Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults

OBJECTIVETo examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort.RESEARCH DESIGN AND METHODSWe collected fecal samples from 5,572 Finns (mean age 48.7 years; 54.1% women) in 2002 who were followed up for incident type 2 diabetes until 31 December 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident diabetes using multivariable-adjusted Cox regression models. We first used the eastern Finland subpopulation to obtain initial findings and validated these in the western Finland subpopulation.RESULTSAltogether, 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected four species and two clusters consistently associated with incident diabetes in the validation models. These four species were Clostridium citroniae (hazard ratio [HR] 1.21; 95% CI 1.04–1.42), C. bolteae (HR 1.20; 95% CI 1.04–1.39), Tyzzerella nexilis (HR 1.17; 95% CI 1.01–1.36), and Ruminococcus gnavus (HR 1.17; 95% CI 1.01–1.36). The positively associated clusters, cluster 1 (HR 1.18; 95% CI 1.02–1.38) and cluster 5 (HR 1.18; 95% CI 1.02–1.36), mostly consisted of these same species.CONCLUSIONSWe observed robust species-level taxonomic features predictive of incident type 2 diabetes over long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome can potentially be used to improve disease prediction and uncover novel therapeutic targets for diabetes.     

Outcome in patients with early rheumatoid arthritis treated according to the “sawtooth” strategy

Objective. To investigate the outcome of early rheumatoid arthritis (RA) when treated according to the “sawtooth” strategy, and to compare the results with the findings of other studies. Methods. In this prospective study, 142 patients with early RA were treated actively with slow-acting antirheumatic drugs (SAARDs) for an average of 6.2 years, and were closely monitored clinically. Several outcome measures were applied, and the results were compared with findings in previously described cohorts. Results. The mean cumulative number of SAARDs used during the study was 3.3. Treatment changes were made because of inefficacy more often than because of adverse events. The percentage of patients whose disease entered remission increased with time to 32% (45 of 142). Only 24% of the patients (34 of 142) had deterioration to Steinbrocker functional class III or IV. The “sawtooth” treatment strategy seemed to improve the outcome of the patients with early RA. Conclusion. In the majority of patients with early RA, “sawtooth” therapy remains beneficial for at least 6 years. However, in one-fourth of the patients, the disease fails to respond to this drug treatment strategy.     

Health and social service use among old people in the last 2 years of life

This study focuses on differences in health and social service use in the last 2 years of life among Finnish people aged 70–79, 80–89, and 90 or older and on the variation in service use in the various municipalities. The data set, derived from multiple national registers, consists of 75,578 people who died in 1998–2001. The services included hospitals and long-term-care facilities, use of regular home care, and prescribed medicines. General hospital and public long-term care were the services most commonly used: general hospitals for younger age groups and public long-term care for older groups. The number of inpatient days in hospital was lower with increasing age, but older age groups used long-term care more frequently. Men had more hospital inpatient days than women, but women used more long-term care. The number of hospital inpatient days increased rapidly in the last months of life, almost doubling in the final month. Days in public long-term care increased regularly in the last 2 years of life. Variation in both hospital and long-term care by municipality was remarkable. The results indicate that, among people aged 70 years and older, age is a major determinant of care in the last 2 years of life. The variation in the use of care by municipality and the differences between men and women deserve more detailed analysis in future.     

Promoter‐specific alterations of APC are a rare cause for mutation‐negative familial adenomatous polyposis

In familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation‐negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation‐dependent probe amplification (MLPA, P043‐B1). Promoter‐specific events of APC were addressed by targeted resequencing, MLPA (P043‐C1), methylation‐specific MLPA, and Sanger sequencing of promoter regions. A novel 132‐kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele‐specific APC expression. No promoter‐specific point mutations or hypermethylation were present in any family. In conclusion, promoter‐specific alterations are a rare cause for mutation‐negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele‐specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations. © 2014 Wiley Periodicals, Inc.     

SLEEVEPASS: A randomized prospective multicenter study comparing laparoscopic sleeve gastrectomy and gastric bypass in the treatment of morbid obesity: preliminary results

Background

The long-term efficacy of laparoscopic Roux-en-Y gastric bypass (RYGB) in the treatment of morbid obesity has been demonstrated. Laparoscopic sleeve gastrectomy (SG) as a single procedure has shown promising short-term results, but the long-term efficacy of SG has not yet been demonstrated. The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospective multicenter randomized setting.

Methods

A total of 240 morbidly obese (BMI?=?35–66?kg/m2) patients evaluated by a multidisciplinary team were randomized to undergo either RYGB or SG. There were 117 patients in the RYGB group and 121 in the SG group; two patients had to be excluded after randomization. Both study groups were comparable regarding age, gender, BMI, and comorbidities.

Results

There was no 30-day mortality. The median operating time was significantly shorter in the SG group (66?min vs. 94?min, p?p?=?0.292). Nine (7.4 %) SG patients and 20 (17.1 %) RYGB patients had minor complications (p?=?0.023). The overall morbidity was 13.2 % after SG and 26.5 % after RYGB (p?=?0.010). There were three (2.5 %) early reoperations after SG and four (3.3 %) after RYGB (p?=?0.719).

Conclusions

At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB. There were no significant differences in major complications or early reoperations. Long-term follow-up is required to determine the effect on weight loss, resolution of obesity-related comorbidities, and improvement of quality of life.     

Two-ring hybrid external fixation of distal tibial fractures: a review of 47 cases

BACKGROUND: The healing of a metaphyseal fracture line is a major problem in cases of distal tibial fracture treated with external fixation. METHODS: Forty-seven distal tibial fractures treated with two-ring Ilizarov hybrid external fixation (16 AO/OTA type A and 31 type C, 10 open) were followed up. Fracture reduction and union time was evaluated and IOWA and RAND 36-Item Health Survey scores were used to assess functional outcome. RESULTS: Thirty-five fractures united uneventfully in a median time of 20 weeks, but 12 fractures needed additional procedures because of delayed union. According to univariate analysis, the risk factors for a longer time needed for fracture union were translational displacement and current smoking, and the risk factors for reoperation because of delayed union translational displacement fibular fracture fixation, and the number of cigarettes smoked per day. In multivariate analysis, translational displacement was a risk factor for both longer time to fracture union and reoperation and fibular fracture fixation was a risk factor for reoperation. If the translational displacement was less than 3 mm, the reoperation rate was 6%, whereas if the displacement was more than 3 mm, it was 83%. Reoperation was performed on 50% of the patients who underwent fibular fixation and on 15% of the patients who did not undergo fibular fixation. There were only marginal decreases in the range of motion and arthritis scores in the AO/OTA fracture types other than type C3. There were no significant differences in RAND 36 scores between the general Finnish population aged 18 to 64 years and our patients. CONCLUSIONS: Hybrid external fixation of distal tibial fractures is associated with delayed union, which is closely related to the degree of residual translational displacement after reduction. Fixation of an associated fibular fracture does not help to achieve better contact in the tibial fracture and increases the risk of delayed union.     

Apolipoprotein E ε4 allele frequency is increased in Parkinson’s disease only with co-existing Alzheimer pathology

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency. Received: 15 January 1998 / Revised, accepted: 24 March 1998