Pulmonary adverse events due to immune checkpoint inhibitors: A literature review.

Cancer immunotherapy aims to stimulate the immune system to fight against tumors, utilizing the presentation of molecules on the surface of the malignant cells that can be recognized by the antibodies of the immune system. Immune checkpoint inhibitors, a type of cancer immunotherapy, are broadly used in different types of cancer, improving patients' survival and quality of life. However, treatment with these agents causes immune-related toxicities affecting many organs. The most frequent pulmonary adverse event is pneumonitis representing a non-infective inflammation localized to the interstitium and alveoli. Other lung toxicities include airway disease, pulmonary vasculitis, sarcoid-like reactions, infections, pleural effusions, pulmonary nodules, diaphragm myositis and allergic bronchopulmonary aspergillosis. This review aims to summarize these pulmonary adverse events, underlining the significance of an optimal expeditious diagnosis and management.

Histone deacetylase inhibitors as a new anticancer option: How far can we go with expectations? delivery systems.

Histone modification that occurs through the process of acetylation plays a key role in the epigenetic regulation of gene expression. The balance between histone deacetylases (HDACs) and histone acetyltransferases controls this process. Histone deacetylase inhibitors (HDACIs) can induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Therefore, HDAIs represent a group of enzymes that can be used for the development of pharmaceutical agents against a variety of malignant diseases. The mechanisms of their anticancer effect depend on many factors. HDACIs vorinostat, romidepsin and belinostat have been approved for some T-cell lymphomas and panobinostat for multiple myeloma. Other HDACIs are tested in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed.

Sympathetic Nerve Injury in Thyroid Cancer.

The double innervation of the thyroid comes from the sympathetic and parasympathetic nervous system. Injury rates during surgery are at 30% but can be minimized by upwardly preparing the thyroid vessels at the level of thyroid capsule. Several factors have been accused of increasing the risk of injury including age and tumor size. Our aim was to investigate of there is indeed any possible correlations between these factors and a possible increase in injury rates following thyroidectomy. Seven studies were included in the meta-analysis. Statistical correlation was observed for a positive relationship between injury of the sympathetic nerve and thyroid malignancy surgery (p 2 = 74%) No statistical correlations were observed for a negative or positive relationship between injury of the sympathetic nerve and tumor size. There was also no statistically significant value observed for the correlation of the patients' age with the risk of sympathetic nerve injury (p = 0.388). Lack of significant correlation reported could be due to the small number of studies and great heterogeneity between them.

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.

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.

All that Glitters is not Cholecystitis. A Rare Presentation of Acute Pericarditis Mimicking Cholecystitis and Review of the Literature.

Acute pericarditis is the most common inflammatory disorder of the pericardium, responsible for approximately 5% of visits to the emergency departments, concerning chest pain without myocardial infarction. We report a case of a 41-year-old man who presented to our hospital, complaining about retrosternal and epigastrium pain. The transthoracic echocardiogram showed pericardial effusion while the electrocardiogram and laboratory findings revealed acute pericarditis. An abdominal ultrasound revealed gallbladder edema. The pericardial effusion was treated with pericardial catheter insertion, diuretics, and nonsteroidal anti-inflammatory drugs. This case shows that acute pericarditis can be clinically presented with many ways, one of them being gallbladder edema. Furthermore, in this case-based review we present all cases of simultaneous appearance of pericarditis and acalculous cholecystitis or gallbladder edema.

Prognostic value of the immunohistochemistry markers CD56, TTF-1, synaptophysin, CEA, EMA and NSE in surgically resected lung carcinoid tumors.

Lung carcinoid tumor is a type of neuroendocrine tumor, which is subdivided into typical carcinoid (TC) and atypical carcinoid (AT), based on the rate of mitosis and the presence of necrosis. Several prognostic factors for lung carcinoids have been reported in the literature, including the type, Ki67 index, stage, chemotherapy and radiation therapy. In the present study, 108 cases with resected carcinoid lung tumors were enrolled and the expression of CD56, thyroid transcription factor 1, synaptophysin, carcinoembryonic antigen, epithelial membrane antigen and neuron-specific enolase (NSE) in the resected tissue specimens was immunohistochemically analyzed. Patients with positive staining for NSE had an unfavorable survival prognosis compared with patients with negative staining for NSE (137.2 vs. 150.0 months, P=0.044). According to univariate analysis, none of the above immunohistochemistry markers was associated with survival, and according to multivariate analysis, NSE was an independent influencing factor for survival inpatients with AT (P=0.046) and furthermore, the stage was an independent factor of survival in patients with TC (P=0.005).

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.

Role of histone deacetylase inhibitors in diabetic cardiomyopathy in experimental models (Review).

In diabetes, metabolic dysregulation, caused by hyperglycemia, leads to both structural and functional changes in cardiomyocytes and subsequently leads to the development of cardiomyopathy. Histone deacetylases (HDAC) are enzymes that regulate gene transcription. Their actions have been examined in the development of multiple disorders, such as cardiovascular diseases and diabetes. The use of HDAC inhibitors (HDACIs), as potential therapeutic agents against disease progression has yielded promising results. The present review article reports preclinical trials identified in which HDACIs were administered to mice suffering from diabetic cardiomyopathy (DCM), and discusses the role and mechanisms of action of HDAC and HDACIs in DCM. A review of the literature was performed using the PubMed database, aiming to identify publications in the English language concerning the role of HDACIs in DCM. More specifically, key words, separately and in various combinations, such as HDACIs, HDAC, diabetes, cardiomyopathy, heart failure and ischemia/reperfusion injury, were used. Furthermore, the references from all the articles were cross-checked in order to include any other eligible studies. The full-text articles assessed for eligibility were eight, covering the period from 2015 to 2019; finally, all of them were included. The use of HDACIs exhibited encouraging results against DCM progression through various mechanisms, including the reduction of reactive oxygen species generation, inflammatory cytokine production and fibrosis, and an increase in autophagy and angiogenesis.

The Role of SNHG15 in the Pathogenesis of Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides which cannot be translated into proteins. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA whose dysregulation has been found to have an important impact on carcinogenesis and affect the prognosis of cancer patients in various cancer types. Hepatocellular carcinoma (HCC) is one of the most common cancers with a poor long-term prognosis, while the best prognostic factor of the disease is its early diagnosis and surgery. Consequently, the investigation of the mechanisms of hepatocarcinogenesis, as well as the discovery of efficient molecular markers and therapeutic targets are of great significance. An extensive literature search was performed in MEDLINE in order to identify clinical studies that tried to reveal the role of SNHG15 in HCC. We used keywords such as 'HCC', 'hepatocellular carcinoma', 'SNHG15' and 'clinical study'. Finally, we included four studies written in English, published during the period 2016-2021. It was revealed that SNHG15 is related to the appearance of HCC via different routes and its over-expression affects the overall survival of the patients. More assays are required in order to clarify the potential role of SNHG15 as a prognostic tool and therapeutic target in HCC.

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 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.

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.

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.

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.

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.

Inflammatory Fibroid Polyp of the Gastrointestinal Tract: A Systematic Review for a Benign Tumor.

BACKGROUND/AIM: Inflammatory fibroid polyp (IFP) is a rare, usually solitary and intraluminal polypoid benign tumor that can affect any part of the gastrointestinal (GI) tract, although in the majority of cases it affects the stomach. This lesion is characterized by proliferation of highly vascular fibrous tissue and infiltration by a variable number of different inflammatory cells. Its etiology is unknown. Our aim was to describe all the reported data concerning IFP. MATERIALS AND METHODS: An extensive search of the PubMed Index was performed for publications with titles or abstracts containing the terms: "inflammatory fibroid polyp" with/without "Vanek". Results were filtered for publications in English and concerning only humans. One hundred and twenty-four publications were finally included in this review. RESULTS: IFP has a female predominance. It affects patients in their 5th decade of life, although there are cases of patients from 4 to 84 years of age. IFP usually affects the stomach and more specifically the gastric antrum but can be detected throughout the GI tract. A significant number of cases remain asymptomatic but the most frequent presentations of IFP are abdominal pain, acute abdomen and GI bleeding. Most cases are treated by endoscopic resection of the lesion. No recurrence nor IFP-specific complications have been reported. Histopathology of IFP varies. CONCLUSION: It is relatively safe to conclude that both the etiology and the timing of diagnosis might change the histopathology, immunohistological staining and tissue structure of IFP. Suggested theories should be taken into consideration with caution as the etiology and pathophysiological mechanisms of IFP are unknown.

Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.

Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC.

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.