Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

Background: Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Methods: Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/µL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/µL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Results: Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. Conclusions: PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. Clinical Trials Registration: NCT03041051.

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.

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.

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.

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.

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.

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.

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.

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.

PCSK9 Inhibitors and Cardiovascular Disease: Impact on Cardiovascular Outcomes.

Cardiovascular Disease (CVD) remains the leading cause of morbidity and mortality in the western world. Hypolipidemic drugs have long been used for the primary and secondary prevention of heart disease. However, the high frequency of recurrent events in patients despite hypolipidemic therapy has increased the need for new more targeted therapeutic approaches. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are monoclonal antibodies to the PCSK9 gene and represent a new class of drugs that have been shown to further decrease LDL-C when administered as a monotherapy or in combination with statins. In addition to LDL reduction, PCSK9 inhibitors are shown to decrease apolipoprotein B and lipoprotein (a) levels without major adverse effects. Whether or not PCSK9 inhibitors can actually reduce the incidence of cardiovascular events and ameliorate CVD prognosis is yet to be clarified. This review summarizes recent literature on the safety and efficacy of PCSK9 inhibitors on CVD outcome and its potential role in the management of patients with high-risk cardiovascular disease.

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.

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.

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.

Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an extremely diverse group of breast tumors, with aggressive clinical behavior, higher rates of distant recurrence and worse overall survival compared to other types of breast cancers. The genetic, transcriptional histological and clinical heterogeneity of this disease has been an obstacle in the progression of targeted therapeutic approaches, as a ubiquitous TNBC marker has not yet been discerned. In terms of that, current studies focus on the classification of TNBC tumors in subgroups with similar characteristics in order to develop a treatment specialized for each group of patients. To date, a series of gene expression profiles analysis in order to identify the different molecular subtypes have been used. Complementary DNA microarrays, PAM50 assays, DNA and RNA sequencing as well as immunohistochemical analysis are some of the methods utilized to classify TNBC tumors. In 2012, the Cancer Genome Atlas (TCGA) Research Network conducted a major analysis of breast cancers using six different platforms, the genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays, in order to assort the tumors in homogenous subgroups. Since then, an increasing number of breast cancer data sets are being examined in an attempt to distinguish the classification with biological interpretation and clinical implementation. In this review, the progress in molecular subtyping of TNBC is discussed, providing a brief insight in novel TNBC biomarkers and therapeutic strategies.

Screening and Risk Assessment of Coronary Artery Disease in Patients With Type 2 Diabetes: An Updated Review.

Current literature indicates that there is a strong correlation between coronary artery disease (CAD) and type 2 diabetes. The arteriosclerotic progression occurs earlier and in a greater extent in the diabetic than in the non-diabetic population. In diabetic subjects, the detection of arterial disease does not always precede the development of an acute arterial incident. Herein, we reviewed studies published within the last 5 years in order to reveal the risk factors for coronary artery disease in patients with type 2 diabetes. In addition, we aimed to discuss how to diagnose in an early stage or even screen the presence of coronary artery disease in asymptomatic diabetic patients. Possible blood markers as predictors of CAD, which are mostly related to the lipidemic profile of subjects, are included in this review. Less invasive imaging methods than conventional coronary angiography, included in the article, are gradually used more in the diagnosis of CAD and show high effectiveness. Data from 23 articles with 22,350 patients having type 2 diabetes were summarized and presented descriptively.

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies.

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) and unfortunately is not associated with good prognosis. Treatment of breast cancer mainly depends on chemotherapy, due to the lack of specifically approved targeted therapies for TNBC. It is of paramount importance to find new therapeutic approaches, as resistance to chemotherapy frequently occurs. Herein, we present clinical studies published within the last five years, in order to reveal possible targeted therapies against TNBC. We aimed to discuss factors against TNBC, such as tyrosine kinase inhibitors, anti-androgens, poly ADP-ribose polymerase-1 (PARP-1) inhibitors, anti-angiogenic factors, immune checkpoints and histone deacetylase inhibitors (HDACI). Furthermore, the PI3K/AKT/mTOR pathway seems to be a promising field for the development of new anti-TNBC targeted therapies. Data from 18 clinical trials with patients suffering from TNBC were summarized and presented descriptively.