Individualized Treatment Approach Research Articles

Fertility preservation in persons with gender incongruence and male-assigned sex at birth

According to current guidelines, patients with gender incongruence seeking treatment must receive appropriate education and counselling from healthcare professionals on the various options for fertility preservation. Gender-affirming hormonal treatment leads in persons assigned male at birth to a reduction of LH, FSH, and testosterone, which is associated with a regression of spermatogenesis (up to complete loss) and subsequent testicular atrophy. Individuals starting gender-affirming hormonal treatment after having experienced male puberty may provide an ejaculate sample for sperm cryopreservation. In cases where no sperm is detected in the ejaculate due to gender-affirming hormonal treatment, or if the sampling of ejaculate is no longer possible or causes excessive psychological distress, (microsurgical) testicular sperm extraction [(m)TESE] should be offered. Electroejaculation under anaesthesia is rarely effective, as hormonal treatment impairs spermatogenesis. Similarly, microsurgical epididymal sperm aspiration (MESA) is not typically effective for the same reason. If adolescents with gender incongruence undergo puberty blockade and/or gender-affirming hormonal treatment at an early stage of puberty (possible from Tanner stage 2), this prevents the maturation of spermatogonial stem cells into mature sperm. Puberty blockade with GnRH reduces the secretion of LH and FSH by the pituitary gland, which, in turn, suppresses the production of testosterone in the Leydig cells and the stimulation of spermatogenesis in the testicles. In such cases, the cryopreservation of spermatogonial stem cells is possible, similar to how it is offered in some countries for peri-pubertal patients prior to necessary germ cell-toxic treatments. In Germany, there is a relevant network (Androprotect), which was founded in Münster in 2012. Via Androprotect, this procedure is also offered for adolescent individuals with gender incongruence. This approach is considered experimental as no established treatment exists for the refertilisation of affected adults at a later stage, although several procedures for in-vitro sperm maturation and tissue transplantation are under development. The care of patients with gender incongruence should include individual counselling provided by experienced professionals in an interdisciplinary treatment team. Individual treatment approaches should be offered to facilitate shared decision-making (based on informed consent) to ensure that each individual can make an informed and appropriate decision regarding fertility preservation.

Clinical symptoms and functional impairment in attention deficit hyperactivity disorder (ADHD) co-morbid tic disorder (TD) patients: a cluster-based investigation

BackgroundAttention deficit hyperactivity disorder (ADHD) and tic disorder (TD) are two common neurodevelopmental disorders that frequently occur in childhood, and these two disorders often coexist. Cluster analysis provides a novel perspective on the heterogeneity of these commonly observed clinical disorders.MethodsWe recruited patients with comorbid ADHD and TD from Beijing Children's Hospital between May 2022 and August 2023, collecting data on their symptoms and functional impairments. The number of clusters was determined using the elbow method, and K-means clustering was conducted. Fisher discriminant analysis and silhouette score were used for validation. Additionally, we assessed premonitory urge, strengths, and difficulties among groups. We also collected samples with ADHD alone and performed cluster analyses.ResultsThe number of clusters for the ADHD comorbid TD sample was determined to be two by the elbow method. The results of the cluster analysis showed that the ADHD comorbid TD sample could be divided into the severe TD group and the severe ADHD group. The severe TD group exhibits more pronounced tic symptoms, yet their age, ADHD symptoms, and functional impairment are all significantly lower than those of the severe ADHD group. Compared to samples with ADHD alone, the distribution of age and functional impairment among individuals does not change with the addition of TD symptoms, maintaining a parallel relationship with the severity of ADHD symptoms.ConclusionPatients with co-occurring ADHD and TD can be classified into two clusters based on age, symptoms, and functional impairment. In clinical interventions for these patients, while ADHD may require more attention, it is also crucial to identify the core symptoms of the patients. The heterogeneity in clinical symptom presentations highlights the need for individualized treatment approaches.

