Envisioning Academic Global Oncologists: Proposed Competencies for Global Oncology Training From ASCO.

Recognizing the rising incidence, prevalence, and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has committed to expanding its engagement at a global level. In 2017, the ASCO Academic Global Oncology Task Force sought to define the potential role for ASCO in supporting global oncology as an academic field. A set of recommendations to advance the status of global oncology as an academic discipline were created through a consensus-based process involving participation by a diverse group of global oncology and global health practitioners; these recommendations were then published. The recommendations included developing a set of global oncology competencies for trainees and faculty interested in a career in academic global oncology. Here, we describe the global oncology competencies developed by this task force. These competencies consist of knowledge and skills needed in general global health as well as cancer-specific care and research, including understanding global cancer health disparities, defining unique resources and needs in low- and middle-resource settings, and promoting international collaboration. Although the competencies were originally developed for US training programs, they are intended to be widely applicable globally. By formalizing the training of oncologists and supporting career pathways in the field of global oncology, we can make progress in achieving global equity in cancer care and control.

Correction: Bolocan et al. Convolutional Neural Network Model for Segmentation and Classification of Clear Cell Renal Cell Carcinoma Based on Multiphase CT Images. J. Imaging 2023, 9, 280.

In the original publication [...].

Convolutional Neural Network Model for Segmentation and Classification of Clear Cell Renal Cell Carcinoma Based on Multiphase CT Images.

(1) Background: Computed tomography (CT) imaging challenges in diagnosing renal cell carcinoma (RCC) include distinguishing malignant from benign tissues and determining the likely subtype. The goal is to show the algorithm's ability to improve renal cell carcinoma identification and treatment, improving patient outcomes. (2) Methods: This study uses the European Deep-Health toolkit's Convolutional Neural Network with ECVL, (European Computer Vision Library), and EDDL, (European Distributed Deep Learning Library). Image segmentation utilized U-net architecture and classification with resnet101. The model's clinical efficiency was assessed utilizing kidney, tumor, Dice score, and renal cell carcinoma categorization quality. (3) Results: The raw dataset contains 457 healthy right kidneys, 456 healthy left kidneys, 76 pathological right kidneys, and 84 pathological left kidneys. Preparing raw data for analysis was crucial to algorithm implementation. Kidney segmentation performance was 0.84, and tumor segmentation mean Dice score was 0.675 for the suggested model. Renal cell carcinoma classification was 0.885 accurate. (4) Conclusion and key findings: The present study focused on analyzing data from both healthy patients and diseased renal patients, with a particular emphasis on data processing. The method achieved a kidney segmentation accuracy of 0.84 and mean Dice scores of 0.675 for tumor segmentation. The system performed well in classifying renal cell carcinoma, achieving an accuracy of 0.885, results which indicates that the technique has the potential to improve the diagnosis of kidney pathology.

Wolcott-Rallison Syndrome, a Rare Cause of Permanent Diabetes Mellitus in Infants-Case Report.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient's need for comfort and lack of distress with the clinicians' need for adequate information regarding the patient's glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

Fully digital workflow for retrofitting a new crown to an existing removable partial denture.

A fully digital technique for retrofitting a new crown to a removable partial denture (RPD) is presented. The conventional crown preparation was followed by intraoral scanning of the preparation, the antagonists, and the occlusal relationship and by scanning the RPD both in situ and outside the oral cavity. All the standard tessellation language (STL) files were indexed in a design software program, and the new crown was designed. After conventional dynamic adaptation against the antagonist teeth in the software program, the existing RPD was designated as the antagonist cast, and a second regular static adaptation was performed. This straightforward approach produced a crown which fit the occlusal rest and reciprocating arm without sending the existing prosthesis to the dental laboratory.

Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial.

PURPOSE: Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years' follow-up. METHODS: Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up. RESULTS: Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78-1.93) for DFS, 1.31 (0.86-2.01) for PFS, and 1.10 (0.57-2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups. CONCLUSION: The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014).

Recommendations from the ASCO Academic Global Oncology Task Force.

In recognition of the rising incidence and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has prioritized efforts to enhance its engagement at a global level. Among the recommendations included in the 2016 Global Oncology Leadership Task Force report to the ASCO Board of Directors was that ASCO should promote the recognition of global oncology as an academic field. The report suggested that ASCO could serve a role in transitioning global oncology from an informal field of largely voluntary activities to a more formal discipline with strong research and well-defined training components. As a result of this recommendation, in 2017, ASCO formed the Academic Global Oncology Task Force (AGOTF) to guide ASCO's contributions toward formalizing the field of global oncology. The AGOTF was asked to collect and analyze key issues and barriers toward the recognition of global oncology as an academic discipline, with an emphasis on training, research, and career pathways, and produce a set of recommendations for ASCO action. The outcome of the AGOTF was the development of recommendations designed to advance the status of global oncology as an academic discipline.

Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis.

OBJECTIVE: Expression of dipeptidylpeptidase 4 (DPP-4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP-4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP-4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis (SSc). METHODS: Expression of DPP-4 in skin biopsy samples and dermal fibroblasts was analyzed by real-time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP-4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP4 using sitagliptin and vildagliptin. The effects of DPP4 inhibition were analyzed in human dermal fibroblasts and in different mouse models of SSc (each n = 6). RESULTS: The expression of DPP-4 and the number of DPP-4-positive fibroblasts were increased in the fibrotic skin of SSc patients, in a transforming growth factor ß (TGFß)-dependent manner. DPP-4-positive fibroblasts expressed higher levels of myofibroblast markers and collagen (each P < 0.001 versus healthy controls). Overexpression of DPP4 promoted fibroblast activation, whereas pharmacologic inhibition or genetic inactivation of DPP4 reduced the proliferation, migration, and expression of contractile proteins and release of collagen (each P < 0.001 versus control mice) by interfering with TGFß-induced ERK signaling. DPP4-knockout mice were less sensitive to bleomycin-induced dermal and pulmonary fibrosis (P < 0.0001 versus wild-type controls). Treatment with DPP4 inhibitors promoted regression of fibrosis in mice that had received bleomycin challenge and mice with chronic graft-versus-host disease, and ameliorated fibrosis in TSK1 mice (each P < 0.001 versus untreated controls). These antifibrotic effects were associated with a reduction in inflammation. CONCLUSION: DPP-4 characterizes a population of activated fibroblasts and shows that DPP-4 regulates TGFß-induced fibroblast activation in the fibrotic skin of SSc patients. Inhibition of DPP4 exerts potent antifibrotic effects when administered in well-tolerated doses. As DPP4 inhibitors are already in clinical use for diabetes, these results may have direct translational implications for the treatment of fibrosis in patients with SSc.

Individuals with autism have higher 8-Iso-PGF2α levels than controls, but no correlation with quantitative assay of Paraoxonase 1 serum levels.

Autism spectrum disorder (ASD) represents a very large set of neurodevelopmental issues with diverse clinical outcomes. Various hypotheses have been put forth for the etiology of autism spectrum disorder, including issues pertaining to oxidative stress. In this study, we conducted measurements of serum 8-Iso-Prostaglanding F2 α (8-iso-PGF2α, which is the results of non-enzimatically mediated polyunsaturated fatty acid oxidation) in a population of individuals with autism and a control group of age and sex matched controls. A quantitative assay of Paraoxonase 1 (PON1) was conducted. Data regarding comorbidities, structural MRI scans, medication, intelligence quotient (IQ) and Childhood Autism Rating Scale scores (CARS) were also included in our study. Our results show that patients diagnosed with autism have higher levels of 8-iso-PGF2α than their neurotypical counterparts. Levels of this particular metabolite, however, do not correlate with quantitative serum levels of Paraoxonase 1, which has been shown to be altered in individuals with autism. Neither 8-iso-PGF2α nor quantitative levels of PON1 provide any meaningful correlation with clinical or neuroimaging data in this study group. Future research should focus on providing data regarding PON 1 phenotype, in addition to standard quantitative measurements, in relation to 8-iso-PGF2α as well as other clinical and structural brain findings.

Cancer Care and Control as a Human Right: Recognizing Global Oncology as an Academic Field.

The global burden of cancer incidence and mortality is on the rise. There are major differences in cancer fatality rates due to profound disparities in the burden and resource allocation for cancer care and control in developed compared with developing countries. The right to cancer care and control should be a human right accessible to all patients with cancer, regardless of geographic or economic region, to avoid unnecessary deaths and suffering from cancer. National cancer planning should include an integrated approach that incorporates a continuum of education, prevention, cancer diagnostics, treatment, survivorship, and palliative care. Global oncology as an academic field should offer the knowledge and skills needed to efficiently assess situations and work on solutions, in close partnership. We need medical oncologists, surgical oncologists, pediatric oncologists, gynecologic oncologists, radiologists, and pathologists trained to think about well-tailored resource-stratified solutions to cancer care in the developing world. Moreover, the multidisciplinary fundamental team approach needed to treat most neoplastic diseases requires coordinated investment in several areas. Current innovative approaches have relied on partnerships between academic institutions in developed countries and local governments and ministries of health in developing countries to provide the expertise needed to implement effective cancer control programs. Global oncology is a viable and necessary field that needs to be emphasized because of its critical role in proposing not only solutions in developing countries, but also solutions that can be applied to similar challenges of access to cancer care and control faced by underserved populations in developed countries.

Treatment of a Prader-Willi Patient with Recurrent Catatonia.

Prader-Willi is a genetic disorder characterized by neonatal hypotonia, hyperphagia, short stature, hypogonadism, and mental delay. This disorder can result from multiple mechanisms, most commonly a deletion of paternal chromosome 15, leaving a single maternally derived chromosome 15. Individuals who have a maternal uniparental disomy of chromosome 15 have a higher risk for developing psychosis compared to other forms of Prader-Willi. The following report details the treatment course of a 24-year-old female with Prader-Willi and recurrent catatonia. The patient initially had a positive lorazepam challenge test but subsequently failed treatment with benzodiazepines. She then received eight electroconvulsive therapy (ECT) treatments after which she showed improvement from initial catatonic state. However, the resolution in her symptoms did not follow a linear course but would show periods of improvement followed by a return of catatonic features. This case provides an example of the complexity of treatment of a patient with a genetic disorder and recurrent catatonia.

Treatment of breast cancer in countries with limited resources.

Early and accurate diagnosis of breast cancer is important for optimizing treatment. Local treatment of early stage breast cancer involves either mastectomy or breast-conserving surgery followed by whole-breast irradiation. The pathologic and biologic properties of a woman's breast cancer may be used to estimate her probability for recurrence of and death from breast cancer, as well as the magnitude of benefit she is likely to receive from adjuvant endocrine therapy or cytotoxic chemotherapy. Ovarian ablation or suppression with or without tamoxifen is an effective endocrine therapy in the adjuvant treatment of breast cancer in premenopausal women with estrogen receptor (ER)-positive or ER-unknown breast cancer. In postmenopausal women with ER- and/or progesterone receptor (PR)-positive or PR-unknown breast cancer, the use of tamoxifen or anastrozole is effective adjuvant endocrine therapy. The benefit of tamoxifen is additive to that of chemotherapy. Cytotoxic chemotherapy also improves recurrence rates and survival, with the magnitude of benefit decreasing with increasing age. Substantial support systems are required to optimally and safely use breast-conserving approaches to local therapy or cytotoxic chemotherapy as systemic therapy. Locally advanced breast cancer (LABC) accounts for at least half of all breast cancers in countries with limited resources and has a poor prognosis. Initial treatment of LABC with anthracycline-based chemotherapy is standard and effective. Addition of a sequential, neoadjuvant taxane thereafter increases the rate of pathologic complete responses. Neoadjuvant endocrine therapy may benefit postmenopausal women with hormone receptor-positive LABC. After an initial response to neoadjuvant chemotherapy, the use of local-regional surgery is appropriate. Most women will require a radical or modified radical mastectomy. In those women in whom mastectomy is not possible after neoadjuvant chemotherapy, the use of whole-breast and regional lymph node irradiation alone is appropriate. In those women who cannot receive neoadjuvant chemotherapy because of resource constraints, mastectomy with node dissection, when feasible, may still be considered in an attempt to achieve local-regional control. After local-regional therapy, most women should receive additional systemic chemotherapy. Women with LABC that has a positive or unknown hormone receptor status benefit from endocrine therapy with tamoxifen. The treatment of LABC requires multiple disciplines and is resource intensive. Efforts to reduce the number of breast cancers diagnosed at an advanced stage thus have the potential to improve rates of survival while decreasing the use of limited resources.

Histochemical and histoenzymic researches in coronary sudden death.

Using Lie's technique in order to evidence the fuchsinophilia of the early ischaemic zones and Falck-Hillarp's technique to appreciate the disappearance of the myocardial adrenergic network, the authors followed up the concordance between the precocity of the ischaemia and the frequency of the acidophilia. Studying 54 cases of coronary sudden death by using 100-300 slides in each case, the fuchsinophilic zones were evidenced in 46 per cent of the cases, aspects indicating the morphologic substrate of the sudden death with ectopic ventricular electrical activity centres. The results of fluorescence Falck-Hillarps's technique are the same as those obtained by light microscopy, which is to be preferred in routine practice. Farber-Louvière's microscopic histoenzymic method for succinate-dehydrogenase presents multiple advantages, so that it is preferable to Kollin-Neoral's macroscopic reaction.