Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.

Virulence Factor Genes and Antimicrobial Susceptibility of Staphylococcus aureus Strains Isolated from Blood and Chronic Wounds.

Staphylococcus aureus is one of the predominant bacteria isolated from skin and soft tissue infections and a common cause of bloodstream infections. The aim of this study was to compare the rate of resistance to various antimicrobial agents and virulence patterns in a total of 200 S. aureus strains isolated from patients with bacteremia and chronic wounds. Disk diffusion assay and in the case of vancomycin and teicoplanin-microdilution assay, were performed to study the antimicrobial susceptibility of the isolates. The prevalence of genes encoding six enterotoxins, two exfoliative toxins, the Panton-Valentine leukocidin and the toxic shock syndrome toxin was determined by PCR. Of the 100 blood strains tested, the highest percentage (85.0%, 31.0%, and 29.0%) were resistant to benzylpenicillin, erythromycin and clindamycin, respectively. Out of the 100 chronic wound strains, the highest percentage (86.0%, 32.0%, 31.0%, 31.0%, 30.0%, and 29.0%) were confirmed as resistant to benzylpenicillin, tobramycin, amikacin, norfloxacin, erythromycin, and clindamycin, respectively. A significantly higher prevalence of resistance to amikacin, gentamicin, and tobramycin was noted in strains obtained from chronic wounds. Moreover, a significant difference in the distribution of sea and sei genes was found. These genes were detected in 6.0%, 46.0% of blood strains and in 19.0%, and 61.0% of wound strains, respectively. Our results suggest that S. aureus strains obtained from chronic wounds seem to be more often resistant to antibiotics and harbor more virulence genes compared to strains isolated from blood.

Cumulative Effects of Particulate Matter Pollution and Meteorological Variables on the Risk of Influenza-Like Illness.

The cold season is usually accompanied by an increased incidence of respiratory infections and increased air pollution from combustion sources. As we are facing growing numbers of COVID-19 cases caused by the novel SARS-CoV-2 coronavirus, an understanding of the impact of air pollutants and meteorological variables on the incidence of respiratory infections is crucial. The incidence of influenza-like illness (ILI) can be used as a close proxy for the circulation of influenza viruses. Recently, SARS-CoV-2 has also been detected in patients with ILI. Using distributed lag nonlinear models, we analyzed the association between ILI, meteorological variables and particulate matter concentration in Bialystok, Poland, from 2013-2019. We found an exponential relationship between cumulative PM2.5 pollution and the incidence of ILI, which remained significant after adjusting for air temperatures and a long-term trend. Pollution had the greatest effect during the same week, but the risk of ILI was increased for the four following weeks. The risk of ILI was also increased by low air temperatures, low absolute humidity, and high wind speed. Altogether, our results show that all measures implemented to decrease PM2.5 concentrations would be beneficial to reduce the transmission of SARS-CoV-2 and other respiratory infections.

Change in the geometry of positive- and negative-powered soft contact lenses during wear.

Contact lens wear causes mutual interactions between the ocular surface and the lens, which may affect comfort as well as vision. The aim of this study was to examine deformations in modern positive- and negative-powered silicone hydrogel soft contact lenses (SiH SCLs) after 7 days of continuous wear. This pre-post interventional study included 64 eyes: 42 eyes with myopia of -3.00 D and 22 eyes with hyperopia of +3.00 D. All patients underwent general ophthalmic examination, corneal topography/tomography, total corneal and epithelial thickness mapping, and specular microscopy before and after the wearing period. SiH SCLs made of senofilcon A were worn continuously for 7 days on all eligible eyes. The geometry of the new and used lenses was measured 3 to 6 minutes after removal in two perpendicular planes using a custom-made swept source optical coherence tomography (SS-OCT) system for in vitro measurements. The anterior and posterior radii of curvature decreased in -3.00 D lenses in two perpendicular planes. This effect correlated significantly with average keratometry of the cornea. Sagittal lens height was lower in +3.00 D lens after wear, which correlated moderately with the corneal sagittal height. A significant decrease in central corneal epithelial thickness was observed after wearing +3.0 D lenses. In conclusion, SiH SCLs made of senofilcon A undergo minor deformations after 7-day continuous wear. Geometry modifications are different for -3.00 D and +3.00 D lenses, and they imitate the shape of the anterior eye surface. These geometric changes are accompanied by a decrease in the central thickness of corneal epithelium after +3.00 D lens wear.

Pediatric Enteroviral Central Nervous System Infections in Bialystok, Poland: Epidemiology, Viral Types, and Drivers of Seasonal Variation.

Enteroviruses are common causes of infections of the central nervous system (CNS) that in temperate climates tend to peak in the summer. The aim of the study was to describe epidemiology, drivers of seasonality, and types of enteroviruses causing infections of the CNS in children in Northeastern Poland. We prospectively collected data on children hospitalized with infection of the CNS attributed to enteroviruses in Bialystok, Poland, from January 2015 to December 2019. In total, 224 children were included. Nineteen different enterovirus types were identified in isolates collected from 188 children. Coxsackie B5 (32%), echovirus 30 (20%), and echovirus 6 (14%) were the three most common types. Enteroviruses were more prevalent during the summer-fall season. Infections caused by echovirus 30 peaked early in June and coxsackievirus B5 in July, whereas echovirus 6 peaked late in October. Phylogenetic analyses of these three enterovirus types showed multiple lineages co-circulating in this region. Mean air temperatures and precipitation rates were independently associated with monthly number of cases. Considering lack of effective treatment or vaccine, easy transmission of enteroviruses between susceptible individuals, their high mutation rate and prolonged time of viral shedding, continued monitoring and surveillance are imperative to recognize enteroviral infections of the CNS and the changes in circulation of enteroviruses in Poland.

Correlation of retinal sensitivity in microperimetry with vascular density in optical coherence tomography angiography in primary open-angle glaucoma.

PURPOSE: To evaluate the correlation between retinal sensitivity in microperimetry (MP) with vessel density (VD) using optical coherence tomography angiography (OCTA) in primary open-angle glaucoma (POAG). METHODS: We enrolled 30 participants (52 eyes) with POAG and 15 participants (23 eyes) in the healthy control group. All participants were examined for retinal structure using OCTA to assess VD and Spectral domain OCT (SD-OCT) to assess ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Retinal sensitivity was tested with MP and standard automatic perimetry (SAP). RESULTS: The VD in moderate/severe POAG was lower than that in mild POAG and healthy control in the macular superficial vascular plexus (SVP) (38.7±6.3% vs. 42.9±5.2%, 49.7±2.6% respectively, P<0.001) and peripapillary radial peripapillary capillaries (pRPC) (36.4±5.7% vs. 43.6±6.6%, 49.1±2.4% respectively, P<0.001). The Pearson's correlations between function-structure parameters were strongest with MP average sensitivity threshold and SVP VD in the area of whole macula (r = 0.68); followed by SAP mean deviation (MD) and pRNFL thickness (r = 0.63); SAP MD and pRPC VD (r = 0.59) and MP average threshold and GCC thickness (r = 0.54). We found the AUROCs for discriminating between glaucomatous and healthy eyes were highest for structural parameters as follows: pRNFL (0.94), macular SVP whole (0.92), pRPC (0.92) and GCC (0.91). Pairwise comparison of the above parameters showed no difference (P>0.05). CONCLUSION: The relationship between microvascular damage in the macular SVP whole and the decrease of MP average sensitivity threshold is stronger than the pRNFL thickness measurements and SAP parameters. OCTA and MP techniques are valuable methods that allow clinically monitor structural and functional changes in glaucomatous eyes.

Effect of Temperatures Used in Food Storage on Duration of Heat Stress Induced Invasiveness of L. monocytogenes.

The unpropitious conditions of the food processing environmenttrigger in Listeria monocytogenes stress response mechanisms that may affect the pathogen's virulence. To date, many studies have revealed that acid, osmotic, heat, cold and oxidative stress modify invasiveness of L. monocytogenes. Nonetheless, there is limited data on the duration of the stress effect on bacterial invasiveness. Since most food is stored at low or room temperatures we studied the impact of these temperatures on the duration of heat stress effect on invasiveness of 8 L. monocytogenes strains. Bacteria were heat-treated for 20 min at 54 °C and then incubated at 5 and 20 °C up to 14 days. A decrease in invasiveness over time was observed for bacteria not exposed to heating. It was found that heat shock significantly reduced the invasion capacity of all strains and the effect lasted between 7 and 14 days at both 5 and 20 °C. In conclusion, 20-min heating reduces invasion capacity of all L. monocytogenes strains; however, the stress effect is temporary and lasts between 7 and 14 days in the food storage conditions. The invasiveness of bacteria changes along with the incubation time and is temperature-dependent.

Disinfectant Susceptibility of Biofilm Formed by Listeria monocytogenes under Selected Environmental Conditions.

Listeria monocytogenes is a one of the most important food-borne pathogens. Its ability to form biofilm contributes to increased resistance to disinfectants and inefficient disinfection, posing a serious threat for the food industry, and in the end the consumer. The aim of this study was the comparison of the biofilm formation ability of L. monocytogenes strains on stainless steel, under different environmental conditions (temperature, pH, NaCl concentration, nutrients availability), and the assessment of biofilm susceptibility to disinfectants. The bactericidal activity of four disinfectants in two concentrations (100% and 50% of working solution) against biofilm was conducted on four clinical strains, four strains isolated from food and one reference strain ATCC 19111. It was found that biofilm susceptibility to disinfectants was influenced by environmental conditions. Biofilm susceptibility correlated with the decrease of temperature, pH, nutrients availability and salinity of the environment. The least sensitive to disinfectants was biofilm produced at pH = 4 (the bacterial number ranged from 0.25 log CFU × cm-2 to 1.72 log CFU × cm-2) whereas the most sensitive was biofilm produced at pH = 9 (5.16 log CFU × cm-2 to 7.84 log CFU × cm-2). Quatosept was the most effective disinfectant, regardless of the conditions. In conclusion, biofilm susceptibility to disinfectants is strain-dependent and is affected by environmental conditions.

Efficacy and safety of pegylated interferon α and ribavirin in patients monoinfected with HCV genotype 4.

INTRODUCTION: Dual therapy (PegIFN and ribavirin) (DT) was the standard of care in patients infected with HCV genotype 4 (HCV-4) until 2014. Nowadays, new treatment options are available including interferon (IFN)-based and other IFN-free regimens. AIM: To assess the efficacy (SVR24) and safety of DT and the selected predictor factors of SVR in HCV-4 infected patients. MATERIAL AND METHODS: One hundred and twelve patients (62 men) of median age 23 years were treated with DT for 48/72 weeks (107/5) in the years 2006-2014. Most of them were treatment naïve (80.4%) and with fibrosis F ≤ 2 (83.1%). To select a subset of independent predictors of SVR Logistic Regression Analysis was applied. RESULTS: SVR24 was achieved in 46/112 (41.1%) patients. The mean viral load was 5.55 log10 IU/ml. Lack of therapy experience increases the odds of achieving SVR (OR = 4.17; 1.04-16.67), whereas more advanced fibrosis and higher baseline viral load tend to decrease the probability of SVR (OR = 0.05; 0.01-0.52 and OR = 0.44; 0.17-1.13, respectively). In contrast, the weight loss is associated with higher probability of virological response (OR = 4.31; 1.37-13.60). Two hundred and seventy-nine adverse events (AEs) were reported in 96 individuals. The rates and types of AEs were similar in patients treated with PegIFN-α2a/RBV and PegIFN-α2b/RBV. Overall, 3 (2.7%) patients discontinued therapy prematurely because of serious AEs. CONCLUSIONS: SVR24 was low. Loss of weight was a new positive predictive factor of SVR found in our study. Most of the AEs were typical of those previously reported for DT.

Impact of selected predictive factors on sustained virologic response in HCV genotype 4 infected patients treated with pegylated interferon alpha and ribavirin

BACKGROUND: Dual therapy (PegIFN and ribavirin) (DT) had been the standard of care in patients infected with HCV genotype 4 (HCV-4) until 2014. Thereafter, new treatment options were available including IFNbased and other IFN-free regimens. Objectives: The aim was to assess the efficacy (SVR24) of DT and a selection of predictive factors of SVR in HCV-4 infected patients. METHODS: 112 patients (62 men) of median age 23 years were treated with DT for 48/72 weeks (107/5). Most of them were treatment naïve (80.4%) and with fibrosis F≤2(83.1%). Individuals with prior hepatitis B virus (HBV) infection, i.e. positive antibodies to the hepatitis B core antigen (anti-HBc), negative hepatitis B surface antigen and undetectable serum HBV DNA were included into the analysis. RESULTS: SVR24 was achieved in 46/112(41.1%) patients. Null response (NR) was recognized in 24.1%, partial response in 13.4%, relapse in 10.7% and breakthrough in 6.2% of patients. SVR24 was associated with lack of previous treatment experience, younger age (<40 years), pretreatment viral load <2x105 IU/ml, less advanced fibrosis (F≤2) and >10% loss of baseline weight. Anti-HBc was detected in 25(22.3%) patients out of which four (16%) achieved SVR24 in comparison to 42(48.8%) patients with anti-HBc negative (p<0.005); NR was observed in 10(40%) individuals vs 17(19.8%) in anti-HBc negative patients. CONCLUSIONS: SVR24 was low. The age <40 years, less advanced fibrosis, pretreatment viral load <2x105 IU/ml, lack of previous treatment experience, loss of body weight were the positive predictive factors of SVR24. Prior HBV infection correlated with poorer SVR24 and NR.

Long-term outcomes of thyroid dysfunction in patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

INTRODUCTION: Thyroid dysfunctions (TDs) are associated with pegylated interferon and ribavirin (PegIFN-α/RBV) therapy in patients with chronic hepatitis C (CHC) and are considered as possible extrahepatic manifestation of HCV infection OBJECTIVES: This study aimed to assess the long-term outcomes of TDs in patients with CHC treated with PegIFN-α/RBV METHODS: A total of 1,047 treatment-naïve patients with CHC were treated with PegIFN-α/RBV. TSH and FT4 were assessed at baseline, every 3 months during therapy and 6, 12 and 24 months after the end of therapy. Analysis was performed for two groups of patients depending on the absence (group A, n=77) or presence (group B, n=39) of TDs at baseline RESULTS: At baseline, TDs' prevalence was 3.7%; 53.8% hypothyroidism, 38.5% goiters, and 7.7% hyperthyroidism. 77 (7.4%) out of 1,008 euthyroid patients developed TDs; 45.5% hypothyroidism, 33.8% hyperthyroidism, 19.5% destructive thyroiditis, and 1.3% goiters. TDs' remission (TDR) was achieved in 59/116 (50.9%) of treated patients; 64.9% in group A and 23.1% in group B (p<0.001). Hyperthyroidism as compared to hypothyroidism increases the odds of TDR (OR=4.87 (1.65-14.35), p=0.004), whereas preexisting TDs and higher baseline viral load tend to decrease the probability of TDR (OR=0.21 (0.07-0.58), p=0.003 and OR=0.4 (0.22-0.73), p=0.003, respectively) CONCLUSIONS: The prevalence of TDs was low but over one-third of patients in whom TDs developed under PegIFN-α/RBV therapy did not recover. In one-fourth of patients with preexisting TDs remissions were observed. Treatment with PegIFN-α in the past must be taken into account as a potential cause of TDs

Continuous up to 4 Years Entecavir Treatment of HBV-Infected Adolescents - A Longitudinal Study in Real Life.

