Large Series Research Articles

Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes.

Transition of cytosine to thymine in CpG dinucleotides is the most frequent type of mutation in cancer. This increased mutability is commonly attributed to the spontaneous deamination of 5-methylcytosine (5mC), which is normally repaired by the base-excision repair (BER) pathway. However, the contribution of 5mC deamination in the increasing diversity of cancer mutational signatures remains poorly explored. We integrate mutational signatures analysis in a large series of tumor whole genomes with lineage-specific epigenomic data to draw a detailed view of 5mC deamination in cancer. We uncover tumor type-specific patterns of 5mC deamination signatures in CpG and non-CpG contexts. We demonstrate that the BER glycosylase MBD4 preferentially binds to active chromatin and early replicating DNA, which correlates with lower mutational burden in these domains. We validate our findings by modeling BER deficiencies in isogenic cell models. Here, we establish MBD4 as the main actor responsible for 5mC deamination repair in humans.

Low Success Rate of Closed Reductions when Treating Dislocations after Reverse Shoulder Arthroplasty: A Study by the ASES Complications of RSA Multicenter Research Group.

Postoperative dislocation is a known complication following reverse shoulder arthroplasty (RSA), but treatment patterns and outcomes remain unclear. The purpose of this study was to identify treatment patterns, rate of successful closed reductions, and factors associated with unsuccessful closed reductions for dislocations after RSA in a large multicenter patient cohort. A multicenter retrospective review was performed for patients receiving primary or revision RSA from June 2013 to May 2019 across fifteen institutions in the United States. Patients that sustained a postoperative shoulder dislocation (defined as complete loss of articulation between the humeral component and glenosphere confirmed on imaging) with a minimum of 3-month follow-up were included. The time from surgery to dislocation, nature of the dislocation, complications associated with the dislocation, initial treatment, success of closed reduction, recurrent dislocations, and subsequent treatments including revision procedures, were recorded. Univariate analysis was performed to identify patient factors associated with failure of an initial closed reduction attempt. A cumulative postoperative dislocation incidence of 2.1% (n=138) was observed out of 6,621 patients undergoing RSA. The median time to dislocation was 7 weeks (interquartile range = 33 weeks), with 61.6% (n=85) occurring within the first 90 days after surgery. Initial treatment consisted of closed reduction (n=87, 63.0%), open reduction (n=1, 0.7%), revision arthroplasty (n=43, 31.2%), or benign neglect (n=7, 5.1%). Those treated without an initial closed reduction had higher incidence of associated complications (45.1% vs. 14.9%). Among patients initially treated with a closed reduction, 27 (31.0%) were successful (required no further interventions), 15 (17.2%) subsequently required a revision procedure, and 43 (49.4%) sustained an additional dislocation. The only patient or surgical factor associated with an unsuccessful closed reduction was increased BMI (31.8±6 vs. 28.9±5.2, P=0.02). Of the 43 patients that sustained an additional dislocation, 10 received another closed reduction and 30 received revision surgery. Among the 10 patients that received a second closed reduction, 5 remained stable (50.0%). Overall, 92 patients (66.7%) required a revision arthroplasty procedure during the study period, whereas 22 (22.5%) required multiple revision procedures. Ultimately, 18 patients (13.0%) remained unstable (benign neglect) at final follow-up. In this large multicenter series of postoperative dislocations following RSA, a closed reduction was initially attempted in the majority of patients, but only about one-third were successful and required no further intervention. Unsuccessful closed reductions were associated with higher patient BMI. Revision surgery for dislocations was complicated by a high rate of recurrent dislocations and re-revision surgery.

BN SO30 - One hundred consecutive Laparoscopic Heller's Cardiomyotomy & Fundoplication – a personal series

Abstract Background Oesophageal Achalasia (OA) is an uncommon primary oesophageal motility disorder, characterised by the loss of inhibitory neurons in the oesophageal myenteric plexus. The primary goal of treating OA is to alleviate dysphagia caused by the functional obstruction of the distal oesophagus due to the inability of the lower oesophageal sphincter (LOS) to relax appropriately after swallowing. Heller's cardiomyotomy (HCM) remains a standard treatment for OA. The aim of this study was to assess the symptomatic improvement and post-operative outcomes following HCM with fundoplication at our centre. Method All patients underwent HCM through laparoscopic blunt muscle separation technique, between January 2005 and March 2024, by a single surgeon. Retrospective review of electronic and compiled paper patient records were analysed to assess patient demographics, preoperative symptoms, operative details, length of stay (LOS), complications, post-operative symptoms, gastroscopy and pneumatic dilation (PD) as well as revisional surgery. Primary outcomes assessed were binary changes in key symptoms of weight loss, dysphagia, retrosternal pain and regurgitation. Comparison of pre and post-operative outcomes were performed using paired t-test. A p-value of <0.05 was considered statistically significant. Results 100 procedures involving 99 patients (average age 50 years, 43% female), 1 conversion to open and 1 revision at 3 years. ASA grades were 1 (27%), 2 (58%), and 3 (15%). Median LOS was one day, median follow-up 99 months. Post-operatively; weight loss persisted in 11% of patients from 48%, dysphagia reduced from 98% to 42%, retrosternal chest pain from 39% to 20% and regurgitation from 57% to 24% (all p<0.05). 2 patients required (PD) ≤30 days (CD≥3). 36 patients underwent PD at median of 13 months, 20 needed repeat PD. None of the patients developed cancer. Conclusion As demonstrated in this large series of 100 consecutive patients, HCM remains one of the best treatment modalities for OA. Key symptoms of OA significantly reduced following HCM. Our technique avoided the use of energy devices, ensured a short hospital stay and durable symptom improvement, lends support to its continued application in managing this condition.

The efficacy of high pressure liquid chromatography (HPLC) in detecting congenital glycosylation disorders (CDG)

Abstract Objectives Congenital disorders of glycosylation (CDG) are a family of rare inherited metabolic disorders. This study aimed to examine the carbohydrate-deficient transferrin (CDT) screening results of 1,328 patients with suspected CDG by using transferrin- high pressure liquid chromatography (Tf- HPLC) method and to evaluate the performance of the method as a reference diagnostic tool. Methods Relative CDT levels (CDT concentrations expressed as percent of total transferrin) were determined in serum samples by HPLC. The method sensitivity, specificity and positive predictive value (PPV) were further calculated. Results Abnormal transferrin isoform profile consistent with CDG Type-I and CDG Type-II were determined in 50 cases; in 44 cases asiolo-Tf (7.63 ± 5.44 %) and disialo-Tf (36.29 ± 9.04 %), in six cases monosialo-Tf (3.95 ± 0.95 %) and trisialo-Tf (25.05 ± 4.46 %) were determined and decreased tetrasialo-Tf (49.75 ± 11.59 %) was identified in all cases. Two cases having abnormal CDT pattern were molecularly diagnosed with hereditary fructose intolerance and galactosemia and 11 cases diagnosed with CDG based on clinical and molecular analysis showed a normal pattern. The sensitivity, specificity and positive predictive values of Tf-HPLC method were 81.96 %, 99% and 96 %, respectively. Conclusions Tf-HPLC is a useful, highly sensitive, cost-advantageous and reliable method for the detection and preliminary diagnosis of CDG for laboratories working with large sample series.

Abstract 4136984: Low Occurence of Fetal Extranodal Findings and AV Interval Prolongation in Prospectively Followed High Titer Anti-Ro Pregnancies

