Optimal Treatment Regimen Research Articles

Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.

Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%). In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.

A RETROSPECTIVE EVALUATION OF MORBIDITY AND MORTALITY IN ASSOCIATION WITH INFESTATION BY THE MITE STERNOSTOMA TRACHEACOLUM IN AN AVIARY-HOUSED POPULATION OF GOULDIAN FINCHES (CHLOEBIA GOULDIAE).

The Rhynonyssid mesostigmatic mite, Sternostoma tracheacolum, is a well-documented endoparasitic hematophagous arthropod of the respiratory tracts of multiple avian species, particularly Estrildid finches and canaries. In this retrospective study, 175 medical and 278 pathology records for the Gouldian finch (Chloebia gouldiae) population (N = 377) at the San Diego Zoo between 2013 and 2021 were analyzed to evaluate the effectiveness of ivermectin-based prophylaxis. A multivariable negative binomial regression model was constructed to evaluate the population effects of monthly treatments on morbidity or mortality associated with respiratory mites. While controlling for other factors in the model, the prophylactic treatment did not significantly reduce the monthly rate of mite-associated morbidity or mortality (IRR = 1.017, 95% CI: 0.997-1.036, P = 0.0759); however, low proportions of the population were prophylactically treated over time. Different factors were significant when separately evaluating adjusted associations with respiratory morbidity and mortality. The findings suggest increased rates of respiratory morbidity for each successive year of the study period (IRR = 1.180, 95% CI: 1.046-1.342, P = 0.0090) and increased rates of mite-associated mortality occurring annually between May and October (IRR = 1.697, 95% CI: 1.034-2.855, P = 0.0404) compared to the wet winter season. Our findings highlight the need to continually evaluate and optimize treatment regimens in zoological collections. Further investigations into this host-parasite relationship and potential treatments and preventive therapies are warranted.

Re-Print: New Perspectives in Immunotherapy: The importance of Dendritic Cells in Allergen-Specific Immunotherapy

Allergen-specific immunotherapy is the only treatment capable of altering the natural course of the allergic disease. Clinical trials show that immunotherapy is safe and effective for many patients. However, it still faces problems related to efficacy, safety, long treatment duration and low patient adherence. Contrary to what was imagined, the shift in immunity from Th2 to Th1 is not the key to successful treatment. Recent advances in the knowledge of Treg and Breg cells and tolerance mechanisms have been essential to explain the immunological changes resulting from immunotherapy. In this context, there has been intense research into the development of adjuvants with the aim of increasing safety, optimizing treatment regimens and improving patient adherence. Allergens were modified (glycoconjugates) with carbohydrates derived from Saccharomyces Cerevisae to increase their uptake and presentation through carbohydrate receptors present in Dendritic Cells, benefiting from the ability to act in inducing tolerance to initiate immune responses. Dendritic cells are the most professional antigen presenters of the APC system. They represent the bridge between innate and adaptive immunity and are capable of initiating and maintaining immune responses. In light of new evidence, they constitute a key therapeutic target to obtain an adequate response to allergen-specific immunotherapy with the potential to contribute to innovation in the field of immunotherapy.

Complex Approach to the Management of Acneiform Rash Induced by Epidermal Growth Factor Receptor Inhibitors

