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Background: Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews.Methods: We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle-ear immittance, and recording of otoacoustic emissions.Results: Two frame-shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant.Conclusions: The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin, whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations. [ABSTRACT FROM AUTHOR]

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).)