Treatment-related Adverse Effects Research Articles

OS04.4.A LONG- AND SHORT-TERM SURVIVORS AMONG ADULT PATIENTS WITH DIFFUSE WHO GRADE 2-3 GLIOMA: CLINICAL FEATURES, MOLECULAR RECLASSIFICATION AND DNA METHYLATION PATTERNS

Abstract BACKGROUND Diffuse gliomas show considerable heterogeneity in terms of survival. The WHO classifications of 2016 and 2021 improved prognostic stratification due to the definition of biologically and clinically homogeneous tumor entities. However, further prognostic models considering clinical and molecular factors are needed to balance survival benefit with adverse treatment-related long-term effects in therapeutic decisions. MATERIALS AND METHODS Patients with diffuse gliomas of WHO grades 2 and 3 diagnosed in 2000 - 2019 have been included. Long term survivors (LTS) were defined as patients with an overall survival (OS) of >10 years after radiological diagnosis, whereas short-term survivors (STS) had an OS of <1 year. Histological diagnosis was performed by a board-certified neuropathologist. DNA methylation analysis of formalin-fixed, paraffin-embedded tumor tissue was conducted using the Illumina EPIC 850k platform. The Heidelberg Methylation Classifier was applied to obtain methylation-based diagnoses. RESULTS Of 697 patients with WHO grade 2 and 3 glioma, 182 (26.1%) were LTS, and 42 (6.0%) were STS. LTS were younger than STS (median age: 36 vs. 59.5; p<0.001) and had a higher Karnofsky Performance Score at diagnosis (median: 90% vs. 80%; p<0.001). LTS more frequently presented with epileptic seizures (p<0.001), while more STS had motoric (p<0.001), sensory (p=0.021), and visual deficits (p=0.027) as well as aphasia (p<0.001) and behavioral changes (p=0.009). Histological diagnoses (including pre-2016) showed astrocytic histology in 117 (70.9% LTS, 29.1% STS), oligodendroglial in 61 (93.4% LTS, 6.6% STS), oligo-astroglial in 43 (97.7% LTS, 2.3% STS) and not otherwise specified in 3 (all STS; p<0.001). Molecular reclassification of pre-2016 diagnoses (n = 143) yielded divergent entities in 46 (32.2%) cases. Overall, integrated molecular diagnoses included astrocytoma (isocitrate dehydrogenase [IDH]-mutant] in 65 patients (95.4% LTS and 4.6% STS), oligodendroglioma (IDH-mutant, 1p/19q-codeleted) in 64 patients (98.4% LTS and 1.6% STS), IDH-wildtype gliomas in 24 patients (100% STS), anaplastic pilocytic astrocytoma in 2 STS, diffuse midline glioma (H3K27-altered) in 1 STS, and dysembryoplastic neuroepithelial tumor in 1 LTS, while not otherwise specified diagnoses were found in 4 patients (75% LTS, 25% STS; p<0.001). Unsupervised clustering based on DNA methylation profiling revealed two major clusters consisting of IDH-wildtype STS (cluster A) and IDH-mutant patients (cluster B; 94.6% LTS, 5.4% STS). In cluster B, one subcluster (n = 8) contained 3/4 IDH-mt STS. Further analyses of these cases including validation with publicly available DNA methylation data are ongoing. CONCLUSION LTS and STS show distinct clinical and molecular features. Further profiling of cases with divergent survival could provide more refined prognostic stratification.

Association of the clinical profile and overall survival of pediatric patients with acute lymphoblastic leukemia.

The clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death. Retrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses. 109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%). The rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained.

Efficacy and safety of tixagevimab-cilgavimab versus SARS-CoV-2 breakthrough infection in the hematological conditions.

Managing SARS-CoV-2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab-cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real-life data in a heterogeneous cohort are few. The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab-cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch-and-wait strategy, followed in our center, during a median follow-up of 249 (45-325) days. An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment-related adverse effects. Age ≥70years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p<0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p=.002). Patients treated with tixagevimab-cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15days, p<.001). The concurrent treatment with anti-CD20 monoclonal antibodies and B-non-Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.

The Effect of Cardiac Rehabilitation on Quality of Life and 6-Minute Walk Test in Breast Cancer Survivors

Background Breast cancer (BC) is the most diagnosed cancer in women, contributing to 24.6% of malignancies in females and responsible for 15% of all cancer-related deaths among women worldwide.[1] Over the last 20 years, BC survival rates have significantly improved.[1] However, this survivorship is often marked by fatigue, poor quality of life (QoL), reduced functional capacity along with treatment-related adverse effects.[2] The implementation of a model similar to cardiac rehabilitation (CR) program as a preventive strategy may provide a potential solution to improve functional capacity, quality of life and reduce cardiovascular disease (CVD) risk in cancer survivors.[3] Objective to investigate the effect of 12-week completed cardiac rehabilitation program on quality of life (using FACT-B questionnaire) and 6-minute walk test in breast cancer survivors. Patients and Methods In this 2-arm parallel prospective, randomized, controlled clinical trial, sixty breast cancer survivors 3 months to 1 year after completion of chemotherapy were recruited at Ain Shams University hospitals and divided into two groups Study group (n = 30); participated in 12-week CR program and Control group (n = 30) did not participate in CR program but still received the usual cancer care. Cardiac rehabilitation program consisted of education, diet control, drug adherence, 12 weeks exercise sessions, Behavior and psychosocial management, Sexual activity education Smoking cessation. Functional capacity was assessed before and after study period by sixminute walk test (6MWT) and exercise test (using modified Bruce protocol). All patients were personally interviewed for assessment of quality of life before and after study period using (FACT-B) questionnaire. In addition patients underwent echocardiography assessment before and after study period. Result Sixty female breast cancer survivors were enrolled. Nine patients dropped from CR program, some due to social commitments (n = 2), others due to long distance issues (n = 2), and the remaining were not interested in continuing the program (n = 5). There were no significant differences between the two groups regarding age, baseline BMI, hemoglobin (Hb) levels, medical history, chemotherapy protocol, and radiation. When comparing two groups, the study group showed significant increase in age-predicted 6MWD (p = 0.02), ET (p &amp;lt; 0.001), METs (p &amp;lt; 0.001), QoL score (p &amp;lt; 0.001), along with significant decrease in SBP (p &amp;lt; 0.001), HR (p &amp;lt; 0.001), RPP (p &amp;lt; 0.001). Conclusion The results of this study demonstrated that completed cardiac rehabilitation program improves functional capacity and quality of life in breast cancer survivors. Recommendation We recommend that multicomponent supervised cardiac rehabilitation program should be incorporated within the usual care of breast cancer survivor

Extended one-generation reproductive toxicity study evaluating gardenia blue in Sprague Dawley rats

Gardenia blue powder was administered at 0.5%, 2.5%, or 5.0% in feed to male and female Sprague Dawley rats in an Extended One-Generation Reproductive Toxicity Study (OECD Test Guideline 443). The dosed diet began 14 days before mating and was continued at the same concentration level for the entire study for all parental animals (P0) and offspring (F1). At weaning, offspring were allocated into one of 5 cohorts for different endpoints. P0 and F1 animals had blue urine, blue or black feces, and blue discolorations in gastrointestinal organs, mesenteric lymph nodes, and kidneys. This treatment-related finding was not considered adverse as there were no histopathologic correlates. There was a dose-related increase in sperm concentration in P0 and F1 males. There were dose-related increases in heart weights of F1 postnatal day (PND) 21 males, male and female thyroid weights, and female TSH levels of PND 91 F1 offspring, with no histopathological correlate. There were no consistent treatment-related adverse effects on any other parameters evaluated for general toxicity, reproductive toxicity, developmental neurotoxicity, or developmental immunotoxicity. The highest dietary concentration (5.0%) of gardenia blue powder was the no observed adverse effect level (NOAEL) for male and female rats at all life stages evaluated.