Rationale. Acneiform (papulopustular) rash is the leading dermatological adverse event of EGFR inhibitors. The development of optimal regimens for the supportive treatment of acneiform rash remains an important interdisciplinary problem in supportive oncology. Aims — to comparatively evaluate the clinical efficacy of the supportive treatment for acneiform rash induced by epidermal growth factor receptor inhibitors, including topical treatment with ivermectin cream and balneotherapy. Methods. In an open, prospective, randomized study, data from 114 patients with acneiform rash induced by monoclonal antibodies to EGFR were analyzed. All groups received intermittent supportive treatment according to a single regimen, continuous external therapy included: in group 1 — hypotonic thermal water, in group 2 — ivermectin 1% cream, in group 3 — hypotonic thermal water and ivermectin 1% cream. The observation period was 3 months. Acneiform rash severity was assessed using the CTCAE-NCI v5.0 criteria and a developed acneiform rash clinical severity scale. The intensity of subjective symptoms was assessed using a 10-point visual analog scale (VAS). The modified dermatological life quality index (mDLQI) was used to assess the impact of acneiform rash on patient’s quality of life. Results. A significant decrease in all of the studied parameters was observed in the groups by the end of the 1st week of supportive treatment and remained up to the end of the observation period (p 0.05). There were no statistically significant differences between groups 2 and 3 with respect to the acneiform rash clinical severity scale, but their values were significantly lower than those of group 1 (group 1 vs. group 2, p 0.001; group 1 vs. group 3, p 0.001). The most rapid resolution of all subjective symptoms was observed in group 3. Significantly lower mDLQI values were also observed in group 3 starting from the 1st week of supportive treatment until the end of the follow-up period (р 0.05). No severe adverse reactions were registered in any of the groups during the study. Conclusions. The developed regimens for the supportive treatment of acneiform rash have demonstrated a high efficacy in resolving papulopustular rash and associated subjective symptoms. The use of a complex approach including continuous topical therapy with ivermectin cream and hypotonic thermal water leads to the resolution of rash and relief of subjective symptoms in the shortest time, allows to safely maintain the achieved clinical effect for a long period of observation, has the most significant positive impact on the quality of life of cancer patients.

Improving the predictive accuracy of efficacy evaluation using tumor orthotopic transplant and resection model.

Preclinical efficacy evaluation and tumor drug sensitivity analysis are two main applications of efficacy evaluation. Preclinical efficacy evaluation is to predict whether candidate drugs or therapies may improve patient outcomes in clinical trials. Tumor drug sensitivity analysis is an approach for the personalized evaluation and optimization of approved anti-cancer drugs and treatment regimens. Overall survival (OS) is the gold standard to evaluate the outcome of drugs or therapies in both clinical trials and clinical treatment. Many efficacy evaluation models, such as cell model, tumor cell-line transplant model, patient-derived tumor xenograft model, tumor organoid model, have been developed to assess the inhibitory effect of tested drugs or therapies on tumor growth. In fact, many treatments may also lead to malignant progression of tumors, such as chemotherapy, which can lead to metastasis. Therefore, tumor growth inhibition does not necessarily predict OS benefit. Whether it can prevent or inhibit tumor recurrence and metastasis is the key to whether drugs and therapies can improve patient outcomes. In this perspective, we summarize the current understanding of the pathological progression of tumor recurrence and metastasis, point out the shortcomings of existing tumor transplant models for simulating the clinical scenario of malignant progression of tumors, and propose five improved indicators for comprehensive efficacy evaluation to predict OS benefit using tumor orthotopic transplant and resection model. Improvement in the accuracy of efficacy evaluation will accelerate the development process of anti-cancer drugs or therapies, optimize treatment regimens to improve OS benefit, and reduce drug development and cancer treatment costs.

The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC).

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.

Quantitative modeling of tumor dynamics and development of drug resistance in non-small cell lung cancer patients treated with erlotinib.

Insight into the development of treatment resistance can support the optimization of anticancer treatments. This study aims to characterize the tumor dynamics and development of drug resistance in patients with non-small cell lung cancer treated with erlotinib, and investigate the relationship between baseline circulating tumor DNA (ctDNA) data and tumor dynamics. Data obtained for the analysis included (1) intensively sampled erlotinib concentrations from 29 patients from two previous pharmacokinetic (PK) studies, and (2) tumor sizes, ctDNA measurements, and sparsely sampled erlotinib concentrations from 18 patients from the START-TKI study. A two-compartment population PK model was first developed which well-described the PK data. The PK model was subsequently applied to investigate the exposure-tumor dynamics relationship. To characterize the tumor dynamics, models accounting for intra-tumor heterogeneity and acquired resistance with or without primary resistance were investigated. Eventually, the model assumed acquired resistance only resulted in an adequate fit. Additionally, models with or without exposure-dependent treatment effect were explored, and no significant exposure-response relationship for erlotinib was identified within the observed exposure range. Subsequently, the correlation of baseline ctDNA data on EGFR and TP53 variants with tumor dynamics' parameters was explored. The analysis indicated that higher baseline plasma EGFR mutation levels correlated with increased tumor growth rates, and the inclusion of ctDNA measurements improved model fit. This result suggests that quantitative ctDNA measurements at baseline have the potential to be a predictor of anticancer treatment response. The developed model can potentially be applied to design optimal treatment regimens that better overcome resistance.

Emerging wearable technologies for multisystem monitoring and treatment of Parkinson's disease: a narrative review.

Parkinson's disease (PD) is a chronic movement disorder characterized by a variety of motor and nonmotor comorbidities, including cognitive impairment, gastrointestinal (GI) dysfunction, and autonomic/sleep disturbances. Symptoms typically fluctuate with different settings and environmental factors and thus need to be consistently monitored. Current methods, however, rely on infrequent rating scales performed in clinic. The advent of wearable technologies presents a new avenue to track objective measures of PD comorbidities longitudinally and more frequently. This narrative review discusses and proposes emerging wearable technologies that can monitor manifestations of motor, cognitive, GI, and autonomic/sleep comorbidities throughout the daily lives of PD individuals. This can provide more wholistic insight into real-time physiological versus pathological function with the potential to better assess treatments during clinical trials and allow physicians to optimize treatment regimens. Additionally, this narrative review briefly examines novel applications of wearables as therapy for PD patients.

Frequency and Prognostic Value of Acute Periprocedural Myocardial Injury in Elective Percutaneous Coronary Interventions

Background. Periprocedural myocardial injury (PMI) is an acute complication of percutaneous coronary interventions (PCI) in patients with stable coronary artery disease. Its frequency and relationship with the prognosis of the disease are especially important in elective interventions due to the low risk of ischemic events in this cohort of patients. However, according to the literature, there are significant differences in the criteria for PMI and type 4a myocardial infarction (MI), and, accordingly, their frequency and their prognostic value. Aim. To study the frequency and magnitude of PMI during elective PCI in terms of the level of periprocedural increase in cardiospecific biomarkers, as well as to determine the relationship of PMI with long-term adverse events in patients with chronic coronary artery disease. Materials and methods. A single-center open retrospective cohort study was conducted, which included 435 patients (367/84.4 % men, mean age 58.3±8.6 years) from the elective PCI registry. PMI was diagnosed with an increase in the level of creatine phosphokinase MB fraction (CK-MB) or or cardiac troponin I (cTn I) &gt;1×99 percentile URL (Upper Reference Limit), while the level of increase in biomarkers &gt;1, 2, 3, 4 or &gt;5×99 percentile URL was recorded. An increase in biomarkers &gt;5x99 URL percentile was assessed as a large PMI, and in the presence of clinical and imaging evidence of new loss of viable myocardium, as periprocedural MI type 4a. Depending on the level of periprocedural increase in biomarkers, the relative risk (RR) of developing long-term (within 5 years after index PCI) adverse cardiovascular events, death, as well as clinically significant bleeding and newly diagnosed malignant oncological diseases was calculated. In addition, the correlation between PMI and the above endpoints was summarized using Kaplan-Meier analysis. Results. The frequency of periprocedural PMI diagnosed by increased biomarkers &gt;1×99 percentile URL was 40.2 %, &gt;2×99 percentile URL — 9.7 %, &gt;3×99 percentile URL — 6.7 %, &gt;4×99 percentile URL — 4.8 %, &gt;5×99 percentile URL — 3.5 %, type 4a MI — in 2 patients (0.46 %). An association of “major” PMI (&gt;5x99 percentile URL) with cardiovascular complications within 3 years after elective PCI, including fatal ones, was revealed: for acute myocardial infarction (AMI), RR — 6.516, confidence interval (CI) [2.375-17.881]; for death from cardiovascular causes RR — 6.538, CI [1.695-25.227]. An association of “moderate” PMI (&gt;3, but &lt;5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (&gt;1, but &lt;5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (&gt;1, but &lt;3 ×99 URL percentile) with newly diagnosed malignant oncological diseases within 5 years after index PCI was revealed: RR 2.319; CI [1.248- 4.310]. An association of late thrombotic events, such as stent thrombosis (index and re-interventions), stent occlusion (index and non-index) as a reason for re-intervention within 5 years after index PCI, was found with most PMI subgroups. Kaplan-Meier analysis of the dependence of clinically significant bleeding within 5 years after index PCI on the development of “moderate” PMI (p=0.003), as well as the association of non-cardiovascular death within 5 years after index PCI with “minor” PMI (p= 0.007). Conclusion. Registration of periprocedural increase in cardiac biomarkers should be carried out during planned PCI not only for the purpose of diagnosing and predicting acute and late ischemic events, but also for assessing the risk of developing stent occlusion, clinically significant bleeding and prognostically important comorbidities in the long-term (5-year) period in order to identification of groups of patients requiring active monitoring, additional examination and selection of an optimal treatment regimen at the outpatient stage of rehabilitation.

Progress of PD-1/PD-L1 inhibitor combination therapy in immune treatment for HER2-positive tumors.

Patients with HER2-positive cancers often face a poor prognosis, and treatment regimens containing anti-HER2 have become the first-line treatment options for breast and gastric cancers. However, these approaches are faced with significant challenges in terms of drug resistance. Hence, it is crucial to explore precise treatment strategies aimed at improving survival outcomes. Over the past few years, there has been rapid advancement in the realm of tumor therapy, particularly with the swift progress of immune checkpoint inhibitors, including PD-1/PD-L1 inhibitors. They exert anti-tumor effects by disrupting immune-suppressive factors within the tumor microenvironment. However, monotherapy with PD-1/PD-L1 inhibitors has several limitations. Consequently, numerous studies have explored combinatorial immunotherapeutic strategies and demonstrated highly promising avenues of development. This article aims to review the clinical trials investigating PD-1/PD-L1 inhibitor combination therapy for HER2-positive tumors. Additionally, it provides a summary of ongoing trials evaluating the efficacy and safety of these combined treatments, with the intention of furnishing valuable insights for the clinical management of HER2-positive cancer. Combinatorial immunotherapeutic strategies involving PD-1/PD-L1 inhibitors hold considerable promise in the treatment of HER2-positive tumors. Continued research efforts and clinical trials are warranted to elucidate optimal treatment regimens that maximize therapeutic benefits while minimizing adverse effects.

Estimation of optimal treatment regimes with electronic medical record data using the residual life value estimator.

Clinicians and patients must make treatment decisions at a series of key decision points throughout disease progression. A dynamic treatment regime is a set of sequential decision rules that return treatment decisions based on accumulating patient information, like that commonly found in electronic medical record (EMR) data. When applied to a patient population, an optimal treatment regime leads to the most favorable outcome on average. Identifying optimal treatment regimes that maximize residual life is especially desirable for patients with life-threatening diseases such as sepsis, a complex medical condition that involves severe infections with organ dysfunction. We introduce the residual life value estimator (ReLiVE), an estimator for the expected value of cumulative restricted residual life under a fixed treatment regime. Building on ReLiVE, we present a method for estimating an optimal treatment regime that maximizes expected cumulative restricted residual life. Our proposed method, ReLiVE-Q, conducts estimation via the backward induction algorithm Q-learning. We illustrate the utility of ReLiVE-Q in simulation studies, and we apply ReLiVE-Q to estimate an optimal treatment regime for septic patients in the intensive care unit using EMR data from the Multiparameter Intelligent Monitoring Intensive Care database. Ultimately, we demonstrate that ReLiVE-Q leverages accumulating patient information to estimate personalized treatment regimes that optimize a clinically meaningful function of residual life.

Characteristics and outcomes of peripheral neuropathic pain patients with repeated applications of high-concentration capsaicin cutaneous patch: Results of a retrospective chart review in Germany.

The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. The study was conducted at an outpatient pain center in Wiesbaden, Germany. The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.

Integrating Artificial Intelligence and PET Imaging for Drug Discovery: A Paradigm Shift in Immunotherapy.

The integration of artificial intelligence (AI) and positron emission tomography (PET) imaging has the potential to become a powerful tool in drug discovery. This review aims to provide an overview of the current state of research and highlight the potential for this alliance to advance pharmaceutical innovation by accelerating the development and deployment of novel therapeutics. We previously performed a scoping review of three databases (Embase, MEDLINE, and CENTRAL), identifying 87 studies published between 2018 and 2022 relevant to medical imaging (e.g., CT, PET, MRI), immunotherapy, artificial intelligence, and radiomics. Herein, we reexamine the previously identified studies, performing a subgroup analysis on articles specifically utilizing AI and PET imaging for drug discovery purposes in immunotherapy-treated oncology patients. Of the 87 original studies identified, 15 met our updated search criteria. In these studies, radiomics features were primarily extracted from PET/CT images in combination (n = 9, 60.0%) rather than PET imaging alone (n = 6, 40.0%), and patient cohorts were mostly recruited retrospectively and from single institutions (n = 10, 66.7%). AI models were used primarily for prognostication (n = 6, 40.0%) or for assisting in tumor phenotyping (n = 4, 26.7%). About half of the studies stress-tested their models using validation sets (n = 4, 26.7%) or both validation sets and test sets (n = 4, 26.7%), while the remaining six studies (40.0%) either performed no validation at all or used less stringent methods such as cross-validation on the training set. Overall, the integration of AI and PET imaging represents a paradigm shift in drug discovery, offering new avenues for more efficient development of therapeutics. By leveraging AI algorithms and PET imaging analysis, researchers could gain deeper insights into disease mechanisms, identify new drug targets, or optimize treatment regimens. However, further research is needed to validate these findings and address challenges such as data standardization and algorithm robustness.

Effect of high-dose intravenous methylprednisolone pulse (IVMP) therapy in the survival of patients with anti-melanoma differentiation-associated gene 5-related rapidly progressive interstitial lung disease: a retrospective analysis.

To assess the impacts of high-dose intravenous methylprednisolone pulse (IVMP) therapy in survival and the occurrences of treatment-related infection of patients with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease (MDA5-RPILD). Patients with MDA5-RPILD from June 2017 to August 2022 in our hospital were retrospectively reviewed. IVMP therapy was defined as intravenous methylprednisolone (mPSL) 0.5g/day for 3 consecutive days during hospitalization or 7 days prior to admission and patients were divided into IVMP group and non-IVMP group based on who had ever received IVMP therapy. All-cause mortality and the incidence of adverse events during treatment were compared between the two groups. Sixty-four patients with MDA5-RPILD were enrolled. Among them, twenty-three (35.9%) patients had ever received IVMP therapy. The overall mortality was comparable between IVMP and non-IVMP group (IVMP group: 22/23, 95.7% vs. non-IVMP group: 38/41, 92.7%, p=0.11). And the incidence of treatment-related infections was also close (IVMP group: 21/23, 91.3% vs. non-IVMP group: 32/41, 78.0%, p=0.30). After adjustment for gender, age, smoking history, duration from symptom onset to diagnosis, and combination with steroid-sparing agent treatment, the Cox proportional hazards model showed that IVMP therapy was not associated with an improved survival (adjusted HR 1.10; 95% CI 0.57-2.13; p=0.77). Our study showed that the survival benefits and adverse events were comparable between IVMP-treated and untreated MDA5-RPILD patients. Future prospective trials are needed to investigate the optimal treatment regimen in MDA5-RPILD. Key Points • This observational study found that IVMP therapy may be not associated with an improved outcome in patients with MDA5-RPILD. • Treatment-related infections are common; however, the incidence of treatment-related infections had no difference between IVMP and non-IVMP group.

Neoadjuvant therapy for resectable melanoma.

