Common Side Effects Research Articles

BlephEx-treatment for blepharitis: a prospective randomized placebo-controlled trial

Abstract Background Blepharitis is a chronic inflammatory condition of the eyelids that affects a large proportion of patients in eye care settings. First-line treatments provide only partial relief for many patients. The BlephEx™ device provides automated eyelid debridement and aims to remove pathogenic biofilms from the eyelid margin to treat blepharitis long-term. However, evidence supporting the efficacy of BlephEx™ is limited. Methods In this double-masked randomized controlled trial, 42 patients with symptomatic blepharitis refractory to treatment were assigned to the BlephEx™ treatment or sham treatment group. Outcome measures including Ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer test, and Efron grading scale scores were assessed at baseline and after 4 weeks. A crossover design in which the treatment groups were swapped after 4 weeks was used as a recruitment tool. After receiving treatment, two patients (one per group) were lost to follow-up. Results The sham group exhibited a significant decrease in the Efron Grading Scale score. No significant differences were observed in the other outcomes between the two groups. The BlephEx™ group showed slightly greater decreases in the OSDI and Efron grading scale scores and an increase in the TBUT than did the sham group, but these differences were not statistically significant. Mild discomfort was the most common side effect and occurred equally in both groups. Conclusions No significant difference in outcomes was observed between patients who underwent BlephEx™ therapy and those who received sham treatment. BlephEx™ treatment cannot be recommended for treating blepharitis. Trial registration Retrospectively registered on February 16, 2024 in the DRKS (German Clinical Trials Register under https://drks.de/search/de/trial/DRKS00033492) under the trial registration number DRKS00033492.

Late onset pancytopenia post chimeric antigen receptor T cell therapy triggered by a COVID-19 vaccination: a case report

Cytopenia is a common side effect after chimeric antigen receptor T cell (CAR-T) therapy but is unusual at late timepoints when it is most commonly due to bone marrow (BM) failure, myelodysplasia (MDS) or other secondary malignancies. In this case report, we describe a patient who developed severe aplastic anaemia 18 months after CD19 CAR-T therapy, and shortly after COVID-19 vaccination. This is the first description of severe aplastic anaemia triggered by COVID-19 vaccination as a cause of post-CAR-T cytopenia. The patient described was treated with a combination of eltrombopag and ciclosporin due to frailty and had a rapid and complete clinical response to this therapy, providing an effective option for the treatment of immune-related cytopenia post-CAR-T in an increasingly elderly and frail population.

Smads and AP-1 activation of TGF-β signaling upregulate transcription of Osteoprotegerin in Cementoblasts to inhibit osteoclastogenesis.

Orthodontically induced root resorption (OIRR) is a common side effect during orthodontic tooth treatment (OTM). The function of osteoprotegerin (OPG) is considered to protect cementum from excessive resorption to maintain root integrity. In this study, we observed that the expression of TGF-β1 and OPG was upregulated under the loading of orthodontic force in periodontal tissues. However, the specific molecular mechanisms of TGF-β1-induced OPG expression in cementoblasts are not fully elucidated. This study aims to investigate the effect of Smads and AP-1 stimulated by TGF-β signaling on the transcription of OPG in cementoblasts. Invitro, we demonstrated that TGF-β/Smad and AP-1 signaling involved in TGF-β1-induced extracellular secretion of OPG in conditioned media (CM) from cementoblasts, which further inhibited osteoclastogenesis. Reporter gene plasmids containing OPG promoter sequences of different lengths (0.5-3 kb) were constructed to investigate the potential binding sites of Smads and AP-1. We identified nine binding sites of Smads and AP-1 concentrated in the 0-0.5 and 2.3-3 kb regions of OPG promoter in cementoblasts. ChlP results showed that Smad2/3/4 and c-Jun were bound more to the OPG promoter under TGF-β1 stimulation. Invivo, localized administration of TGF-β1 in the OTM model increased OPG expression, which resulted in the inhibition of OIRR. In summary, TGF-β1-induced Smads and AP-1 can bind to the OPG promoter to promote the transcription, expression, and secretion of OPG in cementoblasts, which inhibits osteoclast differentiation and protects cementum from excessive resorption.

Comparative study of efficacy of intense pulsed light versus Intralesional triamcinolone in the treatment of hypertrophic scars and keloids

Keloids and hypertrophic scars are hyperproliferative response of dermal connective tissue to trauma. Their management remains a challenge for practitioners as there is still no universally accepted treatment, leading to recurrences which are frustrating for patients and clinicians alike. Hence, it becomes essential to determine a modality with highest efficacy, least recurrence and better patient compliance.To compare the therapeutic effectiveness of Intralesional triamcinolone acetonide versus Intense pulsed light for treatment of keloids and hypertrophic scars.A single centre, cross-sectional study was conducted on 60 patients. Patients were randomly allocated in two groups, group one received Intralesional steroids ( ILS)-triamcinolone acetonide and group two was treated by Intense pulsed light(IPL).Both groups were accessed for improvement every 15 days until 5 sessions were complete.Both study groups showed significant changes after treatment. Patients treated with ILS showed greater reduction in height. IPL group showed significant reduction in vascularity . Pigmentary outcomes were more favourable with IPL, whereas with ILS hypopigmentation was noted as a common side effect. Both groups showed significant reduction in pliability.Both regimens showed excellent responses with minimum recurrence rates, indicating their high efficacy in management of keloids and hypertrophic scars.

Do Patient-Reported Outcome Measures (PROMs) Used Within Radiotherapy Clinical Trials Reflect the Impact of Treatment?

This is the first article that investigates whether the patient-reported outcome measures (PROMs) used in clinical trials effectively capture the specific side-effects of radiotherapy and proton beam therapy (PBT) and provides context for researchers selecting PROMs for clinical trials. PROMs from radiotherapy trials were identified from previous research and assessed against the United Kingdom Royal College of Radiologists’ guidelines for tumour-site-specific side-effects. The analysis revealed that none of the 51 identified PROMs captured the full range of side-effects, with only 25 addressing fatigue and 6 addressing radiation-induced skin reactions. Three PROMs failed to identify any common side-effects, and eight identified only one. Overall, 88% of PROMs lacked specificity to radiotherapy and PBT, posing a risk of missing significant differences between treatment techniques. This study emphasises the need for more targeted PROMs in future trials. Until new or improved PROMs are available, great thought and caution should be taken when selecting PROMs for trial endpoints.

Loncastuximab tesirine in previously treated diffuse large B-cell lymphoma: A plain language summary of the LOTIS-2 study.

This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.Participants received loncastuximab tesirine, also referred to as Lonca, for up to 1year, or longer if the treatment was working, and their health was monitored. The primary purpose of the LOTIS-2 study was to find out if participants' lymphoma shrank partially or completely after receiving Lonca. A total of 145 participants who were treated with Lonca lived a median (meaning the middle value in a set of numbers) of 9.5months after starting Lonca treatment. The lymphoma shrank partially or completely in nearly half of participants and shrank completely in 1 in 4 participants. Among participants whose disease either shrank partially or completely in response to Lonca treatment, responses happened relatively quickly, with a median time to response (the time between starting treatment and when the participant's lymphoma either partially or completely shrank) of 41days. In these participants, the lymphoma did not grow or come back for a median of 13.4months. Researchers estimated that 83% of participants whose disease shrank completely remained disease free for at least 1year.Nearly all participants had a side effect from Lonca treatment. The most common side effects were abnormal liver tests (increased gamma-glutamyl transferase), decreased white blood cells (neutropenia), and decreased platelets (thrombocytopenia). One in 4 participants had their treatment stopped due to side effects. The most common side effects that resulted in participants needing to stop Lonca treatment were abnormal liver tests (increased gamma-glutamyl transferase), swelling in the arms or legs (peripheral edema), swelling in an individual spot (localized edema), and fluid around the lungs (pleural effusion). These results show that Lonca is a treatment option with controllable side effects for many patients with DLBCL whose disease did not respond or came back after 2 or more previous treatments. For participants whose lymphoma completely shrank while taking Lonca, those responses to treatment occurred quickly and lasted for over a year.

