD = -0.71; p = 0.09), height SDs (MD = 0.11; p = 0.69), IGF-I SDs (MD = 0.06; p = 0.70), and CA vs. BA (MD = 0.67; p = 0.70)), demonstrated similar and non-inferior outcomes. Treatment adherence is 3 times higher in the Somapacitan group as compared to control (OR = 3.02; p = 0.03) with adherence rates reaching 95% and 88% for Somapacitan and Norditropin®, respectively. The disease burden measurement is similar in Somapacitan and daily growth hormones (MD = -0.62; p = 0.83), as indicated by the Growth Hormone Deficiency-Child Impact Measure. In almost all outcomes, the level of confidence is strong. The confidence level in the data is generally strong, but for CA vs. BA and the subgroup of severe adverse events with heterogeneity >50%, the confidence level is moderate. Although the efficacy and safety profiles of Somapacitan were found to be similar to those of daily growth hormones, a reduced frequency of once-weekly Somapacitan injections led to increased adherence. PROSPERO registration: CRD42023473209.

Adalimumab Biosimilar in Pediatric Inflammatory Bowel Disease: A Retrospective Study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD)

Background: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. Methods: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. Results: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). Conclusions: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective.

Insomnia is more likely to persist than remit after a time of stress and uncertainty: a longitudinal cohort study examining trajectories and predictors of insomnia symptoms.

The study aimed to characterize insomnia symptom trajectories over 12 months during a time of stress and uncertainty, the coronavirus disease 2019 (COVID-19) pandemic. It also aimed to investigate sleep and psychological predictors of persistent insomnia symptoms. This longitudinal cohort study comprised 2069 participants with and without insomnia symptoms during the first year of the pandemic. Participants completed online surveys investigating sleep, insomnia, and mental health at four timepoints over 12 months (April 2020-May 2021). Additional trait-level cognitive/psychological questionnaires were administered at 3 months only. Six distinct classes of insomnia symptoms emerged: (1) severe persistent insomnia symptoms (21.65%), (2) moderate persistent insomnia symptoms (32.62%), (3) persistent good sleep (32.82%), (4) severe insomnia symptoms at baseline but remitting over time (2.27%), (5) moderate insomnia symptoms at baseline but remitting over time (7.78%), and (6) good sleep at baseline but deteriorating into insomnia symptoms over time (2.85%). Persistent insomnia trajectories were predicted by high levels of sleep reactivity, sleep effort, pre-sleep cognitive arousal, and depressive symptoms at baseline. A combination of high sleep reactivity and sleep effort reduced the odds of insomnia remitting. Higher sleep reactivity also predicted the deterioration of good sleep into insomnia symptoms over 12 months. Lastly, intolerance of uncertainty emerged as the only trait-level cognitive/psychological predictor of insomnia trajectory classes. Insomnia was more likely to persist than remit over the first year of the COVID-19 pandemic. Addressing sleep reactivity and sleep effort appears critical for reducing insomnia persistence rates after times of stress and uncertainty.

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.

Metal ions exert pivotal functions within the human body, encompassing essential roles in upholding cell structure, gene expression regulation, and catalytic enzyme activity. Additionally, they significantly influence various pathways implicated in divergent mechanisms of cell death. Among the prevailing malignant tumors of the digestive tract worldwide, gastric cancer stands prominent, exhibiting persistent high mortality rates. A compelling body of evidence reveals conspicuous ion irregularities in tumor tissues, encompassing gastric cancer. Notably, metal ions have been observed to elicit distinct contributions to the progression, drug resistance, and biological attributes of gastric cancer. This review consolidates pertinent literature on the involvement of metal ions in the etiology and advancement of gastric cancer. Particular attention is directed towards metal ions, namely, Na, K, Mg, Ca, Fe, Cu, Zn, and Mn, elucidating their roles in the initiation and progression of gastric cancer, cellular demise processes, drug resistance phenomena, and therapeutic approaches.

Trigeminal neuralgia pain outcomes following microsurgical resection versus stereotactic radiosurgery for petroclival meningiomas: a systematic review and meta-analysis.

