Therapeutic Outcome In Patients Research Articles

P1064 Association of subcutaneous infliximab CT-P13 serum levels and therapeutic outcomes in patients affected by Inflammatory Bowel Disease: A retrospective international multicentric study

Abstract Background The association between therapeutic outcomes and serum levels associated with the use of subcutaneous (SC) IFX CT-P13 in patients with inflammatory bowel disease [IBD] has been poorly studied. We aimed to define SC-IFX thresholds associated with therapeutic outcomes. Methods Patients receiving SC-IFX who had at least one therapeutic drug monitoring [TDM] were enrolled. Therapeutic outcomes were assessed as follows: clinical remission [HBI <5, SCCAI ≤2]; fecal calprotectin [FCAL] remission [<250 mg/g]; C-reactive protein [CRP] remission [CRP <5 mg/L]; deep remission [clinical + biomarker remission]. Chi-squared test for trend was used to analyze serum levels quartile data. Results 177 patients [54% male; 67% Crohn’s disease; Weight ≥ 80 kg 51%; 7% active smoker; 39% on immunosuppressants [IMM]; 9% on steroids; 26% with previous biologic exposure] from 4 centres had a total of 263 TDM measurements. Of these, were available 242 concurrent clinical measurement, 244 CRP and 152 FCAL.Median duration of SC treatment at time of TDM was 24 months (4-135). Proportion of patients achieving outcomes is described in table 1. The median IFX serum level was significantly higher in patients with clinical remission as well as in those with clinical and CRP remission (Figure 1), compared with patients who did not reach these targets. Conversely, there was no significant difference for the FCAL, clinical and FCAL, clinical and CRP and FCAL outcomes. In univariate analysis of factors associated with clinical remission (p<0.1) were sex, concomitant IMM, concomitant steroids, and previous biologic exposure and were included in a multivariate analysis in which only concomitant IMM showed remained significant [OR 0,1796 CI 95% 0,028-0,633]. Quartile analysis showed better outcome on higher drug levels for clinical remission, but not for other outcomes. Based on the ROC analysis and the Youden index, the cut-off levels for the therapeutic outcomes were respectively: clinical remission 12.85 mg/ml [sensitivity 0.85, specificity 0.5]; FCAL remission 11.8 mg/ml [sensitivity 0.82, specificity 0.32]; clinical and CRP remission 14.55 mg/ml [sensitivity 0.77, specificity 0.44]; clinical and FCAL remission 12.05 mg/ml [sensitivity 0.85, specificity 0.35]; clinical, CRP and FCAL remission12.05 mg/ml [sensitivity 0.85, specificity 0.33]. Conclusion An association between drug levels and clinical outcomes was identified in patients with IBD treated with SC IFX. Clinical remission was associated with a level of 12.8 mg/ml but the association between higher drug levels and deeper remission that has been described previously was not seen. References Roblin X, Nancey S, Papamichael K, et al. Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(5):679-685. doi:10.1093/ecco-jcc/jjad188 Iborra M, Caballol B, Garrido A, et al. Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry. J Crohns Colitis. Published online August 22, 2024. doi:10.1093/ecco-jcc/jjae127

Calreticulin-From the Endoplasmic Reticulum to the Plasma Membrane-Adventures of a Wandering Protein.

Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca2+-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER's protein folding response and Ca2+ homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER. However, the identification of CRT in the nucleus and cytosol has established that CRT is a multi-compartmental, multifunctional protein. CRT also plays an important role in cancer progression. Most recently, CRT was identified on the cell surface and shown to be a potent 'eat-me' signal that plays a key role in the uptake of apoptotic and viable cancer cells by phagocytes. Elevated CRT exposure on the outer leaflet of cancer cells has been linked with anticancer immunity and superior therapeutic outcomes in patients with non-small cell lung carcinoma, colorectal carcinoma, acute myeloid leukemia, ovarian cancer, and high-grade serous carcinomas. Mutations in the CRT gene have been identified in a subset of patients with myeloproliferative neoplasms. The most recent studies from our laboratory have revealed a new and significant function for extracellular CRT as a plasminogen receptor. This discovery has profound implications for our understanding of the role of CRT in myeloproliferative neoplasms, specifically, essential thrombocythemia.

