Stromal inflammation, fibrosis and cancer: An old intuition with promising potential.

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment. Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis. Chronic inflammation can promote tumorigenesis via growth factor/cytokine-mediated cellular proliferation, apoptotic resistance, immunosuppression; and free-radical-induced oxidative deoxyribonucleic acid damage. Fibrosis could cause a perturbation in the dynamics of the tumour microenvironment, potentially damaging the genome surveillance machinery of normal epithelial cells. In this review, we will provide an in-depth discussion of various diseases characterised by inflammation and fibrosis that have been associated with an increased risk of malignancy. In particular, we will present a comprehensive overview of the impact of alterations in stromal composition on tumorigenesis, induced as a consequence of inflammation and/or fibrosis. Strategies including the application of various therapeutic agents with stromal manipulation potential and targeted cancer screening for certain inflammatory diseases which can reduce the risk of cancer will also be discussed.

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review.

BACKGROUND: Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis. AIM: To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB. METHODS: The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). RESULTS: Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, P < 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis (P < 0.01) whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis (P < 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results. CONCLUSION: This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

Pooled Testing for Expanding COVID-19 Mass Surveillance.

Diagnostic testing to identify patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role to control the coronavirus disease (COVID-19) pandemic. While several countries have implemented the use of diagnostic testing in a massive scale as a cornerstone for infection control and surveillance, other countries affected by the pandemic are hampered by its limited testing capacity. Pooled testing was first introduced in the 1940s and is now used for screening in blood banks. Testing is done by pooling multiple individual samples together. Only in the case of a positive pool test would individual samples of the pool be tested, thus substantially reducing the number of tests needed. Several studies regarding their use for SARS CoV-2 have been done in the United States, Israel, and Germany. Studies have shown that an individual positive sample can still be detected in pools of up to 32 samples, and possibly even 64 samples, provided that additional polymerase chain reaction (PCR) amplification cycles are conducted with a sensitivity of 96%. Simulation studies to determine optimal pool size and pooling techniques have also been conducted. Based on these studies, pooled testing is shown to be able to detect positive samples with sufficient accuracy and can easily be used with existing equipment and personnel for population-wide screening.

Combating Donor Organ Shortage: Organ Care System Prolonging Organ Storage Time and Improving the Outcome of Heart Transplantations.

INTRODUCTION: Cardiovascular diseases are the number one cause of death globally contributing to 37% of all global deaths. A common complication of cardiovascular disease is heart failure, where, in such cases, the only solution would be to conduct a heart transplant. Every 10 minutes a new patient is added to the transplant waiting list. However, a shortage of human donors and the short window of time available to find a correct match and transplant the donors' heart to the recipient means that numerous challenges are faced by the patient even before the operation could be done, reducing their chances of living even further. METHODS: This review aims to evaluate the application of the Organ Care System (OCSTM) in improving the efficiency of heart storage based on journal articles obtained from PubMed, Elsevier Clinical Key, and Science Direct. RESULTS: Studies have shown that OCS is capable of extending the ischemic time 120 minutes longer than conventional methods without any detrimental effect on the recipient nor donor's safety. Based on the PROTECT I and PROCEED II study, 93% of transplantation recipients using the OCS system passed through the 30-day mortality period. DISCUSSION: OCS is able to prolong the ischemic time of donors' hearts by perfusing the organ at 34°C in a beating state, potentially reducing the detrimental effect of cold storage and providing additional assessment options. Another clear advantage is the implanting surgeon can assess the quality of the donor heart before surgery as well as providing a time safety buffer in unanticipated circumstances that will reduce the mortality risk of transplant recipients.

Evaluation of Serum Biomarkers and Other Diagnostic Modalities for Early Diagnosis of Preeclampsia.

Objective: Preeclampsia (PE) is a multi-systemic complication of pregnancy often characterised with the onset of hypertension and proteinuria after 20 weeks of gestation. Today, PE is the leading cause of maternal and perinatal morbidity and mortality worldwide. An early detection of PE would allow a chance to plan the appropriate monitoring and for clinical management to be immediately done following early detection thus making prophylactic strategies much more effective. Materials and methods: This systematic review aims to evaluate the potential of the various serum biomarkers and diagnostic modalities (uterine artery Doppler, MAP, and maternal history) available for early prediction of PE with articles included and obtained through MEDLINE Full Text, Pubmed, Science Direct, ProQuest, SAGE, Taylor and Francis Online, Google Scholar, HighWire and Elsevier ClinicalKey. Results: Ninety-five articles were found that fulfilled all of our inclusion criteria. Placental growth factor (PlGF), pregnancy associated plasma protein A (PAPP-A), soluble fms-like tyrosine kinase (sFLT) and placental protein 13 (PP-13) were the most commonly studied biomarkers. Whereas uterine Doppler scanning and Mean Arterial Pressure (MAP) were the most commonly studied out of other modalities. Conclusion: Current evidence shows serum biomarkers such as PIGF, PP-13 and sFlt yielded the best results for a single biomarker with others having conflicting results. However, a combination model with other diagnostic modalities performed better than a single biomarker. In the future, new techniques will hopefully provide sets of multiple markers, which will lead to a screening program with clinically relevant performance. However further studies are required to improve current methods.

Risk and Benefits of Statins in Glucose Control Management of Type II Diabetes.

Worldwide statins are considered to be the first-line pharmacological treatment for dyslipidemia and reducing the risk of coronary heart disease. However, recently various studies have shown its adverse effect on glucose control among diabetic patients and the U.S. Food and Drug Administration have revised statin drug labels to include information that increases in fasting serum glucose and glycated hemoglobin levels have been reported. This systematic review objective is to evaluate the risks and benefits of statins in glucose control management of type 2 diabetes patients based on the 44 published journal articles included and obtained through MEDLINE full text, PubMed, Science Direct, Pro Quest, SAGE, Taylor and Francis Online, Google Scholar, High Wire, and Elsevier Clinical Key. Statins were found to affect glucose control through several ways, namely, by affecting insulin production and secretion by ß-pancreatic cells, insulin resistance, insulin uptake by the muscles and adipocytes and production of adipokines. Current evidence available shows that most of the statins give unfavorable side effects with regards to glucose control among diabetic patients. A dose-dependent and time-dependent effect was also observed in some statins which may be present among other statins as well.

The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma.

Basal Cell Carcinoma (BCC) is the most common type of malignant cancer found in the world today with a 3-10% increase in incidence each year. The American Cancer Society reported that 8 out of 10 patients with skin cancer are suffering from BCC with over 2 million new cases each year. BCC needs to be detected at the early stages to prevent local destruction causing disabilities to patients and increasing treatment costs. Furthermore, BCC patients who have undergone surgery are still at risk for recurrence, especially when the surgery performed fails to remove all the BCC cells, even when conventional histopathological testing after surgery has reported a surgically free margin. This review aims to evaluate studies on the use of BerEP4 immunohistochemistry staining on pathological sections of various types of BCC as well as its shortfalls. BerEP4 is a monoclonal antibody which detects specific epithelial-glycoprotein-adhesion-molecules (EpCAM) found on BCC cells. Various studies have shown that BerEP4 has a high sensitivity and specificity in detecting only BCC cells. The use of BerEP4 immunohistochemistry testing for the routine examination of cases of BCC is expected to be able to increase and improve early diagnosis as well as prevent recurrence after surgery.