The non-invasive assessment of hepatic fibrosis.

Hepatic disease accounts for approximately 2 million deaths/year worldwide. Liver fibrosis, as the last stage of numerous chronic liver diseases, is one of the most relevant prognostic factors. The liver biopsy with the histopathological examination is considered to be the "gold standard" for the identification and staging of the hepatic fibrosis. However, liver biopsy is known as an invasive investigation that has multiple limitations. Research studies conducted in the last few years focused on identifying non-invasive type methods for the evaluation of hepatic fibrosis; usually, there are 2 categories of such investigations: serologic tests and imaging techniques. This narrative review presents the non-invasive investigation methods used in the liver fibrosis evaluation. New molecular perspectives on fibrogenesis and fibrosis regression, as well as the appearance of therapeutic antifibrotic agents, justify the necessity of non-invasive tools to detect and grade liver fibrosis.

Low-density lipoprotein cholesterol lowering treatment: the current approach.

In the last 50 years, several clinical and epidemiological studies during have shown that increased levels of low-density lipoprotein cholesterol (LDLc) are associated with the development and progression of atherosclerotic lesions. The discovery of ß-Hydroxy ß-methylglutaryl-CoA reductase inhibitors (statins), that possess LDLc-lowering effects, lead to a true revolution in the prevention and treatment of cardiovascular diseases. Statins remain the cornerstone of LDLc-lowering therapy. Lipid-lowering drugs, such as ezetimibe and bile acid sequestrants, are prescribed either in combination with statins or in monotherapy (in the setting of statin intolerance or contraindications to statins). Microsomal triglyceride transfer protein inhibitors and protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are other drug classes which have been investigated for their potential to decrease LDLc. PCSK9 have been approved for the treatment of hypercholesterolemia and for the secondary prevention of cardiovascular events. The present narrative review discusses the latest (2019) guidelines of the European Atherosclerosis Society/European Society of Cardiology for the management of dyslipidemia, focusing on LDLc-lowering drugs that are either already available on the market or under development. We also consider "whom, when and how" do we treat in terms of LDLc reduction in the daily clinical practice.

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.

Acute Colonic Pseudoobstruction (Ogilvie Syndrome) - A Severe Complication in the Evolution of the Hospitalized or Institutionalized Patients.

Introduction: Ogilvie syndrome, or acute colonic pseudo-obstruction (ACPO), represents a pathological entity, potentially with a severe outcome, due to the acute important dilation of the large bowel, in the absence of a mechanical luminal obstruction. Usually, it occurs in patients admitted in intensive care unit, that associate severe surgical or medical pathologies. The mechanism of the ACPO has not been completely explained, but it is assumed that the motor function of the colon may be affected, as a result of autonomic regulation disturbance. Early diagnosis and treatment help reduce the risk of severe outcome, such as ischemia or perforation. Material and Method: In addition to our experience, a literature search was elaborated in order to evaluate the incidence, the etiology, the clinical presentation and the diagnosis of the ACPO. Results and Conclusions: The present study may be of help in the process of guiding the optimal management of a critically ill patient is at high risk of developing colonic pseudo-obstruction.

Polypharmacy in Type 2 Diabetes Mellitus: Insights from an Internal Medicine Department.

BACKGROUND AND OBJECTIVES: Polypharmacy heavily impacts the quality of life of patients worldwide. It is a necessary evil in many disorders, and especially in type 2 diabetes mellitus, as patients require treatment both for this condition and its related or unrelated comorbidities. Thus, we aimed to evaluate the use of polypharmacy in type 2 diabetes mellitus vs. non-diabetes patients. MATERIALS AND METHODS: A cross-sectional retrospective observational study was conducted. We collected the medical records of patients hospitalized in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania, for a period of two months (01/01/2018-28/02/2018). Patients diagnosed with type 2 diabetes mellitus were included in the study group, whereas patients who were not diabetic were used as controls. RESULTS: The study group consisted of 63 patients with type 2 diabetes mellitus (mean age 69.19 ± 9.67 years, range 46-89 years; 52.38% males). The control group included 63 non-diabetes patients (mean age 67.05 ± 14.40 years, range 42-93 years, 39.68% males). Diabetic patients had more comorbidities (10.35 ± 3.09 vs. 7.48 ± 3.59, p = 0.0001) and received more drugs (7.81 ± 2.23 vs. 5.33 ± 2.63, p = 0.0001) vs. non-diabetic counterparts. The mean number of drug-drug and food-drug interactions was higher in type 2 diabetes mellitus patients vs. controls: 8.86 ± 5.76 vs. 4.98 ± 5.04, p = 0.0003 (minor: 1.22 ± 1.42 vs. 1.27 ± 1.89; moderate: 7.08 ± 4.08 vs. 3.54 ± 3.77; major: 0.56 ± 0.74 vs. 0.37 ± 0.77) and 2.63 ± 1.08 vs. 2.19 ± 1.42 (p = 0.0457), respectively. CONCLUSIONS: Polypharmacy should be an area of serious concern also in type 2 diabetes mellitus, especially in the elderly. In our study, type 2 diabetes mellitus patients received more drugs than their non-diabetes counterparts and were exposed to more drug-drug and food-drug interactions.

