Retrospective Clinical Trials Research Articles

Optimal Sequence for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: An Evidence-Based Review.

Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.

Current Patient Management for Bacterial Meningitis Simultaneously Affected by Stroke.

Bacterial meningitis (BM) is a critical central nervous system infection characterized by increased risks of complications and potentially fatal outcomes. The chances of full recovery are significantly reduced in the presence of concomitant neurovascular complications such as ischemic and hemorrhagic strokes, intracerebral hemorrhage, and cerebral sinus thrombosis. Effective treatment of BM requires a targeted approach that simultaneously addresses the causative pathogen and manages the neurologically related complications. However, clinicians continue to face challenges in determining optimal pharmacotherapy for these patients.The presence of neurological complications is pivotal in determining patient outcomes, contributing to high disability and mortality rates. Early medical management is crucial and begins with essential stabilization followed by rapid diagnostic testing and the administration of empirical broad-spectrum antimicrobial therapy. The use of targeted antibiotics based on culture results is standard, with adjunct therapies such as dexamethasone and, in some cases, anticoagulants playing supportive roles. Despite the deployment of such comprehensive therapeutic strategies, the variability in treatment response and the high incidence of adverse outcomes necessitate ongoing research. This includes exploring novel therapeutic approaches and enhancing current clinical practices through retrospective studies and clinical trials to mitigate the high morbidity and mortality rates associated with BM and its complications. Strategic management is crucial for patient recovery, considering the substantial risk, a broad spectrum of complications, and fatal outcomes from this meningeal infection and stroke. The use of antimicrobial therapy with intravenous adjunct dexamethasone isthe current standard of care for patients with cerebrovascular complications and acute BM. In addition, other options that can provide benefits in complicated cases include anticoagulants and neurosurgery. Further investigation into treatment algorithms for patients with meningeal infection complicated by stroke and/or increased intracranial pressure is still needed.

Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver, following hepatocellular carcinoma (HCC). Surgical resection remains the only potentially curative treatment for ICC. However, due to its high malignancy and propensity for postoperative recurrence, the prognosis for ICC is generally poor, and there is currently little standardized approach for adjuvant therapy following curative surgery. This article aims to explore adjuvant treatment strategies for ICC post-curative surgery by reviewing retrospective studies and clinical trials conducted in recent years. The analysis focuses on the effectiveness, challenges, and potential developments in the management of ICC post-surgery, considering the high recurrence rates and the need for improved therapeutic approaches to enhance patient outcomes. Additionally, we discuss the various types of adjuvant treatments that have been explored, including chemotherapy, radiation therapy, and targeted therapies. The goal is to provide a comprehensive overview of the current landscape and highlight promising directions for future research to improve survival and quality of life for ICC patients.

Evaluation of Orthodontic Treatment Modalities for Obstructive Sleep Apnoea: A Systematic Review.

Obstructive sleep apnoea (OSA) poses a significant health burden globally, necessitating effective intervention strategies to mitigate its adverse consequences. Orthodontic treatment modalities offer promising avenues for addressing OSA by targeting the underlying anatomical abnormalities and restoring unobstructed airflow during sleep. This systematic search was conducted across multiple electronic databases using predefined search terms and inclusion criteria. Studies eligible for inclusion encompassed a range of study designs, including randomized controlled trials, prospective and retrospective studies, clinical trials, and observational studies. Outcome measures included changes in apnoea-hypopnoea index (AHI), oxygen saturation levels, polysomnographic variables, skeletal/cephalometric changes, nasal parameters, upper airway morphology, and clinical symptoms. Initially, 756 records were identified through database searches, with 21 studies meeting the inclusion criteria after meticulous screening and selection. Orthodontic interventions, including rapid maxillary expansion (RME), personalized oral appliances, mandibular positioning devices, and comprehensive orthodontic protocols, demonstrated significant promise in ameliorating OSA symptoms among paediatric populations. Improvements in AHI, nasal resistance, sleep parameters, and upper airway dimensions were consistently observed across various studies, highlighting the potential of orthodontic treatments in mitigating OSA severity. This systematic review underscores the efficacy of orthodontic treatment modalities in addressing OSAamong paediatric populations. Despite certain limitations in study design and outcome measures, the review emphasizes the need for further well-designed randomized controlled trials to validate and optimize these interventions for paediatric patients with OSA. Enhanced understanding and implementation of orthodontic treatments hold promise for alleviating the burden of OSA on global health and well-being.

The Effects of Presurgical Orthodontic Treatment on the Outcome of Secondary Bone Graft for Individuals With Cleft Lip and Palate

Background/Objective: Alveolar bone graft (ABG) or repair has become a routine part of treatment protocols for individuals with cleft lip and/or palate. However, the necessity and potential benefits of presurgical orthodontic treatment in influencing the outcomes of secondary alveolar bone grafting remain inconclusive. This systematic review aimed to assess the impact of presurgical orthodontics on preparing patients for secondary alveolar bone grafts. Study Design: The authors systematically searched for relevant articles in PubMed, Web of Science, and Embase databases spanning the period from January 1, 2000, to December 31, 2023, using keywords related to alveolar bone grafting and orthodontic treatment for patients with cleft lip and/or palate. The review encompassed various study designs, including prospective and retrospective studies, observational studies, cross-sectional studies, randomized and nonrandomized clinical trials, cohort studies, and case-control studies. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the risk of bias was evaluated in studies selected for full-text review. Results: The search strategy identified 809 publications. After initial screening and application of exclusion criteria, 11 studies were included for final review. Three were prospective studies, 8 were retrospective studies, and 3 were cross-sectional cohort studies. On the basis of ROBINS-I and RoB 2 risk assessment, 9 studies were found to be of moderate risk of bias, one study was categorized as of high risk of bias, and 1 study was categorized as low risk of bias. Conclusions: Drawing from the latest and most reliable studies, 7 out of 11 included studies provided compelling evidence that presurgical orthodontics preceding alveolar bone grafting (ABG) leads to significantly improved outcomes compared with cases without presurgical orthodontic intervention. Notably, individuals with specific conditions, such as severely collapsed upper arch and mispositioned upper incisors, appear to derive the greatest benefits from presurgical orthodontic treatment. However, a call for additional studies characterized by high methodological quality and with longer follow-up periods is emphasized to enhance the safety considerations for both practitioners and patients concerning the utilization of presurgical orthodontics in the treatment of individuals with cleft lip and palate.

Clinical Results of Primary Repair Versus Reconstruction of the Anterior Cruciate Ligament: A Systematic Review and Meta-analysis of Contemporary Trials.

Primary anterior cruciate ligament (ACL) repair has gained renewed interest in select centers for patients with proximal or midsubstance ACL tears. Therefore, it is important to reassess contemporary clinical outcomes of ACL repair to determine whether a clinical benefit exists over the gold standard of ACL reconstruction (ACLR). To (1) perform a meta-analysis of comparative trials to determine whether differences in clinical outcomes and adverse events exist between ACL repair versus ACLR and (2) synthesize the midterm outcomes of available trials. Systematic review; Level of evidence, 3. The PubMed, OVID/Medline, and Cochrane databases were queried in August 2023 for prospective and retrospective clinical trials comparing ACL repair and ACLR. Data pertaining to tear location, surgical technique, adverse events, and clinical outcome measures were recorded. DerSimonian-Laird random-effects models were constructed to quantitatively evaluate the association between ACL repair/ACLR, adverse events, and clinical outcomes. A subanalysis of minimum 5-year outcomes was performed. Twelve studies (893 patients; 464 ACLR and 429 ACL repair) were included. Random-effects models demonstrated a higher relative risk (RR) of recurrent instability/clinical failure (RR = 1.64; 95% confidence interval [CI], 1.04-2.57; P = .032), revision ACLR (RR = 1.63; 95% CI, 1.03-2.59; P = .039), and hardware removal (RR = 4.94; 95% CI, 2.10-11.61; P = .0003) in patients who underwent primary ACL repair versus ACLR. The RR of reoperations and complications (knee-related) were not significantly different between groups. No significant differences were observed when comparing patient-reported outcome scores. In studies with minimum 5-year outcomes, no significant differences in adverse events or Lysholm scores were observed. In contemporary comparative trials of ACL repair versus ACLR, the RR of clinical failure, revision surgery due to ACL rerupture, and hardware removal was greater for primary ACL repair compared with ACLR. There were no observed differences in patient-reported outcome scores, reoperations, or knee-related complications between approaches. In the limited literature reporting on minimum 5-year outcomes, significant differences in adverse events or the International Knee Documentation Committee score were not observed.

