The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre-eclampsia, intra-uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante-natal bleeding or intra-partum or postpartum haemorrhage was observed. However, FVL was associated with birth-weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI₉₅) 1·04–3·31] and neonatal death (OR 14·79; CI₉₅ 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy-related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies.     

Effect of percutaneous coronary intervention on coronary blood flow at rest in myocardial sites remote from the intervention site in patients with stable angina pectoris

Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion.     

Anorectal Physiology in Solitary Ulcer Syndrome: A Case-Matched Series

PURPOSE Solitary ulcer syndrome is a rare condition characterized by inflammation and chronic ulcer of the rectal wall in patients suffering from outlet constipation. Despite similar surgical options (rectopexy, anterior resection), solitary ulcer syndrome may differ from overt rectal prolapse with regard to symptoms and pathogenesis. The present work analyzed differences between these conditions in a case-control physiology study. METHODS From 1997 to 2002, 931 consecutive subjects were investigated in a single physiology unit for anorectal functional disorders. Standardized questionnaires, anorectal physiology, and evacuation proctography were included in a prospective database. Diagnosis of solitary ulcer syndrome was based on both symptoms and anatomic features in 25 subjects with no overt rectal prolapse (21 females and 4 males; mean age, 37.2 ± 15.7 years) and no past history of anorectal surgery. They were compared with age-matched and gender-matched subjects: 25 with outlet constipation (also matched on degree of internal procidentia), 25 with overt rectal prolapse without any mucosal change, and 14 with overt rectal prolapse and mucosal changes. RESULTS Subjects with solitary ulcer syndrome reported symptomatic levels (digitations, pain, incontinence) similar to those of patients with outlet constipation, but they had significantly more constipation and less incontinence than patients with overt rectal prolapse. Compared with each of the three control groups (dyschezia, rectal prolapse without mucosal change, and rectal prolapse with mucosal change), subjects with solitary ulcer syndrome more frequently had an increasing anal pressure at strain (15 vs. 5, 3, and 1, respectively ; P < 0.01) and a paradoxical puborectalis contraction (15 vs. 9, 1, and 1, respectively; P < 0.05). With respect to evacuating proctography, complete rectal emptying was achieved less frequently in this group (5 vs. 12, 23, and 10, respectively; P < 0.05). Compared with patients with overt rectal prolapse, mean resting and squeezing anal pressures were significantly higher in both groups of subjects with solitary ulcer syndrome and with outlet constipation. Prevalence and levels of anatomic disorders (perineal descent, rectocele) did not differ among the four groups except for rectal prolapse grade and prevalence of enterocele (higher in overt rectal prolapse group). Interestingly, and despite matched controls for degree of intussusception, individuals with solitary ulcer syndrome had circular internal procidentia more often compared with those suffering from outlet constipation without mucosal lesions (15 vs. 8, P < 0.05). CONCLUSION This case-controlled study quantifies functional anal disorders in patients suffering from solitary ulcer syndrome. Despite no proven etiologic factor, sphincter-obstructed defecation and circular internal procidentia both may play an important part in the pathogenesis and an exclusive surgical approach may not be appropriate in this context. Presented at the meeting of the American Gastroenterology Association, New Orleans, Louisiana, May 18, 2004.     

Characterization of pandemic influenza immune memory signature after vaccination or infection

The magnitude, quality, and maintenance of immunological memory after infection or vaccination must be considered for future design of effective influenza vaccines. In 2009, the influenza pandemic produced disease that ranged from mild to severe, even fatal, illness in infected healthy adults and led to vaccination of a portion of the population with the adjuvanted, inactivated influenza A(H1N1)pdm09 vaccine. Here, we have proposed a multiparameter quantitative and qualitative approach to comparing adaptive immune memory to influenza 1 year after mild or severe infection or vaccination. One year after antigen encounter, severely ill subjects maintained high levels of humoral and polyfunctional effector/memory CD4⁺ T cells responses, while mildly ill and vaccinated subjects retained strong cellular immunity, as indicated by high levels of mucosal homing and degranulation markers on IFN-γ⁺ antigen-specific T cells. A principal component analysis distinguished 3 distinct clusters of individuals. The first group comprised vaccinated and mildly ill subjects, while clusters 2 and 3 included mainly infected individuals. Each cluster had immune memory profiles that differed in magnitude and quality. These data provide evidence that there are substantial similarities between the antiinfluenza response that mildly ill and vaccinated individuals develop and that this immune memory signature is different from that seen in severely ill individuals.     

Arguments for an individualized closure of the pancreatic remnant after distal pancreatic resection

AIM:To analyze risk factors for postoperative pancreatic fistula(POPF) rate after distal pancreatic resection(DPR).METHODS:We performed a retrospective analysis of 126 DPRs during 16 years.The primary endpoint was clinically relevant pancreatic fistula.RESULTS:Over the years,there was an increasing rate of operations in patients with a high-risk pancreas and a significant change in operative techniques.POPF was the most prominent factor for perioperative morbidity.Significant risk factors for pancreatic fistula were high body mass index(BMI) [odds ratio(OR) = 1.2(CI:1.1-1.3),P = 0.001],high-risk pancreatic pathology [OR = 3.0(CI:1.3-7.0),P = 0.011] and direct closure of the pancreas by hand suture [OR = 2.9(CI:1.2-6.7),P = 0.014].Of these,BMI and hand suture closure were independent risk factors in multivariate analysis.While hand suture closure was a risk factor in the low-risk pancreas subgroup,high BMI further increased the fistula rate for a high-risk pancreas.CONCLUSION:We propose a risk-adapted and indication-adapted choice of the closure method for the pancreatic remnant to reduce pancreatic fistula rate.