ABSTRACT
BACKGROUND: Hemorrhage associated with placenta accreta spectrum (PAS) is a leading cause of maternal morbidity and mortality. Estimating blood loss in these individuals is a critical component of comprehensive preoperative planning. OBJECTIVE: A semi-quantitative score based on transvaginal ultrasound was developed and tested to predict PAS, estimate its severity, and blood loss in individuals with clinical and ultrasound evidence suggesting PAS. STUDY DESIGN: A secondary analysis was conducted of prospectively collected data from a quaternary center of patients with suspected accreta on 2D ultrasound and clinical suspicion. A pre-determined scoring system was applied based on three components: 1) uterine wall (score 0: no loss of hypo-translucent uterine wall with overlying placenta in the lower uterine segment; 1: loss of hypo-translucent <3-cm defect; 2: 3-6-cm defect; and 3: >6-cm defect); 2) arterial vascularity at the uterine wall defect (score 0: no vessels observed; 1: 1-2 vessels over the defect; 2: 3-5 vessels; and 3: >5 vessels) and 3) cervical involvement (score 0: normal cervical length without previa; 1: previa with normal cervical length; 2: short cervix with previa, minimal vascularity and small lacunae; 3: short cervix with previa, increased vascularity and large lacunae). Each patient's three domain scores determined a cumulative, final score of 0-9. Patients were managed at the discretion of a multi-disciplinary team and patient's preference among the following options: cesarean delivery with placenta removal, cesarean delivery with placenta in-situ (conservative) with or without delayed hysterectomy, or cesarean hysterectomy. The frequency of different degrees of placental invasion per pathology examination per score unit was registered. Multiple linear regression analysis was performed for association of blood loss according to score adjusted by risk factors for PAS. RESULTS: A total of 73 patients were evaluated. All 11 patients who had a score of 0 had cesarean delivery with placenta removal without evidence of intraoperative PAS, thus resulting in a 100% negative predictive value. The remaining 62 had scores between 1-9. Among patients with scores 0-3 (n=20), only one had intraoperative PAS, yielding a negative predictive value of 97%. Higher scores were associated with severe PAS forms (r=0.301, p=0.02). Based on the associations between PAS scores, clinical correlation, and blood loss, we divided patients into four categories: Category 0: PAS score 0; Category 1: scores 1-3; Category 2: scores 4-6; and Category 3: scores 7-9. The median blood loss in Category 0â¯=â¯635 ± 352 mL, Category 1â¯=â¯634 ± 599 mL, Category 2â¯=â¯1549 ± 1284 mL, and Category 3â¯=â¯1895 ± 2106 mL (p <0.001). On multivariable analysis, Category 2 (ßâ¯=â¯0.97, p <0.01) and Category 3 (ßâ¯=â¯1.26, p <0.003) were associated with significantly greater blood loss than Category 0, irrespective of type of surgery. CONCLUSION: The transvaginal ultrasound score separates groups at low risk (Category 0) and at higher risk of PAS (Categories 1-3). Categories 1-3 may provide important clinical information to estimate the risk of severe forms of PAS and of blood loss during surgery.
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Buccal cavernous hemangiomas are uncommon vascular lesions, particularly in adult patients. We present a case of a 23-year-old male with a progressive left cheek swelling over three years. Clinical examination and radiographic imaging revealed a solid, multilobulated mass in the left buccal and masticator spaces. Surgical excision was performed, and histopathological analysis confirmed the diagnosis of a cavernous hemangioma. This case underscores the importance of recognizing and appropriately managing rare vascular lesions in adult patients.
ABSTRACT
While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).
ABSTRACT
BACKGROUND: Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study. METHODS: In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment. FINDINGS: From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. INTERPRETATION: This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach. FUNDING: National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.
Subject(s)
Antigens, CD19 , Immunotherapy, Adoptive , Sialic Acid Binding Ig-like Lectin 2 , Adult , Aged , Female , Humans , Male , Middle Aged , Antigens, CD19/immunology , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Maximum Tolerated Dose , Receptors, Chimeric Antigen/immunology , Sialic Acid Binding Ig-like Lectin 2/immunology , Aged, 80 and overABSTRACT
Importance: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes. Objective: To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes. Design: Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023. Setting: Fetal surgery was performed at a quaternary care center. Participants: A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis. Interventions or Exposures: We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. Main Outcomes and Measures: The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion. Results: We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level. Conclusions and Relevance: There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.
ABSTRACT
The concurrent presentation of a low-grade appendiceal mucinous neoplasm (LAMN) and a borderline Brenner tumor (BT) of the ovary are exceedingly rare. Brenner tumors stand out as a particularly uncommon form, making up only around 5% of all benign epithelial tumors of the ovary. Among the ovarian Brenner, the borderline subtype is even rarer. Appendiceal neoplasm (LAMN) and right ovarian BT cannot be distinguished due to their anatomical position. LAMN is often an incidental finding and at later stages when left undiagnosed may lead to pseudomyxoma peritonei (PMP). This case describes a postmenopausal woman in her 50s experiencing abdominal pain and bloating for a week. Elevated carcinoembryonic antigen (CEA) levels and imaging suggested a potential right ovarian tumor. Interestingly, it revealed a unique combination of borderline Brenner tumor of the right ovary and low-grade appendiceal mucinous neoplasm.
ABSTRACT
In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer.
Subject(s)
Antineoplastic Agents , Drug Liberation , Folic Acid , Hyaluronic Acid , Micelles , Pentacyclic Triterpenes , Polymers , Triterpenes , Xenograft Model Antitumor Assays , Animals , Humans , Female , Triterpenes/chemistry , Triterpenes/administration & dosage , Triterpenes/pharmacokinetics , Triterpenes/pharmacology , MCF-7 Cells , Polymers/chemistry , Folic Acid/chemistry , Folic Acid/administration & dosage , Hyaluronic Acid/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Particle Size , Mice , Drug Carriers/chemistry , Mice, Nude , Mice, Inbred BALB C , Rats, Sprague-Dawley , Cell Survival/drug effects , Drug StabilityABSTRACT
Multiple primary tumors are rare but their incidence is increasing nowadays with advancements in diagnostic methods and the extended survival of individuals previously treated for malignancies. However, synchronous occurrence of gastric cancer (GC) and colonic cancer (CC) is a rare entity. A 41-year-old male came with complaints of epigastric pain associated with anorexia, rapid weight loss, and occasional constipation. Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis reported mucosal thickening in the antrum, likely GC with circumferential wall thickening of the transverse colon with pericolic fat stranding suggestive of CC. Upper gastrointestinal endoscopy and colonoscopy were also done and a biopsy was taken from representative sites, which confirmed malignancy. He completed three cycles of chemotherapy preoperatively and underwent subtotal gastrectomy, D2 lymphadenectomy, gastrojejunostomy, jejunojejunostomy, and transverse colectomy simultaneously. Histopathological examination confirmed moderately differentiated gastric adenocarcinoma penetrating into the subserosa and well-differentiated colonic adenocarcinoma invading the muscularis propria. Immunohistochemical analysis of mismatch repair (MMR) proteins was done to determine the association with hereditary nonpolyposis colorectal cancer syndrome (HNPCC) or Lynch syndrome. The patient underwent postoperative chemotherapy along with immunotherapy. To conclude, synchronous occurrence of primary GC and primary CC with similar MMR protein expression in immunohistochemistry is an uncommon entity.
Subject(s)
Macula Lutea , Retinal Ganglion Cells , Tomography, Optical Coherence , Humans , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence/methods , Macula Lutea/diagnostic imaging , Macula Lutea/pathology , Oculomotor Muscles/surgery , Male , Female , Nerve Fibers/pathology , Follow-Up Studies , Ophthalmologic Surgical Procedures/methods , Adult , Strabismus/surgeryABSTRACT
Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3-4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.
Subject(s)
Immunotherapy, Adoptive , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Sialic Acid Binding Ig-like Lectin 2 , Humans , Sialic Acid Binding Ig-like Lectin 2/immunology , Child , Adult , Female , Male , Adolescent , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Young Adult , Receptors, Chimeric Antigen/immunology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Child, Preschool , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/metabolismABSTRACT
STUDY DESIGN: Systematic review. OBJECTIVES: The aim of this study is to analyze the complications related to multilevel anterior cervical discectomy and fusion (ACDF) using osteobiologics other than bone morphogenetic protein (BMP). METHODS: A systematic review of the literature was conducted using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search to identify studies reporting complications in multilevel ACDF surgery using osteobiologics other than bone morphogenetic protein was performed in August 2020. The study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: A total of 584 articles were found after searching the databases and removing duplicates. Next, screening was performed in a double reviewer process, and 153 eligible articles-with 4 retrospective studies-in full-text were selected; these met all inclusion criteria. A total of 197 patients received 3-level ACDF, while 72 patients received 4-level ACDF. Osteobiologics were used in all selected articles, allograft was used in 4 studies, autologous bone graft was utilized in 3 articles, and hydroxyapatite was used in 1 article. The main complications reported were dysphagia, adjacent segment disease, and pseudarthrosis. CONCLUSIONS: Given the limited evidence, no conclusions on complications in multilevel ACDF using osteobiologics other than BMP could be made. However, descriptively, the most common complications found were dysphagia, adjacent segment disease, and pseudoarthrosis. Further prospective studies separately analyzing complications in multilevel ACDF by osteobiologics and a number of treated levels are needed.
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Study Design: Systematic literature reviewObjective: To critically analyze the literature and describe the complications associated with the use of allograft in 1- or 2- level anterior cervical discectomy and fusion (ACDF)Methods: A systematic search of PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov databases was conducted for literature published between January 2000 and August 2020 reporting complications associated with the use of allograft in 1- or 2- level ACDF.Results: From 584 potentially relevant citations, 21 met the inclusion criteria (4 randomized controlled trials (RCT), 4 prospective, and 13 retrospective studies). The patient number varied between 26 and 463 in comparative studies (RCT and non-RCT) and between 29 and 345 in non-comparative studies. Fusion rate was reported in 14 studies and ranged between 68.5-100%. The most frequently reported complication was post-operative dysphagia or dysphonia, with incidences ranging between .5% and 14.4%. Revision surgery was the second most reported complication (14 studies) and ranged between 0% and 10.3%. Wound-related complications were reported in 6 studies and ranged between 0% and 22.8%.Conclusion: The overall reporting of complications was low with very few comparative studies. Reported complications with allografts are within the range of other osteobiologics and autografts and in most cases may not attributable to the use of osteobiologics and may be complications of the procedure itself. Comparative studies with a more robust methodology analyzing complications with allograft and other osteobiologics are needed to inform current practice with strong recommendations.
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STUDY DESIGN: Methodological study for guideline development. OBJECTIVE: AO Spine Guideline for Using Osteobiologics (AO-GO) project for spine degenerative pathologies was an international, multidisciplinary collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in Anterior Cervical Fusion and Decompression (ACDF). The aim was to formulate precisely defined, clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics, considering regional preferences and cost-effectiveness. METHODS: Guideline was completed in two phases: Phase 1- evidence synthesis; Phase 2- recommendation development based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In Phase 1, key questions identified by a panel of experts were addressed in a series of systematic reviews of randomized and non-randomized studies. In Phase 2, the GRADE approach was used to formulate a series of recommendations, including expert panel discussions via web calls and face-to-face meetings. DISCUSSION: AO-GO aims to bridge an important gap between evidence and use of osteobiologics in spine fusion surgeries. Owing to differences in osteobiologics preparation and functional characteristics, regulatory requirements for approval may vary, therefore it is highly likely that these products enter market without quality clinical trials. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making processes in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries. In Phase 3, the guideline will be disseminated and validated using prospectively collected clinical data in a separate effort of the AO Spine Knowledge Forum Degenerative in a global multicenter clinical study.
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STUDY DESIGN: Systematic literature review. OBJECTIVES: To analyze the evidence available reporting complications in single or two-level anterior cervical discectomy and fusion (ACDF) using a demineralized bone matrix (DBM), hydroxyapatite (HA), or beta-tricalcium phosphate (ß-TCP). METHODS: A systematic review of the literature using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases was performed in August 2020 to identify studies reporting complications in one or two-level ACDF surgery using DBM, HA, or ß-TCP. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 1857 patients were included, 981 male and 876 female, across 17 articles; 5 prospective, and 12 retrospectives. We noted heterogeneity among the included studies concerning the study design and combination of graft materials utilized in them. However, we noted a higher incidence of adjacent segment disease (17.7%) and pseudoarthrosis (9.3%) in fusion constructs using DBM. Studies using ß-TCP reported a higher incidence of pseudoarthrosis (28.2%) and implant failures (17.9%). CONCLUSIONS: Degenerative cervical conditions treated with one or two-level ACDF surgery using DBM, HA, or ß-TCP with or without cervical plating are associated with complications such as adjacent segment disease, dysphagia, and pseudarthrosis. However, consequent to the study designs and clinical heterogeneity of the studies, it is not possible to correlate these complications accurately with any specific graft material employed. Further well-designed prospective studies are needed to correctly know the related morbidity of each graft used for achieving fusion in ACDF.
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Background: Endometrial cancer is one of the most commonly diagnosed cancers in women worldwide. Aim and Objectives: To study the expression of estrogen receptor (ER), progesterone receptor (PR) and p53 immunohistochemistry (IHC) markers in subtyping endometrial carcinoma. Materials and Methods: A total of 100 cases of carcinoma endometrium submitted during January 2016 to October 2018 were included in our study. The ER, PR and p53 expressions were scored as per the adopted scoring system. Agreement between ER, PR and p53 IHC expression and the consensus HE diagnosis, FIGO grading and tumour staging were assessed using Chi square tests. Results: There was a statistical association between ER, PR and p53 status and tumour histologic type with a P value < 0.01. There was no statistical significance observed between ER and PR expressions and different FIGO grades. Statistical significance (P = 0.036) between p53 and different FIGO grades seen. No statistical significance was observed between ER, PR and p53 expressions and different tumour stages and tumour invasiveness. There was a statistical association between ER and PR status and lymph node metastasis. p53 did not show a statistical significance. Conclusion: Combination of ER, PR and p53 IHC markers can be used to distinguish type 1 and type 2 endometrial cancers. PR expression is more specific than ER in endometrioid carcinomas. p53 expression is more specific in serous carcinoma, however, p53 IHC alone cannot be used to distinguish different grades of endometrioid carcinomas as there is variability of staining in endometrioid carcinomas.
Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/pathology , Immunohistochemistry , Tumor Suppressor Protein p53/metabolism , Receptors, Progesterone/metabolism , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Estrogens , Receptors, Estrogen/metabolismABSTRACT
In recent years, Onco-immunotherapies (OIMTs) have been shown to be a potential therapy option for cancer. Several immunotherapies have received regulatory approval, while many others are now undergoing clinical testing or are in the early stages of development. Despite this progress, a large number of challenges to the broad use of immunotherapies to treat cancer persists. To make immunotherapy more useful as a treatment while reducing its potentially harmful side effects, we need to know more about how to improve response rates to different types of immunotherapies. Nanocarriers (NCs) have the potential to harness immunotherapies efficiently, enhance the efficiency of these treatments, and reduce the severe adverse reactions that are associated with them. This article discusses the necessity to incorporate nanomedicines in OIMTs and the challenges we confront with current anti-OIMT approaches. In addition, it examines the most important considerations for building nanomedicines for OIMT, which may improve upon current immunotherapy methods. Finally, it highlights the applications and future scenarios of using nanotechnology.
Subject(s)
Drug Delivery Systems , Neoplasms , Humans , Neoplasms/drug therapy , Immunotherapy , NanomedicineABSTRACT
Idiosyncratic adverse events to phenytoin therapy, such as agranulocytosis and acute liver failure, though rare, may be life-threatening. Simultaneous occurrence of both adverse events is exceedingly rare; only two cases have been reported in the literature to date. We describe such a case in a 15-year-old girl. Prompt haematological and hepatic recovery occurred after discontinuation of the drug. Given the widespread use of phenytoin in seizure disorders, clinicians prescribing this drug should be aware of its potential complications. Early recognition can considerably improve outcomes.
Subject(s)
Agranulocytosis , Epilepsy , Liver Failure, Acute , Child , Female , Humans , Adolescent , Phenytoin/adverse effects , Agranulocytosis/chemically induced , Agranulocytosis/diagnosis , Agranulocytosis/drug therapy , Epilepsy/drug therapy , Liver Failure, Acute/chemically induced , Liver Failure, Acute/diagnosisABSTRACT
ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.
Subject(s)
Lymphoma, Mantle-Cell , Neurotoxicity Syndromes , Humans , Adult , Lymphoma, Mantle-Cell/therapy , Immunotherapy, Adoptive/adverse effects , Adaptor Proteins, Signal Transducing , Antigens, CD19 , Brain , Cytokine Release SyndromeABSTRACT
STUDY DESIGN: Network meta-analysis. OBJECTIVES: To compare the fusion outcome and complications of different 1 or 2-level anterior cervical decompression and fusion (ACDF) constructs performed with and without the application of autografts. METHODS: We performed an independent and duplicate search in electronic databases including PubMed, Embase, Web of Science, Cochrane, and Scopus for relevant articles published between 2000 and 2020. We included comparative studies reporting fusion rate and complications with and without the use of autografts in ACDF across 5 different fusion constructs. A network meta-analysis was performed in Stata, categorized based on the type of fusion constructs utilized. Fusion constructs were ranked based on p-score approach and surface under cumulative ranking curve (SUCRA) scores. The confidence of results from the analysis was appraised with Cochrane's CINeMA approach. RESULTS: A total of 2216 patients from 22-studies including 6 Randomized Controlled Trials (RCTs) and 16 non-RCTs were included in network analysis. The mean age of included patients was 49.3 (±3.62) years. Based on our meta-analysis, we could conclude that use of autograft in 1- or 2-level ACDF did not affect the fusion and mechanical implant-related complications. The final fusion and mechanical complication rates were also not significantly different across the different fusion constructs. The use of plated constructs was associated with a significant increase in post-ACDF dysphagia rates [OR 3.42; 95%CI (.01,2.45)], as compared to stand-alone constructs analysed. CONCLUSION: The choice of fusion constructs and use of autografts does not significantly affect the fusion and overall complication rates following 1 or 2-level ACDF surgery.