Efficacy and Safety of Therapeutic Plasma Exchange in Children with Neuroimmunological Disorders: A Limited Unicentral Study.

Objectives: Therapeutic plasma exchange (TPE) is a plasmapheresis procedure whose Safety data for pediatric neuro-immunological disorders (PNID) is confined. The present research documents TPE's safety and feasibility data in these conditions. Materials & Methods: The current study involved six distinct groups of patients with PNID undergoing TPE: neuromyelitis optic spectrum disorder (NMOSD), autoimmune encephalitis (AIE), acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), Guillain-Barre syndrome (GBS), and optic neuritis (ON). This study documented complications related to each TPE process. In addition, TPE's efficacy was studied in these patients. Results: The present study recorded adverse effects in 18 patients with PNID that received 121 TPE cycles: five cycles (4.13%) in MS, three (2.48%) in AIE subgroup, one (0.82%) in ADEM, and two (1.65%) in GBS. No severe complications were observed among the patients. Conclusion: Patients with PNID tolerated therapeutic plasma exchange, which was a safe process.

Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

Impact of depressive symptoms on adverse effects in people with epilepsy on antiseizure medication therapy.

OBJECTIVE: We studied the impact of depressive symptoms on adverse effects (AEs) in people with epilepsy (PWE) on antiseizure medication (ASM) therapy. An effect of depression on the AE burden has already been reported. We studied the correlation of various depressive symptoms with specific AEs to assess which AEs are especially prone to being confounded by particular depressive symptoms. METHODS: PWE filled in a variety of questionnaires including the "Neurological Disorder Depression Inventory for Epilepsy" (NDDI-E), "Emotional Thermometers 4" (ET4) and "Liverpool Adverse Events Profile" (LAEP). Depression was defined by a NDDI-E score > 13. Depressive symptoms consisted of NDDI-E and ET4 items. Discriminant analysis identified those AEs (=LAEP items) that were most highly influenced by depression. Logistic regression analysis yielded correlations of different depressive symptoms with specific AEs. RESULTS: We included 432 PWE. The strongest discriminators for depression were the LAEP items "Depression", "Nervousness/agitation," and "Tiredness". Out of all depressive symptoms "Everything I do is a struggle" most strongly correlated with total LAEP score (odds ratio [OR] = 3.1) and correlated with all but one LAEP item. Other depressive symptoms correlated to varying degrees with total LAEP and item scores. The number of ASMs, lack of seizure remission, and female gender correlated with high LAEP scores. SIGNIFICANCE: To the best of our knowledge, we are the first to show that various depressive symptoms correlate with specific LAEP items. This information can be helpful for quick evaluation of whether the reporting of different LAEP items may be confounded by particular depressive symptoms. This is relevant because changes in therapy may differ depending on if AEs are confounded by depressive symptoms. Simply reporting a particular depressive symptom may give a clue to whether specific AEs are confounded by depression. Our findings confirm the importance of screening for depression in all PWE. PLAIN LANGUAGE SUMMARY: In this study we measured depressive disorder and side effects caused by medication used to treat epilepsy with self-reported questionnaires in a cohort of people with epilepsy. We found depressive disorder to influence the perception of side effects that are caused by drugs used to treat epilepsy. This knowledge can help to identify if the reporting of side effects is influenced by depression. Treating depression may help to reduce side effects and may thus increase the tolerability of anti-epileptic medication. People who tolerate their medication are more likely to take it and are thus less likely to develop epileptic seizure.

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region.

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

Drug-induced osteoporosis and mechanisms of bone tissue regeneration through trace elements.

Osteoporosis is associated with an imbalance in bone formation, with certain drugs used in disease treatment being implicated in its development. Supplementation with trace elements may contribute to bone regeneration, offering an alternative approach by enhancing bone mineral density (BMD) and thereby thwarting the onset of osteoporosis. This review aims to assess the mechanisms through which trace elements such as copper (Cu), iron (Fe), selenium (Se), manganese (Mn), and zinc (Zn) are linked to increased bone mass, thus mitigating the effects of pharmaceuticals. Our findings underscore that the use of drugs such as aromatase inhibitors (AIs), proton pump inhibitors (PPIs), antiretrovirals, glucocorticoids, opioids, or anticonvulsants can result in decreased BMD, a primary contributor to osteoporosis. Research indicates that essential elements like Cu, Fe, Se, Mn, and Zn, through various mechanisms, can bolster BMD and forestall the onset of the disease, owing to their protective effects. Consequently, our study recommends a minimum daily intake of these essential minerals for patients undergoing treatment with the aforementioned drugs, as the diverse mechanisms governing the effects of trace elements Cu, Fe, Mn, Se, and Zn facilitate bone remodeling.

Clinical characterization of hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors: a review of published cases.

OBJECTIVE: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments. METHODS: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases. RESULTS AND DISCUSSION: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26-86). The mean time to the onset of symptoms was 10.3 weeks (7 days-14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described. CONCLUSION: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

Switch to Lisdexamfetamine in the Treatment of Attention-Deficit Disorder at a Psychiatric Outpatient Clinic for School-Aged Children: A Danish Cohort Study.

Objectives: This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. Results: One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). Implications: The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.

The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma-two sides of the same coin?

Tissue-resident memory T cells (TRM cells) have become an interesting subject of study for antitumor immunity in melanoma and other solid tumors. In the initial phases of antitumor immunity, they maintain an immune equilibrium and protect against challenges with tumor cells and the formation of primary melanomas. In metastatic settings, they are a prime target cell population for immune checkpoint inhibition (ICI) because they highly express inhibitory checkpoint molecules such as PD-1, CTLA-4, or LAG-3. Once melanoma patients are treated with ICI, TRM cells residing in the tumor are reactivated and expand. Tumor killing is achieved by secreting effector molecules such as IFN-γ. However, off-target effects are also observed. Immune-related adverse events, such as those affecting barrier organs like the skin, can be mediated by ICI-induced TRM cells. Therefore, a detailed understanding of this memory T-cell type is obligatory to better guide and improve immunotherapy regimens.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Factors associated with early hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

PURPOSE: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years. METHODS: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment. RESULTS: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51-66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2-15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5-21.5). CONCLUSION: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment.

The clinical role of remimazolam: Protocol for a scoping review.

BACKGROUND: Remimazolam, a novel benzodiazepine, shows promise as an alternative to traditional sedatives and hypnotic agents in procedural sedation and general anaesthesia. While preliminary research indicates potential advantages over conventional agents, such as faster onset, predictable duration, and improved safety profile, the extent and quality of existing evidence remain unclear. This scoping review aims to investigate the current clinical role of remimazolam and provide a broad and comprehensive overview. METHODS: The proposed review will adhere to the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews. A comprehensive search will be conducted across major peer-reviewed databases and grey literature will be sought. All studies involving individuals undergoing procedural sedation or general anaesthesia with remimazolam will be eligible. Data extraction will encompass trial and participant characteristics, intervention details, reported outcomes, comparative efficacy versus midazolam and propofol, patient and operator experience and economic costs. RESULTS: We will provide a descriptive summary supplemented by statistics, figures and tables where applicable. CONCLUSION: The outlined scoping review aims to assess the clinical use of remimazolam in procedural sedation and as the hypnotic component of general anaesthesia. The review will map the current body of evidence of remimazolam and identify knowledge gaps, contributing to understanding its clinical implications and guiding future research efforts in procedural sedation and general anaesthesia.

Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics.

Introduction: The standard approach to treatment in psychiatry is known as "treatment as usual" (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics. Methods: In this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug-gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC). Results: Pharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent. Conclusion: With the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug and gene-gene-drug interactions.

Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Bowel-Associated Dermatosis-Arthritis Syndrome: A Case Report.

Introduction: Gastric bypass surgery is an effective surgical intervention for morbid obesity. However, it is not without risk. Gastric bypass surgery may produce malabsorptive or surgical complications, which can result in nutritional deficiencies as well as syndromes related to bacterial overgrowth in the blind loops of the bowel. Case Presentation: Severe nutritional deficiencies may occur due to patient noncompliance with the prescribed regimen, or arise secondary to malabsorptive or mechanical surgical complications. We describe a case of a 37-year-old female who underwent gastric bypass surgery and experienced a recalcitrant eczematous eruption with sporadic subcutaneous, purulent nodules which completely resolved after the reversal of her bariatric procedure. Conclusion: Since 2001, the number of morbidly obese patients who have undergone bariatric surgery has been increasing. As a result, clinicians can expect to more frequently encounter complications that can result from these procedures.

High dose total marrow irradiation (TMI) does not increase long-term toxicity of myeloablative fludarabine/busulfan (FluBu4) conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT).

OBJECTIVES: Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long-term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. METHODS: We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow-up post-transplant. The rate of long-term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. RESULTS: The baseline characteristics did not differ between the two groups. The control group had a longer median follow-up (71.2 mo) than the TMI group (38.5 mo) (p = .004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p = .12 and p = .7, respectively). There was no grade 4 adverse event. CONCLUSION: Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long-term adverse events after allogeneic HSCT.

Detection and analysis of signals of adverse events of memantine based on the US food and drug administration adverse event reporting system.

BACKGROUND: Despite its widespread use, the adverse effects (AEs) of memantine have not been well documented, and there is a need to find new ways to analyze the AEs of memantine. RESEARCH DESIGN AND METHODS: AEs in which the primary suspected drug was memantine were retrieved from the FAERS database. The proportional report ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) were used to detect potential positive signals between memantine and AEs. SAS, MySQL, EXCEL, and R language software were used for data processing and statistical analysis. RESULTS: This study gathered a total of 5808 reports of AEs associated with memantine. Of these reports, a greater proportion of female patients (51.17%) than male patients (36.33%) had AEs. The AEs reported by FAERS were mainly in psychiatric category (n = 2157, IC025 = 2.69), various neurologic disorders (n = 1608, IC025 = 2.04), systemic disorders and various site reactions (n = 842, IC025 = 1.29). Unexpected ocular adverse events have been reported, ophthalmic vein thrombosis (n = 4, IC025 = 3.47) and scleral discolouration (n = 7, IC025 = 3.1), which may worsen glaucoma. CONCLUSIONS: This study observed conceivable new AEs signals and may supply important assist for scientific monitoring and threat identification of memantine.

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

BACKGROUND: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. METHODS: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). RESULTS: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. CONCLUSIONS: The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Effects of CYP2D6 gene polymorphism on plasma concentration and therapeutic effect of olanzapine.

This study aimed to evaluate the relationship between gene polymorphisms of metabolic enzymes, particularly the CYP2D6 gene, and the plasma concentration of olanzapine, as well as treatment response in patients with chronic schizophrenia. We recruited olanzapine-treated patients and examined their plasma olanzapine levels. Additionally, a common mutation site within each of the nine exons of the full-length CYP2D6 sequence was assayed. The Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Overall Clinical Impression were used to assess schizophrenic symptoms, whereas the Barnes Akathisia Scale and Extrapyramidal Symptom Rating Scale were used to evaluate adverse effects. The results showed no significant differences in plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects among different CYP2D6 genotypes. However, an association between olanzapine concentrations and improvement in clinical symptoms and adverse reactions was observed. In conclusion, the CYP2D6 genotype did not significantly impact plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects.