Background
Locally advanced rectal cancer is customarily treated with neoadjuvant chemoradiotherapy (CRT) followed by a total mesorectal excision. During the course of CRT, previously non-detectable ...distant metastases can appear. Therefore, a restaging CT scan of the chest and abdomen was performed prior to surgery. The aim of this study was to determine the frequency of a change in treatment strategy after this restaging CT scan.
Methods
Patients treated with neoadjuvant CRT for locally advanced rectal cancer between January 2003 and July 2013 were included retrospectively. To determine the value of the restaging CT scan, the surgical treatment as planned before CRT was compared with the treatment ultimately received.
Results
A total of 153 patients (91 male) were eligible, and median age was 62 (32–82) years. The restaging CT scan revealed the presence of distant metastases in 19 patients (12.4, 95 % confidence interval CI 7.0–17.8). In 17 patients (11.1, 95 % CI 6.1–16.1), a change in treatment strategy occurred due to the detection of metastases with a restaging CT scan.
Conclusion
A restaging CT scan after completion of neoadjuvant CRT may detect newly developed metastases and consequently alter the initial treatment strategy. This study demonstrated the added value of the restaging CT scan prior to surgery.
The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, ...potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).
Patients with progression of treatment refractory RAF/RASwt glioblastoma were included for treatment with panitumumab in DRUP when measurable according to RANO criteria. The primary endpoints of this study are clinical benefit (CB: defined as confirmed objective response OR or stable disease SD ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 in 8 patients had CB in stage 1.
Between 03-2018 and 02-2022, 24 evaluable patients were treated. CB was observed in 5 patients (21%), including 2 patients with partial response (8.3%) and 3 patients with SD ≥ 16 weeks (12.5%). After median follow-up of 15 months, median progression-free survival and overall survival were 1.7 months (95% CI 1.6-2.1 months) and 4.5 months (95% CI 2.9-8.6 months), respectively. No unexpected toxicities were observed.
Panitumumab treatment provides limited CB in patients with recurrent RAF/RASwt glioblastoma precluding further development of this therapeutic strategy.
Introduction
Fetal gender is associated with preterm birth; however, a proper subdivision by onset of labor and corresponding neonatal outcome by week of gestation is lacking.
Material and methods
...Data from the Netherlands Perinatal Registry (1999–2010) were used to calculate relative risk ratios for gender by week of gestation and gender‐related risk on adverse neonatal outcomes using a moving average technique. White European women with an alive fetus at onset of labor were included. Adverse neonatal outcomes were defined as neonatal mortality and a composite of neonatal morbidity. Onset of labor was categorized as spontaneous onset with intact membranes, premature rupture of membranes, and induction or elective cesarean section.
Results
The study population comprised 1 736 615 singleton deliveries (25+0–42+6 weeks). Male fetuses were at increased risk of spontaneous preterm birth with intact membranes compared with a female fetus with a peak between 27 and 31 weeks relative risk (RR) 1.5; 95% CI 1.4–1.6. Male fetuses were also at increased risk of preterm premature rupture of membranes between 27 and 37 weeks (RR 1.2; 95% CI 1.16–1.23). No gender effect was seen for medically indicated preterm birth. No significant differences were seen for neonatal mortality. Males were at significantly increased risk of composite neonatal morbidity from 29 weeks onwards (RR 1.3; 95% CI 1.3–1.4).
Conclusions
Male fetal gender is a relevant risk factor for spontaneous preterm birth, both for intact membranes and for preterm premature rupture of membranes in white European women. In addition, male infants are at increased risk of neonatal morbidity.
Objectives
Nursing home residents often suffer from multi-morbidities and geriatric syndromes leading to lower quality of life or mortality. Oropharyngeal dysphagia (OD) and malnutrition are profound ...conditions in this complex profile of multi-morbidities and are associated with deprived mental –and physical health status, e.g. aspiration pneumonia or dehydration. This study aimed to assess the association between OD and malnutrition in Dutch nursing home residents.
Design
Data for this cross-sectional study were obtained from the annual National Prevalence Measurement of Quality of Care (LPZ).
Setting
The National Prevalence Measurement of Quality of Care was conducted in Nursing Homes in The Netherlands.
Participants
Participants were nursing home residents age 65 or older and admitted to psychogeriatric- or somatic wards.
Measurements
The measurements were taken by trained nurses from the participating nursing homes. Anthropometric measurements and unintended weight loss (%) were assessed to determine nutritional status (malnutrition). OD was assessed by means of a standardized questionnaire assessing clinically relevant symptoms of OD such as swallowing problems or sneezing/coughing while swallowing. Cox regression was applied to assess the association between malnutrition and clinically relevant symptoms of OD in older Dutch nursing home residents.
Results
Approximately 12% of the residents suffered from swallowing problems and 7% sneezed/coughed while swallowing liquids or solid foods. Approximately 10% of the residents was malnourished. Residents with OD symptoms were more often malnourished compared to residents without OD symptoms. Approximately 17% of the problematic swallowers were concurrently malnourished. Increased risk for malnutrition was found in residents suffering from swallowing problems (PR 1.5, 95%CI 1.2–1.9), as well as in residents that sneezed/ coughed while swallowing (PR 1.3, 95%CI 1.0–1.7). Stratification based on wards revealed that problematic swallowers from somatic wards were at a high risk of malnutrition (PR 1.9, 95%CI 1.3–2.8).
Conclusion
Clinically relevant symptoms of oropharyngeal dysphagia, such as swallowing problems and sneezing/coughing while swallowing are associated with increased risk of malnutrition in psychogeriatric and somatic Dutch nursing home residents.
Wilson disease (WD) is an autosomal recessive copper overload disorder of the liver and basal ganglia. WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans‐Golgi ...network that primarily facilitates hepatic copper excretion. Current treatment comprises reduction of circulating copper by zinc supplementation or copper chelation. Despite treatment, a significant number of patients have neurological deterioration. The aim of this study was to investigate the possibility that defects arising from some WD mutations are ameliorated by drug treatment aimed at improvement of protein folding and restoration of protein function. This necessitated systematic characterization of the molecular consequences of distinct ATP7B missense mutations associated with WD. With the exception of p.S1363F, all mutations tested (p.G85V, p.R778L, p.H1069Q, p.C1104F, p.V1262F, p.G1343V, and p.S1363F) resulted in reduced ATP7B protein expression, whereas messenger RNA abundance was unaffected. Retention of mutant ATP7B in the endoplasmic reticulum, increased protein expression, and normalization of localization after culturing cells at 30°C, and homology modeling suggested that these proteins were misfolded. Four distinct mutations exhibited residual copper export capacity, whereas other mutations resulted in complete disruption of copper export by ATP7B. Treatment with pharmacological chaperones 4‐phenylbutyrate (4‐PBA) and curcumin, a clinically approved compound, partially restored protein expression of most ATP7B mutants. Conclusion: These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. (HEPATOLOGY 2009;50:1783–1795.)
To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently ...improving survival.
International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence.
A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence.
Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001 and asymptomatic patients hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001.
Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection.
Purpose
Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study ...is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab.
Methods
An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab.
Results
A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years,
n
= 44 LA SCCHN,
n
= 16 R/M SCCHN,
n
= 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6–10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications.
Conclusion
A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.
Summary Background Existing approaches for the screening and treatment of asymptomatic bacteriuria in pregnancy are based on trials that were done more than 30 years ago. In this study, we reassessed ...the consequences of treated and untreated asymptomatic bacteriuria in pregnancy. Methods In this multicentre prospective cohort study with an embedded randomised controlled trial, we screened women (aged ≥18 years) at eight hospitals and five ultrasound centres in the Netherlands with a singleton pregnancy between 16 and 22 weeks' gestation for asymptomatic bacteriuria. Screening was done with a single dipslide and two culture media. Dipslides were judged positive when the colony concentration was at least 1×105 colony-forming units (CFU) per mL of a single microorganism or when two different colony types were present but one had a concentration of at least 1×105 CFU per mL. Asymptomatic bacteriuria-positive women were eligible to participate in the randomised controlled trial comparing nitrofurantoin with placebo treatment. In this trial, participants were randomly assigned 1:1 to receive either nitrofurantoin 100 mg or identical placebo tablets, and were instructed to self-administer these tablets twice daily for 5 consecutive days. Randomisation was done by a web-based application with a computer-generated list with random block sizes of two, four, or six participants rendered by an independent data manager. 1 week after the end of treatment, they provided us with a follow-up dipslide. Women, treating physicians, and researchers all remained unaware of the bacteriuria status and treatment allocation. Women who refused to participate in the randomised controlled trial did not receive any antibiotics, but their outcomes were collected for analysis in the cohort study. We compared untreated and placebo-treated asymptomatic bacteriuria-positive women with asymptomatic bacteriuria-negative women and nitrofurantoin-treated asymptomatic bacteriuria-positive women. The primary endpoint was a composite of pyelonephritis with or without preterm birth at less than 34 weeks, analysed by intention to treat at 6 weeks post-partum. This trial is registered with the Dutch Trial Registry, number NTR3068. Findings Between Oct 11, 2011, and June 10, 2013, we enrolled 5621 women into our screening cohort, of whom 5132 were eligible for screening. After exclusions for contaminated dipslides and patients lost to follow-up, in our final cohort of 4283 women, 248 were asymptomatic bacteriuria positive, of whom 40 were randomly assigned to nitrofurantoin and 45 to placebo for the randomised controlled trial, whereas the other 163 asymptomatic bacteriuria-positive women were followed without treatment. The proportion of women with pyelonephritis, preterm birth, or both did not differ between untreated or placebo-treated asymptomatic bacteriuria-positive women and asymptomatic bacteriuria-negative women (6 2·9% of 208 vs 77 1·9% of 4035; adjusted odds ratio OR 1·5, 95% CI 0·6–3·5) nor between asymptomatic bacteriuria-positive women treated with nitrofurantoin versus those who were untreated or received placebo (1 2·5% of 40 vs 6 2·9% of 208; risk difference −0·4, 95% CI −3·6 to 9·4). Untreated or placebo-treated asymptomatic bacteriuria-positive women developed pyelonephritis in five 2·4% of 208 cases, compared with 24 0·6% of 4035 asymptomatic bacteriuria-negative women (adjusted OR 3·9, 95% CI 1·4–11·4). Interpretation In women with an uncomplicated singleton pregnancy, asymptomatic bacteriuria is not associated with preterm birth. Asymptomatic bacteriuria showed a significant association with pyelonephritis, but the absolute risk of pyelonephritis in untreated asymptomatic bacteriuria is low. These findings question a routine screen-treat-policy for asymptomatic bacteriuria in pregnancy. Funding ZonMw (the Netherlands Organisation for Health Research and Development).
Background Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) ...Syncope Guidelines regarding diagnostic yield, accuracy and costs. Methods A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. Results We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving euro908 per patient; 95% CI euro34 to euro1782). Conclusions ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. Trial registration Netherlands Trial Register, NTR6268 Keywords: Transient loss of consciousness, Healthcare efficiency, Syncope, Epilepsy, Admission, Tilt table testing, QALY
Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival ...is largely unknown.
Using data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.
A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade ≥3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity hazard ratio (HR
) = 0.77; 95% confidence interval (CI), 0.63-0.93. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF ± steroids for steroid-refractory toxicity compared with patients who were managed with steroids only (HR
= 1.61; 95% CI, 1.03-2.51), with a median OS of 17 and 27 months, respectively.
Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.
.
PDF