Petroclival meningiomas (PCMs) are challenging lesions to treat because of their deep location and proximity to critical neurovascular structures. Patients with these lesions commonly present because of local mass effect. A symptom that proves challenging to definitively manage is trigeminal neuralgia (TN), which occurs in approximately 5% of PCM cases. To date, there is no consensus on whether microsurgical resection or stereotactic radiosurgery (SRS) leads to better outcomes in the treatment of TN secondary to PCM. In this systematic review and meta-analysis, the authors aimed to evaluate the available literature on the efficacy of microsurgical resection versus SRS for controlling TN secondary to PCM. The Embase, MEDLINE, Scopus, and Cochrane databases were queried from database inception to May 17, 2022, using the search terms "(petroclival AND meningioma) AND (trigeminal AND neuralgia)." Study inclusion criteria were as follows: 1) reports on patients aged ≥ 18 years and diagnosed with TN secondary to PCM, 2) cases treated with microsurgical resection or SRS, 3) cases with at least one posttreatment follow-up report of TN pain, 4) cases with at least one outcome of tumor control, and 5) publications describing randomized controlled trials, comparative or single-arm observational studies, case reports, or case series. Exclusion criteria were 1) literature reviews, technical notes, conference abstracts, or autopsy reports; 2) publications that did not clearly differentiate data on patients with PCMs from data on patients with different tumors or with meningiomas in different locations (other intracranial or spinal meningiomas); 3) publications that contained insufficient data on treatments and outcomes; and 4) publications not written in the English language. References of eligible studies were screened to retrieve additional relevant studies. Data on pain and tumor outcomes were compared between the microsurgical resection and SRS treatment groups. The DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction was used to pool estimates from the included studies. Two comparative observational studies and 6 single-arm observational studies describing outcomes after primary intervention were included in the analyses (138 patients). Fifty-seven patients underwent microsurgical resection and 81 underwent SRS for the management of TN secondary to PCM. By the last follow-up (mean 71 months, range 24-149 months), the resection group had significantly higher rates of pain resolution than the SRS group (82%, 95% CI 50%-100% vs 31%, 95% CI 18%-45%, respectively; p = 0.004). There was also a significantly longer median time to tumor recurrence following resection (43.75 vs 16.7 months, p < 0.01). The resection group showed lower rates of pain persistence (0%, 95% CI 0%-6% vs 25%, 95% CI 13%-39%, p = 0.001) and pain exacerbation (0% vs 12%, 95% CI 3%-23%, p = 0.001). The most common postintervention Barrow Neurological Institute pain score in the surgical group was I (66.7%) compared with III (27.2%) in the SRS group. Surgical reintervention was less frequently required following primary resection (1.8%, 95% CI 0%-37% vs 19%, 95% CI 1%-48%, p < 0.01). Microsurgical resection is associated with higher rates of TN pain resolution and lower rates of pain persistence and exacerbation than SRS in the treatment of PCM. SRS with further TN management is a viable alternative in patients who are not good candidates for microsurgical resection.

Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation.

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.

Abstract WP129: Half of Acute Cortical Lesions in Minor Acute Ischemic Stroke Patients Persist on Flair at 30-day

Introduction: Ischemic lesions seen on acute DWI often result in chronic infarction on FLAIR. However, in minor stroke a proportion of cortical lesions seem to disappear. The objective of this study was to characterize the persistence rate of acute cortical lesions on FLAIR and associated imaging markers on 3DT1 at 30-day. Methods: Consented minor stroke patients (NIHSS&lt;6) presented acutely (&lt;24 hrs) received MRI at baseline, 5-day, and 30-day. One qualifying cortical lesion per patient was evaluated on baseline DWI for volume, white matter involvement, and on follow-up FLAIR for signal intensity ratio (SIR): comparison of lesion vs contralateral homologous tissue. Three independent raters blinded to hemisphere and exact location of the DWI lesion evaluated 3DT1 and FLAIR on follow-up (Figure). Results: Of 159 consented patients, 30 met criteria, and lesions of 28 patients (18%) evolved as hyperintense on FLAIR at 5-day. The 28 patients had a median age of 70 years, 54% female, median admit NIHSS of 2, and 32% were treated with IV alteplase. Of the 28 lesions, 17 (61%) had white matter involvement at baseline, and 14 (50%) were not evident on FLAIR at 30-day. Comparing those hyperintense vs not evident on FLAIR, raters identified 79% vs 21% (p&lt;0.003) cavitation in white matter, 36% vs 0% (p&lt;0.01) cavitation in gray matter, 57% vs 0% (p&lt;0.001) laminar necrosis, and 100% vs 14% (p&lt;0.001) cortical thinning on 3DT1. Lesions that persisted on FLAIR vs lesions not evident at 30-day had larger baseline DWI lesion volume: 2.2mL vs 0.3mL (p=0.024), and differences in SIR: 1.63 vs 1.3 (p=0.009) at 5-day, and 1.56 vs 1.1 (p=0.003) at 30-day. Conclusions: Half of the acute cortical lesions persisted on FLAIR at 30-day. Imaging markers on 3DT1 were more frequently associated with FLAIR evident lesions, but in ~1/3 of lesions not hyperintense, readers identified 3DT1 changes. Quantitative analysis is underway to confirm this observation.

Fabrication and characterization of low-cost kaolin based tubular ceramic membrane for microalgal harvesting

Tubular membranes with natural kaolin as a key precursor were fabricated in this study. Membranes with five different compositions were prepared, and the optimized membrane (77% kaolin, 2% boric acid, 2% sodium metasilicate, 4% sodium carbonate, and 15% calcium carbonate) was used to harvest microalgal culture. The pore size, porosity, water permeability, chemical and mechanical strength of the membranes were investigated. An assessment of the cost related to the membrane fabrication was also conducted. The fabricated membranes had porosity of ∼26–47%, a pore diameter of 0.123–0.182 µm, water permeability of 4.2 × 10−8 – 17.1 × 10−8 m3 m−2 s−1 kPa−1, along with good mechanical and chemical strength. The optimized membrane was tested for microfiltration of microalgae Monoraphidium sp. KMC4 with 1.5 g L−1 of initial concentration at a persistent cross-flow rate (1.11 × 10−5 m3 s−1) and various transmembrane pressures (69 kPa - 345 kPa). The separation results yielded an average permeate flux of 1.85 × 10−5 m3 m−2 s−1 at 276 kPa transmembrane pressure. Complete algal cell recovery and substantial nutrient passage (>88%) were observed within the pressure range of 69 kPa to 345 kPa. Fouling mechanism was explained by fitting four distinct pore-blocking models, of which the cake filtration model provided the most accurate fit as compared to the complete, intermediate and standard pore-blocking models. Additionally, the total organic carbon varied in the range of 31.6–63.2 mg L−1. This essentially explained the source of pore blocking.