Treatment with Statins in Elderly Patients.

Elderly patients are a special category of patients, due to the physiological changes induced by age, the great number of comorbidities and drug treatment and last, but not least, to the cognitive dysfunction frequently encountered in this population. Cardiovascular disease is the most important cause of morbidity and mortality in elderly individuals worldwide. The rate of cardiovascular events increases after 65 years in men and after 75 years in women. Myocardial infarction and stroke are the leading disorders caused by atherosclerosis, that lead to death or functional incapacity. Elderly people have a greater risk to develop atherosclerotic cardiovascular disease. The incidence and prevalence of atherosclerosis increase with age and the number of cardiovascular events is higher in elderly patients. The most efficient treatment against atherosclerosis is the treatment with statins, that has been shown to decrease the risk both of stroke and coronary artery disease in all age groups. The advantages of the treatment become evident after at least one year of treatment. Primary prevention is the most important way of preventing cardiovascular disease in elderly individuals, by promoting a healthy lifestyle and reducing the risk factors. Secondary prevention after a stroke or myocardial infarction includes mandatory a statin, to diminish the risk of a recurrent cardiovascular event. The possible side effects of statin therapy are diabetes mellitus, myopathy, and rhabdomyolysis, hepatotoxicity. The side effects of the treatment are more likely to occur in elderly patients, due to their multiple associated comorbidities and drugs that may interact with statins. In elderly people, the benefits and disadvantages of the treatment with statins should be put in balance, especially in those receiving high doses of statins.

Genital self-mutilation: A challenging pathology (Review).

Genital self-mutilation is a pathology that leads to numerous and important discussions, rarely presented in the medical literature. There have been many attempts to explain the reasons behind these medical phenomena, but single cases have been generally reported, making it extremely difficult to draw valid conclusions. It is acknowledged that there are psychotic and non-psychotic causes, from psychiatric problems and sexual identity disorders to cultural or religious reasons, alcohol or recreational drug consumption, unconventional types of sexual satisfaction or self-satisfaction. Recent theories consider self-mutilation as a phenomenon of reducing distress or tension, as an expression of feelings of anger or sorrow. It is believed that 55-85% of those who have resorted to self-mutilation have at least once in their life tried to commit suicide. There is evidence that early discovery and intervention as well as proper treatment in regards to psychosis can significantly reduce the number of self-mutilation episodes, with a protective role of these individuals. Cases of genital self-mutilation may be considered real medical emergencies, sometimes extremely challenging and accompanied by severe complications. Injury of the genital area is usually accompanied by numerous early or long-term complications due to the marked vascular area and to the microbial flora present in this part of the body. The degree of mutilation is an unforeseen aspect that the medical staff may have to encounter during the intervention, sometimes testing their imagination and surgical skills when dealing with such a case. Understanding the causes of these self-aggressive behaviors, which may be life-threatening, is critical and multidisciplinary mobilization is needed after treatment of the acute phases. The outcome of these patients depends on integrated collaborative work. These cases represent a serious reason for frustration for the physicians involved in solving them, and knowledge of these issues is valuable to urologists, psychiatrists and other health professionals.

Therapeutic potential of interleukin-15 in cancer (Review).

The immune system is dysfunctional in cancer, and therapeutic approaches designated to restore immunity and increase long-term overall survival are desirable. The role of immunotherapy is to trigger the immune system to recognize and destroy tumor cells. Interleukin-15 (IL-15) is a member of the common gamma-chain (γc) cytokines that promote the differentiation and expansion of T cells, B cells and natural killer (NK) cells, leading to enhanced antitumor responses. This suggests that IL-15 is a promising candidate for anticancer therapy. Renewed interest in cancer immunotherapy has led to an increased number of preclinical studies and clinical trials that have investigated the reliability and potency of IL-15-based agents, not only as single therapy, but also in combination with others. This review provides a description of these studies which show the advantages and disadvantages of IL-15 as an immunotherapeutic agent. We present here the role of IL-15 and pharmacologically improved IL-15 superagonists as a single treatment or in combination with other therapeutic agents.

Overactive bladder: A review and update.

Overactive bladder syndrome is a chronic, disabling condition with physical, psychological and social consequences that significantly affects the quality of life of millions of patients worldwide. The economic impact of this disorder is crucial. Overactive bladder syndrome is a little-known condition, with different manifestations from patient to patient, which causes a great deal of frustration to the medical staff involved. The patient requires a clear explanation and the full support of the attending physician. It is extremely important to establish a correct diagnosis and an effective individualized treatment. The collaboration and understanding of these patients are extremely important aspects. Improving the quality of life in these patients is the main purpose in managing this condition. There are several treatment modalities that may be used progressively, with favorable albeit inconsistent results. This condition remains extremely challenging for specialists and, unfortunately, always one of maximum interest.

Subtotal Colectomy as Part of Debulking Surgery for Advanced-stage Ovarian Cancer.

BACKGROUND/AIM: The presence of extensive lesions of peritoneal carcinomatosis is found in a significant number of cases of extended digestive resection surgery, such as subtotal colectomy. The aim of this study was to report a series of 17 cases that necessitated performing subtotal colectomy as part of cytoreductive surgery for advanced-stage ovarian cancer. PATIENTS AND METHODS: Between 2012 and 2020 subtotal colectomy was associated as part of the debulking effort in 17 cases. RESULTS: The median age at the time of surgery was 59 years, while the initial stage at the time of diagnosis was IIIC in 14 cases, and respectively IV in three cases. Optimal debulking surgery was achieved in all cases. The continuity of the digestive tract was reestablished in 11 cases, while in the remaining 6 cases a terminal ileostomy was performed. CONCLUSION: Extended digestive tract resections may be needed in certain cases in order to maximize the debulking effort in patients with advanced-stage ovarian cancer.

Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (Review).

Patients with type 2 diabetes exhibit higher cardiovascular risk than normal individuals. Optimal blood glucose levels are rarely achieved in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a new antidiabetic drug class with multiple metabolic effects. Some trials have evaluated their safety, but it has been recently demonstrated that this new class has cardiovascular benefits, through other mechanisms than glycemic control. The use of GLP-1RAs was associated with a significant reduction of cardiovascular and all-cause mortality, with a safe profile related to pancreatitis or thyroid cancer, as compared with placebo. This review presents the cardiovascular and metabolic benefits of GLP-1 RAs versus placebo, in patients with type 2 diabetes. Semaglutide and liraglutide demonstrated a reduction in cardiovascular events, with similar rates on cardiovascular mortality. Ongoing trials assess the cardiovascular benefits and side effects of dulaglutide treatment. Exenatide and liraglutide demonstrated the decrease of blood pressure values, weight reduction and improvement of dyslipidemia. Liraglutide induced, both in vivo and in vitro, an improvement of blood circulation, increasing the nitric oxide level and inhibiting the adhesion and procoagulant factors. Also, liraglutide demonstrated beneficial effects on cardiac remodeling after myocardial infarction, but more large trials are required. However, the international guidelines recommend using GLP-1 RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line agents in patients intolerant to metformin.

New oral anticoagulants - possible extension to other indications (Review).

Anticoagulant treatment is necessary in various conditions, with curative or preventive purposes. Until recently, the only oral anticoagulants available have been vitamin K antagonists. To overcome the disadvantages of the antivitamin K oral anticoagulants, new oral anticoagulants (NOACs) have been developed and included in clinical trials. After more than 60 years of using vitamin K antagonists, the introduction of NOACs represent a medical breakthrough, with promising prospects. Due to their promising results and better safety profile, NOACs have become an appealing alternative to vitamin K antagonists in a short period of time. NOACs have been approved for the prevention and treatment of venous thromboembolism and for the prevention of stroke in patients with nonvalvular atrial fibrillation. Starting with postoperative venous thromboprophylaxis after hip replacement surgery, NOACs have been approved also for other clinical situations. Rivaroxaban is the first oral anticoagulant approved to be used in combination with an antiplatelet agent to prevent atherothrombotic events in adults with coronary artery disease and/or peripheral artery disease. However, further investigation is needed to establish which group of patients would benefit most from this medical approach. Furthermore, preliminary studies have shown that NOACs seem to be a reasonable choice of anticoagulation for patients with cancer, but further studies are expected.

Benefits of erectile function recovery programs after radical prostatectomy (Review).

Radical prostatectomy is one of the most frequent therapeutic options used for the management of patients diagnosed with prostate cancer. Normal erectile function after radical prostatectomy is a great problem for numerous patients and a real challenge for urologists worldwide. The advancements that have been made over the years in terms of minimally invasive surgery, as well as in terms of surgical techniques, have reduced the incidence of erectile dysfunction, but even so, its rate remains high and the post-operative recovery of erectile function is a long and costly process. Phosphodiesterase 5 inhibitors have provided excellent results and have become the first-line treatment for these patients, followed by intracavernous injections with alprostadil. Several studies have underlined the impact of phosphodiesterase 5 inhibitors in terms of preventing the fibrotic changes that are responsible for the irreversible erectile dysfunction. The general opinion is that an erectile function recovery process should be started as soon as possible after surgery to prevent the negative effects of neuropraxia.

Autonomic dysfunctions in multiple sclerosis: Challenges of clinical practice (Review).

Multiple sclerosis, demyelinating, inflammatory, degenerative, and chronic disease, raises many challenges in terms of disease management. The autonomic nervous system is affected by neuroinflammation but also contributes to its maintenance and the evolution of the disease. Multiple sclerosis interfering with parasympathetic or sympathetic modulation may influence the immune response. Less attention is paid to autonomic dysfunctions, although they produce a serious impact on the quality of life. In addition to motor disabilities, patients also have non-motor dysfunctions. Regardless of its clinical forms, patients with multiple sclerosis may have autonomous disturbances such as bladder, sexual, cardiovascular, thermoregulatory, gastrointestinal dysfunction and fatigue. These must be identified based on medical history, clinical symptoms, and specific paraclinical tests. In addition to the multitude of immunomodulatory therapeutic agents that influence the progression of the disease, the therapy of autonomic dysfunctions remains difficult to address. However, their identification and treatment lead to increased quality of patient management and avoid complications of this disease.

Congenital systemic candidiasis: a comprehensive literature review and meta-analysis of 44 cases.

Systemic candidiasis is a frequent complication in neonatal units, but congenital systemic candidiasis is an unusual diagnosis, observed in both full-term and preterm infants, with less than 50 cases reported to date. Congenital candidiasis presents with a wide spectrum of symptoms, ranging from diffuse skin eruptions to severe systemic disease, resulting in fetal demise or early neonatal death. Although management guidelines have been published almost two decades ago, due to the rarity of this type of infection, conclusive recommendations are difficult to establish, since they are based on anecdotal experience. In this paper, we present a comprehensive meta-analysis of the current scientific knowledge regarding congenital candidiasis, which spans 54 years and includes a total of 44 cases.

Measurement of skin viscoelasticity: A non-invasive approach in allergic contact dermatitis.

Non-invasive bioengineering technologies are constantly being developed, as they can provide useful insights and contribute to the improvement of medical care and scientific education. The purpose of this study was to assess skin viscoelasticity using the suction chamber method in patients with allergic contact dermatitis vs. healthy subjects, before and after applying a moisturizer safety testing cream. This was a prospective controlled study over a 3-year period (March 2016-March 2019), with 81 subjects being divided in two balanced groups: Patients with allergic contact dermatitis and healthy subjects, respectively. The skin viscoelasticity was determined for all subjects with Cutometer®, using the suction method, by performing a dynamic assessment of parameters before and after applying a moisturizing cream. The results indicate a decrease in the elasticity parameters in both groups, indicating an improvement of the elastic properties under the treatment. Skin capacity to return to its previous form after the deformation, i.e., pure elasticity and biological elasticity, showed overall elevated values in the group with contact dermatitis, demonstrating the efficacy of the emollient cream after applying it for 28 days (increase by 11.7 and 4.9% respectively, compared with baseline, when patients had dry, untreated skin). However, in healthy subjects, these parameters do not achieve important values, but they remain rather stable over time with a very slight improvement (6.6% after 28 days). The Cutometer is an easy to use, efficient and widely used instrument for measurements in studies that perform a quantitative assessment of the effectiveness of different formulations intended for application on the skin.

Vaccination in multiple sclerosis - Challenging practices (Review).

Infections are an ever-present problem in the medical community, even more so for patients with multiple sclerosis (MS), for whom these infections have been linked to relapses and neurological disabilities. Even though it was believed that MS can be caused by an infection, research does not support this theory. MS is a chronic inflammatory disease considered to be autoimmune. Vaccination is proven to be one of the most effective means to prevent infections, but still it is surrounded by controversy in the general populations, as well as in the MS group. Vaccines are generally considered safe for MS patients. The exceptions from this, which turn into contraindications, are a medical history of allergic reactions to one of the vaccine components and immunosuppressed patients in the particular case of live vaccines. Given the presumed autoimmunity of the disease, some medication for MS is immunosuppressive and any live vaccine should be administered before starting treatment. Although there is still confusion regarding this subject, the current guidelines have clearer recommendations about vaccinations in MS patients and especially in treated MS patients.

Dyslipidemia: A Trigger for Coronary Heart Disease in Romanian Patients with Diabetes.

Previous studies have reported age and gender disparities in the occurrence and therapeutic approach of dyslipidemia and (or) coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate these differences in Romanian patients with T2DM. A cross-sectional, observational, retrospective study was conducted using the medical records of T2DM patients who attended the outpatient facility of the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest, Romania for routine check-ups in a six-month period. We analyzed the records of 217 diabetic patients (mean age 69 ± 11 years; 51.15% women). We found no significant gender differences in the occurrence of dyslipidemia, CHD or CHD + dyslipidemia or in terms of statin prescription. However; patients aged 65 years or older were significantly more affected by dyslipidemia, CHD or CHD + dyslipidemia, versus subjects aged <65 years. Further, they were more likely to be prescribed statin therapy (p < 0.0001 for all). Statins were prescribed to 67.24% of the patients with dyslipidemia; 61.01% of the subjects with CHD; and to 91.48% of the patients who had both conditions. e recorded no gender differences in the occurrence of CHD and (or) dyslipidemia in Romanian T2DM patients. Patients aged 65 years or older had a higher prevalence of CHD and/or dyslipidemia, and were more likely to be prescribed statins, versus younger counterparts. However, many T2DM patients with CHD and (or) dyslipidemia were undertreated: Nearly 33% of the subjects with dyslipidemia, and nearly 40% of the ones with CHD were not prescribed statins.

Squamous Cell Carcinoma from Abscessed, Mature Cystic Ovarian Teratoma - A Case Report and Literature Review.

BACKGROUND/AIM: Malignant transformation of mature cystic ovarian teratoma is a scarce eventuality, only rare cases being reported so far. Furthermore, development of this transformation in the setting of an abscessed tumor is even scarcer. The aim of this study was to report the case of a 47-year-old patient submitted to surgery for such a lesion. CASE REPORT: The patient was investigated for diffuse pelvic pain and diagnosed with a 10×7×8 cm mass at the level of the left adnexa with imaging findings suggesting the presence of an ovarian teratoma. The patient was submitted to surgery involving a total hysterectomy with bilateral adnexectomy, lymphadenectomy and peritoneal biopsies. The histopathological examination demonstrated the presence of squamous cell carcinoma areas transformation in association with areas of abscess. Postoperatively the patient was submitted to six cycles of platinum-based chemotherapy and concurrent external radiotherapy. At one-year follow-up she is free of recurrent disease. CONCLUSION: Although malignisation of mature cystic ovarian teratoma is a rare event, it should not be omitted when mature ovarian teratoma is suspected; however, association between malignant transformation and abscess is a scarcer eventuality.

Heart failure and chronic obstructive pulmonary disease: a review.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are important causes of morbidity and mortality worldwide. The association between the two conditions have significant systemic effects and a chronic, progressive evolution, affecting exercise tolerance and quality of life. The diseases share common risk factors, such as smoking, advanced age, and low-grade systemic inflammation. The majority of symptoms and physical signs, such as dyspnoea, orthopnea, nocturnal cough, exercise intolerance, muscle weakness may coexist in both pathologies. Thus, the differential clinical diagnosis between exacerbation of COPD and HF decompensation may be difficult. Natriuretic peptides are sensitive biomarkers of HF, used mostly to exclude HF if their values are less than 100 pg/mL for Brain Natriuretic Peptide (BNP), respectively less than 300 pg/mL for N-terminal-pro Brain Natriuretic Peptide (NT-proBNP). Natriuretic peptides are very useful in emergency, for the differential diagnosis of acute dyspnoea. Echocardiography is the standard imaging technique of HF diagnosis and should be performed in all patients with potential HF. Treatment of patients with both HF and COPD should include drugs that prolong survival in HF, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, cardioselective beta1-blockers, aldosterone antagonists, and long-acting bronchodilators (an antimuscarinic rather than a beta2-agonist). The prognosis of patients with both diseases is worse than in patients with only one of the two conditions. These patients represent a continuous challenge of diagnosis and treatment for the clinicians and require a close monitoring of cardiopulmonary function.