Predictors of biochemical and structural response to medical therapy in patients with active acromegaly following surgery: a real-world perspective

BackgroundSomatostatin receptor analogs (SRAs) and dopamine agonists (DAs) are the main medical treatments for patients with acromegaly who fail to achieve remission after surgery. We aimed to explore the potential role of select clinical, biochemical, and radiological factors in predicting biochemical and structural responses to medical therapy in a real-world setting.MethodsThis retrospective cohort study included 58 patients with active acromegaly following surgery treated with Octreotide long-acting release (LAR) (± Cabergoline). Biochemical outcomes were defined as the tight biochemical response (TBR; normal insulin-like growth factor-1(IGF-1)) and biochemical control (BC; IGF-1 ≤ 1.2 upper limit of normal (ULN)). The structural response was defined as > 25% reduction in one dimension of the tumor at the last visit. Univariate and multivariate analyses assessed the predictors of biochemical and structural response.ResultsThe mean age of the participants was 41.5 ± 11.7 years. They were followed for a median of 27.6 (19.2–43.2) months. At the last visit, TBR and BC were achieved in 48.3% and 51.7% of the patients. Moreover, 51.4% of the patients showed a structural response. Applying the age-sex adjusted model, post-operative IGF-1 was inversely associated with TBR [OR 0.34, P = 0.006] and BC [OR 0.30, P = 0.004]. Moreover, Knosp grading < 3 compared to ≥ 3, and T2-hypointensity compared to the non-T2-hypointensity were associated with higher odds of TBR [OR 3.98, P = 0.04], [OR 27.63, P = 0.01], and BC [OR 5.80, P = 0.01], [OR 35.15, P = 0.01], respectively.ConclusionsPost-operative IGF-1, Knosp grading, and T2-hypointensity could be considered for an individualized treatment plan in acromegaly. Accordingly, we propose an individual multidisciplinary treatment approach for patients not achieving remission after surgery.

Evaluation of glycemia risk index and continuous glucose monitoring-derived metrics in type 1 diabetes: a real-world observational study.

The Glycemia Risk Index (GRI) quantifies the risk of glycemic events by considering both hypoglycemic and hyperglycemic episodes, offering a comprehensive evaluation of glycemia. While associations between GRI and various glycometric indicators have been established in clinical trials using continuous glucose monitoring (CGM), real-world assessments, particularly with intermittent scanning CGM (isCGM), are underexplored. This study examines these associations and their clinical implications in individuals with Type 1 Diabetes (T1D). We conducted a retrospective study involving individuals with T1D undergoing intensive insulin therapy. All participants had used isCGM for at least three months. We collected clinical, metabolic, and glycemic data and calculated the GRI, with its components for hypoglycemia (CHypo) and hyperglycemia (CHyper). We then assessed the correlation between the GRI and traditional glycemic metrics in relation to the coefficient of variation (CV). The study included 194 patients (105 males, 89 females) with a median age of 21.5 years for adults and 16 years for adolescents. Of these, 62.4% were on multiple daily injections, and 37.6% used insulin pumps. GRI showed a significant negative correlation with Time in Range (%TIR70 - 180) (p < 0.001) and a positive association with various glycemic measures such as glycemic variability (r = 0.33, p < 0.001). Individuals with lower glycemic variability (CV< 36%) had significantly higher %TIR70 - 180 (63% vs. 39%, p < 0.01) and lower GRI (40 vs. 45.8, p < 0.01), CHyper (20 vs. 24, p = 0.01), and CHypo (2.6 vs. 3.4, p < 0.01). GRI correlates with key glycemic metrics, indicating its potential utility in comprehensive glycemia assessment. These findings highlight the importance of individualized treatment approaches and suggest GRI's clinical relevance in optimizing glycemic management strategies for individuals with T1D. The online version contains supplementary material available at 10.1007/s40200-025-01569-w.

Comparative Analysis of Host and Virus-Driven Variables Affecting Response to Ribavirin and Interferon Therapy in Hepatitis C Patients

Current guidelines advocate for individualized treatment approaches for the management of Hepatitis C, that incorporate baseline assessments of viral genotype, host comorbidities, and socioeconomic factors to maximize therapeutic success. Objectives: To analyze the impact of host and virus-driven variables on treatment response in patients receiving ribavirin and interferon therapy. Methods: This prospective cohort study was conducted on 138 patients aged 18–65 with confirmed chronic HCV infection who were eligible for interferon and ribavirin therapy. The patients were followed up to a 24-week post-treatment to assess recovery measured in terms of sustained virological response (SVR). The host-driven factors included age, gender, BMI, and the presence of IL28B polymorphism while virus-driven factors included HCV genotype and baseline viral load. Results: The study sample predominantly consisted of male (55.1%), and genotype 3 virus accounted for 68.1% of participants. A high proportion (76.1%) of participants achieved SVR. Factors associated with better treatment outcomes included younger age (90.7% in the 31–45 age group), gender (89.5% of male), normal BMI (91.2% of those with a BMI of 18.5–24.9), and the favorable IL28B polymorphism CC genotype (91.8%). Low baseline viral load was observed in 60.1% of patients, and those with genotype 3 had better SVR rates. Conclusions: It was concluded that younger age, male gender, normal BMI, favorable IL28B polymorphism along with low baseline viral load, and genotype 3 were positively associated with achieving SVR.

