Martini Ziekenhuis

Background Since the early introduction of peanut to prevent IgE‐mediated peanut allergy, other case series have suggested an increased incidence of peanut‐triggered Food Protein Induced Enterocolitis Syndrome (FPIES). Data on the prevalence of peanut‐induced FPIES in prospective cohorts are lacking. Methods The PeanutNL cohort is a prospective cohort that included infants at risk of peanut allergy (n = 706) as well as infants with reactions to peanut at home after early introduction (n = 186). They all introduced peanut before the age of 12 months. Oral food challenges were performed to introduce peanut or to evaluate reactions to peanut at home. Results Of the 706 infants that were included for first introduction of peanut, 2 had reactions with a phenotype compatible with FPIES (0.3%). Of the 186 infants with reactions to peanut at home, 6 were diagnosed with FPIES (3.2%). Seven out of 8 cases had ingestions of peanut without reactions at home or during clinical introduction before FPIES became apparent. During a 3‐year follow‐up, six infants (75%) were shown to be tolerant to peanut before the age of 3 years. Conclusion The prevalence of challenge‐proven peanut‐induced FPIES in a Dutch cohort of atopic infants that introduced peanut between the ages of 4 and 11 months is 0.3%. The majority of cases were tolerant to peanut before the age of 3 years. When introducing peanut in the first year of life, physicians should be aware of FPIES reactions, but it should not be a reason to avoid early introduction of peanut.

Purpose of review Sarcopenia and frailty are common conditions, associated with worse clinical outcomes during critical illness. Recent studies on sarcopenia and frailty in ICU patients are presented in this review, aiming to identify accurate diagnostic tools, investigate the effects on clinical and functional outcomes, and propose possible effective interventions. Recent findings The recent change of the sarcopenia definition underlines the importance of muscle strength over mass, this is however challenging to assess in ICU patients. There is currently no unified sarcopenia definition, nor standard frailty assessment tool; Clinical Frailty Scale is most frequently used in the ICU. Meta-analyses show worse clinical and functional outcomes for frail as well as sarcopenic patients admitted to the ICU, regardless of admission diagnosis. Frailty is a dynamic condition, worsening in severity by the time of hospital discharge, but showing improvement by 6 months post-ICU. Therapeutic interventions for frailty and sarcopenia remain limited. Although mobilization strategies show promise in improving functional and cognitive outcomes, inconsistent outcomes are reported. Heterogeneity in definitions, patient populations, and care practices challenge interpretation and comparison of study results and recognition of beneficial interventions. This highlights the need for more research. Summary The importance of preexisting sarcopenia and frailty is recognized in ICU patients and associated with worse clinical outcomes. Multidimensional interventions are most promising, including patient-tailored mobilization and nutrition.

Background Multimorbidity is common among patients with atrial fibrillation (AF) and is associated with worse outcomes. We aimed to investigate the association between multimorbidity, AF progression and AF symptom severity in patients with paroxysmal AF. Methods and Results The RACE V (Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilization in the Progression of AF) study included patients with paroxysmal AF and continuous rhythm monitoring. Multimorbidity was defined as ≥2 comorbidities (heart failure, hypertension, diabetes, coronary heart disease, kidney dysfunction, moderate or severe mitral valve regurgitation, or obesity). AF symptom severity was assessed via the University of Toronto AF Severity Scale questionnaire. The associations between multimorbidity, AF progression, and AF symptom severity were determined using logistic regression analyses. Median age was 65 (58–71) years and 179 of 417 patients (43%) were women, with a median of 1 (1–2) comorbidities. Median follow‐up was 2.2 (1.6–2.8) years. Multimorbidity was associated with AF progression (odds ratio [OR], 2.02 [95% CI, 1.10–3.72], P =0.024) and increased AF symptom severity (OR, 2.67 [95% CI, 1.79–3.99], P <0.001). There was a positive dose–response relation between the number of comorbidities and AF progression (OR, 1.40 [95% CI, 1.09–1.79], P =0.008), as well as AF symptom severity (OR, 1.64 [95% CI, 1.35–1.99], P <0.001). These results remained significant after adjusting for age. Conclusions In patients with paroxysmal AF, multimorbidity was associated with AF progression and AF symptom severity. The risk of AF progression and AF symptom severity increased with every additional comorbidity. Registration URL: clinicaltrials.gov . Unique Identifier: NCT02726698.

