Patient with actinomycosis of the cervicofacial and abdominal area, case report. / Wielopostaciowosc promienicy ­ jednoczesna aktynomikoza obszaru szyjno-twarzowego i brzusznego, opis przypadku.

Actinomycosis is a very rare, infectious disease, which is especially difficult to diagnose due to non-specific symptoms and the ability to emulate neoplasms or inflammatory changes. Due to those facts, it is often misdiagnosed or diagnosed too late to be successfully treated. This article presents the case of 31-year-old Caucasian female with recurrent upper respiratory tract infections and tonsillitis as the potential risk factors of actinomycosis. Upon examination of material collected through the course of tonsillectomy, the patient was diagnosed with actinomycosis of the left palatine tonsil. Despite the introduction of antibiotic therapy, initial progression was noted with the appearance of numerous, hypodense changes in the liver and the spleen, which regressed during further antibiotic treatment. According to our team's knowledge, this is the first described case of a patient with actinomycosis occurring simultaneously in the cervico-facial and abdominal area. The unusual localization and potential dissemination of actinomycosis should be considered in clinical practice.

Direct-acting antivirals in women of reproductive age infected with hepatitis C virus.

Eliminating hepatitis C virus (HCV) infection in the population of women of reproductive age is important not only for the health of women themselves but also for the health of newborns. This study aimed to evaluate the implementation of this goal by analysing the effectiveness of contemporary therapy in a large cohort from everyday clinical practice along with identifying factors reducing therapeutic success. The analysed population consisted of 7861 patients, including 3388 women aged 15-49, treated in 2015-2022 in 26 hepatology centres. Data were collected retrospectively using a nationwide EpiTer-2 database. Females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs. 15.7%) and less frequently showed comorbidities (40.5% vs. 44.2%) and comedications (37.2% vs. 45.2%). Hepatocellular carcinoma, liver transplantation, HIV and HBV coinfections were reported significantly less frequently in women. Regardless of the treatment type, females significantly more often reached sustained virologic response (98.8%) compared to males (96.8%). Regardless of gender, genotype 3 and cirrhosis were independent factors increasing the risk of treatment failure. Women more commonly reported adverse events, but death occurred significantly more frequently in men (0.3% vs. 0.1%), usually related to underlying advanced liver disease. We have demonstrated excellent effectiveness and safety profiles for treating HCV infection in women. This gives hope for the micro-elimination of HCV infections in women, translating into a reduced risk of severe disease in both women and their children.

Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study.

PURPOSE: Results of the low-dose radiation therapy (LDRT) in patients with pneumonia due to COVID-19 has been presented. METHODS: Fifteen patients received a single-fraction radiation dose of 1 Gy to the bilateral lungs due to pre-ARDS pneumonia in the course of COVID-19. Follow-up was performed on days 1, 3, 5, 7, 14 after LDRT. RESULTS: Eleven patients (73%) were released up until day 28. Median hospitalization was 20 days; 28-day mortality was 13%. Median O2 saturation improved within 24 h after LDRT in 14/15, with median SpO2 values of 84.5% vs. 87.5% p = 0.016, respectively. At day 14 of hospitalization, 46% did not require oxygen supplementation. Significant decline in CRP and IL-6 was observed within 24 h post LDRT. No organ toxicities were noted. CONCLUSION: LDRT is feasible, well tolerated and may translate to early clinical recovery in patients with severe pneumonia. Further studies are needed to determine optimal candidate, time and dose of LDRT for COVID-19 patients with pneumonia.

Remdesivir Decreases Mortality in COVID-19 Patients with Active Malignancy.

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

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.

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study).

PURPOSE: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement. MATERIAL AND METHODS: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants). RESULTS: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p â€‹< â€‹0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p â€‹< â€‹0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p â€‹< â€‹0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 â€‹pg/ml (OR-2.14), D-dimer concentration over 1000 â€‹ng/ml (OR-1.62) and PLT count below 150,000/µl (OR-1.57). CONCLUSIONS: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 â€‹pg/ml, D-dimer>1000 â€‹ng/ml and PLT<150,000/µl.

Immunosenescence and multiple sclerosis.

Changes in the immune system associated with ageing are known as immunosenescence. This is characterised by a decline in immune response, chronic inflammation and an increased risk of autoimmune diseases. A chronic inflammatory process with persistent production of proinflammatory mediators increases the risk for morbidity and mortality related to age, and has been dubbed 'inflamm-ageing'. Immunosenescence is associated with a decrease in the number of naive T and B cells, NK cells and disruption of the pro- and anti-inflammatory balance by changes in the production of cytokines. In fact, ageing of the immune system has a complex network of underlying causes which include not only natural mechanisms of senescence but also chronic disorders, lifestyle, environmental and epigenetic factors, and infections. Moreover, immunosenescence has an influence on the course of chronic diseases which have an onset in young adults, such as multiple sclerosis (MS). Current disease modifying therapies (DMTs) in MS aim to reduce the frequency of relapses and to slow disease progression, but they do not necessarily stop the accumulation of disability related to disease progression. Some features of immunosenescence found in aged healthy controls are already observed in MS patients at a younger age. The older population is characterised by an increased susceptibility to infections, a poor response to vaccinations, and a higher risk of developing cancer, vascular diseases and neurodegeneration. Immunosenescence is an important factor influencing the course of MS, and the safety and effectiveness of DMTs. The relationship between the pathogenic process underlying the development of MS and immunosenescence requires further investigation.

Severe Breakthrough COVID-19 Cases during Six Months of Delta Variant (B.1.617.2) Domination in Poland.

The emergence of a highly transmissible and a more pathogenic B.1.617.2 (delta) variant of SARS-CoV-2 has brought concern over COVID-19 vaccine efficacy and the increased risk of severe breakthrough infections. The objective of this study was to assess the frequency and the clinical characteristics of severe breakthrough COVID-19 cases recorded in 10 Polish healthcare units between 1 June and 31 December 2021, a period during which a rapid surge in the share of B.1.617.2 infections was seen, while a significant number of populations were already fully vaccinated. Overall, 723 individuals who completed the initial vaccination regime (fully vaccinated group) and an additional 18 who received a booster dose were identified­together, they represented 20.8% of all the COVID-19 patients hospitalized during the same period in the same healthcare institutions (0.5% in the case of a group that received a booster dose). Although laboratory and clinical parameters did not differ between both groups, patients who received a booster tended to have lower CRP, IL-6, PCT, and d-dimer levels and they required oxygen therapy less frequently. The most common early COVID-19 symptoms in the studied group were fatigue, cough, fever (>38 °C), and dyspnea. Individuals with no detectable anti-spike IgG antibodies constituted 13%; the odds of being a humoral non-responder to the vaccine were increased in patients aged >70 years. Fully vaccinated patients hospitalized after more than 180 days from the last vaccine dose were significantly older and they were predominantly represented by individuals over 70 years and with comorbidities, particularly cardiovascular disease. Contrary to mRNA vaccines, most patients vaccinated with adenoviral vector vaccines were infected within six months. A total of 102 fatal cases (14% of all deaths among vaccinated individuals; 0.7% in the case of a group that received a booster dose) were recorded, representing 17.6% of all the COVID-19 fatalities recorded in June−December 2021 in the considered healthcare units. The odds of death were significantly increased in men, individuals aged >70 years, patients with comorbidities, and those identified as humoral non-responders to vaccination; in fully vaccinated patients the odds were also increased when the second vaccine dose was given >180 days before the first COVID-19 symptoms. The mortality rate in immunocompromised subjects was 19%. The results indicate that compared to vaccinated individuals, severe COVID-19 and deaths in the unvaccinated group were significantly more prevalent during the B.1.617.2-dominated wave in Poland; and, it highlight the protective role of a booster dose, particularly for more vulnerable individuals.

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.

Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy.

(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Impact of Kidney Failure on the Severity of COVID-19.

BACKGROUND: Patients with kidney failure are at an increased risk of progression to a severe form of coronavirus disease 2019 (COVID-19) with high mortality. The current analysis was aimed to assess the impact of renal failure on the severity of COVID-19 and identify the risk factors of the fatal outcome in this population. METHODS: The analysis included patients from the SARSTer database, a national real-world study evaluating treatment for COVID-19 in 30 Polish centers. Data were completed retrospectively and submitted online. RESULTS: A total of 2322 patients were included in the analysis. Kidney failure was diagnosed in 455 individuals (19.65%), of whom 373 presented moderate stage and 82 patients, including 14 dialysis individuals, presented severe renal failure. Patients with kidney failure were significantly older and demonstrated a more severe course of COVID-19. The age, baseline SpO2, the ordinal scale of 4 and 5, neutrophil and platelet count, estimated glomerular filtration rate, and C-reactive protein concentration as well as malignancy and arterial hypertension were the independent predictors of 28-day mortality in logistic regression analysis. CONCLUSIONS: Underlying kidney disease in patients with COVID-19 is among the leading factors associated with a higher risk of severe clinical presentation and increased mortality rate.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study.

BACKGROUND: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients. AIM: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting. METHODS: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis. RESULTS: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy. CONCLUSION: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.

Actinomycosis - a forgotten chronic infectious disease - case report series.

Actinomycosis is one of the greatest 'chameleons' among infectious diseases. It may imitate inflammation, abscess or a neoplasmatic tumor. Moreover, correct diagnosis is even more challenging due to the fact that the disease takes on various forms like: cervicocephalic, abdominal, or affects the reproductive organs. In order to highlight the diagnostic difficulties of actinomycosis, we have decided to describe six cases of female patients (aged 31-73 years, mean age: 52 years) hospitalized due to actinomycosis in the Department of Infectious Diseases and Hepatology between 2014-2019. Additionally, a case of one patient was described in detail as the course of her disease was exceptionally non-specific. Only in 2 of 6 patients the primary diagnosis was correct. The four other patients were initially suspected with cancer or inflammation. Three of the patients were diagnosed with the abdominal form of actinomycosis, one - neck and head, and one presented both locations. Only histopathological examinations during invasive procedures allowed to state the final diagnosis. An adequate diagnosis was associated with a number of additional tests and delayed appropriate treatment. WBC and CRP were within normal range in all patients. Four patients completed treatment successfully after 60-192 days, one is still on therapy and one is lost to follow-up. In conclusion, common features of actinomycosis presented in this case series include predominance of female gender, abdominal localization and lack of typical symptoms. What is more, therapy with antibiotics, mainly doxycycline and beta-lactams resulted in complete regression of lesions in the majority of cases. Given the examples of our patients we believe that actinomycosis should be considered in the differential diagnosis of all abdominal tumors, especially in women. Abbreviations: WBC - white blood cells, CRP - C-reactive protein, CT - computed tomography, IUD - Intra-Uterine Device, i.v. - intravenous.

Prophylaxis of hepatitis B virus (HBV) infection reactivation - recommendations of the Working Group for prevention of HBV reactivation.

Hepatitis B virus (HBV) is one of the main causes of chronic liver diseases and hepatocellular carcinoma. After infection the majority of HBV-infected patients achieve immune control leading to HBV-DNA stabilization at a low level. The risk of HBV reactivation rises significantly when HBV-infected patients receive immunosuppressive treatments. Presented recommendations provide guidelines for management of patients scheduled or undergoing therapies, which through their immunomodulatory activity contribute to the impairment of antiviral immunity, including chemotherapy, immunosuppressive treatment or biological therapy.

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

AIM OF THE STUDY: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy. MATERIAL AND METHODS: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used. RESULTS: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic. CONCLUSIONS: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.

siRNA drug development against hepatitis B virus infection.

INTRODUCTION: Hepatitis B virus (HBV) infection is the worldwide leading cause of liver cirrhosis and hepatocellular carcinoma. Currently available medication can suppress viral replication in the majority of patients, but clearance of the viral antigens can be achieved in only about 10%. AREAS COVERED: RNA interference is a very attractive therapeutic option since a well-designed compound could possibly inhibit all HBV mRNA and thus synthesis of all its antigens, which could combine antiviral and immunomodulatory modes of action. The aim of the article is to provide current knowledge on possible use of small interfering RNA (siRNA) molecules in the treatment of chronic HBV infection. EXPERT OPINION: Based on the current status of clinical trials, we should expect that within the coming five years at least one siRNA molecule will be registered for clinical use. However, most important at this stage of development will be the safety profile, improving the route of administration, selection of the optimal combination with other anti-HBV drugs (nucleoside analogues, interferons) and finally selection of the optimal system introducing siRNA molecules into infected cells. Current therapeutic options for HBV, the siRNA mechanism of action, as well as preclinical and clinical studies with siRNA molecules are presented in this article.

Surgical treatment of liver tumors - own experience and literature review.

Despite advances, the treatment of focal liver lesions is still challenging. It requires the experience of a surgeon, improvement of existing and the development of new techniques. The aim of this article is to present a literature review and summarize our experience in liver surgery. Twenty-one patients with various liver tumors were treated in 2015 at the Department of Surgical Oncology of Bialystok Center for Oncology. Mostly patients were diagnosed with colorectal cancer liver metastases or hepatocellular carcinoma. Nine anatomical, 6 non-anatomical resections and 6 radiofrequency ablations were performed. Among 9 resections, 6 bisegmentectomies, resection of the 4b segment, and left-side and right-side hemihepatectomy were performed. Resections were associated only with minor postoperative complications. No perioperative mortality was noted. Preliminary outcomes of resections and radiofrequency ablations of liver lesions even in a low volume surgical center are promising and are associated with a relatively low rate of complications.

Recommendations for the treatment of hepatitis B in 2017.

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.