Long-term Treatment Research Articles

Distinct trajectories of symptomatic response in ulcerative colitis during filgotinib therapy: A post hoc analysis from the SELECTION study.

Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long-term treatment response trajectories may improve UC management. We aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time. In these post hoc analyses of SELECTION, group-based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom-based patient trajectories using data from patients who responded to filgotinib 200 or 100mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient-level multi-component endpoint of comprehensive disease control (CDC) was assessed in each group. GBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1year), were receiving filgotinib 200mg and were biologic-naive versus the relapsing trajectory groups (4%-9% vs. 4%-5%; 43%-65% vs. 36%-46%; 54%-70% vs. 35%-58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%-32% vs. 0%-7%). Beneficial long-term response trajectories and achievement of CDC with filgotinib were associated with being biologic-naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC. NCT02914522.

The Influence of Rapid Heat Treatment During the Formation of Aluminum-Polysilicon Contacts on the Electrical Parameters of CMOS Microcircuits

The influence of rapid heat treatment (450 °C, 7 s) on the electrical parameters of CMOS integrated circuits during the formation of ohmic contact between aluminum metallization and polysilicon is considered. The following volt-ampere characteristics of the dependence of drain current on voltage were chosen as the analyzed parameters of n- and p-channel transistors: at the gate when diode-connected; on the drain at different gate voltages; on the drain in the channel breakdown mode without applying potential to the gate. A comparison of these parameters was carried out with respect to microcircuits manufactured using standard technology (450 °C, 20 min) to form these contacts. Analysis of the results showed that the use of rapid heat treatment to form an ohmic aluminum-polysilicon contact can significantly improve the above characteristics of n-MOS and p-MOS transistors. From the current-voltage characteristics of n- and p-channel transistors it follows that in the region of gate voltages greater than 0.65 V, the drain current after long-term heat treatment is higher than after quick heat treatment. Analysis of the current-voltage characteristics of the drain current versus the drain voltage showed that the drain current when using long-term heat treatment is significantly higher than after rapid heat treatment. In this case, for long-term heat treatment, there is a decrease in the channel breakdown voltage only for n-channel transistors and an increase in the drain current in the region of more than 5 V for both n- and p-channel transistors. Such improvements occur by eliminating the formation of polysilicon conglomerates in the aluminum contact, significantly reducing the epitaxial recrystallization of silicon doped with aluminum on the silicon surface, as well as reducing the microrelief of the interface of this contact and reducing the growth in the size of contact windows due to the lateral interaction of aluminum with polysilicon.

Impact of Long-Term Atorvastatin Therapy on the Development of Chronic Lung Allograft Dysfunction in Patients with Azithromycin Prophylaxis after Lung Transplantation

ObjectiveTo assess the impact of long-term atorvastatin (ATO) therapy on reducing recipient inflammation and immune response, thus lowering the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients. This study aimed to investigate the effects of ATO on overall survival, lung function recovery, and its influence on inflammatory factors alongside azithromycin (AZI) prophylaxis. MethodsThis retrospective single-center study included lung transplant recipients from January 2017 to December 2022. Patients who survival >1 year after lung transplantation and who were receiving AZI prophylaxis for >6 months were selected. Outcome measures involved pulmonary function assessments at various time points after AZI treatment, complete blood cell analysis, and inflammatory factor evaluations. ResultsThe incidence of CLAD was significantly lower in the long-term ATO group compared with those not on ATO (P = .011). Long-term ATO treatment significantly delayed CLAD onset after lung transplantation (850 days vs. 630 days; P = .041), with patients showing notably enhanced lung function recovery within 6 months of AZI therapy compared with the non-ATO group. Neutrophil levels decreased in patients with CLAD, and interleukin-6 concentrations significantly decreased in the AZI + ATO group compared with the AZI group. Overall patient survival was significantly better in the AZI+ATO group than in the AZI group (P = .02). ConclusionIn cases where CLAD develops despite AZI prophylaxis, long-term ATO treatment may lead to short-term improvements in lung function. It could also decrease inflammation levels in lung transplant recipients and enhance overall survival. The combination of AZI and long-term ATO therapy may be beneficial for CLAD prevention.

Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system.

Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.

Prolonged treatment of compactin, atorvastatin, lovastatin or simvastatin decreased glucose consumption and expressions of proteins for glucose metabolism and insulin signaling in L6 skeletal muscle cells

Statins inhibit mevalonate synthesis and successfully lower plasma cholesterol levels and decrease the risk of cardiovascular diseases in humans, but also lead to myalgia in some patients. We hypothesize that statins may modulate glucose metabolism and insulin signaling in the skeletal muscle cells during and after differentiation, and in turn lead to side effects. Here, differentiating and differentiated L6 muscle cells were treated with 1 μM of different class of statins (compactin, pravastatin, atorvastatin, lovastatin and simvastatin) with or without insulin or mevalonate for extended periods of time. The glucose consumption and expression levels of proteins for glucose metabolism and insulin receptor (IR)/Akt signaling were determined. The prolonged statin treatments (except pravastatin) decreased glucose consumption in L6 skeletal muscle cells. In differentiating L6 cells, compactin, lovastatin or simvastatin decreased the expression levels of proteins involved in glucose metabolism and insulin signaling, including glucose transporter 4 (GLUT4), pyruvate dehydrogenase (PDH), glycogen synthase (GS), glycogen synthase kinase 3β (GSK3β) and insulin receptor β subunit (IRβ). In differentiated L6 cells, long-term treatment of compactin or simvastatin also decreased levels of proteins in glucose metabolism and IR/Akt signaling, including GLUT4, GSK3β, IRβ and PI3K p110α. Insulin treatment restored statin-mediated impairments in L6 cells. The insulin-mediated phosphorylation of Akt Ser473 was attenuated in differentiating and differentiated L6 cells in the presence of atorvastatin (differentiated only), compactin, lovastatin or simvastatin. In addition, mevalonate supplementation reversed the statin-mediated impairments in differentiated and differentiating L6 cells. Statin affected glucose usage and insulin signaling by inhibiting mevalonate synthesis in L6 cells. Our results provides a possible mechanism of adverse effects of statins in skeletal muscle and calls for cautious use of the medication in patients with impaired insulin sensitivity and glucose metabolism.

The influence of telehealth-based interventions in patients with cancer in the digital era of society 5.0: A literature review

Background: Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells, which can result in death if not managed. It is important for cancer patients to be able to participate in long-term treatment programs. Therefore, a good support system, healthcare professionals' support, and the utilization of information technology in healthcare services are needed. The management of cancer is also expected to adapt to the era of Society 5.0. The use of Telehealth has been recommended by the World Health Organization (WHO) to support current healthcare services. The implementation of the combination of telehealth is expected to be a solution for holistic cancer care in the digital era. Purpose: To explore the effectiveness of telehealth-based interventions on cancer patients in the digital era of society 5.0. Method: Literature review using online databases such as Sage Journals, Science Direct, Clinical Key Nursing, and PubMed. Inclusion criteria: articles on the application of telehealth for cancer patients, available in full text in English, published between 2020-2023. Exclusion criteria: articles published before 2020, articles that do not discuss telehealth in cancer patients, and literature review studies. Results: Analysis of the 13 articles used shows the important role of combining telehealth (telenursing, telepalliative, telerehabilitation, teleoncology), which is beneficial not only for cancer patients but also for nurses and other healthcare professionals in providing good quality, safe, effective, and efficient healthcare services in the digital era of society 5.0. Conclusion: Telehealth-based cancer rehabilitation demonstrates a positive impact that warrants further evaluation and study.

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Long-term phenobarbital treatment is effective in working-age patients with epilepsy in rural Northeast China: a 10-year follow-up study.

