The challenges of androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.

Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement.

Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L).

Epidemiology of botulism in the north-western Romania-a 7-year survey.

Botulism is a rare, acute, life-threatening neuro-paralysis. The digestive onset may raise diagnostic issues. The objective of our study was to analyze the clinical and epidemiological data of patients diagnosed with botulism and hospitalized in "Gavril Curteanu" Municipal Clinical Hospital (Oradea, Romania). Detection of the Clostridium botulinum neurotoxin (type B) in the laboratories of the National Institute of Medical-Military Research Development "Cantacuzino", Bucharest, Romania (using the mouse bioassays method) confirmed the diagnostics. The statistical analysis was performed using the IBM SPSS software. Forty-eight patients with the diagnosis of foodborne botulism were hospitalized between 2012 and 2018 (36.92% of the total number of cases of botulism reported in Romania). The winter-spring period was the period when most cases were registered (36 patients, p=0.020). Women from rural areas were predominant (but not statistically significant), and the patients' mean age was 39.93±12.59 years. The most common source/cause of botulism was the consumption of homemade ham. The incubation period was 26.68±22.94 h, and 2.25±1.68 days passed from the clinical onset to diagnosis. The results prove that botulism is still a public health issue, especially in areas where homemade products are prepared using inappropriate/unsafe recipes/procedures.

Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.

Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.

Efficiency of antiviral treatment in COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is responsible for generating a global effort to discover urgent therapeutic solutions to limit the human damage caused by COVID-19. In the period of April to June 2020, 105 patients diagnosed with COVID-19 met the conditions for inclusion in the present study. They were treated with antiviral therapy according to local guidelines: D group (53 cases), treated with darunavir/ritonavir (DRV/r); and K group (52 cases), treated with lopinavir/ritonavir (LPV/r). Patients from the K group required 7.5 days of hospitalization less compared to those from the D group (P<0.001). The blood oxygen saturation values recorded in the groups were statistically different [K group (94.02±3.12%) vs. D group (92.13±4.24%), P=0.010]. The percentage of patients with unsatisfactory clinical evolution were non-significantly higher in the D group compared with the K group [20 (37.74%) vs. 12 (23.08%), P=0.157]. We did not note statistically significant differences between the two groups tracked considering the values for the Brescia-COVID Respiratory Severity Scale (BCRSS) of the patients with unsatisfactory clinical evolution, nor of the chest CT' evolution after 10 days of therapy. We did not register significant adverse effects after antiviral therapy in the two groups. Antiviral therapy with LPV/r had some favorable results compared to DRV/r in patients with COVID-19. Both therapies were well tolerated.

Statin intolerance: new data and further options for treatment.

PURPOSE OF REVIEW: Hypercholesterolemia is a major risk factor for cardiovascular diseases. Administration of statins represents the cornerstone of the prevention and treatment of cardiovascular disease, with demonstrated long-term safety and efficacy. This review aims to revisit statin intolerance mechanisms, as well as to discuss new data and therapeutic options. RECENT FINDINGS: Although statins are well tolerated, myopathy and other adverse effects are a challenging problem, being the main reason for poor adherence to treatment and failure in lowering cardiovascular risk. Statin intolerance is the subject of ongoing research, as these drugs are widely used. There are alternative options of treatment if statin intolerance emerges, that is, lowering the dose, intermittent dosages, and/or combining a statin with other drugs, such as ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, bempedoic acid, angiopoietin-like 3 protein inhibitors, and nutraceuticals. If even the lowest statin dose cannot be tolerated, a nonstatin regimen is recommended to reduce LDL cholesterol levels. SUMMARY: Treatment options in statin intolerance include combinations of a lower dose of statin with other lipid-lowering regimens or only nonstatin drugs in the presence of complete intolerance. New hypolipidemic therapies that address gene editing are emerging, and may prove useful in the future.

Prediction of NAFLD occurrence in prediabetes patients.

Non-alcoholic fatty liver disease (NAFLD) is a component of metabolic syndrome that significantly increases the cardiovascular risk of patients with glucose metabolism alterations. This study identified the prevalence of NAFLD, predictors of NAFLD and explored the link between insulin sensitivity, insulin resistance and leptinemia in 143 patients registered with prediabetes. Abdominal ultrasound was performed, and fasting insulin, postprandial insulin, leptin levels, common clinical/biochemical determinations were assessed. Certain variables that can predict NAFLD existence were determined and it was found that there is a high prevalence of NAFLD in patients with prediabetes. In univariate analysis, statistically significant associations (P<0.05) were found between waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, HDL-cholesterol, insulin sensitivity, ß-cell function, leptin and NAFLD presence. The coefficients for the variables which obtain statistically significant association (P<0.05) are low, except for leptin which is the biochemical parameter that (in both univariate and multivariate analysis) is a strong predictor of NAFLD presence.

Interactions between leptin and insulin resistance in patients with prediabetes, with and without NAFLD.

This study explored the link between insulin sensitivity, insulin resistance and leptinaemia in people with prediabetes with and without non-alcoholic fatty liver disease (NAFLD). A total of 143 prediabetes patients were evaluated in the study. Ultrasonography was used for diagnosis of NAFLD, and fasting insulin, postprandial insulin, leptin levels, common clinical/biochemical determinations were determined. In total, 69 (48.25%) of the patients were diagnosed with NAFLD and 74 (51.75%) without NAFLD. Leptin values correlated statistically with fasting insulin in prediabetes patients, while in the patients that were also diagnosed with NAFLD the correlation was stronger. Values of log-leptin <1 ng/ml were found in 64% of patients with prediabetes without NAFLD, and in 2% of patients with prediabetes and NAFLD. In the context of the association between serum leptin levels and a worse biochemical profile in prediabetes patients on one hand, and fatty liver disease and a worse biochemical profile in prediabetes patients on the other, leptin can be considered a possible candidate molecule that mediates the biochemical alterations identified in these patients.

The impact of infection with hepatitis C virus on cardiovascular risk.

Chronic hepatitis C virus (HCV) infection represents a systemic disease, with a natural progression to hepatic steatosis, fibrosis, and finally, cirrhosis, with an increased risk of hepatocellular carcinoma. Besides the hepatic alterations, the systemic manifestations of chronic HCV infection, such as endothelial dysfunction and atherosclerosis, oxidative stress, insulin resistance, immunological alterations, are nowadays recognized as cardiovascular risk factors. Hepatitis C is associated with insulin resistance and increased risk for type 2 diabetes mellitus, carotid atherosclerosis and stroke, coronary artery disease and chronic heart failure, with a significant impact on the mortality and morbidity. This article represents an overview of the most prevalent and important systemic alterations of chronic HCV infection, with emphasis on their cardiovascular and metabolic effects due to a treatable disease.

Financial Burden of Stroke Reflected in a Pilot Center for the Implementation of Thrombolysis.

Stroke represents a serious illness and is extremely relevant from the public health point of view, implying important social and economic burdens. Introducing new procedures or therapies that reduce the costs both in the acute phase of the disease and in the long term becomes a priority for health systems worldwide. The present study quantifies and compares the direct costs for ischemic stroke in patients with thrombolysis treatment versus conservative treatment over a 24-month period from the initial diagnosis, in one of the 7 national pilot centres for the implementation of thrombolytic treatment. The significant reduction (p < 0.001) of the hospitalization period, especially of the days in the intensive care unit (ICU) for stroke, resulted in a significant reduction (p < 0.001) of the total average costs in the patients with thrombolysis, both at the first hospitalization and for the subsequent hospitalizations, during the period followed in the study. It was also found that the percentage of patients who were re-hospitalized within the first 24-months after stroke was significantly lower (p < 0.001) among thrombolyzed patients. The present study demonstrates that the quick intervention in cases of stroke is an efficient policy regarding costs, of Romanian Public Health System, Romania being the country with the highest rates of new strokes and deaths due to stroke in Europe.

Finasteride and androgenic alopecia; from therapeutic options to medical implications.

Androgenic alopecia (AGA) is an esthetic condition with varying psycho-social implications, easily accepted by some patients and tolerated only with difficulty by others. Modern therapeutic options such as 5α-reductase inhibitors have significant outcomes, but also exert significant side effects in a subset of patients. The literature describes three distinct situations regarding finasteride administration, a compound largely used for AGA. Some studies show finasteride to be very safe with minimal or no side effects. Other studies take a more cautious approach, recognizing such side effects but, at the same time, considering the putative relationship between finasteride and adverse effects to be disputable, given that placebo administration in AGA is associated with relatively similar or even more severe side effects. Finally, some authors/studies are concerned that, when compared to placebo, finasteride administration may result in side effects with greater frequency and severity, and sometimes that persist even after treatment cessation in the form of post-finasteride syndrome. Several factors presented in this paper appear to explain finasteride inconsistency regarding its therapeutic and side effects. Such factors should be further investigated and used to categorize subjects into distinct subgroups, either predisposed to adverse reactions or more tolerant of the finasteride administration.

Paraneoplastic syndromes: the way to an early diagnosis of lung cancer.

Pulmonary malignancies are the leading cause of cancer mortality around the world. The late diagnosis of lung cancer, in advanced stages, is mainly due to atypical clinical presentation. Paraneoplastic syndromes have been first described in 1825, as a group of symptoms related to a malignant disease, which are not the effect of the primary neither of the metastatic tumor. The paraneoplastic syndromes have been reported in all types of lung cancer, but more frequently in small cell lung cancer, due to its origin in neuroendocrine cell precursors. The most frequent associated syndromes described in the literature are neurological and endocrine. In most patients paraneoplastic syndromes occur prior to other symptoms of malignancy. The presence or the severity of these syndromes is not correlated with the stage of cancer. Most of the paraneoplastic syndromes disappear once the primary tumor is removed and reappear in case of cancer recurrence or metastasis. This paper is a review of paraneoplastic syndromes in lung cancer.

Apical Hypertrophic Cardiomyopathy: The Ace-of-Spades as the Disease Card.

UNLABELLED: Apical cardiac hypertrophy (Yamaguchi syndrome) is a relatively rare form of hypertrophic cardiomyopathy. A 67-year-old woman presented with exertional angina and moderate dyspnea. Her electrocardiogram showed sinus rhythm, flattened T waves in the limb leads and a strain pattern in the V2-V6 leads. Echocardiographic examination showed that apical wall thickness of the left ventricle (LV) was 19 mm. Coronary angiography was normal, but left ventriculography revealed a spade-like shaped LV cavity, typical for apical cardiac hypertrophy. The diagnostic criteria for apical cardiac hypertrophy are: 1) asymmetric LV hypertrophy - predominantly at the apex of the ventricle; 2) LV wall thickness of 15 mm or more during diastole; and 3) apical to posterior wall thickness ratio of 1.5 or more determined by 2-dimensional echocardiography or cardiac magnetic resonance imaging. Although relatively rare, Yamaguchi syndrome must enter into the differential diagnosis of patients presenting with exertional angina pectoris. KEY WORDS: Angina pectoris; Hypertrophic cardiomyopathy.

Diuretics, first-line antihypertensive agents: are they always safe in the elderly?

INTRODUCTION: Diuretics are frequently recommended as antihypertensive agents. Some of the main side effects of diuretic therapy are hypokalaemia and hyponatremia. The objective of the study was to describe the frequency of hyponatremia in a group of elderly hypertensive patients treated with diuretics. METHOD: The study included 202 elderly hypertensive patients (over 65 years old), treated with diuretics at least 4 weeks before hospitalization, consecutivly admitted in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest during a period of 4 months. RESULTS: The distribution by sex: 103 (52.28%) men and 94 (47.71%) women. The mean age of the patients was 72 ± 8 years. Incidence of hyponatremia was 24.87% (49 patients) in the whole group. From the 49 hyponatremic patients, 31 (63.26%) were women and 18 (36.73%) men. The distribution by age of hypertensive hyponatremic female patients was: between 65-70 years old--4 patients (12.90%), between 70-75 years old--7 patients (22.58%), over 75 years old--20 patients (64.51%). The distribution by age of hypertensive hyponatremic male patients was: between 65-70 years old--3 patients (16.66%), between 70-75 years old--2 patients(11.11%), over 75 years old--13 patients (72.22%). Most of the patients affected (73.46%) used a thiazide-type diuretic, the other 26.54% being on loop diuretics. CONCLUSIONS: Elderly hypertensive patients were more likely to develop hyponatremia after age 75. Female patients had a higher frequency of hyponatremia than male patients. The main cause of hyponatremia in patients treated with diuretics was thiazide.

Clinical characteristics of obese patients with hypertension and chronic ischemic heart disease.

UNLABELLED: Obesity is a risk factor for arterial hypertension, type 2 diabetes and cardiovascular diseases. Some studies reported an obesity paradox: obese patients with cardiovascular diseases have better prognosis than patients with body mass index BMI <25 kg/m2. The objective of the study was to identify the differences between the clinical characteristics of obese hypertensive patients with chronic ischemic heart disease in comparison with lean hypertensive patients with chronic ischemic heart disease. MATERIALS AND METHOD: The study included 219 patients with hypertension and chronic ischemic heart disease, consecutively hospitalized in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania. We analyzed data from the hospital record database. RESULTS: 73 from the 219 patients were obese (33.33%). Of the 219 patients, 15.98% had a BMI 20-24.9 kg/m2, 50.68% BMI 25-29.9 kg/m2, 22.37% BMI 30-34.9 kg/m2, 6.84% BMI 35-39.9 kg/m2, 4.10% BMI > 40 kg/m2. The majority of obese patients were women: 67.12% women and 32.87% men. Obese patients (BMI > 30 kg/m2) had a higher prevalence of diabetes, dyslipidemia, left ventricle hypertrophy and heart failure than those with normal weight (BMI 20-24.9 kg/m2). Blood pressure control was achieved in 51.52% of normally weight patients, as compared to 34.69% of obese patients (BMI > 30 kg/m2). Diabetes was controlled in 42.85% of normally weight patients, as compared to 18.36% of obese patients. CONCLUSIONS: In conclusion, in patients with hypertension and chronic ischemic heart disease, the clinical profile worsens as BMI increases. Also, there is an inverse relationship between control rates of arterial hypertension and diabetes and BMI. Blood pressure was uncontrolled in a high percentage of obese hypertensive patients with ischemic heart disease.