Synchronous Insulinoma and Glucagonoma: A Review of the Literature.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

Bilateral Adrenalectomy in a Patient With Refractory Primary Aldosteronism Due to Adrenal Hyperplasia.

Primary aldosteronism (PA) is a frequent cause of secondary hypertension. The main cause of PA is bilateral adrenal hyperplasia, and treatment is usually medical with mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone. In this paper, we present a rare clinical case of a middle-aged female with refractory arterial hypertension and hypokalemia that complementary medical tests confirmed PA due to bilateral hyperplasia, and despite a maximum dose of spironolactone and oral potassium supplements, there was no clinical response. Because of this, finally, the patient needed surgical treatment based on bilateral adrenalectomy, which was effective. This is unusual and poorly described in the medical literature.

Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.

Is Laterality Prognostic in Resected KRAS-Mutated Colorectal Liver Metastases? A Systematic Review and Meta-Analysis.

BACKGROUND: It is debated whether primary tumor laterality (PTL) is prognostic in all patients with colorectal liver metastases (CRLM) or only those with KRAS wild-type or KRAS-mutated tumors; Methods: We systematically reviewed PubMed for studies reporting on resected CRLM originating from left-sided (LS) versus right-sided (RS) colon cancer stratified by KRAS status. Individual participant data (IPD) were used if available. Given that there are two definitions of PTL, we performed two meta-analyses for KRAS-mutated and two for wild-type patients. To assess if an interaction underlies the possible difference between the effects of PTL in KRAS-mutated vs. wild-type CRLM, we similarly performed two meta-analyses of interaction terms; Results: The meta-analyses included eight studies and 7475 patients. PTL had a prognostic association with OS in patients with wild-type tumors (HR for LS: 0.71 [0.60-0.84]), but not in those with KRAS-mutated tumors (HR: 0.99 [0.82-1.19]). This difference stemmed from a truly variable effect of PTL for each KRAS status (mutated vs. wild-type) as the meta-analysis of interaction terms showed a significant interaction between them (HR:1.38 [1.24-1.53]). Similar results were obtained when the second definition of PTL (LS to not include the rectum) was used; Conclusions: KRAS status modifies the association of tumor site with survival. Right-sided tumors are associated with worse OS only in patients with wild-type CRLM.

An Uncommon Case of Dulaglutide-Related Morbilliform Drug Eruption.

Dulaglutide is a once-weekly injectable glucagon-like peptide-1 (GLP-1) receptor agonist that has shown a durable glycemic efficacy as well as beneficial effects on body weight and major adverse cardiovascular events (MACE) outcomes, making it an important option for the treatment of type 2 diabetes. Common side effects of dulaglutide include nausea, diarrhea, and abdominal distension, and these are usually mild to moderate in severity and tend to diminish over time. Morbilliform drug eruptions to dulaglutide are very rare, with only one case reported until now. We report another case of dulaglutide-morbilliform drug eruption to alert the attending physicians that dulaglutide-related adverse skin reactions should be kept in mind as generalized use of dulaglutide and other GLP-1 receptor agonists are expected to remain in widespread clinical use in the future.

The Role of TPOAb in Thyroid-Associated Orbitopathy: A Systematic Review.

INTRODUCTION: Thyroid-associated orbitopathy (TAO) is one of the most common autoimmune inflammatory disorders of the orbit. The presence of anti-thyroid antibodies is believed to play a role in the pathogenesis and clinical status of the TAO patients. Herein, we review the usefulness of TPOAb as a biomarker for TAO. METHODS: A systematic search in MEDLINE library was conducted. Results: Twenty studies were included. TPO is expressed in orbital tissues, and the polymorphism rs11675434 SNP has proven to be associated with clinically evident TAO. Studies in pediatric patients have shown a positive correlation between high TPOAb levels and TAO. In contrast, results in adults are inconsistent. Some studies imply a protective role of TPOAb, yet the majority did not find any association. Some authors have suggested an implication of TPOAb in the pathophysiology of TAO in TRAb-negative patients. CONCLUSIONS: The role of TPOAb in TAO remains unclear and controversial.

Medical Flossing and the Pilates Method: Their Effectiveness on the Strength, Endurance, and Functionality of Healthy Individuals.

The flossing method is an emerging therapeutic intervention based on the use of a floss-band that is circumnavigated at the various points of the body being treated. It is optimally combined with an appropriate exercise program to induce ischemia and release the fascia by applying pressure and movement to functional models. The Pilates method teaches the person to focus on the muscles, especially those responsible for the correct posture. It also helps the individual to become aware of the way he/she breathes. Both methods have positive effects on exercise and rehabilitation. However, medical flossing has not been as well researched as the Pilates method. This study aims to examine the effectiveness of both methods on the strength, endurance, and functionality of healthy individuals. A review of the literature on medical flossing and Pilates was conducted. A systematic research took place from 2014 to 2019. Publications in non-English or non-Greek language were excluded. The articles were retrieved from not only PubMed, Scielo, and Elsevier databases, but also Google Scholar. Both methods are understudied in relation to their effectiveness on the strength, endurance, and functionality of healthy individuals. More studies are required to estimate the effects of both methods on healthy individuals.

Cushing's syndrome in pregnancy: a review of reported cases.

Cushing's syndrome (CS) causes hypogonadotropic hypogonadism and anovulatory infertility due to hypercortisolism, and it is very rare in pregnancy. CS in pregnancy is associated with important maternal-foetal morbidity and mortality, such as preeclampsia and premature delivery. A systematic search was conducted in the MEDLINE library to retrieve articles reporting cases of CS in pregnant women, during the period between 2010 and 2020.Thirty-five reported cases are presented focusing on the ability of diagnosis, treatment therapies, and foetal outcomes. Diagnosis of CS during pregnancy can be challenging and is often delayed, adrenal adenoma being the predominant cause. Both medical treatment and surgery aiming at restoring the cortisol balance reduce maternal and foetal complications.

Experimental Agents for the Treatment of Atherosclerosis: New Directions.

Cardiovascular and related metabolic disorders constitute a worldwide health challenge. Atherosclerosis is a chronic inflammatory condition based on both dyslipidemia and inflammation. Therefore, even when dyslipidemia is controlled, the risk of atherosclerosis remains. Among the most efficient inflammatory mediators used as therapeutic tools in cardiovascular disease are the interleukins, which are pro-inflammatory mediators like cytokines. Moreover, a protein kinase inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and an inhibitor of a leukocyte adhesion molecule, P-Selectin, have also presented therapeutic potential for this disorder. Colchicine, being an inexpensive therapeutic option, has been proved to be suitable for the prevention of atherosclerosis. In this review, we summarize all the studies, from 2010 to 2020, in which treatment approaches based on the agents mentioned above are evaluated in the management of atherosclerosis.

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance.

BACKGROUND: Statin intolerance refers to the inability of a patient to tolerate statin therapy, presenting muscle aches, pains, weakness and muscle inflammation. Thus, numerous patients are not treated with suitable statin-based therapy or take only very low doses. As a result, the desired decrease in low-density lipoprotein cholesterol (LDL-C) is not achieved, resulting in patients at a high risk for cardiovascular events, requiring an alternative lipid-lowering treatment. Common treatments manage to reduce the LDL-C level by up to 20%. Recently, new alternative treatment options have been proved to lower the LDL-C level by up to 70%. These treatment strategies are based on human monoclonal antibodies against protein convertase subtilisin/kexin 9 (PCSK9). MATERIALS AND METHODS: Herein, we review the efficiency of anti-PCSK9 in treatment of hypercholesterolemic patients with statin intolerance. We focused on the use of PCSK9 inhibitors in statin-intolerant patients and we estimated the clinical results concerning the reduction of the mean LDL-C concentration and the side effects that were observed. RESULTS: In the majority of cases, treatment strategy based on PCSK9 was successful and achieved the end-points. CONCLUSION: PCSK9 inhibition can be considered as a treatment of option for lipid-lowering in statin-intolerant patients.

The Impact of Peripheral Eosinophil Counts and Eosinophil to Lymphocyte Ratio (ELR) in the Clinical Course of COVID-19 Patients: A Retrospective Study.

BACKGROUND/AIM: Eosinophils are blood cells responsible for response against parasites and allergens. Eosinophil to lymphocyte ratio (ELR) is a biomarker for inflammatory conditions. Our aim was to evaluate the role of eosinophils and ELR in COVID-19 patients. PATIENTS AND METHODS: The study included 96 patients hospitalized with COVID-19. They were classified into moderate to severe cases and critical cases. Eosinophils and ELR were determined in both groups, in patients that died or survived and were correlated to duration of hospitalization. RESULTS: There was a statistically significant decrease in eosinophils and ELR between patients that died and patients that survived (p<0.05), and in mean values of the two biomarkers (p<0.05 for eosinophils and p<0.05 for ELR) between patients hospitalized for more or less than 15 days among those with moderate to severe disease. CONCLUSION: Lower eosinophil counts and ERL could probably predict worse outcome in COVID-19 patients.

Concomitant Existence of Bilateral Adrenal Adenomas. To Operate or Not?

Nowadays, through the wide use of both magnetic resonance imaging and computed tomography, the diagnosis of adrenal incidentaloma is becoming increasingly frequent. Pheochromocytomas are neuroendocrine tumors which produce catecholamine, and they are characterized by headaches, palpitations, sweating and hypertension. Aldosterone-secreting adrenal cortical adenomas can cause various metabolic and cardiovascular diseases due to aldosterone excess. Our aim is to present a rare case of a concomitant existence of pheochromocytoma in the right adrenal and a functioning adrenal cortical adenoma in the left, worthwhile mentioning since the appearance of these two entities in different location in the same patient is unprecedented. The treatment remains challenging.

Is There a Correlation of TSI Levels and Incidental Papillary Thyroid Carcinoma in Graves Disease? A Review of the Latest Evidence.

PURPOSE: Our aim is to clarify if there is an association between the TSI levels and the development of thyroid carcinoma in patients with Grave's disease. METHODS: A systematic search concerning original studies from 2010 to 2020 was carried out through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The terms used are 'Graves' disease' and /or 'Incidental Papillary thyroid cancer' and 'TSI' levels. Retrospective studies upon the subject were concluded in the analysis. RESULTS: Only three retrospective studies were found involving 916 patients with Graves' disease and Euthyroid goiter. No significant correlation has been found between TSI and the occurrence of thyroid carcinoma in patients with Graves' disease. CONCLUSION: Very little research has been conducted upon the subject. More assays are required in order to identify a possible prognostic role of TSI levels in Papillary thyroid carcinoma in patients with Graves disease.

Animal Models for the Calculation of Circulating Tumor Cells for Experimental Demonstration.

Metastasis is a process which is characterized by the existence of tumor cells in the bloodstream. This is a necessary situation in order for the malignant cells to be transported to other organs. Thus, the importance of circulating tumor cells (CTCs) in the study of carcinogenesis is widely accepted. These tumor cells are nowadays a topic of intensive research all over the world. CTCs are expressed from tumor cells and the clinical analysis of this expression may help the recognition of a tumor in an earlier stage and also there is an effort to monitor the tumor burden according to these cells. Although a plethora of clinical studies has been conducted, it is still unclear whether the use in clinical aspect will prove to be beneficial in the near future. Few animal models with neoplasia have been studied concerning the circulating tumor cells and it is likely that CTCs may have a predictive, diagnostic or therapeutic value. Herein, the authors review all studies in which human CTCs were transplanted into animals. Therefore, more clinical studies using standardized methods for measuring CTCs are required to elucidate these issues.

Lipid-lowering Drugs and Neurocognitive Function: A Systematic Review.

BACKGROUND/AIM: Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials. MATERIALS AND METHODS: A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function. RESULTS: Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo. CONCLUSION: Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed.

Government Debt Crisis and the Impact on National Health Systems: A Retrospective Study and Policy Recommendations to Greece.

This article aims to explore the impact of the government debt crisis on the national health system (NHS) using a representative sample of respondents in Greek hospitals and provides certain suggestions regarding health policies that could be implemented at the national or local level. This study was conducted at the Evangelismos & Eye Polyclinic of Athens General Hospital in Athens, Greece. The study period was January and February of 2016, and the study included 600 outpatients who frequently submitted to follow-ups and consented to participate. Based on the results of this study, the participants had an average health status, while 94.2% of them had medical insurance. The predominant reason (88%) for choosing public hospitals instead of private practices was insufficient income. Further investigation revealed a significant positive correlation between the participant's age and the number of hospital visits, the number of medical tests performed, and their satisfaction from the health services provided. Finally, a probit-model was used in order to study factors that could potentially influence their level of satisfaction from the services they used.

SGLT2 Inhibitors and Cardiovascular Outcomes: Do they Differ or there is a Class Effect? New Insights from the EMPA-REG OUTCOME trial and the CVD-REAL Study.

A new group of hypoglycemic drugs has been used to treat diabetes type 2. This group is active sodium glucose co-transporter (SGLT2) or SGLT2 inhibitors. It has been shown that besides the treatment of diabetes, this drug class is responsible for the mildness of the cardiovascular events shown in patients with diabetes type 2. However, there is an intriguing question regarding the range of SGLT2 inhibitors and if there is a difference between them or if there is a class effect among their results. EMPA-REG OUTCOME trial and the CVD-study are used to answer this question. Additional information from the DECLARE-TIMI 58 and Dapa-HF trials is studied.

Cardiovascular and Renal Outcomes of Incretin-based Therapies: A Review of Recent Clinical Trials.

BACKGROUND: To report the cardiovascular and renal effects of incretin-based therapies. METHODS: The studies of clinical trials on incretin-based therapy published in medical journals from the years 2010 to 2017 were comprehensively searched using MEDLINE and EMBASE with no language restriction. The studies were reviewed and the cardiovascular and renal risks reported were recorded. RESULTS: Incretin-based therapeutics represent novel and promising anti-diabetes drugs, the direct cardiovascular actions which may translate into demonstrable clinical benefits on cardiovascular outcomes. Furthermore, incretin-based therapies do not adversely affect renal function.

Pseudotumoral form of schistosomiasis mimicking neuroendocrine tumor: a case report and brief review of the differential diagnosis of retroperitoneal masses.

Differential diagnosis of retroperitoneal masses may become complex and requires careful anamnesis, physical examination and several complementary tests. We present the clinical case of a male patient aged 45 years who was diagnosed with a 4cm paraaortic lesion compatible with neuroendocrine tumor in the abdominal computed tomography (CT) exam. The workup performed with SPECT-CT, somatostatin receptors scintigraphy, MIBG scintigraphy, 24-hour urine total and fractionated catecholamines and 24-hour urine 5-OH indoleacetic did not confirm the first diagnostic impression. Finally, the lesion was biopsied and presence of micro-organisms was revealed. Further exams confirmed schistosomiasis as the cause of the paraaortic lesion. Histological diagnosis can be helpful with regard to the differential diagnosis of retroperitoneal masses.