Clinical Course Of Infection Research Articles

Prevalence of SARS-CoV-2 in children from a cohort of 2192patients

HintergrundIn Deutschland sind aktuell (Stand 18.06.2020) 187.764 SARS-CoV-2-Infektionen gemeldet. 6,9 % der Infizierten sind dabei unter 19 Jahre. Es gibt erste Hinweise darauf, dass Kinder häufig asymptomatisch sind und einen milderen Verlauf zeigen.Ziel der ArbeitZiel dieser Arbeit war es, eine Aussage bezüglich der Infektionsprävalenz in dieser speziellen Patientengruppe zu ermöglichen.Material und MethodenIm Rahmen der SARS-CoV-2-Pandemie wurden zwischen dem 13.03.2020 und dem 18.06.2020 alle Kinder und Jugendlichen, welche entweder zum Ausschluss einer SARS-CoV-2-Infektion oder als Verdachtsfall einen Abstrich auf SARS-CoV‑2 erhielten, erfasst. Die Daten wurden auf standardisierten Anamnesebogen gesammelt und retrospektiv anonymisiert ausgewertet.ErgebnisseIn dem Zeitraum wurden 2192 Kinder und Jugendliche auf SARS-CoV‑2 abgestrichen. 37 Patienten wurden positiv getestet (1,7 %). 36/37 waren Verdachtsfälle, und 28/37 waren symptomatisch. Führende Symptome waren trockener Husten, Schnupfen und Fieber. Drei Kinder mussten stationär betreut werden. Keines zeigte einen schweren Verlauf. Unter den Getesteten waren 505 Patienten, die aufgrund ihrer chronischen Grunderkrankung als Risikopatienten eingestuft wurden, von denen 3 (0,6 %) einen positiven Nachweis mit asymptomatischem bzw. mildem Verlauf hatten.SchlussfolgerungHiermit können die ersten Daten bestätigt werden, wonach Kinder und Jugendliche häufig asymptomatische oder klinisch milde Infektions- bzw. Erkrankungsverläufe zeigen. Zudem fanden wir keinen Hinweis für eine hohe Dunkelziffer für SARS-CoV-2-Infektionen in dieser regionalen pädiatrischen Kohorte.

Outcomes of COVID-19 Infection in Patients Receiving Ruxolitinib and Hypomethylating Agent Therapy

IntroductionThe ongoing novel coronavirus disease 2019 (COVID-19) pandemic has provoked questions about treatment decisions in patients with hematologic malignancies. Of note, several anti-cancer agents have been shown to have preclinical activity against the SARS-CoV-2 virus, including ruxolitinib (Jakafi), as well as the hypomethylating agents (HMA) decitabine (Dacogen) and azacitidine (Vidaza). In addition, ruxolitinib has previously been shown to have potent activity against the cytokine response, similar to that seen in COVID-19 infections. The optimal management of patients on these agents who become infected with COVID-19 is unknown and it is not clear if the use of these agents modifies the clinical course of infection. We describe a case series of patients with hematologic malignancies receiving therapy with these agents while infected with COVID-19.MethodsWe conducted a retrospective chart review of consecutive patients between March 1 and May 21, 2020 who were receiving therapy with ruxolitinib, azacitidine, or decitabine when diagnosed with COVID-19 by SARS-CoV-2 PCR assay within the Mount Sinai Health System. The indications for these agents included acute lymphocytic leukemia, acute myeloid leukemia, myelofibrosis, polycythemia vera, and myelodysplastic syndromes. Patients who last received the agent more than thirty days prior to COVID-19 diagnosis were excluded from our series.ResultsSixteen patients on HMA or ruxolitinib were diagnosed with COVID-19 within our health system during this span. Full patient characteristics and clinical data are described in Tables 1a and 1b. Seven patients were receiving ruxolitinib and nine patients were on HMA: eight on azacitidine and one on decitabine. Of the patients on HMA, eight had therapy held after confirmed COVID-19 infection, and one was continued on therapy. Overall mortality in the HMA cohort was 88.9% (8/9), including 7/8 in the therapy-held group and the one patient for whom therapy was continued. Of the patients on ruxolitinib, three had therapy held and four were continued after confirmed infection. Overall mortality in the ruxolitinib cohort was 57.1% (4/7), with 75% (3/4) in the therapy-held and 33% (1/3) mortality in the therapy-continued groups. All patients who died (n = 12) required either non-invasive positive pressure ventilation or mechanical ventilation. Across all agents, patients who survived (n = 4) required no higher level of supplemental oxygen than non-rebreather mask, and one did not require hospitalization. Cytokine levels were on average higher on admission for the ruxolitinib-held group but were not associated with mortality or increased oxygen requirement.DiscussionHigh mortality rates were observed for both ruxolitinib and HMA in this high-risk group of patients with hematologic malignancy regardless of whether therapy was held. HMA was commonly held at time of infection: further investigation will be needed to elucidate any potential in-vivo anti-SARS-CoV-2 activity for these reagents. Mortality was numerically less in patients in receiving ruxolitinib who continued therapy, however this should be interpreted with caution given our small cohort. Further clinical trials to address the use of ruxolitinib are necessary and are ongoing. These data can help guide further investigation regarding use of anti-cancer therapy in patients with hematologic malignancy diagnosed with COVID-19.DisclosuresMascarenhas:Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution).

COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak

ObjectivesThe aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy. BackgroundThe worldwide severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has created unprecedented challenges for public health, demanding exceptional efforts for the successful management and treatment of affected patients. Heart transplant patients represent a unique cohort of chronically immunosuppressed subjects in which SARS-CoV-2 may stimulate an unpredictable clinical course of infection. MethodsSince February 2020, we enrolled all 47 cases (79% male) in a first cohort of patients, with a mean age of 61.8 ± 14.5 years, who tested positive for SARS-CoV-2, out of 2,676 heart transplant recipients alive before the onset of the COVID-19 pandemic at 7 heart transplant centers in Northern Italy. ResultsTo date, 38 patients required hospitalization while 9 remained self-home quarantined and 14 died. Compared to the general population, prevalence (18 vs. 7 cases per 1,000) and related case fatality rate (29.7% vs. 15.4%) in heart transplant recipients were doubled. Univariable analysis showed older age (p = 0.002), diabetes mellitus (p = 0.040), extracardiac arteriopathy (p = 0.040), previous PCI (p = 0.040), CAV score (p = 0.039), lower GFR (p = 0.004), and higher NYHA functional classes (p = 0.023) were all significantly associated with in-hospital mortality. During the follow-up two patients died and a third patient has prolonged viral-shedding alternating positive and negative swabs. Since July 1st, 2020, we had 6 new patients who tested positive for SARS-CoV-2, 5 patients asymptomatic were self-quarantined, while 1 is still hospitalized for pneumonia. A standard therapy was maintained for all, except for the hospitalized patient. ConclusionsThe prevalence and mortality of SARS-CoV-2 should spur clinicians to immediately refer heart transplant recipients suspected as having SARS-CoV2 infection to centers specializing in the care of this vulnerable population.

Coronavirus 2019 Disease (COVID-19), Systemic Inflammation, and Cardiovascular Disease.

Acute respiratory failure associated with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide and presents critical challenges for the public health and medical communities The World Health Organization (WHO) has declared SARS-CoV-2 a public health emergency of international concern, with a global estimate of over 7 million human infections and more than 400000 deaths worldwide as of June 12, 2020 A 2020 report by the China Medical Treatment Expert Group for Coronavirus disease 2010 (COVID-19) (2) showed that the clinical spectrum of the viral infection is dominated by fever (up to 88 7% of patients during hospitalization) and cough (67 8% of patients) followed by symptoms such as headache, fatigue, or shortness of breath

Tracking the Trajectory of Functional Humoral Immune Responses Following Acute HIV Infection.

Increasing evidence points to a role for antibody-mediated effector functions in preventing and controlling HIV infection. However, less is known about how these antibody effector functions evolve following infection. Moreover, how the humoral immune response is naturally tuned to recruit the antiviral activity of the innate immune system, and the extent to which these functions aid in the control of infection, are poorly understood. Using plasma samples from 10 hyper-acute HIV-infected South African women, identified in Fiebig stage I (the FRESH cohort), systems serology was performed to evaluate the functional and biophysical properties of gp120-, gp41-, and p24- specific antibody responses during the first year of infection. Significant changes were observed in both the functional and biophysical characteristics of the humoral immune response following acute HIV infection. Antibody Fc-functionality increased over the course of infection, with increases in antibody-mediated phagocytosis, NK activation, and complement deposition occurring in an antigen-specific manner. Changes in both antibody subclass and antibody Fc-glycosylation drove the evolution of antibody effector activity, highlighting natural modifications in the humoral immune response that may enable the directed recruitment of the innate immune system to target and control HIV. Moreover, enhanced antibody functionality, particularly gp120-specific polyfunctionality, was tied to improvements in clinical course of infection, supporting a role for functional antibodies in viral control.

Reversal of T Cell Exhaustion in Chronic HCV Infection

The long-term consequences of T cell responses’ impairment in chronic HCV infection are not entirely characterized, although they may be essential in the context of the clinical course of infection, re-infection, treatment-mediated viral clearance and vaccine design. Furthermore, it is unclear whether a complete reinvigoration of HCV-specific T cell response may be feasible. In most studies, attempting to reverse the effects of compromised immune response quality by specific blockades of negative immune regulators, a restoration of functional competence of HCV-specific T cells was shown. This implies that HCV-induced immune dysfunction may be reversible. The advent of highly successful, direct-acting antiviral treatment (DAA) for chronic HCV infection instigated investigation whether the treatment-driven elimination of viral antigens restores T cell function. Most of studies demonstrated that DAA treatment may result in at least partial restoration of T cell immune function. They also suggest that a complete restoration comparable to that seen after spontaneous viral clearance may not be attained, pointing out that long-term antigenic stimulation imprints an irreversible change on the T cell compartment. Understanding the mechanisms of HCV-induced immune dysfunction and barriers to immune restoration following viral clearance is of utmost importance to diminish the possible long-term consequences of chronic HCV infection.

The treatment of children infected with COVID-19 in a non-core hospital

According to the World Health Organization (WHO), viral diseases form serious public health problem. WHO announced that the disease caused by the new virus named coronavirus disease 2019 or Coronavirus disease 2019 (COVID-19), and the virus causing the infection was named SARS-Cov-2 by the International Committee on Taxonomy of Viruses. Children usually have asymptomatic or mild forms. However, children with comorbidity are in risk of developing severe forms of COVID-19. The review presents modern ideas about the amount of laboratory tests in cases of suspected presence of the SARS-CoV-2 virus, methods of radio diagnostic (computer tomography, x-ray, thorax ultrasound), features of the clinical course of infection in children depending on the severity of the of infection and indicated detailed criteria for severe forms of coronavirus infection. Special attention is focused on the clinical monitoring of children in a non-core hospital: the detection of leukopenia and lymphopenia, CRP level control, monitoring of coagulation disorders, providing tests on other respiratory viruses. Specific recommendations, comprehensive to date, on the use of drugs for the treatment of children with COVID-19 upon admission to a non-core hospital are given. The organisational issues of treatment children infected with COVID-19 in a non-core hospital are described in details. Special attention is focused on the compliance of strict safety rules by staff working with infected patients entering and leaving the Red zone. Thus, the proper organisation of the units for the treatment of children infected with COVID-19 in a non-core hospital, taking into account the features of their disease, will make it possible to provide complete and high-quality treatment of infection during the pandemic.

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate.

AimThe COVID‐19 pandemic is caused by infection with the SARS‐CoV‐2 virus. The major mutation detected to date in the SARS‐CoV‐2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.ResultIncreased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.ConclusionThese results imply that G614 is a more pathogenic strain of SARS‐CoV‐2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID‐19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis.

To determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID-19). Literature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID-19 patients. Search strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID-19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta-analysis using pooled prevalence estimates in a random-effects model were calculated. Ten studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%-75.23%) prevalence among patients with COVID-19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%-68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%-57.24%) and 86.60% (95% CI, 72.95%-95.95%) prevalence, respectively. Olfactory and gustatory dysfunction are common symptoms in patients with COVID-19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta-analysis to report on the prevalence of these symptoms in COVID-19 patients.

Genetic variations in the host dependency factors ALCAM and TPST2 impact HIV-1 disease progression.

Recently, the activated leukocyte cell adhesion molecule (ALCAM) and tyrosylprotein sulfotransferase 2 (TPST2) have been identified as important host dependency factors (HDFs) for in-vitro HIV-1 replication. To determine whether these genes play a role in HIV-1 pathogenesis, we analysed whether naturally occurring genetic variations were associated with the clinical course of infection. Single nucleotide polymorphisms (SNPs) in ALCAM and TPST2 were analysed in a cohort of 304 HIV-1-infected men who have sex with men and survival analysis was used to determine their effect on the outcome of untreated HIV-1 infection. Flowcytometry was used to determine the effect of SNPs on CD4 T-cell activation prior to HIV-1 infection and 1 and 5 years after infection. In-vitro HIV-1 infections were performed to analyse the effect of the SNPs on HIV-1 replication. We observed that the minor allele of rs1344861 in ALCAM was associated with accelerated disease progression, whereas the minor allele of rs9613199 in TPST2 was associated with delayed disease progression. In-vitro infection assays did not demonstrate any differences in HIV-1 replication associated with rs9613199. However, the increase in CD4 T-cell immune activation levels during HIV-1 infection was less pronounced in infected individuals homozygous for rs9613199, which is in agreement with delayed disease progression. Our data demonstrate that ALCAM and TPST2 play a role in HIV-1 pathogenesis. SNPs in these genes, without known functional implications, had a major effect on disease progression, and therefore, these HDFs may be attractive and effective targets for new treatment strategies.

Nef-Mediated CD3-TCR Downmodulation Dampens Acute Inflammation and Promotes SIV Immune Evasion

SUMMARYThe inability of Nef to downmodulate the CD3-T cell receptor (TCR) complex distinguishes HIV-1 from other primate lentiviruses and may contribute to its high virulence. However, the role of this Nef function in virus-mediated immune activation and pathogenicity remains speculative. Here, we selectively disrupted this Nef activity in SIVmac239 and analyzed the consequences for the virological, immunological, and clinical outcome of infection in rhesus macaques. The inability to downmodulate CD3-TCR does not impair viral replication during acute infection but is associated with increased immune activation and antiviral gene expression. Subsequent early reversion in three of six animals suggests strong selective pressure for this Nef function and is associated with high viral loads and progression to simian AIDS. In the absence of reversions, however, viral replication and the clinical course of infection are attenuated. Thus, Nef-mediated downmodulation of CD3 dampens the inflammatory response to simian immunodeficiency virus (SIV) infection and seems critical for efficient viral immune evasion.

COVID-19: what is next for public health?

COVID-19: what is next for public health?

Epidemija influenze A H1N1 2019. godine u Zlatiborskom okrugu

Introduction: Influenza A H1N1 occurs worldwide sporadically or epidemically. There have been several epidemics of this disease in recent decades. Millions of people fell ill and hundreds of thousands died. The clinical picture varies from asymptomatic to lethal outcome. Older age, male gender and obesity are the most common risk factors for adverse disease. The aim of the research was to examine the clinical course and outcome of the disease of patients with pneumonia during the epidemic of influenza A H1N1 in 2019 in the Zlatibor district. Methods: Epidemiological, clinical, microbiological and radiographic data of patients with influenza A H1N1 treated at the Department of Infectious and Tropical Diseases and the Intensive Care Unit of the General Hospital of Uzice were retrogradely collected and analyzed. Virological and serological analyzes were performed at the Institute of Immunology and Virology "Torlak" in Belgrade. The diagnosis of acute respiratory distress syndrome (ARDS) was made according to the Berlin definition. Statistical analysis was performed using the Statistical Package for Social Sciences SPSS (version 16.0). Results: Out of a total of 274 patients, women accounted for 52.9%. The most common age was 61 to 70 years. 55.4% of patients had comorbidities, 61.8% of that had cardiovascular disease. C reactive protein was elevated in 79.2% of patients. Pneumonia confirmed by radiographic findings was present in 82.8% of patients, 51.5% of that had bilateral pneumonia. Four patients were pregnant, GML 5-9. Two of them had a mild clinical course of infection, one moderate with unilateral pneumonia. All three had a favorable disease outcome. A fourth pregnant woman was admitted in a severe clinical condition and was immediately referred to a tertiary health institution where the disease ended in death. 10.2% of patients were treated in the intensive care unit. Complications occurred in 23.7% of patients, ARDS in 52.3% of that. 55.9% of patients with ARDS were aged 61 to 70 years, and 58.8% were male. Among patients with ARDS, 94.1% had associated diseases, most often CVD (85.3%). C reactive protein was elevated in 85.3% of patients with ARDS. In 8.4% of patients, the disease had an unfavorable course and ended in death. Among these patients, 65.2% were women, and 73.9% were over 65 years of age. Associated diseases were present in 95.6% of these patients, cardiovascular diseases was present in 87% of that. Conclusion: During the influenza epidemic in 2019 in the Zlatibor district, pneumonia, most often bilateral, was most often in patients aged 61-70 with associated cardiovascular diseases. These were also the main risk factors for complications and adverse disease outcome. ARDS was the most common comlication and risk factor for the lethal outcome of the diseases.

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients.

ABSTRACTIntroduction:Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit.Methods:Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction.Results:The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit.Conclusion:The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.

Hepatitis C virus (HCV) genotype 1b displays higher genetic variability of hypervariable region 1 (HVR1) than genotype 3

Hepatitis C virus (HCV) is characterized by high genetic variability, which is manifested both at the inter-host and intra-host levels. However, its role in the clinical course of infection is less obvious. The aim of the present study was to determine the genetic variability of HCV HVR1 (hypervariable region 1) of genotype 1b and 3 in plasma of blood donors in the early seronegative stage of infection (HCV-RNA+, anti-HCV−) and in samples from chronically infected patients using next-generation sequencing. Sequencing errors were corrected, and haplotypes inferred using the ShoRAH software. Genetic diversity parameters (intra-host number of variants, number of nucleotide substitutions and diversity per site) were assessed by DNA SP and MEGA. During the early infection, the number of variants were significantly lower in subjects infected with genotype 3 than with genotype 1b (p < 0.02). Similarly, intra-host number of variants, number of nucleotide substitutions and diversity per site were lower in genotype 3 chronic infection (p < 0.0005). In addition, early infection was characterized by significantly lower HVR1 variability values (p < 0.04) when compared to chronic infection for both genotypes. It seems that the observed differences in HVR1 variability represent an inherent property of particular viral genotypes.

Genetic characterization of Anaplasma phagocytophilum strains from goats (Capra aegagrus hircus) and water buffalo (Bubalus bubalis) by 16S rRNA gene, ankA gene and multilocus sequence typing

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks and causes tick-borne fever in domestic ruminants such as sheep, cattle and goats. However, in contrast to sheep and cattle little is known about the clinical course of infection in goats. We report here on three cases of symptomatic infection with A. phagocytophilum in two goats (Capra aegagrus hircus) and one water buffalo (Bubalus bubalis). The animals showed symptoms and laboratory findings similar to sheep and cattle. To our knowledge, this is the first report on the symptomatic infection of water buffalos with A. phagocytophilum. The infecting strains were genetically characterized by 16S rRNA gene, ankA gene and multilocus sequence typing (MLST). Four other strains from asymptomatically infected goats were also included. The ankA sequences from five goats were part of the formerly described ankA gene clusters I and IV that are known to contain A. phagocytophilum strains from sheep and cattle. However, the sequences from one goat and from the water buffalo belonged to ankA gene cluster II that was formerly described to be restricted to roe deer. A similar observation was made for MLST as three goats clustered with sequences from sheep and cattle, whereas three other goats and the water buffalo were found to be part of the roe deer cluster. However, since most of the strains from sheep and cattle were distinct from the roe deer strains, roe deer might not represent major reservoir hosts for tick-borne fever in domestic ruminants. When differing parts of the 16S rRNA gene were used for typing the results were conflicting. This shows that the use of a standardized typing method such as MLST is highly desirable to generate easily comparable results.

A headache with surprising outcome: first case of brucellosis caused by Brucella suis biovar 1 in Germany

In July 2018, brucellosis was diagnosed in a German patient without a travel history to regions endemic for Brucella. Microbiological analysis, including whole-genome sequencing, revealed Brucella suis biovar 1 as the etiologic agent. Core-genome-based multilocus sequence-typing analysis placed the isolate in close proximity to strains originating from Argentina. Notably, despite a strong IgM response, the patient did not develop Brucella-specific IgG antibodies during infection. Here, we describe the clinical course of infection, the extensive epidemiological investigations, and discuss possible routes of transmission.

Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences.

Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host's genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.

HCV-Specific T Cell Responses During and After Chronic HCV Infection.

Hepatitis C virus (HCV)-specific T cell responses are closely linked to the clinical course of infection. While T cell responses in self-limiting infection are typically broad and multi-specific, they display several distinct features of functional impairment in the chronic phase. Moreover, HCV readily adapts to immune pressure by developing escape mutations within epitopes targeted by T cells. Much of our current knowledge on HCV-specific T cell responses has been gathered under the assumption that this might eventually pave the way for a therapeutic vaccine. However, with the development of highly efficient direct acting antivirals (DAAs), there is less interest in the development of a therapeutic vaccine for HCV and the scope of T cell research has shifted. Indeed, the possibility to rapidly eradicate an antigen that has persisted over years or decades, and has led to T cell exhaustion and dysfunction, provides the unique opportunity to study potential T cell recovery after antigen cessation in a human in vivo setting. Findings from such studies not only improve our basic understanding of T cell immunity but may also advance immunotherapeutic approaches in cancer or chronic hepatitis B and D infection. Moreover, in order to edge closer to the WHO goal of HCV elimination by 2030, a prophylactic vaccine is clearly required. Thus, in this review, we will summarize our current knowledge on HCV-specific T cell responses and also provide an outlook on the open questions that require answers in this field.

Clostridium difficile infection in patients hospitalized in the gastroenterology ward - retrospective analysis.

Clostridium difficile associated colitis became over last years a worldwide medical issue. It involves patients of the Polish hospitals too. The aim of the study was the analysis of CDAD incidence and the course of infection in Gastroenterology Ward of Regional Specialist Hospital of Zgierz, 2012-2015. Retrospective analysis of the medical documentation of 79 patients with CDAD was performed. Demographic and epidemiological data and the clinical course of infection were analyzed. The study group comprised of women in 59,5% and men in 40,5%. The patients' average age was 70,5 years. The average hospitalization period was 10,3 days. CDAD infection seasonality was proved, with statistically significant peak in springtime. 73% of patients were previously hospitalized and 85% - had co-morbidities. 76% of patients underwent antibiotherapy, whilst 29% - used PPI prior to CDAD diagnosis. 50,6% of patients had severe CDAD diagnosed. The recurrence reached 14%. In 19% of patients CDAD resulted in death. The results of the study confirm increase of the incidence of the patients with CDAD in Gastroenterology Ward over 4-years' observation. The prevalence was higher among 65+ patients, after prior hospitalization and antibiotherapy. The co-morbidities was a significant risk factor, especially common in severe cases. The results we obtained confirm substantial importance of Clostridium difficile infection leading to antibiotherapy- associated diarrhea among adults, causing prolonged hospitalization, increased prevalence and mortality of patients. Getting to know and minimizing the risk factors will prevent the future outbreak of the disease.