Med. Sci., Volume 9, Issue 3 (September 2021) – 11 articles

Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002–2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03–1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies. Full article

Rapamycin is an exogenous compound that has been shown to improve cognition in Alzheimer’s disease mouse models and can regulate pathways downstream of the insulin receptor signaling pathway. Insulin is also known to improve cognition in rodent models of Alzheimer’s disease. Central nervous system (CNS) insulin must first cross the blood–brain barrier (BBB), a specialized network of brain endothelial cells. This transport process is regulated by physiological factors, such as insulin itself, triglycerides, cytokines, and starvation. Since rapamycin treatment can alter the metabolic state of rodents, increase the circulating triglycerides, and acts as a starvation mimetic, we hypothesized rapamycin could alter the rate of insulin transport across the BBB, providing a potential mechanism for the beneficial effects of rapamycin on cognition. Using young male and female CD-1 mice, we measured the effects of rapamycin on the basal levels of serum factors, insulin receptor signaling, vascular binding, and BBB pharmacokinetics. We found chronic rapamycin treatment was able to affect basal levels of circulating serum factors and endothelial cell insulin receptor signaling. In addition, while acute rapamycin treatment did affect insulin binding at the BBB, overall transport was unaltered. Chronic rapamycin slowed insulin BBB transport non-significantly (p = 0.055). These results suggest that rapamycin may not directly impact the transport of insulin at the BBB but could be acting to alter insulin signaling within brain endothelial cells, which can affect downstream signaling. Full article

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters. Full article

Background: The German S3- guideline on local therapy of leg ulcers and diabetic foot ulcers is in the process of being updated. Major goals are to improve the guidelines’ applicability and to take steps towards a living guideline according to current methodological standards. The aim of this article is to describe the main measures to achieve these goals. Methods: The context of the guideline in the field of local wound care and the stakeholder requirements are briefly described. Based on a derived framework, the project team adjusted the methods for the guideline. Results: Main adjustments are more specific inclusion criteria, online consensus meetings and the use of an authoring and publication platform to provide information in a multi-layered format. A new set of practice-oriented key questions were defined by the guideline panel to foster the formulation of action-oriented recommendations. Conclusions: The set of new key questions addressing practical problems and patients’ preferences as well as the adjustments made to improve not only the guidelines’ applicability, but also the feasibility of the further dynamic updating processes in the sense of a living guideline, should be steps in the right direction. Full article

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed. Full article

Despite recent advances in immune-modulatory drugs, pharmacological therapies have been proven ineffective in severe presentations of multiple sclerosis (MS), including secondary progressive MS. At present, therapeutic interventions’ performance is primarily focused on ameliorating symptoms to improve the patient’s quality of life (QOL). Among complementary treatments, nutrition has been considered a decisive factor to control symptoms and enhance the wellness of MS patients. Although no special diets are associated with MS, the impact of diet and dietary supplements on the course of progressive forms of the disease has been studied during the last few years. Fatigue is among the most common and disabling symptoms reported by MS patients. Fatigue has been defined in the Multiple Sclerosis Council for Clinical Practice Guidelines (MSCCPG, 1998) as a “subjective lack of physical and/or mental energy that the individual perceives as an interference with habitual and desired activities”. This study aimed to compare the psychometric functioning of the “Fatigue Severity Scale” (FSS) and the “Modified Fatigue Impact Scale” (MFIS) in our sample of people with MS. Specifically, during chronic treatment, the change in these two parameters with two vitamin-rich dietary supplements (Citozym^® and Ergozym^®) was evaluated. The impact of these nutritional supplements revealed differences in antioxidant and anti-inflammatory parameters among the volunteers in the treatment group, with a subsequent improvement in fatigue. In conclusion, the results obtained have confirmed the effectiveness of complementary nutritional therapies, evaluated essentially based on hematological biomarkers, through which it is possible to act on disability to improve the QOL of MS patients. Full article

Cutaneous burn injury is associated with epidermal loss in the zone of coagulation zone and delayed tissue loss in the zone of stasis. Thus, thermal stress can trigger both necrosis and regulated cell death (RCD) or apoptosis. Experimental in vitro and in vivo work has clearly demonstrated apoptotic events of thermally injured keratinocytes that are accompanied by morphological and biochemical markers of regulated cell death. However, in vivo data for the different pathways of regulated cell death are sparse. In vitro experiments with heat-stressed human keratinocytes have demonstrated death receptor involvement (extrinsic apoptosis), calcium influx, and disruption of mitochondrial membrane potential (intrinsic apoptosis) in regulated cell death. In addition, caspase-independent pathways have been suggested in regulated cell death. Keratinocyte heat stress leads to reduced proliferation, possibly as a result of reduced keratinocyte adhesion (anoikis) or oncogene involvement. Understanding the underlying mechanisms of RCD and the skin’s responses to thermal stress may lead to improved strategies for treating cutaneous burn trauma. Full article

Background: This study aimed to investigate the association between endocrine therapy and weight gain with a history of breast cancer. Methods: This was a retrospective cohort study. Recruited patients consisted of those receiving endocrine therapy and those not receiving endocrine therapy. Weight at diagnosis was collected from medical records, and current body mass was measured using a digital scale (time since diagnosis was 4.0 ± 1.9 years). Moreover, we measured current physical activity using an accelerometer and dietary intake using a validated questionnaire. The primary analysis was a t-test for the body-mass change after diagnosis between the two groups. Results: We recruited 300 patients and collected data from 292. Mean weight gain after diagnosis was 1.3 ± 3.9 kg, and the change in body mass of patients taking endocrine therapy (1.3 ± 4.0 kg) was not significantly different from that of patients not taking endocrine therapy (1.4 ± 3.8 kg, p = 0.92). There was no association of endocrine therapy, physical activity, and dietary intake with a 5% weight gain after adjusting confounding factors (e.g., breast cancer stage and chemotherapy). Conclusions: Caution is required with generalization because of sampling bias and ethnic differences. Full article

Aim: To determine the frequency, mode of transmission, and outcome of Coronavirus Disease 2019 (COVID-19) among healthcare workers (HCWs) in a tertiary care cardiac center in the Kingdom of Saudi Arabia (KSA). Methods: This is a retrospective study of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected HCWs and was conducted from 2 March to 31 December 2020. Data related to the presence of COVID-19 symptoms, mode of transmission, hospitalization, and mortality were collected from the patients’ medical records. Results: Of the 4462 patients tested for COVID-19 by real-time reverse transcriptase polymerase chain reaction (RT-PCR), 203 (4.5%) HCWs were positive; of these, 125 (61.6%) were males, and the most common age group was <40 years. The most commonly encountered health professionals were nurses (74, 36.4%), followed by therapists/technicians (48, 23.6%), housekeepers (25, 12.3%), and physicians (21, 10.4%). The majority (184, 90.6%) of the HCWs contracted COVID-19 in the community, and only 19 (9.4%) were healthcare-associated infections. Of the infected HCWs, 169 (83.3%) had mild symptoms and were managed in home isolation. The most common symptoms were fever (128, 63.1%), body ache (124, 61.8%), headache (113, 55.7%), dry cough (123, 60.6%), sore throat (97, 47.8%), body weakness (97, 47.8%), and fatigue (94, 46.3%). Comparing males and females, there was a significantly higher number of female nurses; in contrast, there was a higher number of male physicians, housekeepers, therapists/technicians, and other specialty HCWs. A significantly lower number of nurses, therapists/technicians were infected in the ≥40 years age group compared to <40 years. Furthermore, a significantly higher difference was observed among non-Saudi nurses compared to Saudi nurses. No mortality was documented among the included HCWs. Conclusions: In the largest tertiary cardiac center in KSA, most HCWs who contracted COVID-19 developed mild symptoms; nurses and those aged <40 years were most commonly infected, and most infections were acquired in the community. HCWs’ adherence to mitigation measures outside of the workplace is vital to curb the current pandemic and decrease nosocomial transmission risk. Full article

Type-2 diabetes (T2DM) is a risk factor for the development of pancreatic ductal adenocarcinoma (PDAC) and is characterized by insulin resistance and hyperinsulinemia. Besides the well-known growth-promoting activity of insulin or the other members of the Insulin/Insulin-like Growth factor (IGF) axis, we here describe an inducing effect of insulin on PD-L1 expression in PDAC cells. Treatment of the PDAC cell lines BxPc3, A818-6, and T3M4 with insulin increased PD-L1 expression in a time- and dose dependent fashion, as shown by Western blot and qPCR analysis. siRNA mediated knock-down showed that the effects of insulin on PD-L1 depend on the insulin and IGF receptors (InsR and IGFR, respectively). In addition, a crosstalk of insulin-induced ERK activation and Epidermal Growth Factor (EGF) triggered PD-L1 expression. This involves different mechanisms in the three cell lines including upregulation of InsR-A expression in A818-6 and modulation of the adaptor protein Gab1 in BxPc3 cells. As a consequence of the insulin-induced PD-L1 expression, PDAC cells suppress the proliferation of activated human CD8+ T-cells in coculture experiments. The suppression of CD8+ cell proliferation by insulin-pretreated PDAC cells was reversed by PD-1 blockade with Pembrolizumab or by PD-L1 siRNA. Furthermore, the clinical relevance of these observations was supported by detecting a coexpression of cytoplasmic InsR (characteristic for its activation) and PD-L1 in tumor tissues from PDAC patients. Our findings provide a novel insight into the protumorigenic role of insulin in PDAC. Recognizing the impact of insulin on PD-L1 expression as part of the immune privilege, strategies to interfere with this mechanism could pave the way towards a more efficient immunotherapy of PDAC. Full article

Background: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare tumor composed of adenocarcinoma and neuroendocrine carcinoma components. This study reports a case series of gastric MiNEN and discusses issues related to its diagnosis, management, and outcomes. Methods: We retrospectively analyzed data from patients with gastric MiNEN who underwent surgical resection at our service from 2009 to 2020. Patients with gastric adenocarcinoma served as a comparison group. Clinical, pathologic, and surgical characteristics were compared. Results: During the selected period, 5 gastric MiNEN patients and 597 patients with gastric adenocarcinoma were included. Among the clinical variables, age, sex, BMI, and laboratory exams were similar between the two groups. Only ASA classification was different (p = 0.015). Pathological variables such as tumor size, lymphovascular invasion, number of retrieved lymph nodes, and pTNM staging were also similar between both groups. Lastly, early surgical outcomes and long-term survival did not differ between gastric MiNEN and adenocarcinoma patients. Conclusion: A MiNEN is a rare tumor that represents less than 1% of GC patients undergoing curative treatment, and demonstrated clinicopathological characteristics and outcomes similar to gastric adenocarcinoma. Full article