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Background The spleen is one of the most common solid organs injured in blunt abdominal trauma with significant mortality. The management of splenic injury has significantly changed over the last few decades, ranging from certain splenectomies to non-operative management (NOM). Although several retrospective studies have been published on the NOM of minor spleen injuries, few studies have analyzed the results of NOM for high-grade splenic injuries. The pertinent question that we attempt to answer is, "Is it possible to manage extensive splenic injuries non-operatively?". Objectives To study the feasibility of NOM for the American Association for the Surgery of Trauma (AAST) Grade 3, 4, and 5 splenic injuries and to assess the demographic profile and cases for AAST Grade 3, 4, and 5 splenic injuries. Methods and methodology We, retrospectively, studied patients admitted with AAST Grade 3, 4, and 5 splenic injuries from blunt abdominal trauma admitted at the Government Medical College, Thiruvananthapuram, India, between January 2014 and October 2020. Their demographics, grade of splenic injuries, associated injuries, and methods of management were collected, and statistical analysis was done. Results The study included 132 patients with AAST Grade 3, 4, and 5 splenic injuries. Fifty percent of patients had Grade 3 injuries, 39.4% had Grade 4 injuries, and 10.6% were found to have Grade 5 splenic injuries. Grade 3 and 4 injuries were mainly managed non-operatively, while Grade 5 injuries had a failure rate of nearly 65% when managed non-operatively. Additionally, 73.5% of splenic injuries were successfully managed non-operatively. A significant association was noted between the severity of injuries and the need for operative management (p<0.001). Meanwhile, 64.29% of the patients with Grade 5 splenic injuries ended up needing operative management, as opposed to 34.62% in Grade 4 and 12.12% in Grade 3 splenic injuries. Conclusion We suggest that NOM may be undertaken successfully in appropriately designed areas with close observation for hemodynamically stable patients with extra vigilance in the case of the elderly and those with associated injuries. There should be a low threshold for switching to operative management, especially in Grade 5 injuries., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chandran et al.)

Background Retroperitoneal sarcomas (RPS) are rare and complex tumors originating from the retroperitoneal space, an anatomical region nestled behind the abdominal cavity and shielded by the posterior abdominal wall. Late clinical presentation is a hallmark of retroperitoneal sarcomas. The symptoms are often nonspecific, and nodal metastases are rare. Computed tomography (CT) remains the investigation of choice, and a preoperative biopsy is usually not needed. Surgical resection remains the mainstay of treatment, along with adjuvant radiation and chemotherapy. Survival rates are in general poor, even after complete resection. In this study, we attempt to shed some light on the clinicopathological profiling of retroperitoneal sarcomas and their survival outcomes. Objective The objective of this study is to assess the demographic, clinical, and pathological profiling of patients with retroperitoneal sarcoma and to study the survival of patients with retroperitoneal sarcoma. Methodology We conducted a hospital-based retrospective observational study in a tertiary care center in South India between January 2011 and January 2021. We included all patients with histopathologically proven retroperitoneal sarcoma. Metastatic cases and those who underwent chemotherapy or radiation prior to presentation were excluded. Their demographics, pathological reports, and survival were followed up and collected, and statistical analysis was done. Results The study included 16 cases with retroperitoneal sarcomas across the decade in which the data was collected, confirming the rarity of the tumor, out of which more than 40% of patients were above the age of 60. The most common symptom was found to be a bloating sensation in nine patients, followed by abdominal pain in three patients. Seventy-five percent of the patients were found to have a T4 (i.e., a size of more than 15 cm) tumor at presentation. Well-differentiated liposarcoma was found to be the most common pathological variant accounting for 25% of the cases. The mean survival was found to be 8.05 years, which dropped to 5.74 years in Grade 3 tumors. Conclusion Retroperitoneal sarcomas are rare tumors of which liposarcoma is the most common variant. A significant reduction in the mean survival was identified in Grade 3 sarcomas compared to the cumulative survival time of Grade 1 and Grade 2 retroperitoneal sarcomas., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chandran et al.)

We report a case of a patient who had a coronary angioplasty and received heparin, clopidogrel, and ticagrelor on the evening of bilateral total knee arthroplasties performed under combined spinal epidural anesthesia. After a multidisciplinary meeting, the epidural catheter was removed 5 days after the dose of clopidogrel. With the catheter still in place, ticagrelor was continued to prevent stent thrombosis. Removing an epidural catheter in a patient on antiplatelet therapy must be done after a risk-benefit assessment, multidisciplinary collaboration, and stringent neurologic monitoring. The focus should be on prevention of a spinal hematoma, and rapid diagnosis and treatment to optimize the neurologic outcome., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: A randomized trial in glioblastoma patients with methylated-MGMT (m-MGMT) found an improvement in median survival of 16.7 months for combination therapy with temozolomide (TMZ) and lomustine, however the approach remains controversial and relatively under-utilized. Therefore, we sought to determine whether comprehensive genomic analysis can predict which patients would derive large, intermediate, or negligible benefits from the combination compared to single agent chemotherapy., Methods: Comprehensive genomic information from 274 newly diagnosed patients with methylated-MGMT glioblastoma (GBM) was downloaded from TCGA. Mutation and copy number changes were input into a computational biologic model to create an avatar of disease behavior and the malignant phenotypes representing hallmark behavior of cancers. In silico responses to TMZ, lomustine, and combination treatment were biosimulated. Efficacy scores representing the effect of treatment for each treatment strategy were generated and compared to each other to ascertain the differential benefit in drug response., Results: Differential benefits for each drug were identified, including strong, modest-intermediate, negligible, and deleterious (harmful) effects for subgroups of patients. Similarly, the benefits of combination therapy ranged from synergy, little or negligible benefit, and deleterious effects compared to single agent approaches., Conclusions: The benefit of combination chemotherapy is predicted to vary widely in the population. Biosimulation appears to be a useful tool to address the disease heterogeneity, drug response, and the relevance of particular clinical trials observations to individual patients. Biosimulation has potential to spare some patients the experience of over-treatment while identifying patients uniquely situated to benefit from combination treatment. Validation of this new artificial intelligence tool is needed., (© 2021. The Author(s).)

Background and Purpose: This work aims at optimizing and studying the feasibility of imaging the brachial plexus at 1.5T using 3D nerve-SHeath signal increased with INKed rest-tissue RARE imaging (3D SHINKEI) neurography sequence by comparing with routine sequences., Materials and Methods: The study was performed on a 1.5T Achieva scanner. It was designed in two parts: (a) Optimization of SHINKEI sequence at 1.5T; and (b) Feasibility study of the optimized SHINKEI sequence for generating clinical quality magnetic resonance neurography images at 1.5T. Simulations and volunteer experiments were conducted to optimize the T2 preparation duration for optimum nerve-muscle contrast at 1.5T. Images from the sequence under study and other routine sequences from 24 patients clinically referred for brachial plexus imaging were scored by a panel of radiologists for diagnostic quality. Injury detection efficacy of these sequences were evaluated against the surgical information available from seven patients., Results: T2 preparation duration of 50 ms gives the best contrast to noise between nerve and muscle. The images of 3D SHINKEI and short-term inversion recovery turbo spin-echo sequences are of similar diagnostic quality but significantly better than diffusion weighted imaging with background signal suppression. In comparison with the surgical findings, 3D SHINKEI has the lowest specificity; however, it had the highest sensitivity and predictive efficacy compared to other routine sequences., Conclusion: 3D SHINKEI sequence provides a good nerve-muscle contrast and has high predictive efficacy of nerve injury, indicating that it is a potential screening sequence candidate for brachial plexus scans at 1.5T also., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Medical Physics.)

Competing Interests: Conflict of interest statement: J.V. is the president and cofounder of the Vilcek Foundation, whose mission is to raise awareness of immigrant contributions to the United States. P.N. has received remuneration for promotional work for the Vilcek Foundation.

Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients. Drug treatment simulations based on unique patient-specific disease networks were used to generate treatment predictions. To evaluate the accuracy of the genomics-informed computational platform, we conducted a pilot prospective clinical study (NCT02435550) enrolling confirmed MDS and AML patients. Blinded to the empirically prescribed treatment regimen for each patient, genomic data from 50 evaluable patients were analyzed by CBM to predict patient-specific treatment responses. CBM accurately predicted treatment responses in 55 of 61 (90%) simulations, with 33 of 61 true positives, 22 of 61 true negatives, 3 of 61 false positives, and 3 of 61 false negatives, resulting in a sensitivity of 94%, a specificity of 88%, and an accuracy of 90%. Laboratory validation further confirmed the accuracy of CBM-predicted activated protein networks in 17 of 19 (89%) samples from 11 patients. Somatic mutations in the TET2 , IDH1/2 , ASXL1 , and EZH2 genes were discovered to be highly informative of MDS response to hypomethylating agents. In sum, analyses of patient cancer genomics using the CBM platform can be used to predict precision treatment responses in MDS and AML patients., (© 2019 by The American Society of Hematology.)

Competing Interests: Conflict of interest statement: J.V. is the president and cofounder of the Vilcek Foundation, whose mission is to raise awareness of immigrant contributions to the United States. P.N. has received remuneration for promotional work for the Vilcek Foundation.

Competing Interests: Conflict of interest statement: J.V. is the president and co-founder of the Vilcek Foundation, whose mission is to raise awareness of immigrant contributions to the United States. P.N. has received remuneration for promotional work for the Vilcek Foundation.

Background: The personalization of cancer treatments implies the reconsideration of a one-size-fits-all paradigm. This move has spawned increased use of next generation sequencing to understand mutations and copy number aberrations in cancer cells. Initial personalization successes have been primarily driven by drugs targeting one patient-specific oncogene (e.g., Gleevec, Xalkori, Herceptin). Unfortunately, most cancers include a multitude of aberrations, and the overall impact on cancer signaling and metabolic networks cannot be easily nullified by a single drug., Methods: We used a novel predictive simulation approach to create an avatar of patient cancer cells using point mutations and copy number aberration data. Simulation avatars of myeloma patients were functionally screened using various molecularly targeted drugs both individually and in combination to identify drugs that are efficacious and synergistic. Repurposing of drugs that are FDA-approved or under clinical study with validated clinical safety and pharmacokinetic data can provide a rapid translational path to the clinic. High-risk multiple myeloma patients were modeled, and the simulation predictions were assessed ex vivo using patient cells., Results: Here, we present an approach to address the key challenge of interpreting patient profiling genomic signatures into actionable clinical insights to make the personalization of cancer therapy a practical reality. Through the rational design of personalized treatments, our approach also targets multiple patient-relevant pathways to address the emergence of single therapy resistance. Our predictive platform identified drug regimens for four high-risk multiple myeloma patients. The predicted regimes were found to be effective in ex vivo analyses using patient cells., Conclusions: These multiple validations confirm this approach and methodology for the use of big data to create personalized therapeutics using predictive simulation approaches.