Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

Challenges in the Differential Diagnosis of COVID-19 Pneumonia: A Pictorial Review.

COVID-19 pneumonia represents a maximum medical challenge due to the virus's high contagiousness, morbidity, and mortality and the still limited possibilities of the health systems. The literature has primarily focused on the diagnosis, clinical-radiological aspects of COVID-19 pneumonia, and the most common possible differential diagnoses. Still, few studies have investigated the rare differential diagnoses of COVID-19 pneumonia or its overlap with other pre-existing lung pathologies. This article presents the main radiological features of COVID-19 pneumonia and the most common alternative diagnoses to establish the vital radiological criteria for a differential diagnosis between COVID-19 pneumonia and other lung pathologies with similar imaging appearance. The differential diagnosis of COVID-19 pneumonia is challenging because there may be standard radiologic features such as ground-glass opacities, crazy paving patterns, and consolidations. A multidisciplinary approach is crucial to define a correct final diagnosis, as an overlap of COVID-19 pneumonia with pre-existing lung diseases is often possible and suggests possible differential diagnoses. An optimal evaluation of HRTC can help limit the clinical evolution of the disease, promote therapy for patients and ensure an efficient allocation of human and economic resources.

Reversal of brain aging by targeting telomerase: A nutraceutical approach.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age­related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18­month­old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR­ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle­aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Risk Factors and Genetic Predisposition in Colorectal Cancer: A Study on Young and Old Adults.

According to GLOBOCAN 2018 data Colorectal cancer (CRC) represents the third most commonly diagnosed cancer in the world and has the second-highest mortality rate. The incidence of CRC has been rising worldwide, the majority of cases being in developing countries mostly due to the adoption of an unhealthy lifestyle. The main driving factors behind CRC are a sedentary lifestyle, obesity, red meat consumption, alcohol, and tobacco; however, early detection screenings and standardized treatment options have reduced CRC mortality. Better family history and genetic testing can help those with a hereditary predisposition in taking preventative measures.

Metabolic Impact of Diabetes Mellitus Type 2 in Hepatitis C Virus Infected Patients.

OBJECTIVE: Patients with chronic hepatitis C are subjected to a greater risk of cardiovascular disease and difficult to control diabetes mellitus type 2 (T2DM) comparatively to people that have never contracted Hepatitis C Virus (HCV). We aimed to investigate the impact of T2DM on HCV patients with the help of Fibromax test results compared to nonT2DM patients, and the metabolic differences between the 2 study groups. Our long term goals are to observe the long term impact of achieving systemic virusologic response (SVR) by means of Direct-Acting antivirals (DAA) between the 2 cohorts. RESEARCH DESIGN AND METHODS: We selected a lot of 200 patients with HCV that will undergo interferon-free DAA-based antiviral treatment for HCV and we used the results of the Fibromax Test to compare the biological parameters of T2DM and nonT2DM patients. RESULTS Among patients with T2DM compared to NonT2DM there is a significant correlation on Steatotest, NashTest, GGT, Glycemia, body weight, height and BMI. Test also showed that 15,5% of the test group had elevated glycemia, indicating the probability of developing diabetes in the future. CONCLUSIONS: Our results suggest that HCV patients that also have T2DM are subjected to a combined higher risk of accelerated steatosis development, steatohepatitis, added difficulty in controlling glycemic levels. All these previous elements combined with a prevalence for patients to be overweight have a negative metabolic impact. Eradication of HCV with the help of DAA is important in order to help improving the metabolic impact of diabetes on steatosis, steatohepatitis. An added benefit is better management of glycemic control by decreasing insulin use and eliminating one risk factor of T2DM.

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19.

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.

Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy.

The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC.

Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model.

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.

A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming.

Immunoexpression of MMP-8, MMP-9 and TIMP-2 in dilated cardiomyopathy.

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.

The incidence of skin lesions in contrast media-induced chemical hypersensitivity.

Contrast agents are used in radiology to increase the sensibility and specificity of radiological techniques. Some of these compounds have side effects that include organ toxicity (with kidney being the most affected organ) and hypersensitivity reactions. We performed multiple PubMed searches from January, 2008 to January, 2018 for studies regarding adverse reactions to compounds used as contrast agents in imagistic techniques. The initial research identified 929 records written in English. After further excluding 223 non-human studies, 292 articles that had irrelevant designs as reviews, meta-analysis, commentaries, editorials and case reports, 414 studies were selected for retrieval. After reading the abstracts, we excluded 363 studies as they had little relevance to the study. In total, 51 full-articles were assessed for eligible studies to be included. Finally, 20 articles were included in the analysis. In our systematic literature search the incidence of overall skin immediate reactions to iodinated contrast media (ICM) had an incidence between 1.15 and 0.12%, depending on the cohort analyzed in the studies. The percentage of cutaneous manifestations in the cohort that experienced immediate hypersensitivity reactions was between 33.33 and 87.7%. The most frequent skin manifestations were urticaria, rashes, pruritus and limited facial edema. Non-iodinated contrast agents have a safer profile compared with ICM, the incidence of immediate adverse reactions being very low in gadolinium-based contrast agents and other agents used for contrast-enhanced ultrasound. The incidence of delayed reactions was between 10.1 and 0.03%. In the studies analyzed by us the main adverse reactions due to delayed hypersensitivity phenomena were cutaneous manifestations that were present between 70.27 and 100% of the cases. Regarding the risk factors for developing immediate adverse reactions, being female was a predisposing factor accompanied by history of allergy and history of reactions to contrast media. An accurate anamnesis of the patients and a correctly conducted pretreatment can limit the incidence and the severity of the adverse reactions and also can avoid the life occurrence of life-threatening reactions.

Antimicrobial resistance in bacterial pathogens among hospitalised patients with severe invasive infections.

The most severe infections are invasive infections, due to the fact that the germs can accumulate in multiple sites and produce a body-wide infection known as sepsis. Septic shock has the highest mortality rate among non-traumatic medical conditions. In this study, we aimed to evaluate the incidence and prevalence of invasive infections in a hospital environment. Another second objective was to establish the aetiology of invasive infections in our hospital and the antibiotic resistance profile of the germs involved, which are both important for determining the therapeutic approach for the treatment of these infections. The study included 505 hospitalized patients from which we collected a total of 974 blood cultures. For the analysis of the blood cultures, we used an automated incubator. The bottles flagged as positive were subcultured on blood agar, and the grown colonies were identified using an identification system. Invasive infections had a prevalence rate of 27.72% in our hospital. From the 974 blood cultures, we isolated 170 bacterial strains: Staphylococcus aureus (SA; 63 strains, 37.06%), Klebsiella spp. (27 strains, 15.88%), coagulase-negative staphylococci (CoNS; 18 strains, 10.59%), Enterococcus spp. (17 strains, 10.00%), Escherichia coli (12 strains, 7.06%), Streptococcus spp. (11 strains, 6.47%) and other bacterial species. The prevalence of methicillin-resistant SA (MRSA) in our study was 36.51% from the SA strains. The MRSA prevalence differed significantly according to age (37.50% in adults vs. 28.57% in children, P=0.047) and ICU admission (42.42% in ICU patients vs. 30.00% in non-ICU patients, P=0.018). We performed a multivariate analysis of the invasive infection risk which detected as significant predictors the admission into the cardiology ward and plastic surgery ward. On the whole, the findings of this study indicate that the high prevalence of Gram-positive cocci in blood cultures, mostly SA, with multidrug resistance has important consequences for the management of invasive infections.

Colon cancer: clinical, macroscopic and microscopic aspects.

Although in developed countries the incidence of colorectal cancer is decreasing through the introduction of well-designed screening systems, the worrying worldwide increase of the mortality rate by colorectal neoplasm indicates the need for a thorough characterization of this pathology. Clinical, endoscopic, histopathological and immunohistochemical data provide important information for creating categories of patients that can benefit from intensive screening methods and for establishing the prognosis based on these data. Approximately 80% of the colorectal cancer develops from adenomas, which shows that early detection of premalignant lesions is an important step in reducing global incidence and mortality. Our study aims at providing information about the clinical, imaging and histopathological characterization of colorectal neoplasm and premalignant lesions. A total of 98 patients were evaluated, including 72 patients diagnosed with colorectal cancer and 26 with premalignant lesions. Patients underwent colonoscopy with biopsy specimens that were examined histopathologically. From the epidemiological data, we observe a higher incidence in men with a men/women ratio of 2/1, with a median age in colorectal cancer patients of 63.93 years. Different data on signs and symptoms were observed according to the colonoscopy location, with a slight difference between symptoms of patients with premalignant lesions compared to those diagnosed with colorectal neoplasm. Endoscopy showed that the rectum was the most frequent location, followed by the left colon, the tumor having a vegetative aspect in most cases. Histopathology confirms that the most common subtype is adenocarcinoma, described in 67 of the studied cases. The moderate differentiation degree is present in more than half of the cases.