Background and purpose: Adding adjuvant durvalumab to chemoradiotherapy (CRT) improves overall survival (OS) rates in locally advanced Non-Small-Cell Lung Cancer (NSCLC). However, recent data suggests that this new modality increases the incidence of radiation pneumonitis (RP). The aim of this study was to test the hypothesis that the incidence of RP after CRT and adjuvant durvalumab was higher than after CRT alone among patients with locally advanced NSCLC. Materials and methods: The study population comprised all patients with NSCLC who completed CRT with curative intent between February 2013 and October 2020. From 2018 on, adjuvant durvalumab was administered in selected patients after completion of CRT. Patient and treatment data together with RP data (CTCAEv4.0, scored up to 9 months after CRT), were prospectively collected as part of our standard follow-up program. Results: A total of 284 patients were included, of which 90 (30.5%) received adjuvant durvalumab. Incidence of grade ≥2 RP increased in patients receiving durvalumab compared to CRT only (17.8% vs. 8.8%; p < 0.05), especially between 6 to 9 months after completing CRT. Adjuvant durvalumab and mean lung dose (MLD) were associated with a higher incidence of grade ≥2 RP (odds ratio [OR]: 2.43 and 1.14, respectively; p < 0.05). Current smoking was found to be a protective factor (OR: 0.38; p < 0.05). Interpretation: Adjuvant durvalumab significantly increased the incidence of grade ≥2 RP in this real-world cohort of NSCLC patients. Patients receiving adjuvant durvalumab remain prone to develop grade ≥2 RP longer after completing CRT compared to patients treated with CRT only.

Purpose This registry-based study aims to examine the variation in biopsy and resection indications for glioblastoma patients across Dutch hospitals and to identify patient- and hospital-related factors associated with the surgical treatment. Methods Data from all 7443 adults with first-time glioblastoma surgery at 12 hospitals were obtained from the prospective population-based Quality Registry Neurosurgery in the Netherlands between 2011 and 2021. Patients were stratified by either biopsy or resection. We analyzed variation in American Association of Anesthesiologist (ASA) classification, Karnofsky Performance Score (KPS), gender and age distribution between the different centers. Between-hospital variation in biopsy percentage was analyzed using a funnel plot. Logistic regression was used to identify associated patient- and hospital-related factors. Results In total, 32% of the newly diagnosed glioblastoma patients underwent a biopsy, with wide variations between the different centers (23–56%). Patients-related variables such as higher age or ASA classification and lower KPS were significantly associated with the indication for biopsy. After correction for these factors, between-hospital variation persisted, with two institutes performing more biopsies than expected and one less than expected. Median overall survival was 12.5 months (95% CI 12.2–12.9) in the resection group and 5.6 months (95% CI 5.1–6) in the biopsy group, with wide variations between the different centers. Conclusion A substantial between-hospital variation in biopsy percentages was found. Patient factors (age, ASA classification and KPS) but also hospital factors (such as academic setting) impact surgical decisions. Variation persisted also after correction for potential confounders, indicating that other factors play a role in decision-making.

Objective: Cochlear implant (CI) is a well-established treatment for adults with sensorineural hearing loss and without benefit from hearing aids. The Italian guidelines date back 15 years; given the expansion of indications for CI, including single side deafness and asymmetrical hearing loss, it became necessary to establish updated guidelines. Methods: Thirteen experts and 2 patient representatives selected the key questions and drew up recommendations. The document was developed following GRADE methodology. The methodological team of the Mario Negri Pharmacological Research Institute performed systematic reviews for each question and supported the overall process. Results: Five key questions were identified and recommendations formulated, with subgroups and considerations on implementation. Conclusions: Though the systematic research of scientific literature found a scarcity of randomised trials and an overall poor conduct and reporting quality of primary studies and systematic reviews, strong or conditional recommendations in favour of CI have been formulated for different subgroups of patients. Further studies should enrol a larger number of participants and use consistent instruments to evaluate hearing outcomes, in order to increase the comparability of results and data pooling with meta-analysis.

Surviving a burn can dramatically alter a child’s life, yet few studies examined long-term health-related quality of life (HRQL). This study assessed HRQL 5–7 years post-burn in children with mild/intermediate and severe burns and identified associated factors. Parents of children (5− < 18 years) who were hospitalized or had burn surgery between 08/2011 and 09/2012 completed the Burn Outcomes Questionnaire (BOQ). Outcomes were compared between two subgroups: children with mild/intermediate burns (<10% total body surface area (TBSA) burned) versus severe burns ((1) aged <10 years old at the time of injury with >10% (TBSA) burned; (2) aged ≥10 years with >20% TBSA burned; or (3) >5% full-thickness burns). A total of 102 children were included (mean age at survey: 8.4 (3.0) years; mean former TBSA: 7.1%). At a mean of 5.7 years post-burn, many parents rated their child’s health as excellent (46.1%) or very good (35.3%), with few reporting issues with ‘pain’ (2.3%), ‘physical function and sports’ (1.6%), and ‘upper extremity function’ (0.9%). Parents of children with severe burns indicated significantly more problems with ‘appearance’ (89.2% versus 71.5%; p = 0.014) and ‘parental concern’ (94.1% versus 84.8%; p = 0.021). Upper limb burns, facial burns, burn size, length of hospital stay, full-thickness burns, and the number of surgeries predicted poorer outcomes. In general, these findings indicate positive long-term HRQL, though especially children with full-thickness burns and/or surgical interventions face a higher risk of reduced HRQL. The results can be used to inform children and their families about the long-term implications. Furthermore, healthcare professionals can use these insights to identify children at higher risk of poorer long-term HRQL.

Objective: Many factors can lead to residency attrition. The underlying process however and how these factors interact remains unclear. Understanding this process can provide background to put the available evidence into perspective. The aim of the study was to develop an explaining model that describes voluntary residency attrition. Design: Development of an explanatory model based on qualitative research METHOD: Semi-structured interviews with orthopaedic surgery residents in the Netherlands who dropped out of training, were analysed using the constructivist grounded theory approach. Results: 17 interviews were analysed. Reasons for attrition were different for each individual and often a result of a cumulative effect of negative experiences. Individual expectations and needs determine residents' experience with the content of the profession, the professional culture and the learning climate. Personal circumstances and personal characteristics influence expectations and needs. Specific aspects of the residency programme contributing to attrition were type of patient care, required skills, work-life balance and interpersonal interaction (between residents among themselves and between residents and supervisors). Conclusion: This study provides an explaining model of residency attrition that incorporates existing theories and fits well with the results of previous studies.

Background and purpose: For medial knee osteoarthritis (OA), operative and nonoperative treatment options are available. Two widely applied unloading therapies are a valgus unloader brace and a high tibial osteotomy (HTO). We aimed to compare the effects of a valgus unloader knee brace with an HTO on knee pain after 1 year in patients with symptomatic medial knee OA.Methods: We recruited patients from 9 Dutch hospitals between August 2014 and February 2019 for an open-labeled multi-center randomized controlled trial (Dutch Trial Register NL4200). Patients aged 18 to 65 years with symptomatic medial compartmental knee OA were randomized to either a valgus unloader brace or an HTO. The primary outcome was the pain subscale of the Knee injury and Osteoarthritis Outcome score (KOOS) after 1 year. Patients were evaluated at 3, 6, 9, 12, and 24 months.Results: 51 patients were included in the study, of whom 23 were randomized to the unloader brace and 28 to the HTO. The HTO, compared with the unloader brace, showed a significant and clinically relevant difference at 12 months of follow-up in KOOS pain of –28 (95% confidence interval –43 to –13).Conclusion: We found that, on group level, an HTO is more effective in reducing knee pain than an unloader brace after 12 months.

Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurring <3 months after the index arthroplasty and treated with debridement, antibiotics, and implant retention (DAIR). Patients from Europe and the USA were included. We took advantage of the fact that an early oral antibiotic switch is routine practice in Europe as opposed to a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for (i) a second unintended DAIR procedure, (ii) implant removal, (iii) suppressive antibiotic treatment, or (iii) PJI-related death, all within one year after DAIR. Results: A total of 668 patients were included. A total of 277 received IV antibiotics for <14 days, 232 between 14 and 27 days, and 159 for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4%, and 42.1%, respectively (p = 0.80). This observation remained when excluding patients who failed during IV therapy. A longer duration of IV therapy seemed beneficial for those patients with a high pre-operative C-reactive protein level and lack of modular component exchange. Conclusion: In early post-operative PJIs, a longer duration of IV therapy is not associated with a lower failure rate but may be continued until a sufficient bacterial load reduction has been achieved.

Knowledge about trends and epidemiology of pediatric burns is useful to identify patterns, to advance medical research, and to design prevention programs and resource allocation. The aim of this study is to describe the epidemiology and trends of pediatric burns between 2009 and 2022 in the three Dutch burn centers. A secondary objective of this study is to evaluate the influence of the COVID-19 pandemic on the pattern of pediatric burns. A register-based cohort study was conducted based on data from the Dutch Burn Repository R3. Patients between 0 and 17 years at the time of the burn injury admitted between 2009 and 2022 to one of the three burn centers were included. Descriptive statistics were used to investigate the incidence and patient, burn, and treatment characteristics. The COVID-19 pandemic years (2020–2021) were compared with the pooled results from pre-COVID-19 years (2017–2019). A total of 4017 patients were included in this study, of which 3085 (77%) were overnight admissions. The incidence and absolute number of pediatric burn admissions gradually increased over the years, with a small temporary decrease in 2020–2021. Patient and burn characteristics remained relatively consistent over the years. Three quarters of all patients were between 0 and 3 years old, and the majority were boys (59%). A decreasing ratio of length of stay per % total burned surface area and an increase in day admissions was observed since 2016 onwards, which intensified during the COVID-19 pandemic. Conclusions: There was a slight increase in the number of pediatric admissions to the burn centers between 2009 and 2022. Young children (0–3 years) remain the most frequently affected group. A shorter relative length of stay was observed, as well as an increase in day admissions, which was reinforced by the COVID-19 pandemic. What is known: • Burns are a leading cause of death and disability among children globally. The largest group affected are young children (0-3 years) and most are scald burns. • In the Netherlands, since the late nineties there has been a trend towards more admissions to specialized burn centers, especially for young children with less severe burns. What is new: • There was a slight increase in the number of pediatric admissions to the burn centers between 2009 and 2022, with a temporary decrease during the COVID-19 pandemic (2020-2021). • Admissions now tend to be shorter per percentage total burned surface area (TBSA), with an increase in day admissions, which intensified during the COVID-19 years.