This study evaluated the long-term (up to 4 years) efficacy and safety of entecavir ETV treatment and analysed the significance of baseline and on-treatment factors in long-term ETV outcomes in adolescents with chronic hepatitis B (CHB). We determined the cumulative virological and serological outcomes of 44 adolescents with CHB receiving ETV for up to 4 years. To investigate the dynamics of HBV DNA, ALT activity and hepatitis B e antigen (HBeAg) seroconversion over time and their associations with the considered factors, generalized estimating equation (GEE) models were used. The cumulative rates of undetectable HBV DNA (<20 IU/ml) and HBeAg seroconversion after 4 years were 89.7% and 55.4%, respectively. In the study group, we showed that having undetectable HBV DNA at the 6th or 12th month of therapy predicted the achievement of a sustained response rate (SRR, defined as the loss of HBV DNA, loss of HBeAg and ALT normalization) at year 3 of ETV therapy (P = 0.048, OR = 5.83; P = 0.012; OR = 14.57, respectively). The GEE analysis indicated that of the different factors, the duration of ETV therapy had a strong impact on the achievement of virological suppression, HBeAg seroconversion and SRR in adolescents. Each month after the initiation of therapy, the odds of loss of HBV DNA increased by approximately 5% (OR = 1.05, P<0.0001), on average. Additionally, the GEE analysis revealed that adolescents with an age at infection of ≥10 years had 3 times higher odds of achieving undetectable HBV DNA than patients with a younger infection age (OR = 3.67, P = 0.028). None of the ETV-treated patients reported significant adverse effects. ETV is an effective and safe treatment option for adolescents with CHB. Undetectable HBV DNA in the 6th and/or 12th month of ETV treatment and older age at infection could predict maintained virological suppression.

Tenofovir rescue therapy in chronic hepatitis B patients who failed previous nucleoside analogue treatment.

BACKGROUND: Tenofovir (TDF) is considered as the first line therapy for chronic hepatitis B. This study presents the results of TDF monotherapy in patients who failed previous nucleoside analogue treatment. METHODS: The study included 29 patients treated with TDF 245 mg once daily for 18 months after lamivudine monotherapy (LAM arm: n = 15) or sequential therapy with lamivudine and entecavir (LAM → ETV arm: n = 14). The previous antiviral therapy was discontinued due to lack of efficacy. All patients had HBV DNA between 2.1 and 8.23 log10 IU/ml and 15 were HBeAg-positive, while 45% of patients had increased ALT activity. Undetectable HBV DNA (<20 IU/ml) at months 3, 6, 12 and 18 was the primary endpoint in the study, while HBeAg/HBsAg loss/seroconversion and ALT normalisation were secondary endpoints. RESULTS: Primary nonresponse to TDF was not observed. HBV DNA was undetectable in 80, 80, 80 and 93% in LAM arm and 50, 71, 86 and 86% in LAM → ETV arm patients, at 3, 6, 12 and 18 months of TDF therapy, respectively. One patient achieved anti-HBeAg seroconversion. 86.5% of patients had normal ALT activity at the end of the study. The baseline HBV DNA load, HBeAg status and the length of the duration of TDF therapy appeared significantly associated with the response to the therapy. HBV DNA clearance occurred faster in HBeAg-negative patients than in those positive for HBeAg. CONCLUSIONS: TDF is an effective antiviral medication in patients with previous exposure to LAM or LAM and ETV. Final proportion of patients who achieved undetectable HBV DNA and had normal ALT activity in both arms, was similar.

Renal impairment in patients with chronic hepatitis C treated with first generation protease inhibitors.

BACKGROUND: The incidence, course and risk factors associated with renal impairment (RI) in patients treated with triple therapy (TT) with pegylated interferon, ribavirin and telaprevir/boceprevir (PR/TVR/BOC) vs. dual therapy (DT) with PR were analyzed in this study. The association between RI and the decline of hemoglobin (Hb) was also examined. METHODS: Retrospective analysis included 110 patients with genotype 1b chronic HCV infection, aged 18 - 80 years, who underwent TT (48TVR/14BOC) or DT (48 patients). The estimated glomerular filtration rate (eGFR), serum creatinine concentration (SCr) and Hb were measured at baseline, at weeks 4, 12, 24, 48 of treatment, and post-treatment week 24. RESULTS: RI occurred in 9/62 (14.5%) patients who underwent TT, eight of whom were treated with TVR, one with BOC, and none treated with DT. The risk factors associated with RI were the following: TT (p = 0.0078), usage of nephrotoxic drugs (p = 0.0288), and older age (p < 0.0001). RI was reversible. A drop of Hb was associated with RI, older age and TT. CONCLUSIONS: RI is not a rare but a reversible complication of TT. It is necessary to monitor SCr and eGFR, especially in patients with a potential risk factor of RI occurrence. The Hb drop is more severe in patients with RI than in those without it.