. Background: Third-degree atrioventricular block (AVB) is the most common manifestation of Anti-Ro antibody associated fetal cardiac disease. Extranodal findings of isolated cardiac echogenicity, valvulitis with insufficiency and AV interval prolongation have been reported but not described in large prospective series. Aims: To report the occurrence and outcomes of extranodal findings in subjects followed prospectively since 2020 in STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV block Likely to Occur Quickly) and the Registry for Neonatal Lupus (RNL). Methods: We reviewed fetal echo reports from pregnant STOP BLOQ and RNL Anti-Ro antibody subjects. Pregnancies with high (>1000 EU for anti-Ro52 or 60) antibody titers measured in a core research lab underwent surveillance with home fetal heart rate monitoring (FHRM) 3x/day and weekly or bi-weekly fetal echos from 17- 26 gestational weeks. Low titer subjects underwent echo or no surveillance based on local site protocol. We evaluated cardiac function, effusions, cardiac echogenicity and its location, any tricuspid (TV) or mitral (MV) insufficiency trivial or >trivial) and AV conduction times (<150, 150-170 or >170 ms) Results: Echo reports were available in 622 prospectively followed pregnancies (376 high (40/376 with a previously affected child) and 246 low-titer pregnancies. All had subjectively normal ventricular function and none had effusions. Seven fetuses, 2 low and 5 high titer at 19 (range 16.7-21.7) weeks demonstrated cardiac echogenicity (n=6), AV or semilunar valve insufficiency (n=2) or AV interval 150-170 ms (n=2) (Table). Subjects 1 and 2, both high titer and treated with prophylactic Plaquenil (400 mg/d before 10 gestational weeks), had prior fetal AVB. Subject #1 had normal AV conduction but MV and TV echogenicity and moderate insufficiency of both valves which resolved in days after IVIG and dexamethasone (dex) treatment, but 3° AVB developed at 19 weeks after dex wean. Subjects 2-7 received no treatment and extranodal findings did not progress to cardiac dysfunction or AVB. During the same time period, 10 high titer subjects developed 2° or 3° AVB. Conclusion: Anti-Ro associated extranodal findings are rare, occurring in 1% of pregnancies overall and in 5% of pregnancies with a previously affected child. Unlike AVB, extranodal findings can occur in low titer pregnancies. The role of treatment for isolated extranodal findings in the absence of cardiac dysfunction is unclear.

S‐Aryl Substitution Enhances Acidity of the 1,2,4‐Triazolium Scaffold

AbstractThe 1,2,4‐triazolium scaffold in asymmetric organocatalysis results in remarkable rate accelerations, with reactions typically occurring via N‐heterocyclic carbene (NHC) intermediates. Although the most acidic NHC pre‐catalyst class, there remains scope for further increases in acidity particularly for aqueous organocatalysis applications. The acidity‐enhancing effects of thio‐substituents on carbon acidity are well‐documented but not explored in the 1,2,4‐triazolium scaffold. Herein, we report the synthesis of a large series of N, N‐dialkyl‐C(3)‐S‐aryltriazolium ions and quantitative kinetic evaluation of C(5)‐H acidity. The direct attachment of S‐aryl substituents to the triazolium heterocycle results in substantial increases in protofugalities (kinetic acidities) with second order rate constants (kDO) for C(5)‐H deprotonation by DO− base that are 2.9–60.3 fold higher than for reference 1,4‐dimethyl‐1,2,4‐triazolium iodide in D2O solution. Protofugalities for the N, N‐dialkyl‐C(3)‐S‐aryltriazolium series are similar to commonly used bicyclic N‐aryl‐1,2,4‐triazolium organocatalysts despite having two electron donating N‐alkyl substituents. This highlights the future potential of this NHC design which could enable the introduction of two chiral alkyl substituents close to the C(5) carbenic position with pre‐catalyst acidity controlled by distal C(3)‐S‐aryl substitution. Detailed X‐ray structural data‐protofugality correlations enabled evaluation of the S‐aryl substituent effect origins. C(5)‐H pKa values (16.9–18.6) were calculated by utilisation of experimental protofugalities.

NCOG-21. ADJUVANT RADIATION THERAPY IN ATYPICAL MENINGIOMA TREATMENT DOES NOT IMPROVE PROGRESSION FREE SURVIVAL OR OVERALL SURVIVAL: A RETROSPECTIVE COHORT STUDY

Abstract Treatment of atypical meningiomas (AMs) presents a challenge due to their aggressive nature and tendency to recur. While there is clear evidence for the role of surgical resection of AMs, the use of adjuvant radiation therapy (ART) is a topic of ongoing debate. The aim of this study is to explore the impact of ART following surgical resection of AMs. The primary outcomes of interest are progression free survival (PFS) and overall survival (OS). Records were reviewed for all patients treated for Ams at our institution between January 1, 2014 and January 1, 2024. Patients were grouped into two cohorts, those who were initially treated with surgical resection only and those who also received adjuvant RT. PFS and OS were compared between the two groups using Kaplan Meier curves and Log Rank test. Additionally, multivariable cox proportional hazard models were used to adjust for age, MIB, and resection Simpson grading. There were 76 patients who were initially treated with surgery only and 23 patients who had surgery and ART. No significant difference in PFS or OS was observed between the groups (p=0.3522 and p=0.3636, respectively); including after adjusting for age, MIB, and Simpson grading (HR= 1.55 [0.64-3.76], p= 0.330; and HR = 0.95 [0.31-2.93] p= 0.934, respectively). On multivariate analysis, MIB >10 was associated with a significant difference in PFS (HR=2.76 [1.15-6.59], p=0.023). With ART, PFS was 91% at 12 and 60% at 36 months (versus 89% and 57%, respectively, with surgery only). OS was 95% at 12 and 88% at 36 months (versus 91% and 85%, respectively, with surgery only). In this series, ART was not observed to significantly improve PFS or OS compared to surgery alone. Larger series are needed to determine if there is a subset of patients who benefit from ART.

Intracranial angioleiomyoma mimicking meningioma: an uncommon tumor with favorable outcome and frequent GJA4 mutation.

Intracranial angioleiomyoma (IALM) is a rare neoplasm mimicking meningioma. We aimed to explore the clinical and molecular characteristics of IALMs. We included 40 patients with IALMs who had tumor resection at our center from 2009 to 2022. Clinicopathological and radiological characteristics were extracted and analyzed thoroughly. GJA4 mutation status was detected and correlated with clinical characteristics. IALMs accounted for about 10% of all angioleiomyoma and had a significant male predominance compared to extracranial angioleiomyoma (p=0.04). However, there was no age difference between extracranial angioleiomyomas and IALMs. In our IALM cohort, orbital (35%) were the most common tumor location, followed by tentorium (25.0%), cavernous sinuous (17.5%). Vision decrease, diplopia and exophthalmos (40%) were the most common symptom. The radiological characteristics of ILAMs were similar to meningiomas; 20 patients (57.1%) in our cohort were misdiagnosed as meningioma preoperatively. Gross total resection was achieved in all patients. The postoperative pathology showed median Ki-67 index was 1% (range: 0-10%). Vision improvement or exophthalmos relief was achieved in 12 of 16 patients (75.0%). During the long-term follow-up (mean 70.3 months, range 30 - 128 months), no patient experienced tumor recurrence or died of tumor progression, indicating that IALM was clinically benign. GJA4 mutation (p. Gly41Cys) was detected in 17 (42.5%) patients. Of note, the correlations analysis revealed that orbital and cavernous sinus areas (64.7%) were the leading location that harbor GJA4 mutations. Tumors with mutant GJA4 were associated with positive progesterone receptor (PR) expression (p=0.02).This first large case series demonstrated that IALM predominantly affected males, was located in the cavernous sinus and orbital areas, and often manifested visual impairment and diplopia. IALM had favorable outcome. Notably, IALMs frequently exhibited a GJA4 mutation, which was linked to the cavernous sinus and orbital locations, as well as PR expression.

Is intercalary frozen autograft augmented with intramedullary cement and bridging plates fixation a durable reconstruction?

AimsWe analysed the survival, complications, and function of frozen autograft augmented with intramedullary cement and bridging plates fixation for intercalary bone defect reconstruction in primary bone sarcomas.Patients and MethodsA retrospective cohort study was conducted on 72 patients with primary bone sarcomas (34 males, 38 females) between January 2016 and June 2023. The average age was 22.0 ± 13.6 years (6 to 61 years) and the pathological type included osteosarcoma (55), followed by adamantinoma (5), Ewing’s sarcoma (4), undifferentiated pleomorphic sarcoma (4), chondrosarcoma (3), and malignant tenosynovial giant cell tumor (1). The oncological outcomes included local control, metastasis, progression-free survival and overall survival. The functional outcomes were evaluated by the Musculoskeletal Tumor Society Score (MSTS-93), the Toronto Extremity Salvage Score (TESS), and the motion of the joint.ResultsThe mean follow-up time was 50.0 ± 27.4 months (12 to 99 months). 10 patients died of the disease, 9 patients were alive with disease and 53 patients were alive with no evidence of disease. The average 5-year overall survival of autograft was 85.8% (95% CI, 72.1-93.1%). The average MSTS-93 score was 96% ( 67–100%) and the average TESS score was 98% (74–100%). Twenty-four patients (33.3%) had at least one complication in the follow-up period. The most common complications were nonunion (9.7%, 7/72) and local recurrence (9.7%, 7/72), followed by leg length discrepancy (6.9%, 5/72), infection (5.6%, 4/72), implant failure (4.2%, 3/72), delayed union (2.8%, 2/72), and graft fractures (1.4%, 1/72). Tumor site was an independent risk factor for bone nonunion (OR, 22.23; p = 0.006).ConclusionsWe presented a large technique series for preventing autograft-related complications (especially for autograft fractures) of intercalary frozen autograft reconstruction. This method showed promising functional outcomes and provided durable reconstruction.Level of evidencelevel IV therapeutic study.

