Background
Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or ...without antibiotics for a first episode of uncomplicated acute diverticulitis.
Methods
Patients with CT‐proven, primary, left‐sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy. The primary endpoint was time to recovery during 6 months of follow‐up. Main secondary endpoints were readmission rate, complicated, ongoing and recurrent diverticulitis, sigmoid resection and mortality. Intention‐to‐treat and per‐protocol analyses were done.
Results
A total of 528 patients were included. Median time to recovery was 14 (i.q.r. 6–35) days for the observational and 12 (7–30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0·91 (lower limit of 1‐sided 95 per cent c.i. 0·78; P = 0·151). No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3·8 versus 2·6 per cent respectively; P = 0·377), ongoing diverticulitis (7·3 versus 4·1 per cent; P = 0·183), recurrent diverticulitis (3·4 versus 3·0 per cent; P = 0·494), sigmoid resection (3·8 versus 2·3 per cent; P = 0·323), readmission (17·6 versus 12·0 per cent; P = 0·148), adverse events (48·5 versus 54·5 per cent; P = 0·221) and mortality (1·1 versus 0·4 per cent; P = 0·432). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006). Per‐protocol analyses were concordant with the intention‐to‐treat analyses.
Conclusion
Observational treatment without antibiotics did not prolong recovery and can be considered appropriate in patients with uncomplicated diverticulitis. Registration number: NCT01111253 (http://www.clinicaltrials.gov).
Antibiotics not needed
Purpose
The aim of this systematic review is to identify risk factors that can predict complicated diverticulitis. Uncomplicated diverticulitis is a self-limiting and mild disease, but 10% of ...patients with diverticulitis develop complications requiring further treatment. It is important to estimate the risk of developing complicated diverticulitis at an early stage to set the right treatment at initial presentation.
Methods
Embase, MEDLINE, and Cochrane databases were searched for studies reporting on risk factors for complicated diverticulitis. Complicated diverticulitis was defined as Hinchey ≥Ib or severe diverticulitis according to the Ambrosetti criteria. Meta-analyses were performed when at least four studies reported on the outcome of interest. This study was conducted according to the PRISMA guidelines.
Results
A total of 12 studies were included with a total of 4619 patients. Most were of reasonable quality. Only the risk factors “age” and “sex” were eligible for meta-analysis, but none showed a significant effect on the risk for complicated diverticulitis. There was reasonable quality of evidence suggesting that high C-reactive protein; white blood cell count; clinical signs including generalized abdominal pain, constipation and vomiting; steroid usage; a primary episode; and comorbidity are risk factors for complicated diverticulitis.
Conclusion
Although high-level evidence is lacking, this study identified several risk factors associated with complicated diverticulitis. Individually, these risk factors have little value in predicting the course of diverticulitis. The authors propose a prognostic model combining these risk factors which might be the next step to aid the physician in predicting the course of diverticulitis and setting the right treatment at initial presentation.
Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated ...whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis.
Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO
), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors.
We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO
1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1), fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3).
A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .
Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients' needs. Little is known about the combination of liquid biopsies and computer ...extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the "clinical-radiological" model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.
Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are ...largely determined by dietary protein digestion and amino acid absorption kinetics.
We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.
We included data from 18 randomized controlled trials with a total of 602 participants age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3 who consumed various quantities of intrinsically ʟ-1-13C-phenylalaninelabeled whey (n = 137),casein (n = 393), or milk (n = 72) protein and received intravenous infusions of ʟ-ring-2H5-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein–derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.
A total of 50% ± 14% of dietary proteinderived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary proteinderived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary proteinderived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein–;derived phenylalanine appearing in the circulation, respectively (P = 0.001).
Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848,NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492.
Aim
To determine the diagnostic value of serological infection markers and body temperature in discriminating complicated from uncomplicated diverticulitis.
Methods
Patients in whom diverticulitis ...was pathologically or radiologically proven at presentation were included. Patients were classified as either complicated (Hinchey Ib, II, III and IV) or uncomplicated (Hinchey Ia) diverticulitis. The discriminative value of C‐reactive protein (CRP), white blood cell (WBC) count and body temperature at presentation was tested.
Results
A total of 426 patients were included in this study of which 364 (85%) presented with uncomplicated and 62 (15%) with complicated diverticulitis. Only CRP was of sufficient diagnostic value (area under the curve 0.715). The median CRP in patients with complicated diverticulitis was significantly higher than in patients with uncomplicated disease (224 mg/l, range 99–284 vs 87 mg/l, range 48–151). Patients with a CRP of 25 mg/l had a 15% chance of having complicated diverticulitis. This increased from 23% at a CRP value of 100 mg/l to 47% for 250 mg/l or higher. The optimal threshold was reached at 175 mg/l with a positive predictive value of 36%, negative predictive value of 92%, sensitivity of 61% and a specificity of 82%.
Conclusion
WBC count and body temperature are of no value in discriminating complicated from uncomplicated diverticulitis. Only CRP can be used as an indicator for the presence of complications, but a low CRP does not mean that complicated disease can safely be excluded. Therefore, radiological examination remains central in the diagnostic work‐up of patients presenting with diverticulitis.
We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell ...transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing <50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing <50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm difference, 6.5%; 95% confidence interval, 0.9%-12%; P = .03). This randomized trial demonstrates the efficacy of an echinocandin for antifungal prophylaxis in neutropenic patients.
Background
The results of the DIRECT trial, an RCT comparing conservative management with elective sigmoid resection in patients with recurrent diverticulitis or persistent complaints, showed that ...elective sigmoid resection leads to higher quality of life. The aim of this study is to determine the cost‐effectiveness of surgical treatment at 1‐ and 5‐year follow‐up from a societal perspective.
