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JCO Clinical Cancer Informatics May 2024Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology...
PURPOSE
Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.
METHODS
A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and treatment data were extracted from the EHR using a methodology adaptable to any disease site. Data accuracy was assessed by manual review. Accuracy before and after implementation of synoptic reporting was determined for MRI data.
RESULTS
A total of 516 patients with localized rectal cancer were included. In the era after institutional adoption of synoptic reports, the dynamic operations platform extracted T (tumor) category data from the EHR with 95% accuracy compared with 87% before the use of synoptic reports, and N (lymph node) category with 88% compared with 58%. Correct extraction of pelvic sidewall adenopathy was 94% compared with 78%, and extramural vascular invasion accuracy was 99% compared with 89%. Neoadjuvant chemotherapy and radiation data were 99% accurate for patients who had synoptic data sources.
CONCLUSION
Using dynamic operations platforms enables automated cross-platform integration of multiparameter oncology data with high fidelity in patients undergoing multimodality treatment for rectal cancer. These pipelines can be adapted to other solid tumors and, together with standardized reporting, can increase efficiency in clinical research and the translation of actionable findings toward optimizing patient outcomes.
Topics: Humans; Rectal Neoplasms; Female; Male; Middle Aged; Magnetic Resonance Imaging; Aged; Databases, Factual; Electronic Health Records; Adult; Reproducibility of Results; Neoplasm Staging
PubMed: 38759125
DOI: 10.1200/CCI.23.00219 -
International Journal of Particle... Mar 2024Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes...
PURPOSE
Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT).
MATERIALS AND METHODS
Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive ( = 9) or adjuvant PT ( = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once ( = 19) or twice ( = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement.
RESULTS
With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension ( = .003) and gross residual tumor ( = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% ( = 13).
CONCLUSION
This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.
PubMed: 38757074
DOI: 10.1016/j.ijpt.2024.100008 -
JAAD International Sep 2024Mohs micrographic surgery with melanocytic immunohistochemistry (MMS-I) is increasingly utilized for special site melanoma treatment. Yet, frequency and risk factors...
BACKGROUND
Mohs micrographic surgery with melanocytic immunohistochemistry (MMS-I) is increasingly utilized for special site melanoma treatment. Yet, frequency and risk factors associated with upstaging of all-stage cutaneous melanomas treated with MMS-I remain undefined.
OBJECTIVE
Determine upstaging frequency and factors associated with tumor upstaging for all-stage melanomas treated with MMS-I.
METHODS
In this retrospective, single-center case series, all cases of invasive and in situ melanoma treated with MMS-I between 2008 and 2018 were reviewed. Patient and tumor characteristics were recorded and compared between tumors that were and were not upstaged from their initial T stage.
RESULTS
Of the 962 melanoma MMS-I cases identified, 44 (4.6%) were upstaged, including 5.6% of in situ and 2.5% of invasive tumors. Risk factors for upstaging included lack of excisional intent at the time of initial biopsy ( < .01), nonlentigo maligna subtype ( = .03), female sex ( = .02), and initial in situ diagnosis ( = .03). Nonstatistically significant characteristics evaluated included patient age ( = .97), initial Breslow depth ( = .18), and biopsy type ( = .24).
LIMITATIONS
Retrospective study design.
CONCLUSIONS
All-stage cutaneous melanomas treated with MMS-I are associated with low upstaging rates. Tumor upstaging is associated with lack of excisional intent, female sex, and in situ tumors.
PubMed: 38756446
DOI: 10.1016/j.jdin.2024.02.006 -
Cell Transplantation 2024Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin...
Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment. We herein investigated whether the addition of adipose tissue-derived stem cells (ADSCs) to GHNF affected the outcome. A silicone spacer sandwiched between two GHNFs with (AG group) or without (GHNF group) ADSCs, or a silicone spacer alone (Silicone group) was implanted into the subcutaneous space of healthy mice at 6 weeks before transplantation, then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Intraportal transplantation (IPO group) was also performed to compare the transplant efficiency. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, and inflammatory mediators were evaluated. The results in the subcutaneous transplantation were compared using the Silicone group as a control. The results of the IPO group were also compared with those of the AG group. The AG group showed significantly better blood glucose changes than the Silicone and the IPO groups. The cure rate of AG group (72.7%) was the highest among the groups (GHNF; 40.0%, IPO; 40.0%, Silicone; 0%). The number of vWF-positive vessels in the subcutaneous space of the AG group was significantly higher than that in other groups before transplantation ( < 0.01). Lectin angiography also showed that the same results ( < 0.05). According to the results of the ADSCs tracing, ADSCs did not exist at the transplant site (6 weeks after implantation). The positive rates for laminin and collagen III constructed around the transplanted islets did not differ among groups. Inflammatory mediators were higher in the Silicone group, followed by the AG and GHNF groups. Pretreatment using bioabsorbable scaffolds combined with ADSCs enhanced neovascularization in subcutaneous space, and subcutaneous islet transplantation using GHNF with ADSCs was superior to intraportal islet transplantation.
Topics: Animals; Islets of Langerhans Transplantation; Adipose Tissue; Gelatin; Mice; Hydrogels; Male; Diabetes Mellitus, Experimental; Stem Cells; Islets of Langerhans; Blood Glucose; Mice, Inbred C57BL
PubMed: 38756050
DOI: 10.1177/09636897241251621 -
Scientific Reports May 2024The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is...
The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface. These knobs and the proteins that are concentrated within them allow the parasites to escape the immune response and host spleen clearance by mediating cytoadherence of the iRBC to the endothelial wall, but this also slows down blood circulation, leading in some cases to severe cerebral and placental complications. In this work, we have applied genetic and biochemical tools to identify proteins that interact with P. falciparum KAHRP using enhanced ascorbate peroxidase 2 (APEX2) proximity-dependent biotinylation and label-free shotgun proteomics. A total of 30 potential KAHRP-interacting candidates were identified, based on the assigned fragmented biotinylated ions. Several identified proteins have been previously reported to be part of the Maurer's clefts and knobs, where KAHRP resides. This study may contribute to a broader understanding of P. falciparum protein trafficking and knob architecture and shows for the first time the feasibility of using APEX2-proximity labelling in iRBCs.
Topics: Erythrocytes; Plasmodium falciparum; Protozoan Proteins; Humans; Proteomics; Malaria, Falciparum; DNA-(Apurinic or Apyrimidinic Site) Lyase; Ascorbate Peroxidases; Protein Binding; Biotinylation; Endonucleases; Peptides; Proteins; Multifunctional Enzymes
PubMed: 38755230
DOI: 10.1038/s41598-024-61295-w -
Cell Death & Disease May 2024The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers... (Review)
Review
The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.
Topics: Humans; Liver Neoplasms; T-Lymphocytes; Animals; Tumor Microenvironment
PubMed: 38755133
DOI: 10.1038/s41419-024-06726-2 -
Journal of ISAKOS : Joint Disorders &... May 2024Autologous tendon cell implantation (OrthoATI™) therapy has demonstrated efficacy in treating patients with tendinopathy at various anatomical sites. This study...
Age and donor site do not affect cell growth and biologic activity in Autologous Tendon-cell Implantation (OrthoATI™) for treatment of patellar tendon and palmaris longus tendon.
OBJECTIVES
Autologous tendon cell implantation (OrthoATI™) therapy has demonstrated efficacy in treating patients with tendinopathy at various anatomical sites. This study evaluates the effect of patient age, gender and tendon biopsy site on morphology, growth and gene expression of autologous tendon cells used to treat chronic tendinopathy.
METHODS
Patients undergoing OrthoATI™ for tendinopathies between 2020 and 2022 were initially treated by biopsies taken from patella tendon (PT) or palmaris longus tendon (PL). Autologous tenocytes were treated at a Good Manufacturing Practice (GMP) cell laboratory where they were isolated, cultured and expanded for four to six weeks. Cell morphology was assessed using phase contrast microscopy. Droplet digital PCR (ddPCR) was utilised for gene expression analysis. Dichotomous results were compared between groups using x or Fisher's exact tests with no adjustment for multiple comparisons. The non-parametric Mann-Whitney U and Kruskal-Wallis tests were utilised for the sex and age (<35y, 35-44y, 45-54y, >55y) analyses respectively. All analyses were performed using IBM SPSS v27, and a two-tailed P-value of <0.05 was considered statistically significant.
RESULTS
149 patients were included in the analysis. The PT was biopsied in 63 patients, and PL in 86 patients. There were no observer effects for age and gender between PT and PL groups. There was no statistical significance between the PT and PL tendons for cell morphology, average cell population doubling time (PDT) (PT 83.9 vs PL 82.7 hours, p=0.482), cellular yield (PT 16.2 vs PL 15.2×10 , p=0.099), and cell viability (PT 98.7 vs PL 99.0%, p=0.277). Additionally, ddPCR analyses showed no statistical significance found in tenogenic gene expression including collagen type I (COL1, p=0.86), tenomodulin (TNMD, p=0.837) and scleraxis (SCX, p=0.331) between PT- and PL-derived tendon cells. An age stratification analysis found no effect on growth and gene expression. COL1 was found to be higher in males when compared to females (P<0.001), but otherwise no difference was seen in growth and gene expression in the gender analysis. No post-biopsy clinical complications were reported for either group.
CONCLUSION
This study has shown that the growth and bioactivities of tendon cells from tendon biopsies for OrthoATI™ are not affected by tendon donor site and age.
LEVEL OF EVIDENCE
IV.
PubMed: 38754838
DOI: 10.1016/j.jisako.2024.05.007 -
Respirology Case Reports May 2024EBUS-TBNA has represented a revolution in the diagnosis of intrathoracic pathologies, particularly in lung cancer staging, replacing more invasive methods such as...
EBUS-TBNA has represented a revolution in the diagnosis of intrathoracic pathologies, particularly in lung cancer staging, replacing more invasive methods such as mediastinoscopy. However, its role in diagnosing rare benign or malignant mediastinal disorders is still a matter of debate. Over the past few years, the role of EBUS-guided cryobiopsy has been increasingly emerging as an innovative and minimally invasive technique in diagnosing these disorders, with an excellent safety profile. In this case report, we present the case of a young man brought to our attention after already undergoing a non-diagnostic trans thoracic needle aspiration (TTNA) procedure for lung consolidations. In our department, he underwent an initial EBUS-TBNA procedure with inconclusive rapid on-site evaluation (ROSE), leading to the decision to perform an EBUS-guided cryobiopsy, which yielded a diagnosis of granulomatosis with polyangiitis without complications. This clinical case demonstrates that in specific contexts, EBUS-cryobiopsy represents an excellent diagnostic tool.
PubMed: 38751968
DOI: 10.1002/rcr2.1385 -
The Journal of Biological Chemistry May 2024Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient...
Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE) (associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers. We determined crystal structures of Alvinella pompejana (Ap) ASCC1 and Human (Hs) PDE domain revealing high resolution details and features conserved over 500 million years of evolution. Extending understanding of the KH domain Gly-X-X-Gly sequence motif, we define a novel structural Helix-Clasp-Helix (HCH) nucleotide binding motif and show ASCC1 sequence-specific binding to CGCG-containing RNA. The V-shaped PDE nucleotide binding channel has two His-Φ-Ser/Thr-Φ (HXT) motifs (Φ being hydrophobic) positioned to initiate cyclic phosphate bond hydrolysis. A conserved atypical active-site histidine torsion angle implies a novel PDE substrate. Flexible active site loop and arginine-rich domain linker appear regulatory. Small angle X-ray scattering (SAXS) revealed aligned KH-PDE RNA binding sites with limited flexibility in solution. Quantitative evolutionary bioinformatic analyses of disease and cancer-associated mutations support implied functional roles for RNA binding, phosphodiesterase activity, and regulation. Collective results inform ASCC1 roles in transactivation and alkylation damage responses, its targeting by structure-based inhibitors, and how ASCC1 mutations may impact inherited disease and cancer.
PubMed: 38750793
DOI: 10.1016/j.jbc.2024.107368 -
European Journal of Medical Research May 2024Odontogenic keratocysts exhibit frequent recurrence, distinctive histopathological traits, a tendency towards aggressive clinical behavior, and a potential linkage to... (Review)
Review
OBJECTIVES
Odontogenic keratocysts exhibit frequent recurrence, distinctive histopathological traits, a tendency towards aggressive clinical behavior, and a potential linkage to the nevoid basal cell carcinoma syndrome. The aim of this systematic review is to compile insights concerning the control of this condition and assess the effectiveness of various treatment approaches in reducing the likelihood of recurrence.
MATERIALS AND METHODS
The following systematic review adhered to the PRISMA guidelines. The systematic revision was registered on PROSPERO and structured around the questions related to the population, intervention, control, outcome and study design (PICOS).
RESULTS
After conducting a search on the PubMed database, we initially identified 944 records. After using end-note software to remove duplicate entries, results totally with 462 distinct records. A thorough review of the titles and abstracts of these articles led to the selection of 50 papers for in-depth examination. Ultimately, following the application of our eligibility criteria, we incorporated 11 articles into our primary outcome analysis.
CONCLUSION
Among the studies examined, the most common location for these lesions was found to be in the area of the mandibular ramus and the posterior region of the mandible. In cases where the exact location wasn't specified, the mandible emerged as the predominant site. When we considered the characteristics of these lesions in studies that mentioned locularity, most were described as unilocular in two studies, while in two other studies, the prevalence of multilocular lesions was observed. Risk factors associated with keratocyst recurrence include younger patient age, the presence of multilocular lesions, larger lesion size, and a longer anteroposterior dimension. Certain treatment methods have demonstrated a lack of relapses. These include the use of 5-fluorouracil, marsupialization, enucleation with peripheral ostectomy or resection, enucleation and curettage, as well as resection without creating continuity defects. However, it is important to note that further research is essential. Prospective studies and randomized trials are needed to collect more comprehensive evidence regarding the effectiveness of various treatment approaches and follow-up protocols for managing odontogenic keratocysts.
CLINICAL RELEVANCE
Odontogenic keratocysts still enter into differential diagnoses with other lesions that affect the jaw bones such as ameloblastama and other tumor forms, furthermore it is not free from recurrence, therefore the therapeutic approach to the lesion aimed at its elimination can influence both the possible recurrence and complications, knowledge of the surgical methods that offer the most predictable and clinically relevant result for the management of follow-up and recurrences.
Topics: Humans; Odontogenic Cysts
PubMed: 38750607
DOI: 10.1186/s40001-024-01854-z