Specific Side Effects Research Articles

The nutritional impact of CD19-targeted CAR-T therapy versus BEAM chemotherapy for adult patients with lymphoma.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapy demonstrating durable remissions in patients with refractory or relapsing non-Hodgkin's B-cell lymphoma. Maintaining a patient's nutritional status has been demonstrated to improve outcomes in cancer treatment. However, no studies have investigated how CAR-T therapy affects nutritional status, nor compared its impact with other cancer treatments for this patient group. The primary aim of the present study was to investigate the effect of CAR-T therapy on the prevalence of nutrition impact symptoms (NIS) and nutritional status within 30 days post-treatment of patients with lymphoma compared to a conditioning regimen for autologous haematopoetic stem cell transplant (carmustine/BCNU, Etoposide, cytarabine/Ara-C, Melphalan [BEAM] auto-haematopoetic stem cell transplant [HSCT]). Clinical notes of patients with lymphoma who underwent either CAR-T therapy or BEAM auto-HSCT between 2018 and 2021 were reviewed. Data extracted included body weight measurements and NIS, including decreased appetite, nausea, vomiting, diarrhoea, constipation, mucositis, cytokine release syndrome (CRS) and neurotoxicity at baseline and 30 ± 7 days post-treatment. In total, 129 adults with lymphoma (n = 88 CAR-T vs. n = 41 BEAM) were included. Nutritional status was assessed in both groups at baseline prior to treatment. Mean absolute weight change was significantly different between groups (3.05 kg in CAR-T, -5.9 kg in BEAM, p ≤ 0.001). This was also significant when weight loss was categorised into percentage weight loss (p = 0.01). CAR-T patients experienced a significantly lower prevalence of decreased appetite (52.3% vs. 97.6%) nausea (25% vs. 78%,) vomiting (10.2% vs. 53.7%), diarrhoea (43.2% vs. 96.7%) and mucositis (5.7% vs. 75.6%) combined across all levels of severity compared to BEAM chemotherapy (all p ≤ 0.01). CRS and neurotoxicity, which are specific side effects of CAR-T therapy, were moderately positively associated with weight loss. Weight loss, percentage weight loss and NIS were significantly reduced in CAR-T compared to BEAM treatment. However, patients who experienced neurotoxicity during treatment did have significant weight loss.

Genome-wide association studies of response and side effects to the BNT162b2 vaccine in Italian healthcare workers: Increased antibody levels and side effects in carriers of the HLA-A*03:01 allele.

The remarkable variability of response to vaccines against SARS-CoV-2 is apparent. The present study aims to estimate the extent to which the host genetic background contributes to this variability in terms of immune response and side effects following the administration of the BNT162b2 vaccine. We carried out a genome wide association study (GWAS) by genotyping 873 Italian healthcare workers who underwent anti-SARS-CoV-2 vaccination with the BNT162b2 vaccine and for whom information about anti-SARS-CoV-2 spike antibodies titers and vaccine side effects were available. The GWAS revealed a significant association between the HLA locus and the anti-SARS-CoV-2 Spike antibodies level at 2 months following the first dose of vaccine (SNP: rs1737060; p = 9.80 × 10-11 ). In particular, we observed a positive association between the antibody levels and the presence of the HLA-A*03:01 allele. The same allele was found associated with a 2-2.4-fold increased risk of experiencing specific side effects such as fever, chills and myalgia and a 1.5-1.8-fold increased risk of joint pain, nausea, fatigue, headache and asthenia, independently of age and sex. This study confirms that the heterogeneity in the immune response to the BNT162b2 vaccine and in its side effects are at least partially influenced by genetic variants. This information, integrated with individual biological and lifestyle-related correlates, could be of use in the definition of algorithms aimed at the identification of subjects in which the administration of additional vaccine doses would be particularly beneficial to maintain immunity against the virus.

Preferences of German and Swiss melanoma patients for toxicities versus melanoma recurrence during adjuvant treatment (GERMELATOX-A-trial).

Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk for toxicity. This study addressed for the first time in a multicenter setting the attitudes and preferences of melanoma patients for adjuvant treatment with (c)ICI and TT. In this study ("GERMELATOX-A"), 136 low-risk melanoma patients from 11 skin cancer centers were asked to rate side effect scenarios typical for each (c)ICI and TT with mild-to-moderate or severe toxicity and melanoma recurrence leading to cancer death. We asked patients about the reduction in melanoma relapse and the survival increase at 5years they would require to tolerate defined side-effects. By VAS, patients on average valued melanoma relapse worse than all scenarios of side-effects during treatment with (c)ICI or TT. In case of severe side effects, patients required a 15% higher rate of DFS at 5years for (c)ICI (80%) compared to TT (65%). For survival, patients required an increase of 5-10% for melanoma survival during (c)ICI (85%/80%) compared to TT (75%). Our study demonstrated a pronounced variation of patient preferences for toxicity and outcomes and a clear preference for TT. As adjuvant melanoma treatment with (c)ICI and TT will be increasingly implemented in earlier stages, precise knowledge of the patient perspective can be helpful for decision making.

Retrospective evaluation of erlotinib and gefitinib used in the military health system from the perspective of drug-drug interactions.

e15108 Background: Erlotinib and gefitinib are epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) approved primarily for non-small cell lung cancer treatment, with pharmaceutical drug-drug interactions (DDIs) that are vague and poorly understood. Previous studies show that concomitant use of EGFR-TKIs with fluoxetine or losartan results in inhibition of both fluoxetine and losartan. Since DDIs can cause significant clinical ramifications, drugs that may interact with erlotinib or gefitinib must be identified. Methods: Data review was performed by Military Health System (MHS) data experts with data provided by the Joint Pathology Center (JPC) from the Department of Defense (DoD) Cancer Registry, the comprehensive ambulatory/professional encounter record (CAPER) and the pharmacy data transaction service (PDTS). Patients treated for cancer were identified, and the CAPER database was used to identify comorbidities. The PDTS database identified prescription drugs filled during erlotinib/gefitinib use, for all cancers. Patients were sorted into subgroups, (1) completed treatment (erlotinib or gefitinib was the last drug that patients completed, without recorded side effects), or (2) discontinued treatment (patients were treated with erlotinib or gefitinib but had recorded side effects and/or switched treatment). PDTS data and retrospective analysis of encounter notes, were used to sort medications into those that were taken before or after (“.”, “,”, “/”, or space between drugs) and those that were taken at the same time (“+”, “-/+”, or “and” between drugs). Results: 348 patients had diagnosis data, with 234 patients having completed treatment and 114 patients having discontinued treatment. Patients who discontinued treatment were diagnosed with more health issues than patients who completed treatment. A total of 258 patients had pharmacy data filled for erlotinib (240 patients) or gefitinib (18 patients). Of these, 177 patients completed treatment and 81 patients discontinued treatment. Patients in the completed treatment group filled 1 to 75 drugs, median range 11-20 drugs. Patients in the discontinued treatment group filled 3 to 103 drugs, median range 31-40 drugs. Patients who discontinued treatment filled more drugs than patients who completed treatment. The 20 most filled drugs, associated with side effects during erlotinib or gefitinib usage and the specific associated side effects were identified. Conclusions: This review cannot conclude that any drug resulted in erlotinib or gefitinib discontinuation. However, associations between top filled drugs and side effects have been made. Proof of concept in vitro laboratory testing should be done with these identified drugs, to confirm mechanistic interactions that may lead to clinical effects.

First integrative oncology clinic in the Veteran Affairs (VA) Pittsburgh healthcare system.

e24041 Background: Integrative oncology (IO) is PROACTIVE and combines complementary with conventional care. The VA's comprehensive collection of integrative services is already in place. However, providers are often unaware of these, therefore veteran cancer patients don’t benefit from them. Prostate cancer is the most common cancer within the VA (31.8%), Aside from radiation/chemotherapy side effects (dry mouth, stomatitis, fatigue, neuropathy, gastrointestinal ) prostate cancer patients also have hormonal issues (hot flashes, low bone density, sexual dysfunction). Conventional treatments focus on symptoms (REACTIVE). Complementary and IO approaches are evidence-based toward specific treatment-related side effects. By educating and offering integrative approaches, we empower veterans to take charge of their health and well-being. Shifting our focus from treating only the disease to treating the entire patient, will improve health outcomes. Methods: Recruit 40 prostate cancer patients with fatigue, radiation-induced diarrhea, neuropathy, nausea, vomiting, anorexia, constipation, sexual dysfunction, and emotional issues(depression, anxiety, poor sleep, lack of energy). Identify/train providers to focus on concerning areas. Develop VA Personal Health Plans (PHP) to identify patients mission, aspiration, and purpose (MAP). Offer acupuncture, yoga, Reiki, TaiChi, meditation, biofeedback for headaches - Video Support group. Assessment tools. In late 2022, we reached our goal of 40 prostate cancer patients and opened clinic enrollment to patients of all cancer types. Results: The pilot IO clinic began in 2020, with 40 patients. In 2022, we expanded services to patients with other cancer types. Integrative options improved surgical outcomes, minimize chemotherapy /radiation side effects, boost morale, and optimize clinical outcomes. There is a high-interest level among oncology staff and patients. Resources are abundant but need organization and refinement to effectively present IO to our patients. Conclusions: There is huge potential for integrative oncology to improve the clinical, laboratory, and quality-of-life outcomes of cancer patients. We were able to construct a program within the Veteran Affairs, using existing integrative resources with high patient engagement. Currently, we plan to expand services to other VA sites nationwide.

The effects of bromelain on osteoarthritis symptoms: A systematic review

Background and aims: Osteoarthritis (OA) is the most common skeletal and excruciating disease worldwide. This study aimed to investigate bromelain’s effect and underlying mechanism on OA symptoms. Methods: This systematic review was designed according to the PRISMA guidelines. An extensive search was undertaken in various databases, including PubMed, Web of Science, EMBASE, and Scopus. Finally, 14 articles were retrieved considering the inclusion and exclusion criteria of the study. The desired data were extracted and entered into an Excel file, and the outcomes of the studies underwent investigation. Results: Bromelain downregulates inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), IL-8, IL-1β, and interferon γ expression in synovial fibroblasts. In addition, bromelain inserts analgesic effects by decreasing vascular permeability to bradykinin and inhabitation its generation. Bromelain counteracts by increasing the levels of TNF-α, IL-1β, inducible nitric oxide synthase (iONS) levels, and lipid peroxidation while reducing those of superoxide dismutase, catalase, and prolidase. Another main antinociceptive effect property of bromelain is associated with its anti-inflammatory effect by relieving neuroinflammation and synovial membrane inflammation. Conclusion: Bromelain indicated good therapeutic effects on reducing OA symptoms due to its anti-inflammatory and antioxidant effects. Although no specific bromelain-related side effects were not reported in the included studies, it is recommended that more laboratory studies should be conducted with different doses and appropriate methodology.

GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting

The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.

Comparison of the Onset and End of Specific and Major Side Effects in Iranian Teenage Participants Vaccinated With COVID-19 Vaccine: Sinopharm and Soberana.

Clinical trials were conducted on children on side effects after vaccination. We tried to assess the frequency and onset of the main symptoms in children who were vaccinated. We aimed to evaluate early and delayed adverse effects after coronavirus disease 2019 (COVID-19) vaccine among Iranian pediatrics and adolescents in a national survey. This cross-sectional study included people <18 years who received the Soberana (PastoCoVac) and Sinopharm vaccines since 2021. The basic information was gender, age, type of vaccine, and reaction after vaccination besides the main events that occurred for them. The required data were collected via a predetermined checklist by trained interviewers through phone calls by their parents or legal guardians. The independent t test and Fisher exact test were used. P values less than 0.05 were considered significant. A total of 11,042 participants (age range, 10-18 years) consisting of 5374 boys (47.8%) and 5768 girls (52.2%) were studied and 88.1% of the children (n = 9727) were vaccinated by Sinopharm and 11.9% (n = 1315) by Soberana. The data of kidney-related side effects had delayed improvement of side effects after the Sinopharm compared with the Soberana vaccines (P = 0.012). Cardiovascular and hematological side effects showed early-onset (P = 0.006) and delayed improvement of side effects (P = 0.002) after the Soberana vaccine compared with the Sinopharm vaccine. Neurological side effects showed delayed improvement of side effects after the Soberana vaccine compared with the Sinopharm vaccine (P = 0.027). Joint-related side effects showed early-onset (P = 0.004) and delayed improvement of side effects (P = 0.023) after the Soberana vaccine compared with the Sinopharm vaccine. Respiratory side effects showed delayed improvement of side effects after the Soberana vaccine compared with the Sinopharm vaccine (P = 0.013), and dermatological side effects showed early-onset (P = 0.050) and delayed improvement of side effects (P = 0.035) after the Soberana vaccine compared with the Sinopharm vaccine. There was not any statistically significant difference regarding gastrointestinal side effects between the 2 vaccines (P > 0.05). The cardiovascular and hematological, joint-related (non-neurologic musculoskeletal) and dermatological side effects after the Soberana vaccine appear earlier and end later compared with the Sinopharm vaccine. Improvement of renal side effects in the Sinopharm vaccine group and improvement of neurological and respiratory side effects in the Soberana vaccine group occurred with delay compared with other vaccines.

Abstract P1-01-04: Comparing the Effects of TC and Anthracycline-based Chemotherapy in Women with Breast Cancer HER2 Negative Treated in the Adjuvant Setting – An individual Patient Meta-Analysis

Abstract Background: Among women, breast cancer is the most common diagnosis of non-skin cancer and the fifth cause of oncological-related death worldwide. Adjuvant chemotherapy has been shown to extend overall survival (OS) and disease-free survival (DFS). Anthracyclines are cytotoxic regimens largely used in breast cancer, mainly in patients with risk factors or high burden of disease. The docetaxel and cyclophosphamide (TC) regimen is a Taxane-based treatment, and is an alternative option when anthracyclines are not indicated. However, anthracyclines have a myriad of adverse effects including alopecia, cardiac-related side effects and myelotoxicity. The question that remains is in which breast cancer population anthracycline chemotherapy should be omitted. Methods: A literature search was performed in Embase, Medline, and the Cochrane Libraries up to February 28 2022. We conducted an individual patient-level meta-analysis of 11,902 participants of 7 randomised controlled trials. The target population was adult women, with a histologically confirmed HER2 negative, stage I-III breast cancer who were treated with TC versus anthracycline-based chemotherapy in adjuvant setting under randomised-controlled trials. To analyse OS and DFS, we utilized the generic inverse variance method for time-to-event outcomes using hazard ratio (HR). A sensitivity analysis of risk of bias (ROB) was undertaken to examine the effects of high/moderate risk studies on each study endpoint. The assessment of certainty of evidence was conducted based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results: With a median follow up of 60 months, the pooled analysis from 7 studies with available data on OS, and from 6 studies on DFS. From a total of 11,778 there was a total of 288 and 281 events of death in the TC and in the anthracycline-based chemotherapy groups, respectively. The analysis of OS revealed HR 1.01, 95% CI (0.86 – 1.19), p = 0.88; high certainty of evidence. From a total of 11,902 participants, there were 639 and 595 recurrence events in the TC and in the anthracycline-based chemotherapy groups, respectively. The analysis of DFS revealed HR 1.07, 95% CI 0.95-1.22, p=0.26; moderate certainty of evidence. No relevant absolute risk of death or recurrence events were found between the two treatments. In the quality of evidence assessment, the heterogeneity across all the studies is likely not more than what is due to chance (i2&amp;lt; 14%). The risk of bias was not a serious concern, and the publication bias was undetected for the endpoints OS and DFS. Conclusion: In this study population, TC chemotherapy likely results little to no difference in OS or DFS compared to anthracyclines-based chemotherapies. Despite the large number of participants and minimum heterogeneity across all the studies, there was no evidence of significant benefit or harm between the treatments. Overall, there is a high to moderate quality of evidence that adjuvant TC chemotherapy does not increase OS or DFS when compared to anthracycline-based chemotherapy in patients with breast cancer HER2-negative. Albeit the choice between the two chemotherapies would need to be balanced considering the specific side-effects that each treatment is likely to cause. Citation Format: Danilo Giffoni M. M. Mata, Mary Smowton. Comparing the Effects of TC and Anthracycline-based Chemotherapy in Women with Breast Cancer HER2 Negative Treated in the Adjuvant Setting – An individual Patient Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-01-04.

Inpatient psychotherapy of depressive disorders: options and challenges

The psychotherapy of depressive disorders has become established as acentral component of inpatient treatment in psychiatric and psychosomatic hospitals and furthermore constitutes an important component of the residency training in Germany; however, the number of studies examining the effectiveness and efficacy is limited. This narrative review summarizes the current state of research on inpatient psychotherapy for depressive disorders. The results of meta-analyses as well as practice-based observational studies from routine treatment in Germany, disorder-specific special programs, and side effects of inpatient psychotherapy are summarized. The number of studies on the efficacy of inpatient psychotherapy of depressive disorders is overall low. The main finding of the largest recent meta-analysis indicates that psychotherapy in clinics and other facilities has asignificant effect on depressive symptoms, with small to moderate effect sizes in randomized controlled studies. The effects are mostly maintained even after 9-15months follow-up. An observational study from routine treatment with avery large sample size reported large pre-post and pre-follow-up effect sizes. It additionally revealed factors that appear to be difficult to change during inpatient psychotherapy, negatively affect treatment success and could be specifically addressed in future trials. Special programs, such as inpatient Interpersonal Psychotherapy (IPT) and the inpatient Cognitive Behavioral Analysis System of Psychotherapy (CBASP) indicate acceptance and efficacy/effectiveness in an initial randomized controlled (IPT) study and in observational (CBASP) studies. Side effects of inpatient psychotherapy were reported by 60-94% of patients with depressive disorders, whereby a perceived dependence on the therapist or the therapeutic setting was identified as afrequent side effect. Overall, the results of the narrative review reveal that inpatient psychotherapy appears to be meaningful and effective for many patients with depressive disorders. Specific side effects, cost-effectiveness, and the question of differential indications (what works for whom?) should be further investigated.

НОРМАТИВНО-ПРАВОВАЯ ОСНОВА ОБЕСПЕЧЕНИЯ МЕНТАЛЬНОЙ БЕЗОПАСНОСТИ РОССИЙСКОЙ ФЕДЕРАЦИИ

Mental threats to individual and group identity lead to a large-scale crisis and jeopardize the future of Russia and the Russian world as a civilizational (not ethnic) project. Globalization processes and their specific side effects pose a significant danger to the mentality. The most serious destructive effect on the mentality is exerted by external manipulation practices, in particular, by the instruments of “soft power”. The problem of external influence is becoming one of the most important problems of ensuring national security in the modern world. An orientation is being formed not only on passive protection, but also on preventive actions in this area. The legal and regulatory framework for the mental security of the Russian Federation is fully consistent with the emerging threats and the necessary efforts to counter them. At the same time, there are opportunities for its improvement in the direction of the final separation of mental security into an independent integral segment of national security, which will make it possible to more effectively solve the problems and tasks that arise in this area.

A Canadian vasculitis patient-driven survey to highlight which prednisone-related side effects matter the most.

Although management of vasculitis has evolved over the last decades, glucocorticoids (GC) have remained the cornerstone of treatment. The side effects (SE) of GC are well known by the clinicians; their importance for patients with vasculitis has not been investigated as extensively as in other rheumatological conditions. An online questionnaire surveyed between April 29th. to July 31st, 2022 with Vasculitis Foundation Canada about the patient experience and SE of prednisone. The survey included 5 questions about prednisone dose and duration, 21 about specific SE (with a rating of 1-10, and one question each on worst prednisone, and worst vasculitis, SE), and four other questions about knowledge and perception of possible alternatives to prednisone (namely, avacopan). A total of 97 patients (53 GPA/MPA, 44 other vasculitides) completed the survey. Their mean duration of GC use was 62.7±83.7 months, and 49.5% of patients were still on GC (daily dose, 8.4±6.2mg). All the patients reported ≥1 GC-related SE, and 67.0% reported ≥11/19 pre-specified SE of interest. Among ranked SEs, acne was the lowest score, whereas moon face/torso hump had the highest score, just above weight gain, insomnia and decreased quality of life. Around half of the GPA/MPA patients and one-third of the others had heard about avacopan, and 68% of patients (similarly in both groups) stated they would prefer being the first to take a very new medication, such as avacopan, instead of prednisone. Ranking given to some GC-related SEs may differ between patients and physicians. GC toxicity/SE indexes should reflect this difference.

The effect of adding curcumin to sodium valproate in treatment of patients with bipolar disorder in the acute phase of mania: A randomized double-blind clinical trial.

Inflammatory processes play a role in the etiopathogenesis of bipolar disorder type 1. Full therapeutic responses are seldom seen and the ongoing inflammatory processes in the brain could lead to neuronal loss. Curcumin, a relatively safe herbal compound, has been shown to have anti-inflammatory effects. The present randomized double-blind clinical trial study aimed to investigate the effect of adding curcumin to the treatment regimen of BID. This randomized double-blind clinical trial was conducted on 78 patients diagnosed with BID according to the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria. The sample were divided into two groups. Patients in both groups received sodium valproate starting at a dose of 600 milligrams per day and administered up to 20 milligrams per kilogram per day or the highest dosage of the patient's tolerance. Patients in the intervention group also received curcumin as nanomicelle in soft gelatin capsules 40 milligrams per day. The control group received placebo tablets with the same characteristics as the curcumin tablets. They were assessed by a psychiatrist using the Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), and a medication side effect questionnaire at the beginning of the study, as well as in the first, second, and fourth weeks of the study. Among the 78 patients chosen to participate in the project, 54 people completed the trial. No specific side effect was observed in the two groups. Both groups showed an increase in their MMSE scores compared to the beginning of the study (value of p < 0.001). Although this increase was not statistically different between the two groups (value of p = 0.68). The YMRS score of both groups decreased significantly by the end of the study (value of p < 0.001); however, this decrease was not significantly different between the two groups (value of p = 0.64). In addition, the two groups experienced a significant increase in their CGI scores throughout the study (value of p < 0.001), this increase however was not statistically different between the two groups (value of p = 0.88). The present study suggested that curcumin may not be a useful adjuvant agent in the management of patients with BID receiving sodium valproate as treatment.Clinical trial registration: Iranian Registry of Clinical Trials (IRCT), identifier IRCT2016102530504N1.

Enzalutamide in the treatment of metastatic castrate-sensitive prostate cancer

The treatment landscape for metastatic castrate-sensitive prostate cancer has changed dramatically in the past decade because of the approval of chemotherapy and novel androgen therapies in combination with androgen deprivation therapy. The addition of these agents has resulted in overall benefits and progression-free survival for patients. The National Institute for Health and Care Excellence recently approved enzalutamide in the treatment of metastatic castrate-sensitive prostate cancer. Oncology nurse prescribers are central to the care of prostate cancer, providing holistic assessment and management of the disease and treatment side effects. A comprehensive understanding of the mechanism of action and specific side effects of androgen receptor inhibitors will enable an oncology nurse to provide timely interventions with a high standard of care.

The effect of Pimpinella Anisum herbal tea on human milk volume and weight gain in the preterm infant: a randomized controlled clinical trial

Background and aimsHuman milk supports pre-term infants to thrive. Yet human milk production can be inhibited when infants are born prematurely. Pimpinella Anisum has been evidenced to increase milk production and infant weight gain in previous animal studies. The present study aimed to determine the effect of Pimpinella Anisum herbal tea on human milk volume and preterm infant weight in human populations for the first time.MethodsHuman milk supports pre-term infants to thrive. Yet human milk production can be inhibited when infants are born prematurely. Pimpinella Anisum has been evidenced to increase milk production and infant weight gain in previous animal studies. The present study aimed to determine the effect of Pimpinella Anisum herbal tea on human milk volume and preterm infant weight in human populations for the first time.ResultsThere was a statistically significant difference in terms of milk volume in the first, third, fourth, fifth, sixth and seventh days between the three groups of intervention, placebo, and control (p < 0.05). On the first day, the mean volume of pumped milk in the intervention group was significantly higher than the control group (p = 0.008). On the second day, there was no statistically significant difference between groups. On the third, fourth, fifth, sixth and seventh days, the mean volume of pumped milk in the intervention group was significantly higher than the placebo and control groups (p < 0.05). There was no statistically significant difference in terms of preterm infant weight on days 0, 3 and 7 between the three groups.ConclusionThe use of Pimpinella Anisum or ‘Anise’ tea can increase the volume of human milk and since no specific side effects have been reported in its use, it may be incorporated easily, cheaply, and effectively in practice where appropriate to the benefit of preterm infant nutrition worldwide.

COVID-19 Vaccination Reactions and Risk of Breakthrough Infections Among People With Diabetes: Cohort Study Derived From Community Reporters.

This exploratory study compares self-reported COVID-19 vaccine side effects and breakthrough infections in people who described themselves as having diabetes with those who did not identify as having diabetes. The study uses person-reported data to evaluate differences in the perception of COVID-19 vaccine side effects between adults with diabetes and those who did not report having diabetes. This is a retrospective cohort study conducted using data provided online by adults aged 18 years and older residing in the United States. The participants who voluntarily self-enrolled between March 19, 2021, and July 16, 2022, in the IQVIA COVID-19 Active Research Experience project reported clinical and demographic information, COVID-19 vaccination, whether they had experienced any side effects, test-confirmed infections, and consented to linkage with prescription claims. No distinction was made for this study to differentiate prediabetes or type 1 and type 2 diabetes nor to verify reports of positive COVID-19 tests. Person-reported medication use was validated using pharmacy claims and a subset of the linked data was used for a sensitivity analysis of medication effects. Multivariate logistic regression was used to estimate the adjusted odds ratios of vaccine side effects or breakthrough infections by diabetic status, adjusting for age, gender, education, race, ethnicity (Hispanic or Latino), BMI, smoker, receipt of an influenza vaccine, vaccine manufacturer, and all medical conditions. Evaluations of diabetes medication-specific vaccine side effects are illustrated graphically to support the examination of the magnitude of side effect differences for various medications and combinations of medications used to manage diabetes. People with diabetes (n=724) reported experiencing fewer side effects within 2 weeks of vaccination for COVID-19 than those without diabetes (n=6417; mean 2.7, SD 2.0 vs mean 3.1, SD 2.0). The adjusted risk of having a specific side effect or any side effect was lower among those with diabetes, with significant reductions in fatigue and headache but no differences in breakthrough infections over participants' maximum follow-up time. Diabetes medication use did not consistently affect the risk of specific side effects, either using self-reported medication use or using only diabetes medications that were confirmed by pharmacy health insurance claims for people who also reported having diabetes. People with diabetes reported fewer vaccine side effects than participants not reporting having diabetes, with a similar risk of breakthrough infection. ClinicalTrials.gov NCT04368065; https://clinicaltrials.gov/study/NCT04368065.

The Best Time to Dental Implant Placement in Patients with Head and Neck Cancers: An Ever-going Debate

With 500,000 new cases diagnosed each year, head and neck cancers (HNC) are among the most prevalent cancers in the world. The most effective organ-sparing therapy for patients with locally advanced HNC is concurrent chemoradiotherapy (C-CRT). Many HNC patients lose multiple teeth and develop soft and hard tissue defects over the course of the disease and treatment, leading to functional limitations and cosmetic deformity. Such devastating effects harm the patient's ability to eat, chew, and swallow as well as their psychological, financial, and social well-being. Additionally, multiple tooth losses and subpar oral rehabilitation services can cause cachexia, rapid weight loss, and weakened immunity. The use of conventional prostheses to address tooth losses may not be permitted due to detrimental changes in the structure of the oral cavity. Conventional prostheses may aggravate the harmful side effects of radiotherapy, including xerostomia, mucositis, and a deterioration of bone healing processes. Dental implants may be a better choice for oral rehabilitation. However, because the area of bone involved in implant placement is frequently within the irradiation zone, dental implant planning and timing in HNC patients can be extremely difficult. Additionally, the placement of dental implants may precipitate some specific side effects of cancer treatments, such as osteoradionecrosis. Because the best time to use dental implants is one of the essential components of successful dental rehabilitation for HNC survivors and has not yet been clarified in the literature, this review article aims to gather and provide information in the head and neck region by reviewing the available literature.

Graphene oxide-gastrointestinal drugs for no side effect: Ultrasound synthesis and characterization

Graphene oxide nanosheets compound (GO) was synthesized and characterized by TEM and XRD. Furthermore, the gastrointestinal drugs (GD) were mixed with graphene oxide nanogel (0.1%) by ultrasound to give the nanocomposite (GO-GD). These nanocomposites were used orally to remove the side effects of the pure gastrointestinal drugs. The invitro results on rats proved that no significant side effects were determined. Moreover, this study includes, for the first time, the influence of functional groups and their relationship to possible side effects on humans. In this study, the comparison was based on the use of only two classes of drugs, which are proton pump inhibitors and histamine 2 blockers. A significant number of chemicals for the treatment of the gastrointestinal system have been selected, which are (omeprazole, pantoprazole, esomeprazole, lansoprazole, nizatidine, cimetidine, famotidine, rabeprazol, and ranitidine). Upon further exuding, the chemical composition of the selected chemicals, it was found that they contain a five- or six- membered aromatic ring(s) to which aliphatic groups of long, medium or short chains are linked. Accordingly, chemical functional groups containing hetero atoms, which are sulfur, oxygen and/or nitrogen, were determined for further investigations. Based on this study, it was found that the functional groups have a significant effect on the specific side effects, and therefore, the continuation of such studies will provide later a mechanism to determine the side effects.

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient.

The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients. In the second 10 years (from 2010 to the present), the main objective of CML therapy moved from survival, considered achieved as a goal, to treatment-free remission (TFR). Two phenomena emerged: no more than 50-60% of CML patients could be candidates for discontinuation and over 50% of them molecularly relapse. The increased cumulative incidence of specific TKI off-target side effects was such relevant to compel to discontinue or reduce the TKI administration in a significant proportion of patients and to avoid a specific TKI in particular settings of patients. Therefore, the treatment strategy must be adapted to each category of patients. What about the patients who do not get or fail the TFR? Should they be compelled to continue the TKIs at the maximum tolerated dose? Alternative strategies based on the principle of minimal effective dose have been tested with success and they are now re-evaluated with more attention, since they guarantee survival and probably a better quality of life, too. Moving from treating the disease to treating the patient is an important change of paradigm. We can say that we are entering a personalized CML therapy, which considers the patients' age, their comorbidities, tolerability, and specific objectives. In this scenario, the new techniques supporting the monitoring of the patients, such as the digital PCR, must be considered. In the present review, we present in deep this evolution and comment on the future perspectives of CML therapy.

How to Improve the Quality of Life of Patients with Prostate Cancer Treated with Hormone Therapy?

Prostate cancer (PC) is a hormone-sensitive tumor. Androgen deprivation therapy (ADT) is the cornerstone of systemic therapy for patients with intermediate or high-risk localized, recurrent, and metastatic prostate cancer. Although generally well tolerated, ADT can lead to short- and long-term adverse events that can worsen the quality of life of patients with PC. In the last decade, the introduction of novel generation androgen receptor pathway inhibitors (ARPI) has resulted in an improvement in the prognosis of patients with metastatic PC when used in combination with ADT. The use of ARPI in increasingly early stages of the disease determines a longer exposure of patients to these treatments. Although ARPIs are normally well-tolerated drugs, they generally cause an increase in toxicity compared to ADT alone, being able to worsen some adverse events already induced by ADT or leading to the development of specific side effects. Although there are no specific treatments for all the adverse events induced by hormonal therapies, it is essential to know the possible toxicities induced by the different treatments and to start procedures to prevent and/or recognize and consequently treat them early in order to not compromise the quality of life of the patients with PC. The aim of this review is to describe the adverse events induced by hormonal therapies. We will first describe the side effects induced by both ADT and ARPI and then the specific adverse events of the different ARPIs. Furthermore, we will try to highlight the possible therapeutic options to prevent or mitigate the toxicity induced by hormone therapies in order to improve the quality of life of the patients with PC.