The effect of azithromycin on sputum inflammatory markers in bronchiectasis.

BACKGROUND: Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity. METHODS: During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants. RESULTS: At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV1 < 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 - 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 - 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients. CONCLUSION: One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.

The BATTLE study: Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis. Study protocol of a double blind, randomized, placebo-controlled trial: study protocol.

Background: Patients with bronchiectasis typically suffer from chronic symptoms such as a productive cough with or without exacerbations leading to hospitalization, causing reduced quality of life (QoL) and mortality. Long-term inhaled antibiotics to treat chronic bronchial infection is registered for use in cystic fibrosis (CF) bronchiectasis. However, in patients with non-CF bronchiectasis data on long-term antibiotics are limited. Objective: To investigate the effectiveness of maintenance tobramycin inhalation solution (TIS) in bronchiectasis patients without cystic fibrosis. Study design: The BATTLE study is a randomized, double blind placebo controlled, multicenter study in the Netherlands performed in patients aged ≥18-year-old with confirmed bronchiectasis, at least two exacerbations in the preceding year, and minimal one positive sputum culture with gram negative pathogens or Staphylococcus aureus, sensitive to tobramycin in the preceding year and at baseline. Patients will be treated with TIS once daily (OD) or placebo (saline 0.9%) OD for 52 weeks followed by a run-out period of 4 weeks after the last dose. The primary outcome is the yearly rate of pulmonary exacerbations. Among secondary outcome parameters are time to exacerbation, lung function, QoL, microbiological evaluation and safety. Discussion: The BATTLE study is designed to determine the efficacy and safety of maintenance TIS OD in bronchiectasis patients colonized by different pathogens and could lead to important new evidence for TIS therapy in this population.The BATTLE study is registered in Clinical trials.gov with registration number: NCT02657473.

[Acute care during the first corona wave. Minor health damage for patients without covid-19 in a Dutch hospital]. / Acute zorg tijdens de eerste coronagolf.

GOAL: To study the effect of the first COVID-19 wave in combination with the lockdown on acute care in the Netherlands. DESIGN: Retrospective cohort study METHOD: For this study, data was collected from patients who visited the emergency department (ED) and Cardiac Care Unit of Noordwest Ziekenhuisgroep in Alkmaar and Den Helder. This data collection took place from 1 February to 28 June in 2019 and during the same period in 2020. The number of visits per day was investigated. The outcome measures for hospital occupation were the number of admissions per day and the average length of stay. Outcome measures for health damage were length of stay and mortality. RESULTS: The number of ED visits fell by 27% during the lockdown. For the specialties of internal medicine and pulmonary medicine, the number of admissions from the ED was the same during the lockdown, but the length of stay was longer. For all other specialties, the number of admissions from the ED was lower during the lockdown, but the admission duration was the same. Mortality was higher and hospital stay longer for patients admitted to the specialties of internal medicine and pulmonary medicine. In all other specialisms studied, there was no higher mortality or longer hospital stay. CONCLUSION: From the start of the lockdown, there was a sharp drop in the number of ED visits. The number of ED visits recovered slowly after this drop. For specialties that did not treat COVID-19 patients, hospital occupation was lower than usual. The number of admissions from the ED had decreased for these specialties. Based on the outcome measures length of stay and mortality, we were unable to find any indications of health damage as a result of the drop in admissions.

Impact of Body Composition on Surgical Outcome in Rectal Cancer Patients, a Retrospective Cohort Study.

BACKGROUND: Obesity is becoming a bigger health problem every year. Current research shows that the obesity-related metabolic problems are strongly associated with visceral fat and not subcutaneous fat. Visceral obesity (VO) is associated with a worse postoperative outcome in multiple fields of abdominal surgery. On the other hand, muscle mass is related to better postoperative outcome. In rectal cancer patients, we studied the influence of visceral obesity and muscle mass on postoperative complications. METHODS: The visceral fat area (VFA) and skeletal muscle area (SMA) were determined on preoperative CT scans in 406 patients. The preoperative comorbidity, per-operative outcome and postoperative complications were extracted retrospectively from the patient files. VO was defined as a VFA > 100 cm2. Correlations between body composition, postoperative complications and LOS were studied. RESULTS: In our study, 67% of the patients were classified as visceral obese. Mean body mass index (BMI) was higher in the VO group (26.6 ± 3.5 vs 23.5 ± 2.8; p < 0.001). Visceral obese patients had a higher prevalence of cardiac comorbidity (29% vs 13% p = 0.001), hypertension (36% vs 20% p = 0.002) and diabetes mellitus (16% vs 5% p = 0.002). In addition, VO patients had more operative blood loss (431 vs 310 mL; p = 0.008), longer operating time (166 vs 149 min p = 0.003) and more wound infections (14% vs 8% p = 0.048). Visceral obesity was associated with more complications (OR: 1.63 p = 0.043) and longer LOS (risk estimate: 1.18 p = 0.009). CONCLUSION: VO patients more often had a history of cardiac disease, hypertension and diabetes mellitus. Visceral obesity correlated with a worse outcome after surgery for rectal cancer.

Mini Nutritional Assessment and Mortality after Hip Fracture Surgery in the Elderly.

BACKGROUND: Hip fracture surgery in elderly patients is associated with a poor postoperative outcome and a high mortality. Malnutrition is a frequent problem in elderly patients and may be associated with mortality after hip fracture surgery. The Mini Nutritional Assessment (MNA) is a valuable tool to identify malnourished patients and those at risk for malnutrition. OBJECTIVE: To evaluate the association between the preoperative MNA score and mortality after surgery for hip fractures in elderly patients. METHODS: Patients with a hip fracture and an indication for surgery were included in our study. This study was part of a randomized trial on the effect of taurine on postoperative outcome in elderly hip fracture patients. The MNA was assessed on admission before surgery. Length of stay, postoperative complications and mortality were documented. The association of the MNA score on postoperative outcome and mortality was analyzed using Cox regression analysis. RESULTS: The one-year survival rate in 226 elderly hip fracture patients was 79%. In-hospital mortality rates and 1-year mortality were 27% and 46% in malnourished patients, 12% and 26% in patients at risk for malnutrition and 7% and 17% in well-nourished patients as assessed by MNA. CONCLUSION: Preoperative malnutrition measured by the MNA is associated with mortality in elderly hip fracture patients.

Dexa Body Composition Assessment in 10-11 Year Healthy Children.

INTRODUCTION: Obesity is a growing health problem associated with metabolic derangements and cardiovascular disease. Accumulating evidence links the accumulation of visceral adipose tissue (VAT) to these obesity related health risks in adults. Childhood obesity is associated with a lifetime risk of cardiovascular disease and poses a serious challenge to future health care. In children, there is much less data on the prevalence and gender differences of visceral obesity than in adults. This study aims to provide reference values for VAT in children 10-11 years of age. METHODS: In a cross-sectional study performed in the north western part of theNetherlands, healthy children of 10-11 years of age, were recruited from primary schools. Anthropometric data consisting of height, weight, waist circumference (WC) and BMI were measured. Body composition was measured using DXA, providing measures for bone mineral content, total fat mass (TFM), lean body mass (LBM) and VAT. RESULTS: 217 children were eligible for this study. Girls appeared to have a greater TFM (31.4% vs 27.5% of total body weight (TBW); P < .01) but lower VAT (0.3% vs 0.5% of TBW;P < .01) than boys, whereas boys had higher LBM (65.4% vs 69.3% TBW;P < .01). Median VAT area (cm2) was 41.1 for boys and 22.4 for girls (P < .01). Moderate to strong correlations were found for WC and BMI with VAT (boys: r = .664 and r = .630; Girls r = .699 and r = .546 respectively all P < .001). DISCUSSION: This study shows gender specific differences in VAT percentiles in healthy non-obese 10-11 year old children as measured by DXA that may serve as reference values in children. Independent of BMI and WC, girls tend to have more TFM but less VAT and LBM than boys.

Preoperative Methods to Reduce Liver Volume in Bariatric Surgery: a Systematic Review.

