Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial.

BACKGROUND: Adjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent. METHODS: In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I-III and IV-V). The primary outcome was LOS. RESULTS: Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0-5.0 days) than in the placebo group (5.0 days, 95% CI 4.6-5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent. CONCLUSION: Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk-benefit ratio is optimal.

The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency.

Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in 's-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as 'no PAD'. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63-0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62-0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51-0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85-1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential 'specific IgA or IgM antibody deficiency' in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.

Serum cytokine patterns in immunoglobulin m monoclonal gammopathy-associated polyneuropathy.

INTRODUCTION: Polyneuropathy with immunoglobulin M monoclonal gammopathy (IgM-PNP) is associated with the presence of IgM antibodies against nerve constituents such as myelin associated glycoprotein (MAG) and gangliosides. METHODS: To test whether B-cell-stimulating cytokines are increased in IgM-PNP, we measured serum concentrations of 11 cytokines in 81 patients with IgM-PNP and 113 controls. RESULTS: Median interleukin (IL)-6 concentrations were higher in patients with IgM-PNP, and median IL-10 concentrations were higher in the subgroup with anti-MAG IgM antibodies. These serum concentrations were not increased in 110 patients with multifocal motor neuropathy. DISCUSSION: Median IL-6 and IL-10 serum concentrations differ between patients with anti-MAG neuropathy and other patients with IgM-PNP compared with healthy and neuropathy controls. These differences may indicate differences in immune-mediated disease mechanisms. Muscle Nerve 59:694-698, 2019.

Genetics in community-acquired pneumonia.

PURPOSE OF REVIEW: Host defense against community-acquired pneumonia depends on an intact innate and acquired immune system. This review analyses the correlation between specific defects and polymorphisms of immunity genes with susceptibility for pneumonia. RECENT FINDINGS: Mutations in BTK, Bruton's tyrosine kinase, lead to X-linked agammaglobulinemia, a disease characterized by recurrent respiratory tract infections, including pneumonia. BTK inhibitors, which are used for treatment of leukemia, have pneumonia as side effect. Polymorphisms in B lymphocyte growth and differentiation factors, including IL-6 and IL-10, Fcg RIIa receptors, as well as genetic variants of ACE, angiotensin-converting enzyme, also are associated with increased susceptibility for pneumonia. SUMMARY: Delineation of underlying genetic defects and polymorphisms may add in diagnosis, therapy, and prognosis of community-acquired pneumonia. In case of humoral immunodeficiency, antibody replacement therapy may be indicated.

Wheezing and infantile colic are associated with neonatal antibiotic treatment.

BACKGROUND: Cohort studies have suggested that early-life antibiotic treatment is associated with increased risk of atopy. We determined whether antibiotic treatment already in the first week of life increases the risk of atopic and non-atopic disorders. METHODS: The INCA study is a prospective observational birth cohort study of 436 term infants, with follow-up of 1 year; 151 neonates received broad-spectrum antibiotics for suspected neonatal infection (AB+), vs a healthy untreated control group (N = 285; AB-). In the first year, parents recorded daily (non-) allergic symptoms. At 1 year, doctors' diagnoses were registered and a blood sample was taken (n = 205). RESULTS: Incidence of wheezing in the first year was higher in AB+ than AB- (41.0% vs 30.5%, P = .026; aOR 1.56 [95%CI 0.99-2.46, P = .06]). Infantile colics were more prevalent in AB+ compared to AB- (21.9% and 14.4% P = .048), and antibiotic treatment was an independent risk factor for infantile colics (aOR 1.66 (95%CI 1.00-2.77) P = .05). Allergic sensitization (Phadiatop >0.70kUA/L) showed a trend toward a higher risk in AB+ (aOR 3.26 (95%CI 0.95-11.13) P = .06). Incidence of eczema, infections, and GP visits in the first year were similar in AB+ and AB-. CONCLUSION: Antibiotic treatment in the first week of life is associated with an increased risk of wheezing and infantile colics. This study may provide a rationale for early cessation of antibiotics in neonates without proven or probable infection.

Romboutsia hominis sp. nov., the first human gut-derived representative of the genus Romboutsia, isolated from ileostoma effluent.

A Gram-stain-positive, motile, rod-shaped, obligately anaerobic bacterium, designated FRIFIT, was isolated from human ileostoma effluent and characterized. On the basis of 16S rRNA gene sequence similarity, strain FRIFIT was most closely related to the species Romboutsia ilealis CRIBT (97.7 %), Romboutsia lituseburensis DSM 797T (97.6 %) and Romboutsia sedimentorum LAM201T (96.6 %). The level of DNA-DNA relatedness between strain FRIFIT and R. ilealis CRIBT was 13.9±3.3 % based on DNA-DNA hybridization. Whole genome sequence-based average nucleotide identity between strain FRIFIT and closely related Romboutsia strains ranged from 78.4-79.1 %. The genomic DNA G+C content of strain FRIFIT was 27.8 mol%. The major cellular fatty acids of strain FRIFIT were saturated and unsaturated straight-chain C12-C19 fatty acids as well as cyclopropane fatty acids, with C16 : 0 being the predominant fatty acid. The polar lipid profile comprised five phospholipids and six glycolipids. These results, together with differences in phenotypic features, support the proposal that strain FRIFIT represents a novel species within the genus Romboutsia, for which the name Romboutsiahominis sp. nov. is proposed. The type strain is FRIFIT (=DSM 28814T=KCTC 15553T).

YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the prognostic value of four biomarkers, YKL-40, chemokine (C-C motif) ligand 18 (CCL18), surfactant protein-D (SP-D) and CA 15-3, in patients admitted with community-acquired pneumonia (CAP). These markers have been studied extensively in chronic pulmonary disease, but in acute pulmonary disease their prognostic value is unknown. METHODS: A total of 289 adult patients who were hospitalized with CAP and participated in a randomized controlled trial were enrolled. Biomarker levels were measured on the day of admission. Intensive care unit admission, 30-day, 1-year and long-term mortality (median follow-up of 5.4 years, interquartile range (IQR): 4.7-6.1) were recorded as outcomes. RESULTS: Median YKL-40 and CCL18 levels were significantly higher and levels of SP-D were significantly lower in CAP patients compared to healthy controls. Significantly higher YKL-40, CCL18 and SP-D levels were found in patients classified in pneumonia severity index classes 4-5 and with a CURB-65 score ≥2 compared to patients with less severe pneumonia. Furthermore, these three markers were significant predictors for long-term mortality in multivariate analysis and compared with C-reactive protein and procalcitonin level on admission, area under the curves were higher for 30-day, 1-year and long-term mortality. CA 15-3 levels were less predictive. CONCLUSION: YKL-40, CCL18 and SP-D levels were higher in patients with more severe pneumonia, possibly reflecting the extent of pulmonary inflammation. Of these, YKL-40 most significantly predicts mortality for CAP.

High-sensitivity cardiac troponin T predicts mortality after hospitalization for community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Mortality after hospitalization with community-acquired pneumonia (CAP) is high, compared with age-matched controls. Available evidence suggests a strong link with cardiovascular disease. Our aim was to explore the prognostic value of high-sensitivity cardiac troponin T (cTnT) for mortality in patients hospitalized with CAP. METHODS: CTnT level on admission was measured (assay conducted in 2015) in 295 patients hospitalized with CAP who participated in a randomized placebo-controlled double-blind trial on adjunctive dexamethasone treatment. Outcome measures were short- (30-day) and long-term (4.1-year) mortalities. RESULTS: CTnT levels were elevated (≥14 ng/L) in 132 patients (45%). Pneumonia severity index (PSI) class was 4-5 in 137 patients (46%). Short- and long-term mortality were significantly higher in patients with elevated cTnT levels. cTnT level on admission combined with PSI classification was significantly better in predicting short-term mortality (area under the operating curve (AUC) = 0.903; 95% CI = 0.847-0.960), compared with PSI classification alone (AUC = 0.818; 95% CI = 0.717-0.919). An optimal cTnT cut-off level of 28 ng/L was independently associated with both short- and long-term mortality (OR = 21.9; 95% CI = 4.7-101.4 and 10.7; 95% CI = 5.0-22.8, respectively). CONCLUSION: Elevated cTnT level on admission is a strong predictor of short- and long-term mortalities in patients hospitalized with CAP.

