Safety Of Treatment In Patients Research Articles

Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study

ObjectiveTo report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. MethodsAnalysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. ResultsOf the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27–0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19–0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18–1.34). Selinexor treatment was generally manageable, with no new safety signals identified. ConclusionIn the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

Efficacy and safety of fruquintinib-based treatment in patients with refractory bone and soft tissue sarcomas after developing resistance to several TKIs: A multicentered retrospective study.

Efficacy and safety of fruquintinib-based treatment in patients with refractory bone and soft tissue sarcomas after developing resistance to several TKIs: A multicentered retrospective study.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies.

Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Tumor regression and safe distance of distal margin after neoadjuvant therapy for rectal cancer.

Neoadjuvant therapy has been widely employed in the treatment of rectal cancer, demonstrating its utility in reducing tumor volume, downstaging tumors, and improving patient prognosis. It has become the standard preoperative treatment modality for locally advanced rectal cancer. However, the efficacy of neoadjuvant therapy varies significantly among patients, with notable differences in tumor regression outcomes. In some cases, patients exhibit substantial tumor regression, even achieving pathological complete response. The assessment of tumor regression outcomes holds crucial significance for determining surgical approaches and establishing safe margins. Nonetheless, current research on tumor regression patterns remains limited, and there is considerable controversy surrounding the determination of a safe margin after neoadjuvant therapy. In light of these factors, this study aims to summarize the primary patterns of tumor regression observed following neoadjuvant therapy for rectal cancer, categorizing them into three types: tumor shrinkage, tumor fragmentation, and mucinous lake formation. Furthermore, a comparison will be made between gross and microscopic tumor regression, highlighting the asynchronous nature of regression in the two contexts. Additionally, this study will analyze the safety of non-surgical treatment in patients who achieve complete clinical response, elucidating the necessity of surgical intervention. Lastly, the study will investigate the optimal range for safe surgical resection margins and explore the concept of a safe margin distance post-neoadjuvant therapy.

Short- and long-term outcomes of acute diverticulitis in patients with transplanted kidneys.

The safety of nonoperative treatment for patients with transplanted kidneys who develop acute diverticulitis is unclear. Our primary aim was to examine the long-term sequelae of nonoperative management in this group. We performed a population-based retrospective cohort study using linked administrative databases housed at ICES in Ontario, Canada. We included adult (≥18 years) patients admitted with acute diverticulitis between April 2002 and December 2019. Patients with a functioning kidney transplant were compared with those without a transplant. The primary outcome was failure of conservative management (operation, drainage procedure or death due to acute diverticulitis) beyond 30 days. The cumulative incidence function and a Fine-Grey subdistribution hazard model were used to evaluate this outcome accounting for competing risks. We examined 165 patients with transplanted kidneys and 74 095 without. Patients with transplanted kidneys were managed conservatively 81% of the time at the index event versus 86% in nontransplant patients. Short-term outcomes were comparable, but cumulative failure of conservative management at 5 years occurred in 5.6% (95% CI 2.3%-11.1%) of patients with transplanted kidneys versus 2.1% (95% CI 2.0%-2.3%) in those without. Readmission for acute diverticulitis was also higher in transplanted patients at 5 years at 16.7% (95% CI 10.1%-24.7%) versus 11.6% (95% CI 11.3%-11.9%). Adjusted analyses showed increased failure of conservative management [subdistribution hazard ratio (sHR) 3.24, 95% CI 1.69-6.22] and readmissions (sHR 1.55, 95% CI 1.02-2.36) for patients with transplanted kidneys. Most patients with transplanted kidneys are managed conservatively for acute diverticulitis. Although long-term readmission and failure of conservative management is higher for this group than the nontransplant population, serious outcomes are infrequent, substantiating the safety of this approach.

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. Multicentre retrospective cohortstudy of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study

ObjectivesThe irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting.Materials and methodsBetween September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib.ResultsA total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years.ConclusionThis study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.

(402) Peyronie's Disease Treatment- Active Vs. Stable Phase- Retrospective Review of Cases

Abstract Introduction Peyronie's disease (PD) may be treated with collagenase clostridium histolyticum (CCH) during the stable phase. However, the effectiveness and safety of this treatment during the active phase remain unclear. To address this, we investigated and compared the outcomes of patients receiving treatment in the active phase versus the stable phase of PD. Objective To assess the effectiveness and safety of CCH treatment in patients diagnosed with PD during the active phase. Methods A retrospective review was conducted on men who underwent at least one cycle of CCH injections for PD with a single fellowship-trained urologist between 2017 and 2023. Active PD was defined as occurring within one year from the onset of symptoms. The severity of penile curvature was measured at the point of maximal curvature and assessed at baseline and after each CCH cycle. In addition to the CCH treatment, patients were prescribed daily phosphodiesterase inhibitors (PDEi) and coenzyme-Q10 (CoQ-10). The treatment response was defined as any improvement in curvature from baseline to the final assessment. The characteristics and outcomes of patients were compared between those with active and stable PD. Results Of 107 patients who underwent CCH treatment, 75 were diagnosed with stable PD and 32 with active PD. There were no significant differences observed between the two groups in terms of age (58.1 vs. 57.9 years, p = 0.89), baseline curvature (58.4 vs. 60.5 degrees, p = 0.60), or the number of CCH cycles received (6.6 vs. 6.3 cycles, p = 0.57). Among the active PD patients, 26 (81.2%) experienced an improvement in curvature, which was comparable to the stable PD group (58 (77.3%), p = 0.85). There were no significant differences in the degree of curvature improvement (14.4 vs. 14.0 degrees, p = 0.91) or the percentage of improvement from baseline (22.67% vs. 24.05%, p = 0.86) between the active and stable PD patients. In the subset of patients who showed an improvement in curvature angle, there was no notable distinction in the percentage of improvement from baseline between the stable and active phases (37.4% vs 34.8%, p=0.63). Among the treated patients, we observed two cases of potential penile fractures in the stable phase. All adverse events were conservatively managed. Conclusions Patients treated with CCH during the active phase achieved comparable outcomes to those in the stable phase. There were no additional adverse events in the active phase treatment group. These data suggest that early active phase treatment yields similar effectiveness as treatment administered during the stable phase. Treatment during the active phase could be a disease modifier and may change the course of progression. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo, Roman Health.

Interrelationship among Personal Characteristics, Perceptions, and Self-Efficacy on Electronic Medical Record System (ERNRS) Use among Health Professionals

Improvements in the quality and safety of patient treatment are enhanced with the use of electronic medical records (EMRs). Despite the use of EMR, no established data existed on perceptions and self-efficacy and their relationship at the local level. The study assessed the interrelationships among personal characteristics, perceptions, and self-efficacy on EMR system use among 306 health professionals of a tertiary private hospital in Pasig, Metro Manila, Philippines, for the second quarter of 2023 who were chosen utilizing a proportionate stratified random sampling. This quantitative research used the descriptive, correlational design. Findings revealed that most respondents were young adults, females, had bachelor's degrees, had good typing ability, and had training in EMR systems. Most belonged to the medical department, used the system moderately, and served for 1-3 years. Overall, perceptions of EMR and self-efficacy were good. All the personal characteristics had a relationship with perceptions of EMR. All personal characteristics, except gender, were correlated with self-efficacy. However, gender was not. Lastly, perceptions of EMR had a relationship with self-efficacy. To address the findings, an action plan for telehealth utilization was created. In conclusion, perceptions of EMR and self-efficacy are influenced by personal characteristics, while perceptions of EMR influence self-efficacy.

OP18 Efficacy and safety of darvadstrocel treatment in patients with complex perianal fistulas and Crohn’s Disease: results from the global ADMIRE-CD II phase 3 study

Abstract Background Complex perianal fistulas are a serious complication in patients with Crohn’s disease (CD). Darvadstrocel (DVS), a suspension of expanded adult allogeneic adipose-derived mesenchymal stem cells, is approved in Europe and Japan for treatment of complex Crohn’s perianal fistulas (CPF). The global ADMIRE-CD II phase 3 randomized double-blind placebo-controlled study evaluated the efficacy and safety of DVS for treatment of complex CPF. Methods Patients aged 18–75 years with clinically controlled, inactive or mildly active CD and complex CPF (≤2 internal openings [IO] and ≤3 external openings [EOs]) who had an inadequate, or a loss of response to immunosuppressive agents or biologics were included. Patients were randomized 1:1 to receive a local injection of DVS as a single dose (120 x 106 cells/24 mL) or placebo. In all patients, fistula preconditioning included vigorous curettage and seton placement 2–3 weeks before treatment, and seton removal, a further curettage and closure of IOs immediately before treatment. The primary endpoint was combined remission (closure of all treated EOs that were draining at baseline, despite gentle finger compression, and absence of collections &amp;gt;2 cm confirmed by MRI) at 24 weeks. Secondary endpoints included combined remission at 52 weeks, clinical remission (closure of all treated EOs without MRI confirmation) at 24 and 52 weeks, and time to clinical remission at 24 weeks. Safety was monitored up to 52 weeks. Results From 19 Oct 2017 to 26 Jul 2023, 568 patients received DVS (n = 283) or placebo (n = 285) with fistula preconditioning; 56.3% of patients enrolled in Europe and Israel, and 43.7% in North America. Mean (SD) age, sex and race were similar in the DVS and placebo arms (38.4 [11.9] vs 37.7 [10.8] years; 42.8% vs 45.6% female; 85.9% vs 89.1% White). Combined remission rates at 24 weeks did not statistically differ between treatments (48.8% DVS vs 46.3% placebo) and there were no differences in secondary endpoints (Table 1; Figure 1). Based on health authority guidelines, post hoc analyses of patients randomized before COVID-19 (11 March 2020; n = 141 DVS, n = 143 placebo) were performed: combined remission rates at 24 weeks were 46.8% (DVS) and 38.5% (placebo). The safety profile for DVS was consistent with prior studies with no new safety signals (Table 1). Conclusion The efficacy outcomes assessed did not statistically differ between DVS and placebo, and the placebo response rate (with fistula preconditioning) was higher than expected. Post hoc analyses revealed lower placebo response rates in patients randomized before COVID-19 (similar to the pivotal ADMIRE CD I study) than the overall placebo arm. DVS was well tolerated.

P646 Clinical decision support in the prevention of adverse effects associated with immunosuppressive drugs in patients with Inflammatory Bowel Disease

Abstract Background With the goal of effective and early prevention and detection of medication-related adverse effects, an explosion of technological advances is taking place. However, none of these systems are currently intelligent enough to ensure safe prescribing of treatments on their own. Purpose To design and integrate clinical decision rules (CDR) to increase the safety of immunosuppressive treatments in patients with inflammatory bowel disease (IBD) into an electronic prescribing assistance software (HIGEA). Methods This is a descriptive study conducted in a tertiary university hospital in Madrid (Spain). 1. We reviewed the technical product information sheet of the immunomodulatory drugs used in the treatment of patients with IBD and the current recommendations and clinical practice guidelines on the management of IBD. 2. The CDR were developed within a multidisciplinary team of physicians and pharmacists by integrating data from pharmacogenetics, microbiology, biochemistry, immunology and haematology laboratories, the electronic medical record and the electronic prescribing programme. 3. Integration was performed using a standard language (HL7). Results The technical product information sheet of 33 immunomodulatory drugs (19 biological therapies, 6 small molecules and 8 traditional disease-modifying drugs) and the clinical practice guidelines for the treatment of IBD of the European Crohn's and Colitis organisation (ECCO) and the Spanish working group on Crohn's disease and ulcerative colitis (GETECCU) were reviewed. A total of 169 CDR were developed: 2 related to pharmacogenetics laboratory values, 26 to microbiology, 38 to biochemistry, 24 to immunology, 42 to haematology, 28 to clinical history and 9 related to concomitant use of other drugs. Of the 169 CDR, 50 (29.58 %) were related to screening prior to initiation of immunosuppressive treatment, 10 (5.92%) to drug interactions and 109 (64.5%) related to clinical conditions requiring adjustment or discontinuation of immunosuppressive treatment. Conclusion The incorporation of personalised clinical rules into the medical prescription and pharmaceutical validation process will allow the selection of patients in whom there could be a safety problem with immunosuppressive treatment, increasing the percentage of early detected and avoided adverse events. Future steps will be to evaluate the impact of the implementation of the CDR tool on increasing safety, reducing healthcare costs and improving patient health outcomes.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5months (95% confidence interval [CI], 8.1-12.9) and 6.0months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p=0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p=0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p=0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p=0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p<0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario

ObjectiveTo develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. MethodsA group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. ResultsFour PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. ConclusionsThe treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Efficacy and safety of combined anlotinib-oral etoposide treatment for patients with platinum-resistant ovarian cancer.

Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1-68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9-100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3-11.6). The incidence of adverse events (any grade) was 100%, and the incidence of grade 3-4 adverse events was 54.5%. Anlotinib combined with etoposide emerged effective for the treatment of PROC.

Эффективность и безопасность разных режимов cахароснижающего лечения у лиц с синдромом раздраженного кишечника в сочетании с сахарным диабетом 2 типа

Among the disorders associated with type 2 diabetes mellitus, intestinal functional changes (irritable bowel syndrome — IBS) are an insufficiently studied problem. The purpose — a prospective study of the efficacy and safety of various hypoglycemic treatment regimens in patients with IBS and type 2 diabetes mellitus. Material and methods The study included 107 patients aged 48.9 ± 9.4 years with type 2 diabetes mellitus and clinical manifestations of IBS, who were divided into 4 groups depending on the prescribed hypoglycemic therapy: patients of group A received metformin, group B — a combination of metformin with saxagliptin, group C — a combination of metformin with liraglutide or exenatide, group D — combination of metformin with dapagliflozin. The duration of the study was not less than 5 months. Results. Treatment in all groups resulted in a significant decrease in the average values of HbA1c, fructosamine, insulin, C-peptide and the HOMA-IR index, an increase in the values of the NOMA-B index, p &lt; 0.05. A more significant absolute and relative decrease in the levels of HbA1c, insulin and HOMA-IR index was observed in groups C and D in comparison with groups A and B. The use of various classes of hypoglycemic drugs in people with IBS and type 2 diabetes mellitus was characterized by satisfactory tolerability and was associated with a significant decrease in clinical manifestations of constipation, diarrhea, abdominal pain, gastroesophageal reflux, and a positive effect on glycemic levels. The criteria for predicting the effectiveness and safety of hypoglycemic treatment in patients with a combination of IBS and type 2 diabetes mellitus were the diabetes duration &lt; 7 years, the values of HOMA-IR &lt;5 and NOMA-B ³ 60, the absence of smoking, the uric acid concentration in blood &lt; 350 mmol/ l, the absence of hypothyroidism and the choice of dapagliflozin as a component of hypoglycemic therapy.

A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies

ABSTRACT Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (>24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade.

Clinical efficacy and safety of endovascular treatment for patients with wake-up stroke with large vessel occlusion guided by NCCT-ASPECTS.

To evaluate the clinical efficacy and safety of 6 to 24 h endovascular therapy (EVT) in patients with wake-up stroke (WUS) with acute large vessel occlusion (LVO) of the anterior circulation guided by noncontrast computed tomography-Alberta stroke program early CT score (NCCT-ASPECTS). Fifty-three patients with WUS with acute LVO of the anterior circulation who were treated at the Sir Run Run Shaw Hospital of Zhejiang Medical College from January 2018 to March 2021 were retrospectively analyzed. The patients were divided into NCCT-ASPECTS or CT perfusion groups. Baseline data, perioperative data, and 90-d prognostic information were compared between the two groups. Multivariable logistic regression analysis was used to determine the independent factors influencing outcomes. There were no significant differences in the good prognosis, symptomatic intracranial hemorrhage, and mortality rates between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the puncture-recanalization time was an independent factor for good prognosis. Based on NCCT-ASPECTS guidance, EVT in patients with WUS for acute LVO of the anterior circulation within 6 to 24 h may be safe and effective.

Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice

BackgroundThe randomised double-blinded placebo-controlled EXIST-1–3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.ResultsThe study included 64 patients with TSC (median age: 19, range 0.9–54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0–106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3–4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment.ConclusionsSeizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.

The Safety of Drug Treatment in Patients with Neuropathic Pain: Data from Ambulatory Care in a Real-Life Setting

Introduction: Drug treatment can be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated ADRs in patients admitted to the Ambulatory of Pain Medicine of the University Hospital Renato Dulbecco in Catanzaro. Methods: We conducted a prospective analysis between 1 February 2021 and 20 July 2023 on patients with neuropathic pain referred to the Ambulatory of Pain Medicine of “Renato Dulbecco” University Hospital in Catanzaro (Calabria, Italy). Patients aged &gt;18 years with clinical signs of neurologic pain and a score upon completing the Douleur Neuropathique en 4 Questions (DN4) questionnaire of ≥4 were included. The association between drugs and ADR or between drugs and drug–drug-interactions (DDIs) was evaluated using Naranjo’s probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2370 patients referred to the ambulatory of pain medicine. After the evaluation of inclusion and exclusion criteria, 33.5% of patients were enrolled. All patients presented at least one comorbidity and daily used a mean of five drugs (range 3–11). Using the Naranjo score, the development of ADRs was documented in 112 patients (score 6). Using parametric and non-parametric statistical analysis, we failed to report an association between ADR and dosage or ADR and patient characteristics. Conclusion: Our results show the development of ADRs in 18% of patients with neuropathic pain. This low percentage of drug interaction could be a limitation in real life because it is probably due to the site of the study and the appropriate prescription of drugs. Therefore, it shows that it is necessary to motivate healthcare to pay attention to the prescription of drugs in poly-treated patients to reduce the risk of ADRs.

Navigating uncertainties of introducing artificial intelligence (AI) in healthcare: The role of a Norwegian network of professionals

Artificial Intelligence (AI) technologies are expected to solve pressing challenges in healthcare services worldwide. However, the current state of introducing AI is characterised by several issues complicating and delaying their deployments. These issues concern topics such as ethics, regulations, data access, human trust, and limited evidence of AI technologies in real-world clinical settings. They further encompass uncertainties, for instance, whether AI technologies will ensure equal and safe patient treatment or whether the AI results will be accurate and transparent enough to establish user trust. Collective efforts by actors from different backgrounds and affiliations are required to navigate this complex landscape. This article explores the role of such collective efforts by investigating how an informally established network of professionals works to enable AI in the Norwegian public healthcare services. The study takes a qualitative longitudinal case study approach and is based on data from non-participant observations of digital meetings and interviews. The data are analysed by drawing on perspectives and concepts from Science and Technology Studies (STS) dealing with innovation and sociotechnical change, where collective efforts are conceptualised as actor mobilisation. The study finds that in the case of the ambiguous sociotechnical phenomenon of AI, some of the uncertainties related to the introduction of AI in healthcare may be reduced as more and more deployments occur, while others will prevail or emerge. Mobilising spokespersons representing actors not yet a part of the discussions, such as AI users or researchers studying AI technologies in use, can enable a ‘stronger’ hybrid knowledge production. This hybrid knowledge is essential to identify, mitigate and monitor existing and emerging uncertainties, thereby ensuring sustainable AI deployments.