68Ga-Pentixafor PET/CT for the assessment of therapeutic outcomes following superselective adrenal arterial embolization in patients with primary aldosteronism

BackgroundSuperselective adrenal artery embolization (SAAE) represents a novel therapeutic strategy for managing primary aldosteronism (PA). Currently, the evaluation of its efficacy is primarily restricted to clinical indicators, with a notable deficiency in imaging evaluation methodologies. In recent years, several studies have investigated the application of 68Ga-Pentixafor PET/CT for the classification of PA. However, there is a scarcity of specific research investigating the role of PET/CT in the evaluation of efficacy of this condition. Consequently, this study aims to evaluate the therapeutic efficacy of SAAE in patients with PA using 68Ga-Pentixafor PET/CT, with the objective of establishing imaging evaluation methodologies for assessing PA patients post-SAAE treatment.ResultsOf the 27 patients, 2 achieved complete clinical remission, while 25 experienced partial remission. Biochemically, 13 patients attained complete remission, 13 had partial remission, and 1 did not. For patients with aldosterone-producing adenoma, both visual and semi-quantitative analyses of PET/CT effectively assessed changes in radioactive uptake of the lesion. For idiopathic hyperaldosteronism patients, PET/CT parameters were more effective than visual analysis in evaluating SAAE efficacy. A significant difference in the ΔTLR-40 min parameter was observed across biochemical outcomes (P = 0.041), with patients having ΔTLR-40 min ≥ 0.07 showing better outcomes (AUC = 0.789, P = 0.041).Conclusions68Ga-Pentixafor PET/CT enables timely assessment of therapeutic outcomes in patients with PA following SAAE, thereby improving clinical decision-making and patient management.

Practice Guidelines for the Value Evaluation of Clinical Pharmacy Services (version 2).

To optimize the construction of pharmaceutical services in medical institutions, advance the development of clinical pharmacy as a discipline, enhance the level of clinical pharmacy services, systematically implement and evaluate clinical pharmacy practices, and improve patient therapeutic outcomes, we have developed the Practice Guidelines for the Value Evaluation of Clinical Pharmacy Services (Version 2). This guideline was designed following the World Health Organization (WHO) Guideline Development Manual. The Delphi method was employed to identify clinical questions. A comprehensive systematic search was conducted to collect existing evidence on relevant issues, and the systematic reviews, evidence grading, and evidence summaries were subsequently compiled. The guideline employs the Joanna Briggs Institute (JBI) evidence level system from Australia and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system introduced by WHO in 2004 to classify the quality of evidence. Consensus on the recommendations and evidence levels was achieved through the Delphi method, resulting in the formation of the Practice Guidelines for the Value Evaluation of Clinical Pharmacy Services (Version 2). Through a questionnaire survey of over 100 experts and the Delphi method voting, 23 preliminary indicators for evaluating the value of clinical pharmacy services were identified. The content of these included indicators was searched according to the PICO principle, followed by systematic reviews, meta-analyses, network meta-analyses, and related original research. Each search strategy was reviewed and approved by the guidelines steering committee. Ultimately, three dimensions for evaluating the value of clinical pharmacy were identified, encompassing 15 indicators, resulting in 20 recommendations. This guideline presents a set of metrics to assess the quality and effectiveness of clinical pharmacy services, which is crucial for enhancing and elevating clinical pharmacy services in healthcare institutions. http://www.guidelines-registry.org/guide/28502a74-7038-439c-bdee-d355747e2a9d, identifier: PREPARE-2022CN756.

The effect of early rehabilitation on therapeutic outcomes in ICU patients on mechanical ventilation: A meta-analysis.

