Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US.

OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Proteolysis of γ-tubulin small complex proteins is mediated by the ubiquitin-proteasome system.

Microtubule nucleation is mainly mediated by the γ-tubulin ring complex (γTuRC), whose core components are γ-tubulin and γ-tubulin complex proteins GCP2-6. A substantial fraction of γ-tubulin also exists with GCP2 and GCP3 in a tetramer called the γ-tubulin small complex (γTuSC). To date, the mechanisms underlying the turnover of γ-tubulin and GCPs have remained unclear. Here, we show that γ-tubulin, GCP2, and GCP3 are proteolyzed by the ubiquitin-proteasome system, and we identify cullin 1, cullin 4A, and cullin 4B as the E3 ligases that mediate the ubiquitination and, consequently, the degradation of γ-tubulin. Notably, we found that γTuSC disassembly promotes the degradation of γ-tubulin, GCP2, and GCP3, which indicates a role for γTuSCs in the stabilization of its components.

Overexpression of ICAM-1 Predicts Poor Survival in High-Grade Serous Ovarian Carcinoma: A Study Based on TCGA and GEO Databases and Tissue Microarray.

Intercellular cell adhesion molecule-1 (ICAM-1), an important adhesion molecule in the immunoglobulin superfamily, is expressed on many cell types. Recent studies have identified ICAM-1 as a potential oncogene that promotes the development of epithelial ovarian cancer (EOC); it was also found to be associated with poor survival. However, the clinical significance of its expression in high-grade serous ovarian carcinoma (HGSOC) is unclear. Thus, this study aimed to investigate the significance of ICAM-1 expression in HGSOC. Data on ICAM1 expression and mutations in serous ovarian carcinoma (SOC) were obtained from the Cancer Genome Atlas (TCGA), and ICAM1 mRNA expression data in HGSOC were obtained from the Gene Expression Omnibus (GEO) database. ICAM-1 expression was evaluated by immunohistochemistry in HGSOC and normal fallopian tube tissues microarray. In TCGA data, amplification/mutation of ICAM1 was identified in 12% of serous ovarian carcinoma samples, and overexpression of ICAM1 mRNA predicted reduced overall survival in SOC. From TCGA and GEO data, SOC patients with ICAM1 mRNA overexpression treated with chemotherapeutic drugs that contained taxol or taxol and platin together had significantly reduced progression-free survival. According to GEO data, ICAM1 mRNA expression was found significantly higher in HGSOC than in control samples. In our study, ICAM-1 overexpression was observed in 63.1% (65/103) of HGSOCs. As a prognostic biomarker, overexpression of ICAM-1 predicted reduced recurrence-free and overall survival and is an independent risk factor for poor prognosis. These findings suggest that overexpression of ICAM-I is an independent indicator of poor prognosis for HGSOC and that it can serve as an effective clinical prognostic biomarker for this disease.

Start-Up of a Biofilter in a Full-Scale Groundwater Treatment Plant for Iron and Manganese Removal.

In recent years, biological purification technology has been widely developed in the process of iron and manganese removal from groundwater. The cultivation and maturation of the biological filter layer are key for biological iron and manganese removal processes. The time needed for maturation varies significantly with the water quality, filter and filter media conditions and operation parameters; sometimes it takes only one or two months, sometime more than half a year. In this paper, the feasibility of adopting an intermittent operation for the cultivation of biofilter was investigated with productive filters in a groundwater treatment plant, and the comparative test of the filter column was conducted. The results showed that the intermittent operation had little effect on the cultivation of the biofilter because dissolved oxygen would be gradually exhausted during the filter-suspension process, making the filter layer anaerobic, thus possibly inhibiting the growth and reproduction of IMOB (Iron and Manganese Oxidizing Bacteria). At the same time, the test shows that when the mature biological filter needs the suspension operation, the emptying method should be considered to avoid the destruction of the biological layer.

Primary Cervical Malignant Melanoma: 2 Cases and a Literature Review.

Primary cervical malignant melanoma (MM) is an extremely rare tumor, and we are only aware of 44 reported cases. Further information is needed with regard to this disease's clinicopathologic features. Two patients (55 and 81 yr old) with postmenopausal vaginal bleeding were diagnosed with primary cervical MM on the basis of hematoxylin-eosin staining and immunohistochemistry findings. Our literature review revealed that the average age in cases of primary cervical MM was 59 yr (range, 34-81 yr); 93% of patients presented with vaginal bleeding, and 82% of patients were diagnosed at an early clinical stage (International Federation of Gynecology and Obstetrics stages I-II). Primary cervical MM is an extremely rare cervical tumor and is associated with a poor prognosis. Histologic morphology and immunohistochemistry are very important considerations for diagnosing this disease, which must be differentiated from cervical undifferentiated carcinoma, leiomyosarcoma, and malignant peripheral schwannoma.

[Arsenic(â ¤) Removal by Granular Adsorbents Made from Backwashing Residuals from Biofilters for Iron and Manganese Removal].

Granular adsorbents for arsenic removal (GA) made from the backwashing residuals from iron and manganese removal biofilters for groundwater were characterized and examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy, X-ray diffraction (XRD), and BET surface area measurement. The results showed that the GA had rough surfaces, developed pores, and were mainly amorphous, with small fractions of crystalline quartz and hematite. The surface area of the GA, which consists of many mesopores, was 43.8 m2·g-1. The kinetic studies revealed that arsenate adsorption on the GA was described by a pseudo-second-order kinetic equation, and the Freundlich isotherm equation fit the arsenate adsorption well (R2=0.994). The maximum adsorption capacity calculated by the Langmuir isotherm equation for As(Ⅴ) was 5.05 mg·g-1. Further studies showed that the GA operated well for As(Ⅴ) removal over a broad range in pH from 1.1 to 9.5. The coexistence of HCO3- and SO42- had no great influence on arsenic adsorption, while the H2PO4- and SiO32- showed negative effects. The GA can be regenerated well, and 82% of the original adsorption capacity was maintained after three regeneration cycles.

Ovarian microcystic stromal tumor with undetermined potential: case study with molecular analysis and literature review.

Ovarian microcystic stromal tumor is a relatively rare tumor type. This tumor is characterized by a unique microcyst structure, and essentially all tumors show benign biological behavior. Here, we report a case with a primary ovarian microcystic stromal tumor that experienced recurrence. Pathological findings showed that the original tumor, relapsed tumor in the ovary, and the recurrent tumor in the iliac fossa presented similar histologic features. The tumor mainly consisted of microcysts, solid cellular regions, and a fibrous stroma. Immunohistochemically, the tumor cells were positive for ß-catenin, CD10, vimentin, and WT-1. Mutational analysis revealed a missense mutation (c.1590C>T; pG530E) in exon 15 of the APC gene and another missense mutation (c.740G>A; pA247V) in exon 1 of the KRAS gene. We also reviewed other published cases to evaluate the prognosis and treatment. This is the first report to describe a microcystic stromal tumor of the ovary presenting with undetermined biological potential.

Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y1 Receptor.

The human P2Y1 receptor (P2Y1R) is a purinergic G-protein-coupled receptor (GPCR) that functions as a receptor for adenosine 5'-diphosphate (ADP). An antagonist of P2Y1R might potentially have antithrombotic effects, whereas agonists might serve as antidiabetic agents. On the basis of the antagonist-bound MRS2500-P2Y1R crystal structure, we constructed computational models of apo-P2Y1R and the agonist-receptor complex 2MeSADP-P2Y1R. We then performed conventional molecular dynamics (cMD) and accelerated molecular dynamics (aMD) simulations to study the conformational dynamics after binding with agonist/antagonist as well as the P2Y1R activation mechanism. We identified a new agonist-binding site of P2Y1R that is consistent with previous mutagenesis data. This new site is deeper than those of the agonist ADP in the recently simulated ADP-P2Y1R structure and the antagonist MRS2500 in the MRS2500-P2Y1R crystal structure. During P2Y1R activation, the cytoplasmic end of helix VI shifts outward 9.1 Å, the Ser1463.47-Tyr2375.58 hydrogen bond breaks, a Tyr2375.58-Val2626.37 hydrogen bond forms, and the conformation of the χ1 rotamer of Phe2696.44 changes from parallel to perpendicular to helix VI. The apo-P2Y1R system and the MRS2500-P2Y1R system remain inactive. The newly identified agonist binding site and activation mechanism revealed in this study may aid in the design of P2Y1R antagonists/agonists as antithrombotic/antidiabetic agents, respectively.

Primary tumor site and anti-EGFR monoclonal antibody benefit in metastatic colorectal cancer: a meta-analysis.

AIM: This meta-analysis aimed to document the impact of primary tumor site on anti-EGFR monoclonal antibody (mAb) benefit in metastatic colorectal cancer. MATERIALS & METHODS: Tumors with metastatic left-sided colorectal cancer (LCC) were compared with tumors with metastatic right-sided colon cancer (RCC) with respect to anti-EGFR mAb objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) benefit. RESULTS: Comparing LCC with RCC, LCC was found to have significantly superior anti-EGFR mAb ORR (p < 0.00001), OS (p < 0.00001) and PFS (p < 0.00001) benefit. Additionally, anti-EGFR mAb therapy significantly improved both OS and PFS for LCC compared with no anti-EGFR mAb therapy, but not for RCC. The test of interaction was also apparent for OS (p = 0.0002) and PFS (p = 0.0002). CONCLUSION: This meta-analysis demonstrated that LCC had markedly superior anti-EGFR mAb treatment benefit compared with RCC.

Decreased risk of developing cancer in subjects carrying SLC52A3 rs13042395 polymorphism: proof from a meta-analysis.

AIM: This study aimed to conduct a meta-analysis to explore the association between SLC52A3 rs13042395 polymorphism and cancer risk. MATERIALS & METHODS: A comprehensive literature search was performed to confirm the relationship evaluated using STATA 12.0 software. RESULTS: Overall, SLC52A3 rs13042395 C>T polymorphism was associated with cancer risk in two genetic models (TT vs CC: odds ratio: 0.86; 95% CI: 0.80-0.93; p < 0.001, TT vs CC + CT: odds ratio: 0.88; 95% CI: 0.82-0.95; p = 0.001). Significant associations were found between SLC52A3 rs13042395 polymorphism and decreased cancer risk among esophageal cancer, Asians, female, normal BMI and old age groups. No significant associations were observed in alcohol and smoking groups. CONCLUSION: SLC52A3 rs13042395 C>T polymorphism might be a potential biomarker for cancer susceptibility.

Imaging findings of multiple infantile hepatic hemangioma associated with cardiac insufficiency.

BACKGROUND: Infantile hepatic hemangioma (IHH) as a benign liver tumor in infancy and childhood is commonly associated with high output cardiac failure. The present study aims to describe the imaging findings in a patient who was diagnosed as having multiple IHH with congestive cardiac insufficiency. METHODS: The imaging findings and clinical manifestations of the patient with multiple IHH associated with cardiac insufficiency were retrospectively reviewed. RESULTS: Ultrasonography showed multiple intrahepatic lesions with mixed echoes and markedly expanded hepatic veins and the inferior vena cava of the patient. Echocardiography revealed right heart insufficiency and pulmonary hypertension. Contrast-enhanced MRI showed early mild enhancement of lesions and more obvious delayed enhancement. The patient died after combined therapy of surgery and hormone. CONCLUSIONS: The imaging findings of multiple IHH associated with cardiac insufficiency are typical and diagnostic. Early imaging assessment may facilitate the diagnosis and treatment of the disease.

Efficacy of electrocoagulation in sealing the cystic artery and cystic duct occluded with only one absorbable clip during laparoscopic cholecystectomy.

BACKGROUND: Even though laparoscopic cholecystectomy (LC) emerged over 20 years ago, controversies persist with regard to the best method to ligate the cystic duct and artery. We proposed to assess the effectiveness and safety of electrocoagulation to seal the cystic artery and cystic duct after their occlusion with only one absorbable clip. MATERIALS AND METHODS: We retrospectively compared the clinical data for 635 patients undergoing LC using electrocoagulation to seal the cystic artery and cystic duct that were occluded with only one absorbable clip (Group 1) and 728 patients undergoing LC using titanium clips (Group 2). In parallel, 30 rabbits randomized into six groups underwent cholecystectomy. After cystic duct ligation with absorbable or titanium clips, the animals were sacrificed 1, 3, or 6 months later, and intraabdominal adhesions were assessed after celiotomy. RESULTS: The mean operative time was significantly shorter (41.6 versus 58.9 minutes, P<.01) in Group 1 than in Group 2. No cystic duct leaks occurred in any patients from Group 1, compared with seven leaks among the 728 (0.96%) patients from Group 2 (P<.05). The morbidity was significantly higher in Group 2 than in Group 1 (3.43% versus 1.58%). Mean intraoperative blood loss and hospitalization length were not significantly different between the two groups, and no deaths occurred in either group. In animal experiments, adhesion was tighter for absorbable than for titanium clips, but fibrous tissue encapsulation was thinner at the site of titanium clips. CONCLUSIONS: Electrocoagulation of the cystic artery and cystic duct that were occluded with only one absorbable clip is safe and effective during LC. This approach is associated with shortened operative times and reduced leakage, compared with the standard method using metal clips.

[Coracoclavicular ligament reconstruction using autologous double-strand palmaris longus tendon and artificial ligament for the treatment of acromioclavicular joint dislocation].

OBJECTIVE: To investigate clinical effects of coracohumeral ligament reconstruction with autologous double-strand of long palmaris longus tendon and artificial ligament for the treatment of acromioclavicular joint dislocation. METHODS: From April 2006 to June 2009, 31 patients with acromioclavicular joint dislocation were treated with coracohumeral ligament reconstruction using autologous double-strand palmaris longus tendon and artificial ligament. There were 18 males and 13 females, ranging in age from 18 to 60 years, with an average of 35 years. Twenty-six patients were acute trauma and other 5 patients were chronic trauma. Preoperative symptoms included different degrees of pain, restricted movement, and instability of acromioclaviecular joint. The X-ray showed acromioclavicular joint dislocation. RESULTS: The patients had good incision union without vascular and nerve injuries. All the patients were followed up, and the average duration was 23 months. The JOA scores decreased from preoperative (38.8 +/- 1.5) to (73.2 +/- 1.1) at 1 month after operation,and (93.5 +/- 0.8)at the last follow-up. Twenty-eight patients got an excellent result, 2 good and 1 fair. CONCLUSION: The reconstruction of coracohumeral ligament using autologous double-strand palmaris longus tendon and artificial ligament is an effective method for the treatment of acromioclavicular joint dislocation.