Implementation of breast cancer continuum of care in low- and middle-income countries during the COVID-19 pandemic

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Burden of tracheal, bronchus, and lung cancer in North Africa and Middle East countries, 1990 to 2019: Results from the GBD study 2019

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Employing 18F-FDG PET/CT for distinguishing benign from metastatic adrenal masses

Background: Metastatic adrenal disease can occur in a wide diversity of malignancies. Distinguishing benign from metastatic adrenal masses in oncologic patients is vital. Objective: To appraise the 18F-FDG PET/CT performance for distinguishing benign from metastatic adrenal masses. Material and methods: In the current prospective study, 21 patients with proven extra-adrenal primary malignancy, having adrenal masses ≥10 mm on the axial CT images of their PET/CT examinations, were enrolled. Positive PET findings for malignancy were considered if the mass showed FDG uptake equivalent to or more prominent than the FDG liver uptake. Alternatively, negative PET findings for malignancy were considered if the mass showed FDG uptake not as much of the FDG liver uptake. Afterward, the obtained results were correlated with serial imaging follow-up or histopathological diagnosis by surgery or percutaneous biopsy as the diagnostic standard of reference. Results: An overall number of 24 adrenal masses was diagnosed. Positive PET/CT results were found in 14 adrenal masses. All were finally considered to be metastases by serial imaging follow-up (n = 8) and histopathological analysis by surgery (n = 1) and percutaneous biopsy (n = 5). Accordingly, no false positive result was obtained. Negative PET/CT results were observed in 10 adrenal masses, 9 of them were finally confirmed to be benign by serial imaging follow-up. The remaining mass was finally confirmed to be metastasis by percutaneous biopsy and hence, it represented the false negative result. 93% sensitivity, 100% specificity and 96% accuracy for identifying adrenal metastases were obtained. Conclusion: 18F-FDG PET/CT is a precise, non invasive modality for distinguishing benign from metastatic adrenal masses in oncologic patients

Can unenhanced multiparametric MRI substitute gadolinium-enhanced MRI in the characterization of vertebral marrow infiltrative lesions?

Purpose: To assess the diagnostic effectiveness of unenhanced-multiparametric magnetic resonance imaging (mp MRI) as an alternative to gadolinium (Gad)-enhanced MRI in the characterization of vertebral marrow infiltrative lesions. Patients and methods: A prospective evaluation of fifty-six patients with suspected or untreated vertebral metastases undergoing MRI of the spine at 1.5 T was carried out. Two groups of sequences were assigned and compared for the characterization of marrow infiltrative lesions: group [A] unenhanced-mp MRI (including T1-weighted, T2-weighted, short time inversion recovery (STIR), diffusion weighted imaging (DWI) and in/opposed phase sequences) and group [B] gadolinium-enhanced MRI (including T1-weighted, T2-weighted, STIR and T1-weighted fat-suppressed gadolinium-enhanced sequence). Qualitative and quantitative image analysis was performed and compared. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for both imaging techniques were calculated. Results: There was no statistical significant difference between unenhanced-multiparametric MRI and gadolinium-enhanced MRI as regards their diagnostic performance in differentiating benign from malignant vertebral marrow infiltrative lesions (p > 0.05) with calculated sensitivity (94% vs. 97%), specificity (92% vs. 88%), positive predictive value (94% vs. 91%), negative predictive value (92% vs. 95%) and (93% vs. 93%) accuracy. Conclusion: Unenhanced-multiparametric MRI is compatible with gadolinium-enhanced MRI in reliable characterization of marrow infiltrative lesions. The routine MRI protocol of cancer patients should be altered to accommodate the evolving MRI technology and cost effectively substitute the need for a gadolinium enhanced scan

Can Three-dimensional (3D) power Doppler and uterine artery Doppler differentiate between fibroids and adenomyomas?

Purpose: To determine if the three-dimensional power Doppler and uterine arteries Doppler were able to differentiate between fibroids and adenomyomas. Methods: 123 patients who were scheduled for hysterectomy were enrolled in the study. They were evaluated by ultrasound before hysterectomy. We included only cases with either fibroids or adenomymas. For each benign myometrial mass, mass volume, 3D power Doppler vascularization index (VI), flow index (FI) and vascularization flow index (VFI) and uterine artery Doppler indices were measured. The results were compared with the histopathological examination. Results: No significant difference was detected between the volume of the fibroids or the adenomyomas (P = 0.896). There was significant difference in the vascular location of the power Doppler flow between fibroids and adenomyomas being more scattered in adenomyoma and more peripheral in fibroids (P < 0.00). In fibroids, higher 3D power Doppler vascular flow (VI = 2.42 ± 2.0, FI = 39.931 ± 5.8 and VFI = 1.29 ± 1.54) than adenomyomas (VI = 1.19 ± 1.04, FI = 28.33 ± 6.88, VFI = 0.89 ± 0.49). That was statistically significant (P = 0.005, 0.00, 0.004) respectively. The uterine artery Doppler indices (RI, PI) showed no significant difference between fibroids and adenomyoma (P = 0.349, 0.067). Conclusion: 3D power Doppler can differentiate between fibroids and adenomyomas. The uterine arteries Doppler Can’t differentiate between fibroids and adenomyomas

Optimizing Treatment Selection and Sequencing Decisions for First-Line Maintenance Therapy of Newly Diagnosed Advanced Ovarian Cancer– International considerations amongst upper middle- and high-income countries (UMIC and HIC)

The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, primarily from low- and middle-income countries, met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with BRCA1/2 mutations; hence, BRCA testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on BRCA and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteria has hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention

In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity

(1) Background: The coronavirus (COVID-19) pandemic is still a major global health problem, despite the development of several vaccines and diagnostic assays. Moreover, the broad symptoms, from none to severe pneumonia, and the various responses to vaccines and the assays, make infection control challenging. Therefore, there is an urgent need to develop non-invasive biomarkers to quickly determine the infection severity. Circulating RNAs have been proven to be potential biomarkers for a variety of diseases, including infectious ones. This study aimed to develop a genetic network related to cytokines, with clinical validation for early infection severity prediction. (2) Methods: Extensive analyses of in silico data have established a novel IL11RA molecular network (IL11RNA mRNA, LncRNAs RP11-773H22.4 and hsa-miR-4257). We used different databases to confirm its validity. The differential expression within the retrieved network was clinically validated using quantitative RT-PCR, along with routine assessment diagnostic markers (CRP, LDH, D-dimmer, procalcitonin, Ferritin), in100 infected subjects (mild and severe cases) and 100 healthy volunteers. (3) Results: IL11RNA mRNA and LncRNA RP11-773H22.4, and the IL11RA protein, were significantly upregulated, and there was concomitant downregulation of hsa-miR-4257, in infected patients, compared to the healthy controls, in concordance with the infection severity. (4) Conclusion: The in-silico data and clinical validation led to the identification of a potential RNA/protein signature network for novel predictive biomarkers, which is in agreement with ferritin and procalcitonin for determination of COVID-19 severity

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661–PTPN11 mRNA Axis

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221–miR-661–PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients’ sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers