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Objective: Since February 2022, the number of casualties in the Russian-Ukrainian war have dramatically increased, with a high incidence of penetrating traumatic brain injuries (pTBIs). To date, there has been limited evaluation of pTBI of the anterior skull base involving the paranasal sinuses. The objective of this study was to highlight the authors' experience with this injury pattern and identify specific factors associated with favorable short-term (1-month) outcome and survival., Methods: The authors conducted a single-institution retrospective review of patient data collected from the 1st year of the Russian-Ukrainian war at a frontline civilian Ukrainian hospital. To prevent complications from conservative treatment of pTBI with paranasal sinus injury, a protocol of early primary neurosurgical treatment including debridement/hematoma evacuation, repair of dural defects with vascularized pericranial flaps, and titanium plating of external/skull base defects was implemented. Using 1-month postoperative Glasgow Outcome Scale scores, the authors defined a favorable outcome as good recovery/moderate disability and a poor outcome as severe disability/vegetative state/death. Patient demographics, injury characteristics, imaging findings, and postoperative complications were assessed. Logistic regression models were used to estimate the effect of patient characteristics on unfavorable outcome or survival., Results: From February 2022 to February 2023, there were 141 pTBIs (20%) involving the paranasal sinuses, 134 (95%) due to blast fragmentation. One hundred eighteen patients (84%) had a favorable outcome. Most patients with pTBIs (69%) had other nonbrain-related injuries. While 48 patients (34%) presented with preoperative CSF leak, only 1 patient (0.7%) had persistent postoperative CSF leak, which was managed with lumbar drainage. High admission Glasgow Coma Scale (GCS) score, favorable injury lateralization (single hemisphere involved), and low Injury Severity Score (ISS) were associated with significantly increased odds of favorable short-term outcome, whereas high admission GCS scores and no midline shift were associated with significantly increased odds of survival., Conclusions: This was the largest single-year study on neurosurgical treatment of wartime pTBI involving the paranasal sinuses. Implementation of primary neurosurgical intervention at the time of presentation demonstrated promising early results and a shift away from expectant management of this injury pattern. The association of high admission GCS score, low ISS, favorable injury lateralization, and no midline shift on favorable short-term outcomes or survival has not been previously documented with this injury pattern.

Objective: Primary rod fracture after surgery for adult spinal deformity (ASD) is a leading cause of revision, with recent prospective multicenter fracture rates reported at 11%-14% by 2 years. Consequently, the addition of supplemental rods has been explored to reduce fractures. Here the authors describe their experience with a novel iliac accessory rod technique in which each accessory rod anchors to an independent iliac bolt caudally via lateral connector, and attaches to the primary rod rostrally via side-to-side connector., Methods: This retrospective, single-center case series included patients who underwent thoracolumbar/lumbar fusion for ASD between March 2019 and August 2023. Data on baseline demographics, radiographic parameters, surgical characteristics, complications, rod fracture, and revision rates were collected. Paired, 2-tailed t-tests were used to compare pre- and postoperative radiographic outcomes. Rod fracture rates were compared to prior investigations via chi-square goodness of fit testing. The technique for iliac accessory rod placement is described., Results: The study consisted of 82 patients (mean age 66 years, 51% female, 26% with prior fusion) with a median follow-up of 2 years (IQR 28-104 weeks). A total of 50 patients (61%) had ≥ 2-year follow-up. Each surgery involved an average of 4 posterior column osteotomies and 8 segments. Iliac accessory rods were cobalt chromium and were placed bilaterally in 87% of constructs. Postoperative alignment improved significantly in the following parameters: maximum coronal Cobb angle, fractional curve, sagittal vertical axis, lumbar lordosis, thoracic kyphosis, and pelvic incidence to lumbar lordosis mismatch (p < 0.001 for all comparisons). Of 50 patients with ≥ 2-year follow-up, rod fracture occurred in 1 (2.0%), which was incidentally found and required no intervention. The present rod fracture rate was significantly lower than the authors' historically reported institutional rate of 21% for traditional dual-rod constructs, and the 11%-14% reported in recent prospective multicenter studies that used traditional and supplemental rod constructs (p < 0.05 for all comparisons). Reoperation occurred in 12 patients (14.6%); 7 (8.5%) for proximal junctional kyphosis and 5 (6.1%) for wound complication., Conclusions: Here the authors describe their experience with a novel iliac accessory rod technique to prevent rod fracture in patients undergoing surgery for ASD. The 2-year rod fracture rate (2.0%) in this study is significantly lower than the authors' historical dual-rod fracture rate, and other prospective multicenter investigations. Future studies with longer follow-up are needed to determine the durability of this technique.

Implant-related complications in surgery for adult spinal deformity (ASD) account for roughly $1 billion US health care expenditures over 5 years, with a majority due to primary rod fracture.1,2 Traditional two-rod constructs have demonstrated rod fracture rates of up to 40%, with a median time to fracture of 3 years.3 Current supplementary rod techniques for decreasing rod fractures inadequately address the issue of increased strain across the lumbosacral junction.4 Here, we describe a novel four-rod technique using "iliac accessory rods," designed to mitigate rod fractures by reinforcing osteotomy levels and dispersing biomechanical stress across the lumbosacral junction. Compared with other supplementary rod techniques for ASD, iliac accessory rods anchor to independent iliac bolts.5 The added fixation points across the lumbosacral junction (4 iliac bolts total) substantially offloads stress on primary rods, most of which fracture near the lumbosacral junction.3 Additionally, connecting these rods to primary rods rostrally via side-to-side connectors, above the osteotomy levels, ensures mobile osteotomy segments are reinforced. Presented is a 78-year-old woman with ASD and worsening lower back pain, radiculopathy, and bilateral leg weakness who failed nonoperative management. She underwent T9 to bi-iliac instrumented fusion with L1-S1 posterior column osteotomies, L4-S1 transforaminal lumbar interbody fusions, and bilateral iliac accessory rod fixation. Postoperatively, she recovered well and had improvement in her symptoms. Imaging revealed correction of spinal alignment. The patient consented to the procedure, and the participants and any identifiable individuals consented to publication of his/her image. Institutional Review Board approval was waived because of institutional exemption policy., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Study Design: Retrospective, mono-centric cohort research study., Objectives: The purpose of this study is to validate a novel artificial intelligence (AI)-based algorithm against human-generated ground truth for radiographic parameters of adolescent idiopathic scoliosis (AIS)., Methods: An AI-algorithm was developed that is capable of detecting anatomical structures of interest (clavicles, cervical, thoracic, lumbar spine and sacrum) and calculate essential radiographic parameters in AP spine X-rays fully automatically. The evaluated parameters included T1-tilt, clavicle angle (CA), coronal balance (CB), lumbar modifier, and Cobb angles in the proximal thoracic (C-PT), thoracic, and thoracolumbar regions. Measurements from 2 experienced physicians on 100 preoperative AP full spine X-rays of AIS patients were used as ground truth and to evaluate inter-rater and intra-rater reliability. The agreement between human raters and AI was compared by means of single measure Intra-class Correlation Coefficients (ICC; absolute agreement; >.75 rated as excellent), mean error and additional statistical metrics., Results: The comparison between human raters resulted in excellent ICC values for intra- (range: .97-1) and inter-rater (.85-.99) reliability. The algorithm was able to determine all parameters in 100% of images with excellent ICC values (.78-.98). Consistently with the human raters, ICC values were typically smallest for C-PT (eg, rater 1A vs AI: .78, mean error: 4.7°) and largest for CB (.96, -.5 mm) as well as CA (.98, .2°)., Conclusions: The AI-algorithm shows excellent reliability and agreement with human raters for coronal parameters in preoperative full spine images. The reliability and speed offered by the AI-algorithm could contribute to the efficient analysis of large datasets (eg, registry studies) and measurements in clinical practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression., Methods: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry., Results: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding., Conclusions: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luenstedt, Hoping, Feuerstein, Mauerer, Berlin, Rapp, Marx, Reichardt, von Elverfeldt, Ruess, Plundrich, Laessle, Jud, Neeff, Holzner, Fichtner-Feigl and Kesselring.)

Background and Objective: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community., Methods: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers. The online survey consisted of an initial importance prioritization task, a best-worst scaling case 1 instrument, and open-ended questions. Rating counts were used for analysis. The best-worst scaling used a balanced incomplete block design., Results: One hundred and one participants responded to the survey invitation with 66 completing the best-worst scaling. The most important research topics related to the synthesis of preferences across studies, transferability across populations or related diseases, and method topics including comparison of methods and non-discrete choice experiment methods. Prioritization differences were found between respondents whose primary affiliation was academia versus other stakeholders. Academic researchers prioritized methodological/less studied topics; other stakeholders prioritized applied research topics relating to consistency of practice., Conclusions: As the field of health preference research grows, there is a need to revisit and communicate previous work on preference selection and study design to ensure that new stakeholders are aware of this work and to update these works where necessary. These findings might encourage discussion and alignment among different stakeholders who might hold different research priorities. Research on the application of previous preference research to new contexts will also help increase the acceptance of health preference information by decision makers., (© 2023. The Author(s).)

Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercellular site-specific network of cancer-associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell-dependent antigen presentation and consecutive effector T cell exhaustion. Furthermore, we demonstrated major similarities of this murine metastatic CRC model with human disease and - based on the results of our analysis - provided an auspicious site-specific immunomodulatory treatment approach for stage IV CRC by intraperitoneal checkpoint inhibition.

Background: Substance use is a global issue, with around 30 to 35 million individuals estimated to have a substance-use disorder. Motivational interviewing (MI) is a client-centred method that aims to strengthen a person's motivation and commitment to a specific goal by exploring their reasons for change and resolving ambivalence, in an atmosphere of acceptance and compassion. This review updates the 2011 version by Smedslund and colleagues., Objectives: To assess the effectiveness of motivational interviewing for substance use on the extent of substance use, readiness to change, and retention in treatment., Search Methods: We searched 18 electronic databases, six websites, four mailing lists, and the reference lists of included studies and reviews. The last search dates were in February 2021 and November 2022., Selection Criteria: We included randomised controlled trials with individuals using drugs, alcohol, or both. Interventions were MI or motivational enhancement therapy (MET), delivered individually and face to face. Eligible control interventions were no intervention, treatment as usual, assessment and feedback, or other active intervention., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane, and assessed the certainty of evidence with GRADE. We conducted meta-analyses for the three outcomes (extent of substance use, readiness to change, retention in treatment) at four time points (post-intervention, short-, medium-, and long-term follow-up)., Main Results: We included 93 studies with 22,776 participants. MI was delivered in one to nine sessions. Session durations varied, from as little as 10 minutes to as long as 148 minutes per session, across included studies. Study settings included inpatient and outpatient clinics, universities, army recruitment centres, veterans' health centres, and prisons. We judged 69 studies to be at high risk of bias in at least one domain and 24 studies to be at low or unclear risk. Comparing MI to no intervention revealed a small to moderate effect of MI in substance use post-intervention (standardised mean difference (SMD) 0.48, 95% confidence interval (CI) 0.07 to 0.89; I 2 = 75%; 6 studies, 471 participants; low-certainty evidence). The effect was weaker at short-term follow-up (SMD 0.20, 95% CI 0.12 to 0.28; 19 studies, 3351 participants; very low-certainty evidence). This comparison revealed a difference in favour of MI at medium-term follow-up (SMD 0.12, 95% CI 0.05 to 0.20; 16 studies, 3137 participants; low-certainty evidence) and no difference at long-term follow-up (SMD 0.12, 95% CI -0.00 to 0.25; 9 studies, 1525 participants; very low-certainty evidence). There was no difference in readiness to change (SMD 0.05, 95% CI -0.11 to 0.22; 5 studies, 1495 participants; very low-certainty evidence). Retention in treatment was slightly higher with MI (SMD 0.26, 95% CI -0.00 to 0.52; 2 studies, 427 participants; very low-certainty evidence). Comparing MI to treatment as usual revealed a very small negative effect in substance use post-intervention (SMD -0.14, 95% CI -0.27 to -0.02; 5 studies, 976 participants; very low-certainty evidence). There was no difference at short-term follow-up (SMD 0.07, 95% CI -0.03 to 0.17; 14 studies, 3066 participants), a very small benefit of MI at medium-term follow-up (SMD 0.12, 95% CI 0.02 to 0.22; 9 studies, 1624 participants), and no difference at long-term follow-up (SMD 0.06, 95% CI -0.05 to 0.17; 8 studies, 1449 participants), all with low-certainty evidence. There was no difference in readiness to change (SMD 0.06, 95% CI -0.27 to 0.39; 2 studies, 150 participants) and retention in treatment (SMD -0.09, 95% CI -0.34 to 0.16; 5 studies, 1295 participants), both with very low-certainty evidence. Comparing MI to assessment and feedback revealed no difference in substance use at short-term follow-up (SMD 0.09, 95% CI -0.05 to 0.23; 7 studies, 854 participants; low-certainty evidence). A small benefit for MI was shown at medium-term (SMD 0.24, 95% CI 0.08 to 0.40; 6 studies, 688 participants) and long-term follow-up (SMD 0.24, 95% CI 0.07 to 0.41; 3 studies, 448 participants), both with moderate-certainty evidence. None of the studies in this comparison measured substance use at the post-intervention time point, readiness to change, and retention in treatment. Comparing MI to another active intervention revealed no difference in substance use at any follow-up time point, all with low-certainty evidence: post-intervention (SMD 0.07, 95% CI -0.15 to 0.29; 3 studies, 338 participants); short-term (SMD 0.05, 95% CI -0.03 to 0.13; 18 studies, 2795 participants); medium-term (SMD 0.08, 95% CI -0.01 to 0.17; 15 studies, 2352 participants); and long-term follow-up (SMD 0.03, 95% CI -0.07 to 0.13; 10 studies, 1908 participants). There was no difference in readiness to change (SMD 0.15, 95% CI -0.00 to 0.30; 5 studies, 988 participants; low-certainty evidence) and retention in treatment (SMD -0.04, 95% CI -0.23 to 0.14; 12 studies, 1945 participants; moderate-certainty evidence). We downgraded the certainty of evidence due to inconsistency, study limitations, publication bias, and imprecision., Authors' Conclusions: Motivational interviewing may reduce substance use compared with no intervention up to a short follow-up period. MI probably reduces substance use slightly compared with assessment and feedback over medium- and long-term periods. MI may make little to no difference to substance use compared to treatment as usual and another active intervention. It is unclear if MI has an effect on readiness to change and retention in treatment. The studies included in this review were heterogeneous in many respects, including the characteristics of participants, substance(s) used, and interventions. Given the widespread use of MI and the many studies examining MI, it is very important that counsellors adhere to and report quality conditions so that only studies in which the intervention implemented was actually MI are included in evidence syntheses and systematic reviews. Overall, we have moderate to no confidence in the evidence, which forces us to be careful about our conclusions. Consequently, future studies are likely to change the findings and conclusions of this review., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: In surgical treatment of adolescent idiopathic scoliosis (AIS), only a few studies measure both, radiological parameters and PROMs and correlate them., Methods: Prospectively collected AIS-data of one scoliosis-center within a multicenter German-Spine-Society-Study. All patients underwent instrumented posterior spinal correction and fusion with pedicle-screw-dual-rod-systems from 05/2019 to 01/2021. The data were retrospectively analyzed., Inclusion Criteria: age 11-17 years, follow-up (FU) at least 12 months. Clinical data, radiographic parameters, and PROMs (SRS-30-questionnaire) were collected. 100% of patients had X-ray images, 88.2% completed SRS-30. Parameters were given as mean ± SD. Differences and subdivision by lower instrumented vertebra (LIV) were analyzed by students t-test (significancy a = 0.05), associations by Pearson's correlation., Result: Total of 51 patients: 15 ± 1.4 years, BMI 20.7 ± 3.7 kg/m 2 , FU 16.6 ± 6.1 months, fusion length 9.2 ± 2.3 segments, implant density 93 ± 9%, surgical time 215 ± 71 min, mean blood loss 504 ± 360 ml. Mean preoperative Cobb angle of main curve 64 ± 14°, of secondary main curve 46 ± 12°, corrected by 68 ± 11%, 56 ± 17%, respectively. Mean thoracic rib and lumbar hump significantly decreased by - 8.5 ± 7.0° and - 7.7 ± 8.9° (p < 0.5). High thoracic rib hump almost unchanged, - 0.4 ± 2.8° (p = 0.3). Thoracic kyphosis (- 0.9 ± 12.8°, p = 0.6), lumbar lordosis (1.5 ± 10.1°, p = 0.3), clavicle angle (- 0.5 ± 2.7°) and spinopelvic parameters (p > 0.5) did not significantly change, only LIV-tilt from 24.5 ± 6.7° to 6.5 ± 4.3° (p < 0.05). PROMs significantly improved (p < 0.05), no significant improvement for function/activity (p = 0.4). Preoperative mean total-score was 3.6 ± 0.5, 4.2 ± 0.3 at FU(p < 0.05). Self-image improved in 67%. Moderately strong correlation for PROMs: the better LIV-tilt (r = - 0.5) correction and the shorter surgery time (r = - 0.4), the better SRS-30 total-score. No correlation for curve correction and patient's satisfaction., Conclusion: In summary, results of this study demonstrate good surgical correction and significant improvement of most PROMs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As the rate of people openly identifying as transgender or gender diverse (TGD) is increasing, UK cancer genetics services are seeing growing numbers of TGD patients. Lack of appropriate clinical guidelines and a scarcity of robust data about the impact of gender-affirming treatments on cancer risk has led to uncertainty of how best to support TGD patients, and inequity in standards of care. To address this gap, the UK Cancer Genetics Group and Central & South Genomic Medicine Service Alliance facilitated a 2-day meeting to develop national consensus to support the management of TGD patients with inherited cancer risks. Key stakeholders from a broad range of clinical specialties, patients advocates, and those with lived experience discussed and voted on recommendations for best practice. The consensus was reached on topics including family history questionnaires, pedigrees, clinical information, breast tissue management, gynaecological and prostate management, patient pathways, and education. Further work is required to reach consensus on the breast screening recommendations for TGD patients assigned female at birth who have had masculinising chest surgery. Here we present a summary of the processes used to reach consensus, and the recommendations from this meeting., (© 2023. The Author(s).)

With genomic testing being increasingly integrated into every day clinical practice and a wide range of practitioners ordering genetic tests, it is important that the scope of the genetic counselling role continues to evolve alongside these changes. We present an exemplary role for genetic counsellors in a highly specialised service within England's National Health Service for people who have or are suspected to have rare genetic types of Ehlers Danlos syndrome. The service employs genetic counsellors and consultants from the fields of genetics and dermatology. The service also works closely with other specialists and related charities and patient organisations. The genetic counsellors in the service provide routine genetic counselling such as diagnostic and predictive testing, but their role also includes the writing of patient literature and emergency and well-being resources, delivering workshops and talks, and the development of qualitative and quantitative research on the patient experience. Data from such research has informed the development of patient self-advocacy and supportive resources, raised awareness amongst healthcare professionals and enhanced the standard of care and outcomes for patients. The service aims to be an example of innovation and accessibility and provides a model that can be potentially adopted by other highly specialised services of rare genetic diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Adolescent idiopathic scoliosis (AIS) often correspond with hypo thoracic kyphosis (TK) or even lordosis. The aim of this study was to analyze the influence of posterior instrumentation in thoracic AIS., Methods: Analysis of prospectively collected AIS-data with structural thoracic curves (Lenke type 1 & 2), operated 2010-2019 with pedicle screw dual rod systems in one scoliosis center. Follow-up (FU) minimum 24 months. Coronal and sagittal angles measured based on standing long-cassette-X-rays: thoracic major (MC), proximal thoracic (PC) and lumbar curve (LC), TK, lumbar lordosis (LL)., Statistical Analysis: values as mean ± SD, differences by student's t-test (significancy a = 0.05), Pearson's correlation, sub-analysis with sagittal modifier (-, N, +)., Results: A total of 127 AIS could be identified (63% type 1, 37% type 2). Mean FU 32.2 ± 16.6 months, mean age 14 ± 1.5 years. Mean Correction of MC 73 ± 12%, PC 51 ± 17%, LC 69 ± 21% with a significantly better correction of PC in Lenke 2 curves(p < 0.05). On average, TK (FU-preop) decreased by -2.1 ± 12.1°(p < 0.05) in all AIS. Whereas TK in type 1 was unchanged (p = 0.9), TK significantly decreased by - 6.0 ± 12.7°(p < 0.05) in type 2. No significant difference in LL. TK in hypokyphotic cases increased by 9.5 ± 5.5°(p < 0.05), stayed almost unchanged (- 1.4 ± 9.1°,p = 0.2) in normokyphotic, decreased by - 17.2 ± 14.2°(p < 0.05) in hyperkyphotic cases. Only hypokyphotic cases had a moderately strong correlation between correction of LC (r = 0.6) and PC (r = - 0.4) (frontal plane) and change from pre- to postoperative TK (sagittal plane) (r = 0.6). No relevant correlations for normo- and hyperkyphotic AIS. Postoperative hypokyphosis was significantly more often in Lenke 2 (16.3% vs. 2.6%, p < 0.05). Rod diameter (5,5 mm versus 6 mm) had no significant influence., Conclusion: Significant correction of hypo- and hyperkyphosis can be achieved with posterior spinal fusion (pedicle screw dual rod systems), whereas normokyphotic spines stay unchanged. However, Lenke 2 curves have a significantly higher risk for a postoperative thoracic hypokyphosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Adolescent idiopathic scoliosis (AIS) is often associated with thoracic hypokyphosis or even lordosis., Objectives: To analyze the influence of posterior correction and fusion in thoracic, structurally double-curved AIS., Material and Methods: Out of 127 thoracic AIS (Lenke types 1 and 2) recorded prospectively, idiopathic double thoracic curve AIS were analyzed retrospectively. Surgery 2010-2019 with pedicle screw double rod systems in a scoliosis center. Follow-up (FU) at least 2 years. Frontal and sagittal angles (whole-spine radiographs, 2 planes): thoracic curve (MK), proximal-thoracic curve (PK) and lumbar curve (LK), thoracic kyphosis (TK), lumbar lordosis (LL)., Statistical Analysis: values as MW ± SD, students t‑test (significance a = 0.05), Pearson's correlation, sub-analysis with sagittal modifiers (-, N, +)., Results: A total of 47 AIS-double thoracic curve were identified, mean FU 29.3 ± 12.2 months, mean age 14 ± 1.5 years. The mean correction (FU-preop) of MK was 67%, PK 53%, LK 73%, each significant, (p < 0.05). On average, TK (FU-preop) decreased by -6.5 ± 11.6° (p < 0.05), no significant change from FU (p = 0.6). TK (FU-preop) increased by 8.6 ± 5.0° (p < 0.05) in hypokyphotic cases, significantly decreased by -4.8 ± 9.6° in normokyphotic AIS and -25.3 ± 11.1° in hyperkyphotic cases, respectively (p < 0.05). In hypokyphosis: moderately strong correlation between correction PK (r = -0.5) and spontaneous correction LK (r = 0.8) (frontal plane) and change from pre- to postop TK (sagittal plane) (p < 0.05). Moderate correlation for hyperkyphosis: correction PK (r = -0.5) and postop TK (p < 0.05). No relevant correlations for normokyphosis. 17% had postop hypokyphosis, of which 0% had preop hypokyphosis. Rod diameter (5.5 mm vs. 6 mm) had no significant effect on TC., Conclusions: Posterior instrumented correction and fusion (pedicle screw dual rod systems) can significantly correct both lateral curves in idiopathic double thoracic curves, although it is associated with an increased risk of postop thoracic hypokyphosis, especially in preoperatively normokyphotic patients., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Inflammasomes are intracellular protein complexes that promote an inflammatory host defense in response to pathogens and damaged or neoplastic tissues and are implicated in inflammatory disorders and therapeutic-induced toxicity. We investigated the mechanisms of activation for inflammasomes nucleated by NOD-like receptor (NLR) protiens. A screen of a small-molecule library revealed that several tyrosine kinase inhibitors (TKIs)-including those that are clinically approved (such as imatinib and crizotinib) or are in clinical trials (such as masitinib)-activated the NLRP3 inflammasome. Furthermore, imatinib and masitinib caused lysosomal swelling and damage independently of their kinase target, leading to cathepsin-mediated destabilization of myeloid cell membranes and, ultimately, cell lysis that was accompanied by potassium (K + ) efflux, which activated NLRP3. This effect was specific to primary myeloid cells (such as peripheral blood mononuclear cells and mouse bone marrow-derived dendritic cells) and did not occur in other primary cell types or various cell lines. TKI-induced lytic cell death and NLRP3 activation, but not lysosomal damage, were prevented by stabilizing cell membranes. Our findings reveal a potential immunological off-target of some TKIs that may contribute to their clinical efficacy or to their adverse effects.

Background: The widely used Swiss neighbourhood index of socioeconomic position (Swiss-SEP 1) was based on data from the 2000 national census on rent, household head education and occupation, and crowding. It may now be out of date., Methods: We created a new index (Swiss-SEP 2) based on the 2012-2015 yearly micro censuses that have replaced the decennial house-to-house census in Switzerland since 2010. We used principal component analysis on neighbourhood-aggregated variables and standardised the index. We also created a hybrid version (Swiss-SEP 3), with updated values for neighbourhoods centred on buildings constructed after the year 2000 and original values for the remaining neighbourhoods., Results: A total of 1.54 million neighbourhoods were included. With all three indices, the mean yearly equivalised household income increased from around 52,000 to 90,000 CHF from the lowest to the highest index decile. Analyses of mortality were based on 33.6 million person-years of follow-up. The age- and sex-adjusted hazard ratios of all-cause mortality comparing areas in the lowest Swiss-SEP decile with areas of the highest decile were 1.39 (95% confidence interval [CI] 1.36-1.41), 1.31 (1.29-1.33) and 1.34 (1.32-1.37) using the old, new and hybrid indices, respectively., Discussion: The Swiss-SEP indices capture area-based SEP at a high resolution and allow the study of SEP when individual-level SEP data are missing or area-level effects are of interest. The hybrid version (Swiss-SEP 3) maintains high spatial resolution while adding information on new neighbourhoods. The index will continue to be useful for Switzerland's epidemiological and public health research.

Background & Aims: CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are essential to maintain immunological tolerance and have been shown to promote liver allograft tolerance in both rodents and humans. Low-dose IL-2 (LDIL-2) can expand human endogenous circulating Tregs in vivo, but its role in suppressing antigen-specific responses and promoting Treg trafficking to the sites of inflammation is unknown. Likewise, whether LDIL-2 facilitates the induction of allograft tolerance has not been investigated in humans., Methods: We conducted a clinical trial in stable liver transplant recipients 2-6 years post-transplant to determine the capacity of LDIL-2 to suppress allospecific immune responses and allow for the complete discontinuation of maintenance immunosuppression (ClinicalTrials.gov NCT02949492). One month after LDIL-2 was initiated, those exhibiting at least a 2-fold increase in circulating Tregs gradually discontinued immunosuppression over a 4-month period while continuing LDIL-2 for a total treatment duration of 6 months., Results: All participants achieved a marked and sustained increase in circulating Tregs. However, this was not associated with the preferential expansion of donor-reactive Tregs and did not promote the accumulation of intrahepatic Tregs. Furthermore, LDIL-2 induced a marked IFNγ-orchestrated transcriptional response in the liver even before immunosuppression weaning was initiated. The trial was terminated after the first 6 participants failed to reach the primary endpoint owing to rejection requiring reinstitution of immunosuppression., Conclusions: The expansion of circulating Tregs in response to LDIL-2 is not sufficient to control alloimmunity and to promote liver allograft tolerance, due, at least in part, to off-target effects that increase liver immunogenicity. Our trial provides unique insight into the mechanisms of action of immunomodulatory therapies such as LDIL-2 and their limitations in promoting alloantigen-specific effects and immunological tolerance., Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT02949492)., Impact and Implications: The administration of low-dose IL-2 is an effective way of increasing the number of circulating regulatory T cells (Tregs), an immunosuppressive lymphocyte subset that is key for the establishment of immunological tolerance, but its use to promote allograft tolerance in the setting of clinical liver transplantation had not been explored before. In liver transplant recipients on tacrolimus monotherapy, low-dose IL-2 effectively expanded circulating Tregs but did not increase the number of Tregs with donor specificity, nor did it promote their trafficking to the transplanted liver. Low-dose IL-2 did not facilitate the discontinuation of tacrolimus and elicited, as an off-target effect, an IFNγ-orchestrated inflammatory response in the liver that resembled T cell-mediated rejection. These results, supporting an unexpected role for IL-2 in regulating the immunogenicity of the liver, highlight the need to carefully evaluate systemic immunoregulatory strategies with investigations that are not restricted to the blood compartment and involve target tissues such as the liver., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC is not only a genetic disease with several mutations in specific oncogenes and/or tumor suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also a multifactorial disease including environmental factors. Cancer cells communicate with their environment mostly via soluble factors such as cytokines, chemokines or growth factors to generate a favorable tumor microenvironment (TME). The TME, a heterogeneous population of differentiated and progenitor cells, plays a critical role in regulating tumor development, growth, invasion, metastasis and therapy resistance. In this context, cytokines from cancer cells and cells of the TME influence each other, eliciting an inflammatory milieu that can either enhance or suppress tumor growth and metastasis. Additionally, several lines of evidence exist that the composition of the microbiota regulates inflammatory processes, controlled by cytokine secretion, that play a role in carcinogenesis and tumor progression. In this review, we discuss the cytokine networks between cancer cells and the TME and microbiome in colorectal cancer and the related treatment strategies, with the goal to discuss cytokine-mediated strategies that could overcome the common therapeutic resistance of CRC tumors.

Study Design: A retrospective single center cohort study with prospective collected data from an institutional spine registry., Objectives: To determine whether restoration of lordosis L5/S1 is possible with both anterior lumbar interbody fusion (ALIF) and transforaminal lumbar interbody fusion (TLIF) and to find out which technique is superior to recreate lordosis in L5/S1., Methods: Seventy-seven patients with ALIF and seventy-nine with TLIF L5/S1 were included. Operation time, estimated blood loss), and complications were evaluated. Segmental lordosis L5/S1 and L4/5, overall lordosis, and proximal lordosis (L1 to L4) were measured in X-rays before and after surgery. Oswesery disability index and EQ-5D were assessed before surgery, and 3 and 12 months after surgery., Results: Mean operation time was 176.9 minutes for ALIF and 195.7 minutes for TLIF (p = 0.048). Estimated blood loss was 249.2 cc for ALIF and 362.9 cc for TLIF (p = 0.005). In terms of complications, only a difference in dural tears were found (TLIF 6, ALIF none; p = 0.014). Lordosis L5/S1 increased in the ALIF group (15.8 to 24.6°; p < 0.001), whereas no difference was noted in the TLIF group (18.4 to 19.4°; p = 0.360). Clinical results showed significant improvement in the Oswesery disability index (ALIF: 43 to 21.9, TLIF: 45.2 to 23.0) and EQ-5D (ALIF: 0.494 to 0.732, TLIF: 0.393 to 0.764) after 12 months in both groups, without differences between the groups., Conclusion: ALIF and TLIF are comparable methods for performing fusion at L5/S1, with good clinical outcomes and comparable rates of complications. However, there is only a limited potential for recreating lordosis at L5/S1 with a TLIF., Competing Interests: M. Quante hat einen Beratervertrag mit der Fa. Silony und erhält Honorare für Vorträge von der Fa. Nuvasive Inc. sowie der Fa. Silony. B. Thomsen hat eine Beratungstätigkeit für die Fa. Silony. M. Köszegvary hat einen Beratervertrag mit der Fa. Silony und erhält Honorare für Vorträge von der Fa. Nuvasive Inc. H. Halm hat einen Beratervertrag mit Patentvergütungskomponente mit der Fa. Nuvasive. Die Fa. Silony finanziert darüber hinaus eine Studienleiterin („study nurse“). C. Berlin, N. Bürger, F. Pecsi und U. Platz geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account., Methods: We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated., Results: During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m 3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m 3 . Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined., Conclusion: With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The SARS-CoV-2 (COVID-19) pandemic has accelerated the development and use of digital health platforms to support individuals with health-related challenges. This is even more frequent in the field of cancer care as the global burden of the disease continues to increase every year. However, optimal implementation of these platforms into the clinical setting requires careful planning and collaboration. An implementation project was launched between the Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Centre-Ouest-de-I'Île-de-Montreal and BELONG-Beating Cancer Together-a person-centred cancer navigation and support digital health platform. The goal of the project was to implement content and features specific to the CIUSSS, to be made available exclusively for individuals with cancer (and their caregivers) treated at the institution. Guided by Structural Model of Interprofessional Collaboration, we report on implementation processes involving diverse stakeholders including clinicians, hospital administrators, researchers and local community/patient representatives. Lessons learned include earlier identification of shared goals and clear expectations, more consistent reliance on virtual means to communicate among all involved, and patient/caregiver involvement in each step to ensure informed and shared decision making.

Postoperative shoulder imbalance (PSI) is a common complication following adolescent idiopathic scolio- sis (AIS) surgery. There is little data available in literature on prediction of PSI. Prospectively collected data of AIS with thoracic curve (Lenke 2), operated in 2014-2018 at a single scoliosis-center, were analyzed retrospectively using X-rays of whole spine and traction films (TA): age, Cobb-angle of proximal (PC), major thoracic (MC) and lumbar curve (LC), shoulder height [mm], clavicle angle [°], T1-tilt [°], plumb line [mm]. Results as mean ± standard deviation. Change over time (postOP- FU) compared using t-test (≥=0.05). Correlation of preOP parameters and curve correction with PSI (|≥|15mm) was analyzed by correlation (Pearson)- and regression-classification-analysis. 32 AIS, average age of 14±1.3 yrs. FU 16 months (84%). Curve correction was 52.5% (PC), 70.1% (MC), 69.9% (LC), significant change in FU for PC (-2.4°, p>0.05), not for MC, LC (p=0.2, p=0.6). Shoulder height was negative if right- side up: 2.9±15.1mm (preOP), 5.5±15.0 mm (TA), 17.9±14.9mm (postOP), 17.4±8.4mm (FU). 28% had preOP shoulder imbalance, 69% postOP and 44% FU had PSI. Shoulder height on TA correlated to change preOP to FU (r=0.62) and preOP shoulder height (r=-0.85), clavicle angle had strong correlation (r=- 0.81). Regression-classification-analysis: correction of MC>62.4%, 81.5% of cases had PSI; with correction of MC>64.9% and LC>93.2%, 51.9% of cases had PSI. PSI is a common in Lenke2 AIS. In preOP planning TA, shoulder position and clavicle angle should be considered to prevent PSI. Correction of MC should be moderate, overcorrection of the LC avoided.

Objectives: This article aims to measure the willingness of the Swiss public to participate in personalised health research, and their preferences regarding data management and governance., Setting: Results are presented from a nationwide survey of members of the Swiss public., Participants: 15 106 randomly selected Swiss residents received the survey in September 2019. The response rate was 34.1% (n=5156). Respondent age ranged from 18 to 79 years, with fairly uniform spread across sex and age categories between 25 and 64 years., Primary and Secondary Outcome Measures: Willingness to participate in personalised health research and opinions regarding data management and governance., Results: Most respondents preferred to be contacted and reconsented for each new project using their data (39%, 95% CI: 37.4% to 40.7%), or stated that their preference depends on the project type (29.4%, 95% CI: 27.9% to 31%). Additionally, a majority (52%, 95% CI: 50.3% to 53.8%) preferred their data or samples be stored anonymously or in coded form (43.4%, 95% CI: 41.7% to 45.1%). Of those who preferred that their data be anonymised, most also indicated a wish to be recontacted for each new project (36.8%, 95% CI: 34.5% to 39.2%); however, these preferences are in conflict. Most respondents desired to personally own their data. Finally, most Swiss respondents trust their doctors, along with researchers at universities, to protect their data., Conclusion: Insight into public preference can enable Swiss biobanks and research institutions to create management and governance strategies that match the expectations and preferences of potential participants. Models allowing participants to choose how to interact with the process, while more complex, may increase individual willingness to provide data to biobanks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Currently, the proportion of women in academic education and residency is predominant, but specialty-specific distribution of leading positions is partly reciprocal (orthopedics/surgery). Are there any differences that indicate a gender-dependent redistribution in leadership positions already in the selection of postgraduate training?, Methods: Online survey with orthopedics/trauma surgery (OUC) and neurosurgery (NCH) residents. Comparison with gynecology (GYN). Statistical analysis, mean in percent, statistical differences using t‑ or chi 2 -test (significance level α = 0,05)., Results: Returned questionnaire = 277, complete participation = 250. Female residents: OUC:52%, NCH:57%, GYN:85%. A total of 49% were told in medical school that a subject was inappropriate for gender reasons (f57-76%, m10-33%). The most frequent reason for a subject: all = "operating activity". The second most frequent reason: OUC-f = "good working atmosphere", OUC-m = "establishment", NCH-f = "career" and "good working atmosphere", NCH-m = "good working atmosphere", GYN-f = "establishment", GYN-m = "career". The most frequent reason against: OUC/GYN = "hardly any possibility to become established", NCH = "negative leadership style by superiors". For female residents in OUC/NCH, work/family balance had the smallest influence on the choice of specialty. Their subjective evaluation of compatibility was significantly the worst, and overall OUC/NCH was significantly worse than GYN. Although female residents in NCH were more likely to justify the specialty choice based on career goals, male residents in OUC/NCH were more likely to aim for a higher hierarchical position., Discussion: The results of this study emphasize that disciplines receive a gender-specific conditioning already at the undergraduate level, which has a clear impact on the choice of specialty. The image in this regard needs to be reconsidered, as even surgical subjects will predictably have to rely on more female specialists., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

More than half of all patients with colorectal cancer (CRC) develop distant metastasis and, depending on the local stage of the primary tumor, up to 48% of patients present peritoneal carcinomatosis (PC). PC is often considered as a widespread metastatic disease, which is almost resistant to current systemic therapies like chemotherapeutic and immunotherapeutic regimens. Here we could show that tumor cells of PC besides being senescent also exhibit stem cell features. To investigate these surprising findings in more detail, we established a murine model based on tumor organoids that resembles the clinical setting. In this murine orthotopic transplantation model for peritoneal carcinomatosis, we could show that the metastatic site in the peritoneum is responsible for senescence and stemness induction in tumor cells and that induction of senescence is not due to oncogene activation or therapy. In both mouse and human PC, senescence is associated with a senescence-associated secretory phenotype (SASP) influencing the tumor microenvironment (TME) of PC. SASP factors are able to induce a senescence phenotype in neighbouring cells. Here we could show that SASP leads to enhanced immunosenescence in the TME of PC. Our results provide a new immunoescape mechanism in PC explaining the resistance of PC to known chemo- and immunotherapeutic approaches. Therefore, senolytic approaches may represent a novel roadmap to target this terminal stage of CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Braumüller, Mauerer, Berlin, Plundrich, Marbach, Cauchy, Laessle, Biesel, Holzner and Kesselring.)

Objective: While surgical decompression is an important treatment modality for cervical spondylotic myelopathy (CSM), it remains unclear if the severity of preoperative myelopathy status affects potential benefit from surgical intervention and when maximum postoperative improvement is expected. This investigation sought to determine if retrospective analysis of prospectively collected patient-reported outcomes (PROs) following surgery for CSM differed when stratified by preoperative myelopathy status. Secondary objectives included assessment of the minimal clinically important difference (MCID)., Methods: A total of 1151 patients with CSM were prospectively enrolled from the Quality Outcomes Database at 14 US hospitals. Baseline demographics and PROs at baseline and 3 and 12 months were measured. These included the modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), quality-adjusted life-years (QALYs) from the EQ-5D, and visual analog scale from the EQ-5D (EQ-VAS). Patients were stratified by preoperative myelopathy severity using criteria established by the AO Spine study group: mild (mJOA score 15-17), moderate (mJOA score 12-14), or severe (mJOA score < 12). Univariate analysis was used to identify demographic variables that significantly varied between myelopathy groups. Then, multivariate linear regression and linear mixed regression were used to model the effect of severity and time on PROs, respectively., Results: For NDI, EQ-VAS, and QALY, patients in all myelopathy cohorts achieved significant, maximal improvement at 3 months without further improvement at 12 months. For mJOA, moderate and severe myelopathy groups demonstrated significant, maximal improvement at 3 months, without further improvement at 12 months. The mild myelopathy group did not demonstrate significant change in mJOA score but did maintain and achieve higher PRO scores overall when compared with more advanced myelopathy cohorts. The MCID threshold was reached in all myelopathy cohorts at 3 months for mJOA, NDI, EQ-VAS, and QALY, with the only exception being mild myelopathy QALY at 3 months., Conclusions: As assessed by statistical regression and MCID analysis, patients with cervical myelopathy experience maximal improvement in their quality of life, neck disability, myelopathy score, and overall health by 3 months after surgical decompression, regardless of their baseline myelopathy severity. An exception was seen for the mJOA score in the mild myelopathy cohort, improvement of which may have been limited by ceiling effect. The data presented here will aid surgeons in patient selection, preoperative counseling, and expected postoperative time courses.

Background: Postoperative shoulder imbalance is a common complication in adolescent idiopathic scoliosis and may impair patient satisfaction. The little data in the literature on the prediction and treatment of postoperative shoulder imbalance is incongruous. According to some studies, postoperative shoulder imbalance depends on the superior instrumented vertebral bodies, skeletal maturity, extent of correction and flexibility of the major curve., Question: Can preoperative radiological parameters from X-ray and traction films as well as correction of the curves be used to identify a factor impacting on postoperative shoulder imbalance?, Material and Methods: Prospective data in adolescent idiopathic scoliosis with thoracic curve (Lenke type 1), operated on between 2015 and 2018 at a scoliosis centre, were analysed retrospectively based on full-length X-rays of the spine (pre-/postOP and follow-up (FU)) and preoperative-traction films: age; correction of proximal, main and lumbar curve; shoulder height [mm]; clavicle angle [°]; T1 tilt [°]; coronal plumb line deviation [mm]. The findings were expressed as means with standard deviation. Changes in parameters over time (postOP-FU) were compared by t test (significance level α = 0.05). The correlation between preOP parameters and extent of correction with postoperative shoulder imbalance (≥ 15 mm) was determined by Pearson correlation and regression classification analysis., Outcomes: 55 patients with adolescent idiopathic scoliosis, mean age of 15 ± 1.4 years. The FU-rate after a mean of 15 months was 80% (n = 44). Correction of proximal, main and lumbar curve: 47.0%, 75.8% and 68.8%, respectively, without statistically significant change (Δ) in FU (p > 0.05). Shoulder height was - 11.0 ± 12.7 mm (preOP), 15.5 ± 13.4 mm (postOP), 10.1 ± 10.6 mm (FU) (p < 0.05). 38% of those with adolescent idiopathic scoliosis had preOP right shoulder elevation; 55% (postOP) and 32% (FU) respectively had postoperative shoulder imbalance (left shoulder elevation). Strong statistical correlation was found for Δshoulder position (FU-preOP) with pre-OP shoulder position (r = - 0.7), and Δshoulder position (pre-OP traction films) (r = 0.5) with pre-OP clavicle angle (r = - 0.5). On regression classification analysis, 81.8% of cases did display postoperative shoulder imbalance if proximal curve correction was ≤ 64.4%; main and lumbar curve correction, Δshoulder elevation (preOP traction films) played a secondary role., Discussion: One common complication even in Lenke type 1 adolescent idiopathic scoliosis is postoperative shoulder imbalance. Preoperative planning should include traction films, preoperative shoulder position and clavicle angle to avoid postoperative shoulder imbalance. Moderate correction of proximal curve is critical for postoperative shoulder balance., Competing Interests: C. Berlin, M. Quante and E. von Richthofen declare no conflict of interest. H. Halm. has a consulting and patent remuneration contract with the Nuvasive Inc. and a consulting contract with Silony. Silony also finances a study nurse./C. Berlin, M. Quante und E. von Richthofen geben an, dass kein Interessenkonflikt besteht. H. Halm. hat einen Beratervertrag mit Patentvergütungskomponente mit der Firma Nuvasive Inc. sowie einen Beratervertrag mit der Firma Silony. Die Firma Silony finanziert darüber hinaus eine Studienleiterin (study nurse)., (Thieme. All rights reserved.)

Aims: Underrepresentation of migrants, women, and older adults in cardiovascular disease (CVD) trials may contribute to disparate care and survival. Among patients who underwent percutaneous coronary intervention (PCI), we aimed to investigate the associations of (i) underrepresented groups with major adverse cardiac events (MACE), CVD mortality, and non-CVD mortality, (ii) underrepresented groups with cardiac rehabilitation (CR) uptake, and (iii) CR uptake with outcomes., Methods and Results: We included 15 211 consecutive patients from the CARDIOBASE Bern PCI registry (2009-18). In multi-state models comparing transition probabilities of events, sex was not associated with increased risk of any event. For each year increase in age, the increased risk of non-CVD and CVD mortality was 8% [95% confidence interval (CI) 6-9%]. Being migrant was associated with a lower risk of non-CVD mortality [hazard ratio (HR) (95% CI) 0.49 (0.27-0.90)] but not with CVD mortality. In logistic regression analysis, CR uptake was lower among women [odds ratio (95% CI) = 0.72 (0.57-0.86)] and older adults [0.32 (0.27-0.38)], but not among migrants. In cox regression, CR was independently associated with lower all-cause [HR (95% CI) = 0.12 (0.03-0.37)] and CVD mortality [0.1 (0.02-0.7)], but not with MACE [1.08 (0.8-1.4)]., Conclusion: Among underrepresented groups undergoing PCI, age, but not migration status nor sex, contributed to disparities in mortality. Migrant status did not result in lower attendance of CR. Considering the protective associations of CR on CVD mortality independent of age, sex, and migration status, the lower uptake in women and older adults is noteworthy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Research Question: How are perinatal outcomes of live-born singletons after stimulated and unstimulated IVF different from perinatal outcomes in (i) children born in a tertiary centre and (ii) all children born in Switzerland?, Methods: This cohort study compared the perinatal outcomes of two birth cohorts and the national live birth registry. Relative risks were calculated using modified Poisson regression and clustering for siblings and adjustment for maternal age, parity and childs sex., Results: Of the 636,639 live births, 311 were in the Bern IVF Cohort (144 stimulated, 167 unstimulated), 2332 in the tertiary centre and 633,996 in the Swiss Live Birth Registry (SLBR). Perinatal outcomes following IVF did not differ compared with births in the SLBR (adjusted relative risk [aRR]; 95% confidence interval [CI]), with the exception of the increased risk of small for gestational age (1.31; 1.01 to 1.70, P = 0.04; aRR 1.12; 0.87 to 1.45, P = 0.39). Children born following stimulated IVF had a higher risk of low birthweight (2.17; 1.27 to 3.69, P < 0.01; aRR 1.72; 1.01 to 2.93, P = 0.05), and of being small for gestational age (1.50; 1.05 to 2.14, P = 0.03; aRR 1.31; 0.92 to 1.87; P = 0.13), whereas children born after unstimulated IVF had no increased risks compared with the SLBR. Higher Caesarean rate after IVF was mainly associated with higher maternal age., Conclusion: Singletons in the Bern IVF Cohort do not show less favourable perinatal outcomes. Gonadotrophin stimulation seems to have an effect, because lower risks were associated with unstimulated IVF., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Excess mortality quantifies the overall mortality impact of a pandemic. Mortality data have been accessible for many countries in recent decades, but few continuous data have been available for longer periods., Objective: To assess the historical dimension of the COVID-19 pandemic in 2020 for 3 countries with reliable death count data over an uninterrupted span of more than 100 years., Design: Observational study., Setting: Switzerland, Sweden, and Spain, which were militarily neutral and not involved in combat during either world war and have not been affected by significant changes in their territory since the end of the 19th century., Participants: Complete populations of these 3 countries., Measurements: Continuous series of recorded deaths (from all causes) by month from the earliest available year (1877 for Switzerland, 1851 for Sweden, and 1908 for Spain) were jointly modeled with annual age group-specific death and total population counts using negative binomial and multinomial models, which accounted for temporal trends and seasonal variability of prepandemic years. The aim was to estimate the expected number of deaths in a pandemic year for a nonpandemic scenario and the difference in observed and expected deaths aggregated over the year., Results: In 2020, the number of excess deaths recorded per 100 000 persons was 100 (95% credible interval [CrI], 60 to 135) for Switzerland, 75 (CrI, 40 to 105) for Sweden, and 155 (CrI, 110 to 195) for Spain. In 1918, excess mortality was 6 to 7 times higher. In all 3 countries, the peaks of monthly excess mortality in 2020 were greater than most monthly excess mortality since 1918, including many peaks due to seasonal influenza and heat waves during that period., Limitation: Historical vital statistics might be affected by minor completeness issues before the beginning of the 20th century., Conclusion: In 2020, the COVID-19 pandemic led to the second-largest infection-related mortality disaster in Switzerland, Sweden, and Spain since the beginning of the 20th century., Primary Funding Source: Foundation for Research in Science and the Humanities at the University of Zurich, Swiss National Science Foundation, and National Institute of Allergy and Infectious Diseases.

Colorectal cancer is among the leading causes of cancer-associated deaths worldwide. Treatment failure and tumor recurrence due to survival of therapy-resistant cancer stem/initiating cells represent major clinical issues to overcome. In this study, we identified lysine methyltransferase 9 (KMT9), an obligate heterodimer composed of KMT9α and KMT9β that monomethylates histone H4 at lysine 12 (H4K12me1), as an important regulator in colorectal tumorigenesis. KMT9α and KMT9β were overexpressed in colorectal cancer and colocalized with H4K12me1 at promoters of target genes involved in the regulation of proliferation. Ablation of KMT9α drastically reduced colorectal tumorigenesis in mice and prevented the growth of murine as well as human patient-derived tumor organoids. Moreover, loss of KMT9α impaired the maintenance and function of colorectal cancer stem/initiating cells and induced apoptosis specifically in this cellular compartment. Together, these data suggest that KMT9 is an important regulator of colorectal carcinogenesis, identifying KMT9 as a promising therapeutic target for the treatment of colorectal cancer. SIGNIFICANCE: The H4K12 methyltransferase KMT9 regulates tumor cell proliferation and stemness in colorectal cancer, indicating that targeting KMT9 could be a useful approach for preventing and treating this disease., (©2021 American Association for Cancer Research.)

In manufacturing companies, cognitive processing is required from assembly workers to perform correct and timely assembly of complex products, often with varied specifications and high quality demands. This paper explores assembly operators' perceptions of cognitive/mental workload to provide a holistic understanding of the work conditions that affect cognitive demands and performance. While the physical loading aspects of assembly work are well known, most empirical literature dealing with cognitive/mental loading in manufacturing tends to examine a few particular aspects, rather than address the issue with a holistic system view. This semi-structured interview study, involving 50 industrial assembly operators from three Swedish companies, explores how assemblers perceive that their cognitive performance and well-being is influenced by a wide variety of factors within the context of mechanical product assembly. The interview transcripts were analysed using a priori coding, followed by bottom-up Thematic Analysis. The results indicate that a variety of systemic effects on assemblers' cognitive performance can be classified as job demands or resources. Quite often, the absence of a resource mirrors a related demand, and "good assembly conditions", as described by the interviewees, often re-frame demands as desirable challenges that foster motivation and positive feelings towards the work. The identified demands and resources stem from task design, timing, physical loading, intrinsic and extrinsic motivators, social teamwork and the product's "interface" design. Despite organisational differences and conditions between the three companies that took part in the study, the results are largely consistent.

Corrective surgery remains a definitive treatment for adult spinal deformity, improving pain and disability. With these cases, instrumentation to the pelvis with iliac fixation is recommended. Whether iliac or S2-Alar-Iliac (S2AI) trajectories are used, sacroiliac joint pain and long-term sacroilitis can be common after long-fusion constructs.1-3 Sacroiliac fusion with triangular titanium implants during fusion can reduce back pain associated with sacroiliac joint degeneration,3 provides reduction in sacroiliac joint motion and stress when added to S2AI screws, and potentially enhances mechanical stability of fusion constructs.4 Here, we present a technique for placing triangular titanium sacroiliac implants (iFuse BedrockTM; SI-BONE Inc, Santa Clara, California) alongside S2AI screws using a robotic platform (Mazor X; Medtronic Sofamor Danek, Medtronic Inc, Dublin, Ireland). Navigated robotics allows reduction in human error with implant placement, and potentially decreased operative time/fluoroscopy.5-7 Key surgical steps include placement of K wires for S2AI and bilateral SI-implants, tapping, replacing SI-implant K wires with guide pins, placing S2AI screws, and finally placing the SI-implant. Final placement is verified with intraoperative fluoroscopy. The patient described is a 61-yr-old woman with worsening adult degenerative scoliosis, lower back pain, left leg radicular pain, and mild right leg pain who failed conservative treatment. Examination revealed diminished strength in both legs. Imaging was significant for moderate sigmoid scoliosis, discogenic disease, and osteoarthritis at all levels. She consented to undergo corrective surgery. Postoperatively, the patient experienced resolution of her leg weakness and pain. Imaging demonstrated appropriate positioning of hardware. Prospective studies on the efficacy of the SI-implant are underway., (© Congress of Neurological Surgeons 2021.)