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer

Patients undergoing radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) experience a range of debilitating adverse effects (AEs). Patient-reported outcome (PRO) measures to quantify these AEs are a necessary and important component of health care; however, currently available PRO options often measure only disease-related symptoms or AEs of non-RT treatments. To develop a brief PRO measure of the most common AEs associated with RT for HNSCC. This was a qualitative study that followed the US Food and Drug Administration guidelines to develop a brief measure of patient-reported RT-related AEs (the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy [FACT-HN-RAD] measure). The study included (1) a literature review of clinical trials; (2) secondary analysis of retrospective concept elicitation interviews (CEIs); (3) electronic surveys of practicing radiation oncologists; (4) mapping of existing items to inform the development of the draft version of the measure; and (5) validation of content and face validity via patient cognitive interviews. Analysis was performed of CEI data and interviews with practicing radiation oncologists. Data analysis was conducted from July 1, 2022, to April 21, 2023. Surveys and qualitative interviews. The most common patient-reported RT-related AEs among patients with HNSCC. Of 19 CEI participants, 14 (mean [range] age, 67 [49-86] years; 12 [86%] men and 2 [14%] women) described RT-related AEs and were included in the secondary analysis. Eleven (79%) patients reported difficulty swallowing; 8 (57%), oral pain; 7 (50%), dry mouth; 7 (50%), weight loss; 6 (43%), skin burning; 5 (36%), loss of taste; 5 (36%), voice changes (36%); and 5 (36%), fatigue. Nine radiation oncologists (mean [range] time in practice, 8 [1-42] years; 5 [56%] men and 4 [44%] women) reported the most common AEs: 9 (100%) reported dysgeusia; 7 (78%), xerostomia; 7 (78%), mucositis or oral pain; 8 (89%), dysphagia or odynophagia; 6 (67%), dermatitis; and 3 (33%), fatigue. Together these data informed the development of an 8-item AE-focused measure of pain, dysphagia, xerostomia, dysgeusia, voice changes, dermatitis, fatigue, and weight loss. Cognitive interviews with 10 patients (mean [range] age, 61 [29-84] years; 8 [80%] men and 2 [20%] women) demonstrated strong face validity; all (100%) reported that the measure reflected their experience with RT and stated that the length of the questionnaire was "just right." The 8-item FACT-HN-RAD measure captures the most common patient- and physician-reported AEs related to RT for HNSCC. This measure offers a means to serially monitor patient-reported treatment-related AEs and recovery over time in both clinical and research settings. Future work will evaluate the psychometric validity of the measure.

Management of hypertension in patients with cancer: challenges and considerations.

The survival rates of many cancers have significantly improved due to recent advancements in cancer screening and therapeutics. Although better cancer outcomes are encouraging, additional health challenges have surfaced, the utmost of which is the burden imposed by various cardiovascular and renal toxicities of anticancer therapies. To improve the overall outcome of patients with cancer, it is essential to understand and manage these treatment-related adverse effects. The cardiovascular side effects of antineoplastic therapies are well-known and include left ventricular dysfunction, heart failure, myocardial ischaemia, QT prolongation, arrhythmia and hypertension. Among these, hypertension is the most common complication, prevalent in about 40% of all cancer patients, yet frequently overlooked and undertreated. This review explores the intricate connection between cancer and hypertension and provides distinct approaches to diagnosing, monitoring and managing hypertension in patients with cancer. We also outline the challenges and considerations that are relevant to the care of patients receiving anticancer drugs with prohypertensive potential.

A comprehensive review of dermoscopy in melasma.

Melasma is a common acquired hyperpigmentation disorder that predominantly affects females with skin of colour. It is difficult to treat and impacts on people's quality of life, owing to its predilection for the face. In addition to helping make the correct diagnosis, dermoscopy can assist in the exclusion of differential diagnoses, to inform treatment decision-making and to recognize treatment-related adverse effects.

Current therapies for classic myeloproliferative neoplasms: A focus on pathophysiology and supportive care.

This article concisely evaluates current therapies that have received regulatory approval for the treatment of classic myeloproliferative neoplasms (MPNs). Pertinent pathophysiology and supportive care are discussed. Emerging therapies are also briefly described. MPNs are a heterogeneous group of diseases characterized by acquired abnormalities of hematopoietic stem cells (HSCs), resulting in the generation of transformed myeloid progenitor cells that overproduce mature and immature cells within the myeloid lineage. Mutations in JAK2 and other driver oncogenes are central to the genetic variability of these diseases. Cytoreductive therapies such as hydroxyurea, anagrelide, interferon, and therapeutic phlebotomy aim to lower the risk of thrombotic events without exposing patients to an increased risk of leukemic transformation. However, no comparisons can be made between these therapies, as reduction of thrombotic risk has not been used as an endpoint. On the other hand, Janus kinase (JAK) inhibitors such as ruxolitinib, fedratinib, pacritinib, and momelotinib (an investigational agent at the time of writing) directly target the constitutively activated JAK-signal transducer and activator of transcription (JAK-STAT) pathway of HSCs in the bone marrow. Mutations of genes in the JAK-STAT signaling pathway provide a unifying understanding of MPNs, spur therapeutic innovations, and represent opportunities for pharmacists to optimize mitigation strategies for both disease-related and treatment-related adverse effects. Treatment options for MPNs span a wide range of disease mechanisms. The growth of targeted therapies holds promise for expanding the treatment arsenal for these rare, yet complex diseases and creates opportunities to optimize supportive care for affected patients.

TIPS-13 A PHASE II STUDY OF NEOADJUVANT CAMRELIZUMAB AND APATINIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS

Abstract BACKGROUND A single arm clinical trial (NCT04588987) about combination therapy of programmed cell death protein 1 blockades camrelizumab with antiangiogenic agent apatinib has been initiated to investigate their effectiveness for patients with recurrent high-grade Gliomas (HGG). METHODS Patients with recurrent HGG will receive single-dose intravenous injection of camrelizumab (200 mg) and daily oral administration of apatinib (250 mg/day for 7 days) 14 days before surgery for recurrent tumor. Sequential therapy will begin 2 weeks after surgery with the biweekly injection of camrelizumab and 4 weeks after surgery with the daily administration of apatinib. RESULTS Up to date (March 9, 2023), 18 patients are enrolled (13 for recurrent glioblastomas and 5 for anaplastic astrocytoma), with a medial follow-up time is 19 months. The median cycles of postoperative combination therapies were 4.5 cycles (95%CI: 3.87-5.12 ), with median progression-free survival of 4.0 months (95%CI: 2.78-5.28 ). One patient (1/18, 5.5%) discontinue the combination treatment because the patient often underwent the extended periods of hospitalization because of unacceptable liver dysfunction, and the other patient (1/18, 5.5%) withdraw the from the trail after receiving the surgery. All enrolled patients appeared one or more treatment-related adverse effects. The most common adverse effects were constipation(58%), hypertension (52%), leukocytopenia (52%), and nausea (47%). CONCLUSION the short-term results indicated that the combination therapy might be beneficial for patients with recurrent HGG and improve the patients’ overall survivals. We will present our detailed progress and results on the conference.

An individualized approach to the management of Cushing disease.

Cushing disease caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary corticotroph adenoma leads to hypercortisolaemia with high mortality due to metabolic, cardiovascular, immunological, neurocognitive, haematological and infectious conditions. The disorder is challenging to diagnose because of its common and heterogenous presenting features and the biochemical pitfalls of testing levels of hormones in the hypothalamic-pituitary-adrenal axis. Several late-night salivary cortisol and 24-h urinary free cortisol tests are usually required as well as serum levels of cortisol after a dexamethasone suppression test. MRI might only identify an adenoma in 60-75% of patients and many adenomas are small. Therefore, inferior petrosal sinus sampling remains the gold standard for confirmation of ACTH secretion from a pituitary source. Initial treatment is usually transsphenoidal adenoma resection, but preoperative medical therapy is increasingly being used in some countries and regions. Other management approaches are required if Cushing disease persists or recurs following surgery, including medications to modulate ACTH orblock cortisol secretion or actions, pituitary radiation, and/or bilateral adrenalectomy. All patients require lifelong surveillance for persistent comorbidities, clinical and biochemical recurrence, and treatment-related adverse effects (including development of treatment-associated hypopituitarism). In this Review, we discuss challenges in the management of Cushing disease in adults and provide information to guide clinicians when planning an integrated and individualized approach for each patient.