Plain language summary: tarlatamab for patients with previously treated small cell lung cancer.

This is a summary of a phase 2 clinical study called DeLLphi-301. The study looked at how effective and safe a medicine called tarlatamab was in participants with small cell lung cancer (SCLC). Participants previously received at least two other treatments for their SCLC. Tarlatamab is a new medicine that locates a protein called DLL3 on the cancer, which allows T cells to attack the cancer. T cells belong to the body's natural defense system known as the immune system. The DeLLphi-301 study separated participants into two groups to receive tarlatamab 10mg or 100mg to determine which dose best shrank SCLC with minimal side effects. All participants received a small first dose (1mg tarlatamab) to decrease the risk of an immune system reaction called cytokine release syndrome (CRS). Tarlatamab was given through the participant's vein once every 2weeks. This method of administration is known as intravenous (IV) infusion. In the group given 10mg tarlatamab, 40% of participants responded to treatment (cancer shrank). In the group given 100mg tarlatamab, 32% of participants responded to treatment (cancer shrank). After taking tarlatamab at either dose, 59% of participants lived for at least 6months without their cancer growing or getting worse.The most common side effect was CRS, which occurred in 51% of participants in the group given 10mg tarlatamab and 61% of participants in the group given 100mg tarlatamab. Other common side effects were decreased appetite, fever, constipation, and anemia. Some participants had a type of immune reaction called immune effector cell-associated neurotoxicity syndrome (ICANS). A small number of participants (3%) stopped taking tarlatamab because of side effects related to tarlatamab. The study found that tarlatamab given every 2weeks shrank SCLC in participants with SCLC who received previous treatments. Participants given the 10mg tarlatamab dose had fewer side effects than those given the 100mg tarlatamab dose.Clinical Trial Registration: NCT05740566 (DeLLphi-304) (ClinicalTrials.gov).

Abstract 4147627: A Pharmacovigilance Study of Bempedoic Acid: Balancing Risks and Benefits

Introduction: Bempedoic acid has been approved by FDA since Feb 2020 as an adjunct to maximally tolerated statin therapy for the reduction of LDL-C, specifically in individuals afflicted by atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid is also a viable alternative for patients intolerant to statins. Most recently, it has been approved to use for primary prevention of hyperlipidemia, alone or in combination with a statin. It is important to study its side effect profile as it is anticipated to be used more frequentlynin the future. Methods: We explored reported adverse events (AEs) of bempedoic acid using FDA Adverse Event Reporting System (FAERS). A total of 1202 adverse effects were reported until March 31, 2024. 69.97% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (32.53%) vs women (53.24%) and in three age groups of 18-64, 65-85, and >85 years. Results: A total of 586 (48.7%) events were serious adverse effects. Most common side effects were myalgia which included muscle pain, extremity pain and muscle spasm (25.04%), arthralgia including back pain and bone pain (18.47%), nausea (6.6%), headache(5.5%), gout (4.4%). Among the patients with adverse effects, 4.75% had cardiac side effects which included atrial fibrillation (12%), palpitation (29%), angina pectoris (18%), Myocardial Infarction (5%). Discussion: A thorough understanding of bempedoic acid's complex pharmacology empowers healthcare professionals to tailor treatment plans based on individual patient requirements. This enables informed decision-making in prescribing, optimizing dosage regimens, and mitigating potential adverse reactions. Most studies have been relatively short term in order to confirm the long term side effect profile. It would be beneficial to be cautious in using this medication for patients with above mentioned clinical conditions like myalgia, arthralgia, gout, rhabdomyolysis, atrial fibrillation, angina pectoris. Conclusion: Long term pharmacovigilance is needed to assess the safety profile of bempedoic acid over extended use. With the current increasing use of bempedoic acid, there is a need for more data on safety profiles. In future, further randomized trials are required to better assess the safety profile.

Antineoplastic therapy affects the in vitro phenotype and functionality of healthy human bone marrow-derived mesenchymal stromal cells.