Effective management of epilepsy in working-age patients is essential to reduce the burden on individuals, families, and communities. This study aimed to assess the long-term efficacy of phenobarbital (PB) in working-age patients with epilepsy in rural Northeast China and identify the risk factors for seizures during treatment. Patients aged 18-65 years diagnosed with convulsive epilepsy in rural areas of Jilin Province between 2010 and 2024 were included, and demographic and clinical data were recorded. Seizure frequency, self-efficacy, adherence, and adverse events (AEs) were assessed monthly. Of the 3,568 participants, 288 (8.1%) withdrew from the study and 159 (4.5%) died. During the first year of treatment, 75.2% of patients experienced a ≥50% reduction in seizure frequency compared with baseline (considered as treatment effectiveness); 53.7% of patients were seizure-free. By the tenth year, 97.7% of patients showed treatment effectiveness, and 89.6% were seizure-free. Self-efficacy was improved in 37.8% of patients in the first year and in 72% of patients by the tenth year. The independent risk factors for seizures during treatment were higher baseline seizure frequency [odds ratio (OR) = 1.431, 95% confidence interval (CI): 1.122-1.824], presence of multiple seizure types (OR = 1.367, 95% CI: 1.023-1.826), and poor adherence (OR = 14.806, 95% CI: 3.495-62.725), with significant differences observed in the first, third, and fifth years. The most commonly reported AEs were drowsiness (43.3%), dizziness (25.0%), and headaches (17.0%), most of which were mild and decreased over time. Age at enrollment was the only factor influencing withdrawal (hazard ratio = 0.984, 95% CI: 0.973-0.996, p = 0.010), with a substantial number of patients who withdrew (32.6%) relocating for work. Cardiovascular disease was the primary cause of death, and age at enrollment was the only risk factor (hazard ratio = 1.026, 95% CI: 1.009-1.043, p = 0.002). Working-age adults with epilepsy demonstrated a favorable response and tolerability to PB monotherapy. Baseline seizure frequency, seizure type, and adherence consistently predicted prognosis throughout the treatment period. Withdrawal was mainly explained by work-related pressures in this age group. Therefore, it is essential to implement interventions that support patient adherence to therapy and maintain stable regimens.

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis

The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available. To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks. The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023. Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily. Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline. From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose. In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks. Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.

Prospective Real-Life Multicenter Study of Tildrakizumab 200 mg for Moderate-to-Severe Psoriasis: Who Is the Ideal Patient?

Introduction: Tildrakizumab, a humanized monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown promise in the management of moderate-to-severe plaque psoriasis, offering potential improvements in clinical outcomes and quality of life. Objectives: The study aimed to identify patient characteristics that indicate the initiation of a 200-mg dosage of tildrakizumab in a real-world setting, focusing on factors that enhance treatment efficacy and safety. Methods: This prospective study included 54 adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab 200 mg from March 2023 to March 2024 across 13 Italian Dermatology Units. Data collected included demographics, disease duration, comorbidities, and previous treatments. PASI, BSA, and DLQI scores were recorded at baseline, week 4, 16, and 28. Safety was assessed through adverse event reporting. Univariate analysis was performed to identify baseline characteristics significantly associated with achieving PASI ≤ 5 at week 16. Results: Significant reductions in PASI scores were observed at week 4 (9 ± 6.9, p&lt;0.001), with further improvements at weeks 16 (3.9 ± 4.2, p&lt;0.001) and 28 (2.9 ± 4.4, p&lt;0.001). Univariate analysis showed that obese patients (BMI &gt; 30) had higher odds (OR = 4.333, p &lt; 0.05) of achieving PASI ≤ 5. Longer disease duration and starting with a 100 mg dose also correlated with better outcomes. The safety profile was favorable, with minimal adverse events reported. Conclusions: Tildrakizumab 200 mg is effective and safe for moderate-to-severe psoriasis, particularly in obese patients. These findings support its use as a long-term treatment option.

Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. Patients aged ≥ 18years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

Chronic constipation

Chronic constipation is one of the most common health disorders in all of medicine. Its extent ranges from mild discomfort, which is usually easy to improve, to severe functional limitations that may significantly reduce quality of life and may be refractory to various treatment approaches. Our understanding of the pathomechanism has grown considerably in recent years and has also led to important new therapeutic developments. The resulting treatment options and recommendations are presented in the current update of the S2k constipation guideline in an evidence-based and practical manner. The respective significance of traditional and recent drug developments is classified and categorized in modern "step-up" treatment strategies. In particular, numerous important aspects of everyday practice are addressed, such as questions on long-term treatment and therapeutic options in specific constellations (adequate treatment of constipation in older people, constipation during pregnancy, and drug-induced [especially opioid-induced]constipation).The most important new developments (i.e. new therapeutic approaches, but also re-evaluations of "traditional" laxatives and the importance of careful diagnostics in therapy-refractory patients) are summarized in this article.

Long-Term Antifungal Treatment in a Patient With Confirmed Allergic Bronchopulmonary Aspergillosis

Long-Term Antifungal Treatment in a Patient With Confirmed Allergic Bronchopulmonary Aspergillosis

Diagnostic aspects of pediatric embryonal tumors of the central nervous system: what should know pediatrician

Background. Early identification of pediatric central nervous system (CNS) tumors is important in relation to disease prognosis, as well as long-term treatment outcomes, which determine subsequent quality of life. The predominance of embryonal tumors (ETs) in early childhood actualizes the problem of timely verification of the diagnosis. Factors contributing to the extension of diagnostic time in the presented patient’s cohort include the inability to adequately verbalize complaints in young children, a wide range of clinical presentations, including nonspecific ones, the relatively low incidence of ET in the population and the low level of oncological alertness among specialists. This determines the need for a more careful assessment of the clinical manifestations and disease-associated symptoms by doctors of all specialties and, especially, primary care specialists. Aim. Analysis of clinical symptoms at the disease’s onset in pediatric CNS ET in order to determine their associations with the tumor’s characteristics (site, hystologic type) and the patient’s features. Materials and methods. A retrospective analysis of data from 124 pediatric patients with CNS ET who received treatment from 2010 to 2023 in the departments of pediatric oncology of the Almazov National Medical Research Center and the St. Petersburg Scientific Research Center for Medical Sciences (o) named after. N. P. Napalkov. The analyzed parameters were the age of manifestation, initial symptoms, duration of the anamnesis and the period before verification of the diagnosis, localization and histological type of tumors. For statistical analysis, Fisher’s exact test, modified Pearson test, Kruskal-Wallis and Mann-Whitney tests, as well as (to assess the duration of anamnesis) the Cox model were used. Results. The most common type of CNS ET in the study group was medulloblastoma (MB; 66.1%). The average age of patients, in general, was 61 months, boys predominated (58%). The median age varied depending on the histological tumor type: the maximum was 72 months in patients with medulloblastoma and the minimum was 9 months in children with atypical teratoid rhabdoid tumor (ATRT). Both medians are significantly different from the total median (29 months) of all other tumors (p = 6.53 ∙ 10-4 and p = 0.029, respectively). The most frequent symptoms in patients with ET were nausea and vomiting (68%), headache (50%), and gait disturbances (25.6%). Increased head circumference/bulging fontanel (p = 0.0016) and torticollis (p = 0.0057) were the most common symptoms associated with younger age. Headache (p = 1.30 ∙ 10-9), nausea and vomiting (p = 0.019), diplopia (p = 0.0057), weight loss (p = 0.017) and dizziness (p = 0.013) were associated with older age. Headache was predominated symptom in medulloblastoma (p = 2.60 ∙ 10-4) compared to other ETs, and less common in ATRT (p = 1.51 ∙ 10-4), which may be due to the patient’s age. Fontanel bulging in medulloblastoma, unlike other ET, was not observed, which is also associated with age. Seizures were observed in all cases of CNS neuroblastoma - significantly more often (p = 0.034) than in other ETs. The most common tumor location was the posterior cranial fossa (PCF) (83.6%). PCF localization was associated with headache (p = 0.05, borderline significance) and nausea/vomiting (p = 0.040). Parietal localization was associated with seizures (p = 0.041). Four patients in the cohort had asymptomatic disease’s manifestations. The diagnosis was established by a routine screening examination. The absence of symptoms was associated with location outside the PCF (p = 0.011) and with younger age (p = 0.053, borderline significance). The diagnosis was established in a significantly shorter time if children had symptoms such as nausea and vomiting (p=0.0017), paresis and paralysis (p=0.0059). Conclusion. In patients with CNS ETs, statistically significant relationships are revealed between age, histological type, tumor site and certain symptoms. Nevertheless, the absence of strictly specific clinical manifestation determines the indications for a careful assessment of the pediatric somatic and neurological status and timely neuroimaging in children when even potential symptoms typical for CNS tumors are identified.

Contributors to Organ Damage in Childhood Lupus: Corticosteroid Use and Disease Activity.

Awareness of paediatric-specific predictors of damage in Childhood-lupus is needed to inform mitigation measures. To ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage. Analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS)≤2, low activity (AMS ≤ 4), moderate-high activity (AMS > 4) and those with no corticosteroids. Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone (Hazard Ratio, HR 2.20, [CI 1.33-3.62]), time-adjusted mean Physicians Global Assessment (PGA) (HR 2.87, [CI 1.48-5.56]) and AMS score (HR 1.13, [CI 1.03-1.24], all p< 0.05). Within the low activity subgroup, any methylprednisolone (HR 2.61, [CI 1.04-6.53]) and time-adjusted mean PGA (HR 3.41, [CI 1.52-7.76]) were associated with damage (both p< 0.05). Within the moderate-high activity subgroup, any methylprednisolone (HR 2.29, [CI 1.31-4.00]), time-adjusted mean PGA (HR 2.66, [CI 1.20-5.87]) and AMS score (HR 1.15, [CI 1.03-1.29]), were predictive of damage (all p< 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal activity (HR 1.33, CI [1.78-8.08]) and no corticosteroids subgroups (HR 3.64, CI [1.83-7.24], both p< 0.005). Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, to reduce disease activity and long-term treatment toxicity, such as treat-to-target.

Long-term outcome of tacrolimus-based immunosuppressive treatment for patients with paediatric-onset lupus nephritis.

We have previously reported the mid-term efficacy and safety of tacrolimus (Tac)-based immunosuppressive therapy in such patients, and herein, we aimed to determine their long-term outcomes (over 10 years). We retrospectively evaluate the data of 13 consecutive patients with biopsy-proven long-standing LN who underwent a long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti-dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period. The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79-152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0-46.0 U/mL); serum anti-dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10-year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti-dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare-ups. No serious adverse effects were observed. Our results suggest that long-term Tac-based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric-onset LN in a real-world setting.

Chronic Lower Respiratory Diseases detection based on Deep Recursive Convolutional Neural Network

Recently, symptoms of Chronic Obstructive Pulmonary Disease (COPD) have been identified concerning long-term continuous treatment. Furthermore, predicting the life probability of patients with COPD is crucial for formative ensuing treatment and conduct plans. Additionally, it plays a vital role in providing complementary solutions using technologies such as Deep Learning (DL) to address experiments in the medical field. Early and timely analysis of clinical images can improve prognostic accuracy. These include COPD, pneumonia, asthma, tuberculosis and fibrosis. Conventional methods of diagnosing COPD often rely on physical exams and tests such as spirometers, chest and genetic analysis. However, respiratory diseases pose an enormous comprehensive health burden for many patients. Thus these methods are not always accurate or obtainable. However, succeeding in their accuracy involves a nonspecific diagnosis rate, time-consuming manual procedures, and extensive clinical imaging knowledge of the radiologist. To solve this problem, we use a Deep Recursive Convolutional Neural Network (DRCNN) method to detect chronic lower respiratory disease. Initially, we collected the images from the Kaggle repository, and evaluate the result based on the following stage. The first stage is pre-processing using a Gaussian filter to reduce noise and detect the edges. The second stage is segmentation used on Image Threshold Based Segmentation (ITBS), used for counting the binary image and separating the regions. In the third stage, we use the chi-square test to select the best features and evaluate the image values for each feature and threshold. Finally, classification using DRCNN detects CLRD classifying better than the previous method. In synthesis, CLRD can be detected by many staging measures, such as sensitivity, specificity, accuracy, precision, and Recall