Assessment of Changes in Tumor Volume Following Chemotherapy For Nodular Sclerosıng Hodgkin Lymphoma (NSHL)

Objective: Hodgkin lymphoma is a critical malignancy which may be seen during childhood and adolescence. Since it may be observed in younger patients, treatment strategies should be considered thoroughly to achieve optimal results in terms of local control and treatment related adverse effects. Systemic therapy plays a critical role in treatment of Hodgkin lymphoma. In this study, we evaluated changes in tumor volume following chemotherapy for nodular sclerosing Hodgkin lymphoma (NSHL).

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study.

Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.

Systemic Neoadjuvant and Adjuvant Therapies in the Management of Hepatocellular Carcinoma—A Narrative Review

The burden of hepatocellular carcinoma (HCC) continues to pose a significant global health problem. Several systemic therapies have recently been shown to improve survival for patients with unresectable disease. However, evidence to support the use of neoadjuvant or adjuvant systemic therapies in patients with resectable disease is limited, despite the high risk of recurrence. Neoadjuvant and adjuvant systemic therapies are being investigated for their potential to reduce recurrence after resection and improve overall survival. Our review identified various early-phase clinical trials showing impressive preliminary signals of pathologic complete response in resectable disease, and others suggesting that neoadjuvant therapies—particularly when combined with adjuvant strategies—may convert unresectable disease to resectable disease and cause significant tumor necrosis, potentially decreasing recurrence rates. The role of adjuvant therapies alone may also play a part in the management of these patients, particularly in reducing recurrence rates. Heterogeneity in trial design, therapies used, patient selection, and a scarcity of randomized phase III trials necessitate the cautious implementation of these treatment strategies. Future research is required to identify predictive biomarkers, optimize the timing and type of therapeutic combinations, and minimize treatment-related adverse effects, thereby personalizing and enhancing treatment strategies for patients with resectable and borderline resectable HCC.

Efficacy and safety of perampanel for epilepsy: a systematic review and meta-analysis of real-world studies.

The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy. A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals. A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain. Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis.

Treatment Outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir in Direct-Acting Antiviral-Experienced Hepatitis C Virus Patients: A Systematic Review and Meta-Analysis.

About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions (p < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.

An updated review on acne

Acne is a common chronic inflammatory skin disorder that affects individuals of all ages, particularly during adolescence. It is characterized by the formation of comedones, papules, pustules, and, in severe cases, nodules and cysts. While acne is primarily associated with the pilosebaceous unit, its pathogenesis involves multiple factors, including hormonal imbalances, increased sebum production, abnormal follicular keratinization, and the colonization of Propionibacterium acnes.This review aims to provide an updated understanding of acne, focusing on its pathogenesis, clinical presentation, and current management strategies. The pathogenesis of acne involves complex interactions between hormones, sebum production, follicular keratinization, and inflammation. Various predisposing factors, such as genetic susceptibility, diet, and environmental influences, also contribute to the development and exacerbation of acne. Management of acne encompasses a multifaceted approach, including topical and systemic therapies. Topical agents such as retinoids, benzoyl peroxide, and antibiotics target different aspects of acne pathogenesis, helping to normalize follicular keratinization, reduce inflammation, and inhibit bacterial growth. Systemic therapies, including oral antibiotics, hormonal agents, and isotretinoin, are often used for moderate to severe cases or those resistant to topical treatments. Additionally, this review highlights emerging therapies and advancements in acne management. Recent research has explored novel treatment options such as laser and light-based therapies, photodynamic therapy, and the use of probiotics and botanical extracts. These interventions show promise in targeting specific aspects of acne pathogenesis and reducing treatment-related adverse effects. Furthermore, the psychological impact of acne and its influence on quality of life are discussed. Acne can significantly affect an individual's self-esteem, body image, and social interactions, underscoring the importance of a holistic approach to patient care. In conclusion, this updated review provides a comprehensive overview of acne, including its pathogenesis, current treatment strategies, and emerging therapies. Understanding the multifactorial nature of acne and staying abreast of advancements in its management will help healthcare professionals provide effective and individualized care to patients suffering from this common dermatological condition. Acne is a common chronic inflammatory skin disorder that affects individuals of all ages, particularly during adolescence. It is characterized by the formation of comedones, papules, pustules, and, in severe cases, nodules and cysts. While acne is primarily associated with the pilosebaceous unit, its pathogenesis involves multiple factors, including hormonal imbalances, increased sebum production, abnormal follicular keratinization, and the colonization of Propionibacterium acnes.This review aims to provide an updated understanding of acne, focusing on its pathogenesis, clinical presentation, and current management strategies. The pathogenesis of acne involves complex interactions between hormones, sebum production, follicular keratinization, and inflammation. Various predisposing factors, such as genetic susceptibility, diet, and environmental influences, also contribute to the development and exacerbation of acne. Management of acne encompasses a multifaceted approach, including topical and systemic therapies. Topical agents such as retinoids, benzoyl peroxide, and antibiotics target different aspects of acne pathogenesis, helping to normalize follicular keratinization, reduce inflammation, and inhibit bacterial growth. Systemic therapies, including oral antibiotics, hormonal agents, and isotretinoin, are often used for moderate to severe cases or those resistant to topical treatments. Additionally, this review highlights emerging therapies and advancements in acne management. Recent research has explored novel treatment options such as laser and light-based therapies, photodynamic therapy, and the use of probiotics and botanical extracts. These interventions show promise in targeting specific aspects of acne pathogenesis and reducing treatment-related adverse effects. Furthermore, the psychological impact of acne and its influence on quality of life are discussed. Acne can significantly affect an individual's self-esteem, body image, and social interactions, underscoring the importance of a holistic approach to patient care. In conclusion, this updated review provides a comprehensive overview of acne, including its pathogenesis, current treatment strategies, and emerging therapies. Understanding the multifactorial nature of acne and staying abreast of advancements in its management will help healthcare professionals provide effective and individualized care to patients suffering from this common dermatological condition.