Exhaled biomarkers and gene expression at preschool age improve asthma prediction at 6 years of age.

RATIONALE: A reliable asthma diagnosis is difficult in wheezing preschool children. OBJECTIVES: To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children. METHODS: Two hundred two preschool recurrent wheezers (aged 2-4 yr) were prospectively followed up until 6 years of age. At 6 years of age, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function, and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age in diagnosing asthma at 6 years of age was determined with a validation set. Biomarkers in exhaled breath condensate, exhaled volatile organic compounds (VOCs), gene expression, and airway resistance were measured. MEASUREMENTS AND MAIN RESULTS: At 6 years of age, 198 children were diagnosed (76 with asthma, 122 with transient wheeze). Information on exhaled VOCs significantly improved asthma prediction (AUC, 89% [increase of 28%]; positive predictive value [PPV]/negative predictive value [NPV], 82/83%), which persisted in the validation set. Information on gene expression of toll-like receptor 4, catalase, and tumor necrosis factor-α significantly improved asthma prediction (AUC, 75% [increase of 17%]; PPV/NPV, 76/73%). This could not be confirmed after validation. Biomarkers in exhaled breath condensate and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression, and API had an AUC of 95% (PPV/NPV, 90/89%). CONCLUSIONS: Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children. Clinical trial registered with www.clinicaltrial.gov (NCT 00422747).

Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis.

Infliximab is effective as a third-line therapeutic for severe sarcoidosis; however, long-term efficacy is unknown. The aim of this study was to assess the relapse rate after discontinuation of infliximab in sarcoidosis patients and predict relapse by analysis of the activity marker soluble interleukin (IL)-2 receptor (sIL-2R) and maximum standardised uptake value (SUVmax) of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET). In this retrospective cohort study, the proportion of relapse was analysed using the Kaplan-Meier method and predicting factors were studied using Cox regression. 47 sarcoidosis patients who started infliximab therapy were included in the risk analysis. Kaplan-Meier analysis revealed a median time to relapse of 11.1 months and showed that 25% of the cohort relapsed within 4 months. Both mediastinal SUVmax ≥ 6.0 on FDG PET (hazard ratio 3.77, p<0.001) and serum sIL-2R ≥ 4000 pg · mL(-1) (hazard ratio 2.24, p=0.033) at start of therapy predicted relapse. In multivariate analysis, a mediastinal SUVmax ≥ 6.0 at initiation of therapy was an independent predictor of relapse (hazard ratio 4.33, p<0.001). The majority of patients that discontinued infliximab therapy relapsed. High serum sIL-2R and high SUVmax on FDG PET at initiation of therapy were significant predictors of relapse. These results suggest close monitoring of patients in this category when they discontinue infliximab treatment.

Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats.

BACKGROUND/OBJECTIVES: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic prophylaxis and enteral nutrition contributed to the higher mortality rate. METHODS: Male Sprague-Dawley rats were allocated to four groups: 1) acute pancreatitis (n = 9), 2) acute pancreatitis and probiotic prophylaxis (n = 10), 3) acute pancreatitis and enteral nutrition (n = 10), and 4) acute pancreatitis, probiotic prophylaxis and enteral nutrition (n = 11). Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Enteral nutrition, saline, probiotics and placebo were administered through a permanent jejunal feeding. Probiotics or placebo were administered starting 4 days before induction of pancreatitis and enteral nutrition 1 day before start until the end of the experiment, 6 days after induction of pancreatitis. Tissue samples and body fluids were collected for microbiological and histological examination. RESULTS: In all animals, serum amylase was increased six hours after induction of pancreatitis. After fulfilling the experiment, no differences between groups were found in histological severity of pancreatitis, degree of discomfort, weight loss, histological examination of small bowel and bacterial translocation (all p > 0.05). Overall mortality was 10% without differences between groups (p = 0.54). CONCLUSION: No negative association was found between prophylactic probiotics and enteral nutrition in acute pancreatitis. No new clues for a potential mechanism responsible for the higher mortality and bowel ischaemia in the PROPATRIA study were found.

Characterization of Romboutsia ilealis gen. nov., sp. nov., isolated from the gastro-intestinal tract of a rat, and proposal for the reclassification of five closely related members of the genus Clostridium into the genera Romboutsia gen. nov., Intestinibacter gen. nov., Terrisporobacter gen. nov. and Asaccharospora gen. nov.

A Gram-positive staining, rod-shaped, non-motile, spore-forming obligately anaerobic bacterium, designated CRIBT, was isolated from the gastro-intestinal tract of a rat and characterized. The major cellular fatty acids of strain CRIBT were saturated and unsaturated straight-chain C12-C19 fatty acids, with C16:0 being the predominant fatty acid. The polar lipid profile comprised six glycolipids, four phospholipids and one lipid that did not stain with any of the specific spray reagents used. The only quinone was MK-6. The predominating cell-wall sugars were glucose and galactose. The peptidoglycan type of strain CRIBT was A1σ lanthionine-direct. The genomic DNA G+C content of strain CRIBT was 28.1 mol%. On the basis of 16S rRNA gene sequence similarity, strain CRIBT was most closely related to a number of species of the genus Clostridium, including Clostridium lituseburense (97.2%), Clostridium glycolicum (96.2%), Clostridium mayombei (96.2%), Clostridium bartlettii (96.0%) and Clostridium irregulare (95.5%). All these species show very low 16S rRNA gene sequence similarity (<85%) to the type strain of Clostridium butyricum, the type species of the genus Clostridium. DNA-DNA hybridization with closely related reference strains indicated reassociation values below 32%. On the basis of phenotypic and genetic studies, a novel genus, Romboutsia gen. nov., is proposed. The novel isolate CRIBT (=DSM 25109T=NIZO 4048T) is proposed as the type strain of the type species, Romboutsia ilealis gen. nov., sp. nov., of the proposed novel genus. It is proposed that C. lituseburense is transferred to this genus as Romboutsia lituseburensis comb. nov. Furthermore, the reclassification into novel genera is proposed for C. bartlettii, as Intestinibacter bartlettii gen. nov., comb. nov. (type species of the genus), C. glycolicum, as Terrisporobacter glycolicus gen. nov., comb. nov. (type species of the genus), C. mayombei, as Terrisporobacter mayombei gen. nov., comb. nov., and C. irregulare, as Asaccharospora irregularis gen. nov., comb. nov. (type species of the genus), on the basis of additional data collected in this study. In addition, an emendation of the species Peptostreptococcus anaerobius and the order Eubacteriales is provided.

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia.

AIM: The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration-time curve (AUC) of oral dexamethasone in patients hospitalized with CAP. METHODS: In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4 mg intravenous or 6 mg oral dexamethasone for 4 consecutive days. Serial blood samples were obtained before and after drug administration. RESULTS: Median AUC to infinity was 626 µg l(-1) h (IQR 401-1161) for the intravenous group and 774 µg l(-1) h (IQR 618-1146) for the oral group. The AUC ratio of 6 mg oral and 4 mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82), which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose. CONCLUSIONS: Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients.

Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia; an observational analysis.

BACKGROUND: The aim of this study was to investigate the clinical outcome and especially costs of hospitalisation for community-acquired pneumonia (CAP) in relation to microbial aetiology. This knowledge is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP. METHODS: We performed our observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010. Hospital administrative databases were extracted for all resource utilisation on a patient level. Resource items were grouped in seven categories: general ward nursing, nursing on ICU, clinical chemistry laboratory tests, microbiology exams, radiology exams, medication drugs, and other.linear regression analyses were conducted to identify variables predicting costs of hospitalisation for CAP. RESULTS: Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%.Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index (indicative for severe disease), Staphylococcus aureus, or Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor. CONCLUSIONS: Median costs of hospitalisation for CAP are almost €4,000 per patient. Nursing costs are the main cause of these costs.. Apart from prevention, low-cost interventions aimed at reducing length of hospital stay therefore will most likely be cost-effective.

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory generated during the SARS-CoV-2 pandemic, either by infection or vaccination, offer protection against future coronaviruses? Or rather than protection, could antibody-dependent enhancement have taken place, a mechanism by which circulating corona antibodies enhance the severity of COVID-19? Another related phenomenon, the original antigenic sin, would also predict that the effectiveness of the immune response to future coronaviruses would be impaired because of the reactivation of memory against irrelevant epitopes. The currently available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

The long and winding road of faecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy.

INTRODUCTION: Immune checkpoint inhibition (ICI) therapy has revolutionized the treatment of cancer. Inhibitory molecules, either on the tumor or on cells of the immune system, are blocked, allowing the immune system of the patient to attack and eradicate the tumor. Not all patients respond to ICI therapy, and response or non-response has been associated with composition of gut microbiota. AREA COVERED: Fecal microbiota transplantation (FMT) is used as adjunctive therapy in order to improve the outcome of ICI. ClinicalTrials.gov, and other databases were searched (October 2022) for studies dealing with gut microbiota modification and the outcome of ICI. EXPERT OPINION: There is ample evidence for the beneficial effect of FMT on the outcome of ICI therapy for cancer, especially melanoma. Progress is being made in the unraveling of the mechanisms by which microbiota and their metabolites (butyrate and the tryptophan metabolite indole-3-aldehyde) interact with the mucosal immune system of the host. A better understanding of the mechanisms involved will allow the identification of key bacterial species which mediate the effect of FMT. Promising species are Faecalibacterium prausnitzii, Eubacterium rectale, Bifidobacterium adolescentis, B. bifidum, and B. longum, because they are important direct and indirect butyrate producers.

The Impact of SARS-CoV-2 Immune Status and Societal Restrictions in Controlling COVID-19 across the World.

To control the COVID-19 pandemic, many countries implemented vaccination and imposed societal restrictions both at the national level and for international travel. As a check of corona status, COVID passes have been issued. A COVID pass could be obtained when either fully vaccinated against COVID-19, or after recovering from a documented COVID-19 episode, or after a recent (24-48 h) negative SARS-CoV-2 antigen test. A global analysis of SARS-CoV-2 immune status determined by past infection and/or vaccination, vaccination rates, as well as societal restrictions in controlling the COVID-19 pandemic is presented. The data show that across the world, vaccination was more effective in reducing SARS-CoV-2 infections with the delta variant than the omicron variant. Strict societal restrictions could control spread of the virus, but relief of the restrictions was associated with an increase in omicron infections. No significant difference in SARS-CoV-2 infections were found when comparing countries or territories which did or did not implement a COVID pass.

Addition of vitamin D status to prognostic scores improves the prediction of outcome in community-acquired pneumonia.

BACKGROUND: Vitamin D plays a role in host defense against infection. Vitamin D deficiency is common worldwide. The prognostic value of vitamin D levels in pneumonia is unknown. In this study, we aimed to investigate the impact of vitamin D status on outcome in community-acquired pneumonia (CAP). METHODS: We conducted a prospective cohort study in 272 hospitalized patients with CAP. Levels of 25-hydroxyvitamin D, leukocytes, C-reactive protein, and total cortisol and the Pneumonia Severity Index (PSI) and CURB-65 scores were measured on admission. Major outcome measures were intensive care unit (ICU) admission and 30-day mortality. RESULTS: One hundred forty-three patients (53%) were vitamin D deficient (<50 nmol/L), 79 patients (29%) were vitamin D insufficient (50-75 nmol/L), and 50 patients (18%) were vitamin D sufficient (>75 nmol/L). Vitamin D deficiency was associated with an increased risk of ICU admission and 30-day mortality. Vitamin D status was an independent predictor of 30-day mortality (area under the curve [AUC] =0.69; 95% confidence interval [CI], .57-.80). Multivariate regression analysis including all predictors for outcome resulted in a final model including vitamin D status and the PSI score, with a significantly higher prognostic accuracy compared with the PSI score alone (AUC=0.83; 95% CI, .71-.94). CONCLUSIONS: Vitamin D deficiency is associated with adverse outcome in CAP. Vitamin D status is an independent predictor of 30-day mortality and adds prognostic value to other biomarkers and prognostic scores, in particular the PSI score. CLINICAL TRIALS REGISTRATION: NCT00471640.