Analysis of Aetiological Agents in Infectious Endocarditis in the Central Military Emergency University Hospital "Dr. Carol Davila" Bucharest.

BACKGROUND: Infective endocarditis (IE) is a pathological condition caused by various microbial agents that can lead to severe complications affecting the heart. Accurate diagnosis is crucial for the effective management of patients with IE. Blood culture is the gold standard for identifying the primary infectious agents, which is a key factor in diagnosing IE using the modified Duke criteria. OBJECTIVE: The main objective of this study was to investigate the distribution of the etiological agents of IE and the most common secondary diagnoses associated with it. METHOD: A total of 152 patients aged 23-95 years with a diagnosis of IE and proven etiology (through blood cultures or serological tests) were included in this study. RESULTS: The most common etiological agent identified through blood tests was Enterococcus faecalis, which was detected in 39 patients (23.5%). Staphylococcus aureus was the second most common agent and was identified in 33 patients (19.9%), followed by Staphylococcus epidermidis, which was identified in 12 patients (13.1%). Nine patients (5.8%) had high levels of anti-Coxiella burnetti IgG phase I and II antibodies. CONCLUSIONS: IE is a leading cause of death in the Department of Infectious Diseases. Early and accurate diagnosis, along with interdisciplinary treatment, can significantly increase the chances of patient survival. Currently, Enterococcus faecalis and Staphylococcus aureus are the dominant etiological agents of IE, highlighting the need to revise protocols for prophylaxis, diagnosis, and initial treatment of this condition.

A Surprising Case of Triple Acute Hepatitis Infection.

Viral hepatitis continues to be the leading cause of morbidity and mortality worldwide, but the burden has significantly diminished thanks to the large-scale use of vaccines and antivirals. However, there are still challenges regarding viral hepatitis management, especially when more than one pathogenic agent is involved. We present the case of a 45-year-old woman who had a simultaneous infection involving three hepatitis viruses: HAV, HBV, and HEV.

MRI Evolution of a Patient with Viral Tick-Borne Encephalitis and Polymorphic Seizures.

Some neurotropic viruses induce specific lesions in the deep structures, such as basal ganglia and thalamus. These anatomical structures play an important role in initiating and maintaining different types of epileptic seizures. We present the case of a 25-year-old male, transferred to our clinic one week after the onset of the symptomatology, with a recent history of traveling to Turkey and Egypt. At the moment of his hospital admission, his symptoms included altered consciousness, agitation, and seizures. Shortly after, his state worsened, requiring intubation. Viral tick-borne encephalitis diagnoses were favored by the CSF (cerebrospinal fluid) analysis, EEG (Electroencephalography), MRI (magnetic resonance imaging) images presenting symmetric hyper signal in the basal ganglia, and IgM antibodies for anti-tick-borne encephalitis. These lesions persisted for several weeks, and the patient's seizures were polymorphic, originally generalized onset motor, generalized onset non-motor, and focal myoclonic. The patient achieved his independence, seizures decreasing both in intensity and frequency; the MRI images became almost normal. The reduction in antiepileptic doses was not followed by seizure recurrence.

Air Pollution and Its Devastating Effects on the Central Nervous System.

Air pollution is a real public health problem, it being one of the five most common causes of mortality in developing countries. However, pollution studies have focused on the cardiovascular and pulmonary systems in recent decades. Recently, researchers have moved towards a new direction, tracing a direct link between pollution and stroke. Stroke has many known risk factors such as smoking, a sedentary lifestyle, and hypertension. Pollution is universally widespread, already a matter of public interest, so that, although intuitive, it is difficult to connect the two. The particles found in the air that we breathe, regardless of their origin, can attack the body in different ways, causing inflammation, and triggering a true cascade of phenomena that end up attacking the central nervous system and other organs. This article tries to explain the series of phenomena that determine the harmful effect of particles present in the air, with an increased focus on the central nervous system and especially on strokes. A deeper understanding of these phenomena helps in guiding future studies and finding viable solutions to protect people at risk.

Characterization of the Open-Label Lead-In Period of Two Randomized Controlled Phase 3 Trials Evaluating Dapagliflozin, Saxagliptin, and Metformin in Type 2 Diabetes.

INTRODUCTION: To examine the utility of sequential versus dual add-on approaches in patients who have type 2 diabetes and inadequate glycemic control with metformin therapy alone, we characterized the efficacy and safety of dual therapy with dapagliflozin or saxagliptin added to metformin in the open-label lead-in periods of two phase 3 trials (study 1, NCT01619059; study 2, NCT01646320) that evaluated triple therapy in patients with inadequately controlled type 2 diabetes. METHODS: During the lead-in periods of each trial, patients [glycated hemoglobin (HbA1c) 8.0-11.5%] who had been receiving metformin ≥ 1500 mg/day for ≥ 8 weeks received metformin immediate release at an equivalent dose plus dapagliflozin 10 mg/day (study 1; N = 482) or saxagliptin 5 mg/day (study 2; N = 349) for 16 weeks. Efficacy end points were assessed at week - 2 before randomization. RESULTS: Mean change in HbA1c [95% confidence interval (CI)] from lead-in baseline (study 1, 9.3%; study 2, 9.4%) was - 1.6% (- 1.7, - 1.5) in study 1 and - 1.3% (- 1.5, - 1.2) in study 2. Mean changes (95% CI) from lead-in baseline in weight and fasting plasma glucose were - 2.4 kg (- 2.6, - 2.1) and - 47.5 mg/dL (- 52.8, - 42.3) for study 1 and - 0.5 kg (- 0.8, - 0.2) and - 28.5 mg/dL (- 35.8, - 21.2) for study 2. At the end of the lead-in period, 22.0% of patients achieved HbA1c < 7.0% in study 1 and 17.5% in study 2. Dual therapy was well tolerated, with hypoglycemia incidence < 1% in both studies. CONCLUSION: Dual therapy improved glycemic control and was well tolerated; however, most patients required additional therapy to further improve HbA1c towards target, suggesting that an early move to triple therapy with oral glucose-lowering drugs rather than a stepwise approach may be beneficial for patients with high HbA1c levels on metformin therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01619059, NCT01646320. FUNDING: AstraZeneca.

Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes.

OBJECTIVE: To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment. RESEARCH DESIGN AND METHODS: Patients receiving treatment with stable metformin (stratum A) (screening HbA1c level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA1c 7.5-10.5% [58-91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA1c level of <7% (53 mmol/mol). RESULTS: Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA1c reduction than placebo (-0.82 vs. -0.10% [-9 vs. -1.1 mmol/mol], P < 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA1c level of <7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (∼1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%). CONCLUSIONS: Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy.

Drug-induced hypo- and hyperprolactinemia: mechanisms, clinical and therapeutic consequences.

INTRODUCTION: The altered profiles of prolactin secretion in the anterior hypophysis, generated by pathological, pharmacological or toxicological causes, have special consequences on multiple functions in both genders. AREAS COVERED: This selective review presents the main mechanisms controlling prolactin secretion, focusing on the interplay of various neurotransmitters or xenobiotics, but also on the role of psychic or posttraumatic stress. A detailed analysis of several pharmacotherapeutic groups with hyperprolactinemic effects emphasize on the relevance of the pharmacokinetic/pharmacodynamic mechanisms and the clinical significance of the long term administration. EXPERT OPINION: Accurate monitoring and evaluation of the hyperprolactinemia induced by xenobiotics is strongly recommended. The typical antipsychotics and some of the atypical agents (amisulpride, risperidone, paliperidone), as well as some antidepressants, antihypertensives and prokinetics, are the most important groups inducing hyperprolactinemia. The hyperprolactinemic effects are correlated with their affinity for dopamine D2 receptors, their blood-brain barrier penetration and, implicitly, the requested dose for adequate occupancy of cerebral D2 receptors. Consequently, integration of available pharmacokinetic and pharmacodynamic data supports the idea of therapeutic switch to non-hyperprolactinemic agents (especially aripiprazole) or their association, for an optimal management of antipsychotic-induced hyperprolactinemia. Possible alternative strategies for counteracting the xenobiotics-induced hyperprolactinemia are also mentioned.