Aims/hypothesis
The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes.
Methods
In total, 605 patients ...aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure.
Results
Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction.
Conclusions/interpretation
This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to ‘unmasking’ these patients.
Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, ...probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life.
In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic® Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS-pro. Differences in bacterial abundance and diversity were assessed by conventional statistics.
The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby microbiota composition at phylum level evolved more and more towards an adult-like configuration.
Perinatal supplementation with Ecologic® Panda, to children at high-risk for atopic disease, had minor effects on gut microbiota composition during the supplementation period. No long lasting differences were identified. Regardless of intervention or atopic disease status, children had a shared microbiota development over time determined by age that continued to develop between two and six years.
Background
Despite improvements in the multimodality treatment for patients with locally recurrent rectal cancer (LRRC), oncological outcomes remain poor. This study evaluated the effect of induction ...chemotherapy and subsequent chemo(re)irradiation on the pathologic response and the rate of resections with clear margins (R0 resection) in relation to long-term oncological outcomes.
Methods
All consecutive patients with LRRC treated in the Catharina Hospital Eindhoven who underwent a resection after treatment with induction chemotherapy and subsequent chemo(re)irradiation between January 2010 and December 2018 were retrospectively reviewed. Induction chemotherapy consisted of CAPOX/FOLFOX. Endpoints were pathologic response, resection margin and overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and metastasis free survival (MFS).
Results
A pathologic complete response was observed in 22 patients (17%), a “good” response (Mandard 2–3) in 74 patients (56%), and a “poor” response (Mandard 4–5) in 36 patients (27%). An R0 resection was obtained in 83 patients (63%). The degree of pathologic response was linearly correlated with the R0 resection rate (
p
= 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (
p
= 0.004,
p
= 0.003, and
p
= 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (
p
= 0.020 and
p
= 0.028, respectively).
Conclusions
Induction chemotherapy in addition to neoadjuvant chemo(re)irradiation is a promising treatment strategy for patients with LRRC with high pathologic response rates that translate into improved oncological outcomes, especially when an R0 resection has been achieved.
Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy (CRT) have improved local control of rectal cancer; however, we have been ...unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs.
Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features.
On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042).
LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.
Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic ...low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients.
Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria.
307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease.
Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.
Background. Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive, and often biased. We intended to determine the relative risks of common ...infections in patients with type 1 and type 2 diabetes mellitus (DM1 and DM2, respectively). Methods. In a 12-month prospective cohort study conducted as part of the Second Dutch National Survey of General Practice, we compared 705 adult patients who had DM1 and 6712 adult patients who had DM2 with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically attended episodes of infection of the respiratory tract, urinary tract, and skin and mucous membranes. We applied multivariable and polytomous logistic regression analysis to determine independent risks of infections and their recurrences in patients with diabetes, compared with control patients. Results. Upper respiratory infections were equally common among patients with diabetes and control patients. Patients with diabetes had a greater risk of lower respiratory tract infection (for patients with DM1: adjusted odds ratio AOR, 1.42 95% confidence interval {CI}, 0.96–2.08; for patients with DM2: AOR, 1.32 95% CI, 1.13–1.53), urinary tract infection (for patients with DM1: AOR, 1.96 95% CI, 1.49–2.58; for patients with DM2: AOR, 1.24 95% CI, 1.10–1.39), bacterial skin and mucous membrane infection (for patients with DM1: AOR, 1.59 95% CI, 1.12–2.24; for patients with DM2: AOR, 1.33 95% CI, 1.15–1.54), and mycotic skin and mucous membrane infection (for patients with DM1: AOR, 1.34 95% CI, 0.97–1.84; for patients with DM2: AOR, 1.44 95% CI, 1.27–1.63). Risks increased with recurrences of common infections. Conclusions. Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection. Studies are warranted into management of such infections in patients with diabetes.
Aims
To investigate the relationship between diabetes duration and diabetes‐related distress and to examine the impact of micro‐ and macrovascular complications and blood glucose‐lowering treatment ...on this relationship.
Methods
We conducted a cross‐sectional study in people with Type 2 diabetes who participated in the Dutch Diacourse study (n = 590) and completed the Problem Areas in Diabetes questionnaire. Data on diabetes duration, micro‐ and macrovascular complications and blood glucose‐lowering treatment were collected. Multiple linear regression analysis was used to investigate the association between diabetes duration and diabetes‐related distress, and to examine whether complications and treatment could explain this association.
Results
A significant linear and quadratic association between diabetes duration and diabetes‐related distress was found (duration: β = 0.27, P = 0.005; duration2: β = ‐0.21, P = 0.030). The association between duration and distress could be explained by microvascular complications and insulin treatment, which were both more often present in people with a longer diabetes duration, and were associated with higher levels of diabetes‐related distress (β = 0.20, P < 0.001 and β = 0.16, P = 0.006 respectively). Duration, age, gender, complications and treatment together explained 13.1% of the variance in distress.
Conclusions
Diabetes duration was associated with diabetes‐related distress. This association can be explained largely by the presence of diabetes‐related microvascular complications and insulin treatment. Healthcare providers should focus on distress in people with Type 2 diabetes in different stages over the course of illness, especially when complications are present or when people are on insulin treatment. As well as diabetes duration, complications and blood glucose‐lowering treatment, diabetes‐related distress is likely to be influenced by many other factors.
What's new?
Most studies examining the association between diabetes duration and diabetes‐related distress have not found a linear association. Less is known about the quadratic association between diabetes duration and diabetes‐related distress.
In the present study, we found an association between duration and distress that was not only linear, but quadratic as well.
This association could be explained in large part by the presence of microvascular complications and insulin treatment.
Healthcare providers should focus on diabetes‐related distress at different stages over the course of illness, especially in people with Type 2 diabetes who have microvascular complications or are on insulin treatment.
Abstract
Background
The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes ...(LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients.
Methods
This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life.
Discussion
This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis.
Trial registration
Clinicaltrials.gov:
NCT04838496
, registered on 02–04-2021 Netherlands Trial Register: NL9790.
Protocol version
Version 3 dd 11–4-2022.
Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need ...for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %;
P
< 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.
A recent overview of all CVD models applicable to diabetes patients is not available.
To review the primary prevention studies that focused on the development, validation and impact assessment of a ...cardiovascular risk model, scores or rules that can be applied to patients with type 2 diabetes.
Systematic review.
Medline was searched from 1966 to 1 April 2011.
A study was eligible when it described the development, validation or impact assessment of a model that was constructed to predict the occurrence of cardiovascular disease in people with type 2 diabetes, or when the model was designed for use in the general population but included diabetes as a predictor.
A standardized form was sued to extract all data of the CVD models.
45 prediction models were identified, of which 12 were specifically developed for patients with type 2 diabetes. Only 31% of the risk scores has been externally validated in a diabetes population, with an area under the curve ranging from 0.61 to 0.86 and 0.59 to 0.80 for models developed in a diabetes population and in the general population, respectively. Only one risk score has been studied for its effect on patient management and outcomes. 10% of the risk scores are advocated in national diabetes guidelines.
Many cardiovascular risk scores are available that can be applied to patients with type 2 diabetes. A minority of these risk scores has been validated and tested for its predictive accuracy, with only a few showing a discriminative value of ≥0.80. The impact of applying these risk scores in clinical practice is almost completely unknown, but their use is recommended in various national guidelines.
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