The standard of care for patients with resectable stage III/IV melanoma classically included upfront resection with adjuvant therapy. However, in more recent years, the amount of systemic therapies available for neoadjuvant use for these patients has increased. This article reviewed clinical trials investigating neoadjuvant therapy for patients with resectable stage III/IV melanoma. The outcomes of these trials have identified optimal treatment regimens to maximise patient response and minimize toxicities. Additionally, the date demonstrate advantages to neoadjuvant treatment compared to adjuvant therapy alone. Further research is needed to utilize a patient's response to neoadjuvant treatment for prognostication and creation of an individualized treatment plan.

Aberrant MET Receptor Tyrosine Kinase Signaling in Glioblastoma: Targeted Therapy and Future Directions.

Brain tumors represent a heterogeneous group of neoplasms characterized by a high degree of aggressiveness and a poor prognosis. Despite recent therapeutic advances, the treatment of brain tumors, including glioblastoma (GBM), an aggressive primary brain tumor associated with poor prognosis and resistance to therapy, remains a significant challenge. Receptor tyrosine kinases (RTKs) are critical during development and in adulthood. Dysregulation of RTKs through activating mutations and gene amplification contributes to many human cancers and provides attractive therapeutic targets for treatment. Under physiological conditions, the Met RTK, the hepatocyte growth factor/scatter factor (HGF/SF) receptor, promotes fundamental signaling cascades that modulate epithelial-to-mesenchymal transition (EMT) involved in tissue repair and embryogenesis. In cancer, increased Met activity promotes tumor growth and metastasis by providing signals for proliferation, survival, and migration/invasion. Recent clinical genomic studies have unveiled multiple mechanisms by which MET is genetically altered in GBM, including focal amplification, chromosomal rearrangements generating gene fusions, and a splicing variant mutation (exon 14 skipping, METex14del). Notably, MET overexpression contributes to chemotherapy resistance in GBM by promoting the survival of cancer stem-like cells. This is linked to distinctive Met-induced pathways, such as the upregulation of DNA repair mechanisms, which can protect tumor cells from the cytotoxic effects of chemotherapy. The development of MET-targeted therapies represents a major step forward in the treatment of brain tumours. Preclinical studies have shown that MET-targeted therapies (monoclonal antibodies or small molecule inhibitors) can suppress growth and invasion, enhancing the efficacy of conventional therapies. Early-phase clinical trials have demonstrated promising results with MET-targeted therapies in improving overall survival for patients with recurrent GBM. However, challenges remain, including the need for patient stratification, the optimization of treatment regimens, and the identification of mechanisms of resistance. This review aims to highlight the current understanding of mechanisms underlying MET dysregulation in GBM. In addition, it will focus on the ongoing preclinical and clinical assessment of therapies targeting MET dysregulation in GBM.

Efficacy of immunotherapy in patients with metastatic melanoma

Introduction. Melanoma is an aggressive form of skin cancer caused by the transformation of melanocytes into malignant cells. Currently, immunotherapy is one of the most promising treatment methods, but searching the most optimal treatment regimens is still ongoing.Objective. To evaluate the effectiveness and safety of the use of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma.Materials and methods. The study included 229 patients (114 men and 115 women) aged 21 to 91 years who received (ICIs) as nivolumab (n = 168; 73,4%) and pembrolizumab (n = 30; 13,1%) monotherapy, and combination of nivolumab and ipilimumab (n = 31; 13,5%). The objective response of the tumor to treatment was recorded in the presence of partial or complete regression of the tumor. The tumor response to treatment was determined in accordance with the iRECIST criteria.Results. Complete regression was observed in 16.7, 15.9 and 8,7% of patients, partial – in 11.1, 11.4 and 17.4%, stabilization was detected in 51.2, 50.0 and 34.8% and progression – in 21.0, 22.7 and 39.1% of patients with first, second and third and more-line setting, respectively. The median response time was 3.14, 5.18 and 3.63 months, the median response duration was 16.21, 8.96 and 30.15 months in first, second and third and more-line setting, respectively. Grade 3–4 immuno-related adverse events (irAEs) were observed in 8 (3.5%) patients.Conclusions. Immunotherapy of metastatic melanoma allows achieving high rates of objective response and disease control (27.5 and 76.9%, respectively). This method of treatment is characterized by an insignificant amount of grade 3–4 irAEs (3.5% according to our data), which indicates an acceptable safety profile.

Efficacy of immunotherapy in patients with non-small cell lung cancer

Introduction. Non-small cell lung cancer (NSCLC) is a form of lung cancer with high incidence and low overall survival. Immunotherapy is a promising treatment method for which the selection of optimal treatment regimens for each individual patient is important.Aim. To evaluate the effectiveness and safety of immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC.Materials and methods. The study included 247 patients (190 men and 57 women) aged 37 to 87 years who received ICIs as monotherapy with nivolumab (n = 58; 23.4%), pembrolizumab (n = 78; 31.6%) and atezolizumab (n = 13; 5.3%), and in the form of combination chemoimmune therapy (n = 98; 39.7%). The objective response of the tumor to treatment was recorded in the presence of partial or complete regression of the tumor. The tumor response to treatment was determined in accordance with the iRECIST criteria.Results. Objective response was achieved in 20.6% of patients, of which 13.7% were on the first line setting, and 7% of patients were on the 2nd or more line setting. Disease control was recorded in 83.3% of patients. Patients receiving combination chemoimmune therapy had a better response to treatment than those receiving monotherapy (χ2 = 9.309; p = 0.020). Grade 3–4 immuno-related adverse events were observed only in 5 (2.02%) patients.Conclusions. NSCLC immunotherapy allows to achieve high rates of objective response and disease control (20.6 and 83.3%, respectively), with a small number of grade 3–4 immuno-related adverse events (2.02% according to our data), which indicates an acceptable safety profile.

Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system.

Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Age, creatinine, neutrophil-to-lymphocyte ratio, and Child-Turcotte-Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633-0.738) and better clinical utility compared with other conventional prognostic models. The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals.

Insights into hospitalization pattern for drug, medicament, and biological substance poisoning, adverse effect, and underdosing in Australia: An ecological study between 1998 and 2019.

Drug, medicament, and biological substance poisoning, adverse effects, and underdosing are significant public health concerns. Gaining insight into the patterns and trends in hospitalizations caused by these occurrences is essential for the development of preventative initiatives, optimization of treatment regimens, and improvement of patient safety. The aim of this study is to examine the trend of hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019. This is an ecological descriptive study that examined hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019. A nationwide hospital admissions database was used for this study. Between 1998 and 2019, a total of 683,869 hospital admission episodes were recorded in Australia. The overall annual number of hospital admissions for various reasons increased by 20.5% from 29,854 in 1998 to 35,960 in 2019, representing a decrease in hospital admission rate of 10.6% [from 158.69 (95% CI 156.90-160.49) in 1998 to 141.91 (95% CI 140.44-143.37) in 2019 per 100,000 persons, trend test, p<0.05]. Overnight-stay admissions accounted for 69.2% of the total number of hospital admissions, and 30.8% were same-day admissions. Rates of same-day hospital admission decreased by 13.3% [from 50.55 (95%CI 49.54-51.57) in 1998 to 43.81 (95%CI 43.00-44.63) in 2019 per 100,000 persons]. Rates of overnight-stay hospital admission decreased by 11.1% [from 108.14 (95%CI 106.66-109.63) in 1998 to 96.17 (95%CI 94.96-97.38) in 2019 per 100,000 persons]. Admissions related to antiepileptic, sedative-hypnotic and antiparkinsonism drugs was the most prevalent hospital admissions type accounting for 26.8%. Females were responsible for 418,751 hospital admission episodes, representing 61.5% of the total number of hospital admission. This study found that while the overall annual number of admissions increased, the rate of admission decreased over the same period. The most common reasons for admissions were antiepileptic, sedative-hypnotic, and anti-parkinsonism drugs. The study also noted increases in admissions related to anaesthetics, therapeutic gases, hormones, and their synthetic substitutes. These findings suggest a concerning rise in the suboptimal use of these medications. In order to combat the increasing incidence of this type of admissions, it is imperative to strengthen public awareness initiatives on medicine safety and abuse.