Fast-track surgery in infants and children

Background/Purpose

Fast-track surgery is not well established for infants and children. The aim of our prospective study was to investigate the feasibility of fast-track concepts for pediatric surgical procedures including laparoscopic techniques.

Methods

Fast-track concepts, including immediate postoperative feeding, immediate mobilization, and morphine sparing pain treatment, were established for pyeloplasty, appendectomy, bowel anastomosis, fundoplication, hypospadia repair, and full/partial nephrectomy. All consecutive patients undergoing these procedures were prospectively investigated from June 2004 to June 2005. Patients with additional relevant diseases, reoperation, and perforated appendicitis were excluded from fast-track treatment. The length of hospital stay was compared with data derived from the German reimbursement system with German diagnosis-related groups for patients with a similar case mix index and hospitals with a similar structure.

Results

Of a total of 159 patients (mean age, 5.8 ± 5.3 years), 113 (71%) were finally treated according to the fast-track protocols. There were no complications associated with fast-track surgery. The intensity of pain during the immediate postoperative period was higher than 5 on a 10-point scale in children older than 4 years. Analgesia was excellent at all other time points. The mean hospital stay of fast-track patients was 2.3 ± 1 days and was significantly shorter (P < .01) compared with German diagnosis-related group data for all procedures (pyeloplasty, 1.9 ± 0.9 vs 12.2 ± 0.2; nephrectomy, 1.9 ± 1.0 vs 14.4 ± 2.8; bowel anastomosis, 3.2 ± 0.6 vs 12.9 ± 2.4; fundoplication, 3.2 ± 0.8 vs 15.2 ± 4.2; appendectomy, 3.7 ± 2.4 vs 6.3 ± 1.8; hypospadia repair, 2.1 ± 1 vs 8.4 ± 1.4). Two readmissions were recorded. Ninety-six percent of patients and parents scored the fast-track concepts as excellent.

Conclusion

The feasibility of fast-track concepts in children is excellent, with short duration of hospitalization and high comfort.     

Inhibition of tyrosine kinases PDGFR and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat

The tyrosine kinase receptor c-kit and its interaction with the ligand, stem cell factor (SCF), play an essential role in the developing testis. C-kit is important for the development of the Leydig cells and for the migration, proliferation and survival of spermatogonia. Platelet-derived growth factor (PDGF) and its tyrosine kinase receptor (PDGFR) are important for the development of Leydig cells and myoid cells. The chemotherapeutic agent, imatinib mesylate (STI571, Glivec; Novartis) inhibits both of these tyrosine kinase receptors. Three-day treatment of immature male rats (SD) with imatinib (150 mg/kg) on postnatal days 5-7 delayed the formation of germ-line stem cell pool, reduced proliferation of type A spermatogonia and induced germ cell apoptosis. PDGFR-mediated proliferation of mesenchymal myoid precursors was also decreased and the length of the seminiferous cord was reduced. However, at the age of 11 weeks the exposed animals had normal epididymal sperm counts, whereas plasma levels of luteinizing hormone and follicle stimulating hormone were significantly increased. Imatinib serves as a good tool to study postnatal formation of the male germ-line stem cell pool and factors determining the final testicular size. As development of the human testis is controlled by the same mechanisms, further studies with primate and human models are needed to explore whether imatinib affects the testis in children as well.     

Potassium sensitivity test (PST) as a measurement of treatment efficacy of painful bladder syndrome/interstitial cystitis: a prospective study with cyclosporine A and pentosan polysulfate sodium

AIMS: Potassium sensitivity test (PST) has been used as an optional tool in diagnosing painful bladder syndrome/interstitial cystitis (PBS/IC). The role of PST in the follow-up of patients with PBS/IC is elusive. We performed PST before and after treatment of PBS/IC with cyclosporine A (CyA) or pentosan polysulfate sodium (PPS), to test whether the result of repeated PST correlates with alleviation of PBS/IC-related symptoms. MATERIALS AND METHODS: Sixty-four patients who participated in a randomized clinical study comparing CyA and PPS in the treatment of PBS/IC were recruited to the present study. Patients underwent 0.4 M PST before and after 6 months of treatment. The primary end point was a change from positive PST to negative among patients who responded to both treatments determined by global response assessment (GRA). RESULTS: Potassium sensitivity test (PST) was more likely to change from positive to negative among patients who responded to their treatment according to GRA (P < 0.001). The PST change follows the clinical course (ICSI score, voiding frequency, VAS score), which was more beneficial in the CyA-treated patients. CONCLUSIONS: Potassium sensitivity test (PST) reflects symptom severity of PBS/IC patients. Change of pre-treatment positive PST to negative correlates well with clinical alleviation of PBS/IC-related symptoms. In patients with persistent symptoms it may be painful and does not offer additional information. Thus, we do not recommend PST to be used as a routine clinical test in monitoring of PBS/IC treatment efficacy.     