BACKGROUND: Patients qualified for gastric bypass surgery have an enlarged and fatty liver. An essential step in gastric bypass surgery is elevation of the left liver lobe to expose the gastroesophageal junction. An enlarged and fatty liver complicates the surgical procedure and increases the risk for laceration of the liver. The aim of our study was to evaluate methods to reduce liver volume in patients prior to gastric bypass surgery. METHODS: A systematic literature search of multiple databases, including PubMed, EMBASE.com, and the Cochrane Library and a hand search of reference lists, was performed. We used the search terms morbid obesity and liver, including their synonyms and controlled terms. Inclusion criteria were as follows: patients with morbid obesity who qualified for bariatric surgery, the use of a preoperative treatment to reduce liver volume, and the use of imaging techniques before and after treatment. RESULTS: In total, 281 patients in 11 different studies were included. Preoperative diets reduced liver size by an average of 14%, alternative methods including nutritional supplements, reduced liver size between 20 and 43%, and an intragastric balloon by 32%. CONCLUSIONS: This review showed that nutritional supplements and intragastric balloon are more effective than low calorie diets in reducing liver volume prior to gastric bypass surgery. However, low calorie diet is the preferable method to reduce liver volume, considering the level of evidence and practical applicability. There is a need for well-designed randomized studies with sufficient power in order to confirm the effectiveness of preoperative methods to reduce liver volume.

Eight years of experience with Enhanced Recovery After Surgery in patients with colon cancer: Impact of measures to improve adherence.

BACKGROUND: Perioperative treatment of patients with colorectal cancer according to the Enhanced Recovery After Surgery (ERAS) protocol has proven to reduce complications and duration of stay. However, strict adherence remains a challenge and the benefits may decrease with lower adherence. In this study, we report on 8 years of adherence to the ERAS protocol and its effect on postoperative outcome in patients with colon cancer. METHODS: In 2006, the ERAS protocol was introduced for treatment of colon cancer patients in the Medical Center Alkmaar, a large teaching hospital. Patients scheduled for elective colon cancer resection were included in this study. Adherence to ERAS items was monitored and along with clinical data prospectively gathered in a database. In 2011, several measures to improve adherence were implemented. RESULTS: In total, 816 patients were included. Mean adherence rate was 73% in 2006 and 2007, 66% in 2008 and 2009, 63% in 2010 and 2011, and 82% in 2012 and 2013. There was a shorter duration of stay in the years with high adherence (5.7 days) compared with the years with low adherence (7.3 days; P < .001). The ERAS items that were the strongest predictors for a shorter duration of stay were no nasogastric tube, early mobilization, early oral nutrition, early removal of epidural, early removal of catheter, and nonopioid oral analgesia. CONCLUSION: It is possible to improve adherence to the ERAS protocol and related outcomes with specific measures. Adherence to the ERAS protocol was related inversely to duration of stay. Only postoperative items of the ERAS protocol were predictive for a shorter duration of stay. Keeping adherence optimal remains an ongoing challenge that requires repeated training and dedicated personnel.

Occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment.

BACKGROUND: This study aimed to explore the occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment and the effect of such poor response on transfusion in total hip arthroplasty patients. METHODS: We studied total hip arthroplasty patients who received erythropoietin before surgery. The primary outcome was the pre-operative increase in haemoglobin (delta haemoglobin) as response to erythropoietin therapy. Additionally, patients were classified in tertiles based on this delta haemoglobin: poor responders (cases), responders and good responders (controls) to erythropoietin. Patient characteristics, comedication and co-morbidity were collected as potential determinants of erythropoietin response. Regression techniques were used to estimate the strength of the associations and to assess the effect of poor response on transfusion requirement. RESULTS: A total of 379 patients receiving erythropoietin were eligible to enter the study. Mean delta haemoglobin was 19.3 g/l (standard deviation 9.4). Factors significantly associated with delta haemoglobin were the use of angiotensin II antagonists [-3.1 g/l; 95% confidence interval (CI) -5.7 to -0.6] and vitamin K antagonists (-6.9 g/l; 95% CI -10.0 to -0.2), together with body mass index (BMI) (-0.3 g/l per unit>; 95% CI -0.5 to -0.2). The additional case-control analysis yielded comparable results. Poor response to erythropoietin was associated with an increased transfusion risk (odds ratio 4.6, 95% CI 2.0-11). CONCLUSION: Use of angiotensin II receptor antagonists and vitamin K antagonists, and having a high BMI were determinants of poor response to short-term pre-operative erythropoietin treatment in total hip arthroplasty patients. Poor responders had a higher risk for perioperative blood transfusion.