The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression.

BACKGROUND: The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression. METHODS: A total of 3,780 patients from the EuroSIDA study under follow-up after 2001 with a current CD4(+) T-cell count ≤200 cells/mm(3) were stratified into five groups: group 1, viral load (VL)<50 copies/ml on cART; group 2, VL 50-99,999 copies/ml on cART; group 3, VL 50-99,999 copies/ml off cART; group 4, VL≥100,000 copies/ml on cART; and group 5, VL≥100,000 copies/ml off cART. Poisson regression was used to identify the risk of (non-fatal or fatal) AIDS- and non-AIDS-related events considered together (AIDS/non-AIDS) or separately as AIDS or non-AIDS events within each group. RESULTS: There were 428 AIDS/non-AIDS events during 3,780 person-years of follow-up. Compared with group 1, those in group 2 had a similar incidence of AIDS/non-AIDS events (incidence rate ratio [IRR] 1.04; 95% CI 0.79-1.36). Groups 3, 4 and 5 had significantly higher incidence rates of AIDS/non-AIDS events compared with group 1; incidence rates increased from group 3 (IRR 1.78; 95% CI 1.25-2.55) to group 5 (IRR 2.36; 95% CI 1.66-3.40), demonstrating the increased incidence of AIDS/non-AIDS events associated with increasing viraemia. After adjustment, the use of cART was associated with a 40% reduction in the incidence of AIDS/non-AIDS events in patients with VL 50-99,999 copies/ml (IRR 0.59; 95% CI 0.41-0.85) and in those with a VL>100,000 copies/ml (IRR 0.66; 95% CI 0.44-1.00). Similar relationships were seen for non-AIDS events and AIDS events when considered separately. CONCLUSIONS: In patients with ongoing severe immunosuppression, cART was associated with significant clinical benefits in patients with suboptimal virological control or virological failure.

[Assessment of energy intake in HIV--positive adults]. / Ocena wartosci energetycznej calodziennych racji pokarmowych osób doroslych HIV-pozytywnych.

The purpose of this study was to determine energy intake in HIV-positive adults. In the study participated 150 adults. Energy intake and percentage of energy from protein, carbohydrate and fat were measured using 24-hour dietary recalls and computer program Wikt 1.3. The results of the study showed that energy intakes were below the dietary reference values for HIV-positive. Moreover the analyzed diets contained too small protein and carbohydrate contents but too high level of fat. Despite of this fact, the majority of respondents had correct BMI value.

Anaesthesia for ophthalmologic surgical procedures in a patient with advanced amyotrophic lateral sclerosis: a case report.

INTRODUCTION: Anaesthesia procedures for surgical interventions in patients with amyotrophic lateral sclerosis (ALS) are not commonly found in clinical practice, and often have special considerations that must be taken into account in treatment planning. As a result, these procedures are rarely subject to publication, rendering it difficult for the anaesthesiologists to find useful and reliable information on this topic. ALS also presents a contraindication to the use of nondepolarising neuromuscular blocking drugs during general anaesthesia. CASE PRESENTATION: In the case presented here, a 52-year old, White man, the progression of the disease to tetraparesis and respiratory failure, in addition to having the patient on chronic mechanical ventilation support, provided additional challenges to the handling team. The maturation of cataracts severely impaired communication with the patient, and surgical treatment of the cataract presented the only means to save communication. Such interventions are generally performed under local anaesthesia with the advice of the attending anaesthesiologist. However, in this case the patients' announcements during the operation would be unreadable to the advising anaesthesiologist. Here, the authors share experiences from a successfully applied combination of topical and general anaesthesia for two cataract operations and a vitrectomy. This was tolerated well by the patient, and without any side-effects. CONCLUSION: The applied treatment resulted in a substantial improvement of the vision and allowed communication to be maintained with the patient.

[HIV infected child in otolaryngological practice]. / Dziecko zakazone HIV w praktyce otolaryngologicznej.

The authors present material about 12 HIV infected children at the age between 0 and 18 years observed and treated in Department of Infectious Diseases Medical University of Gdansk in the period between 1991 till 2006. Retrospectively medical records of 4 of them currently undergoing observation and treatment have been analyzed taking into consideration: ways of HIV infection, applying the possible retroviral profilactic to a mother and a child, the damaging o of immunological condition in the period of observation and treatment as well as the possible head and neck changes. The authors come to conclusion that changes in oral cavity may be the first symptom of child HIV infection and in the oral candidiasis symptoms the possibility of HIV infection should be taken into account.

[Relationship between inflammatory changes revealed in cerebrospinal fluid and prognosis in acute viral encephalitis]. / Zaleznosc pomiedzy wystepowaniem zmian zapalnych w plynie mózgowo-rdzeniowym a rokowaniem w ostrym wirusowym zapaleniu mózgu.

OBJECTIVE: To assess the relationship between inflammatory changes in cerebrospinal fluid (CSF) and prognosis in patients with acute viral encephalitis (AVE). PATIENTS AND METHODS: retrospective medical records analysis of 99 cases of AVE, 37 females and 62 males, age 4-71. Patients were assigned to 2 subgroups: group I--without inflammatory changes in CSF (cytosis < or = 10/mm3 - 40 cases) and group II--with detectable abnormalities in CSF (cytosis >10/mm3 - 59 cases). Long term prognosis and unfavorable outcome were assessed at the moment of discharge from hospital and with a use of questionnaire sent to patients and were described as: 0--complete recovery, 1--long-term disabilities, 2--death. MAIN OBSERVATIONS: Among 99 patients with acute viral encephalitis complete recovery was observed in 61% of cases, in 32% the disease resulted in long term consequences and disabilities and 7% died from reasons related to encephalitis. RESULTS: Patients without inflammatory changes in CSF statistically significantly (p < 0.05) more frequently suffered from coma, early epileptic episodes, respiratory disorders, unfavorable outcome and epilepsy. In a group II statistically significantly more often fever and Herpes simplex etiology were observed. CONCLUSIONS: (1) Among 99 patients in 32% AVE resulted in long-term (subtle as well as severe) disabilities and 7% died from reasons related to AVE. (2) Patients without inflammatory abnormalities in CSF tended to have more severe clinical course and worse prognosis than those with detectable increase of CSF cytosis (>10 cells/mm3).

Coagulation, coma, and outcome in bacterial meningitis--an observational study of 38 adult cases.

OBJECTIVES: The purpose of this study was to evaluate the epidemiology of intravascular coagulation in bacterial meningitis and to recognise the associations with disease severity and outcome. METHODS: Thirty-eight consecutively admitted adult patients with microbiologically proven bacterial meningitis were observed prospectively for platelets count (PLT), platelets-decline (dPLT), prothrombin ratio (PTr), INR, and D-dimer levels during the first three days in relation to disease severity (Glasgow Coma Scale--GCS, APACHE-III) and outcome (Glasgow Outcome Scale--GOS). RESULTS: The prevalence of activated coagulation measured by abnormal laboratory results varied respectively: PTr--30%, INR--36%, PLT--38%, dPLT--50%, and D-dimer--88%. Patients with GCS <9 at admission presented with laboratory results suggesting triggered coagulation: dPLT 48 vs. 15%/day (p=0.0246), INR 1.6 vs. 1.12 (p=0.0014), PTr 76 vs. 93% (p=0.0020). An unfavourable outcome (GOS 1-4) was observed in 42% of patients and was associated with: PLT <170 or >265 G/L (OR--24.4; p=0.0006), PTr <82% (OR--5.00; p=0.0388), INR >1.1 (OR--5.04; 0.0336), and D-dimer >850 ng/ml (OR--24.0; p=0.0033). CONCLUSIONS: Coagulation was activated in a majority of patients with bacterial meningitis and related to coma and unfavourable outcome.

[Occurrence of disseminated intravascular coagulation in purulent meningitis and influence on mortality in 118 patients]. / Wystepowanie wykrzepiania sródnaczyniowego w ropnym zapaleniu opon mózgowo-rdzeniowych i wplyw na smiertelnosc u 118 pacjentów.

UNLABELLED: Disseminated intravascular coagulation (DIC) is an important, but not satisfactory explained risk factor of death in purulent meningitis (PM). OBJECTIVE: Evaluation of: 1) acute thrombocytopenia (ATP) in patients with PM, 2) dynamics in changes of peripheral blood platelet (PLT) count and serum coagulation factors, 3) correlation between acute DIC and mortality in PM. METHODS: Analysis ofATP (platelets < or = 150 K/microL and/or decrease in PLT > or = 100 K/microL/24 hours) and prothrombin ratio, fibrinogen, d-dimmer and antithrombin III in survivors and nonsurvivors in 118 adult patients with PM. 37 further patients have been disclosed because of non-bacterial PM or chronic conditions predisposing to ATP or DIC. MAIN OBSERVATIONS: DIC defined as ATP occurred in 56 %, defined as elevated d-dimmer level in 72%. 16 (14%) patients died. RESULTS: Mortality correlated significantly with the lowest PLT count on first 3. days (p=0,049) and with PLT decline (p=0,015). Differences in survivors/nonsurvivors were observed in: ATP on 1. day 48% vs. 75% (p<0,05), daily PLT decline 9%/day vs. 32%/day (p<0,05), prothrombin ratio 89% vs. 74% (p<0,05) and INR 1,2 vs. 1,7 (p<0,005). CONCLUSION: DIC is an important risk factor in PM. Aggravated DIC do correlate significantly with higher risk of death.

Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry.

OBJECTIVE: Helicobacter DNA has been detected in the hepatobiliary tree of patients with chronic liver diseases (CLD). The presence of H. pylori in the stomach compared with in the liver of the same patients with CLD has not been studied, therefore to the aim of this study was to investigate the presence of Helicobacter DNA and antigens in the liver and stomach of Polish patients with chronic liver diseases using molecular and immunological methods. MATERIAL AND METHODS: Gastric mucosa and liver tissue samples and sera were collected from 97 Polish patients with CLD. Anti-H. pylori antibodies were detected by enzyme immunoassay (EIA), and H. pylori-like antigens detected by immunohistochemistry. Helicobacter DNA was detected in stomach and liver samples using a semi-nested Helicobacter genus-specific polymerase chain reaction (PCR) assay, and Helicobacter species identified by denaturing gradient gel electrophoresis (DGGE) and sequencing analysis of amplified PCR products. RESULTS: H. pylori was identified by DGGE and sequence analysis in 60/62 (97%) and 25/25 (100%) of the gastric and liver Helicobacter genus-positive samples, respectively, whereas DNA of H. heilmannii was detected in 2/62 (3%) of the Helicobacter genus-positive gastric samples. H. pylori cagA gene was detected in 23/62 (36%) and 3/25 (12%) gastric and liver tissue samples, respectively. H. pylori-like antigens were detected in 61/97 (63%) gastric mucosa and in 40/97 (41%) liver tissue samples. CONCLUSIONS: H. pylori-like organisms appeared to dominate the gastric mucosa and liver tissue of Polish patients with CLD. The prevalence of the cagA gene was higher in stomach compared with liver samples, which suggests a possible role of cagA negative H. pylori-like organisms in CLD. On the other hand, no significant correlation was found between the presence of H. pylori-like DNA and antigens in the liver and liver function tests.

[Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final report)]. / Pegylowany interferon alpha-2a z rybawiryna w leczeniu przewleklego wirusowego zapalenia watroby typu C (raport koncowy z badan).

UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland.

Hepatitis B virus (HBV) infection is one of the major global epidemiological problems. The aim of our study was to determine the distribution of HBV genotypes in Poland since the data concerning the spread of HBV viruses in the central-eastern region of Europe is still very limited. HBV DNA was extracted from 58 serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were performed. The HBV virus from 43 serum samples from hepatitis B infected patients was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most prevalent subtype in the Amerindians. Our results coincide with the general European HBV prevalence. However, HBV genotype F, which is not a common genotype in European countries, was detected and so was relatively high occurrence of genotype D, which may reflect historical and ethnical migration events in Poland in the past.

The changing pattern of Kaposi sarcoma in patients with HIV, 1994-2003: the EuroSIDA Study.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has radically changed the clinical course of human immunodeficiency virus (HIV) infection. The goals of the current study were to assess the change in the incidence of Kaposi sarcoma (KS) among European patients with HIV since the introduction of HAART and to identify the factors associated with the development of KS among patients receiving HAART. METHODS: The incidence of KS and the factors associated with the development of this malignancy in patients receiving HAART were evaluated using Poisson regression. Patients examined in the current study were among the 9803 individuals with HIV who were enrolled in the EuroSIDA study, a pan-European multicenter investigation. RESULTS: There was an estimated annual reduction of 39% (95% confidence interval [CI], 35-43%; P < 0.0001) in the incidence of KS between 1994 and 2003. The proportion of acquired immunodeficiency syndrome (AIDS) diagnoses made due to KS during prospective follow-up ranged from 4.1% to 7.5%, and there was no significant change over time in this figure (P = 0.97). Four thousand fourteen patients began receiving HAART during prospective follow-up; 41 of these 4014 were subsequently diagnosed with KS (1.0%). After adjustment in multivariate analyses, patients with higher current CD4 counts were found to have a decreased incidence of KS (incidence rate ratio [IRR], 0.60; 95% CI, 0.53-0.68; P < 0.0001), as were those for whom more time had elapsed since the initiation of HAART (IRR, 0.77; 95% CI, 0.60-0.98; P = 0.037). In contrast, homosexual men were found to have a significantly increased incidence of KS (IRR, 2.12; 95% CI, 1.00-4.54; P = 0.050) CONCLUSIONS: The current incidence of KS among patients with HIV is less than 10% of the incidence reported in 1994; the proportion of AIDS diagnoses made on the basis of KS diagnoses remains near 6%. Most individuals who developed KS while receiving HAART began treatment with low CD4 cell counts and developed KS within 6 months of the initiation of HAART. There continues to be an increased incidence of KS among homosexual men and a greatly reduced incidence of KS among patients with higher CD4 counts.

Evaluation of nevirapine and/or hydroxyurea with nucleoside reverse transcriptase inhibitors in treatment-naive HIV-1-infected subjects.

OBJECTIVE: To examine the effect of adding nevirapine (NVP) and/or hydroxyurea (HU) to a triple nucleoside analogue reverse transcriptase inhibitor (NRTI) regimen in terms of efficacy and tolerability. METHODS: : HIV-1-infected, treatment-naive adults were randomized, using a factorial design, to add NVP and/or HU to the triple NRTI backbone of zidovudine plus lamivudine plus abacavir. Primary endpoint was treatment failure, defined as having plasma HIV RNA levels > 50 copies/ml after week 24, or discontinuation of randomized treatment. Follow-up was 72 weeks. RESULTS: For the 229 subjects, median plasma HIV-1 RNA was 4.61 log10 copies/ml and median CD4 cell count was 269 x 10 cells/l. NVP users reached plasma HIV-1 RNA < 50 copies/ml more rapidly than subjects using no NVP (log-rank test; P = 0.011). In the as-treated analysis, 21.6% of subjects using NVP versus 48.8% using no NVP reached the primary endpoint (P = 0.013). In the intent-to-treat analysis, 83.3% of subjects using HU versus 73.0% using no HU experienced treatment failure (P = 0.060), while no difference was observed in the as-treated analysis (34.5 versus 36.7%). Differences in the intent-to-treat analysis were accounted for by toxicity: 52.6% of subjects using HU experienced toxicity leading to discontinuation of randomized treatment versus 28.7% of subjects using no HU. CONCLUSION: The use of NVP in addition to a triple NRTI regimen improved both short- and long-term antiretroviral efficacy. The use of HU significantly contributed to treatment failure because of toxicity.

Results of treatment of Wilson's disease--own observations.

BACKGROUND: Causative treatment of genetically determined Wilson's disease (WD) has been impossible so far, although gene therapy could be real in the future. Nowadays the principle of treatment is the elimination of the excess of easily mobilized copper, bound by chelating agents, the most important of which is d-penicillamine, through the kidneys. Blocking of the intestinal absorption of copper by administration of zinc preparations, which additionally induce hepatic metallothionein synthesis, is also possible. The aim of our study was to present own observations and results of treatment of Wilson's disease. MATERIAL/METHODS: During the last 16 years, we have observed 33 patients aged 13-60 (mean age 27 years) with various forms of WD. The studied group consisted of 11 females and 21 males, admitted to hospital or seen at the Specialistic Outpatient Department of Hepatology with various diagnoses. In addition to standard laboratory tests, the levels of ceruloplasmin, serum and urine copper, as well as the activity of some hepatic enzymes, proteins and HBV/HCV infection markers were determined. The patients were also examined by a neurologist and an ophthalmologist, with psychiatric consultation if necessary. Taking into account the overall clinical presentation, the patients were divided into the following groups according to the form of the disease: fulminant, acute, hepatic, hepatic with neurological and psychiatric symptoms, neuropsychiatric, asymptomatic. RESULTS: All the patients were initially treated with d-penicillamine. In most of them, no side effects were observed. The treatment was continued according to the levels of copper excreted with urine (for 10 years at the longest). After obtaining clinical improvement with reduced amount of copper excreted with 24-h urine, we tapered d-penicillamine doses or even discontinued the drug, introducing zinc preparations. In asymptomatic carriers, zinc preparations were used throughout the period of treatment. CONCLUSIONS: Early institution of chelation treatment is associated with good prognosis both in hepatic and neurological forms of WD. Zinc preparations are effective and safe in neurological and oligosymptomatic forms of the disease.

Autoimmune hepatitis in the material of Department and Regional Hospital of Infectious Diseases in Gdansk.

BACKGROUND: The aim of the study was the analysis of patients with autoimmune hepatitis (AIH), with respect to diagnostics, clinical course and treatment, based on the material from the wards of infectious diseases. MATERIAL/METHODS: The study was carried out in the group of 106 AIH patients--95 females aged 11-81 (mean age 46 years) and 11 males aged 8-73 (mean age 35 years). The diagnosis of AIH was based on international criteria, including biochemical test results, autoantibodies, and liver tissue morphology. Serological test excluded hepatitis of viral etiology. Diagnostic procedures included also blood cell count, biochemical parameters of liver function with protein fractions, immunoassays (immunoglobulins, autoantibodies), according to commonly used methods. Liver biopsies were performed in 93 patients. RESULTS: The clinical presentation mimicked acute viral hepatitis in 75% of cases, in the remaining 25% corresponded to chronic viral hepatitis. 26% had other coincident disorders of autoimmune etiology. In 84% the initial stage of the disease was characterized with moderately severe course, in 11%--severe, 7% of the patients died--half of them at the initial stage of the disease. The following morphological patterns of hepatic abnormalities were observed: hepatitis chronica agresiva, fibrosis periportalis, hepatitis chronica agresiva in cirrhosim vertens, cirrhosis hepatis activa, hepatitis chronica persistence, hepatitis granulomatosa. Over 40% of patients demonstrated relapses of the disease due to discontinuation of treatment after obtaining clinical and biochemical remission. 51 patients were treated with glucocorticosteroid monotherapy, the same number with glucocorticosteroids combined with azathioprine, 1 female patient underwent liver transplantation. In nearly 30% of patients, the diagnosis of AIH was established after a period of persistence of pathologic symptoms of over a year. CONCLUSIONS: Late diagnoses of AIH indicate insufficient knowledge of the disease among physicians. The methods of treatment used in AIH are not sufficiently effective. Discontinuation of treatment should be preceded in each case by overall assessment of the pathologic process, including biochemical parameters, autoantibody level and liver histopathology.