Safety and Efficacy of Dalbavancin in Real Life: Retrospective Analysis of a Large Monocentric Case Series of Patients Treated for Skin/Soft Tissue and Other Difficult-to-Treat Infections

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%—91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5–17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections.

Biphenotypic Sinonasal Sarcoma: Literature Review of a Peculiar Pathological Entity—The Neurosurgical Point of View

Background: Biphenotypic sinonasal sarcoma (BSNS) is a low-grade tumor of the sinonasal tract with frequent extension to the orbit and skull base. Due to its rare incidence and recent histopathological and molecular characterization, little data are available in regard to its natural history, treatment and surveillance protocol. Methods: A comprehensive literature review in Embase online electronic databases on BSNS was made. The analyzed factors included the patients’ sex and age, presenting symptoms and signs, anatomical origin and pattern of growth of the tumor, immunohistochemical and molecular features, time to treatment, type of treatment, surgical approach, extent of resection, peri- and post-operative complications, adjuvant therapies, clinical outcome, recurrence and overall survival rates. Results: This literature review involved 34 studies for an overall series of 149 cases of BSNS. The female (66.9%) and middle-aged populations (median 54.88 years old) were mainly affected. The most frequent clinical onset was nasal obstruction (81%), followed by facial discomfort (44%), epistaxis (15.5%) and ocular impairment (14.3%). Ethmoid sinus (67.8%) and nasal cavity (45.4%) were the most common anatomical site of tumor origin, while an extension to the orbit and skull base was registered in 28.7% and 24.5% of cases. Surgery was the main treatment, especially in the form of endoscopic endonasal approach (56.9%), and allowed for gross total resection in 79% of cases. The recurrence rate was 26.2%; three cases of tumor-related death were reported. Median follow-up was 4.6 years. Conclusions: Biphenotypic sinonasal sarcoma is a rare and unique tumoral entity in terms of biological and clinical behavior. Based on the current knowledge, surgery plays the leading role in treatment, accounting for gross total tumor resection in most cases, allowing for clinical symptom and sign resolution and presenting a low rate of perioperative complications. The type of approach and the aim of surgery should be assessed case by case according to patient and pathology features and the surgeon’s experience, as well as the aim of the treatment. Further studies including large surgical series and with long follow-up are required to define prognostic factors and guidelines of treatment for this peculiar pathological entity.

Long‐Channel Effects in Randomly Oriented Carbon Nanotube Thin Film Transistors

AbstractCarbon nanotube (CNT) thin film transistors (TFTs) have demonstrated great potential for application in highly sensitive biosensors and large‐area electronics. However, research on the electrical behavior of long‐channel CNT TFTs is lacking; thus, the purposeful improvement in the performance of biosensors or circuits is difficult. In this study, the electrical transport characteristics of ionic‐liquid‐gate CNT TFTs with channel lengths (Lch) ranging from 10 to 400 µm are investigated. The CNT TFTs present classical drift‐diffusion transport at on‐state with a carrier mobility of around 27 cm2 V−1 s−1. In the subthreshold region of the CNT TFTs, an abnormal Lch‐dependent subthreshold swing (SS) relationship, named as the long‐channel effect (LCE)is observed, where SS worsens with increasing Lch. The existence of the junctions between the CNTs results in an unconventional density of states for carriers and a large series resistance for sharing the gate voltage; this dominates the abnormal scaling behavior in the subthreshold region by degrading the electrostatic integrity. The discovery of the abnormal LCE can aid in the construction of device models and purposefully improve the performance of CNT TFTs for biosensors and other large‐scale electronic applications.

Antithrombotic Agents After Free Tissue Transfer in the Pediatric and Adolescent Population.

Even for the experienced microsurgeon, free tissue transfer in pediatric patients is challenging, and large patient series remain scarce in the literature. Moreover, the added value of antithrombotic agents in pediatric free tissue transfer remains unclear. We conducted a retrospective outcome analysis of pediatric free tissue transfer with respect to postoperative antithrombotic treatment at our tertiary academic center. All patients aged 0 to 18 years who underwent free tissue transfer from 1998 to 2022 were included in the study. Seventy patients received 73 free tissue transfers. The most common indications were facial paralysis, trauma, and tumor (49.3%, 21.9%, and 20.5%, respectively). The most common recipient sites were the head and neck (56.1%) and lower extremity (32.8%). We observed a flap revision rate of 12.5% of the cases and one flap loss (1.4%). 58.9% of the population received post-operative antithrombotic agents. The rate of flap revision surgery was similar (11.6% and 10.0%, respectively), with and without antithrombotic treatment (p>0.05). There were no major bleeding complications or deep vein thrombosis. The antithrombotic treatment did not seem to affect the flap revision rate or the bleeding complications in our cohort. Hence, the data do not support the routine administration of antithrombotic treatment in pediatric free flap reconstruction. However, these findings should be solidified in prospective randomized trials.

Minimizing prostate diffusion weighted MRI examination time through deep learning reconstruction

PurposeTo study the diagnostic image quality of high b-value diffusion weighted images (DWI) derived from standard and variably reduced datasets reconstructed with a commercially available deep learning reconstruction (DLR) algorithm. Materials and methodsThis was a retrospective study of 52 patients undergoing conventional prostate MRI with raw image data reconstructed using both conventional 2D Cartesian and DLR algorithms. Simulated shortened DWI acquisition times were performed by reconstructing images using DLR datasets harboring a reduced number of excitations (NEX). Two radiologists independently evaluated the image quality using a 4-point Likert scale. Signal-to-noise ratio (SNR) analysis was performed for the entire cohort and a subset of patients identified as having clinically significant prostate cancer identified at MRI, and later confirmed by pathology. ResultsRadiologists perceived less image noise for both restricted and large field of view (FOV) standard NEX dataset DLR diffusion images compared to conventionally reconstructed images with good interreader agreement. Diagnostic image quality was maintained for all DLR images using variably reduced NEX compared to conventionally reconstructed images employing the standard NEX. Improved signal to noise was observed for the restricted FOV DLR images compared to conventional reconstruction using standard NEX. DLR diffusion images derived from reduced NEX datasets translated to time reductions of up to 68 % and 39 % for the restricted and large FOV series acquisitions, respectively. ConclusionDLR of diffusion weighted images can reduce image noise at standard NEX and potentially reduce prostate MRI exam time when utilizing reduced NEX datasets without sacrificing diagnostic image quality.

IFSO Bariatric Endoscopy Committee Evidence-Based Review and Position Statement on Endoscopic Sleeve Gastroplasty for Obesity Management.

Obesity is a significant global health issue. Metabolic and bariatric surgery (MBS) is the gold standard in the treatment of obesity due to its proven effectiveness and safety in the short and long term. However, MBS is not suitable for all patients. Some individuals are at high surgical risk or refuse surgical treatment, while others do not meet the criteria for MBS despite having obesity-related comorbidities. This gap has driven the development of endoscopic solutions like endoscopic sleeve gastroplasty (ESG), which offers a less invasive alternative that preserves organ function and reduces risks. A recent IFSO International Delphi consensus study highlighted that multidisciplinary experts agree on the utility of ESG for managing obesity in patients with class I and II obesity and for those with class III obesity who do not wish to pursue or qualify for MBS. This IFSO Bariatric Endoscopy Committee position statement aims to augment these consensus statements by providing a comprehensive systematic review of the evidence and delivering an evidence-based position on the value of ESG within the spectrum of obesity management. A comprehensive systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Cochrane guidelines. Systematic Review: The systematic review included 44 articles encompassing 15,714 patients receiving ESG. The studies varied from large case series to cohort studies and a randomized controlled trial (RCT). The mean baseline BMI was 37.56kg/m2. The review focused on weight loss outcomes and safety data. Time point Mean %EWL Mean %TBWL 6months 48.04 15.66 12months 53.09 17.56 18months 57.98 16.25 24months 46.57 15.2 36months 53.18 14.07 60months 45.3 15.9 These results demonstrate significant weight loss following ESG. The pooled serious adverse event (SAE) rate was 1.25%. This low rate of SAEs indicates that ESG is a relatively safe procedure. The quality of evidence from the included observational studies was assessed as very low, primarily due to the inherent limitations associated with observational study designs, such as potential biases and lack of randomization. In contrast, the quality of evidence from the single randomized controlled trial was rated as MODERATE, reflecting a more robust study design that provides a higher level of evidence despite some limitations. The IFSO Bariatric Endoscopy Committee, after conducting a comprehensive systematic review and meta-analysis, endorses endoscopic sleeve gastroplasty (ESG) as an effective and valuable treatment for obesity. ESG is particularly beneficial for patients with class I and II obesity, as well as for those with class III obesity who are not suitable candidates for metabolic bariatric surgery. ESG provides significant weight loss outcomes and demonstrates a favorable safety profile with a low rate of serious adverse events. Despite the limitations of the included observational studies, the randomized controlled trial included in the analysis reinforces the efficacy and safety of ESG and provides an evidence-based foundation for the position statement. Thus, the IFSO position statement supports and provides an evidence base for the role of ESG within the broader spectrum of obesity management.

Surgical Management of Thoracic Dorsal Arachnoid Webs: A 10-Year Single-Institution Experience

ObjectiveThoracic dorsal arachnoid webs are intradural membranes that may cause obstruction of CSF flow and spinal cord compression. While well-recognized, they are rare and there is a paucity of long-term data on their natural history and prognosis. We reviewed radiographic features, surgical indications, and pathologic specimens of patients diagnosed with focal thoracic dorsal arachnoid webs. MethodsA radiology database and surgical case logs were queried for thoracic arachnoid webs at a single hospital system for a ten-year period. A retrospective chart review was performed on identified cases. ResultsWe identified 127 patients with dorsal thoracic arachnoid webs. Arachnoid webs were radiographically classified into three morphologic types: Type 1 (54%) causing spinal cord deformity only, Type 2 (32%) producing cord deformity with myelomalacia, and Type 3 (14%) with cord deformity, myelomalacia, and syringomyelia. These arachnoid webs were commonly centered at the upper thoracic T4 segmental level. Forty-one cases (32%) required surgery, generally for thoracic myelopathy with gait instability (46%) and lower extremity numbness and pain (39%). In patients who underwent surgery, 79% experienced symptomatic improvement and 21% remained stable, after an average of 21 months follow-up evaluation. Surgical pathology revealed fibrous connective tissue (100%) with calcifications (26%) or inflammation (7%). ConclusionsThe majority in a large series of patients with dorsal arachnoid webs did not undergo surgical intervention, but those with myelomalacia and syrinx experienced radiographic and clinical deterioration without surgery. Surgery to treat symptomatic arachnoid webs results in significant clinical improvement with low surgical morbidity.

Outcomes After Palliative Radiotherapy in Patients with Symptomatic Locoregionally Advanced Breast Cancer.

Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiotherapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined. This is a single-institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were analyzed. 164 patients with a median age of 57 years were analyzed with a median follow-up time of 4.97 months. 86% had distant metastases. The most common presenting symptom was pain (87%), followed by ulcerating or fungating lesion (76%) and discharge (45%). The median cumulative biologically effective dose to the gross tumor volume (BEDGTV) was 69 Gy. The 1-year OS and LC rates were 37% and 63%, respectively. Eighty-one percent experienced improvement in symptoms within 3 months after RT, the odds of which increased per Gy BEDGTV (OR 1.029, p=0.003). Acute toxicities were associated with number of fractions and BEDGTV (both p<.001), but not with concurrent systemic therapy nor reirradiation (both p>.05). Trends in pain scores showed a significant change in pain trajectory that was sustained during the first year after RT. OS and LC were not different among patients who received 1 vs 2-10 vs >10 fractions, and between ≤70 vs >70 Gy BEDGTV. In this large series of patients with SLABC, palliative RT was effective at relieving locoregional symptoms with acceptable toxicity, with the likelihood of symptom improvement associated with radiation dose. Survival of these patients remains poor, highlighting the importance of palliative care strategies that minimize overall symptom burden while maximizing quality of life.

Characteristics of Chinese breast cancer patients with double heterozygosity for BRCA1 and BRCA2 germline pathogenic variants.

Despite of very rare, breast cancer patients with double heterozygosity (DH) variants in BRCA1 and BRCA2 genes have been identified in other ethnic groups and seem to be associated with distinctive phenotypes. However, little is known about the frequency and clinical characteristics of Chinese breast cancer patients with BRCA1/2 DH variants. Four hundred and eleven unrelated patients with BRCA1 or BRCA2 pathogenic variants (PVs) were identified in a large series of unselected breast cancer patients. Another two siblings with metachronous bilateral breast cancer were referred for genetic counseling, after which BRCA1/2 DH variants were detected. Four unrelated breast cancer patients with BRCA1/2 DH were identified in the cohort of 411 patients with BRCA1 or BRCA2 PVs, the frequency of BRCA1/2 DH was 0.97%. In total, six BRCA1/2 DH patients from five families were found in this study. In two families, the hereditary pattern of DH was speculated to have originated from both sides of the family. BRCA1/2 DH patients were more likely to have a family history of breast cancer than patients with a BRCA1 (100% vs. 29.2%, P = 0.004) or BRCA2 (100% vs. 29.6%, P = 0.004) single PV. BRCA1/2 DH patients were more likely to be triple-negative breast tumors than patients with single BRCA2 PVs (66.7% vs. 14.1%, P = 0.020), which was comparable to the findings in patients with single BRCA1 PVs (66.7% vs. 56.9%, P = 1.00). Chinese patients with BRCA1/2 DH exhibit a high percentage of family history of breast cancer. The tumor pathological features of BRCA1/2 DH carriers are similar to those of BRCA1 PV carriers.

Comparison of insulinoma-associated protein 1 (INSM1) with traditional neuroendocrine markers in gastrointestinal and pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs)

The traditional diagnostic markers for mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are synaptophysin (SYP), chromogranin A (CHGA) and CD56. However, there is still a lack of a large series of article focused on the expression of insulinoma-associated protein 1 (INSM1) in gastrointestinal and pancreatic MiNENs. This study compared the expression of INSM1 and traditional neuroendocrine markers in MiNENs. In this study, we collected 46 cases of gastrointestinal and pancreatic MiNENs and performed immunohistochemical staining for INSM1, SYP, CHGA, and CD56. Histologically, the neuroendocrine components of MiNENs were all neuroendocrine carcinomas, with small cell neuroendocrine carcinomas accounting for 15.2% (7/46) and large cell neuroendocrine carcinomas accounting for 84.8% (39/46). With respect to immunohistochemical expression, the overall sensitivity of INSM1 was 80.4% (37/46), which was lower than that of SYP (100%, 46/46), but comparable to that of CHGA (67.4%, 31/46) or CD56 (73.9%, 34/46). The overall specificity of INSM1 was 91.3% (42/46), which was greater than that of SYP (63.0%, 29/46) and CD56 (69.6, 32/46), but was not significantly different from that of CHGA (82.6%, 38/46). The proportion of 3 + staining for SYP (100%, 46/46) was greater than that of INSM1 (71.7, 33/46), while the proportion of 3 + staining for CHGA (10.9, 5/46) or CD56 (21.7, 10/46) was lower than that of INSM1. In conclusion, INSM1 exhibited high sensitivity and specificity in the diagnosis of gastrointestinal and pancreatic MiNENs.

BRIVA-ONE study: 12-month outcomes of brivaracetam monotherapy in clinical practice.

This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. This was a multicenter, retrospective, observational, non-interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first-line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure-free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow-up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. A total of 276 patients were included (48 with BRV as first-line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first-line monotherapy group; 90.4% for conversion-to-monotherapy group). Seizure-freedom rates at 12 months were 77.8% (75% for first-line monotherapy group; 78.4% for conversion-to-monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first-line monotherapy group; 40.4% for conversion-to-monotherapy group). Most AEs were mild-to-moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. BRV was effective and well tolerated both as first-line monotherapy and following conversion to monotherapy in a real-world setting of patients with epilepsy. The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new-generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury).