Inselspital, Universitätsspital Bern

Purpose Childhood and adolescent cancer survivors (CACS) experience medical and psychosocial adverse effects. Attention widens to include issues such as socio-bureaucratic hardships. This systematic review synthesized the available evidence on insurance, legal, and financial hardships to better understand the broader picture of socio-bureaucratic hardships as distinct but interrelated types of hardships. Methods A systematic search of PubMed, Scopus, CINAHL, and PsycINFO was conducted for publications related to childhood and adolescent cancer; survivors; and insurance, legal, and financial hardships. Narrative data synthesis was performed on the extracted data. Results This review included N = 58 publications, originating from 14 different countries, most from the last decade (n = 39). We found that a considerable proportion of CACS experience insurance and financial hardships, including foregoing medical care due to financial constraints, problems paying medical bills, and difficulties accessing loans or insurances. Legal hardships, such as workplace discrimination, were less frequently investigated and reported. Conclusions This systematic review highlights the many interrelated socio-bureaucratic hardships faced by CACS. It is important that these hardships are not underestimated or neglected. Our findings can serve as a basis for enhancing and expanding supportive care services and help inform collaborative efforts from research, policy, and practice. Implications for Cancer Survivors This review emphasizes the importance of recognizing and addressing the socio-bureaucratic challenges that extend beyond medical care. Survivors should be informed about available options and be aware of their legal rights to identify instances of injustice and seek appropriate support.

Chronic paronychia is a common condition mainly afflicting middle-aged women. It is usually due to long-standing and repeated irritation and contact with moisture. We observed a male farmer with chronic paronychia. Cow hair was found under the proximal nail fold of the right middle finger. Bacterial culture revealed Mycobacterium elephantis in addition to mixed aerobic and anaerobic bacteria. Avulsion of the radial nail strip and phenolisation of the matrix horn led to a rapid and sustained resolution.

Objective To assess the opinion, practices, and challenges of international key opinion leaders about two minimal invasive surgical techniques in supraglottic laryngeal tumours: transoral laser microsurgery (TLM) and the transoral robotic surgery (TORS). Methods Design of a questionnaire composed of seven sections and fifty questions covering descriptive data of participants, practitioners experience procedural sequences, considerations related to airways, feeding, and voice, intraoperative haemorrhage, postoperative management, and a comparative analysis of TLM and TORS in treating supraglottic laryngeal cancer. Results A total of 27 head and neck surgeons replied to the survey. The experts had an average experience in laryngeal surgery of 20.0 ± 9.4 years, ranging from 5 to 36 years. We noted a significantly shorter installation time in TLM compared to TORS (19% of experts estimated the installation time of over 20 min with TLM vs 44% with TORS; p = 0.02). According to complications, the experts considered that bleeding was the major concern with supraglottic laryngeal surgery, especially intraoperative bleeding in TLM (52% in TLM vs 26% in TORS) (p = 0.09) and postoperative bleeding in TORS (56% in TORS vs 44% in TLM). Conclusion The experts did not identify a clear superiority of one technology (TLM) over the other (TORS). The two techniques seemed equivalent to the experts, except for the control of intraoperative haemostasis and visualisation of the surgical field, where TORS was perceived as superior to TLM.

Introduction Percutaneous screw fixation is a widely used treatment for posterior pelvic ring injuries. Transiliac-transsacral screw fixation has demonstrated superior biomechanical properties over bilateral sacroiliac screws, particularly in the minimally displaced bilateral sacral fractures. Screw placement under fluoroscopic control is still common, while CT navigation is gaining popularity. However, the accurate placement of screws within a safe zone is essential to avoid neurovascular complications. Methods An anatomical study using human cadaveric pelves was conducted to assess radiological landmarks and determine a safe zone in relation to the S1 recess/foramen for transiliac-transsacral screw placement. Results Fourteen pelves were evaluated. Ten pelves were classified as having a satisfactory corridor for screw placement, while four were deemed to have an impossible or high-risk corridor. A safe zone was defined based on the diagonal bisector of the S1 vertebral body, ICD and anterior cortex. Discussion The study findings suggest that lateral fluoroscopic projection can determine a safe entry point for screw placement. Understanding the anatomy and landmarks on lateral fluoroscopic images is crucial for successful screw placement and avoiding complications. Conclusion The S1 body diagonal is consistently located anterior to the S1 recess in lateral fluoroscopic projections, providing a potential safe corridor for transiliac-transsacral screw placement at the S1 level in nondysmorphic pelves. Further research is needed to confirm these findings with CT imaging and evaluate the technical feasibility of screw placement.

Zusammenfassung Patienten mit systemischen autoimmunen rheumatischen Erkrankungen (SARD) haben ein erhöhtes Risiko für die Entwicklung einer interstitiellen Lungenerkrankung (ILD), die häufig prognosebestimmend ist. Richtlinien zu Screening und Monitoring, die aufgrund des hohen Mortalitätsrisikos und der wachsenden medikamentösen Therapieoptionen besonders relevant sind, waren lange nicht verfügbar. Kürzlich wurden amerikanische Leitlinien von Rheumatologen und Pneumologen gemeinsam publiziert. Die europäischen Empfehlungen stehen kurz vor der Veröffentlichung. Zum Screening bei asymptomatischen Hochrisikopatienten oder symptomatischen Patienten wird die Kombination von HRCT und Lungenfunktionstest empfohlen, optional die Sauerstoffmessung vor und nach Belastung. Dasselbe gilt für das Monitoring bei diagnostizierter SARD-ILD, wobei es keine klaren Empfehlungen für eine serielle Bildgebung mittels HRCT gibt. Eine gute Datenlage für die Frequenz von Rescreening und Monitoring fehlt, sodass eine individuelle Abwägung basierend auf Risikofaktoren empfohlen wird. Dieser Artikel ordnet die aktuell verfügbaren Empfehlungen in einen größeren Kontext ein und berücksichtigt dabei auch die neue Datenlage. Das Management dieser Patienten sollte in einem interdisziplinären und interprofessionellen Team erfolgen, um der Komplexität dieser z. T. sehr seltenen Krankheitsbilder Rechnung zu tragen.

BACKGROUND Recent studies have demonstrated the benefit of early ablation in preventing the progression of atrial fibrillation (AF). Clinical practice has reflected this shift in AF management and no longer requires patients to fail antiarrhythmic drugs (AADs) before receiving ablation. However, there is limited evidence on outcomes with pulsed field ablation (PFA) as a first-line therapy. Examination of real-world data may shed light on clinical practices and the effectiveness of PFA with and without a prior history of AAD usage. METHODS EU-PORIA is an all-comer AF registry enrolling consecutive patients treated with the pentaspline PFA catheter at 7 high-volume centers in Europe. This subanalysis evaluates patients with a history of class I/III AAD use versus those with no documented history of class I/III AAD use (first-line patients). Patients with incomplete AAD history, long-standing persistent AF, and those undergoing a repeat ablation procedure were excluded. Patients were treated and followed based on institutional standard of care. Any episode of atrial tachycardia or AF lasting longer than 30 s was considered an arrhythmia recurrence. RESULTS Of 1233 patients enrolled in EU-PORIA, 1091 met the inclusion criteria (mean age, 66 years; 40% females; and persistent AF, 36%). Pulmonary vein isolation-only was used in 90% of the patients, and 10% received extra-PV ablation. Ablation as the first-line approach was chosen in 589 patients, and 502 patients had prior class I/III AAD use. In the first-line PFA group, paroxysmal AF was more frequent (68% versus 59%; P <0.001), and pulmonary vein isolation-only was more frequent (93% versus 86%; P <0.001). At 1-year follow-up, freedom from AF/atrial tachycardia recurrence was similar in the ablation-first versus the ablation after failed AAD group (78% versus 74%, respectively; P =0.076). CONCLUSION In this large real-world PFA registry, freedom from AF/atrial tachycardia recurrence after 1 year was similar in patients undergoing PFA as a first-line treatment and those with prior failed AAD therapy. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05823818.

Objective To evaluate the early and mid-term results of physician-modified candy-plug (pmCP) in patients with type-B or residual type-A aortic dissection (TBRAD). Methods All patients with TBRAD who received false lumen (FL) occlusion with pmCP between September 2018 and May 2024 were analyzed. Primary outcomes were technical and clinical success, and overall mortality. Secondary outcomes were postoperative aortic remodeling and aortic reintervention. Results Seventeen patients (88% male; mean age 69±12 years) underwent FL occlusion with a pmCP. Nine patients (53%) were emergently treated. The technical and clinical successes were 100% and 82%, respectively. One patient (6%) died postoperatively. Early complete FL occlusion was observed in 82% of the patients. One patient (6%) required an early pmCP-related reintervention. During a mean follow-up of 15±5 months, 75% of the patients had complete thoracic FL thrombosis while 13% of them aortic remodeling in the last computed tomography (CT) scan. Aneurysm size remained stable in 69% of the cases. There were no aortic-related re-interventions during follow-up. Conclusions The pmCP technique is a feasible and promising alternative technique, with high primary technical and clinical success rate. Stable aortic diameters can be expected during follow-up, thus reducing the need for further aortic reintervention. Clinical Impact Persistence of false lumen (FL) patency after thoracic endovascular aortic repair (TEVAR) for thoracic aortic dissection (TBAD) remains a significant challenge for physicians. Various strategies have been developed to address retrograde FL patency, including the candy-plug technique. This technique involves modifying thoracic stent grafts and placing an additional plug to occlude the reduced stent graft waist.Since its introduction, three generations of custom-made candy-plug devices (Cook Medical, Bloomington, IN, USA) have been developed. However, delivery times vary across countries and vascular surgery services, complicating procedural planning, particularly in symptomatic patients or cases of rapid FL diameter progression.In this study, we provide a step-by-step description of the physician-modified candy-plug technique and present our preliminary results.

Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000 mg phosphorus equivalent/day) supplemented with either a phosphate binder (low Pi diet) or phosphate capsules (750 mg phosphorus, high Pi diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.

PURPOSE Extracting inclusion and exclusion criteria in a structured, automated fashion remains a challenge to developing better search functionalities or automating systematic reviews of randomized controlled trials in oncology. The question “Did this trial enroll patients with localized disease, metastatic disease, or both?” could be used to narrow down the number of potentially relevant trials when conducting a search. METHODS Six hundred trials from high-impact medical journals were classified depending on whether they allowed for the inclusion of patients with localized and/or metastatic disease. Five hundred trials were used to develop and validate three different models, with 100 trials being stored away for testing. The test set was also used to evaluate the performance of GPT-4o in the same task. RESULTS In the test set, a rule-based system using regular expressions achieved F1 scores of 0.72 for the prediction of whether the trial allowed for the inclusion of patients with localized disease and 0.77 for metastatic disease. A transformer-based machine learning (ML) model achieved F1 scores of 0.97 and 0.88, respectively. A combined approach where the rule-based system was allowed to over-rule the ML model achieved F1 scores of 0.97 and 0.89, respectively. GPT-4o achieved F1 scores of 0.87 and 0.92, respectively. CONCLUSION Automatic classification of cancer trials with regard to the inclusion of patients with localized and/or metastatic disease is feasible. Turning the extraction of trial criteria into classification problems could, in selected cases, improve text-mining approaches in evidence-based medicine. Increasingly large language models can reduce or eliminate the need for previous training on the task at the expense of increased computational power and, in turn, cost.

Importance Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2). Objective To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo. Design, Setting, and Participants OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator’s Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods. Interventions Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks. Main Outcomes and Measures The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16. Results Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity. Conclusions and Relevance In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN. Trial Registration ClinicalTrials.gov Identifier: NCT04501666

Objective Gene expression (transcriptomics) studies have revealed potential mechanisms of interstitial lung disease (ILD), yet sample sizes of studies are often limited and between-subtype comparisons are scarce. The aim of this study was to identify and validate consensus transcriptomic signatures of ILD subtypes. Methods We performed a systematic review and meta-analysis of fibrotic ILD transcriptomics studies using an individual participant data approach, and included studies examining bulk transcriptomics of human adult ILD samples and excluding those focusing on individual cell populations. Patient-level data and expression matrices were extracted from 43 studies and integrated using a multivariable integrative algorithm to develop ILD classification models. Results Using 1459 samples from 24 studies, we identified transcriptomic signatures for idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), idiopathic nonspecific interstitial pneumonia (NSIP), and systemic sclerosis-associated ILD (SSc-ILD) against control samples, which were validated on 308 samples from 8 studies (area under receiver operating curve [AUC]=0.99 [95% CI: 0.99–1.00], HP AUC=0.91 [0.84–0.99], NSIP AUC=0.94 [0.88–0.99], SSc-ILD AUC=0.98 [0.93–1.00]). Significantly, meta-analysis allowed, for the first time, identification of robust lung transcriptomics signatures to discriminate IPF (AUC=0.71 [0.63–0.79]) and HP (AUC=0.76 [0.63–0.89]) from other fibrotic ILDs, and unsupervised learning algorithms identified putative molecular endotypes of ILD associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (D LCO ) % predicted. Transcriptomics signatures were reflective of both cell-specific and disease-specific changes in gene expression. Conclusion We present the first systematic review and largest meta-analysis of fibrotic ILD transcriptomics to date, identifying reproducible transcriptomic signatures with clinical relevance.

Background 90% of glioblastomas (GBM) relapse within two years of diagnosis. In contrast to the initial setting, there is no standard management for recurrent disease and options include hypofractionated stereotactic re-irradiation (re-mHSRT). The aims of this study were to investigate re-mHSRT practice in Swiss neuro-oncology centres. Methods A survey of 18 questions regarding re-irradiation for GBM was created and distributed electronically (SurveyMonkey, USA) to 11 radiation oncologists in Switzerland specialising in brain tumours. We evaluated the clinical outcomes of a multicentre series of patients treated with an established re-mHSRT schedule to benchmark these against the literature and investigated the radiological patterns of relapse after re-mHSRT. Results 8 of 11 (73%) radiation oncologists responded to the survey and re-irradiation practice was heterogeneous. The 10 × 3.5 Gy schedule (RTOG 1205, BRIOChe trials) was used by 5/8 respondents and 47/50 patients with recurrent GBM treated with re-mHSRT with this schedule in daily practice were included in the analysis. The median time to re-mHSRT following completion of adjuvant RT was 23.3 (7-224) months. The median PTV at re-mHSRT was 22.0 cm³ (0.9–190). Combined CTV + PTV margins ranged from 0 to 10 mm and median prescription isodose was 80% (67–100). 14/47 (30%) patients received temozolomide and four (8.5%) continued bevacizumab concomitantly. On multivariable analysis, concomitant systemic therapy predicted for progression-free survival (PFS), HR 2.87 (95% CI 1-03-7.96), p = 0.042. Median PFS following re-mHSRT was 6.6 (0.2–92.5) months and 26/47 patients (55%) received subsequent systemic therapy. The median overall survival (OS) following recurrence was 11.8 months (1.5–92.5), similar to the 10.8 months in the literature with the same schedule. The six-month OS rate was 37/47 (79%), which compares well with the 73% reported in a meta-analysis of 50 publications employing various schedules. In a subgroup analysis of 36/47 (79%) patients with MR follow-up after re-mHSRT, 8/36 (22%) had no radiological evidence of tumour progression at a median follow-up of 9.4 months. 21/28 (75%) radiological relapses were in-field, two were marginal and five were out of field. Conclusions Re-mHSRT with 10 × 3.5 Gy can achieve local control in selected patients with recurrent GBM.

Introduction Malleolar fractures are the most common ankle fractures and a major risk factor for ankle osteoarthritis in the long-term. Little is known about modifiable risk factors for a satisfactory outcome. This study aimed to assess the long-term clinical, functional and radiological outcomes in patients after osteosynthesis. Methods In this retrospective single center study, we assessed the difference in patients who underwent surgical intervention for malleolar fractures sustained between 2007 and 2014. The reduction was assessed on the first postoperative radiograph. At follow-up patients completed a questionnaire, including the European Foot and Ankle Society (EFAS) and Short Form-12 (SF-12) scores to evaluate patient-reported outcomes and quality of life. Ankle osteoarthritis was assessed using the Kellgren and Lawrence classification. Results One hundred seventeen patients, 102 with anatomic reduction and 15 with malreduction, were reached at mean follow-up at 11.4 years and 10.9 years. The mean EFAS score was 18,0 for anatomic and 16,1 for nonanatomic reduction and 6.1 and 4.5 for the sport component. The rate of satisfaction with the result was 8.2 in anatomic reduction and 7.5 in the malreduction. There was no significant difference in the SF-12 group between the two groups. Anatomic reduction is a protective facture for a satisfactory outcome in the univariate model with the hazard ratio of 5.94. Conclusion Anatomic reduction is one of the strongest protective factors for satisfactory outcome after malleolar fractures in a follow-up of more than 10 years.

Aims Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R ² = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693.

Aims: Current evidence of the impact of acute exercise on insulin levels in individuals with type 1 diabetes remains controversial. Therefore, we conducted a systematic review and meta-analysis to explore exercise-induced changes in insulin levels. Materials and methods: We conducted a systematic review (until 05 November 2023) and meta-analysis exploring the effect of exercise on insulin concentration in individuals with type 1 diabetes. We included randomised cross-over studies for rapid-acting insulin and pre- and post-studies for long-acting insulin in individuals with type 1 diabetes performing any type of acute exercise and had a control condition. The exercise-induced change in insulin levels was the outcome of interest. When possible, the mean differences (MDs) in insulin levels were pooled using the DerSimonian and Laird random effect method. Risk of bias was assessed for each included study. Results: Seventeen trials, encompassing 186 participants with type 1 diabetes, were included in the systematic review. Twelve out of 17 studies included participants on rapid-acting insulin regimens and used a cross-over design, whereas five out of 17 single-arm studies included participants on (ultra)long-acting insulin. Seven out of 12 studies on rapid-acting insulins and all the single-arm studies were at high risk of bias. Results suggest a statistically significant, small-to-moderate increase of rapid-acting insulin after 30 min of exercise (MD of 18.44 [95% CI 0.02; 36.86; I2 0%] pmol/L); meanwhile, findings on (ultra)long-acting insulin were inconclusive. Conclusions: A small-to-moderate increase of insulin levels in studies including rapid-acting insulin was found after a bout of physical exercise in individuals with type 1 diabetes. However, current gaps in high-quality evidence challenge our understanding of insulin kinetics around exercise.