Reduction of ventricular arrhythmias with synchronized LV pacing—fact,fiction, or fortuitous

Journal of Interventional Cardiac Electrophysiology -     

Nanotechnology for colorectal cancer detection and treatment

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Across the globe, people in the age group older than 50 are at a higher risk of CRC. Genetic and environmental risk factors play a significant role in the development of CRC. If detected early, CRC is preventable and treatable. Currently, available screening methods and therapies for CRC treatment reduce the incidence rate among the population, but the micrometastasis of cancer may lead to recurrence. Therefore, the challenge is to develop an alternative therapy to overcome this complication. Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells, with enhanced therapeutic efficacy. Additionally, nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies. The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment. These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment. This review discusses contemporary methods of CRC screening and therapies for CRC treatment, while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects. In addition, this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.     

CNS Maturation Process in Children and Adolescents in the Northern Region of the Russian Federation and Its Reflection in the Dynamics of Integral EEG Parameters

Neuroscience and Behavioral Physiology - We present here results from analysis of the formation of brain bioelectrical activity in children and adolescents living in the northern region of Russia...     

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Comparison study of patient demographics and patient-related risk factors for peri-prosthetic joint infections following primary total shoulder arthroplasty

BackgroundWhile studies have demonstrated favorable outcomes in utilization of primary total shoulder arthroplasty (TSA) for the treatment of glenohumeral osteoarthritis (OA), adverse events such as infections can still occur. Periprosthetic joint infections (PJIs) are associated with worse outcomes and patient morbidity. The purpose of this study was to: (1) compare patient demographics amongst TSA patients with and without PJIs following primary TSA; and (2) identify patient-related risk factors for PJIs following primary TSA.MethodsPatients undergoing primary TSA for the treatment of glenohumeral OA were identified using the Mariner administrative claims database by CPT code 23,472. Laterality modifiers were utilized to ensure PJIs were developing in the correct laterality as those patients undergoing primary TSA. Inclusion for the study group consisted of patients who developed PJIs within 2-years after the index procedure, whereas patients who did not develop PJIs served as the comparison cohort. Primary outcomes analyzed included patient demographics and patient-related risk factors for PJIs following primary TSA. A stepwise backwards elimination multivariate binomial logistic regression analyses was performed to determine the odds (OR) of PJIs in patients undergoing primary TSA. A P value less than .05 was considered statistically significant.ResultsThe query yielded 15,396 patients who underwent primary TSA for glenohumeral OA, of which 191 patients developed PJIs and 15,205 did not develop PJIs. The study found statistically significant differences amongst patients who did and did not develop PJIs following primary TSA with respect to age, sex, and presence of comorbid conditions. Risk factors associated with developing PJIs following primary TSA included: pathologic weight loss (OR: 2.06, P < .0001), obesity (OR: 1.56, P = .0001), male sex (OR: 1.52, P = .007), and peripheral vascular disease (OR: 1.46, P = .022).ConclusionAs the number of primary TSAs for the treatment of glenohumeral OA increase worldwide, identifying modifiable risk-factors to reduce the incidence of infection is critical. The study found various modifiable and non-modifiable risk factors associated with developing PJIs following primary TSA. This study is valuable to orthopedists in order to identify and risk-stratify patients with regard to PJI in the setting of primary TSA for OA.Level of EvidenceLevel III; Case-Control Study     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.