A systematic review on safety and surgical and anesthetic risks of elective abdominal laparoscopic surgery in infants to guide laparoscopic ovarian tissue harvest for fertility preservation for infants facing gonadotoxic treatment.

Background: Infertility is an important late effect of childhood cancer treatment. Ovarian tissue cryopreservation (OTC) is established as a safe procedure to preserve gonadal tissue in (pre)pubertal girls with cancer at high risk for infertility. However, it is unclear whether elective laparoscopic OTC can also be performed safely in infants <1 year with cancer. This systematic review aims to evaluate the reported risks in infants undergoing elective laparoscopy regarding mortality, and/or critical events (including resuscitation, circulatory, respiratory, neurotoxic, other) during and shortly after surgery. Methods: This systematic review followed the Preferred reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guideline. A systematic literature search in the databases Pubmed and EMbase was performed and updated on February 15th, 2023. Search terms included 'infants', 'intubation', 'laparoscopy', 'mortality', 'critical events', 'comorbidities' and their synonyms. Papers published in English since 2000 and describing at least 50 patients under the age of 1 year undergoing laparoscopic surgery were included. Articles were excluded when the majority of patients had congenital abnormalities. Quality of the studies was assessed using the QUIPS risk of bias tool. Results: The Pubmed and Embase databases yielded a total of 12,401 unique articles, which after screening on title and abstract resulted in 471 articles to be selected for full text screening. Ten articles met the inclusion criteria for this systematic review, which included 1778 infants <1 years undergoing elective laparoscopic surgery. Mortality occurred once (death not surgery-related), resuscitation in none and critical events in 53/1778 of the procedures. Conclusion: The results from this review illustrate that morbidity and mortality in infants without extensive comorbidities during and just after elective laparoscopic procedures seem limited, indicating that the advantages of performing elective laparoscopic OTC for infants with cancer at high risk of gonadal damage may outweigh the anesthetic and surgical risks of laparoscopic surgery in this age group.

A Dutch paediatric palliative care guideline: a systematic review and evidence-based recommendations for symptom treatment.

BACKGROUND: Children with life-threatening and life-limiting conditions can experience high levels of suffering due to multiple distressing symptoms that result in poor quality of life and increase risk of long-term distress in their family members. High quality symptom treatment is needed for all these children and their families, even more so at the end-of-life. In this paper, we provide evidence-based recommendations for symptom treatment in paediatric palliative patients to optimize care. METHODS: A multidisciplinary panel of 56 experts in paediatric palliative care and nine (bereaved) parents was established to develop recommendations on symptom treatment in paediatric palliative care including anxiety and depression, delirium, dyspnoea, haematological symptoms, coughing, skin complaints, nausea and vomiting, neurological symptoms, pain, death rattle, fatigue, paediatric palliative sedation and forgoing hydration and nutrition. Recommendations were based on evidence from a systematic literature search, additional literature sources (such as guidelines), clinical expertise, and patient and family values. We used the GRADE methodology for appraisal of evidence. Parents were included in the guideline panel to ensure the representation of patient and family values. RESULTS: We included a total of 18 studies that reported on the effects of specific (non) pharmacological interventions to treat symptoms in paediatric palliative care. A few of these interventions showed significant improvement in symptom relief. This evidence could only (partly) answer eight out of 27 clinical questions. We included 29 guidelines and two textbooks as additional literature to deal with lack of evidence. In total, we formulated 221 recommendations on symptom treatment in paediatric palliative care based on evidence, additional literature, clinical expertise, and patient and family values. CONCLUSION: Even though available evidence on symptom-related paediatric palliative care interventions has increased, there still is a paucity of evidence in paediatric palliative care. We urge for international multidisciplinary multi-institutional collaboration to perform high-quality research and contribute to the optimization of symptom relief in palliative care for all children worldwide.

Anesthesia Depresses Cerebrovascular Reactivity to Acetazolamide in Pediatric Moyamoya Vasculopathy.

Measurements of cerebrovascular reactivity (CVR) are essential for treatment decisions in moyamoya vasculopathy (MMV). Since MMV patients are often young or cognitively impaired, anesthesia is commonly used to limit motion artifacts. Our aim was to investigate the effect of anesthesia on the CVR in pediatric MMV. We compared the CVR with multidelay-ASL and BOLD MRI, using acetazolamide as a vascular stimulus, in all awake and anesthesia pediatric MMV scans at our institution. Since a heterogeneity in disease and treatment influences the CVR, we focused on the (unaffected) cerebellum. Ten awake and nine anesthetized patients were included. The post-acetazolamide CBF and ASL-CVR were significantly lower in anesthesia patients (47.1 ± 15.4 vs. 61.4 ± 12.1, p = 0.04; 12.3 ± 8.4 vs. 23.7 ± 12.2 mL/100 g/min, p = 0.03, respectively). The final BOLD-CVR increase (0.39 ± 0.58 vs. 3.6 ± 1.2% BOLD-change (mean/SD), p < 0.0001), maximum slope of increase (0.0050 ± 0.0040%/s vs. 0.017 ± 0.0059%, p < 0.0001), and time to maximum BOLD-increase (~463 ± 136 and ~697 ± 144 s, p = 0.0028) were all significantly lower in the anesthesia group. We conclude that the response to acetazolamide is distinctively different between awake and anesthetized MMV patients, and we hypothesize that these findings can also apply to other diseases and methods of measuring CVR under anesthesia. Considering that treatment decisions heavily depend on CVR status, caution is warranted when assessing CVR under anesthesia.

Feasibility of quantitative sensory testing in juvenile idiopathic arthritis.

OBJECTIVE: Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10-17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children. METHODS: Sixteen patients with JIA aged 9-18 years with one affected knee and a patient-reported pain by Visual Analog Scale (VAS) > 10 on a 0-100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the German Research Network on Neuropathic Pain (DFNS) standard. Disease severity was determined using Juvenile Disease Activity Score (JADAS. Perceived pain was assessed with a visual analogue scale(0-100). Feasibility of QST was tested in patients aged 6-9. RESULTS: Under the age of 9, QST testing showed not to be feasible in 3 out of 5 JIA patients. Patients with JIA aged 9 and older reported an average VAS pain score of 54.3. QST identified a significant reduction in pressure pain threshold (PPT) and increase in cold detection threshold (CDT) compared to healthy controls. PPT is reduced in both the affected and the unaffected knee, CDT is reduced in the unaffected knee, not the affected knee. CONCLUSION: In a Dutch cohort of Patients with JIA, QST is only feasible from 9 years and up. Also, sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in Patients with JIA. PERSPECTIVE: This article shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis.

Prospective 3-arm study on pain and epithelial healing after corneal crosslinking.

PURPOSE: To investigate the effect of 3 regimes on pain and wound healing after corneal crosslinking (CXL). SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN: Prospective cohort study. METHODS: Consecutive progressive keratoconus patients who underwent 9 mW/cm epithelium-off CXL were included. Patients received a bandage contact lens (n = 20), occlusive patch (n = 20), or antibiotic ointment (n = 20) after treatment. Pain scores and quality of life, measured by the McGill Pain Questionnaire and Visual Analogue Scale (VAS), were analyzed. Epithelial healing after 2 days, correlations between pain and psychological factors that influence pain perception (depression anxiety stress score and pain catastrophizing score), and oral pain medication were evaluated. RESULTS: Sixty eyes of 52 patients were analyzed. On average, patients experienced considerable pain after CXL (median VAS score 6.2, range 0 to 10). The postoperative regimen did not significantly affect pain scores, although the antibiotic ointment group reported a higher VAS score (median VAS score 7.2 vs 6.7 and 6.0; P = .57). Occlusive patching showed a trend to quicker resolution of epithelial defects (85% completely healed vs 65% with lenses and 70% with antibiotic ointment; P = .43). Correlations with pain-modulating psychological factors were weak (R < 0.3) and not significant. The use of pain medication corresponded poorly to the prescribed use. CONCLUSION: This study demonstrated clinical equivalence of 3 regimes in combating postoperative pain after routine CXL. Wound healing appeared quicker in the occlusive patch group and therefore might be the best standard of care after CXL. The clinical tradition of using bandage contact lenses should be reevaluated.