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.

Cardiovascular and Metabolic Consequences of Liver Transplantation: A Review.

Liver transplantation (LT) is considered the curative treatment option for selected patients who suffer from end-stage or acute liver disease or hepatic malignancy (primary). After LT, patients should be carefully monitored for complications that may appear, partially due to immunosuppressive therapy, but not entirely. Cardiovascular diseases are frequently encountered in patients with LT, being responsible for high morbidity and mortality. Patients with underlying cardiovascular and metabolic pathologies are prone to complications after the transplant, but these complications can also appear de novo, mostly associated with immunosuppressants. Metabolic syndrome, defined by obesity, hypertension, dyslipidemia, and hyperglycemia, is diagnosed among LT recipients and is aggravated after LT, influencing the long-term survival. In this review, our purpose was to summarize the current knowledge regarding cardiovascular (CV) diseases and the metabolic syndrome associated with LT and to assess their impact on short and long-term morbidity and mortality.

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.

Synthesis and Characterization of Novel Cu(II), Pd(II) and Pt(II) Complexes with 8-Ethyl-2-hydroxytricyclo(7.3.1.0(2,7))tridecan-13-one-thiosemicarbazone: Antimicrobial and in Vitro Antiproliferative Activity.

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H2O)2(OAc)) (1), (Cu(HL)(H2O)2(SO4)) (2), (Cu(L)(H2O)2(NO3)) (3), (Cu(L)(H2O)2(ClO4)) (4), (Cu(L)2(H2O)2) (5), (Pd(L)(OAc))H2O (6), and (Pt(L)2) (7) were synthesized from 8-ethyl-2-hydroxytricyclo(7.3.1.0(2,7))tridecan-13-one thiosemicarbazone (HL). The ligand and its metal complexes were characterized by IR, ¹H-NMR, (13)C-NMR, UV-Vis, FAB, EPR, mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The free ligand and the metal complexes have been tested for their antimicrobial activity against E. coli, S. enteritidis, S. aureus, E. faecalis, C. albicans and cytotoxicity against the NCI-H1573 lung adenocarcinoma, SKBR-3 human breast, MCF-7 human breast, A375 human melanoma and HL-60 human promyelocytic leukemia cell lines. Copper complex 2 exhibited the best antiproliferative activities against MCF-7 human breast cancer cells. A significant inhibition of malignant HL-60 cell growth was observed for copper complex 2, palladium complex 6 and platinum complex 7, with IC50 values of 1.6 µM, 6.5 µM and 6.4 µM, respectively.

Immunological investigations in prostatic pathology--a prospective study.

BACKGROUND: BPH with prostatitis represents one of the most common urological pathologies affecting most men. The etiology of both conditions remains at the discretion of the various assumptions. OBJECTIVES: The body's cellular immune response in prostate adenoma is a less studied aspect which we have focused on, in this paper. The correlation with a wide range of information from specific investigations such as prostate-specific antigen (PSA) and total histopathology was the secondary aim of this work. METHODS: The study included 31 patients who underwent surgery for prostate adenoma (TUR-P, simple prostatectomy) between 08.2013 and 03.2014. Patients presenting urinary tract infection were excluded from the study. Preoperative evaluation of the immunological examination consisted of lymphocyte immunophenotyping (T, B, NK cells) from peripheral blood performed by flow cytometry. Total PSA was performed in serum by enzyme immunoassay EIA. RESULTS: In all forms of anatomoclinical BPH we found the presence of two major cellular changes: decrease of suppressor/cytotoxic T-cells and decrease of B cells. These deficits may confer an increased susceptibility to viral infection and tumor transformation. NK cells were grown in BPH associated with inflammation. PSA-prostate specific antigen values were grown at less than 50% of the patients in all clinical forms of BPH.

Impact of retroperitoneal tumors on the digestive tract (Review).

Primary retroperitoneal tumors are a rare group of neoplasms that often prove to be a real therapeutic challenge. The clinical picture is in most cases nonspecific, being the result of nearby tissue and organ compression, displacement and/or invasion, and it usually includes a variety of deceiving signs and symptoms that may lead to diagnostic errors. During the course of the disease, up to half of the patients diagnosed with retroperitoneal tumors can develop gastrointestinal symptoms, the incidence of such symptoms significantly increasing with tumor size. Therefore, symptoms such as abdominal distension, diffuse abdominal pain or epigastric pain mimicking acute pancreatitis, diarrhea, constipation, jaundice, hematemesis, melena and hematochezia can be found. The mainstream treatment for primary retroperitoneal tumors is surgical excision, chemotherapy and radiotherapy but associated with poor results. Due to their rarity, as well as to the complexity of these tumors, patients should be managed in high volume centers that allow the possibility of a multidisciplinary approach.

Tumoral markers in bladder cancer (Review).

