Carcinosarcoma arising from high-grade serous carcinoma of the ovary without estrogen receptor,WT-1, and PAX8 immunoreactivity

ObjectiveWe encountered a case of high-grade serous carcinoma (HGSC) of the ovary which recurred as carcinosarcoma of the sigmoid colon. Tumor cells of both the primary carcinoma and the secondary carcinosarcoma were negative for estrogen receptor (ER), WT-1, and PAX8. It is well known that most ovarian carcinomas arising from the Müllerian duct are immunoreactive for these biologic parameters. To our knowledge, this is the first case report that provides the results of immunohistochemical analysis of WT-1 and PAX8 for a primary carcinoma and recurrent carcinosarcoma.Case reportA 61-year-old woman had an advanced right ovarian HGSC. After a primary debulking surgery (hysterectomy, bilateral salpingo-oophorectomy and omentectomy) and adjuvant chemotherapy, complete remission was achieved. However, four and a half years later, a tumor arising beside the sigmoid colon was detected. A tumorectomy was performed through combined partial resection of the ileum and sigmoid colon. Microscopically, the tumor was diagnosed as carcinosarcoma of the sigmoid colon, which had originated from HGSC of the ovary. Interestingly, the malignant cells of the primary carcinoma and epithelial components of the recurrent carcinosarcoma were negative for ER, WT-1, and PAX8. These immunohistochemical features were unusual. Three cycles of chemotherapy with the previously used regimen and three additional cycles of doxorubicin and ifosfamide combination chemotherapy were administered. Currently, 3 years after the final chemotherapy was administered, the patient remains healthy.ConclusionHGSC of the ovary can recur as carcinosarcoma. Tumor cells of the primary HGSC without ER, WT-1, and PAX8 expression may have dedifferentiated and recurred as carcinosarcoma.     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Functional outcomes and complications after treatment of distal radius fracture in patients sixty years and over: A systematic review and network meta-analysis

AimThis network meta-analysis aims to compare functional outcomes and complications between conservative treatment and surgery for distal radius fractures in patients aged 60 years and over.MethodsWe searched the PubMed, EMBASE, and Web of Science databases for randomized controlled trials (RCTs) assessing the effect of conservative treatment and surgery for distal radius fractures in patients aged 60 years and over. Primary outcomes included grip strength and overall complications. Secondary outcomes included Disabilities of the Arm, Shoulder, and Hand (DASH) scores, Patient-Rated Wrist Evaluation (PRWE) scores, wrist range of motion and forearm rotation, and radiographic assessment. All continuous outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs), and binary outcomes were assessed using odds ratio (OR) with 95% CIs. The surface under the cumulative ranking curve (SUCRA) was used to determine a hierarchy of treatments. Cluster analysis was performed for grouping treatments based on the SUCRA values of primary outcomes.ResultsFourteen RCTs were included to compare conservative treatment, volar lockedplate (VLP), K-wires fixation, and external-fixation. VLP outperformed conservative treatment for 1-year and minimum 2-year grip strength (SMD; 0.28 [0.07 to 0.48] and 0.27 [0.02 to 0.53], respectively). VLP yielded the optimal grip strength at 1-year and minimum 2-year follow-up (SUCRA; 89.8% and 86.7%, respectively). In a subgroup analysis of patients aged 60 to 80 years old, VLP outperformed conservative treatment in DASH and PRWE scores (SMD, 0.33 [0.10, 0.56] and 0.23 [0.01, 0.45], respectively). In addition, VLP had the fewest complications (SUCRA = 84.3%). Cluster analysis suggested that VLP and K-wire fixation were more effective treatment groups.ConclusionEvidence to date demonstrates that VLP provides measurable benefits in grip strength and fewer complications to those 60 years of age and over, and that benefit is not reflected in current practice guidelines. There is a subgroup of patients where K-wire fixation outcomes are similar to those of VLP; defining this subgroup may yield substantial societal benefits.     

ECFS standards of care on CFTR-related disorders: Updated diagnostic criteria

This paper is the first in a series providing updated guidance on the definition, evaluation and management of people with a Cystic Fibrosis Transmembrane conductance Regulator (CFTR)-Related Disorder (CFTR-RD). The need for this update relates to more precise characterisation of CFTR gene variants and improved assessment of CFTR protein dysfunction. The exercise is co-ordinated by the European CF Society Standards of Care Committee and Diagnostic Network Working Group and involves stakeholder engagement. This first paper was produced by a core group using an extensive literature review and papers graded for their quality. Subsequent wider stakeholder agreement was achieved.The definition of a CFTR-RD remains “a clinical condition with evidence of CFTR protein dysfunction that does not fulfil the diagnostic criteria for CF”. Clearer guidance on CFTR dysfunction and relevant CFTR variants will be provided. Thresholds for clinical presentations are presented and the paradigm that pathobiological processes may be evident in more than one organ is agreed. In this paper we reflect on the early patient journey, highlighting that CF specialists as well as other relevant specialists should be involved in the care of people with a CFTR-RD.