Background Community-acquired sepsis is a life-threatening systemic reaction, which starts within ≤72 h of hospital admittance in an infected patient without recent exposure to healthcare risks. Our aim was to evaluate the characteristics and the outcomes concerning community-acquired sepsis among patients admitted to a Hungarian high-influx national medical center. Methods A retrospective, observational cohort study of consecutive adult patients hospitalized with community-acquired sepsis during a 1-year period was executed. Clinical and microbiological data were collected, patients with pre-defined healthcare associations were excluded. Sepsis definitions and severity were given according to ACCP / SCCM criteria. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were intensive care unit (ICU) admittance, length-of-stay (LOS), source control and bacteraemia rates. Statistical differences were explored with classical comparison tests, predictors of in-hospital all-cause mortality were modelled by multivariate logistic regression. Results 214 patients (median age 60.0 ± 33.1 years, 57% female, median Charlson score 4.0 ± 5.0) were included, 32.7% of them (70/214) had severe sepsis, and 28.5% (61/214) had septic shock. Prevalent sources of infections were genitourinary (53/214, 24.8%) and abdominal (52/214, 24.3%). The causative organisms were dominantly E. coli (60/214, 28.0%), S. pneumoniae (18/214, 8.4%) and S. aureus (14/214, 6.5%), and bacteraemia was documented in 50.9% of the cases (109/214). In-hospital mortality was high (30/214, 14.0%), and independently associated with shock, absence of fever, male gender and the need for ICU admittance, but source control and de-escalation of empirical antimicrobial therapy were protective. ICU admittance was 27.1% (58/214), source control was achieved in 18.2% (39/214). Median LOS was 10.0 ± 8.0, ICU LOS was 8.0 ± 10.8 days. Conclusions Community-acquired sepsis poses a significant burden of disease with characteristic causative agents and sources. Patients at a higher risk for poor outcomes might be identified earlier by the contributing factors shown above.

BackgroundCharacteristics of the blood microbiota among adult patients with community-acquired sepsis are poorly understood. Our aim was to analyze the composition of blood microbiota in adult patients with community-acquired sepsis, and correlate changes with non-septic control patients.MethodsA prospective observational study was carried out by including adult patients hospitalized for community-acquired sepsis at our center between January and November 2019, by random selection from a pool of eligible patients. Study inclusion was done on the day of sepsis diagnosis. Community acquisition was ascertained by a priori exclusion criteria; sepsis was defined according to the SEPSIS-3 definitions. Each included patient was matched with non-septic control patients by age and gender in a 1:1 fashion enrolled from the general population. Conventional culturing with BacT/ALERT system and 16S rRNA microbiota analysis were performed from blood samples taken in a same time from a patient. Abundance data was analyzed by the CosmosID HUB Microbiome software.ResultsAltogether, 13 hospitalized patients were included, 6/13 (46.2%) with sepsis and 7/13 (53.8%) with septic shock at diagnosis. The most prevalent etiopathogen isolated from blood cultures was Escherichia coli, patients mostly had intraabdominal septic source. At day 28, all-cause mortality was 15.4% (2/13). Compared to non-septic control patients, a relative scarcity of Faecalibacterium, Blautia, Coprococcus and Roseburia genera, with an abundance of Enhydrobacter, Pseudomonas and Micrococcus genera was observed among septic patients. Relative differences between septic vs. non-septic patients were more obvious at the phylum level, mainly driven by Firmicutes (25.7% vs. 63.1%; p<0.01) and Proteobacteria (36.9% vs. 16.6%; p<0.01). The alpha diversity, quantified by the Chao1 index showed statistically significant difference between septic vs. non-septic patients (126 ± 51 vs. 66 ± 26; p<0.01). The Bray-Curtis beta diversity, reported by principal coordinate analysis of total hit frequencies, revealed 2 potentially separate clusters among septic vs. non-septic patients.ConclusionIn adult patients with community-acquired sepsis, specific changes in the composition and abundance of blood microbiota could be detected by 16S rRNA metagenome sequencing, compared to non-septic control patients. Traditional blood culture results only partially correlate with microbiota test results.

No abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor β1 (TGFβ1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene −1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 ± 4.8%; CT: 46.8 ± 4.8%; TT: 35.6 ± 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35-4.10, p = 0.003). The cumulative incidence of acute GvHD grade III-IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 −1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 −1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.

Összefoglaló. A fertőzésekhez kapcsolódó immunológiai kórképekre különösen jellemző, hogy mind etiológiai tényezőikben, mind klinikai képükben rendkívül heterogének. Az átfedő és inkomplett megjelenési formák nem ritkák, ami a diagnosztika standardizálását nehezíti. Egyes, a fertőzésekhez opcionálisan kapcsolódó tünetek megfigyelése már több mint egy évszázaddal ezelőtt elvezetett a gócelmélet megszületéséhez, amely eredeti formájában leginkább elnagyolt és naiv feltételezéseken alapult. Folyamatosan bővülő ismereteink ugyanakkor egyre több esetben támasztják alá, hogy az átvészelt, esetleg krónikus vagy perzisztáló fertőzések, illetve a mikrobiom összetétele számos ponton lehet befolyással immunológiai, metabolikus és endokrin homeosztázisunkra. A jelen munkában az ismert összefüggéseket, illetve a meghaladott feltételezéseket is röviden érintve megkíséreljük a rendelkezésre álló ismereteken keresztül áttekinteni a fertőzésekhez kapcsolódó immunológiai jelenségek szürkezónáját, azon kórtani folyamatokat és tüneteket, amelyek létezése igazolható, de terápiás következményeik az egyén szintjén egyelőre bizonytalanok. Orv Hetil. 2021; 162(38): 1526–1532. Summary. Immunologic phenomena related to infections are well known to be truly heterogeneous, both regarding their etiology and the clinical picture. Overlapping symptoms and incomplete presentations are not seldom, which often constitute diagnostic challenge. Certain, optional complications of infectious diseases led to the creation of the focal infection theory more than a century ago, although only on the basis of assumptions derived from elusive and naive theories. However, an expanding body of evidence ever since did underline the impact of previous and persistent infections on the immunologic, metabolic and endocrine homeostasis. Besides briefly touching the well-defined diseases, as well as the outdated theories of this field, we aim to provide an overview of the grey zone of infection-related immunologic phenomena, the existence of which is biologically well established, however, their true significance on an individual basis remains uncertain. Orv Hetil. 2021; 162(38): 1526–1532.