Retroperitoneal hematoma in COVID-19 patients - case series.

COVID-19 patients, particularly those with severe pulmonary involvement, are at an increased thromboembolic risk related, among various causes, to the cytokine storm and excessive activation of the coagulation cascade and platelets. Different intensity of anticoagulation for them is proposed, mainly with low molecular weight heparins (LMWHs); in a confirmed pulmonary embolism (PE) the therapeutic dose of LMWH is routinely used. Some authors suggest that hemorrhagic complications in COVID-19 patients are rare. At the same time, one can find reports on internal bleeding, including retroperitoneal hematoma (RPH) and other abdominal hematomas. CASE REPORTS: The authors describe 5 cases (3 of those aged more than 80 years) with giant RPHs and with moderate/severe COVID-19 pneumonia, treated before RPH diagnosis with different enoxaparin doses. The therapeutic dose was given to the male with verified PE limited to the segmental/subsegmental pulmonary arteries and initially to the female in whom echocardiography was strongly suggestive of PE, yet this diagnosis was excluded on CT angiography. In one patient, the enoxaparin dose was escalated from 40 mg bd to 60 mg bd after the D-dimer increase. Two patients had bleeding complications despite the enoxaparin dose restricted to 40 mg/daily or bd. Two males had a coexistent psoas hematoma while in only one female there was a coexistent femoral hematoma. RPHs occurred between day 4 and 14 of hospitalization and all were treated conservatively. Three patients who died were particularly charged, so their deaths were not merely directly associated with RPH, which was closely analyzed in one autopsy performed. The authors underline that the choice of anticoagulation intensity in patients with COVID-19 pneumonia without venous thromboembolism seems sometimes difficult but recent publications indicate the low prophylactic enoxaparin dose as an optimal option. Anticoagulation dose escalation based only on the D-dimer level may not be appropriate for certain patients; moreover, the D-dimer increase is commonly observed during internal bleeding.

Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium.

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.

Long-Term Survival of Older Patients Hospitalized for COVID-19. Do Clinical Characteristics upon Admission Matter?

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznan, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period (up to 180 days from the hospital admission). In our study, male sex, severe cognitive impairment, underlying heart disease, anemia, and elevated plasma levels of IL-6 were independently associated with greater mortality during hospitalization. During the overall 180-day observation period (from the hospital admission), similar characteristics, excluding male sex and additionally functional impairment, were associated with increased mortality. During the post-discharge period, severe functional impairment remained the only determinant. Therefore, functional capacity prior to diagnosis should be considered when formulating comprehensive prognoses as well as care plans for older patients infected with SARS-CoV-2.

Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine.

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)-three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure.

Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage.

AIM OF THE STUDY: Elevated circulating CD4+ CD25+ Foxp3+ regulatory T cells in patients with chronic hepatitis C (CHC) play an unspecified role in liver fibrosis development. This study aimed to determine whether Treg cells diminish after successful treatment with directacting antivirals (DAA) in patients at different liver fibrosis stages. MATERIAL AND METHODS: We examined 44 patients with CHC (including 29 with liver cirrhosis) seven days before DAA treatment (T0), six months later (T1) and then 22 of them were examined one year (T2) after the first dose. Subsequently, these were compared with 28 volunteers without hepatitis C virus (HCV) (15 with excessive alcohol intake). We assessed the degree of liver fibrosis with FibroScan, aspartate transaminase (AST) to platelet ratio index (APRI), FibroIndex, the Forns index and Fib-4. Circulating Treg cells were measured using flow cytometry. RESULTS: All patients achieved a sustained virological response (SVR). After the treatment, all liver fibrosis indicators decreased significantly. The number of circulating Tregs was lower in healthy controls than in patients with CHC (0.0066 × 103 cells/µl and 0.0084 × 103 cells/µl, respectively, p = 0.048). After the treatment we observed an insignificant change to 0.0047 × 103 cells/µl for T1 (p > 0.05) and a significant fall to 0.0041 × 103 cells/µl for T2 (p = 0.03). There was no correlation between the degree of hepatic fibrosis and number of Tregs or post-treatment dynamics. CONCLUSIONS: Our study shows that Treg cells normalize gradually over a prolonged period of time after a successful DAA treatment. Their number and dynamics remain independent of liver fibrosis degree. The correlation of this revelation with metabolic disorders, increased susceptibility to infections or persistent risk of HCC remains unclear.

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6.

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08-0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort.

BACKGROUND: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. SETTING: EuroSIDA, a European multicenter prospective cohort study. METHODS: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. RESULTS: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/mL), many had low CD4 counts (≤350 cells/µL). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI: 0.86 to 2.40, P = 0.16) or non-AIDS clinical events (aIRR 0.96, CI: 0.74 to 1.25, P = 0.77). CONCLUSIONS: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals.

Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study.

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63-0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value.

Gender as a factor affecting NK cell activity in patients successfully treated for chronic hepatitis C with direct-acting antivirals.

Chronic hepatitis C (CHC) affects the activity of natural killer (NK) cells, but successful interferon- free treatment partially restores it. The goal of this study was to assess whether gender influences NK functionality. We examined 21 post-menopausal women and 24 men with CHC who were treated with direct-acting antivirals (DAA) and 33 healthy volunteers. Using flow cytometry, we analysed KIR2DS4, NKG2D, NKp30, KIR2DL2/DL3, NKG2A and TRAIL on the surface of NK cells. Intracellular granzyme B was also assessed and serum CXCL10 was quantified via ELISA. Overall, patients with CHC had higher expression of KIR2DS4, NKG2A, and NKp30 relative to the control group. Further, CHC patients had a lower percentage of NK cells among lymphocytes relative to the control group. After treatment, KIR2DS4, KIR2DL2/DL, NKG2A, TRAIL and NKp30 on NK cells were decreased whilst the percentage of NK cells and the expression of granzyme B and NKG2D increased. Prior to treatment, serum CXCL10 was elevated, but it was inhibited post-treatment. We observed gender-specific differences in the expression of KIR2DL2/DL3 (higher in women) and NKp30 (elevated in men) compared to CHC/control groups. After treatment, KIR2DL2/DL3, NKp30 and CXCL10 dropped only in the female group while granzyme B increased in the male group. In conclusion, the response of NK cells among men and women of post-menopausal ages with CHC differs. Our research may lead to more studies on the different nature of female and male immune systems in the context of HCV infection and treatment.

Clinical Characteristics and Survival Analysis in a Small Sample of Older COVID-19 Patients with Defined 60-Day Outcome.

The older population is one of the most vulnerable to experience adverse outcomes of COVID-19. Exploring different clinical features that may act as detrimental to this population's survival is pivotal for recognizing the highest risk individuals for poor outcome. We thus aimed to characterize the clinical differences between 60-day survivors and non-survivors, as well as analyze variables influencing survival in the first older adults hospitalized in Poznan, Poland, with COVID-19. Symptoms, comorbidities, complications, laboratory results, and functional capacity regarding the first 50 older patients (≥60 years) hospitalized due to COVID-19 were retrospectively studied. Functional status before admission (dependent/independent) was determined based on medical history. The 60-day survivors (n = 30/50) and non-survivors (n = 20/50) were compared across clinical parameters. The patients had a mean age of 74.8 ± 9.4 years. Overall, 20/50 patients died during hospitalization, with no further fatal outcomes reported during the 60-day period. The non-survivors were on average older (78.3 ± 9.7 years), more commonly experienced concurrent heart disease (75%), and displayed functional dependence (65%) (p < 0.05). When assessing the variables influencing survival (age, heart disease, and functional dependence), using a multivariate proportional hazards regression, functional dependence (requiring assistance in core activities of daily living) was the main factor affecting 60-day survival (HR, 3.34; 95% CI: 1.29-8.63; p = 0.01). In our study, functional dependence was the most important prognostic factor associated with mortality. Elderly with COVID-19 who required assistance in core activities of daily living prior to hospitalization had a three times increased risk to experience mortality, as compared to those with complete independence. Exploring geriatric approaches, such as assessment of functional capacity, may assist in constructing comprehensive survival prognosis in the elderly COVID-19 population.

Pattern Recognition Receptors: Significance of Expression in the Liver.

Pattern recognition receptors (PRRs) are a pivotal part of the immune system. They are distributed in almost every site of higher organisms, able to recognize foreign pathogens or unwanted remnants of metabolism and mount innate immune response. Moreover, PRRs create bridging signaling to initiate adaptive immunity. The liver being the largest organ of the body, exposed to myriads of foreign substances often being immunogenic, is well equipped with PRRs. They act as sentinels of the organ, both in health and disease. In viral hepatitis C at least two of them, RIG-1 and TLR3 sense HCV, induce protective interferon production and create proinflammatory status. The hepatitis B virus is apparently invisible to PRRs, which has recently been denied. Besides, they are active in the course of infection. In liver injury and hepatic fibrogenesis Toll-like receptors (TLRs), predominantly TLR4, TLR3 and TLR9 are associated with gut microflora-related products and DNA from dying hepatocytes, lead to the activation of hepatic stellate cells. The latter initiate production of fibrillar collagens, the main agents forming hepatic fibrosis. Tumor cells of primary liver cancer also express PRRs, mainly TLRs. In concert with non-resolving liver inflammation, they are considered pivotal factors leading to carcinogenesis.

Correlates of inconsistent condom use and drug use among men having sex with men in Poland: a cross-sectional study.

The number of new human immunodeficiency virus (HIV) diagnoses is rising in many parts of Europe. We sought to evaluate the rising prevalence of new HIV diagnoses in Poland, where the majority of newly-diagnosed HIV cases are men having sex with men (MSM). This study aims to measure the prevalence of condom use and drug use and to identify risk factors for contracting sexually transmitted infections (STIs) among MSM in Poland by distributing an anonymous online survey aimed toward MSM. Among the 1438 participants who completed valid surveys, those with low education level and greater than 100 prior sexual partners showed the highest odds for inconsistent condom use (adjusted odds ratio [aOR] 3.027, 2.044, respectively). Participants who identified themselves as heterosexuals, with multiple sexual partners and living in big cities showed the highest odds for drug use (aOR 4.869, 3.305, 1.720, respectively). This study identifies groups at the highest risk of HIV/STIs and provides valuable information for public health experts to develop targeted STI prevention campaigns.

Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances.

Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient's quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient's emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient's liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient's quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient's BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.

Exposure to hepatitis E virus in hemodialysis patients from west-central Poland.

Hepatitis E virus (HEV) causes travel-related but also locally acquired infections in industrialized parts of the world, including European countries. Food and blood transfusions are possible sources of transmission. Infections caused by zoonotic variants of the virus (particularly HEV-3) may progress to chronic liver disease in a nonnegligible proportion of immunocompromised people. The aim of this study was to assess the prevalence of serological markers of HEV infection in 189 patients on renal replacement therapy (RRT, currently on hemodialysis, HD) living in west-central Poland and to determine the factors related to HEV exposure in this group. Testing was carried out using commonly used commercial assays (Wantai Biological Pharmacy Enterprise Co, Beijing, China). Anti-HEV IgG was detected in 94 patients (49.7%); none of the participants had anti-HEV IgM or HEV Ag. Patients on RRT (HD) for less than 6 months were significantly more likely to be anti-HEV IgG-positive than dependent of RRT (HD) for more than half a year (80% vs 47%; P = .014). Exposure to HEV in patients from west-central Poland is frequent, but no clear sources of this infection have been identified. There were no serological features of ongoing liver disease caused by HEV in the study subjects.

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.

Correction to: Significance and Role of Pattern Recognition Receptors in Malignancy.

The authors would like to correct the following error.

Significance and Role of Pattern Recognition Receptors in Malignancy.

Pattern recognition receptors (PRRs) are members of innate immunity, playing pivotal role in several immunological reactions. They are known to act as a bridge between innate and adaptive immunity. They are expressed on several normal cell types but have been shown with increasing frequency on/in tumor cells. Significance of this phenomenon is largely unknown, but it has been shown by several authors that they, predominantly Toll-like receptors (TLRs), act in the interest of tumor, by promotion of its growth and spreading. Preparation of artificial of TLRs ligands (agonists) paved the way to use them as a therapeutic agents for cancer, so far in a limited scale. Agonists may be combined with conventional anti-cancer modalities with apparently promising results. PRRs recognizing nucleic acids such as RIG-1 like receptors (sensing RNA) and STING (sensing DNA) constitute a novel promising approach for cancer immunotherapy.

Takotsubo cardiomyopathy triggered by influenza B.

Influenza is associated with a high prevalence of cardiac complications, including myocarditis and exacerbation of ischemic heart disease or heart failure (HF). However, only four cases of stress-induced takotsubo cardiomyopathy (TC), all of them triggered by virus A influenza, have been reported so far. Another two TC cases after anti-influenza vaccination are also available in the literature. The authors describe a new case of TC, this time provoked by influenza B. An 89-year-old female with a history of hypertension and chronic obstructive pulmonary disease (COPD) was admitted due to a fever (39oC), muscle aches and cough. Pneumonia was excluded in chest X-ray while the test for influenza confirmed virus B infection, so she was given oseltamivir. On the second day of hospitalization, she developed severe HF. ECG showed new negative T waves in inferior and anterolateral leads coexisting with a moderate troponin I and marked brain natriuretic peptide release, while echocardiography revealed left ventricular (LV) apical ballooning with decreased ejection fraction (EF 24%) and global longitudinal strain (GLS -8.1%). Symptomatic treatment of HF was initiated. The symptoms of influenza resolved after 5 days. LV function began to improve after 4 days and became normal after 6 days (EF 58%, GLS -18.1%). Despite an advanced age and the coexisting disorders (COPD, mild cognitive impairment, possible neoplastic disease), the patient was discharged in stable clinical condition on day 10. The authors conclude that in the evaluation of cardiac complications of influenza, TC should be taken into account.