To evaluate the effect of early rehabilitation on therapeutic outcomes of patients in the ICU requiring mechanical ventilation. Electronic databases up to June 15, 2024 were searched. Randomized controlled trials (RCTs) that compared early rehabilitation with standard rehabilitation for patients in the ICU on mechanical ventilation were included. The effects of early rehabilitation on outcomes such as duration of mechanical ventilation (days), ICU length of stay (days), hospital length of stay (days), ICU and in-hospital mortality, and ICU-acquired weakness (ICU-AW) were evaluated using a random-effects model. Nineteen RCTs met the inclusion criteria for this study, involving 3076 patients in the ICU on mechanical ventilation. Meta-analysis based on the random-effects model showed that early rehabilitation significantly reduced the duration of mechanical ventilation, ICU-AW risk, ICU length of stay, and total hospital length of stay. Analysis of the timing of early rehabilitation indicated that implementing early rehabilitation within ⩽48 or ⩽72 h after ICU admission or mechanical ventilation had varying effects on the duration of mechanical ventilation, ICU length of stay, and total hospital length of stay. Early rehabilitation can improve the therapeutic outcomes for ICU patients on mechanical ventilation. The optimal time for implementing early rehabilitation appears to be 48-72 h after ICU admission or initiation of mechanical ventilation, but further research is needed. INPLASY202470068.

Medical Management of the Near-Narrowed Internal Auditory Canal Pathology in the Adult Population: A Preliminary Study.

Background/Objectives: Objective: To discuss therapeutic outcomes in patients with symptomatic near-narrow internal auditory canal (NNIAC). Methods: We retrospectively analyzed the records of 26 symptomatic patients diagnosed with NNIAC, who had been treated with anti-epileptic drugs. In addition to clinical and radiological data, we recorded I-III latencies of auditory brainstem responses prior to and after medical therapy. Results: Among a total of 48 patients with NNIAC, 26 patients were included. Oxcarbazepine, Gabapentin, and Lamotrigine were prescribed among 19 (73%) patients, 6 (23%) patients, and 1 patient (4%), respectively. After treatment, 24 (92.3%) patients described improvement of vestibular symptoms, and 16 (76.2%) reported improvement of auditory symptoms. After treatment with antiepileptic drugs, ipsilateral IPL I-III latencies decreased (less than 2.3 ms) in 16 (84.2%) patients (23 ears out of 42). Conclusions: A low dose of anti-epileptic monotherapy for NNIAC could be effective over the long term and is generally well-tolerated. Further studies are needed to provide more solid evidence of the efficacy and safety of anti-epileptic drugs on a larger number of patients with NNIAC.

Comparative study of therapeutic outcomes in patients who developed hepatolithiasis after hepaticojejunostomy: balloon-assisted enteroscopic approach versus percutaneous transhepatic approach

Comparative study of therapeutic outcomes in patients who developed hepatolithiasis after hepaticojejunostomy: balloon-assisted enteroscopic approach versus percutaneous transhepatic approach

Depression and anxiety, peripheral blood inflammatory factors, and stress levels on therapeutic outcomes in patients with chronic wounds.

The incidence of chronic wounds is rising due to an aging population and lifestyle changes in our country. In addition, as the disease spectrum evolves, chronic wounds have become common clinical issues that seriously threaten health and impose significant social and economic burdens. To investigate how depression, anxiety, peripheral blood inflammatory factors, and stress levels affect therapeutic outcomes in patients with chronic wounds. Retrospectively collected clinical data from 110 patients with chronic wounds treated at Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) between January 2021 and December 2023, categorizing them into effective and ineffective groups based on treatment effects. Differences between both groups were analyzed using univariate analysis, independent risk factors identified via logistic regression, and their predictive value assessed through receiver operating characteristic analysis. Following treatment, 95 cases were classified as the effective group (cured or improved), while 15 cases with improvement formed the ineffective group. Significant differences between both groups were noted in wound area, infection status, daily bed time, Hamilton Anxiety Rating Scale (HAMA) scores, Hamilton Depression Rating Scale (HAMD) scores, and levels of interleukin-6, tumor necrosis factor-alpha, and superoxide dismutase (P < 0.05). Logistic regression analysis identified a wound area ≥ 7 cm2, HAMA ≥ 9 scores, and HAMD ≥ 8 scores were independent risk factors for ineffective treatment in patients with chronic wounds (P < 0.05). The receiver operating characteristic curve analysis revealed that the area under the curve for ineffective treatment based on wound area, HAMA, and HAMD was 0.767, 0.805, and 0.768 respectively. Wound size, anxiety, and depression are significant factors influencing the therapeutic outcomes in patients with chronic wounds that require careful attention, alongside the development of appropriate strategies.

