Ioannis Starakis

Epidemiology of Hantavirus infections in humans: A comprehensive, global overview

Abstract Hantaviruses comprise an emerging global threat for public health, affecting about 30 000 humans annually. Infection may lead to Hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in the Europe and Asia. Humans are spillover hosts, acquiring infection primarily through the inhalation of aerosolized excreta from infected rodents and insectivores. Risk factors for infection include involvement in outdoor activities, such as rural- and forest-related activities, peridomestic rodent presence, exposure to potentially infected dust and outdoor military training; prolonged, intimate contact with infected individuals promotes transmission of Andes virus, the only Hantavirus known to be transmitted from human-to-human. The total number of Hantavirus case reports is generally on the rise, as is the number of affected countries. Knowledge of the geographical distribution, regional incidence and associated risk factors of the disease are crucial for clinicians to suspect and diagnose infected individuals early on. Climatic, ecological and environmental changes are related to fluctuations in rodent populations, and subsequently to human epidemics. Thus, prevention may be enhanced by host-reservoir control and human exposure prophylaxis interventions, which likely have led to a dramatic reduction of human cases in China over the past decades; vaccination may also play a role in the future.

The upgraded role of HER3 and HER4 receptors in breast cancer

The human epidermal growth factor receptor (HER) family comprises four homologous members. The activation of these receptors affects essential tumorigenic processes and plays a crucial role in the pathogenesis of breast cancer. Among HER family members, EGFR and HER2 are the most studied. However, accumulating data provide evidence for the significance of HER3 and HER4 alterations in breast carcinogenesis. The combination of HER2 and HER3 receptors may be critical in breast cancer growth and progression. Moreover, HER3 may provide a route for resistance to agents targeting EGFR or HER2. Although a number of studies have demonstrated that HER3 overexpression is associated with poor prognosis in patients with breast cancer, other studies have indicated that HER3 overexpression may be a positive prognostic factor. With respect to HER4 receptor, the existing evidence suggests that HER4 signalling promotes differentiation and growth inhibition of breast cancer cells. In addition, HER4 is more consistently related with a favourable prognosis in breast cancer. HER4 has multiple different activities in the breast, and many of these functions are mediated by a soluble HER4 intracellular domain. In addition, loss of HER4 expression may represent a marker for resistance to tamoxifen. Because of the functional interdependency among the HER receptors, it is possible that the effect on cell proliferation and tumor growth depends on receptor trans-signalling. Therefore, clarifying how and the extent to which these different signalling pathways interact in breast carcinogenesis, may lead to additional therapeutic opportunities. This review presents an update on the role of HER3 and HER4 receptors in breast cancer. Moreover, we provide current data relating to the prognostic significance of these receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer.

Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency

Metformin treatment is a known pharmacological cause of vitamin B12 (Cbl) deficiency with controversial responsible mechanisms. A possible diagnosis of this deficiency is based mainly on the combination of patients medical history (usually long-term metformin use), clinical examination (possible neuropsychiatric symptoms and signs), laboratory studies which confirm a Cbl deficiency (haematological abnormalities, low serum Cbl levels, elevated serum total homocysteine and methylmalonic acid levels), and exclusion other causes of Cbl deficiency (as pernicious anaemia, food-cobalamin malabsorption syndrome, other drugs, etc.). In our review, recommendations for diagnosis and management of metformin-induced Cbl deficiency (MICD) in diabetic patients based on medical bibliography are presented and discussed.

Hepatitis caused by the herbal remedy Teucrium polium L.

Herbal remedies have become increasingly popular throughout the globe as a result of disappointment with conventional medicines and also of the alleged belief that herbal preparations are basically harmless. On the other hand, their effects can be exceedingly potent or even lethal if used improperly. Drugs and other chemicals account for less than 5% of cases of jaundice or acute hepatitis and smaller number of cases of chronic liver disease. Drug reactions can mimic any hepatobiliary disease, posing a diagnostic challenge for physicians and pathologists. Hepatotoxicity generally occurs after approximately 2 months of ingestion and consists of a non-specific hepatitis, which usually runs a benign course. Typical features include anorexia, nausea, abdominal pain, and jaundice associated with a marked elevation in serum aminotransferases. We present a case of acute hepatitis in a 70-year-old farmer, using Teucrium polium (golden germander) as hypoglycaemic aid. The patient presented only with jaundice, after 1 months consumption of large quantities of this herb in a tea form.

Hantavirus infections for the clinician: From case presentation to diagnosis and treatment

Hantaviruses cause Hantavirus Pulmonary Syndrome (HPS; also called Hantavirus Cardiopulmonary Syndrome) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Asia and Europe. In Scandinavia and northern Europe, a milder form of HFRS is prevalent, termed nephropathica epidemica (NE). HPS presents with acute respiratory failure, mild-moderate renal failure, thrombocytopenia, and reactive lymphocytosis. HFRS has pronounced renal dysfunction and less prominent respiratory involvement, with thrombocytopenia and hemorrhagic findings. Both syndromes have long-term sequelae. Common symptomatology is due to underlying pathophysiology, mainly increased vascular permeability and immune activation. Laboratory and imaging markers predicting disease severity are under research, allowing for more efficient patient management. Diagnosis is presumptive, based on typical clinical findings and patient history of likely rodent exposure. Confirmation of diagnosis is by serological testing and/or RT-PCR. Treatment is mainly comprised of cardiovascular, respiratory, and renal function support, with fluid and electrolyte homeostasis being crucial components of care. In HPS, the use of extracorporeal membrane oxygenation in decompensated patients has also shown to be beneficial.

Targeted Therapy in Colorectal Cancer: Current Status and Future Challenges

Treatment of metastatic colorectal cancer (mCRC) has progressed significantly over the last years, particularly with the introduction of targeted therapies. Two groups of agents targeting either the epidermal growth factor receptor (EGFR) or the vascular endothelial growth factor (VEGF) have been integrated into clinical practice. Currently available agents with established role include the anti-EGFR monoclonal antibodies (mAbs) cetuximab / panitumumab and the anti-VEGF mAb bevacizumab. This review presents an update on the clinical studies evaluating the role of anti-EGFR and anti-VEGF agents in mCRC. Moreover, we provide current data regarding the mechanism of action and pathways mediating resistance to these agents. In addition, we present recent data with respect to biomarkers and we discuss future therapeutic strategies.

Changes of bone mineral density in pre-menopausal women with differentiated thyroid cancer receiving L-thyroxine suppressive therapy

ABSTRACT Objective: We studied the effect of levothyroxine (L-T4) suppressive therapy on bone mineral density (BMD) in pre-menopausal women with total thyroidectomy and radioactive iodine (131I) ablation therapy post-operatively for differentiated thyroid cancer (DTC). Patients and methods: We prospectively studied 26 athyroid pre-menopausal women (median age 39 years, range 28–48 years) receiving suppressive L‐T4 therapy postoperatively for 48 months. BMD was measured by dual energy X‐ray absorptiometry (DEXA) at the femoral neck, femoral trochanter and Wards triangle, before (basal) and during (12th and 48th month) the follow-up period. None of the women gave a medical history that could possibly affect bone metabolism. Patients were free of thyroid cancer in clinical and laboratory examinations at the time of the study. Paired t‐test was used for comparisons among BMD measurements during the suppressive therapy. Results: There were statistically significant decreases of BMD at all measured regions during (12th and 48th month) L‐T4 suppressive therapy. The overall decreases in BMD at the femoral neck, femoral trochanter and Wards triangle were 7.5%, 10.9% and 3.4%, respectively, at the end of the follow-up period. The coefficient of variation (CV) of all BMD measurements was around 10%, showing a rather homogenous group of patients. Our patients had a statistically significant decrease in their body mass index (BMI) and weight at the end of the follow-up period. However, there was no significant correlation between the decrease in BMI and BMD. Patients did not experience significant adverse effects from L‐T4 suppressive therapy during the study. Conclusion: L‐T4 suppressive therapy for at least 1 year in pre-menopausal women with DTC causes a reduction in BMD of the femoral neck, femoral trochanter and Wards triangle.

The hypolipidaemic effects of Spirulina (Arthrospira platensis) supplementation in a Cretan population: a prospective study

BACKGROUND Spirulina (Arthrospira platensis) is a filamentous cyanobacterium used as a food supplement. The objective of the study was to determine the lipid-lowering effects of Spirulina in Cretan Greek dyslipidaemic patients, and to document its effectiveness as a possible alternative treatment for dyslipidaemia. Fifty-two adultCretan outpatients (32 men, 20 women), median age 47 (range, 37-61) years, with recently diagnosed dyslipidaemia, consumed orally 1 g Spirulina (Greek production) per day for 12 weeks. The full lipid profile was measured in fasting blood samples at the beginning and end of the study period. Anthropometric measurements including systolic and diastolic blood pressure, height, weight and body mass index were also recorded. RESULTS At the end of the 3-month intervention period the mean levels of triglycerides, low density lipoprotein-cholesterol, total cholesterol, non-high density lipoprotein-cholesterol levels, and the ratio of total cholesterol to high-density lipoproteincholesterol were significantly decreased: 16.3% (P < 0.0001), 10.1% (P < 0.0001), 8.9% (P < 0.0001), 10.8% (P < 0.0001) and 11.5% (P = 0.0006) respectively, whereas the mean high-density lipoprotein-cholesterol levels were not significantly increased (3.5%). Blood pressure, weight and body mass index remained almost unchanged. CONCLUSIONS Spirulina supplementation at a dose of 1 g daily has powerful hypolipidaemic effects, especially on the triglyceride concentration in dyslipidaemic Cretan outpatients.

Q fever endocarditis.

Coxiella burnetii, the agent of Q fever, produces a variety of clinical syndromes. The most frequent and serious chronic presentation is endocarditis, which presents unspecifically as a blood-culture negative endocarditis. It occurs almost exclusively in patients who have pre-existing valvular disease or who are immunocompromised. Without prompt recognition and appropriate antimicrobial therapy, the course of Q fever endocarditis is severe and potentially fatal. The epidemiology, signs and symptoms, laboratory findings, diagnosis and treatment of Q fever endocarditis are presented in our review.

Nonbacterial Thrombotic Endocarditis (Marantic Endocarditis) in Cancer Patients

The term nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, refers to a spectrum of lesions ranging from microscopic aggregates of platelets to large vegetations on previously undamaged heart valves (most often aortic and mitral) in the absence of a bloodstream bacterial infection. NBTE is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas. In this article, the pathogenesis, incidence, clinical manifestations, diagnosis, and management of NBTE in cancer patients are reviewed.