Methods
Clinical effectiveness and resource use were derived from the DIRECT trial. The actual resource use and quality of life (EQ‐5D‐3L™ score) were documented prospectively per individual patient and analysed according to the intention‐to‐treat principle for up to 5 years after randomization. The main outcome was the incremental cost‐effectiveness ratio (ICER), expressed as costs per quality‐adjusted life‐year (QALY).
Results
The study included 106 patients, of whom 50 were randomized to surgery and 56 to conservative treatment. At 1‐ and 5‐year follow‐up an incremental effect (QALY difference between groups) of 0·06 and 0·43 respectively was found, and an incremental cost (cost difference between groups) of €6957 and €2674 respectively, where surgery was more expensive than conservative treatment. This resulted in an ICER of €123 365 per additional QALY at 1‐year follow‐up, and €6275 at 5 years. At a threshold of €20 000 per QALY, operative treatment has 0 per cent probability of being cost‐effective at 1‐year follow‐up, but a 95 per cent probability at 5 years.
Conclusion
At 5‐year follow‐up, elective sigmoid resection in patients with recurring diverticulitis or persistent complaints was found to be cost‐effective. Registration number: NTR1478 (www.trialregistrer.nl).
Maintained benefits
•Plate fixation and IMN are both viable treatment options for distal tibia fractures, each with its advantages and disadvantages.•Intramedullary nailing is associated with a slightly increased risk ...of mal-union and anterior knee pain.•Plating, however, results in a slightly higher rate of infection.•The treatment of distal tibia fractures should, therefore, be based on a personalized approach and rely on shared decision-making.
Treatment for distal diaphyseal or metaphyseal tibia fractures is challenging and the optimal surgical strategy remains a matter of debate. The purpose of this study was to compare plate fixation with nailing in terms of operation time, non-union, time-to-union, mal-union, infection, subsequent re-interventions and functional outcomes (quality of life scores, knee- and ankle scores).
A search was performed in PubMed/Embase/CINAHL/CENTRAL for all study designs comparing plate fixation with intramedullary nailing (IMN). Data were pooled using RevMan and presented as odds ratios (OR), risk difference (RD), weighted mean difference (WMD) or weighted standardized mean difference (WSMD) with a 95% confidence interval (95%CI). All analyzes were stratified for study design.
A total of 15 studies with 1332 patients were analyzed, including ten RCTs (n = 873) and five observational studies (n = 459). IMN leads to a shorter time-to-union (WMD: 0.4 months, 95%CI 0.1 – 0.7), shorter time-to-full-weightbearing (WMD: 0.6 months, 95%CI 0.4 – 0.8) and shorter operation duration (WMD: 15.5 min, 95%CI 9.3 – 21.7). Plating leads to a lower risk for mal-union (RD: -10%, OR: 0.4, 95%CI 0.3 – 0.6), but higher risk for infection (RD: 8%, OR: 2.4, 95%CI 1.5 – 3.8). No differences were detected with regard to non-union (RD: 1%, OR: 0.7, 95%CI 0.3 – 1.7), subsequent re-interventions (RD: 4%, OR: 1.3, 95%CI 0.8 – 1.9) and functional outcomes (WSMD: -0.4, 95%CI -0.9 – 0.1). The effect estimates of RCTs and observational studies were equal for all outcomes except for time to union and mal-union.
Satisfactory results can be obtained with both plate fixation and nailing for distal extra-articular tibia fractures. However, nailing is associated with higher rates of mal-union and anterior knee pain while plate fixation results in an increased risk of infection. This study provides a guideline towards a personalized approach and facilitates shared decision-making in surgical treatment of distal extra-articular tibia fractures. The definitive treatment should be case-based and aligned to patient-specific needs in order to minimize the risk of complications.
Controversy remains on which patients with displaced scapula fractures benefit from surgery. This retrospective cohort study aims to compare and describe long-term patient-reported outcomes of ...patients with displaced scapula fractures treated both surgically and conservatively.
This study included patients with intra- and extra-articular scapula fractures, treated between 2010 and 2020 in a Swiss level 1 trauma centre. The decision to operate was based on standardized criteria for fracture displacement. Patients with isolated Bankart lesions (Ideberg 1) and process fractures (AO type 14-A) were excluded. Primary outcomes were functional patient reported measures (DASH score) and quality of life (EQ5D score). Secondary outcomes were complications, radiological union, satisfaction with treatment, pain and range of motion.
Out of 486 cases, 74 patients had displaced scapula fractures. Forty patients were treated surgically and 34 were treated conservatively. Significantly more patients with intra-articular fractures and high-energy trauma were treated surgically. Fifty percent returned the questionnaires after a mean follow-up of 47 months (± SD 36). The mean DASH score of this group was 12 (SD 15.6), with a mean of 14.7 (SD 15.9) in the surgery group and 9.8 (SD 14.6) in the non-operative group (p = 0.7). Multivariate analysis did not show statistically significant correlating factors. No significant differences in quality of life were observed. Patients rated their treatment with a mean of 8.6/10 (SD 1.8). Among surgically treated patients, 19 underwent a deltoid sparing procedure with significant shorter time to union than those that underwent deltoid release (23 vs. 49 weeks, p<0.01). Complications occurred in 3/28 surgically treated patients and all three required a reoperation.
In this cohort, functional results after conservative and surgical treatment were similar, despite more complex fractures and more intra-articular fractures being treated surgically. Osteosynthesis of both intra- and extra-articular scapula fractures is safe and leads to good functional results, furthermore, new minimal invasive techniques may lead to faster bone healing and return to work and sports
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