Normal Antigen Research Articles

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy in High-Grade Epithelial Ovarian Cancer

Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC). To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT). This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was conducted at 11 academic cancer centers in North America and Europe. Participants were adults with stage IIIC or IV epithelial ovarian, fallopian, or primary peritoneal carcinoma who had normal cancer antigen 125 levels and at least a partial radiologic response after 3 to 4 cycles of NACT. Patients were randomly assigned to receive either interval cytoreductive surgery performed using MIS or laparotomy. Data analysis was based on the evaluable population. The MIS arm underwent laparoscopic or robotic surgery, vs laparotomy for the control arm. Resection of all visible tumor was attempted, and conversion from MIS to laparotomy was performed when necessary to attain complete resection. Trial feasibility was defined by 3 primary end points: patient accrual rate of at least 5.6 patients per month by the last month of the lead-in pilot phase, conversion from MIS to laparotomy in less than 25% of patients, and a difference in complete gross resection rates of fewer than 20 percentage points between study arms. One hundred women (median [IQR] age, 63 [39-82] years) were included, of whom 49 were randomly assigned to MIS and 51 to laparotomy; 95 were evaluable for surgical outcomes. Most patients (34 [67%] in the laparotomy arm, and 33 [67%] in the MIS arm) had stage IIIC cancer. The monthly accrual rate reached 5.9 patients per month in the final month of the study. Six of 48 evaluable patients (12.5%; 95% CI, 4.7%-25.2%) assigned to MIS underwent conversion to laparotomy. Surgeons achieved a complete gross resection rate in 42 of 48 evaluable patients (88%) assigned to MIS and in 39 of 47 patients (83%) assigned to laparotomy (difference, 4.5 [95% CI, -9.7 to 18.8] percentage points). Results of this lead-in pilot study indicated the feasibility of the LANCE RCT to compare the oncological outcomes of MIS vs laparotomy. ClinicalTrials.gov Identifier: NCT04575935.

DeepNeoAG: Neoantigen epitope prediction from melanoma antigens using a synergistic deep learning model combining protein language models and multi-window scanning convolutional neural networks

Neoantigens, derived from tumor-specific mutations, play a crucial role in eliciting anti-tumor immune responses and have emerged as promising targets for personalized cancer immunotherapy. Accurately identifying neoantigens from a vast pool of potential candidates is crucial for developing effective therapeutic strategies. This study presents a novel deep learning model that leverages the power of protein language models (PLMs) and multi-window scanning convolutional neural networks (CNNs) to predict neoantigens from normal tumor antigens with high accuracy. In this study, we present DeepNeoAG, a novel framework combines the global sequence-level information captured by a pre-trained PLM with the local sequence-based information features extracted by a multi-window scanning CNN, enabling a comprehensive representation of the protein's mutational landscape. We demonstrate the superior performance of DeepNeoAG compared to existing methods and highlight its potential to accelerate the development of personalized cancer immunotherapies.

Acute autoimmune hemolytic anemia in a patient with systemic lupus erythematosus

Introduction Autoimmune hemolytic anemia occurs due to the accelerated destruction of erythrocytes as a result of the dysfunction of immune system cells, which produce antibodies against the normal antigens of the membrane of hematopoietic cells. One of its causes is systemic lupus erythematosus. Materials and methods We present a case of a 20-year-old patient who was hospitalized with acute autoimmune hemolytic anemia, having been diagnosed with SLE at the age of 18 years. At the onset of the disease, hemolytic anemia was a differential diagnostic challenge. Results The differential diagnosis between primary and secondary autoimmune hemolytic anemia (AIHA) was an important step. The presence of antinuclear antibodies (ANA Hep2, Anti-dsDNA, Anti-cardiolipin, Anti-phospholipids, anti-Ro, Anti-Sm B) were important arguments in making the diagnosis. The relapse of AIHA was caused by inadequate treatment, due to a lack of compliance. Pulse therapy combined with methylprednisolone and cyclophosphamide successfully resolved the AIHA. Conclusions Hematological abnormalities are commonly seen in SLE patients, but hemolytic autoimmune anemia is a rare condition. A timely diagnosis of the cause of hemolytic anemia and proper treatment of lupus by correcting autoimmune disorders are crucial in disease management. Pulse therapy combined with corticosteroids and immunosuppressants is effective in acute relapses of hemolytic anemia.

Clinical, Laboratory Aspects and Management of Factor X Deficiency.

Coagulation factor X (FX), originally named Stuart-Prower factor, plays a pivotal role in the coagulation cascade, activating thrombin to promote platelet plug formation and prevent excess blood loss. Genetic variants in F10 may lead to FX deficiency and to impaired coagulation. FX variants are phenotypically classified as being type I, with the concomitant reduction of FX coagulant activity and FX antigen levels or type II, corresponding to a reduction in activity with normal antigen plasma levels. Patients affected with FX deficiency tend to be one of the most seriously affected among those with rare bleeding disorders. They show a variable bleeding tendency strongly associated with FX coagulant activity levels in plasma and may present, in the severe form of the deficiency, life-threatening symptoms such as gastrointestinal and umbilical stump bleeding and intracranial hemorrhages or central nervous system bleeding. Treatment of FX deficiency was originally based on the replacement of the missing factor using fresh frozen plasma, cryoprecipitate and prothrombin complex concentrates; however, a plasma-derived concentrate, shown to be safe and effective in clinical trials, is now available. In addition, novel nonreplacement therapy such as small interference RNA, gene therapy, drug repurposing, and gene editing may also represent novel therapeutic approaches for FX deficiency, but further, much focused studies are needed before considering this emerging therapy in such patients.

Ultrasonographic Evaluation of the Association between the Prostate Volume and Anthropometric Measurements in a Subset of Adult Nigerian Men with Benign Prostatic Hypertrophy

Background: Benign prostatic hypertrophy (BPH), a major cause of men`s morbidity, is positively related to obesity, which is assessed using anthropometric measurements. Despite the scarcity of local literature on this relationship, varying associations between prostate volume (PV), age, and anthropometric parameters have been reported. Objectives: To ascertain the average BPH volume, the predominant age at risk for BPH, and any correlations between PV and anthropometric measurements in our community. Methods: A prospective cross-sectional study conducted on 125 men aged 40–80years, with normal prostatic-specific antigen (PSA) levels, at the Radiology department, Benue State University Teaching Hospital, Makurdi, from May 2023 to May, 2024. PV was calculated by transabdominal ultrasonography. Anthropometric measurements were made using set procedures, from which the body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) were computed. The data was analyzed using SPSS and Microsoft Excel with P value < 0.05. Results: The mean age and PV of participants was 61.6±9.5years and 74.2±52.5ml, respectively with majority, 41 (32.8%) of men in their seventh decade of life. Age and PV did not statistically significantly correlate (P = 0.159); however, BMI, HC, WC and WHTR did (P = 0.000, 0.002, 0.006, and 0.014). Conclusion: The mean sonographic PV was 74.2±52.5ml, with men in their seventh decade being the most at risk for BPH. PV exhibited a statistically significant correlation with some anthropometric parameters but not with respondents' age. The equations and models generated from this study will benefit future research on prostatic growth and early detection of BPH.

Factor V haemostatic diathesis impairing thrombin activation, membrane binding and circulating antigen level due to a novel compound heterozygous mutation, Leu1821Ser and Gly2192Cys.

Congenital factor V (FV) deficiency is a rare clotting disorder affecting ∼1 in 1,000,000, with bleeding severity that ranges broadly for poorly understood reasons. To help understand the molecular basis of the observed phenotype in FV deficient patients, the genetics and biochemistry causing a patient's FV deficiency were evaluated. A 71-year-old female, who had serious life-long bleeding upon provocation and profound menorrhagia that lead to hysterectomy, was found to have 3% of normal plasma FV antigen with normal electrophoretic mobility. Platelet FV was similarly low, although the banding pattern was less fragmented than normal. Plasma clotting activity was <1% of normal. Familial inheritance and DNA sequence analysis from peripheral blood leukocytes were consistent with novel compound heterozygosity with missense mutations in exon XVII, Leu1821 to Ser (L1821S) and exon XXV, Gly2192 to Cys (G2192C). The respective single-mutation variants were expressed and purified. Explaining why the antigen level and activity were inequivalent, thrombin activation of recombinant (r) FV/L1821S was impaired, and rFV/G2192C was unable to bind to a procoagulant phospholipid membrane. These findings are consistent with the observed phenotype, highlighting the importance of understanding FV biochemical function to rationalize clinical bleeding severity when the circulating antigen level is discordant.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Preoperative chemotherapy (with or without radiotherapy) followed by resection. The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Long-term follow-up results of prostate capsule-sparing and nerve-sparing radical cystectomy with neobladder: a single-center retrospective analysis

ObjectiveThis study aims to investigate and analyze the feasibility, oncological outcomes, functional efficacy, and complications with the prostatic capsule sparing (PCS) as well as the nerve sparing (NS) in radical cystectomy for bladder cancer.Patients and methodsBetween January 2007 and December 2021, 67 total cystectomies with PCS and 54 with NS were performed at our institution. The inclusion criteria for PCS were as follows: proactive, fully informed patient consent; negative transurethral resection of the bladder neck; normal prostate-specific antigen (PSA) level &amp;lt; 4 ng/dL; and normal transrectal ultrasonography with biopsy of any suspicious nodes. Patients received complete oncological and functional follow-ups. The Kaplan-Meier method was utilized to characterize survival outcomes after surgery.ResultsThe median follow-up times for PCS and NS were 144 and 122 months, respectively. Cumulative survival estimated the 5- and 10-years cancer-specific survival were 93.0% and 88.7% for the PCS group and 79.7% and 79.6% for the NS group, respectively (p = 0.123). In terms of function, the daytime urinary control at 3, 6, and 12 months postoperatively was 80.60%, 97.01%, and 100% in the PCS group, and 53.70%, 85.19%, and 94.44% in the NS group, respectively (p = 0.002, 0.023, and 0.100); and nocturnal urinary control was 62.69%, 94.03%, and 98.51% in the PCS group, and 40.74%, 72.22%, and 87.04% in the NS group, respectively (p = 0.016, 0.001, and 0.022). The erectile function recovery revealed that 62.69% and 40.74% of patients returned to preoperative levels (International Index of Erectile Function (IIEF)-5 score ≥ 15) in the PCS and NS groups, respectively (p = 0.016). Considering complications within 30 days after surgery, 4.48% and 7.69% patients had Clavien ≥ III complications in the PCS and NS groups, respectively (p = 0.700).ConclusionThe PCS provides better restored urinary control and sexual function than the NS technique and does not affect oncological outcomes. However, PCS is prone to bladder-neck obstruction complications and requires closer long-term follow-up.

Prostatic stromal tumor of uncertain malignant potential: a case report and literature review.

Prostatic stromal tumors, encompassing prostatic sarcoma and stromal tumors of uncertain malignant potential (STUMP), represent an exceedingly rare category of prostatic diseases, with a prevalence of less than 1%. We present a rare case involving a man in his early 40s diagnosed with STUMP. Despite presenting with normal prostate-specific antigen (PSA) concentrations, the patient experienced persistent dysuria and gross hematuria for >7 months, leading to an initial misdiagnosis of benign prostatic hyperplasia. Persistent symptoms prompted further investigation, with magnetic resonance imaging (MRI) revealing a suspicious lesion on the left side of the prostate, initially thought to be malignant. Transrectal prostatic biopsy subsequently confirmed the presence of mucinous liposarcoma, with no medical history of diabetes, coronary heart disease, or hypertension. The treatment approach comprised robot-assisted laparoscopic radical prostatectomy, culminating in a postoperative pathological definitive diagnosis of STUMP. This case underscores the indispensable role of early MRI in the diagnostic process, highlighting the necessity of detailed pathological examination for a conclusive diagnosis. Our report aims to illuminate the diagnostic challenges and potential treatment pathways for STUMP, emphasizing its consideration in the differential diagnosis of prostatic tumors to advance clinical outcomes in this rare but important condition.

Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma

PurposePancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC.MethodsPatients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups.ResultsAmong 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively).ConclusionsOnly patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

Management of multiple cerebral embolisms due to polycythemia vera with acquired von Willebrand syndrome

AbstractPolycythemia vera (PV) is a rare blood disorder associated with thrombosis or acquired von Willebrand syndrome (AvWS); however, their coexistence is unusual. Here, we report about a 59‐year‐old man with PV who developed both ischemic stroke (IS) and AvWS. Although the patient had no history of thrombosis, he had refractory epistaxis 2 years prior. Brain magnetic resonance imaging and angiography (MRI and MRA) revealed new IS and mural thrombi at the left distal carotid artery. Laboratory investigations showed elevated hemoglobin and hematocrit levels with mild leukocytosis and thrombocytosis, corresponding to PV. Additionally, suppressed platelet aggregation and activity despite normal antigen of von Willebrand factor indicated AvWS. Appropriate repeated phlebotomies successfully resolved the MRA abnormalities and prevented IS recurrence, although the patient refused the recommended treatment with hydroxyurea. This case highlights the need for careful management to prevent recurrent IS and major bleeding in patients with PV who develop IS accompanying AvWS.

Intestinal tuft cell immune privilege enables norovirus persistence.

The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (just EGFP death inducing) CD8+ T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8+ T cell-mediated killing-unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells-despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8+ T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8+ T cells neither cleared nor prevented MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8+ T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.

Primary Adenosquamous Carcinoma of the Prostate.

Prostate cancer accounts for 29% of malignant diagnoses among men in the United States and is the second leading cause of death from cancer. Effective screening methods and improved treatment have decreased the mortality rate significantly. This decreased mortality rate, however, does not apply to all histologic variants. Adenosquamous carcinoma of the prostate is an extremely aggressive neoplasm with no current known curative therapy. It is often diagnosed after chemotherapy, radiation, or androgen deprivation therapy for traditional prostatic adenocarcinomas. Primary carcinomas of the prostate with squamous features include, but are not limited to, pure squamous cell carcinoma and adenocarcinoma mixed with squamous cell carcinoma (SCC). Important distinguishable clinical features of adenosquamous carcinoma include normal prostate-specific antigen (PSA) levels, even with advanced disease and osteolytic versus osteoblastic metastatic lesions in adenocarcinoma. Additional entities to consider in the differential diagnosis are squamous metaplasia of the prostate, secondary involvement of pure SCC, and urothelial carcinoma with squamous differentiation. Here, we present a de novo case of adenosquamous carcinoma in a 48-year-old man who rapidly developed extensive metastatic disease.

The prognostic value of preoperative D-dimer to albumin ratio for overall survival and progression-free survival in colorectal cancer.

Introduction: This study aimed to explore the predictive value of the D-dimer-to-albumin ratio (DAR) for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Methods: The Kaplan-Meier method was used to plot survival curves for PFS and OS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the DAR for PFS and OS in patients with CRC. Cox proportional hazards regression analysis was used to analyze prognostic factors influencing outcomes. A nomogram based on the DAR was constructed to predict 1-, 3-, and 5-year prognoses of patients with CRC; its predictive ability was evaluated using the concordance index (C-index) and calibration curves. Additionally, the clinical utility of the DAR-based nomogram was validated using an internal randomized validation cohort. Results: A total of 1,339 patients with CRC who underwent surgery were enrolled. The optimal cut-off value for DAR was determined to be 3.320, dividing patients into low (<3.320 [n = 470]) and high (≥3.320 [n = 869]) DAR groups. Compared with other composite immune inflammatory markers, DAR exhibited superior prognostic predictive efficacy. Patients with a high DAR had a significantly worse prognosis than those with a low DAR (PFS, 50.9% versus [vs.] 69.4%, p < 0.001; OS, 52.9% vs. 73.8%, p < 0.001). DAR also demonstrated significant prognostic stratification for most tumor subgroups, particularly in the stage III-IV subgroup and normal carcinoembryonic antigen subgroup. DAR has been identified as an independent predictive indicator of PFS/OS in patients with CRC. For every standard deviation increase in DAR, the risk for PFS/OS in patients with CRC was reduced by 9.5% (hazard ratio [HR] 1.095 [95% confidence interval (CI) 1.013-1.185]; p = 0.022) and 9.3% (HR 1.093 [95% CI 1.012-1.180]; p = 0.024), respectively. The DAR-based nomogram was confirmed to demonstrate good prognostic prediction accuracy and achieved high evaluation in the internal validation cohort. Conclusion: Preoperative DAR is a promising biomarker for predicting PFS and OS among patients with CRC. The DAR-based prognostic prediction nomogram may serve as an effective tool for the comprehensive assessment of prognosis in patients with CRC.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Clinical significance of decreased or loss of ABO blood group expression in acute myeloid leukaemia: A single-centre retrospective study.

Decreased or loss of ABO blood group antigen expression has been observed in acute myeloid leukaemia (AML) patients. We studied the clinical significance of this group in AML patients. This was a retrospective, single-centre cohort study in which the data were retrieved from April 2009 to December 2019. A total of 1592 AML patients with normal ABO blood group antigen (Group I) and 65 patients of decreased or loss of ABO blood group antigen (Group II) group were enrolled. Data were collected at the time of initial admission for pathological diagnosis. To interrogate the underlying mechanism, publicly available The Cancer Genome Atlas AML data were downloaded. Group II consisted of 3.9% (65/1657) of AML patients. The 90-day survival (D90) probability was higher for Group II with a mean survival of 86.4 days compared to 80.6 days for Group I (p = 0.047). Group II had higher haematocrit (28.6 vs. 27.4%) and lower d-dimer, fibrinogen degradation production and C-reactive protein. Publicly available data revealed that among 11 CpG methylation sites within the ABO gene, 4 sites with elevated methylation level were associated with improved D90 survival probability and demonstrated an inverse correlation with ABO gene expression. Lower expression of the ABO gene showed improved survival trends for D90 (p = 0.058) and 180-day survival (p = 0.072). AML with decreased expression or loss of ABO blood group showed better early survival during D90. Transfusion support for this subgroup of AML patients should be meticulously performed considering serum typing.

Development and Validation of a Nomogram to Predict Overall Survival in Stage I–III Colorectal Cancer Patients after Radical Resection with Normal Preoperative Serum Carcinoembryonic Antigen

We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA.

Phenotypic Heterogeneity and Outcomes in Severe Protein C Deficiency: A Report of Two Patients

Background: Protein C is a zymogen that suppresses the coagulation cascade through proteolysis of factors V and VIII, and therefore its deficiency is a risk factor for thromboembolic events 1. There are two main subtypes of protein C deficiency. In type I protein C deficiency, both protein C antigen and activity levels are decreased, resulting in low protein C or inadequate protein lifespan 2. In type II deficiency, the activity level is lower than the antigen level due to abnormal protein activity 2. Inherited protein C deficiency is caused by either compound heterozygous or homozygous pathogenic variants in the POMC gene. Objective: To describe the clinical presentation and outcomes of 2 severe protein C deficiency cases. Patient #1 is an 8-year-old male with history of neonatal stroke, dense left hemiplegia, and cerebral palsy, who underwent whole exome sequencing due to MRI findings (Figure 1a). This identified an apparently homozygous variant in POMC, c.1154T&amp;gt;C (p. Met385Thr)in exon 9. Both parents were confirmed to be heterozygous carriers. The patient was found to have a normal antigen of 62% and a severely low activity of &amp;lt;10%, suggesting a diagnosis of type II protein C deficiency. He is being considered for extended anticoagulation with a direct Xa or IIa inhibitor or a vitamin K antagonist. Patient #2 was born at 34 weeks and presented immediately following birth with a large occlusive thrombus in the ascending to proximal aorta as well as left ventricular dysfunction and mitral regurgitation (Figure 1b). She was not a candidate for thrombectomy or catheter-directed tissue plasminogen activator (TPA) due to her age and procedural risks. She was given systemic TPA due to severe end organ dysfunction followed by unfractionated heparin (UFH). Due to neurological changes and intracranial hemorrhage (ICH), TPA and UFH were discontinued. Fresh frozen plasma and protein C concentrate were administered and UFH was resumed. Due to worsening ICH, UFH was again stopped, and she developed a left ventricular thrombus, impairing her systemic circulation. Her clinical status worsened, and she became unresponsive to resuscitation efforts, and passed away on DOL 16. Testing identified a protein C antigen and activity level of 10% and &amp;lt;15% respectively. This patient was found to have 2 variants in the PROC gene, c.30C&amp;gt;T (p. Phe10Phe), which is a variant of uncertain significance, and c.1019C&amp;gt;T (p. Thr340Met), which is known to be pathogenic. Discussion: Both cases highlight uncommon presentations of severe protein C deficiency without purpura fulminans. Management of severe protein C deficiency consists of protein C replacement or long-term anticoagulation with warfarin as the standard of care 3,4. However protein C concentrate is costly, requires intravenous access, and can cause hypersensitivity reactions and hemorrhage. Long-term warfarin treatment is burdensome for families, requiring frequent laboratory monitoring with variable time in the therapeutic range. The only curative option for protein C deficiency is liver transplantation, which has additional risks and has rarely been reported in the literature 3,4. Conclusions: These cases illustrate the phenotypic heterogeneity of inherited severe protein C deficiency and demonstrate the challenges of clinical management in this patient population. The International Society on Thrombosis and Haemostasis initiated a severe protein C deficiency registry in 2013 which will standardize and improve treatment of this rare condition.

Evaluation of Patients Referred for Abnormal Digital Rectal Examination With Normal Prostate-Specific Antigen on Best Timed Pathway for Prostate Cancer.

Introduction Currently, there is no recommendation for adjustments to the Best Timed Pathway for Prostate cancer (BTiPP) depending on whether the referral is for raised prostate-specific antigen (PSA) or malignant-feeling prostate on digital rectal examination (DRE). Therefore, all patients undergo MRI scanning.We aim to establish if patients with abnormal DRE only (without raised PSA) should have an adjusted pathway by comparing the biopsy rate and diagnostic yield after an MRI scan. Methods All BTiPP 2021 referral patient notes were reviewed. The patients were categorized into the aDRE group (abnormal DRE with normal PSA) or the rPSA group (raised PSA with or without abnormal DRE).Data and results for MRI and prostate biopsy were evaluated.Diagnostic yield was defined as the percentage of patients who underwent an MRI, who were diagnosed with biopsy-proven cancer. Results 68.5% (74/108) and 70.9% (282/398) of patients underwent upfront MRI in the aDRE and rPSA groups, respectively.Following MRI, the biopsy rate (28.4% (21/74) vs. 42.9% (121/282) (p=0.02)) and the biopsy-proven diagnostic yield (20.3% (15/74) vs. 36.9% (104/282) (p<0.01)) were both significantly lower in the aDRE group. 58% (43/74) of patients in the aDRE group had no posterior lesions on MRI.Only 6.7% (1/15) of biopsy-proven cancers in the aDRE group were solely anterior. Conclusions After MRI, the biopsy rate and diagnostic yield were significantly lower in the aDRE group compared to the rPSA group. Furthermore, a majority of patients referred for aDRE had a normal posterior prostate appearance on MRI. An adjusted pathway for patients referred for aDRE with normal PSA, with DRE by a urologist prior to MRI, should be considered as it would likely reduce unnecessary investigations, treatment, and patient anxiety. These data suggest that this would not risk missing significant cancers.

Initial von Willebrand factor antigen values in adolescent females predict future values.

Diagnosing von Willebrand Disease (VWD) in adolescent females is challenging as menstruation and physiologic stress elevate von Willebrand factor (VWF) laboratory values. To develop a VWF prediction model for adolescent females based on initial VWF results. We identified female patients aged 9 to 21 years with any VWF laboratory test over a 5-year period (2017-2021) at any Texas Children's Hospital facility. Patient demographics, VWF testing, haemoglobin concentration, serum ferritin and site of clinical testing were collected (initial and subsequent laboratory evaluations). A Bayesian linear regression model was developed. Prediction intervals were analysed to identify thresholds for patients in whom repeat testing was unlikely to identify low VWF levels (<50%), consistent with VWD. A total of 6125 adolescent females underwent VWF testing; 1204 (19.7%) had repeat testing. Based on the prediction model, initial VWF antigen values of 80%, 90% and ≥100% carried a 92.6%, 96.6% and ≥98.0% probability of having repeat normal repeat VWF values, respectively.Subjects assessed in outpatient adolescent medicine or gynaecology clinics were more likely to have low VWF values compared to those assessed in the acute care setting (p<.001). Median presenting haemoglobin and serum ferritin were 12.4g/dL and 13ng/mL, respectively and were similar in those with normal versus low VWF antigen values. Repeat testing in adolescent females whose initial VWF antigen values are ≥90% is unlikely to identify additional patients with VWD. Iron deficiency screening should be performed in all adolescent females.