Blood contains microparticles (MPs) derived from a variety of cell types, including platelets, monocytes, and endothelial cells. In addition, tumors release MPs into the circulation. MPs are formed from membrane blebs that are released from the cell surface by proteolytic cleavage of the cytoskeleton. All MPs are procoagulant because they provide a membrane surface for the assembly of components of the coagulation protease cascade. Importantly, procoagulant activity is increased by the presence of anionic phospholipids, particularly phosphatidylserine (PS), and the procoagulant protein tissue factor (TF), which is the major cellular activator of the clotting cascade. High levels of platelet-derived PS + MPs are present in healthy individuals, whereas the number of TF + , PS + MPs is undetectable or very low. However, levels of PS + , TF + MPs are readily detected in a variety of diseases, and monocytes appear to be the primary cellular source. In cancer, PS + , TF + MPs are derived from tumors and may serve as a useful biomarker to identify patients at risk for venous thrombosis. This review will summarize our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis.

Microparticles in Hemostasis and Thrombosis

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

BACKGROUND
Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.


METHODS
We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.


FINDINGS
We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.


INTERPRETATION
Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.


FUNDING
The Canadian Institutes of Health Research.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Defining Responses to Therapy and Study Outcomes in Clinical Trials of Invasive Fungal Diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21572

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.

To study whether the occurrence and type of placental lesions vary according to the time of onset of COVID‐19 in pregnant women.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1471-0528.17458

Development of placental lesions after recovery from COVID‐19 during pregnancy: case–control study

Introduction: Current guidelines recommend neoadjuvant treatment before resection for pancreatic adenocarcinoma invading the splenomesentericoportal venous axis, but comparative studies are lacking. This study compared the outcomes of upfront (UR) and resections after neoadjuvant chemotherapy (NAC) for pancreatic adenocarcinomas with venous invasion. Methods: We retrospectively reviewed clinical data of patients who underwent pancreaticoduodenectomy(PD) with venous resection (VR) for pancreatic adenocarcinoma between January 1 2006, and December 31 2020. Operative, pathologic and survival outcomes were compared between upfront and resections after NAC. Results: There were 169 patients, preoperative chemotherapy was administered to 55 patients and 114 underwent UR. There were no differences in operative time, morbidity and mortality between the two groups of patients(p>0.05). At pathologic examination patients undergoing resection after NAC had statistically significant smaller tumor, higher rate of R0 resection , less lympnodes involvement and lower rate of pathologic venous invasion (p<0.05).The median overall survival was 27.96 months (95% CI: 23.4 -34.5). Overall survival rates at one, 3, 5, 10 years were 82%, 39%, 22% and 11%, respectively. Median overall survival was longer in patients undergoing preoperative treatment (36.1 vs 22.8months; p= 0.02) but similar from the time of resection (26.0 vs 22.8 months; p= 0.55). Multivariate Cox analysis found neoadjuvant treatment (HR: 0.60; 95% CI:0.38-0.97; p =0.03), and perioperative transfusion (HR: 2.25; 95% CI:1.47-3.46; p =0.0002), as independent prognostic factors for overall survival. Conclusions: Neoadjuvant chemotherapy improves the pathologic and survival outcomes of pancreaticoduodenctomy with venous resection for pancreatic adenocarcinomas. 

Upfront versus Resection after Neoadjuvant Chemotherapy for Pancreatic Adenocarcinoma with Venous Involvement: A Comparative Study of Operative, Pathologic and Survival Outcomes

/pdf/correction-pancreatectomy-after-neoadjuvant-folfirinox-2bc42wmf.pdf

Correction: Pancreatectomy After Neoadjuvant FOLFIRINOX Chemotherapy: Identifying Factors Predicting Long-Term Survival.

Biliary strictures are frequently encountered in interventional endoscopy. Their etiological diagnosis may be complicated [1]. Endoscopic ultrasound (EUS) guided biopsies, brush cytology, and wire-guided biopsies allow a diagnosis in most cases. Single-operator cholangioscopy (SOC) has radically changed the diagnostic approach, allowing visualization of the lesion, endoscopic characterization, and targeted biopsies [2]. We report the case of a 71-year-old woman with a history of endometrial adenocarcinoma, with muscular and bone recurrence 4 years after treatment. She developed a sudden jaundice without any other clinical signs. A magnetic resonance cholangiopancreatography found a circumferential parietal thickening of the main bile duct with dilatation of the intrahepatic bile ducts (▶Fig. 1). We decided to perform an EUS, which showed extensive cholangitis in the middle part of the bile duct with circumferential thickening of the bile duct mucosa. A 22 G needle biopsy was performed. Endoscopic retrograde cholangiopancreatography (ERCP) was then performed (▶Fig. 2) with SOC, which showed that the strictured area was indeed a fibrous stenosis with anarchic vascularization (▶Video 1). Biopsies were taken with forceps. Brush cytology and wire-guided biopsies were also performed. The procedure was completed with the placement of three plastic stents (one 15 cm and 8.5 Fr stent in the left bile duct; one 12 cm and 8.5 Fr stent and one 12 cm and 7 Fr stent in the right intrahepatic bile ducts). Histological examination found carcinomatous cells (mutated p53, PAX8+), which were presumed to be metastasis of gynecological origin (▶Fig. 3). The use of SOC allows a finer analysis of indeterminate biliary stenosis. The presence of aberrant vascularization seems to be correlated with the neoplastic nature of the lesion [3]. SOC therefore allows macroscopic analysis of the lesion and targeted biopsies, probably making biliary sampling less random [4, 5].

/pdf/an-unusual-malignant-main-bile-duct-stricture-a-biliary-16he1jau.pdf

An unusual malignant main bile duct stricture: a biliary metastasis of endometrial adenocarcinoma.

Introduction: This study aimed to evaluate the results of synchronous liver resection for metastatic pancreatic ductal adenocarcinomas and to identify prognostic factors for overall survival. Methods: We retrospectively reviewed a clinical data of patients who underwent synchronous resection of pancreatic adenocarcinoma with liver metastases (LMs) between January 1 2008, and December 31 2020. Cox analyses were used to assess prognostic factors for survival. Results: There were 92 patients and preoperative chemotherapy was administered to 52 patients while the remaining underwent upfront surgery. The median overall survival was 18.26 months (95% CI: 14.7 -22.7) with overall survival rates at one, 3, 5 years were 70%, 10%, and 0%, respectively. Median recurrence-free survival was 5.44 months (95% CI: 4.5-6.9). Median overall survival was longer after neoadjuvant chemotherapy (22.7 vs 13.8 months; p= 0.01) but similar after pancreaticoduodenectomy or distal pancreatectomy, (20.8 vs18.2months; p=0.65) and resection of a single or multiple LM (18.9 vs.18.2; p=0.68). Multivariate Cox analysis found CA19-9 levels <500 kU/l (HR: 0.26; 95% CI:0.13-0.53; p =0.0002), R0 resection (HR: 0.28; 95% CI:0.13-0.58; p =0.0006), histologic venous invasion (HR: 2.83; 95% CI:1.35-5.92; p =0.0006) and neoadjuvant chemotherapy (HR: 0.41; 95% CI:0.21-0.78; p =0.007) as independent prognostic factors for overall survival. Conclusions: Oligometasatic liver disease can be resected safely at the time of pancreatic resection. Neoadjuvant chemotherapy and preresectional CA 19-9 serum values could select optimal candidate for surgery. Further experience and comparative studies with exclusive medical treatment are needed to validate surgery for oligometastatic patients. 

Gerlinde Averous

Papers

Development of placental lesions after recovery from COVID‐19 during pregnancy: case–control study

Upfront versus Resection after Neoadjuvant Chemotherapy for Pancreatic Adenocarcinoma with Venous Involvement: A Comparative Study of Operative, Pathologic and Survival Outcomes

Correction: Pancreatectomy After Neoadjuvant FOLFIRINOX Chemotherapy: Identifying Factors Predicting Long-Term Survival.

An unusual malignant main bile duct stricture: a biliary metastasis of endometrial adenocarcinoma.

Resection of Pancreatic Adenocarcinomas with Synchronous Liver Metastases: Analysis of Prognostic Factors for Survival