Advances in Regenerative Medicine for the Treatment of Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) is a debilitating condition characterized by progressive bone tissue necrosis, commonly linked to bisphosphonates, radiation therapy, or trauma. Traditional treatments, such as surgical debridement and conservative management, often fail to fully restore bone function, driving the need for alternative therapeutic strategies. Regenerative medicine, particularly cellular therapies and biomaterials, has emerged as a promising field in ONJ treatment. This review explores recent advancements in regenerative approaches for ONJ, with a focus on Mesenchymal stem cells (MSCs) and bioengineered scaffolds. MSCs, with their dual ability to differentiate into osteoblasts and modulate immune responses, play a crucial role in bone regeneration by both forming new bone tissue and reducing inflammation. Bioengineered scaffolds, such as hydrogels, bioactive ceramics, and nanomaterials, provide essential structural support and create a conducive environment for cellular growth and tissue repair. The combination of MSCs with these biomaterials has demonstrated a synergistic effect, significantly enhancing bone healing and regeneration. Additionally, emerging techniques such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and bone morphogenetic proteins (BMPs) offer new avenues for improving clinical outcomes in ONJ patients. However, several challenges remain, including regulatory barriers, the need for standardized cell isolation and delivery protocols, and scalability issues for clinical application. This review further examines emerging technologies, such as 3D bioprinting and personalized medicine, which offer the potential to tailor regenerative treatments to individual patients, thereby improving both the efficacy and longevity of therapies. In conclusion, while significant progress has been made in the application of regenerative medicine for ONJ, continued research is essential to address current limitations, optimize treatment protocols, and ensure broader clinical adoption. Advances in cellular therapies and biomaterials hold transformative potential for improving therapeutic outcomes in patients with ONJ.

Serum Albumin and Its Trajectory Are Associated With Therapeutic Outcomes in Ulcerative Colitis.

The relationship between serum albumin levels and therapeutic outcomes in ulcerative colitis (UC) has been debated. Additionally, the dynamic changes in albumin levels remain understudied. We conducted a pooled analysis of 5 clinical trials involving 3268 patients with UC. Short- and long-term therapeutic outcomes were assessed at the end of the induction and maintenance phases. Multivariate logistic regression and random effects models were used to pool the predictive effects of albumin levels. The dynamic trajectory of albumin was fitted using latent class growth mixed models. Baseline and week-2 albumin were independent predictors of short-term outcomes, with pooled adjusted odds ratios (aORs) of 1.07 (95% confidence interval [CI],1.05-1.09) and 1.11 (95% CI, 1.08-1.15) per 1 g/L increase for clinical response, respectively. Higher post-induction albumin levels predicted better long-term outcomes, including clinical (aOR, 1.16; 95% CI, 1.12-1.21), endoscopic (aOR, 1.13; 95% CI, 1.10-1.16), and histologic remission (aOR, 1.11; 95% CI, 1.03-1.18). Furthermore, there are 3 classes of albumin trajectories: sustained medium-to-high, rapidly ascending, and poor response. Compared with the sustained medium-to-high class, patients in the poor response class had a lower probability of long-term endoscopic remission (aOR, 0.35; 95% CI, 0.23-0.50; P < .001), whereas no significant difference was observed between the rapidly ascending class and the sustained medium-to-high class. Higher albumin levels were associated with better therapeutic outcomes in patients with UC. However, patients with low but rapidly ascending albumin levels would achieve outcomes comparable to those with medium-to-high levels of albumin.

Advances in Topical Therapies for Clinically Relevant and Prevalent Forms of Alopecia.

Alopecia encompasses diverse conditions that vary by etiology, progression, and clinical presentation, including androgenetic alopecia, alopecia areata, telogen effluvium, and scarring alopecias such as lichen planopilaris and central centrifugal cicatricial alopecia. Managing these conditions requires tailored therapeutic approaches, with topical treatments emerging as effective first-line interventions. This literature review examines topical therapies across alopecia types, assessing mechanisms of action, clinical efficacy, and safety profiles to guide evidence-based clinical practice. Methods involved a comprehensive search across PubMed, SCOPUS, and Web of Science databases, focusing on clinical research published within the past five years. Articles were screened based on relevance to alopecia management, excluding abstracts, non-English studies, and ongoing research. Topics covered include commonly used agents such as minoxidil, corticosteroids, and emerging options like Janus kinase (JAK) inhibitors. Topicals for trichotillomania, such as capsaicin and numbing creams, are highlighted for their behavioral conditioning potential, while treatments like minoxidil and adenosine are explored for telogen effluvium. Findings indicate that topicals provide symptom relief, promote hair regrowth, and often serve as adjuncts to systemic therapies. Minoxidil and corticosteroids demonstrate efficacy in multiple alopecia types, while JAK inhibitors show promise in alopecia areata. This review underscores the value of topical treatments in alopecia management and highlights areas for future research, advocating for individualized approaches to enhance therapeutic outcomes in patients experiencing hair loss.

The New Tumour Biomarker miRNA-371-3p Influences Cisplatin Sensitivity of Testicular Germ Cell Tumour Cell Lines.

Cisplatin is used to treat a variety of malignancies, including testicular germ cell tumours (TGCTs). Although cisplatin-based chemotherapy yields high response rates, a subset of patients develop cisplatin resistance, limiting treatment options and worsening prognosis. Therefore, there is a high clinical need for new therapeutic strategies targeting cisplatin-resistant TGCTs. MicroRNA-371a-3p (miR-371), the new serum biomarker for TGCTs, shows significantly increased expression in cisplatin-resistant TGCT cell lines compared to sensitive parental cell lines. However, the functional impact of miR-371 on cisplatin sensitivity has not been investigated yet. To evaluate the impact of miR-371 on cisplatin sensitivity, antagomirs were used to inhibit miR-371 expression, resulting in a > 98% decrease in miR-371 expression. Cisplatin sensitivity was significantly increased after miR-371 inhibition in cisplatin-resistant and corresponding parental TGCT cell lines, indicating a strongly reduced viability and increased apoptosis after cisplatin treatment in miR-371-inhibited cells. Our results suggest that miR-371 may contribute to the development of cisplatin resistance in TGCTs. Interfering with miR-371 expression can increase the cisplatin sensitivity of tumour cells, which may represent a promising approach to improve future therapeutic outcomes in patients with TGCTs, especially those with cisplatin-resistant disease.

RWD134 Healthcare Pathways and Therapeutic Outcomes of Patients With Spinal Muscular Atrophy: Results From the 12-Year Real-World Study EPI-SMA Based on the French National Healthcare Database (SNDS)

RWD134 Healthcare Pathways and Therapeutic Outcomes of Patients With Spinal Muscular Atrophy: Results From the 12-Year Real-World Study EPI-SMA Based on the French National Healthcare Database (SNDS)

Clinical significance of quantitative assessment of right ventricular amyloid burden with [99mTc]Tc-DPD SPECT/CT in transthyretin cardiac amyloidosis.

To evaluate right ventricular (RV) uptake measured by quantitative [99mTc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA). Patients with ATTR-CA were consecutively enrolled for quantitative [99mTc]Tc-DPD SPECT/CT. Ventricular amyloid burden was quantified by SUVmax and TBR. Differences in RV uptake (focal or diffuse) and associations with clinical characteristics and CMR data were evaluated. The primary endpoint was major adverse cardiac events (MACEs), including all-cause deaths, heart failure hospitalizations, complete atrioventricular block, sustained ventricular tachycardia, and atrial fibrillation/flutter. Prognostic associations were evaluated using Cox regression and Kaplan-Meier survival analysis. A secondary endpoint involved a longitudinal SPECT/CT analysis during Tafamidis therapy. The study included 76 patients, all showing both RV and LV uptake on SPECT imaging. Compared with patients with focal RV uptake, patients with diffuse RV uptake had higher serum troponin T levels (P < 0.05), septal thickness (P < 0.01), and external cardiac circulation volume (ECV) (P < 0.05). RV uptake was correlated with septal thickness, ECV, LV uptake, NT-proBNP and troponin-T (all P < 0.05). Among 53 patients, high LV and RV uptake significantly predicted MACEs (P < 0.001), with a median follow-up time of 16 months. A subgroup of 20 patients showed significant reductions in LV and RV uptake after Tafamidis treatment (P < 0.001). Increasing RV amyloid burden quantified by SPECT/CT is associated with advanced disease stage and predicts MACEs, serving as valuable markers for prognosis and treatment monitoring in ATTR-CA.

Subcutaneous Infliximab Concentration Thresholds for Mucosal and Transmural Healing in Patients With Crohn's Disease.

Predose trough concentrations (Ctrough) of intravenous infliximab (IV-IFX) during maintenance therapy are associated with therapeutic outcomes in patients with Crohn's disease (CD). A subcutaneous formulation of infliximab (SC-IFX) has shown high Ctrough values due to its favourable pharmacokinetics. To evaluate the association of Ctrough of SC-IFX with therapeutic outcomes and the threshold of SC-IFX Ctrough for achieving mucosal healing (MH) and transmural healing (TH) in patients with CD. We performed this cross-sectional study in patients with CD who had received SC-IFX maintenance therapy for ≥ 6 months. We measured SC-IFX Ctrough immediately before SC-IFX injection. We performed ileocolonoscopy/single-balloon enteroscopy and/or magnetic resonance enterography within 3 months of SC-IFX Ctrough measurement. MH was defined as SES-CD-ulcerated surface subscore of 0. TH was defined as simplified MaRIA score of 0. We enrolled 124 patients with MH in 77.9% (74/95) and TH in 36.3% (37/102). SC-IFX Ctrough was significantly higher in patients with MH (24.1 vs.16.9 μg/mL; p = 0.001) and TH (26.0 vs. 20.5 μg/mL; p = 0.007) than in those without. ROC analysis identified that the threshold of SC-IFX Ctrough for MH and TH were 17.5 and 30.3 μg/mL, respectively. Multivariate logistic regression showed that SC-IFX Ctrough was significantly associated with MH (OR 1.16; 95% CI 1.05-1.27; p = 0.002) and TH (OR 1.08; 95% CI 1.02-1.14; p = 0.005). SC-IFX Ctrough was positively associated with MH (≥ 18 μg/mL) and TH (≥ 30 μg/mL) in patients with CD, which may guide treatment decisions to optimise therapeutic response in the era of treat-to-target.

RAS-mutant leukaemia stem cells drive clinical resistance to venetoclax

Cancer driver mutations often show distinct temporal acquisition patterns, but the biological basis for this, if any, remains unknown. RAS mutations occur invariably late in the course of acute myeloid leukaemia, upon progression or relapsed/refractory disease1, 2, 3, 4, 5–6. Here, by using human leukaemogenesis models, we first show that RAS mutations are obligatory late events that need to succeed earlier cooperating mutations. We provide the mechanistic explanation for this in a requirement for mutant RAS to specifically transform committed progenitors of the myelomonocytic lineage (granulocyte–monocyte progenitors) harbouring previously acquired driver mutations, showing that advanced leukaemic clones can originate from a different cell type in the haematopoietic hierarchy than ancestral clones. Furthermore, we demonstrate that RAS-mutant leukaemia stem cells (LSCs) give rise to monocytic disease, as observed frequently in patients with poor responses to treatment with the BCL2 inhibitor venetoclax. We show that this is because RAS-mutant LSCs, in contrast to RAS-wild-type LSCs, have altered BCL2 family gene expression and are resistant to venetoclax, driving clinical resistance and relapse with monocytic features. Our findings demonstrate that a specific genetic driver shapes the non-genetic cellular hierarchy of acute myeloid leukaemia by imposing a specific LSC target cell restriction and critically affects therapeutic outcomes in patients.

Evaluating the impact of brachytherapy duration on therapeutic outcomes in patients with cervical cancer

The total duration of radiotherapy for patients with cervical cancer should be limited to 56 days to optimize treatment outcomes. This study aimed to statistically evaluate the effects of extended radiotherapy duration on survival and complications in 649 patients with cervical cancer treated with brachytherapy at our institution from 2014 to 2019. All patients had undergone intensity-modulated external beam radiation therapy, with 525 receiving two-dimensional (2D) brachytherapy and 124 receiving three-dimensional (3D) brachytherapy. Using the inverse probability of treatment weighting (IPTW) and propensity score matching (PSM), clinical data regarding treatment duration, survival outcomes, and complications were analyzed. PSM revealed that overall survival (OS) did not significantly differ between patients receiving prolonged treatment (&gt;56 days) and those receiving treatment for a standard duration (&lt;56 days) (P &gt; 0.05). However, among patients who had received 2D brachytherapy, prolonged treatment correlated with increased recurrence and metastasis risks (P &lt; 0.001); this trend was not evident in patients receiving 3D brachytherapy (P = 0.287). Higher FIGO stages were associated with worse OS and higher progression risks, which persisted post-IPTW adjustment. Extended radiotherapy duration was linked to a higher incidence of rectal and bladder reactions, particularly in the 2D group. Consequently, strictly controlling radiotherapy duration for patients receiving 2D brachytherapy is essential to reduce recurrence and metastasis risks. Close monitoring of rectal and bladder reactions is also recommended.

Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia

IntroductionHER2 mutations are reported to occur in 2%–5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear. MethodsUsing the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated. ResultsOf the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50–0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57–1.12], P = 0.20). ConclusionsAddition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.

Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome

There is some evidence that the subjective effects of ketamine and other psychedelics like psilocybin are crucial for their therapeutic outcomes, such as treatment of depression or substance use disorder (SUD). We performed a meta-analysis and systematic review on the correlation of subjective symptoms and dissociation versus ketamine-induced therapeutic outcomes in patients with depression or SUD. A similar analysis was conducted for psilocybin-induced therapeutic improvement. We retrieved 23 papers studying ketamine (21 on depression, 2 on SUD) in 471 patients and 8 papers studying psilocybin (6 on depression, 2 on SUD) in 183 patients. Our study demonstrated a modest role for subjective effects mediating therapeutic outcomes, with R2-values ranging from 5–10% for ketamine and for psilocybine the R2 was 24%. A greater mediating effect for psilocybin compared to ketamine was detected, particularly when restricting the analysis to depression. Additionally there is a greater mediating effect in SUD than depression, irrespective of treatment.

114P Epidemiology and therapeutic outcomes of patients with spinal muscular atrophy: results from a 12-year real-world study based on the French National Healthcare database (SNDS)

114P Epidemiology and therapeutic outcomes of patients with spinal muscular atrophy: results from a 12-year real-world study based on the French National Healthcare database (SNDS)