While antineoplastic therapies aim to specifically target cancer cells, they may also exert adverse effects on healthy tissues, like healthy hematopoietic stem and progenitor cells (HSPC), leading to hematotoxicity as a common side effect. Mesenchymal stromal cells (MSC) are a major component of the bone marrow (BM) microenvironment, regulating normal hematopoiesis, while their susceptibility to anticancer therapies and contribution to therapy-related hematotoxicity remains largely unexplored. To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality. Doses below therapeutic effects of etoposide (0.1-0.25µM) inhibited cellular growth and induced cellular senescence in healthy MSC, accompanied by an increased mRNA expression of CDKN1A, decreased trilineage differentiation capacity, and insufficient hematopoietic support. Pharmacological doses of 5-azacitidine (2.5µM) shifted MSC differentiation capacity by inhibiting osteogenic capacity but enhancing the chondrogenic lineage, as demonstrated by histochemical staining and on mRNA level. At the highest clinically relevant dose, neither venetoclax (40nM) nor temozolomide (100µM) exerted any effects on MSC but clearly inhibited cellular growth of cancer cell lines and primary healthy HSPC, pointing to damage to hematopoietic cells as a major driver of hematotoxicity of these two compounds. Our findings show that besides HSPC, also MSC are sensitive to certain antineoplastic agents, resulting in molecular and functional alterations that may contribute to therapy-related myelosuppression. Understanding these interactions could be helpful for the development of strategies to preserve BM MSC functionality during different kinds of anticancer therapies.

German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health.

NCMP-27. NEUROLOGICAL COMPLICATIONS IN LUNG CANCER THERAPIES: UNVEILING THE ELEVATED RISKS IN CHEMOTHERAPY AND TARGETED TREATMENT APPROACHES

Abstract BACKGROUND Neurological complications due to lung cancer treatments are a common side effect, with prevalence ranging from 19% to over 80% depending on the drug administered. Peripheral neuropathy is the most common manifestation of chemotherapy associated neurotoxicity, but there are potential central nervous system impacts as well, such as seizures, dementia, and generalized cognitive impairment. Occurrence of similar effects is less commonly reported with targeted gene therapy for cancer, however the exact prevalence has not been determined. DESIGN/METHODS We searched the US Collaboration network through TriNetX for all cases of lung cancer, identified by ICD-10 code C34. Cohort A was defined as adults 18-70 years old that had lung cancer treated with cisplatin or etoposide. Cohort B was defined as adults 18-70 that had lung cancer treated with crizotinib, alectinib, or epidermal growth factor receptor tyrosine kinase inhibitors. Outcomes were evaluated from 1 day to 5 years after the indexed event. RESULTS We reported 15,268 patients with lung cancer that were prescribed chemotherapy agents matched with 6,490 patients with lung cancer that were prescribed tyrosine kinase inhibitors. Patients prescribed chemotherapy agents were at significantly higher risk for neurological complications post treatment when compared to those treated with tyrosine kinase inhibitors (p < 0.0001). CONCLUSIONS Patients diagnosed with lung cancer on chemotherapy 18-70 years old displayed higher associated risk of various neurological disorder diagnoses. Patients undergoing chemotherapy should be educated about this increased risk and talk with their providers about alternative treatments. Further research should be conducted on the range of potential neurological complications associated with chemotherapy regimens.

Transcranial direct current stimulation in the management of epilepsy: a meta-analysis and systematic review

BackgroundTranscranial direct current stimulation (tDCS) has recently become a novel and non-invasive treatment option for refractory epilepsy. Previous systematic reviews have suggested that tDCS may be effective in treating epilepsy, this study presents the first meta-analysis on its effectiveness.MethodsWe searched PubMed, Embase, Cochrane Library, and Web of Science for relevant randomized controlled trials (RCTs) from database inception to May 2024. The Cochrane risk of bias tool RoB2.0 was used to assess the risk of bias. Primary outcomes included changes in seizure frequency from baseline and the proportion of patients with a ≥50% reduction in seizure frequency.ResultsOf the 608 studies initially identified, 14 were finally included. The pooled results from the random-effects model indicated that tDCS significantly reduced seizure frequency (WMD 0.41, 95% CI 0.24, 0.59). Further subgroup analysis revealed that tDCS significantly reduced seizure frequency in temporal lobe epilepsy, and seizure frequency was more alleviated in studies that had treatment sessions of fewer than 5 times, and followed up within 2 months' post-treatment. Only four studies provided data on patients with a ≥50% reduction in seizure frequency, showing no significant difference (RR 2.96, 95% CI 0.85, 10.32). In the systematic review, three studies analyzed cognitive function changes after tDCS treatment, but none reported significant improvements. The most common side effect during tDCS treatment was transient tingling, and no patients required additional life-support measures due to side effects.ConclusionThe current meta-analysis on available trials indicates that tDCS can effectively reduce seizure frequency in the short term and is well-tolerated. However, its impact on cognitive improvement in epilepsy patients requires further investigation.Systematic review registrationhttps://inplasy.com/inplasy-2024-6-0033/, identifier INPLASY202460033.

NCOG-40. RARE ADVERSE EFFECT OF TEMOZOLOMIDE IN A 65-YEAR-OLD FEMALE WITH GLIOBLASTOMA MULTIFORME: A CASE REPORT

Abstract BACKGROUND Temozolomide, an antineoplastic agent is primarily used to treat certain brain tumors, including glioblastoma multiforme (GBM). Common side effects include nausea, vomiting, constipation, loss of appetite, alopecia (hair loss), headache, fatigue, convulsions and rash. A rare (less than 1%) adverse effect includes aplastic anemia refractory to treatment. Herein we present a case of Temozolomide induced severe bone marrow suppression in a 65-year-old woman with GBM refractory to any treatment CASE PRESENTATION A 65-year-old female presented with dizziness and left-hand numbness. Imaging revealed a right hemisphere mass and she underwent partial resection with pathology showing GBM, IDH wildtype, with CDKN2A/B deletion. She was started on radiation therapy with concurrent temozolomide. After nearly 5 weeks of temozolomide/RT, she developed severe thrombocytopenia/neutropenia with onset of neutropenic fever and severe CMV infection, leading to her demise within a week. DISCUSSION Life threatening refractory cytopenias is a very rare side effect of Temozolomide with a high rate of morbidity/mortality. In the case of our patient, she initially had weekly CBC’s which were stable and hence was switched to a monthly schedule. The patient’s ANC and platelets showed a precipitous drop within a month and ended up with aplastic anemia. The development of this rare complication underscores the importance of increased awareness about this often-fatal adverse event and possibly more frequent monitoring to recognize it early, especially in these patients with an already limited life expectancy. A more tailored approach to monitoring blood work may be needed depending on patient factors. CONCLUSIONS Aplastic anemia refractory to treatment is a rare and life threating adverse effect of temozolomide. The frequency of checking blood work for patients on Temodar has not been definitively established with protocols ranging from once weekly to monthly. Given the potential for this fatal adverse event, it is important to develop better tools to help identify patients in whom more frequent monitoring may be necessary.

Efficacy and Safety of GLP-1 Agonists on Metabolic Parameters in Non-diabetic Patients with Inflammatory Bowel Disease.

Obesity in patients with IBD is increasing, accompanied by an increase in metabolic comorbidities. Although GLP-1 agonists have shown promise in weight reduction, their efficacy and safety in patients with IBD are underexplored. This study evaluated the impact of GLP-1-based therapies on weight loss and metabolic parameters in non-diabetic patients with IBD. We conducted a single-center observational cohort study that included adult patients with IBD who were started on GLP-1-based therapy (semaglutide or tirzepatide) for weight loss from January 2021 to April 2024. The primary outcomes were changes in BMI and total body weight. Secondary outcomes included tolerability, safety, and changes in metabolic risk factors. The study included 36 patients with IBD, predominantly female (64%), with a median age of 45.5 years (IQR 41-51.5 years). The majority (67%) had Crohn's disease (CD) and on advanced therapy (86%). BMI significantly decreased from 34.0 (IQR 31.0-38.2) to 31.0 (IQR 29.0-36.1) with GLP-1-based therapy (p < 0.0001). Total body weight (TBW) significantly decreased by a median of 8.15 kg (IQR 15.9-2.2 kg; p < 0.0001). Although a decrease in total cholesterol and glycated hemoglobin was seen, this was not statistically significant (p = 0.0634 for total cholesterol, p = 0.0536 for glycated hemoglobin). No significant changes were observed in ALT or CRP levels. The most common side effects were nausea (31%) and constipation (25%). Semaglutide and tirzepatide can effectively reduce BMI in non-diabetic patients with IBD with manageable side effects. However, further studies are required to explore the long-term safety of GLP-1 agonists in the IBD population.

Avidity maturation of anti-spike IgG after vaccination in COVID-19 convalescent vs COVID-19 naïve patients.

Antibodies and avidity maturation contribute to long-lasting immunity, and previous COVID-19 seems to enhance the immune response after vaccination. The aim of this study was to compare the immune response after vaccination between COVID-19 convalescents and naïve patients. Blood samples from COVID-19 convalescents and naïve patients, taken 1, 3 and 6 months after the second dose of vaccine (mRNA-vaccine BNT162b2), were analysed for anti-spike IgG and avidity. Questionnaires concerning side effects were used. Thirty-one patients in the COVID-19 cohort and 30 patients in the naïve cohort were included. High levels of anti-spike IgG and avidity index were seen. Anti-spike IgG were significantly higher in the COVID-19 cohort and declining (median 1250, 566, 282 RU/ml vs 565, 187, 65 RU/ml). Avidity did not change over time (median at 6 months 78% vs 65%). The most common side effects were pain at the injection site, malaise and headache. In conclusion, high levels of anti-spike IgG after vaccination were seen and most patients developed high-avidity antibodies, although antibody levels and avidity were higher in the COVID-19 cohort. Over time, the levels of anti-spike IgG declined, yet avidity remained high. Side effects did not differ between groups and were of short duration.

Improving Diagnosis and Management of Opioid-Induced Constipation (OIC) in Clinical Practice: An Italian Expert Opinion

Opioid-induced constipation (OIC) is a very common and troublesome gastrointestinal side effect following the use of opioids. Despite existing international guidelines, OIC is largely underdiagnosed and undertreated. ECHO OIC is a European project designed to improve the diagnosis and management of OIC at the primary care level. The next phase of the ECHO OIC project is to review and adapt the proposed European pathway at national level, considering the local patient journey and clinical practice. A multidisciplinary group of 12 Italian experts reviewed and discussed the European path and formulated a seven-step guide for the practical management of OIC that is also easily applicable in primary care: 1. When prescribing long-term opioids, the physician should inform the patient of the possibility of the onset of OIC; 2. At opioid prescription, doctors should also prescribe a treatment for constipation, preferably macrogol or stimulant laxatives; 3. The patient should be evaluated for OIC within the second week of initiating opioid treatment, by clinical history and Rome IV criteria; 4. In the presence of constipation despite laxatives, prescription of a PAMORA (Peripherally Acting Mu Opioid Receptor Antagonist) should be considered; 5. When prescribing a PAMORA, prescribing information should be carefully reviewed, and patients should be accurately instructed for appropriate use; 6. Efficacy and tolerability of the PAMORA should be monitored regularly by Bowel Function Index, considering a cut-off of 30 for the possible step-up of OIC treatment; 7. After 4 weeks of treatment, if the efficacy of PAMORA is deemed inadequate, discontinuation of the PAMORA, addition of an anti-constipation drugs, change of opioid type, or referral to a specialist should be considered. Spreading knowledge about the OIC problem as much as possible to the health community is crucial to obtain not only an early treatment of the condition but also to promote its prevention.

Chiisanoside from the Leaves of Acanthopanax sessiliflorus Can Resist Cisplatin-Induced Ototoxicity by Maintaining Cytoskeletal Homeostasis and Inhibiting Ferroptosis.

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity of Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated the active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology and activity screening determined that chiisanoside (CSS) plays a crucial role in combating CIO. Transcriptomics combined with network pharmacology analysis and experiments revealed that CSS activates the Dock1/PIP5K1A pathway to suppress the actin-severing protein gelsolin, protecting hair cells from cisplatin-induced cytoskeleton damage. CSS also activates the SLC7A11/GPX4 pathway via TGFBR2, reducing lipid peroxidation and intracellular iron accumulation to suppress cisplatin-induced ferroptosis. This study discovers that the major component CSS in A. sessiliflorus leaves reverses CIO by regulating actin homeostasis via Dock1 and inhibiting ferroptosis through TGFBR2, providing a theoretical basis for expanding CIO treatment targets and related drug development.

The effect of melatonin and probiotics on radiation-induced enteritis in experimental rat models

Radiotherapy plays an important role in the treatment of tumors, and enteritis is a common side effect of this therapy. The aim of present study was to evaluate the protective effect of melatonin and probiotics on radiation-induced intestinal tissue damage in rats. Histopathological, biochemical and microbiological samples were examined. Thirty-two Wistar Albino rats were randomly distributed into four groups: the control group, only radiotherapy (RT) group, radiotherapy plus melatonin (RT + MEL) groups and radiotherapy plus probiotics (RT + PROB) groups. The abdominal-pelvic region of the experimental rat was irradiated with in a single dose of 16 Gy. The melatonin was administered at a single dose of 50 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The probiotic was administered orally every day to the rats for 5 days starting before radiotherapy. There was a statistically significant changes in histopathological (villus atrophy, mitotic activity, apoptotic index, goblet cell swelling, degenerative changes, atypia) and biochemical (oxidant and antioxidant status, IL-1β, IL-6 and TNF- α levels) parameters in the small intestine in the radiotherapy group G2 compared to the G1 control group (p < 0.05). However, a significant decrease was observed with the administration of probiotics and melatonin (p < 0.05). In addition, although positive bacterial growth was detected in the mesenteric lymph node of all rats in the radiotherapy group, there was no statistically significant difference between all groups (p > 0.05). Melatonin and probiotics were found to have a potent radioprotective effect against radiotherapy-induced acute small intestinal tissue damage. However, their superiority over each other was not observed.

Xiao-Ban-Xia Decoction Alleviates Chemotherapy-Induced Nausea and Vomiting by Inhibiting Ferroptosis via Activation of The Nrf2/SLC7A11/GPX4 Pathway.

Chemotherapy-induced nausea and vomiting (CINV) represents the common gastrointestinal side effect for cancer patients. Xiao-Ban-Xia decoction (XBXD), a classical anti-emetic traditional Chinese medicine formula, is frequently used for the clinical treatment of CINV. This study used a cisplatin-induced rat pica model to explore whether the anti-emetic mechanism of XBXD in treating CINV is related to ferroptosis. The inflammatory damage of the gastrointestinal tract is evaluated by HE staining and ELISA. The degree of ferroptosis are validated by the iron deposition, the levels of ROS, MDA, and GSH, and the ultrastructure of mitochondria in the gastric antrum and ileum. The potential ferroptosis-related targets of XBXD against CINV are screened by network pharmacology and further assessed by Western blot. XBXD significantly decreased the kaolin consumption in rats, and improved the inflammatory pathological damage, with decreased levels of HMGB1, IL-1β, and TNF-α. Furthermore, XBXD significantly suppressed ferroptosis, as indicated by the improvement of iron deposition, mitochondrial abnormalities, and oxidative stress. The network pharmacology and Western blot results indicated that XBXD activated the Nrf2/SLC7A11/GPX4 signaling pathway. This study proved that XBXD activates the Nrf2/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis, which represents a critical anti-emetic mechanism of XBXD in combatting CINV.

Lecanemab's Path Forward: Navigating the Future of Alzheimer's Treatment in Europe Amidst the EMA's Rejection.

Lecanemab (Leqembi©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.