Oral toxicological study of titanium dioxide nanoparticles with a crystallite diameter of 6 nm in rats

BackgroundThough titanium dioxide (TiO2) is generally considered to have a low impact in the human body, the safety of TiO2 containing nanosized particles (NPs) has attracted attention. We found that the toxicity of silver NPs markedly varied depending on their particle size, as silver NPs with a diameter of 10 nm exhibited fatal toxicity in female BALB/c mice, unlike those with diameters of 60 and 100 nm. Therefore, the toxicological effects of the smallest available TiO2 NPs with a crystallite size of 6 nm were examined in male and female F344/DuCrlCrlj rats by repeated oral administration of 10, 100, and 1000 mg/kg bw/day (5/sex/group) for 28 days and of 100, 300, and 1000 mg/kg bw/day (10/sex/group) for 90 days.ResultsIn both 28- and 90-day studies, no mortality was observed in any group, and no treatment-related adverse effects were observed in body weight, urinalysis, hematology, serum biochemistry, or organ weight. Histopathological examination revealed TiO2 particles as depositions of yellowish-brown material. The particles observed in the gastrointestinal lumen were also found in the nasal cavity, epithelium, and stromal tissue in the 28-day study. In addition, they were observed in Peyer's patches in the ileum, cervical lymph nodes, mediastinal lymph nodes, bronchus-associated lymphoid tissue, and trachea in the 90-day study. Notably, no adverse biological responses, such as inflammation or tissue injury, were observed around the deposits. Titanium concentration analysis in the liver, kidneys, and spleen revealed that TiO2 NPs were barely absorbed and accumulated in these tissues. Immunohistochemical analysis of colonic crypts showed no extension of the proliferative cell zone or preneoplastic cytoplasmic/nuclear translocation of β-catenin either in the male or female 1000 mg/kg bw/day group. Regarding genotoxicity, no significant increase in micronucleated or γ-H2AX positive hepatocytes was observed. Additionally, the induction of γ-H2AX was not observed at the deposition sites of yellowish-brown materials.ConclusionsNo effects were observed after repeated oral administration of TiO2 with a crystallite size of 6 nm at up to 1000 mg/kg bw/day regarding general toxicity, accumulation of titanium in the liver, kidneys, and spleen, abnormality of colonic crypts, and induction of DNA strand breaks and chromosomal aberrations.

