Citations

Highlights Spino-plastic surgery addresses complex spinal defects using a multidisciplinary approachThe plastic surgeon's role in spinal reconstructive surgery has evolved from reactive to proactive involvement in careVBGs reduce time to spinal fusion without significantly increasing operative time, monitoring, length of stay or transfusions.We discuss the VBGs within the reconstructive ladder, as well as the indications, anatomy and dissection of VBG types.

ABSTRACT In the past two decades, plastic surgeons have advanced to the forefront of spinal surgery, joining orthopedic and neurosurgeons in the multidisciplinary field of spino-plastics. As the global disease burden grows with an increased incidence of spinal pathologies, vascularized bone grafts (VBGs) define the current frontier of spino-plastic surgery. Vascularized bone grafting involves lifting segments of bone with the muscular attachments but without the inclusion of a named vessel. When compared to traditional nonvascular bone grafts and allografts, VBGs have come forward as a favored technique for complex spinal reconstruction due to the unique opportunity to capitalize on the relationship between the tendons and Sharpey's fibers which maintain blood flow to both the bone and muscular segments. This technique ensures robust autologous tissue rearrangement and also takes advantage of the osteoinductive properties of the bone segments, promoting adequate structural support and the perfusion necessary for efficient direct healing and fusion in intricate spine reconstructions. Another one of the many favorable qualities of VBGs is the diversity of sources available to surgeons. The review explores the role of VBGs in enhancing spinal fusion rates and minimizing morbidity compared to traditional approaches. Additionally, a detailed examination of six common VBG sources-the iliac crest, ribs, medial scapula, occiput, spinous processes, and clavicle is included, highlighting each graft's specific techniques and emphasizing the range of options available to spino-plastic surgeons. Highlights Vascularized Bone Grafts (VBGs) have emerged as a favored technique in complex spinal reconstruction.The field of spino-plastic surgery highlights the collaboration between plastic, orthopedic, and neurosurgery.The article outlines the reconstructive ladder for bony defects, with VBGs being a critical addition.Advantages of VBGs include enhanced fusion rates, lower risk of infection, and reduced operative time.Preserving the vascular supply during graft harvest is crucial.Preoperative planning is essential as VBG selection is made on a case-by-case basis.

Accurate staging of nodal involvement in pediatric sarcoma patients is important to determine correct systemic and local therapy, with the goal to reduce subsequent recurrences. However, differences in lymph node staging strategies, definitions, and treatment protocols between the Children’s Oncology Group (COG), European Pediatric Soft Tissue Sarcoma Study Group (EpSSG), and the Cooperative Weichteil Sarkom Studiengruppe (CWS), complicate comparisons. In this article we try to establish internationally recognized recommendations for lymph node assessment and treatment of children and adolescents diagnosed with RMS and NRSTS according to the Consensus Conference Standard Operating Procedure methodology.

AbstractBackgroundHead and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next‐generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC.MethodIn this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases.ResultsThe results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies.ConclusionOur findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases.

7050 Background: The management of Richter transformation (RT) of CLL represents an unmet clinical need. We previously reported modest efficacy of pembrolizumab monotherapy in an initial cohort of patients with RT (Ding, et al, Blood 2017). Here we report updated results of this trial, including an expansion cohort and a combination therapy cohort. Methods: Patients with biopsy proven RT to diffuse large B-cell lymphoma were enrolled and treated with single agent pembrolizumab (200 mg IV Q3W). Patients with progressive disease (PD) or stable disease (SD) after 3 months of pembrolizumab monotherapy were allowed to add a B-cell receptor (BCR) kinase inhibitor. The primary end point was overall response rate (ORR). Results: A total of 26 patients with RT were enrolled (9 in initial cohort and 17 in expansion cohort). The median age was 68.5 years. Ten (38%) patients had del(17p) or TP53 mutation. The median number of prior lines of therapy was 3 (range 1-10). Fifteen (58%) patients had received ibrutinib previously (14 of whom had PD on ibrutinib). With pembrolizumab monotherapy (n=26), the ORR was 23.1%, with 2 (7.7%) complete response (CR), 4 (15.4%) partial response (PR), and 7 (26.9%) SD. Of the 6 patients with confirmed CR or PR, responses occurred after a median of 2 cycles of monotherapy. The median duration of response (DOR) was 3.2 months (95% CI 2.8-NA). The median progression-free survival (PFS) was 2.6 months (95% CI 1.6-3.6). Sixteen patients went on to receive a BCR kinase inhibitor (ibrutinib [n=15], idelalisib [n=1]) in combination with pembrolizumab, after SD or PD on pembrolizumab monotherapy. The ORR to combination therapy was 62.5%, with 4 (25.0%) CR and 6 (37.5%) PR. Of the 10 patients with confirmed CR or PR to combination therapy, responses occurred after a median of 4 cycles of therapy. The median DOR was 4.5 months (95% CI 1.6-NA). The median PFS was 7.6 months (95% CI 2.3-13.3). After a median follow-up of 50.4 (95% CI 34.0-56.0) months, the median overall survival (OS) for all 26 patients with RT was 11.6 months (95% CI 7.5-20.1), and the 2-year OS rate was 27%. Treatment-related adverse events (TRAEs) of any grade occurred in 24 (92%) patients, including anemia (54%), thrombocytopenia (58%), neutropenia (54%), leukopenia (35%), lymphopenia (23%), dyspnea (23%), diarrhea (19%), and nausea (23%). Treatment-related grade 3 or above AEs occurred in 21 (81%) patients, including neutropenia (38%), leukopenia (31%), thrombocytopenia (27%), anemia (15%), febrile neutropenia (12%), and lung infection (12%). Conclusions: This expanded analysis confirmed that pembrolizumab has modest single agent activity in RT. Combination therapy with pembrolizumab and a BCR kinase inhibitor is associated with increased efficacy (ORR >60%), similar to other reports. These results support further investigation of immune checkpoint inhibitor-based combination therapy in RT. Clinical trial information: NCT02332980 .

Importance Neurological manifestations during acute SARS-CoV-2–related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective To assess the association of severe neurological manifestations during a SARS-CoV-2–related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2–related condition. Results Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations ( P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769 ), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047 ), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.