Pancreatic cancer and thromboembolic disease, 150 years after Trousseau

The connection between pancreatic cancer and venous thrombosis has been discussed for almost 150 years. The exact pathophysiological mechanisms are still partly understood, but it is known that pancreatic cancer induces a prothrombotic and hypercoagulable state and genetic events involved in neoplastic transformation (e.g., KRAS, c-MET, p53), procoagulant factors [e.g., tissue factor (TF), platelet factor 4 (PF4), plasminogen activator inhibitor type 1 (PAI-1)], mucin production (e.g., through activation of P- and L-selectin) and pro-inflammatory factors [e.g., cytokines, cyclooxygenase-2 (COX-2)] may be implicated. Also pancreatitis, both acute and chronic, is associated with increased risk of venous thrombosis, but in this circumstance a direct inflammatory process may be more important. This article discusses the incidence, treatment and outcome of venous thromboembolism (VTE) complicating pancreatic disease, with special emphasis on new knowledge obtained during the last fifteen years.     

Acute coronary syndrome following arteriovenous fistula creation in a post CABG patient: A steal phenomenon from coronary artery to subclavian artery

A 70‐year‐old man with a history of coronary artery bypass grafting 15 years back and arteriovenous (AV) fistula creation in the left arm 1 month back presented with acute coronary syndrome (ACS). He had not received dialysis before his referral. We felt the most likely etiology for these complaints was increased cardiac oxygen demand from an increased cardiac output related to the newly formed left AV fistula. Coronary angiography was done to detect any significant stenosis in the native or grafted vessels. This revealed that the left subclavian artery was totally occluded in the ostioproximal segment and the coronary arteries did not have occlusions to explain the ACS setting. CT angiography confirmed the angiographic findings of the totally occluded left subclavian artery followed by a well‐developed and patent left internal mammary artery to left anterior descending artery. This led to the consideration of a steal syndrome from the coronary artery by the subclavian artery distal to the occlusion. A successful percutaneous endovascular intervention on the left subclavian artery occlusion was performed. Subsequently, the patient became asymptomatic and experienced a dramatic increase in left ventricular ejection fraction.     

Comparison of Functional Outcomes,Femoral Rollback and Sagittal Stability of Anterior-Stabilized Versus Posterior-Stabilized Total Knee Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials

PurposeTotal knee arthroplasty (TKA) has improved leaps and bounds in terms of design to improve clinical outcomes and achieve better rehabilitation of the patients. Ultra-congruent inserts (UC) were designed to replace the need for posterior stabilized (PS) implants. The purpose of this review was to evaluate clinical outcomes, femoral rollback, functional scores, range of motion, sagittal laxity, complication rates, and isokinetic performance between UC and PS TKA among RCTsMethodsElectronic databases such as PubMed, Scopus, opengrey, and Cochrane were searched from date of inception up to mid-April 2021, and meta-analysis was performed following PRISMA guidelines. This study analyzed outcomes, femoral rollback, tibial sagittal laxity and isokinetic performance.ResultsTen RCTs identified 852 knees, of which 420 underwent UC TKAs and 432 underwent PS TKA. Compared to UC TKA, a significantly better sagittal stability (p = 0.17) and femoral rollback (p < 0.00001) in PS TKAs was noted, although no statistically significant difference was found in the assessment of the range of motion (p = 0.19) and functional scores. Both the groups had similar isokinetic performance with extensor torque (p = 0.97) and flexor torque (p = 0.37).ConclusionsWe conclude with the current meta-analysis that there are no added benefits for UC over PS inserts and these inserts have a higher sagittal laxity and less femoral roll back in cruciate sacrificing UC knee. But since there are no long-term wear data, UC inserts with CS technique should be used cautiously and may be used only when the PCL cannot be balanced adequately. There is no evidence or only a few to support the superiority of the AS TKA in terms of clinical outcomes or isokinetic performance or femoral external rotation over PS TKA.Level of EvidenceLevel I, Systematic review and meta-analysis of RCTs.     

Autosomal Dominant Polycystic Kidney Disease and Intracranial Aneurysms: Is There an Increased Risk of Treatment?