Background Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort. Methods For this retrospective cohort study, female Lynch syndrome carriers, prospectively registered in the Dutch Lynch syndrome database (StOET), were included up to February 28th 2022. Carriers were linked to the Dutch national pathology (PALGA) database. The number of carriers with/without gynaecological surveillance, number of index carriers with endometrial carcinoma before Lynch syndrome diagnosis were assessed, as well as uptake of risk-reducing surgery and characteristics of endometrial carcinomas including the requisite for adjuvant therapy according to current guidelines. Overall survival after endometrial carcinoma diagnosis was analyzed using Kaplan Meier time to event analyses, cumulative incidence was calculated after adjusting for competing risks (death and prophylactic hysterectomy). Findings In total, 1046 registered female Lynch syndrome carriers were eligible for surveillance, of whom 313 (30.0%) did not have surveillance and 21.4% (n = 224 of 1046) opted for prophylactic hysterectomy. In carriers with surveillance, more cases of endometrial carcinoma and hyperplasia were found than in those without (37 endometrial carcinomas (7.3%) and 28 hyperplasias (5.5%) in 506 carriers with surveillance versus 14 (2.6%) and 4 (0.7%) in 540 carriers without surveillance, respectively); carriers with surveillance were generally younger than those without (median 56 years [IQR 48–65] versus median 65 years [IQR 49–75] at database assembly, respectively; p < 0.0001). Endometrial carcinomas were predominantly of endometrioid type and FIGO stage IA, regardless of surveillance. Adjuvant external beam radiotherapy was required in one patient in both groups. Overall survival after endometrial carcinoma diagnosis did not differ between carriers with or without surveillance or carriers with endometrial carcinoma before LS diagnosis (p = 0.51). For all endometrial carcinomas together, including index carriers, cumulative incidence was 22.7% at age 70. Interpretation In a nation-wide cohort of Lynch syndrome carriers, nearly one-third of eligible carriers did not undergo gynaecological surveillance. Endometrial carcinomas diagnosed during surveillance were slightly more often stage FIGO IA, but this did not seem to substantially decrease the requisite for adjuvant therapy or affect overall survival, questioning effectiveness of current gynaecological management. Prospective research should further assess this, as well as patient preferences. Funding None.

Aim The aim is to evaluate the advantages of the dedicated Adaptive Phonak Digital Bimodal (APDB) fitting formula compared to the traditional National Acoustic Laboratories Non-Linear 2 (NAL-NL2) for contralateral hearing aid (HA) in bimodal cochlear implant (CI) users. Settings and Design Cross-over bicentric study involving 10 adult bimodal Advanced Bionics CI users with usable contralateral hearing. Subjects and Methods Participants were provided with a dedicated Naída Link Q90 HA. Speech recognition in noise was assessed with the Italian Matrix Sentence Test. The competing noise was presented at a fixed level of 55 dB HL. The speech level was changed adaptively to calculate the signal-to-noise ratio (SNR) targeting at a score of 50% correct words. Outcomes were compared in three configurations, with CI only, with APDB and with NAL-NL2. Subjective hearing benefit was assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire in both bimodal configurations. Results Speech intelligibility in noise showed significantly better results for both bimodal configurations ( P < 0.001) compared to CI only (mean 9.1 dB SNR ± 5.7) and for the APDB formula (mean 2.25 dB SNR ± 2.4) compared to NAL-NL2 (mean 3.3 dB SNR ± 2.7; P < 0.05). Responses to the SSQ demonstrated a trend for improvement with APDB compared to NAL2/NAL in the “space” subgroup and a statistically significant difference in favor of APDB for “other sound qualities” ( P < 0.05). Conclusions The APDB fitting formula has been shown to be beneficial for binaural bimodal CI users, both in speech intelligibility test results and subjective perception of hearing comfort.