The Diagnostic Utility of Biochemical Markers and Intestinal Ultrasound Compared with Endoscopy in Patients with Crohn's Disease and Ulcerative Colitis: A Systemic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and Ulcerative colitis (UC). The main goal of treatment is to obtain mucosal healing via endoscopy. More recently, intestinal ultrasounds, along with biochemical markers, have been increasingly popular as point-of-care testing to monitor treatment response. This systemic review and meta-analysis aimed to assess the diagnostic test performance of ultrasonography and biochemical markers (C-reactive protein and fecal calprotectin) compared with endoscopy for detecting inflammation in IBD. Methods: A comprehensive literature search was conducted using PubMed Medline, EMBASE, ScienceDirect, and CINAHL from 1 January 2018 to 1 January 2024. The included studies were prospective and retrospective observational studies, clinical trials, and cross-sectional studies investigating the diagnostic sensitivity and specificity of ultrasonography, biochemical markers, and endoscopy. Studies were selected based on the Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA). Results: Of the 1035 studies retrieved, 16 met the inclusion criteria, and most of the included studies were prospective observational studies. Diagnostic test accuracy was conducted, and the pooled sensitivity and specificity of all the studies revealed that ultrasonography has the highest pooled sensitivity, at 85% (95% CI, 78 to 91%), and specificity, at 92% (95% CI, 86 to 96%), as compared with biochemical markers and endoscopy. More specifically, biochemical markers had a pooled sensitivity and specificity of 85% (95% CI, 81 to 87%) and 61% (95% CI, 58 to 64%), respectively, and endoscopy had 60% (95% CI, 52 to 68%) and 82% (95% CI, 76 to 87%), respectively. However, the results also show substantial heterogeneity in the studies because of various populations, protocols, and outcomes in the studies included. This was especially noted in the assessment of biochemical markers, in which a metaregression was performed showing a nonsignificant p-value of 0.8856 for the coefficient. Conclusions: IUS was found to have the highest pooled sensitivity and specificity of all the included studies for diagnosing inflammation in patients with CD and UC, and this, coupled with biochemical markers, can improve diagnostic utility.

Challenges during pancreatoduodenectomy and ways to overcome them

Background. Pancreaticoduodenal resection (PDR) is the surgical procedure for cancer of the head of the pancreas, distal common bile duct, duodenum and ampulla of Vater. This surgery is associated with a high risk of complications, the development of which can be influenced by various factors. since pancreatic fistula is a key complication of PDR, the choice of the method for pancreatic anastomosis becomes especially important. Material and methods. The search for publications was carried out using the PubMed and Elibrary systems from January 1980 to January 2024. of the 2,300 sources found, 69 were used to write the review. We included data from both retrospective and prospective clinical trials that were devoted to pancreatoduodenectomy for malignant neoplasms, the difficulties encountered in performing this surgery and ways to solve them. Results. Currently, there are more than 60 types of pancreatico-digestive anastomosis, which indirectly indicates the absence of a universal one that ensures the prevention of pancreatic fistula. The treatment outcomes may be influenced by the nature of neoadjuvant treatment, concomitant diseases, anatomical features, presence of obstructive jaundice and methods of its relief. The main mechanisms of influence of negative factors on the development of complications are considered. an individual approach to the patient, taking into account all factors, can significantly reduce the risk of complications.

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin.

Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness and ubiquitous availability, they are highly suitable options for treating the virus. MET's effect extends beyond managing blood sugar, impacting pathways that can potentially decrease the severity and fatality rates linked with COVID-19. It can partially block mitochondrial complex I and stimulate AMPK, which indicates that it can be used more widely in managing viral infections. ATO, however, impacts cholesterol metabolism, a crucial element of the viral replicative cycle, and demonstrates anti-inflammatory characteristics that could modulate intense immune reactions in individuals with COVID-19. Retrospective investigations and clinical trials show decreased hospitalizations, severity, and mortality rates in patients receiving these medications. Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency.

Low Perfusion and Missed Diagnosis of Hypoxemia by Pulse Oximetry in Darkly Pigmented Skin: A Prospective Study.