BACKGROUND AND PURPOSE:Autosomal dominant polycystic kidney disease is associated with an increased risk of intracranial aneurysms. Our purpose was to assess whether there is an increased risk during aneurysm coiling and clipping.MATERIALS AND METHODS:Data were obtained from the National Inpatient Sample (2000–2011). All subjects had an unruptured aneurysm clipped or coiled and were divided into polycystic kidney (n = 189) and control (n = 3555) groups. Primary end points included in-hospital mortality, length of stay, and total hospital charges. Secondary end points included the International Classification of Diseases, Ninth Revision codes for iatrogenic hemorrhage or infarction; intracranial hemorrhage; embolic infarction; and carotid and vertebral artery dissections.RESULTS:There was a significantly greater incidence of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection in the patients with polycystic kidney disease compared with the control group after endovascular coiling. There was also a significantly greater incidence of iatrogenic hemorrhage or infarction in the polycystic kidney group after surgical clipping. However, the hospital stay was not longer in the polycystic kidney group, and the total hospital charges were not higher. Additional analysis within the polycystic kidney group revealed a significantly shorter length of stay but similar in-hospital costs when subjects underwent coiling versus clipping.CONCLUSIONS:Patients with polycystic kidney disease face an increased risk during intracranial aneurysm treatment, whether by coiling or clipping. This risk, however, does not translate into longer hospital stays or increased hospital costs. Despite the additional catheterization-related risks of dissection and embolization, coiling results in shorter hospital stays and similar mortality compared with clipping.

Autosomal dominant polycystic kidney disease (ADPCKD) is a genetic disorder affecting 1 in 1000 individuals worldwide and is associated with an increased risk of intracranial aneurysms, ranging from 4% to 23%^1–6 compared with the general population risk of 2%–3%.^7–10 Patients with ADPCKD are also at increased risk for aneurysm rupture earlier in life (mean age, 35–45 years),^1,11–13 compared with the general population (mean age, 50–54 years).^14,15There is evidence that the associated vascular defects in ADPCKD may be due to mutations in the PKD1 and PKD2 genes, located on the short arm of chromosomes 16 and 4.^16,17 Abnormalities of these genes in mouse models correspond with increased rates of arterial dissection, arterial rupture, and intracranial vascular abnormalities.¹⁸ To our knowledge, only 1 study to date has investigated whether these issues engender an increased risk when treating intracranial aneurysms (whether by endovascular coiling or surgical clipping).² The purpose of this investigation was to assess whether ADPCKD confers an increased peri- and immediate postprocedural risk of aneurysm coiling and clipping.     

A replicon trans-packaging system reveals the requirement of nonstructural proteins for the assembly of bovine viral diarrhea virus (BVDV) virion

A selective trans-packaging system was developed to produce and isolate bovine viral diarrhea virus (BVDV) pseudo-particles with complementing reporter replicons and their packaging proteins expressed in trans with recombinant vaccinia virus. The encapsidation of replicon rNS3-5B was dependent not only on the in trans expression of structural proteins C, E^rns, E1 and E2, but also the nonstructural proteins, p7 and contiguous precursor NS2-3-4A. Nonstructural p7, NS4B, NS5A or NS5B could be expressed in cis and in trans with precursor NS2-3-4A without significantly affecting virion assembly efficiency. NS2-3-4A was identified as an in trans functional precursor in virion assembly. BVDV genomes with mutant NS5B, which did not undergo active replication, were packaged 5-fold less efficiently than the intact genomes demonstrating the importance of replication in virion packaging. These results suggest that genome replication and assembly are closely associated, consistent with a model in which these two steps are coupled for maximum efficiency.     

Induction of autoimmune cholangitis in non‐obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC‐E2) leads to an anti‐mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non‐obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2‐octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti‐mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA‐BSA, but not with BSA alone, develop high titre anti‐mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8⁺ cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.     

Prediction of Caesarean Section from Ultrasound and Clinical Assessment of Fetal Size

EDITORIAL COMMENT: We accepted this paper for publication because the authors have explored the possible value of ultrasound versus clinical assessment of fetal size to see whether they can predict the need for Caesarean section when the baby is large. In this study both the ultrasound and the clinical assessment were impressively accurate and fetal femur length was the most accurate of the ultrasound parameters in assessing fetal weight in predicting the need for Caesarean section. However, as the authors indicate, none of these methods of assessment of fetal size are recommended as an absolute indication for Caesarean section. Every obstetrician uses clinical assessment of the fetus when evaluating management of the patient but the need for clinical judgment remains.
Summary: One hundred and five women with singleton pregnancies and cephalic presentation were assessed. Fundal height and a clinical estimate of fetal weight were recorded. The fetal biparietal diameter, abdominal circumference and femur length were measured with ultrasound. Ultrasound estimated fetal weight was calculated using 3 different formulas (Shepard, Campbell and CUHK). The liquor volume was assessed using the amniotic fluid index.
Ultrasound was able to predict Caesarean section with more reliability than clinical assessment of fetal size or weight. The biparietal diameter, fundal height and amniotic fluid index were poor predictors of mode of delivery. The measurements which best predicted the mode of delivery were the fetal femur length and abdominal circumference. Femur length, but not abdominal circumference, was a statistically better predictor of Caesarean section than clinical estimation of fetal weight. There was no improvement in prediction using ultrasound estimated fetal weight.