Gene Therapy: A Revolutionary Step in Treating Thalassemia.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to the reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. To conclude, gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own setbacks and is something that must be tackled in order to revolutionize it in the medical world. FDA-approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost-a price of USD 2.8 million per patient.

A cost-effectiveness analysis of RefluxStop against relevant therapeutic alternatives for chronic gastroesophageal reflux disease in Sweden

ABSTRACT Introduction The standard treatment for gastroesophageal reflux disease (GERD) is proton pump inhibitors (PPIs). In selected cases, Nissen fundoplication is offered as a surgical treatment option, but alternative endoscopic and minimally invasive surgical alternatives are emerging. RefluxStop is a new technology for the treatment of GERD. Research design and methods A cost-effectiveness analysis of RefluxStop in comparison to PPI therapy and Nissen fundoplication in the Swedish healthcare setting was conducted using a Markov model and available comprehensive population and clinical trial-based long-term data. Benefits were measured in quality-adjusted life-years (QALYs). Uncertainty was determined by deterministic and probabilistic sensitivity analyses. Results The base case incremental cost-effectiveness ratios (ICERs) for RefluxStop in comparison to PPIs and Nissen fundoplications were SEK 48,152 (€ 4,531) and SEK 62,966 (€ 5,925) per QALY gained, respectively. At a cost-effectiveness threshold of SEK 500,000 per QALY gained, RefluxStop has a high likelihood of being cost-effective, with probabilities of 96% and 100% against Nissen fundoplication and PPIs, respectively. The results of the model remained robust with sensitivity analysis. Conclusions RefluxStop may offer a highly cost-effective long-term treatment alternative for chronic GERD patients over lifelong PPI therapy, but also in comparison with laparoscopic Nissen fundoplication.

A novel technique to identify and thermally ablate the greater occipital nerve for patients with occipital neuralgia: a retrospective study with cadaveric and ex-vivo validation.

This manuscript presents the challenges of treating various forms of headaches and the potential of interventional techniques targeting the greater occipital nerve (GON) to alleviate the burden on patients. Occipital neuralgia, characterized by stabbing or shooting pain in the base of the skull, is often associated with primary, cervicogenic, or migraine headaches. While occipital nerve blocks offer temporary relief, durable treatment options are limited. Pulsed radiofrequency (PRF) and thermal radiofrequency ablation (TRFA) have shown promise as minimally invasive procedures for long-term treatment. However, GON is not easily identified using ultrasound or fluoroscopic analysis; thereby, minimizing success of proper ablation. Here, the authors provide a percutaneous strategy to localize the GON and maximize lesion performance. We intend to provide an ex-vivo description of staggered bipolar radiofrequency (RF) lesioning and include the use of staggered bipolar lesioning of the GON and stimulation of the semispinalis capitis. We also analyzed the effectiveness and side effects from this ablation, retrospectively. Patients with chronic refractory GON neuralgia were selected for GON TRFA. A novel double needle technique of sequential electrical stimulation was used to localize the GON and approximate needle to nerve distance. Once the needles were positioned adjacent to the GON, TRFA was performed using a bipolar staggered technique. Twenty-two patients with GON were treated with TRFA using a novel double needle technique. Seventy-two percent of these patients reported greater than 50% pain relief at both 1 and 6 months following the procedure. The results of our ex-vivo study demonstrate that performing TRFA using the parallel needle bipolar approach separated 8 mm apart produced the most desirable lesion dimensions that may correlate with effective ablation of the GON. This study demonstrates a new localization and ablation technique to treat refractory headaches. However, larger studies are needed to confirm our findings.