A novel ubiquitination-related gene signature for overall survival prediction in patients with liver hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is a highly heterogeneous disease, necessitating the discovery of novel biomarkers to enhance individualized treatment approaches. Recent research has shown the significant involvement of ubiquitin-related genes (UbRGs) in the progression of LIHC. However, the prognostic value of UbRGs in LIHC has not been investigated. In this study, the mRNA expression profiles and clinical data were obtained from public databases of LIHC patients. The least absolute shrinkage and selection operator Cox regression model was employed to construct a multigene signature in the TCGA cohort. Our results showed that a twelve UbRGs signature was developed to categorize patients into two risk groups, with significant differences in expression between LIHC and normal tissues. Patients in the high-risk group exhibited significantly reduced overall survival (OS) and progression-free survival compared to those in the low-risk group. The risk score was identified as an independent predictor for OS in multivariate Cox regression analyses. Receiver operating characteristic curve analysis confirmed the predictive capacity of the signature. Functional analysis revealed enrichment of immune-related pathways and differences in immune status between the two risk groups. The risk score was correlated with 35 transcription factors and 26 eRNA enhancers, and positively associated with tumor mutation burden. Patients in the high-risk group demonstrated decreased sensitivity to targeted and chemotherapeutic drugs than those in the low-risk group. In conclusion, our study identified a twelve UbRGs signature that may serve as a prognostic predictor for LIHC patients and and provide valuable insights for cancer treatment.

&lt;i&gt; Helicobacter pylori&lt;/i&gt; Infection and Non-steroidal Anti-inflammatory Drugs Mediated Gastric Ulcer: Insights into Efficacy and Strategies for Gastroprotective Treatments and Disease Management

Context: Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are the primary etiological factors contributing to gastric ulcer disease, characterized by mucosal erosions in the stomach. This condition remains a significant global health challenge, particularly in low- and middle-income countries, where it substantially contributes to morbidity and premature mortality. Complications such as gastrointestinal bleeding and perforation exacerbate the disease burden, underscoring the need for effective preventive and therapeutic strategies. Objectives: To evaluate the effectiveness of proton pump inhibitors, prostaglandin analogues, and histamine-2 (H2) receptor antagonists in preventing and healing gastric ulcers caused by H. pylori and NSAID use. The study aims to identify optimal treatments and explore patient-specific responses for improved, personalized therapy. Methods: This systematic review and meta-analysis evaluated the efficacy of gastroprotective treatments, including proton pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs), in preventing and healing gastric ulcers. A comprehensive search was conducted across PubMed, Embase, and the Cochrane Library. Inclusion criteria focused on Randomized Controlled Trials (RCTs) assessing these treatments in patients with gastric ulcers. Quality assessment was performed using the adapted Newcastle–Ottawa Scale. The DerSimonian and Laird random-effects model was employed to determine pooled effect sizes, with heterogeneity assessed using Cochran’s Q and I² statistics. All analyses were conducted using Stata/MP 17.0. Results: The search identified 2,687 records, with 116 studies meeting the inclusion criteria after rigorous screening and quality assessment. The meta-analysis included studies on PPIs, prostaglandin analogues, and H2RAs, involving 18,042 participants in the treatment groups and 13,255 in the control groups. PPIs significantly reduced the incidence of gastric ulcers (log odds ratio = -1.17, 95% CI: -1.97 to -0.37, P &lt; 0.001) with high heterogeneity (I² = 98.13%). Prostaglandin analogues (log odds ratio = -1.61, 95% CI: -2.49 to -0.73, P &lt; 0.001) and H2RAs (log odds ratio = -0.86, 95% CI: -1.92 to 0.20, P &lt; 0.001) also demonstrated significant protective effects despite high heterogeneity. Conclusions: Gastroprotective treatments, particularly PPIs and prostaglandin analogues, are effective in reducing gastric ulcer incidence. The high heterogeneity among studies suggests the need for individualized treatment approaches. Further research is warranted to refine protocols and optimize patient-specific therapies.

Longitudinally persisting KCNA2-autoantibodies in mild amnestic dementia with Alzheimer´s pathology - Report and literature review.

Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD. We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen. Neuropsychological test results and autoantibody testing in serum over a period of 4-5 years is provided. Our patient exhibited mild dementia syndrome and was diagnosed with AD on the basis of a prototypical biomarker profile (reduced Aβ42/40 ratio and elevated p-tau181 protein in cerebrospinal fluid). Within a 5-year follow-up with regular visits to our memory clinic, we observed a nearly stable neuropsychological profile of mild, amnestic variant dementia that did not noticeably progress. KCNA2 autoantibodies were also detectable in serum over 4 years with increasing titers over time. Combined anti-dementia therapy with donepezil, multimodal therapy including non-pharmacological cognitive therapy, and immunotherapy with intravenous methylprednisolone was carried out as an individual treatment approach. KCNA2 autoantibody persistence in biomarker-supported AD does not necessarily trigger a poor outcome in the long-term, as cognitive impairment did not progress subsequently. At the same time, mild immunotherapy did not result in less immunoreactivity in conjunction with the detection of KCNA2 autoantibodies. This detection of KCNA2 autoantibodies in AD could provide indices of a potentially benign long-term AD course that should be further evaluated in studies.

From Pathophysiology to Personalized Treatment Strategies for Psoriasis

Background: Psoriasis is a chronic inflammatory and proliferative skin disorder characterized by redness and elevated patches covered in scaly, silvery-white skin. The National Psoriasis Foundation categorizes psoriasis into mild, moderate, and severe, impacting 2% to 5% of the global population. This article explores the types, development, and severity categories of psoriasis, delving into its pathophysiology. It also reviews both conventional and herbal topical therapies and their marketed formulations. Aim: The study aimed to contribute to the development of personalized treatment approaches for individuals with psoriasis. Objectives: This article explores the types, development, and severity categories of psoriasis, delving into its pathophysiology. It also reviews both conventional and herbal topical therapies and their marketed formulations. Methods: The article relies on a comprehensive review of existing literature and research studies on psoriasis. Information on types, severity categories, pathophysiology, and available treatments, both conventional and herbal, is gathered and analyzed. Results: The results highlight the potential advantages of incorporating herbal therapies into treatment plans for individuals with psoriasis, especially for those with severe cases. Conclusion: In conclusion, the article emphasizes the importance of individualized treatment plans for managing psoriasis. Both conventional and herbal topical formulations can be viable options, particularly for severe cases. By considering the safety profiles, side effects, and biological activities associated with these treatments, healthcare experts can collaborate with patients to create personalized and effective strategies for addressing the complexities of psoriasis management.

Successful management of an unusual case of pediatric inflammatory myofibroblastic tumor: a case report and literature review

Introduction and importance: Inflammatory myofibroblastic tumor (IMT) is a rare neoplastic condition that primarily affects children and young adults. This case report highlights the challenges in diagnosing and treating pediatric IMT, emphasizing the importance of tailored interventions. Case presentation: An 8-year-old boy presented with respiratory symptoms and was diagnosed with an IMT located in the left main bronchus. Imaging studies revealed a soft tissue mass and lymph node enlargement. Bronchoscopy and biopsy confirmed the diagnosis. The patient underwent bronchoscopic debulking procedures followed by lobectomy and bronchoplasty due to persistent disease. Clinical discussion: IMTs pose diagnostic challenges due to their varied clinical presentation and similarities with other neoplasms. A multidisciplinary approach involving pathologists, radiologists, and surgeons is crucial for accurate diagnosis and optimal treatment planning. The pathogenesis of IMTs is not fully understood, but theories suggest an inflammatory response or involvement of the ALK gene. IMTs can affect various organs, each with distinct symptoms. Imaging modalities lack specificity, emphasizing the importance of histopathological examination. Conclusion: IMTs require individualized treatment approaches based on the location and extent of the tumor. Long-term follow-up is essential for monitoring recurrence and metastasis. Further research is needed to enhance our understanding of IMT biology and develop targeted therapies to improve patient outcomes. This case report underscores the importance of tailored interventions in pediatric IMT cases and highlights the challenges in diagnosis and treatment.

Corticosteroid therapy for treating acute exacerbation of interstitial lung diseases: a systematic review.

Acute exacerbation of interstitial lung disease (AE-ILD) often results in death and poses significant challenges in clinical management. While corticosteroids are frequently employed, the optimal regimen and their clinical efficacy remain uncertain. To address this knowledge gap, we undertook a systematic review to evaluate the impact of steroid therapy on clinical outcomes in patients experiencing AE-ILD. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched multiple databases, identifying 12 454 articles. After removing duplicates and screening titles and abstracts, 447 articles were selected for full-text review. Ultimately, nine studies met inclusion criteria, comparing high-dose corticosteroids with low-dose or non-steroidal interventions in treating AE-ILD. Key outcomes included in-hospital and long-term mortality, as well as AE recurrence. Analysis of nine studies (total n=18 509) revealed differential treatment effects based on the ILD subtype. In non-idiopathic pulmonary fibrosis (IPF) ILD, high-dose corticosteroid therapy (>1.0 mg/kg prednisolone) demonstrated improved survival (adjusted HR 0.221, 95% CI 0.102 to 0.480, p<0.001) and reduced 90-day mortality. Early tapering of high-dose corticosteroids (>10% reduction within 2 weeks) reduced in-hospital mortality (adjusted HR 0.37, 95% CI 0.14 to 0.99). Higher cumulative doses in the first 30 days (5185±2414 mg/month vs 3133±1990 mg/month) were associated with lower recurrence rates (adjusted HR 0.61, 95% CI 0.41 to 0.90, p=0.02). In IPF patients, however, high-dose therapy showed inconsistent benefits, with some studies reporting increased mortality risk (OR 1.075, 95% CI 1.044 to 1.107, p<0.001). This review emphasises the potential benefits of individualised treatment approaches for AE-ILD but highlights the need for caution in making definitive recommendations. Although high-dose corticosteroids may show promise, particularly in non-IPF cases, the current evidence is inconsistent, and the lack of robust supporting literature makes it difficult to draw firm conclusions. Further research through randomised controlled trials is necessary to refine and optimise therapeutic strategies for AE-ILD.

Modern approaches in combined surgical treatment of complex forms of genital prolapse

BACKGROUND: Despite the existence of a considerable number of techniques for surgical correction of genital prolapse, patients and doctors cannot be always sure regarding the efficacy of surgical treatment in achieving satisfactory results. As was the case many years ago, the issues of improving the efficacy, reliability and safety of surgical treatment of genital prolapse, as well as the intent to generate individual treatment approach, taking into account the type of prolapse and medical condition of women, remain pertinent. AIM: The objective of this study is to develop surgical techniques for patients with complex types of pelvic organ prolapse, including women with unfavourable general medical condition. MATERIAL AND METHODS: A comprehensive clinical examination and surgical treatment of 20 patients with II–IV stage pelvic organ prolapse according to the POP-Q classification, who exhibited similar nosological forms of prolapse but disparate comorbidity status, was conducted. Group 1 included 11 patients with complex pelvic organ prolapse who underwent combined laparoscopic pectopexy. Due to the presence of decubitus changes of the cervix and adverse general status, a two-staged strategy was chosen for nine patients of the Group 2, i.e. laparoscopic correction of apical prolapse — uterine suspension with the use of titanium tapes — at the first stage, and modified Manchester (Moscow) operation with the use of titanium tape, colpoperineorrhaphy with levator ani muscles plication — at the second stage. RESULTS: The results of the questionnaire indicated that all patients reported a notable improvement in their quality of life and social integration. In all patients, the symptoms of pelvic organ prolapse significantly improved, and no signs of disease recurrence were present. CONCLUSION: The findings suggest that the proposed surgical techniques for treating pelvic organ prolapse are a viable, efficacious and secure option. They offer swift recuperation and reliable rehabilitation. These techniques have the potential to improve both the physical and social well-being of patients. The described surgical techniques help to restore the normal anatomical position and functions of the organs.

Phenotypes of primary sclerosing cholangitis in children

Background. Primary sclerosing cholangitis (PSC) in children is a rare chronic immune-mediated disease of the biliary tract, which, unlike in adults, has a less aggressive course with da­mage to the intrahepatic bile ducts and is combined with autoimmune hepatitis, creating a special clinical phenotype of PSC, autoimmune sclerosing cholangitis (ASC). Although immunosuppressive therapy is effective in controlling autoimmune inflammation, it does not inhibit the progression of fibrotic changes around the bile ducts, which, unfortunately, leads to the formation of biliary cirrhosis of the liver. Research aimed at studying the clinical course of PSC in children and improving early diagnosis is relevant, especially given the limited access to modern diagnostic methods, such as magnetic resonance cholangiopancreatography, the need for invasive studies, and the lack of standardized diagnostic criteria adapted to childhood, which complicates the diagnosis and treatment of these patients. Objective: to investigate the clinical features of primary sclerosing cholangitis in children and adolescents depending on di­sease phenotype with the aim of develo­ping individualized treatment approaches. Materials and methods. Retrospective and prospective analysis of the clinical course of primary sclerosing cholangitis in children and adolescents who were treated and followed at the Department of Pediatric Hepatology from 2016 to 2024 was conducted. The study included 68 children (62 % boys and 38 % girls) with PSC aged 3 to 18 years (mean age at diagnosis was (11.0 ± 3.9) years). Of these, 38 patients (56 %) had autoimmune sclerosing cholangitis, and 30 (44 %) had isolated PSC without clinical or histological signs of autoimmune hepatitis. Results. At disease onset, 40 % of children with PSC had liver fibrosis graded F3-F4 on METAVIR, with 24 % showing cirrhosis. The most common phenotype in children with PSC was a mixed one involving both large and small bile ducts (63 %). PSC with large bile duct involvement alone was observed in 11 % of cases, 70 % of these children were diagnosed with cirrhosis. Small duct involvement alone was present in 26 % of cases, with cirrhosis in 12.5 % (p = 0.01). Inflammatory bowel disease (IBD) was diagnosed in 84 % of children with PSC: 32 % had ulcerative colitis, 38 % had indeterminate IBD, and 16 % had Crohn’s disease. Pancolitis occurred in 56 % of cases, while 19 % of patients had histological signs of IBD without clinical or endoscopic manifestations. Asymptomatic IBD was diagnosed in 58 % of cases. The clinical course of ASC differed from isolated PSC with significantly higher rates of anemia (47 vs. 27 %, p = 0.03), elevated serum IgG levels (23.9 vs. 12.5 g/l, р &lt; 0.01), and higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin (p &lt; 0.01 for all), non-invasive fibrosis markers (APRI, FIB-4, 2D-SWE) at onset (p &lt; 0.01; p = 0.01; p = 0.04, respectively). Liver fibrosis F3-F4 on METAVIR was more frequently diagnosed in ASC group than in patients with isolated PSC (73 vs. 40 %, p = 0.06). Large bile duct involvement alone was found only in isolated PSC (p &lt; 0.0009). No differences were observed between ASC and isolated PSC in terms of IBD phenotype. Conclusions. PSC in children is represented by 2 phenotypes (ASC and isolated PSC) that occur with almost equal frequency. ASC and isolated PSC have similar phenotypes of biliary and intestinal lesions, however, they differ in terms of clinical course and therapeutic approaches. Involvement of the large bile duct alone in children with PSC is associated with rapid formation of liver fibrosis and cirrhosis. PSC phenotype with involvement of small bile ducts alone has a favorable course in children. Most children with PSC exhibit the PSC-IBD phenotype. Active diagnostic search for biliary and intestinal lesions in children with PSC will facilitate the development of effective personalized approaches to treatment and monitoring, thereby improving disease prognosis.

The primary hyperparathyroidism and its complications: Substantiation of funding volume for hospital pharmacotherapy

This study investigates factors influencing the cost of pharmacotherapy for primary hyperparathyroidism (PHPT) in a hospital setting to optimize therapeutic strategies and rationalize financing. The study was conducted from 2020 to 2023 and included 200 patients with PHPT from two hospitals in Moscow, Russia. The key aspects for analysis were demographic profiles, treatment methods, complications, and associated costs. The majority of patients (52.1%) were aged 60-74 years, while only 2.0% were aged 75 or older. The most frequently prescribed medications were cardiovascular drugs (33.5%) and vitamin supplements (25.1%). Colecalciferol (13.5%), bisoprolol (6.8%), and cinacalcet (4.9%) were the most common individual medications. The study revealed that the cost of conservative treatment without complications was twice that of surgical treatment. These models can aid in justifying and optimizing PHPT treatment financing in hospital settings. The findings highlight the importance of individualized treatment approaches and cost optimization strategies.

Bevacizumab for Vestibular Schwannomas in Neurofibromatosis Type 2: A Systematic Review of Tumor Control and Hearing Preservation.

Background/Objectives: Vestibular schwannomas (VSs), also called acoustic neuromas, are benign tumors affecting the vestibulocochlear nerve, often leading to hearing loss and balance issues. This condition is particularly challenging in patients with neurofibromatosis type 2 (NF2), where VSs tend to develop bilaterally. Conventional treatments, such as surgery and radiotherapy, although effective, carry risks like hearing loss and nerve damage. Bevacizumab, a VEGF-targeting monoclonal antibody, has emerged as a less invasive treatment option, showing potential for tumor volume reduction and hearing preservation. This systematic review aims to assess the efficacy of bevacizumab in controlling tumor volume, preserving hearing, and identifying associated adverse events. Methods: A comprehensive systematic review was performed using PRISMA guidelines. PubMed and Cochrane Library databases were searched for studies evaluating the effects of bevacizumab on VS, focusing on key outcomes like tumor volume reduction, hearing preservation, and adverse events. Data extraction and quality assessment were independently conducted by two reviewers using the Newcastle-Ottawa Scale. Results: Nine studies involving 176 patients were included. Bevacizumab showed a partial tumor volume reduction (≥20%) in 40% of cases and disease stabilization in 50%, while 10% experienced tumor progression. Hearing outcomes revealed improvement in 36% of patients, stabilization in 46%, and deterioration in 18%. Severe adverse effects, including hypertension and thromboembolic events, occurred in 13% of patients, while 18% reported no side effects. Tumor regrowth was observed in some patients after treatment discontinuation, emphasizing the need for long-term monitoring. Conclusions: Bevacizumab demonstrates effectiveness in managing VS, particularly in NF2 patients, by reducing tumor size and preserving hearing in a substantial proportion of cases. However, the variability in patient response and the risk of adverse events underscore the need for individualized treatment approaches and further research, including randomized controlled trials, to optimize its clinical application.

P95 A systematic review of dual biologic or small molecule therapy in patients with psoriasis

Abstract While many treatments exist for psoriasis, there remains a subset of patients who are refractory to conventional treatments, including biologic monotherapy. This patient population has necessitated alternate treatment regimes, including dual biologic and/or small molecule therapy. This systematic review aims to evaluate the efficacy and safety of dual biologic or small molecule therapy in patients with psoriasis and other comorbid inflammatory diseases, necessitating biologics and/or small molecules. Following PRISMA guidelines, Ovid’s Medline and Embase databases were searched, and a protocol was registered in PROSPERO. A total of 21 articles were ultimately included in the review, including 17 case reports, and 4 case series. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. This systematic review examined 38 patients with a mean age of 50.5 years (range: 27–78) who were predominantly female (56.7%). All cases with reported psoriasis duration had long-standing psoriasis with an average duration of 15.3 years. Prior to dual therapy, the most common treatments were biologic monotherapy (67.6%), topical corticosteroids (58.8%), and systemic immunosuppressors and/or immunomodulators (50.0%). The most commonly reported biologic combination was dupilumab and guselkumab (n = 13/38, 34.2%). There were two combinations of a biologic and a JAKi, baricitinib combined with infliximab and ixekizumab, respectively. Secondary indication for dual therapy was most commonly atopic dermatitis (AD) (50.0%) or psoriatic arthritis (26.3%). Dual biologic therapy was efficacious in 85.7% (n = 36/38) of patients, with a mean change in psoriasis area and severity index of 20.0 (P &amp;lt; 0.01). Adverse reactions to dual therapy were infrequent, with only four patients (9.52%) reporting non-dermatological events, three patients (7.14%) reporting dermatological events, and one patient reporting a loss of response to their psoriasis treatment (2.38%). Our findings highlight a cohort of patients with long-standing psoriasis, and other comorbid inflammatory diseases. The majority of patients had attempted conventional therapeutic options without adequate response. The efficacy of dual biologic and/or small molecule therapy offers a promising outlook for this patient population with comorbid inflammatory diseases with 95.2% of patients experiencing therapeutic benefit and a significant mean change in PASI reported. The various combinations of biologics utilized amongst the patients in this cohort highlight a need for individualized treatment approaches tailored to the specific clinical characteristics and comorbidities of each patient. It is important to acknowledge the limitations of the included studies, such as the small sample size and thus future studies with larger sample sizes are needed to examine the effectiveness and safety of combined biologic or small molecule therapy for this patient population.

An epidemiological study on the factors including genetic polymorphism influencing ALT >30 U/L and liver fibrosis progression in metabolic dysfunction-associated steatotic liver disease among the general population.

Identifying the factors contributing to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a lifestyle-related disease, is crucial for preventing future liver-related deaths. This study aimed to epidemiologically investigate factors, including single-nucleotide polymorphisms (SNPs) associated with alanine aminotransferase (ALT) levels >30 U/L and potential risk factors for liver fibrosis, in a general population cohort of patients with MASLD. Among 1059 participants in the health checkup project, 228 who were diagnosed with MASLD were analyzed. Liver fat content and stiffness were measured using FibroScan, and 13 SNPs associated with non-alcoholic fatty liver disease (NAFLD) were measured in addition to other clinical parameters. In the multivariate analysis, male sex, younger age, and high triglyceride levels were significant risk factors for ALT levels >30 U/L (P-value < 0.05). Furthermore, among the 13 SNPs measured, only the GG genotypes of patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 and rs2896019 were significant risk factors for ALT levels >30 U/L (P-value 0.004 and 0.007). The GG genotypes of PNPLA3 rs738409 and rs2896019 had higher FibroScan-aspartate aminotransferase (FAST) and APRI scores than the CC + CG and TT + TG genotypes (P-value < 0.05). In addition, multivariate analysis revealed that the GG genotypes of rs738409 and rs2896019 were significant risk factors independent of cardiovascular metabolic risk for patients with MASLD (P-value 0.038 and 0.021). An individualized treatment approach is warranted for patients with MASLD due to the influence of various factors on its progression, including genetic factors and lifestyle diseases.

Management challenges of ovarian adult-type granulosa cell tumors at a tertiary facility in resource-limited setting: A case series of three patients and review of the current literature.

Adult-type granulosa cell tumors (AGCTs) are rare, low-grade malignant ovarian sex-cord stromal tumors, accounting for approximately 5% of all ovarian tumors. These tumors are characterized by their potential for late recurrence and complex management, which presents significant challenges, particularly in resource-limited settings where access to advanced diagnostic tools and treatment options is restricted. This study highlights a series of rare AGCT cases diagnosed in premenopausal and postmenopausal women in Northern Tanzania. Given the global rarity of AGCTs and the limited literature on the condition, especially in this region, this study aims to address a critical knowledge gap. This report presents a series of three patients diagnosed with ovarian adult-type granulosa cell tumors (AGCTs) based on histological findings. The series underscores the variability in clinical presentations and highlights the significance of individualized treatment approaches in managing these rare tumors. Managing AGCTs in resource-limited settings requires balancing optimal care with available resources. Surgery remains the cornerstone of treatment; however, the lack of advanced diagnostic tools and limited access to adjuvant therapies necessitate a focus on achieving the best possible surgical outcomes and prioritizing rigorous clinical follow-up. This report explores the rarity of AGCTs, reviews existing literature on similar cases, and examines the numerous challenges associated with their management in such settings. Adult granulosa cell tumors are rare, low-grade malignant neoplasms of the ovarian sex-cord stromal origin. These tumors are notable for their potential to recur even years after initial treatment. Consequently, regular follow-up with clinical examinations and tumor marker assessments is recommended. While chemotherapy can provide palliative benefits and manage recurrence, surgery remains the cornerstone of treatment, as illustrated in our case report.

Investigating sex-related differences in brain structure and function in bipolar I disorder using multimodal MRI

BackgroundPast research has highlighted that bipolar I disorder is associated with significant changes in brain structure and function. Notably, the manifestation and progression of bipolar I disorder have been known to differ between males and females. However, the relationship between sex-related differences and bipolar I disorder diagnosis affecting these changes was not fully understood. This study aimed to investigate the sex-by-diagnosis interactions concerning the structural and functional features of the brain in individuals with bipolar I disorder.MethodsBoth structural and functional MRI data were obtained from 105 individuals with bipolar I disorder (36 males and 69 females) and 210 healthy controls (72 males and 138 females). Voxel-wise analyses of gray matter volume and functional connectivity were conducted using a general linear regression model. This model included age, sex, diagnosis, and a sex-by-diagnosis interaction as predictors to explore potential sex-related differences in the brain features of participants with bipolar I disorder.ResultsThe gray matter volume analysis revealed significant sex-by-diagnosis interactions in six brain regions: the left caudate (p < 0.001), left thalamus (p < 0.001), right caudate (p = 0.003), right thalamus (p < 0.001), left anterior cingulate gyrus (p = 0.022), and left middle/posterior cingulate gyrus (p = 0.015). Using these regions as seeds, we detected a significant sex-by-diagnosis interaction in the functional connectivity alteration between the left thalamus and right angular gyrus (p = 0.019).ConclusionsOur findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants. These results hint at potential sex-related differences in the pathophysiology of the limbic system in bipolar I disorder, which may have significant implications for understanding the underlying mechanisms in bipolar I disorder. Our findings could contribute to developing more personalized treatment approaches for individuals with bipolar I disorder.

Exploring cardiovascular implications in systemic lupus erythematosus: A holistic analysis of complications, diagnostic criteria, and therapeutic modalities, encompassing pharmacological and adjuvant approaches.

Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes.