Composition and richness of the serum microbiome differ by age and link to systemic inflammation

Advanced age has been associated with alterations to the microbiome within the intestinal tract as well as intestinal permeability (i.e., “leaky gut”). Prior studies suggest that intestinal permeability may contribute to increases in systemic inflammation—an aging hallmark—possibly via microorganisms entering the circulation. Yet, no studies exist describing the state of the circulating microbiome among older persons. To compare microbiota profiles in serum between healthy young (20–35 years, n?=?24) and older adults (60–75 years, n?=?24) as well as associations between differential microbial populations and prominent indices of age-related inflammation. Unweighted Unifrac analysis, a measure of β-diversity, revealed that microbial communities clustered differently between young and older adults. Several measures of α-diversity, including chao1 (p?=?0.001), observed species (p?=?0.001), and phylogenetic diversity (p?=?0.002) differed between young and older adults. After correction for false discovery rate (FDR), age groups differed (all p values ≤?0.016) in the relative abundance of the phyla Bacteroidetes, SR1, Spirochaetes, Bacteria_Other, TM7, and Tenericutes. Significant positive correlations (p values ≤?0.017 after FDR correction) were observed between IGF1 and Bacteroidetes (ρ?=?0.380), Spirochaetes (ρ?=?0.528), SR1 (ρ?=?0.410), and TM7 (ρ?=?0.399). Significant inverse correlations were observed for IL6 with Bacteroidetes (ρ?=???0.398) and TM7 (ρ?=???0.423), as well as for TNFα with Bacteroidetes (ρ?=???0.344). Similar findings were observed at the class taxon. These data are the first to demonstrate that the richness and composition of the serum microbiome differ between young and older adults and that these factors are linked to indices of age-related inflammation.     

Protective Effect of Rituximab in Chronic Graft-Versus-Host Disease Occurrence in Allogeneic Transplant patients with Epstein Barr Virus Viremia

B cells are involved in chronic graft-versus-host disease (cGVHD) pathogenesis, and Rituximab may have a therapeutic effect on cGVHD in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Herein, we retrospectively evaluated the prophylactic effect of Rituximab on cGVHD in a group of Chinese allo-HSCT patients. A total of 102 patients, who suffered Epstein Barr virus (EBV) viremia within 100 days after allo-HSCT, were included in this study. Fifty patients received Rituximab (375 mg/m² weekly) for EBV viremia, while fifty-two patients did not receive Rituximab. A competing risk model was adopted to compare cumulative incidence of cGVHD, cumulative incidence of relapse (CIR) and transplantation-related mortality (TRM) between two groups. Cumulative incidence of cGVHD in the Rituximab group was lower than in controls (P = 0.0579). Multivariate analyses confirmed that Rituximab was an independent factor for the reduction of cumulative cGVHD incidence (P = 0.0069). No significant difference was observed in CIR (P = 0.39) or TRM (P = 0.48) between two groups and 2-year OS and DFS were comparable (OS, P = 0.667; DFS, P = 0.571). Administration of Rituximab in the early post-transplantation phase may protect against cGVHD in allo-HSCT patients without increasing CIR or TRM.     

Differences in the gut microbiota of dogs (<Emphasis Type="Italic">Canis lupus familiaris</Emphasis>) fed a natural diet or a commercial feed revealed by the Illumina MiSeq platform

Background

Recent advances in next-generation sequencing technologies have enabled comprehensive analysis of the gut microbiota, which is closely linked to the health of the host. Consequently, several studies have explored the factors affecting gut microbiota composition. In recent years, increasing number of dog owners are feeding their pets a natural diet i.e., one consisting of bones, raw meat (such as chicken and beef), and vegetables, instead of commercial feed. However, the effect of these diets on the microbiota of dogs (Canis lupus familiaris) is unclear.

Methods and results

Six dogs fed a natural diet and five dogs fed a commercial feed were selected; dog fecal metagenomic DNA samples were analyzed using the Illumina MiSeq platform. Pronounced differences in alpha and beta diversities, and taxonomic composition of the core gut microbiota were observed between the two groups. According to alpha diversity, the number of operational taxonomic units, the richness estimates, and diversity indices of microbiota were significantly higher (p < 0.05) in the natural diet group than in the commercial feed group. Based on beta diversity, most samples clustered together according to the diet type (p = 0.004). Additionally, the core microbiota between the two groups was different at the phylum, family, and species levels. Marked differences in the taxonomic composition of the core microbiota of the two groups were observed at the species level; Clostridium perfringens (p = 0.017) and Fusobacterium varium (p = 0.030) were more abundant in the natural diet group.

Conclusions

The gut microbiota of dogs is significantly influenced by diet type (i.e., natural diet and commercial feed). Specifically, dogs fed a natural diet have more diverse and abundant microbial composition in the gut microbiota than dogs fed a commercial feed. In addition, this study suggests that in dogs fed a natural diet, the potential risk of opportunistic infection could be higher, than in dogs fed a commercial feed. The type of diet might therefore play a key role in animal health by affecting the gut microbiota. This study could be the basis for future gut microbiota research in dogs.

     

Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes

Aims/hypothesis

Despite improved understanding of the pathophysiology of type 2 diabetes mellitus, explanations for individual variability in disease progression and response to treatment are incomplete. The gut microbiota has been linked to the pathophysiology of type 2 diabetes mellitus and may account for this variability. We conducted a systematic review to assess the effectiveness of dietary and physical activity/exercise interventions in modulating the gut microbiota and improving glucose control in adults with type 2 diabetes mellitus.

Methods

A systematic search was conducted to identify studies reporting on the effect of dietary and physical activity/exercise interventions on the gut microbiota and glucose control in individuals with a confirmed diagnosis of type 2 diabetes mellitus. Study characteristics, methodological quality and details relating to interventions were captured using a data-extraction form. Meta-analyses were conducted where sufficient data were available, and other results were reported narratively.

Results

Eight studies met the eligibility criteria of the systematic review. No studies were found that reported on the effects of physical activity/exercise on the gut microbiota and glucose control. However, studies reporting on dietary interventions showed that such interventions were associated with modifications to the composition and diversity of the gut microbiota. There was a statistically significant improvement in HbA_1c (standardised mean difference [SMD] ?2.31 mmol/mol [95% CI ?2.76, ?1.85] [0.21%; 95% CI ?0.26, ?0.16]; I²?=?0%, p?<?0.01), but not in fasting blood glucose (SMD ?0.25 mmol/l [95% CI ?0.85, 0.35], I²?=?87%, p?>?0.05), fasting insulin (SMD ?1.82 pmol/l [95% CI ?7.23, 3.60], I²?=?54%, p?>?0.05) or HOMA-IR (SMD ?0.15 [95% CI ?0.63, 0.32], I²?=?69%, p?>?0.05) when comparing dietary interventions with comparator groups. There were no significant changes in the relative abundance of bacteria in the genera Bifidobacterium (SMD 1.29% [95% CI ?4.45, 7.03], I²?=?33%, p?>?0.05), Roseburia (SMD ?0.85% [95% CI ?2.91, 1.21], I²?=?79%, p?>?0.05) or Lactobacillus (SMD 0.04% [95% CI ?0.01, 0.09], I²?=?0%, p?>?0.05) when comparing dietary interventions with comparator groups. There were, however, other significant changes in the gut microbiota, including changes at various taxonomic levels, including phylum, family, genus and species, Firmicutes:Bacteroidetes ratios and changes in diversity matrices (α and β). Dietary intervention had minimal or no effect on inflammation, short-chain fatty acids or anthropometrics.

Conclusions/interpretation

Dietary intervention was found to modulate the gut microbiota and improve glucose control in individuals with type 2 diabetes. Although the results of the included studies are encouraging, this review highlights the need for further well-conducted interventional studies to inform the clinical use of dietary interventions targeting the gut microbiota.

     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Aberrant intestinal microbiota in individuals with prediabetes

Aims/hypothesis

Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA_1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health.

Methods

In the present case–control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation.

Results

We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log₂ fold change ?0.64 (SEM 0.23), p _adj ?=?0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log₂ fold change 0.51 (SEM 0.12), p _adj ?=?5?×?10^?4; 0.51 (SEM 0.11), p _adj ?=?1?×?10^?4; 0.60 (SEM 0.21), p _adj ?=?0.0497; and 0.92 (SEM 0.21), p _adj ?=?4?×?10^?4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log₂ fold change ?1.74 (SEM 0.41), p _adj ?=?2?×?10^?3 and ?1.65 (SEM 0.34), p _adj ?=?4?×?10^?4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

Conclusions/interpretation

Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Differences Between the Intestinal Lumen Microbiota of Aberrant Crypt Foci (ACF)-Bearing and Non-bearing Rats

Background

Multiple factors including host–microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process.

Aim

The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer.

Methods

To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing.

Results

The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P?<?0.01). At the genus level, no significant difference was observed in the most predominant genus, Lactobacillus. Instead, Bacteroides and Prevotella were significantly less abundant (P?<?0.01), while Akkermansia was significantly more abundant (P?<?0.05) in ACF-bearing group at the 13th week.

Conclusion

Imbalance of the intestinal microbiota existed between ACF-bearing and non-bearing rats, which could be used as biomarker to predict the genesis of precancerous lesions in the gut.

     

Nursing home-acquired pneumonia presenting at the emergency department

Nursing home-acquired pneumonia (NHAP) is one of the most common infections arising amongst nursing home residents, and its incidence is expected to increase as population ages. The NHAP recommendation for empiric broad-spectrum antibiotic therapy, arising from the concept of healthcare-associated pneumonia, has been challenged by recent studies reporting low rates of multidrug-resistant (MDR) bacteria. This single center study analyzes the results of NHAP patients admitted through the Emergency Department (ED) at a tertiary center during the year 2010. There were 116 cases, male gender corresponded to 34.5 % of patients and median age was 84 years old (IQR 77–90). Comorbidities were present in 69.8 % of cases and 48.3 % of patients had used healthcare services during the previous 90 days. In-hospital mortality rate was 46.6 % and median length-of-stay was 9 days. Severity assessment at the Emergency Department provided CURB65 index score and respective mortality (%) results: zero: n = 0; one: n = 7 (0 %); two: n = 18 (38.9 %); three: n = 26 (38.5 %); four: n = 30 (53.3 %); and five; n = 22 (68.2 %); and sepsis n = 50 (34.0 %), severe sepsis n = 43 (48.8 %) and septic shock n = 22 (72.7 %). Significant risk factors for in-hospital mortality in multivariate analysis were polypnea (p = 0.001), age ≥ 75 years (p = 0.02), and severe sepsis or shock (p = 0.03) at the ED. Microbiological testing in 78.4 % of cases was positive in 15.4 % (n = 15): methicillin-resistant Staphylococcus aureus (26.7 %), Pseudomonas aeruginosa (20.0 %), S. pneumoniae (13.3 %), Escherichia coli (13.3 %), others (26.7 %); the rate of MDR bacteria was 53.3 %. This study reveals high rates of mortality and MDR bacteria among NHAP hospital admissions supporting the use of empirical broad-spectrum antibiotic therapy in these patients.     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.     

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.

     

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.     

The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes

Aims/hypothesis

We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion.

Methods

Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders.

Results

The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30–0 min) response, a lower C-peptide index (30–0 min C-peptide/30–0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all).

Conclusions/interpretation

Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.

     

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

     

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima–media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.     

Damage control surgery in perforated diverticulitis: ongoing peritonitis at second surgery predicts a worse outcome

Purpose

Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery.

Methods

Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann’s procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed.

Results

Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p =?0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p =?0.001), and increased operation time (105 vs. 84 min., p =?0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p <?0.001). Complication rate (44 vs. 24%, p =?0.092), mortality (12 vs. 0%, p =?0.061), overall number of surgeries (3.4 vs. 2.4, p =?0.017), enterostomy rate (76 vs. 36%, p =?0.001), and length of hospital stay (25 vs. 18.8 days, p =?0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p =?0.005) and with fungal infection (100 vs. 49%, p =?0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p <?0.001), enterostomy rate (81 vs. 48%, p =?0.017), and anastomotic leakage (29 vs. 6%, p =?0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p =?0.014).

Conclusion

Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.

     

Risk for latent and active tuberculosis in Germany

Purpose

Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany.

Methods

Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs.

Results

From 2008–2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up.

Conclusions

Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

     

Use of medication reminders in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites—54 % vs Blacks—30 % vs Hispanics—26 %, p = 0.003), and sex (males—50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed—21 % vs unemployed—43 %, p = 0.006). Use of calendars was associated with adherence while away from home (ρ = 0.16, p = 0.03), when busy (ρ = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (ρ = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (ρ = ?0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence.