Perspectives From a Regional Plastic Surgery Centre on Evidence for the Purported Link Between SGLT2 Inhibitors and Fournier's Gangrene

Introduction: The recent report issued by the MHRA indicating an association of Sodium glucose linked transporter type 2 (SGLT2) Inhibitors with the contraction of Fournier's Gangrene (FG), has been drawn with insufficient supporting evidence and without an adequately powered study to make any meaningful assertions or recommendations. We aimed to look specifically at the currently available dataset used to link SGLT2 Inhibitors to FG and highlight what conclusions or inferences can meaningfully be made, in particular the power of any study that would be required to make sensible conclusions.Methods: World literature review of SGLT2 Inhibitors and FG was performed. With a subsequent 10-year review of cases of FG seen in a regional burns and plastics centre. Data was collected retrospectively from the coding department at Whiston Hospital for all patients with necrotising fasciitis. An electronic document management system was used to identify patients with FG specifically as well as their diabetes state and medication history.Results: Seventy-eight patients were admitted with FG, of whom 32 had diabetes mellitus (DM). Of those with DM none was taking an SGLT2 Inhibitor, 17 patients were taking metformin, a further nine patients were taking a second line medication and 14 required insulin injections.Discussions: DM is a known major risk factor for FG, which is clearly observed in our patient cohort. The risk of patients with DM developing FG is irrespective of the medication patients are taking. The current articles and reports published have little ground to claim an association between SGLT2 Inhibitors and FG and are missing the crucial message that needs to be conveyed to the public: that DM is a major risk factor for FG and patients suffering with diabetes need to be extra vigilant.

Age-Associated Epigenetic Alterations, Somatic Mutations, and Their Crosstalk in Alzheimer’s Disease

Aging is the major risk factor for Alzheimer’s Disease (AD), and as life expectancy increases, neurodegeneration will continue to afflict an ever-increasing proportion of the population. While numerous theories are attempting to explain the drivers behind AD pathology, what unites them is the observation that AD is reliably associated with a progressive buildup of age-related molecular changes. Because of the varying clinical presentations of AD in patients with similar genetic backgrounds, it has been postulated that epigenetics may be implicated in its etiology. Building on our prior work showing that AD pathology is linked to alterations in age-related DNA CpG methylation (DNAme) across various brain regions, we use state-of-the-art machine learning approaches to identify patterns of molecular damage in postmortem brain samples. We show that alterations in DNAme are associated with accelerated biological aging, AD, and the APOE e4 genotype, which is a major risk factor for AD. We also demonstrate that these associations are present in the PFC but not cerebellum -- in line with the current understanding of AD progression in the brain. Finally, we perform whole-exome sequencing and protein mass spectrometry on the same brain samples to test our hypothesis as to whether AD-associated alterations of DNAme are linked with the accumulation of somatic mutations that affect the structural and binding properties of protein epigenetic regulators.

Osteoradionecrosis of the Jaws Due to Teeth Extractions during and after Radiotherapy: A Systematic Review

Teeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. Methods: This systematic review was conducted according to PRISMA protocol, and the PROSPERO registration number was CRD42018079986. An electronic search was performed on the following search engines: PubMed, Scopus, and Web of Science. A cumulative meta-analysis was performed. Results: Two thousand two hundred and eighty-one records were screened, and nine were finally included. This systematic review revealed an ORN incidence of 5.8% (41 patients out of 462, 95% CI = 2.3–9.4); 3 ORN developed in the maxilla. No other clinical risk factors were detected. Conclusion: Post-RT teeth extractions represent a major risk factor for ORN development, especially in the mandible, with a diminishing trend in the last years. Further research on other possible risk factors might improve this evidence.

SARS-CoV-2 and Pre-Tamponade Pericardial Effusion. Could Sotos Syndrome Be a Major Risk Factor?

Pericarditis with pericardial effusion in SARS CoV-2 infection is a well-known entity in adults. In children and adolescents, only a few cases have been reported. Here, we present here a case of a 15-year-old girl affected by Sotos syndrome with pre-tamponed pericardial effusion occurred during SARS-CoV-2 infection. A possible relation between SARS-CoV-2 pericarditis and genetic syndromes, as a major risk factor for the development of severe inflammation, has been speculated. We emphasize the importance of active surveillance by echocardiograms when SARS-CoV-2 infection occurs in combination with a genetic condition.

The Seroprevalence of Toxoplasma Gondii in Cats at the House of Maternal Women with Toxoplasmosis in Badung, Indonesia

Toxoplasmosis is a zoonotic disease caused by infection with the parasite called Toxoplasma gondii (T. gondii). The health and social impacts of the infection are enormous, including miscarriage, hydrocephalus, blindness, and mental retardation. The occurrence of toxoplasmosis in maternal women cannot be separated from cats around their houses. This study aimed to determine the seroprevalence of the parasite in cats found in the human carriers residences and identified the risk factors of toxoplasmosis in maternal women in Badung District, Bali Province, Indonesia. A total of 80 cat serum samples were obtained from two residential groups, 40 from the housing where the maternal women were infected and another 40 from where there were no identified sufferers of the disease. All the samples were examined using the enzyme-linked immunosorbent assay (ELISA) method to detect the presence of antibodies T. gondii in feral cat serum. The results showed that 47.5% of the examined subjects had the said antibodies. As much as 65% came from housing with cases of toxoplasmosis in maternal mothers, and 30% came from residences with none. The presence of feral cats is a major risk factor for the transmission of T. gondii to humans.

Identifying the risk factors of antepartum haemorrhage and to evaluate the feto maternal outcome in antepartum haemorrhage cases

Background: Antepartum haemorrhage is an obstetric emergency contributing to a significant percentage of perinatal and maternal morbidity and mortality. Approximately 30% of maternal deaths are caused by ante-partum haemorrhage. In spite of a lot of improvement in antenatal care and intrapartum surveillance, antepar-tum haemorrhage has not reduced. Present study was conducted to assess the causes of APH and to compare the fetomaternal outcome among placenta previa and abruptio placenta group.Methods: The study was conducted in BRD medical college Gorakhpur, over a period of 1 year (October 2019 to September 2020) in which 100 cases of APH were taken and classified into placenta previa and abruptio placenta group and their fetomaternal outcome were compared.Results: In our study, out of 100 cases of APH 69% cases were of placenta previa followed by abruptio placen-ta in 29% cases and rest 2% cases were unclassified APH. Multigravida is the major risk factor in both placenta previa and abruptio placenta group. Second major risk factor in placenta previa group was h/o LSCS and in abruptio placenta group was HDP. Stillbirth was significantly seen in abruptio placenta group whereas Low birth weight babies (1.5-2.5 kg) were more in placenta previa group. Though the maternal outcome is poor in placenta previa group but the fetal outcome is worse in abruptio placenta group.Conclusions: APH neither can be reliably predicted nor can be prevented but only a comprehensive focused experienced team work can reduce maternal and perinatal morbidity and mortality.

Mitochondrial links between brain aging and Alzheimer’s disease

Advancing age is a major risk factor for Alzheimer’s disease (AD). This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging. Correlative and modeling studies can inform this question, but without a firm grasp of what drives aging and AD it is difficult to definitively resolve this quandary. This review speculates over the relevance of a particular hallmark of aging, mitochondrial function, to AD, and further provides background information that is pertinent to and provides perspective on this speculation.