INTRAVITREAL ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO OCULAR HISTOPLASMOSIS: Ten-Year Follow-Up.

PURPOSE: To assess the long-term efficacy of intravitreal antivascular endothelial growth factor injections (IVI), alone or in combination with verteporfin photodynamic therapy (IVI/PDT), for management of choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome (POHS). METHODS: Retrospective, comparative, interventional case series analyzing 82 eyes in 74 patients treated with either IVI or IVI/PDT for presumed ocular histoplasmosis syndrome choroidal neovascularization from January 2006 to January 2021. RESULTS: The average logarithm of the minimum angle of resolution VA in year 5 was 0.40 (20/50) and 0.52 (20/67) for IVI versus IVI/PDT groups, respectively ( P = 0.33), and in year 10 was 0.53 (20/58) and 0.64 (20/86), respectively ( P = 0.50). The average number of annual injections over the first 5 years of follow-up was 3.3 versus 1.7 for IVI versus IVI/PDT groups, respectively ( P < 0.001), and over 10 years was 3.3 versus 1.6, respectively ( P < 0.001). Treatment-free interval of 5 years was reached by 39% versus 60% in IVI versus IVI/PDT groups, respectively ( P = 0.95). CONCLUSION: Our study found both IVI and IVI/PDT to be effective in long-term management of presumed ocular histoplasmosis syndrome choroidal neovascularization, with a fewer number of annual injections and longer treatment-free interval in the combination group. However, given the limitations of a retrospective study, a prospective randomized study is necessary to determine whether the addition of PDT significantly decreases treatment burden.

Stat2 loss disrupts damage signalling and is protective in acute pancreatitis.

The severity of sterile inflammation, as seen in acute pancreatitis, is determined by damage-sensing receptors, signalling cascades and cytokine production. Stat2 is a type I interferon signalling mediator that also has interferon-independent roles in murine lipopolysaccharide-induced NF-κB-mediated sepsis. However, its role in sterile inflammation is unknown. We hypothesised that Stat2 determines the severity of non-infective inflammation in the pancreas. Wild type (WT) and Stat2-/- mice were injected i.p. with caerulein or l-arginine. Specific cytokine-blocking antibodies were used in some experiments. Pancreata and blood were harvested 1 and 24 h after the final dose of caerulein and up to 96 h post l-arginine. Whole-tissue phosphoproteomic changes were assessed using label-free mass spectrometry. Tissue-specific Stat2 effects were studied in WT/Stat2-/- bone marrow chimera and using Cre-lox recombination to delete Stat2 in pancreatic and duodenal homeobox 1 (Pdx1)-expressing cells. Stat2-/- mice were protected from caerulein- and l-arginine-induced pancreatitis. Protection was independent of type I interferon signalling. Stat2-/- mice had lower cytokine levels, including TNF-α and IL-10, and reduced NF-κB nuclear localisation in pancreatic tissue compared with WT. Inhibition of TNF-α improved (inhibition of IL-10 worsened) caerulein-induced pancreatitis in WT but not Stat2-/- mice. Phosphoproteomics showed downregulation of MAPK mediators but accumulation of Ser412-phosphorylated Tak1. Stat2 deletion in Pdx1-expressing acinar cells (Stat2flox/Pdx1-cre ) reduced pancreatic TNF-α expression, but not histological injury or serum amylase. WT/Stat2-/- bone marrow chimera mice were protected from pancreatitis irrespective of host or recipient genotype. Stat2 loss results in disrupted signalling in pancreatitis, upstream of NF-κB in non-acinar and/or bone marrow-derived cells. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Smartphone Application as an Education Platform in Hepato-Pancreato-Biliary Surgery.

Background. There are no data to assess the need for smartphone applications (SA) as an educational tool in hepato-pancreato-biliary (HPB) surgery. The primary objective of this study was to assess if SA can be used as an educational tool in HPB surgery. The secondary objective was to assess if SA can help as a decision-making tool for fellowship applicants in HPB surgery. Methods. A preapproved questionnaire was e-mailed by International Hepato-Pancreato-Biliary Association to all its 2350 members. Results. Two hundred seventy-one surgeons responded to the survey. Eight were excluded for incomplete data. A total of 48.7% of responders were between 28 and 43 years old (generation X) and 45.2% between 44 and 62 years old (baby boomers). A total of 37.6% of the responders considered SA as an effective method to teach future trainees, and there were slightly higher odds of choosing SA as a teaching tool if the responder considered themselves as an innovator (odds ratio: 2.24). A total of 87.8% of the responders believe that SA in HPB surgery can be directed toward surgical trainees' education, and 91.6% believed SA can be directed toward a fellow. Ninety-five percent of the responders believed that SA in HPB surgery can possibly help a future applicant to choose an HPB fellowship program. Conclusion. SA can complement other teaching techniques and educational tools in HPB surgery. In addition, it can potentially be used as a platform for HPB surgery fellowship by helping in making a decision regarding appropriate fellowship programs.

Neutrophil: Lymphocyte ratio as a method of predicting complications following hepatic resection for colorectal liver metastasis.

BACKGROUND AND OBJECTIVES: Approximately 30-50% of patients with colorectal cancer develop liver metastasis for which liver resection is the only hope for potential cure. However, hepatic resection is associated with considerable morbidity. The aim was to detect early complications by utilising the neutrophil: lymphocyte ratio (NLR). METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single institution between 2008 and 2016. Baseline demographics and complications within 30 days following surgery were recorded, with blood tests measured until day 7. Statistical analysis was performed using Mann Whitney and ROC analysis. RESULTS: One hundred eighty-eight operations were included. 47.3% had an associated complication, of which 31.46% were major. The median NLR was 6.31 across the cohort, 5.44 for uncomplicated procedures, 7.0 for complications and 10.65 in major complications. Median NLR was the best parameter for detecting major complications versus minor complications (AUC 0.74) as opposed to lymphocytes (AUC 0.65), neutrophils (AUC 0.60), and CRP (AUC 0.60). The diagnostic ability of NLR increased further when predicting major complications versus an uncomplicated recovery (AUC 0.78), and it was the only significant parameter in the early post-operative period on days 2, 3, and 4 (AUC 0.70, 0.72, and 0.75). CONCLUSIONS: The NLR may have a role in predicting complications following hepatic resection for CLM, and with earlier detection, potentially improving outcomes.

Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis.

PURPOSE: To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010. INTERVENTION: Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT). MAIN OUTCOME MEASURES: Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals. RESULTS: A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up. CONCLUSIONS: There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS.

Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets. METHODS: DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment. RESULTS: DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained. CONCLUSIONS: We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.

Solid-phase synthesis of a library based on biphenyl-containing trypsin-like serine protease inhibitors.

The solid-phase synthesis of a library based on an unusual biphenyl-containing trypsin-like serine protease inhibitor is described. Key to this effort was the synthesis of a highly functionalized aryl boronic acid reagent which required the development of a novel and efficient method to convert a triflate to a pinacolboronate in large scale.

ADAM17-Mediated Reduction in CD14++CD16+ Monocytes ex vivo and Reduction in Intermediate Monocytes With Immune Paresis in Acute Pancreatitis and Acute Alcoholic Hepatitis.

Impaired immune responses and increased susceptibility to infection characterize acute inflammatory conditions such as pancreatitis and alcoholic hepatitis and are major causes of morbidity and mortality. However, the mechanisms that drive this apparent immune paresis remain poorly understood. Monocytes mediate host responses to damage and pathogens in health and disease, and three subsets of monocytes have been defined based on CD14 and CD16 expression. We sought to determine the changes in monocyte subsets in acute pancreatitis (AP) and acute alcoholic hepatitis (AAH), together with functional consequences and mechanisms that underlie this change. Peripheral blood mononuclear cells (PBMCs) from patients with AP or AAH were compared with healthy controls. Monocyte subsets were defined by HLA-DR, CD14, and CD16 expression. Changes in surface and intracellular protein expression and phosphorylation were determined by flow cytometry. Phenotype and function were assessed following stimulation with lipopolysaccharide (LPS) or other agonists in the presence of specific inhibitors of TNFα and a disintegrin and metalloproteinase 17 (ADAM17). Patients with AP and AAH had reduced CD14++CD16+ intermediate monocytes compared to controls. Reduction of intermediate monocytes was recapitulated ex vivo by stimulating healthy control PBMCs with Toll-like receptor (TLR) agonists LPS, flagellin or polyinosilic:polycytidylic acid (poly I:C). Stimulation caused shedding of CD14 and CD16, which could be reversed using the ADAM17 inhibitor, TMI005 but not direct inhibitors of TNFα, a known ADAM17-target. Culturing PBMCs from healthy controls resulted in expansion of intermediate monocytes, which did not occur when LPS was in the culture medium. Cultured intermediate monocytes showed reduced expression of CX3CR1, CCR2, TLR4, and TLR5. We found reduced migratory responses, intracellular signaling and pro-inflammatory cytokine production, and increased expression of IL-10. Stimulation with TLR agonists results in ADAM17-mediated shedding of phenotypic markers from CD16+ monocytes, leading to apparent "loss" of intermediate monocytes. Reduction in CD14++CD16- monocytes and increased CD14++CD16+ is associated with altered responses in functional assays ex vivo. Patients with AP and AAH had reduced proportions of CD14++CD16+ monocytes and reduced phosphorylation of NFκB and IL-6 production in response to bacterial LPS. Together, these processes may contribute to the susceptibility to infection observed in AP and AAH.

Factors affecting length of stay after percutaneous biliary interventions.

OBJECTIVE:: To evaluate the factors affecting the length of hospital stay (LOS) after percutaneous transhepatic biliary drainage (PTBD). METHODS:: A retrospective review of all patients who had undergone PTBD with or without stenting at a UK specialist centre between 2005 and 2016 was conducted. RESULTS:: 692 patients underwent 1976 procedures over 731 clinical episodes for which, the median age was 65 (range 18-100) years, and the median Charlson Index was 3. PTBD was performed for malignant (n = 563) and benign strictures (n = 60), stones (n = 62), and bile leaks (n = 46). The median LOS was 13 (range 0-157) days, and the median interprocedure duration was 9 (range 0-304) days. The median number of procedures per patient was 2 and the median number of days required to complete a set of procedures for a patient (TBID) ranged from 0 to 557 days, with a median of 16 (interquartile range: 8-32) days. Patients with biliary leak had the highest LOS. Biliary stents were mostly placed at the second stage at a median of 6 (range 0-120) days from the first procedure day. Placement of a biliary stent in the first stage of the procedure was associated with shorter LOS (p < 0.001). CONCLUSIONS:: Biliary stenting at index procedure reduces LOS, although it is not always technically possible. Patients with bile leak managed with PTBD have longer LOS. ADVANCES IN KNOWLEDGE:: This study provides data which can help in appropriate consenting, better planning, and efficient resource utilization for patients undergoing PTBD.

Pyridine amides as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series.

Ocular vascular thrombotic events: central retinal vein and central retinal artery occlusions.

We prospectively assessed associations of thrombophilia- hypofibrinolysis with central retinal vein occlusion (CRVO) (40 patients) and central retinal artery occlusion (CRAO) (9 patients). We used polymerase chain reaction measures for thrombophilia (factor V Leiden, prothrombin, C677T MTHFR, platelet glycoprotein PlA1/A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). Serologic thrombophilia measures included protein C, protein S (total and free) and antithrombin III, homocysteine, lupus anticoagulant, anticardiolipin antibodies IgG-IgM, and factors VIII and XI. Serologic hypofibrinolysis measures included Lp(a) and plasminogen activator inhibitor activity. For comparison with 40 CRVO and 9 CRAO patients, 80 and 45 race-gender matched controls were studied. The factor V mutation was more common in CRVO (3/40, 8%) than controls (0/79, 0%), P = .036, as was high (>150%) factor VIII (12/40, 30%) versus (4/77, 5%), P = .0002. Low antithrombin III (<80%) was more common in CRVO (5/39, 13%) than in controls (2/73, 3%), P = .049. Homocysteine was high (> or =13.5 micromol/L) in 5/39 (13%) CRVO patients versus 2/78 controls (3%), P = .04. Three of 9 CRAO patients (33%) had low (<73%) protein C versus 2/37 controls (5%), P = .044. Two of 9 CRAO patients (22%) had high (> or =13.5 micromol/L) homocysteine versus 0/42 controls (0%), P =. 028. Four of 9 CRAO patients had the lupus anticoagulant (44%) versus 4/33 (12%) controls (P = .050). CRVO is associated with familial thrombophilia (factor V Leiden, factor VIII, low antithrombin III, homocysteinemia), and CRAO is associated with familial and acquired thrombophilia (low protein C, homocysteinemia, lupus anticoagulant), providing avenues for thromboprophylaxis, and triggering family screening.

Lung adenocarcinoma presenting as obstructive jaundice: a case report and review of literature.

BACKGROUND: Lung cancer is known to metastasize to the pancreas with several case reports found in the literature, however, most patients are at an advanced stage and receive palliative treatment. CASE PRESENTATION: We describe the case of a 56 year old male patient who presented with a picture of obstructive jaundice. Investigations revealed an obstructing lesion in the pancreas and a further lesion in the lung with benign appearances. The patient underwent a pancreatectomy and, unexpectedly, the histology of the resected specimen demonstrated metastatic adenocarcinoma of bronchogenic origin. He was referred to a cardiothoracic team who proceeded to resect the patient's thoracic lesion before administration of adjuvant chemotherapy. The patient was reviewed 18 months post operatively and remains symptom free with no clinical or radiological evidence of recurrence. We were unable to identify any previous case reports (of lung adenocarcinoma) with such a presentation which were ultimately treated with resection of both lesions. CONCLUSION: Similar situations are bound to arise again in the future and we believe that this report could demonstrate that there is a case for aggressive surgical management in a highly selected group of patients: those with NSCLC and a synchronous solitary pancreatic deposit.

Solid pseudopapillary tumour of the pancreas: clinicopathological analysis.

BACKGROUND: We report on our experience of the surgical management and outcomes of 11 patients with solid pseudopapillary tumour of the pancreas (SPT). We sought to correlate the immunohistochemical staining of these tumours with that previously reported in the literature. METHODS: A retrospective analysis of the clinical presentation, radiological findings, surgical treatment, histopathological characteristics and outcomes for patients surgically managed with SPT at The Royal London Hospital. A literature search was performed to analyse the immunohistochemical stains commonly used to diagnose SPT. RESULTS: Between August 2006 and April 2016, 10 females and one male patient underwent surgery for SPT. The localization of the tumour was in the pancreatic head in two patients, one in the neck, three in the body and five in the tail. All 11 patients had localised disease. Six patients suffered post-surgical complications. Histopathology shows immunoreactivity for: ß-catenin, vimentin, CD-10, CD-56, α1-antitrypsin and negative staining for synaptophysin and chromogranin. At a median of 24 months of follow-up, the disease-free survival rate was 100% and no recurrence was noted. A literature review generated 38 suitable articles with 116 individual cases of SPT, with high expression of vimentin and neuron specific enolase throughout, and low rates of chromogranin and synatophysin positivity. CONCLUSION: SPT is rare and affects mostly young women. An accurate diagnosis is important as the relative indolent behaviour can be managed with surgical resection even when large in size, bringing excellent long-term outcomes.

Predicting complications in hepatic resection for colorectal liver metastasis: the lymphocyte-to-monocyte ratio.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide; whilst approximately 20% of patients have hepatic disease at presentation. Hepatic resection remains the gold standard of care; however, it is associated with significant morbidity. We sought to establish whether the lymphocyte-to-monocyte ratio (LMR) could help predict post-operative complications, thus improving patient outcomes. METHODS: We performed a retrospective cohort study of patients undergoing hepatic resection at a single centre. Baseline demographics and complications within 30 days following surgery were recorded. White blood cell counts and C-reactive protein (CRP) were recorded pre-operatively, and until post-operative day 7. RESULTS: A total of 188 operations were included. About 47.3% of resections had a complicated recovery, of which 31.46% were major. The median LMR was 1.29 across the cohort, 1.60 for uncomplicated procedures, 1.14 for those with complications and 0.85 in major complications. For detecting major complications versus an uncomplicated recovery, median LMR was the best parameter (area under the curve 0.78), whilst it was the only parameter to accurately predict such complications within 48 hours of surgery (area under the curve 0.72 on day 1). It was consistently the most accurate parameter at detecting uncomplicated versus complicated recovery, minor versus major complications, and major complications versus an uncomplicated recovery, at numerous timepoints over the post-operative period. CONCLUSION: The LMR appears better at predicting complications following hepatic resection for colorectal liver metastases, as opposed to conventionally measured parameters.

Embryonic stem cells.

Stem cells are unique cell populations with the ability to choose between self-renewal and differentiation. Embryonic stem (ES) cells have the ability to form any fully differentiated cell of the body. To date, only three species of mammals have yielded long-term cultures of self-renewing ES cells- mice, monkeys, and humans. These cells have some special requirements to maintain their undifferentiated state in culture, e.g., presence of feeder cells, serum, or cytokines. Many scientific studies have tried to manipulate the growth and differentiation conditions with varied success. Studies of development in model systems, such as mice help our efforts to manipulate human stem cells in vitro. Data are now emerging that ES cells can be directed toward lineage-specific differentiation programs. On the basis of this property, it is likely that human ES cells will provide a useful differentiation culture system to study the mechanisms of human development. Recent advances in culturing ES cells and success in exploiting their pluripotency brings great hope for using human ES cell-based reparative therapy in future.

Comparison of outcomes: scleral buckling and pars plana vitrectomy versus vitrectomy alone for primary repair of rhegmatogenous retinal detachment.

OBJECTIVE: To assess the combination of scleral buckling (SB) and pars plana vitrectomy (PPV) versus PPV alone in the primary repair of rhegmatogenous retinal detachments (RRDs). METHODS: The current study was a retrospective, comparative, interventional, consecutive case series of 179 eyes of 174 patients who underwent primary RRD repair by five surgeons between January 1, 2008 and December 31, 2010, utilizing SB with PPV or PPV. Univariate and multivariate analyses were used to compare the efficacy of the two surgical strategies and assess for risk factors of proliferative vitreoretinopathy (PVR). RESULTS: Single surgery anatomic success (SSAS) was similar (P=0.76) between the PPV group (112 of 132 eyes, 85%) and SB with PPV group (39 of 47 eyes, 83%). Final anatomic success was 100% in each group. There was no difference in rates of PVR formation (PPV 16% vs SB with PPV 19%, P=0.70). Final logarithm of the minimum angle of resolution acuity was 0.33 (20/43) in the PPV group and 0.37 (20/47) in the SB with PPV group (P=0.62). Postoperative anterior chamber fibrin was highly correlated with PVR formation (PVR 13% vs no PVR 0.7%, P=0.003; odds ratio =68.37, P=0.007). Separate analysis of medium- to high-complexity cases showed similar SSAS (PPV 86% vs SB with PPV 83%, P=0.45). CONCLUSION: SB with PPV versus PPV alone were similarly efficacious for repair of primary RRDs of varying complexity. SSAS rates, PVR incidence, and final visual acuities were not significantly different.

Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes.

BACKGROUND: Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. SPECIFIC AIM: We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. RESULTS: Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40-60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal-placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. CONCLUSION: OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent thrombophilia evaluation and institution of thromboprophylaxis to prevent adverse maternal and fetal-placental thrombotic events.

The role of perioperative inflammatory-based prognostic systems in patients with colorectal liver metastases undergoing surgery. A cohort study.

BACKGROUND: We aim to evaluate the prognostic value of preoperative and postoperative inflammatory systems in patients who had undergone surgery for colorectal liver metastases, focusing our analysis on the role of C-reactive protein-to-albumin ratio (CAR) and Glasgow prognostic score (GPS). METHODS: A total of 194 patients were enrolled onto this study. Demographics, tumor-related variables, preoperative and postoperative (day 1) inflammatory variables were analyzed as potential prognostic factors. RESULTS: For the whole cohort three and 5-year survival were 68% and 53% respectively. Median follow up was 27 months (IQR 10-42). At multivariate analysis only preoperative GPS (HR 12.06, 95% CI 2.82-51.53; p = 0.0008) was an independent risk factor for poor survival. Patients with a preoperative GPS = 0 had a 3-years survival of 70% while it was 33% for those with GPS = 1 (p < 0.0001). In patients with preoperative GPS = 0 preoperative CAR (HR 1.19, 95%CI 1.05-1.35; p = 0.0059) could identify a sub-population at risk for reduced survival. The optimal cut-off for preoperative CAR (preCAR) was 0.133 (HR 7.11 95% CI 1.37-36.78, p = 0.0063). 3-years survival was 75% and 21% for patients with preCAR>0.133 and ≤ 0.133, respectively (p = 0.0005). The immediate postoperative inflammatory status did not have a significant impact on survival. CONCLUSION: GPS is a significant prognostic factor in patients with colorectal liver metastases undergoing surgery. CAR could be a valuable tool to further stratify patients with preoperative GPS = 0 according to their prognosis.

Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes.

AIM: Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists' diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes. METHODS: We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia-eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs). RESULTS: The 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had ≥1 spontaneous abortion; 17 (22%) had ≥2 spontaneous abortions and/or pre-eclampsia-eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058). CONCLUSION: In females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy, with particular relevance to pregnancy outcomes and venous thromboembolism.

Quantifying the utility of taking pills for preventing adverse health outcomes: a cross-sectional survey.

OBJECTIVES: The utility value attributed to taking pills for prevention can have a major effect on the cost-effectiveness of interventions, but few published studies have systematically quantified this value. We sought to quantify the utility value of taking pills used for prevention of cardiovascular disease (CVD). DESIGN: Cross-sectional survey. SETTING: Central North Carolina. PARTICIPANTS: 708 healthcare employees aged 18 years and older. PRIMARY AND SECONDARY OUTCOMES: Utility values for taking 1 pill/day, assessed using time trade-off, modified standard gamble and willingness-to-pay methods. RESULTS: Mean age of respondents was 43 years (19-74). The majority of the respondents were female (83%) and Caucasian (80%). Most (80%) took at least 2 pills/day. Mean utility values for taking 1 pill/day using the time trade-off method were: 0.9972 (95% CI 0.9962 to 0.9980). Values derived from the standard gamble and willingness-to-pay methods were 0.9967 (0.9954 to 0.9979) and 0.9989 (95% CI 0.9986 to 0.9991), respectively. Utility values varied little across characteristics such as age, sex, race, education level or number of pills taken per day. CONCLUSIONS: The utility value of taking pills daily in order to prevent an adverse CVD health outcome is approximately 0.997.