Bladder tumors are frequently diagnosed urologic malignant diseases with an extremely high recurrence rate compared to other neoplastic tumors. Urothelial bladder carcinomas are mostly identified in their incipient form, as non-muscle invasive, but despite that, a third of them develop into aggressive recurrent disease. The diagnosis of bladder carcinoma at this moment is established using cytology and cystoscopy and is a great challenge for clinicians due to the lack of sensitivity. Urinary biomarkers could improve and enhance the diagnosis and screening techniques and determine a more accurate recurrence rate. However, bladder cancer is a heterogeneous disease and the existence of a single marker test with reduced cost is unlikely; thus, until then, the use of a panel of markers to obtain valuable information is inevitable even though suboptimal for use. To improve this deadlock, new biomarker panels should be identified and prepared to equalize the cost-efficiency balance. The present paper is a literature review concerning the most commonly used tumor markers in urinary bladder cancer as well as the most commonly encountered genetic modifications in such patients.

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.

Hepatic artery reconstruction after extended resection for borderline resectable pancreatic head cancer: A case report.

Pancreatic head cancer is frequently associated with invasion of the surrounding vascular structures, such cases being considered for a long period of time as unresectable. Improvement of the vascular surgery techniques allowed association of extended vascular resections and reconstructions, increasing in this way the percentage of patients benefiting from radical surgery. We present the case of a 47-year-old male patient with no significant medical history diagnosed with a large pancreatic head tumor invading the common and proper hepatic artery as well as the portal vein. The venous reconstruction was performed using a synthetic prosthesis while the left hepatic artery was sutured to the left gastric artery; meanwhile the right hepatic artery was reconstructed using the splenic artery. In conclusion, extended hepatic artery resection followed by arterial reconstruction in association with portal vein resection and prosthetic replacement might be needed in cases presenting large pancreatic head tumors with vascular invasion.

Renal tumor biomarkers (Review).

One of the most common types of cancer worldwide (9th most commonly diagnosed) is renal cell carcinoma (RCC). It is more common in developed countries and it usually develops in individuals between 60 and 70 years of age. The earlier the disease is identified, the lower the morbidity. Therefore molecular markers that exist in blood and urine may be used for earlier detection and diagnosis but also for the follow-up of the patient after treatment, whether surgical or oncological. The trend is to analyze the gene and protein expression as they constitute a source for new biomarkers. These markers are promising but in clinical practice regarding disease management, they are rarely used. Biological markers can be employed in many tumors because they can identify the prognostic value for individual treatment. However, markers for RCC are not validated, and their analysis is currently under investigation. Previous findings have demonstrated that the metastatic potential of RCC can be predicted using the biological features of the tumor cell. It is believed that the transformation from epithelial to mesenchymal phenotype gives the tumor cell the ability to metastasize. The purpose of this review was to identify the most valuable tumor markers that can be clinically used for the prognosis, treatment and follow-up of patients with renal tumors.

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.

Malignant Priapism - What Do We Know About It?

Malignancy as an etiological factor involved in priapism pathogenesis is rare. Malignant priapism (MP) can arise as a result of penile tumor invasion, either from primary penile tumors or from metastatic penile tumors, or due to hematological malignancies. Non-urological penile metastases are associated with significant worse prognosis compared to urological penile metastases, the appearance of priapism in such cases affecting even more the prognosis and the survival of these patients. Patients diagnosed with hematological malignancies and priapism present significant higher survival rates compared to those who develop MP in the context of a non-hematological malignancy, this being related to the fact that hematological malignancies are more sensitive to chemo- and radiotherapy. Most malignant priapism cases are ischemic; therefore the management should be based on the initial steps of the IP therapeutic protocol. Considering the trigger factor that has led to the priapic event specific oncologic treatment can be added as well.

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.

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.

Mast cell activation syndromes - evaluation of current diagnostic criteria and laboratory tools in clinical practice (Review).

Mast cell activation syndromes (MCAS) represent a heterogeneous clinical entity caused by episodic and severe mast cell activation, including primary and secondary mast cell disorders (MCDs). The group of primary or clonal MCDs refers to systemic mastocytosis, other clonal MCAS and hereditary hypertryptasemia, while the secondary MCAS is characterized by normal mast cells (MCs) which are activated by external triggers, such as allergens or physical stimuli. Another category of MCAS is the idiopathic form, when no trigger or genetic mutation can be identified. Symptoms of mast cell activation are due to release of specific mediators and can be seen in many diseases, such as allergies, with localized or systemic clinical manifestations. Confirmation of MCAS is based on diagnostic criteria proposed by an international group of experts and the best available evidence in this field. It is generally accepted that the clinical picture of MCAS is non-specific and there are few available laboratory tools, making it difficult for clinicians to identify and confirm this entity. The diagnosis is established after exclusion of other possible clinical entities in most of the cases. Therefore, the actual diagnostic criteria of MCASs, some relevant clinical aspects and laboratory tools used in clinical practice were reviewed.