Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

Clostridium difficile the hospital plague.

Clostridium difficile infection (CDI) has become one of the major public health threats in the last two decades. An increase has been observed not only in the rate of CDI, but also in its severity and mortality. Symptoms caused by this pathogen are accompanied by intense local and systemic inflammation. We confirmed that Raman microspectroscopy can help us in understanding CDI pathogenesis. A single erythrocyte of patients with CDI shows a difference, approximately 10 times, in the intensity of the Raman spectra at the beginning of hospitalization and after one week of treatment. The intensity level is an indicator of the spread of the inflammation within the cell, confirmed by standard laboratory tests. Many of the observed bands with enormously enhanced intensity, e.g. 1587, 1344, 1253, 1118 and 664 cm(-1), come from the symmetric vibration of the pyrrole ring. Heme variation of recovered cells in the acute CDI state between the first and the seventh day of treatment seems to show increased levels of oxygenated hemoglobin. Intense inflammation alters the conformation of the protein which is reflected in the significant changes in the amide I, II and III bands. There is an observed shift and a significant intensity increase of 1253 and 970 cm(-1) amide III and skeletal protein backbone CC stretching vibration bands, respectively. Principal Component Analysis (PCA) was used to find the variance in the data collected on the first and seventh day. PC2 loading in the 1645-1500 cm(-1) range shows an increase of heme, Tyr, Trp, or Phe vibrations because of changes in the protein microenvironment due to their exposure. Positive maxima at 1621, 1563 and 1550 in the PC2 loading originated from the ring vibrations. These observations indicate that Clostridium difficile toxins induce cytopathogenicity by altering cellular proteins.

Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Measurement of radial bone mineral density in patients after heart transplantation.

Limited physical activity, steroidotherapy and immunosuppression are known risk factors for the development of osteoporosis. The purpose of our current work was to investigate whether patients after heart transplantation (Htx) have an increased incidence of osteoporosis. We compared bone mineral density (BMD) in 32 post-transplant patients with a reference group of 1548 healthy age-matched males. Measurement of BMD was carried out with a Dtx 100 Osteometer on the distal and ultradistal segment of the non-dominant radius. Our results revealed a decreased BMD in HTx patients ranging from 6.9 to 10% in the ultradistal (p = 0.0446) and from 0.4 to 3.5% in the distal segment (p = 0.0593).

[Recurrent suppurative meningitis in a patient after 2 operations for cerebrospinal rhinorrhea]. / Nawrotowy przebieg ropnego zapalenia opon mózgowo-rdzeniowych u chorego dwukrotnie operowanego z powodu wycieku plynu mózgowo-rdzeniowego.

A case of two episodes of purulent meningitis is described. The patient was a young man with nasal liquorrhoea related to previous trauma and operated on twice because of persisting liquorrhoea.

[Conservative treatment of multiple brain abscesses]. / Zachowawcze wyleczenie mnogich ropni mózgu.

Non-surgical treatment of multiple cerebral abscesses in 67 old man was described. Staphylococcus aureus was isolated from cerebral spinal fluid. The patient was treated with antibiotics and metronidazole and was discharged in satisfactory state after 40 days.

[Possibilities of objective evaluation of local reactive cell infiltrates in transplantable tumors]. / Mozliwosci obiektywnej oceny miejscowych nacieków z komórek odczynowych w przeszczepialnych nowotworach.

The studies on infiltrations consisting of reactive cells, i.e. lymphocytes, macrophages and neutrophils within and in the vicinity of neoplastic tissue were performed in order to elucidate the nature of the growth and to asses the role of these cells in human tumors. The objective methods for both qualitative and quantitative evaluation of the infiltrating cells are necessary to obtain comparable results. We report our studies on the numbers and types of reactive cells present in 3 transplantable murine tumors with different immunogenicity (SaL-1, LLC, MCA-Sa). The cytological characterization of cells was performed as following: after enzymic digestion of the tissue the cell suspension was then passed through Millipore filters and dyed. The preliminary evaluation of the percentage of lymphocytes T found in the tumor infiltrations was performed using cytotoxicity test with monoclonal antithymocytic serum (Monoclonal Anti-Mouse Thy 1, 2). We have shown that there are differences in the number and type of reactive cells in infiltrations of the three different tumor tested. With the increasing mass of tumors the percent of reactive cells decreases proportionally.

[The effect of diabetes and cholelithiasis on the course and consequences of acute viral hepatitis type B]. / Wplyw cukrzycy i kamicy zólciowej na przebieg i nastepstwa ostrego wirusowego zapalenia watroby typu B.

Course and consequences of acute hepatitis B on the group of 40 patients with diabetes mellitus and 21 patients with cholelithiasis were estimated with respect to the group has consisted of 82 person with acute hepatitis B without coexisting disorders. Hospitalization time has been longer on the group with diabetes mellitus or cholelithiasis and activity of serum alanine aminotransferase (AlAT) has brought back to normal longer than on the control group. Maximal activity of serum AlAT has been higher on the control group and maximal bilirubin concentration in serum the patients with diabetes mellitus or cholelithiasis has not differed from the control group. Acute hepatitis B passed into chronic hepatitis or cirrhosis of the liver on the group with diabetes mellitus or cholelithiasis frequently, has been observed.

[Effect of furfural on the respiratory system]. / Wplyw furfurolu na uklad oddechowy.

Fifty-one workers of Butadien Plant, exposed to furfurol , had their respiratory system examined. Questionnaire studies demonstrated chronic bronchitis in 23.5% of subjects. Spirometric tests do not show subjective complaints. This seems to be related to hypercortisolemia, as experiments on animals indicate that furfurol inhalations increase corticosteroids concentrations in blood serum.

[Epidemiologic and clinical characteristics of patients with hepatitis type C on the bases of selected parameters]. / Charakterystyka epidemiologiczna i kliniczna chorych na zapalenie watroby typu C na podstawie wybranych parametrów.

We present dates of epidemiological and clinical analysis of patients with chronic hepatitis C. 107 patients were hospitalized in our Chair and Department of Infectious Diseases CM UJ since 1991 till 1995. 41 cases were diagnosed as acute viral hepatitis C and 66 as chronic hepatitis C. In our material 59% cases were nosocomial infections. The certain risk in this group was the surgery (28% of patients). Next possibility of transmission HCV was hospitalization in nonoperative ward (17%). The patients receiving blood or blood products were the next significant risk group of HCV infection. Medical staff is still a certain risk group. About 1/3 of patients have no obvious route of infection. In 70% of patients with hepatitis have the acute phase of HCV infection without any symptoms. 79% cases of acute hepatitis C tends to chronic hepatitis, with high percent of active disease (64%) which can lead after years to cirrhosis or even to hepatocellular carcinoma.

[Diagnostic difficulties in encephalitis: two case reports]. / Trudnosci diagnostyczne w zapaleniach mózgu--opis dwóch przypadków.

The differential diagnosis of psychiatric symptoms in encephalitis, especially in the early phase of the disease may be very difficult. It is particularly hard to distinguish it from the classic psychosis. The diagnostic problems have been presented on the basis of analysis of two case reports of the acute encephalitis in young persons. The presence of fever and pathological changes in the CSF were the most important indicators that helped to establish the diagnosis of encephalitis during the phase of acute psychopathological disorders.

[Risk and circumstances in which people are bitten by dogs in Cracow-- observations from the Consulting Clinic of Infectious Diseases]. / Ryzyko i okolicznosci pogryzienia ludzi przez psy w Krakowie--obserwacje Punktu Konsultacyjnego Kliniki Chorób Zakaznych.

Inquiries about incidence of bites people by dogs have been made in the Consulting Ward for prophylactics of rabies of Chair and Department of Infectious Diseases in Cracow. There are frequent cases of people bitten by dogs, which usually occur in the streets. Victims are usually young. In the most cases there are not connection between victim's behavior and incidence. Dogs however bite without an understandable reasons frequently when they are controlled by their owners. The owners of the dogs often are not aware of their responsibility to prevent their dogs from biting passers-by.

[Meningitis with acute respiratory distress syndrome in adults and jaundice--case report]. / Zapalenie opon mózgowo-rdzeniowych przebiegajace z zespolem ostrej niewydolnosci oddechowej u doroslych i zóltaczka--opis przypadku.

The case of leptospirosis with adult respiratory distress syndrome (ARDS) and severe jaundice in young abattoir worker has been presented. Institution of invasive therapeutic methods: continuous mandatory ventilation (CMV) with positive end-expiratory pressure (PEEP) and plasmapheresis, together with antibioticotherapy resulted in complete recovery. We discuss some characteristic features of the leptospirosis, which with the data from epidemiological history can lead to early diagnosis of this forgotten disease.

[Four cases of bacterial meningitis after epidural anesthesia]. / Cztery przypadki ropnego zapalenia opon mózgowo-rdzeniowych w nastepstwie znieczulenia zewnatrzoponowego.

Four patients with bacterial meningitis, previously anaesthetized epidurally, have been described. In one case the course of the disease was very serious and resulted in irreversible neurological lesion. Although epidural anaesthesia is considered to be a harmless procedure it can cause some purulent complications.

[The role of cytokines in bacterial meningitis]. / Rola cytokin w bakteryjnym zapaleniu opon mózgowo-rdzeniowych.

Bacterial meningitis is the serious infection of the central nervous system (CNS), and stimulated by bacteria inflammatory host response has crucial role in its pathogenesis. The most important elements of this response are cytokines, especially tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10), which have antiinflammatory activity. Production of cytokines in the CNS triggers a cascade of inflammatory mediators. Better understanding of mechanisms which take place during the course of the bacterial meningitis can be useful in differential diagnosis, prognosis and treatment of this disease. Investigations on the role of cytokines in the bacterial meningitis, have great therapeutic implications, and can result in introduction to the treatment antiinflammatory drugs, which can help to reduce mortality rate and number of complications.

[Laryngeal diphtheria in a young woman causes diagnostic difficulties--case report]. / Blonica krtani u mlodej kobiety przyczyna trudnosci diagnostycznych--opis przypadku.

A case of severe laryngeal diphtheria in a young woman was presented. Initially, the presence of a foreign body in the larynx of this patient was suspected. The differential diagnosis of a foreign body should include diphtheric laryngitis as this may cause obstruction of the respiratory tract. This can lead to severe complications.

[Encephalitis as a severe complication of rubella--case report]. / Zapalenie mózgu ciezkim powiklaniem rózyczki--opis przypadku.

The case of severe encephalitis in the course of rubeola in young woman was presented. The self-limited increased level of aminotransferases and hyperglycaemia were reported during the course of disease. Any late complications of the encephalitis were observed and the patient was discharge from the hospital in good condition.