Diagnostic value of free prostate-specific antigen among men with a prostate-specific antigen level of <3.0 microg per liter

Objectives

The percentage of free prostate-specific antigen (%fPSA) improves the diagnostic accuracy for prostate cancer when the serum level of total PSA (tPSA) is elevated. Approximately 14% of men with a tPSA below 3 μg/l have prostate cancer on biopsy, but the diagnostic value of %fPSA in such men is rather unknown. The purpose was to estimate the impact of %fPSA on future prostate cancer risk among men with a normal tPSA in prostate cancer screening.

Subjects and methods

The first round of the Finnish arm of the European Randomized Trial for Screening of Prostate Cancer in 1996 to 1999 comprised 20,793 men aged 55–67 yr. Screen-negative men (tPSA level below 3.0 μg/l, n = 17,680) were followed up until the end of 2003. Cumulative risk of prostate cancer was calculated as a function of %fPSA.

Results

During the median follow-up of 5.8 yr (range, 0–7.7 yr), 327 men were diagnosed with prostate cancer and 25% of them had a Gleason score of 7 or higher. Five years after the first screening, cumulative risk of prostate cancer was 1.7% (95%CI, 1.5–1.9%). Men with a %fPSA in the lowest quartile (<14.2%) showed a 6.9-fold risk compared with those with a level in the highest quartile (>23.7%).

Conclusions

In men with a low serum tPSA, a low %fPSA is a strong predictor of later diagnosis of prostate cancer.     

Alterations in the contents of consciousness in partial epileptic seizures

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.     

Effect of physical activity counseling on physical activity of older people in Finland (ISRCTN 07330512)

The aim of this study was to describe the underlying theory and the implementation of a 2-year individualized physical activity counseling intervention and to evaluate whether benefits persisted 1.5 years after the intervention. The sample included 632 sedentary 75- to 81-year-old participants. Data were collected in 2003-2005. The participants were randomly assigned to an intervention group and a control group. The intervention consisted of an individualized face-to-face meeting followed by telephone contacts every 4 months for 2 years, with the aim to increase participation in specific physical activities as well as to increase habitual physical activity. At the 2-year follow-up, the prevalence of physical activities in the intervention group vs. control group was as follows: supervised calisthenics training 20 vs. 16%, walking for fitness 69 vs. 62%, weight training 13 vs. 8% and water aerobics 19 vs. 7%. For water aerobics and walking for fitness, the treatment effect was significant [water aerobics odds ratio (OR) 2.49, 95% confidence interval (CI) 1.16-5.36, walking for fitness OR 1.58, 95% CI 1.05-2.40]. As to the other activities, the effect did not reach statistical significance. At the 1.5-year post-intervention, the follow-up results indicated that the intervention effect was still evident. The subgroup analyses suggested that physical activity counseling may be most efficacious among people with intact mobility, while those having manifest mobility limitations may not benefit from it. Older people who have manifest mobility limitations may need more face-to-face counseling.     

Serum tau protein elevation in migraine: a cross-sectional case–control study

Background

Headaches are the most common complaints among pediatric populations. Determining the cause and appropriate treatment for headaches may be challenging and costly, and the impact of headaches on the lives of patients and their families is not well understood.

Objective

A systematic literature review was conducted to examine what PROMs are currently used, and to identify quality of life (QoL) concepts important to children suffering from headaches and any known determinants of QoL.

Methods

Embase, Medline, Web of Science, CINAHL, EBSCOhost, PsychINFO, Cochrane CENTRAL and Google Scholar were searched from their inception through to June 2021. Studies investigating QoL, using a validated outcome measure in pediatric patients with headaches, were included. Relevant studies were identified through title and abstract screening and full text review by two independent reviewers. A citation review of included studies was performed. QoL concepts were extracted from the outcome measures that were used in each study to develop a preliminary conceptual model of QoL in children suffering from headaches. Determinants of QoL were also identified and categorized.

Results

A total of 5421 studies were identified in the search. Title and abstract screening resulted in the exclusion of 5006 studies. Among the 415 studies included for full text review, 56 were eligible for final analysis. A citation review resulted in the addition of five studies. Most studies were conducted in high-income countries and included a patient-sample accordingly (n = 45 studies). Sixteen different PROMs were identified in the included studies, of which the PedsQL was used the most often (n = 38 studies).

The most common health concepts reported were physical functioning (n = 113 items), social and psychological wellbeing (N = 117, n = 91 resp.). Twenty-five unique determinants of QoL were extracted from the included studies.

Conclusion

There is a need for a condition-specific PROM to facilitate the measurement of QoL outcomes in the pediatric headache population. A conceptual model was developed based on the findings from the health concepts. Findings from this review could be used for future qualitative interviews with pediatric patients with headaches to elicit and refine important QoL concepts.

     

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background

Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability.

Objective

We sought to characterize the role of EIF4A2 variants in dystonic conditions.

Methods

We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts.

Results

We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees.

Conclusions

Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.