Self-Medication during and after Cancer: A French Nation-Wide Cross-Sectional Study.

(1) Background: Little data are available in Western countries regarding self-medication practices in the context of cancer. The aim of this study was to describe the prevalence of self-medication practices during (cancer patients) and after cancer (cancer survivors). (2) Methods: This multicenter, cross-sectional, and online study was designed to assess self-medication prevalence. Other objectives were explored, notably the medication types, the perceived risks, and the relation with symptoms and quality of life. (3) Results: Among the 518 patients analyzed, 56.4% declared they practiced self-medication. Dietary supplements and pain medications were used by more than half of the patients. Self-medication was practiced in order to manage the adverse effects of anticancer therapies (63.8%), for which pain was the leading indication (39%), and to improve the efficacy of anticancer therapies (43.8%, cancer patients). Patients believed that self-medication could not lead to drug interactions with anticancer therapies (84.9%, cancer patients), or to adverse effects (84.6%, cancer patients and survivors). Self-medication practices were associated with altered social functioning, pain, insomnia, and financial difficulties. (4) Conclusions: Self-medication was performed by more than half of the responders (ongoing or past cancer) and could be a marker of the undermanagement of cancer and treatment-related adverse effects.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: ENKTL is a highly aggressive NHL with a higher incidence in Asia. In 2020 ASH meeting, we reported Sintilimab(anti-PD-1 antibody) plus Chidamide(an oral subtype-selective HDACi) yielded effective antitumor activity, durable response with mild toxicity in patients with relapsed or refractory ENKTL. We then initiated this exploratory study to investigate the efficacy and safety of Sintilimab plus Chidamide(SC) for patients with newly diagnosed ENKTL. Methods: This trial enrolled eligible patients with newly diagnosed ENKTL(ND-ENKTL); ECOG score ≤2; at least one measurable or evaluable lesion. All patients received 2–3 cycles of Sintilimab (200 mg) plus Chidamide (30 mg, twice a week). For patients with early stage, 2 cycles of SC were given, subsequent 2–4 cycles of P-GemOx regimen administered and followed by involved field radiotherapy (IFRT). For advanced stage, patients were treated with 3 cycles of SC and 3–6 cycles of P-GemOx. The primary study endpoints are the ORR of SC and end of treatment assessed according to the lymphoma response to immunomodulatory therapy criteria (LYRIC). Key secondary endpoints included DOR, PFS, OS and safety. Results: From July 2019 to Nov 2021, 42 eligible patients were enrolled from Sun Yat-sen University Cancer Center. The median age was 47.5 (range, 20–81) years, 16(38%) patients with stage III-IV, 15(31%) patients with PINK-E score≥3. All patients were evaluated for efficacy. For stage I-II, 21(81%) patients achieved response, including 18(69%) CR patients with SC. After 2 cycles of SC, 17(94%) of 18 CR patients chosen to continue SC treatment. Only 1 (6%) PR patients accepted 2 cycles of P-GemOx and got CR after chemotherapy. Twenty-five (96%) patients obtained CR after IFRT. For stage III–IV, 9(56%) patients achieved response with 13%(2/16) CR, 3(33.3%) patients experienced rapid progression disease (RPD) in SC portion. Ten (63%) patients entered P-GemOx portion including 1 RPD patient. Thirteen (81%) patient got ORR with 69% (11/16) CR after whole treatment. The median follow-up time was 24.1(5.4–44.3) months. The 2-year PFS and OS rate were 76% and 78%, the prognosis of early stage is better than advanced stage (Fig. 1). Two RPD patients died within one month. Circulating EBV-DNA clearance after SC significantly correlated with superior outcome. Forty(95.2%) patients reported treatment-related adverse effects (TRAEs). The most common TRAEs (≥10%) were neutropenia (43%), thrombocytopenia (38%), elevated transaminase (29%), and anemia (24%). The most common grade 3 TRAEs (≥10%) was elevated transaminase (10%), no grade 4 TRAEs. Keywords: aggressive T-cell non-Hodgkin lymphoma, extranodal non-Hodgkin lymphoma, immunotherapy No conflicts of interests pertinent to the abstract.