Retrospective clinical trials of pulse oximeter accuracy report more frequent missed diagnoses of hypoxemia in hospitalized Black patients than White patients, differences that may contribute to racial disparities in health and health care. Retrospective studies have limitations including mistiming of blood samples and oximeter readings, inconsistent use of functional versus fractional saturation, and self-reported race used as a surrogate for skin color. Our objective was to prospectively measure the contributions of skin pigmentation, perfusion index (PI), sex, and age on pulse oximeter errors in a laboratory setting. We enrolled 146 healthy subjects, including 25 with light skin (Fitzpatrick class I and II), 78 with medium (class III and IV), and 43 with dark (class V and VI) skin. We studied 2 pulse oximeters (Nellcor N-595 and Masimo Radical 7) in prevalent clinical use. We analyzed 9763 matched pulse oximeter readings (pulse oximeter measured functional saturation [Sp o2 ]) and arterial oxygen saturation (hemoximetry arterial functional oxygen saturation [Sa o2 ]) during stable hypoxemia (Sa o2 68%-100%). PI was measured as percent infrared light modulation by the pulse detected by the pulse oximeter probe, with low perfusion categorized as PI < 1%. The primary analysis was to assess the relationship between pulse oximeter bias (difference between Sa o2 and Sp o2 ) by skin pigment category in a multivariable mixed-effects model incorporating repeated-measures and different levels of Sa o2 and perfusion. Skin pigment, PI, and degree of hypoxemia significantly contributed to errors (bias) in both pulse oximeters. For PI values of 1.0% to 1.5%, 0.5% to 1.0%, and <0.5%, the P value of the relationship to mean bias or median absolute bias was <.00001. In lightly pigmented subjects, only PI was associated with positive bias, whereas in medium and dark subjects bias increased with both low perfusion and degree of hypoxemia. Sex and age was not related to pulse oximeter bias. The combined frequency of missed diagnosis of hypoxemia (pulse oximeter readings 92%-96% when arterial oxygen saturation was <88%) in low perfusion conditions was 1.1% for light, 8.2% for medium, and 21.1% for dark skin. Low peripheral perfusion combined with darker skin pigmentation leads to clinically significant high-reading pulse oximeter errors and missed diagnoses of hypoxemia. Darkly pigmented skin and low perfusion states are likely the cause of racial differences in pulse oximeter performance in retrospective studies.

Systematic review evaluating the influence of the prosthetic material and prosthetic design on the clinical outcomes of implant-supported multi-unit fixed dental prosthesis in the posterior area.

The objectives of the study were to assess the survival, failure, and technical complication rates of implant-supported fixed dental prosthesis (iFDPs) with pontic or splinted crown (iSp C) designs in the posterior area and compare the influence of prosthetic materials and prosthetic design on the outcomes. Electronic and manual searches were performed to identify randomized-, prospective-, and retrospective clinical trials with follow-up time of ≥12 months, evaluating the clinical outcomes of posterior iFDPs with pontic or iSp Cs. Survival and complication rates were analyzed using robust Poisson's regression models. Thirty-two studies reporting on 42 study arms were included in the present systematic review. The meta-analysis of the included studies indicated estimated 3-year survival rates of 98.3% (95%CI: 95.6-99.3%) for porcelain-fused-to-metal (PFM) iFDPs, 97.5% (95%CI: 95.5-98.7%) for veneered zirconia (Zr) iFDPs with pontic, 98.9% (95%CI: 96.8-99.6%) for monolithic or micro-veneered zirconia iFDPs with pontic, and 97.0% (95%CI: 84.8-99.9%) for lithium disilicate iFDPs with pontics. The survival rates for different material combination showed no statistically significant differences. Veneered restorations, overall, showed significantly (p < .01) higher ceramic fracture and chipping rates compared with monolithic restorations. Furthermore, there was no significant difference in survival rates (98.3% [95%CI: 95.6-99.3%] vs. 99.1% [95%CI: 97.6-99.7%]) and overall complication rates between PFM iFDPs with pontic and PFM iSp Cs. Based on the data identified by this systematic review, PFM, veneered Zr, and monolithic Zr iFDPs with pontic and iSp Cs showed similarly high short-term survival rates in the posterior area. Veneered restorations exhibit ceramic chipping more often than monolithic restorations, with the highest fracture rate reported for veneered Zr iFDPs.

Significance of Intra-plaque Hemorrhage for the Development of High-Risk Vulnerable Plaque: Current Understanding from Basic to Clinical Points of View.

Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk "vulnerable" plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.

What are the prognostic factors for the development of incontinence-associated dermatitis (IAD): a protocol for a systematic review and meta-analysis

IntroductionIncontinence-associated dermatitis (IAD) is irritant contact dermatitis and skin damage associated with prolonged skin contact with urine and/or faeces. Identifying prognostic factors for the development of IAD may improve management,...

Aspects of hypofractionation in modern radiation oncology

Background. In the modern world, the incidence of cancer diseases is rapidly increasing and is the second most common cause of death. This is preconditioned by the quantitative growth of the senior and elderly population, as well as the growth of the main risk factors for cancer, which is related to the socio-economic development of society. About half of cancer cases require radiation therapy (RT) as a component of multimodal treatment, therefore its improvement, namely the introduction of hypofractionated radiation regimens, is considered today as one of the most effective ways to increase availability of oncological care and optimize the use of health care system resources.&#x0D; Purpose. To find out clinical and medico-social advantages of the hypofractionated approach in radiation oncology in order to optimize the functioning of the health care system by increasing availability of treatment for cancer patients. To highlight the importance of hypofractionated RT in terms of evidence-based medicine for the most common oncological pathology and in neuro-oncology. To demonstrate the influence of the COVID-19 pandemic on the implementation of hypofractionated RT. To present our own experience of using hypofractionated radiation regimens in patients with glioblastoma (GB).&#x0D; Materials and methods. MEDLINE (Pubmed), EMBASE (Ovid), Web of Science (Web of Knowledge) databases were used to search for literature. The search was performed in the English-language sources with the following keywords: «Radiation», «Hypofractionation radiotherapy», «Hypofractionated radiotherapy», «Hypofractionated irradiation»; «Breast cancer»; «Prostate cancer»; «Lung cancer»; «Glioblastoma», COVID-19. Systematic reviews, meta-analyses, randomized controlled trials and retrospective clinical trials were reviewed in full. The primary sources were backreferenced to identify additional relevant studies related to hypofractionated radiation treatment regimens. The last date of the search is 05.25.2023. The authors’ own experience of the hypofractionated approach in the adjuvant radiation treatment of patients with GB is presented briefly, as a reflection of the relevance of the authors’ practical experience to the provisions of the narrative review, based on the results of a retrospective single-center non-randomized study conducted at the State Institution «Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine» in 2014–2020. The oncological results of 110 (69.2%) patients of the hypofractionated RT group (15 fractions, single fraction dose (SFD) 3.5 Gy, total fraction dose (TFD) 52.5 Gy) and 49 (30.8%) patients of the standard RT group (30 fractions, RVD 2.0 Gy, SVD 60.0 Gy) were compared. RT was performed with Trilogy linear accelerator (USA) (6 MeV) using the intensity-modulated radiotherapy method (IMRT). Overall survival (OS) and recurrence-free survival (RFS) in the groups were analyzed.&#x0D; Results and discussion. Hypofractionated approaches, which allow to significantly decrease the duration of radiation treatment, have clinical, medical and social advantages, including: increased comfort for a patient; reduction of the workload on staff and technological equipment of medical facilities; reduction of the cost of treatment. The introduction of hypofractionated RT allows to increase access to cancer care at the global level, reducing disparity in the results of treatment of cancer patients between low- and middle-income countries and the countries with high income level. Hypofractionated radiation regimens are included in the clinical guidelines of professional associations, as for the most common forms of cancer and for malignant brain tumors, and represent the standard of treatment for particular clinical cases. Our experience of using the hypofractionated radiation regimen is based on the adjuvant radiation treatment of 110 patients with GB and in terms of clinical results is a relevant concept presented in a narrative review. The analysis showed no statistical difference between the groups of standard fractionation and hypofractionated RT in OS (Logrank test p = 0.06757) and RFS (Logrank test p = 0.43374). In the hypofractionation group, with an observation time median of 22.3 months, the OS median was 16.5 (95% CI 14.1–18.8) months; median RFS was 9.0 (95% CI 8.0–10.0) months. In the standard radiation regimen group, with a median of observation time of 24.4 months, the median OS was 15.0 (95% CI 14.1–17.1) months; median RFS is 9.0 (95% CI 9.0–10.0) months.&#x0D; Conclusion. Development and implementation of the measures designed to optimize the use of resources of medical facilities of Ukraine is a necessary condition for maintaining high-quality care for cancer patients in the conditions of full-scale military aggression, which has been ongoing since February 24, 2022. Increased application of hypofractionated approaches in radiation oncology can be considered as a potential tool for optimization of the use of resources of the healthcare system of Ukraine and enhancing public health.

Incidence, risk factors, and outcomes of immune-related adverse events (irAEs) in a prospective, pan-tumor population.

2662 Background: IrAEs associated with immune checkpoint inhibitors (ICIs) can result in morbidity and mortality. The incidence, spectrum, and risk factors for irAEs are usually reported from retrospective studies and clinical trials, which typically exclude patients (pts) with pre-existing autoimmune disease (AD). The prevalence and risk factors for irAEs in a diverse, pan-tumor, real-world setting is not well understood. Methods: From 06/2021 to 2/2023, we prospectively enrolled pts receiving ICIs (alone or in combination as standard-of-care) at a tertiary care center in this imCORE network study. Univariate and multivariate logistic regressions and survival curves were used to interrogate risk factors for irAE development and the relationship between irAEs, graded using CTCAE v5.0, and clinical response by RECIST 1.1. Results: 132 pts with prior ICI therapy were prospectively followed. Median age was 65 years (IQR 56-72), 35% were female, 69% were white, and 24% were black. Most common tumor histologies were: hepatocellular, renal cell, bladder, non-small cell lung, and head and neck carcinoma. 23% (n=30/132) received dual ICI (nivolumab+ipilimumab). In the whole cohort, 36.4% (n=48/132) of pts developed any-grade irAE and 10.6% (n=14/132) developed a severe irAE (grades 3-5). There were 2 fatal irAEs (n=1 hepatitis, n=1 myocarditis) representing 1.5% of the total cohort. The median time to first irAE was 1.8 months (mos; IQR 1.2-3.1) for anti-PDL1 monotherapy, 1.2 mos (IQR 0.7-2.2) for dual ICI, 4.4 mos (0.2-8.7) for PDL1+chemotherapy, and 2.1 mos (1.3-3.1) for PDL1+other. A subgroup of pts (10.6%; n=14/132) had pre-existing AD and 50% (n=7/14) had ever received immunosuppression for their AD. Among pts with AD, the incidence of irAEs was 57% (n=8/14) vs 33.9% (n=40/118) among those without AD. Antitumor response for pts with AD was 27.3% vs 25.8% those without AD. Receipt of dual ICI therapy was associated with increased risk of any-grade irAE (OR 2.87 p=0.02) and severe irAE (OR 40.9 p=0.004). Pts with any grade irAEs were significantly more likely to experience a partial/complete response vs pts without irAEs (OR 4.14 p=0.02) and this relationship was preserved after adjustment for single vs dual ICI. Pts who did not develop irAEs had an overall response rate (ORR) of 18.2%, mPFS of 3.5 mos (IQR 1.6-7.3), and mOS 7.3 mos (IQR 3.8-9.9) vs pts who developed any grade irAE who had an ORR of 37.8%, mPFS of 5.9 mos (IQR 3.3-8.8), and mOS 8.6 mos (IQR 4.9-11.4). Conclusions: In this pan-tumor, prospective cohort study of pts receiving ICI therapy in a real world setting, we identified that pts with pre-existing AD and those on dual ICI had increased risk of irAE development. This signals the need for closer monitoring, early recognition, and management of irAEs in these pts. In addition, pts who developed irAEs were more likely to experience partial or complete response in a diverse tumor cohort.

Risk of heart failure in patients with type 2 diabetes receiving insulin therapy: a meta-analysis of observational studies

Aim. To compare the effect of insulin therapy and oral hypoglycemic agents (OHAs) on the risk of heart failure (HF) in patients with type 2 diabetes (T2D) using different databases.Material and methods. The systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis included studies that compared the risk of HF in T2D patients, depending on the OHA therapy in the presence of a group of patients receiving insulin therapy. The inclusion criteria were a duration of treatment of at least two years with at least 1000 included patients. The analysis did not include studies that compared the types and regimens of insulin therapy without a control group (antidiabetic drugs), which included patients with acute complications of type 2 diabetes and unstable conditions associated with comorbidities, in which no clinical outcomes were reported. Search was conducted in August 2022 using several databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) at the Cochrane Library, Elibrary) using the following keywords: heart failure development, 2 type diabetes mellitus, insulin.Results. Of the 1085 publications found in the search, 5 retrospective observational cohort clinical trials, including a total of 179777 patients with a mean duration of treatment of 67,2 months, met all criteria and were included in the analysis. Statistical analysis of the relative risk (RR) of HF in T2D patients receiving insulin therapy revealed a RR increase in all studies with a total RR using fixed effects model of 2,598 (95% confidence interval (CI), 2,346-2,878; p&lt;0,001), while using the random effects model — 2,382 (95% CI, 1,565-3,626; p&lt;0,001). When checking the statistical heterogeneity of the studies, a high heterogeneity was revealed (I2=93,8%).Conclusion. Meta-analysis of 5 retrospective observational studies including 179777 patients with T2D with a mean duration of treatment of 67,2 months showed that insulin therapy (without insulin glargine and degludec) in comparison with OHAs (without sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide type 1 receptor agonists) significantly increased the RR for HF using a fixed effects model by 2,6 times, while using the random effects model — by 2,4 times (p&lt;0,001 for both).

Brachytherapy boost in anal canal cancer - A GEC ESTRO PDR task force meta-analysis.

A meta-analysis is presented comparing clinical outcomes and toxicities between high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy (BT) for anal cancer. Retrospective or prospective clinical trials were identified on electronical databases. Data were collected per Preferred Reporting Items for Systematic Reviews and meta-Analyses guidelines. Pooled effect size for HDR and PDR BT were compared using subgroup analyses. Nine retrospective studies with a total of 481 patients treated were included of which 219 with HDR and 262 with PDR. Significant differences were observed between the two groups for baseline characteristics and treatment. The cumulative proportion of stage T3-T4 was lower in the HDR group, 0.15 [95% confidence interval (CI) 0.07-0.29] vs 0.27 [95%CI 0.09-0.57] in the LDR group, p<0.001. Lower BT doses (in equivalent 2-Gy fraction dose) were given for patients in the HDR group, 11.9Gy [95%CI 8.2-15.5] vs 19.5Gy [95%CI 15.0-24.0] in the PDR group, p<0.001. No significant differences were found for clinical outcomes or toxicities. The pooled effect size of the overall survival at 5years for HDR and PDR was respectively 0.82 [95%CI 0.70-0.94] and 0.82 [95%CI 0.73-0.91], p>0.99. The 5years local control was 0.86 [95% confidence interval (CI) 0.81-0.91] and 0.83 [95%CI 0.77-0.89], p=0.62. Cumulative toxicity-related colostomy proportion was 0.04 [95%CI 0.02-0.09] and 0.03 [95%CI 0.02-0.07], p=0.85. Both modalities provided a good profile of tolerance and are effective organ conservative strategies for patients with anal canal cancer. In parallel with ongoing developments to better determine the optimal fractionation and dose for HDR-BT treatments, especially in large tumors, PDR BT still has a crucial role for dose escalation strategy in advanced cases.

Effect of Dexmedetomidine on Cardiac Surgery Patients.

Dexmedetomidine, an alpha-2 adrenoreceptor agonist that is widely used as a sedative medication, is becoming more and more attractive in clinical application on cardiac surgery patients. In this review, we aim to summarize and discuss both retrospective studies and clinical trials regarding the effect of dexmedetomidine on patients who underwent cardiac surgery (including coronary artery bypass grafting, valve surgery, aortic surgery, percutaneous coronary intervention, and so on), which illustrates that the clinical effects of dexmedetomidine could effectively reduce mortality, major complications, and the intensive care unit and hospital length of stay without comprising safety. In addition, inconsistent results from both retrospective studies and clinical trials have also been demonstrated. Although the effectiveness and safety of dexmedetomidine on cardiac surgery patients is suggested, high-quality clinical trials are needed for further verification.

Proposed Pharmacological Treatments for COVID-19: Previously Confirmed Drugs

Background: The outbreak of severe acute respiratory syndrome coronavirus-2, also called ‘coronavirus disease 2019’ (COVID-19), first appeared in December 2019 in Wuhan, China. COVID-19 is caused by an enveloped single-stranded RNA virus, which has affected more than 14 million people around the world and caused a high rate of mortality. It is notable that discovering new drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is time-consuming. Therefore, reviewing drugs, which have been previously designed for other purposes can be helpful and effective.&#x0D; Objectives: Studying the effects of previously approved drugs is important; thus, in this article, we reviewed studies on proposed drugs against COVID-19.&#x0D; Methods: The articles and information were collected from Google Scholar, ScienceDirect, and Scopus databases. We did our research based on keywords, like “therapeutics”, “pharmacology”, “Coronavirus”, “COVID-19”, “SARS”, and “MERS-CoV”. We also applied some filters, such as title/abstract, and ignored factors that could lead to bias and selective selection.&#x0D; Results: There is currently no cure for coronavirus, and most treatments have been effective to relieve symptoms. The treatment methods and drugs addressed in this article are chosen either from previous drugs against MERS and SARS, drugs that disrupt the life cycle of the coronavirus, or drugs that have been reviewed in retrospective studies and clinical trials.&#x0D; Conclusion: Prevention and treatment of COVID-19 remain a challenge, in particular for coronavirus and the treatments based on boosting the immune system and preventing virus replication. Epidemiological studies have shown that COVID-19 and SARS-COV transmission are relatively similar. This can help to select the appropriate drug. Thus, anti-inflammatory and antiviral drugs, such as remdesivir are used. Antimalarial drugs, such as hydroxychloroquine (HCQ) and chloroquine (CQ) along with estrogen receptor inhibitors, such as toremifene citrate, which has shown effective results against SARS and MERS, can influence the treatment process. However, more clinical trials are needed to determine the efficacy and side effects of drugs.

Efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation for locally advanced cervical cancer: A systematic review and meta-analysis (307)

Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI. Objectives: For locally advanced cervical cancer (LACC) patients without para-aortic lymph node metastasis, the standard treatment is pelvic radiotherapy plus concurrent chemotherapy. After standard treatment, 7-15% of patients had a recurrence in para-aortic lymph nodes. The present study aimed to evaluate the efficacy and side effects of modern radiotherapy in prophylactic extended field irradiation (EFI) for locally advanced cervical cancer (LACC). The present meta-analysis has been registered in PROSPERO (no. CRD42020167302). Methods: A systemic review and meta-analysis of recent studies retrieved from PubMed, EMBASE, and Cochrane databases from the establishment of the database to March 2021 was performed. All LACC patients with negative para-aortic lymph nodes received concurrent chemoradiotherapy. The experimental group consisted of patients undergoing pelvic irradiation plus prophylactic EFI, but the control group was undergoing pelvic irradiation. The primary outcomes were overall survival (OS) and para-aortic control. The secondary outcomes were: disease-free survival (DFS)/progression-free survival (PFS), distant metastasis, pelvic control, and toxicities. The quality of RCT was evaluated by the Cochrane bias risk tool. The quality of the retrospective study was evaluated by the Newcastle Ottawa scale (NOS). Revman5.3 software was used for statistical analysis. Results: A total of 180 studies were evaluated and six literatures met the inclusion criteria. Prophylactic EFI significantly improved 5-year OS (HR: 0.36 [0.22-0.59], p <0.0001) and DFS (3-year: HR: 0.53 [0.32-0.87], p=0.01; 5-year: HR: 0.45 [0.27-0.77], p=0.004). Prophylactic EFI reduced the rate of para-aortic failure (3-year: OR: 0.09 [0.01-0.70], p=0.02; 5-year: OR: 0.09 [0.03-0.30], p<0.0001) and distant metastasis (3-year: OR: 0.22 [0.11-0.45], p <0.0001; 5-year: OR: 0.53 [0.33-0.87], p=0.01). EFI did not increase the gastrointestinal toxicities (acute: OR: 1.94 [0.59-6.35], p=0.27; chronic: OR: 1.24 [0.65-2.40], p=0.51) and acute hematotoxicities (leukopenia: OR: 1.59 [0.98-2.59], p=0.06; thrombocytopenia: OR: 2.81 [0.87-9.03], p=0.08). Conclusions: The results of the present study suggested that prophylactic EFI using modern radiation techniques is beneficial for patients with LACC. Because five out of six pieces of literature included in our study are retrospective studies, prospective, large sample, and multicenter clinical trials are needed to further verify the impact of prophylactic EFI.