Cost-effectiveness and clinical utility of universal pre-admission MRSA screening in total joint arthroplasty patients.

BACKGROUND: For patients undergoing total joint arthroplasty (TJA), pre-admission meticillin-resistant Staphylococcus aureus (MRSA) nasal screening has been widely adopted to prevent postoperative joint infection. However, screening cost-effectiveness and clinical utility have not been adequately evaluated. AIM: To assess the MRSA infection rate, associated costs, and costs of screening at our institution, before and after screening implementation. METHODS: This was a retrospective cohort study examining patients who underwent TJA at a health system in New York State, between 2005 and 2016. Patients were divided into the 'no-screening' group if the operation occurred prior to adoption of the MRSA screening protocol in 2011 and the 'screening' group if afterwards. The number of MRSA joint infections, cost of each infection, and costs associated with preoperative screening were recorded. Fisher's exact test and cost comparison analysis were performed. FINDINGS: The no-screening group had four MRSA infections in 6088 patients over a seven-year period, whereas the screening group had two in 5177 patients over five years. Fisher's exact test showed no significant association between screening and MRSA infection rate (P = 0.694). The cost of postoperative MRSA joint infection treatment was US$40,919.13 per patient, whereas annual nasal screening was US$103,999.97. CONCLUSION: At our institution, MRSA screening had little impact on infection rates and led to increased costs, with 2.5 MRSA infections required annually to meet the costs of screening. Therefore, the screening protocol may be best suited for high-risk populations, rather than the average TJA patient. The authors recommend a similar clinical utility and cost-effectiveness analysis at other institutions implementing MRSA screening programmes.

Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity.

The fruitless search for the cause of Crohn's disease has been conducted for more than a century. Various theories, including autoimmunity, mycobacterial infection and aberrant response to food and other ingested materials, have been abandoned for lack of robust proof. This review will provide the evidence, obtained from patients with this condition, that the common predisposition to Crohn's is a failure of the acute inflammatory response to tissue damage. This acute inflammation normally attracts large numbers of neutrophil leucocytes which engulf and clear bacteria and autologous debris from the inflamed site. The underlying predisposition in Crohn's disease is unmasked by damage to the bowel mucosa, predominantly through infection, which allows faecal bowel contents access to the vulnerable tissues within. Consequent upon failure of the clearance of these infectious and antigenic intestinal contents, it becomes contained, leading to a chronic granulomatous inflammation, producing cytokine release, local tissue damage and systemic symptoms. Multiple molecular pathologies extending across the whole spectrum of the acute inflammatory and innate immune response lead to the common predisposition in which defective monocyte and macrophage function plays a central role. Family linkage and exome sequencing together with GWAS have identified some of the molecules involved, including receptors, molecules involved in vesicle trafficking, and effector cells. Current therapy is immunosuppressant, which controls the symptoms but accentuates the underlying problem, which can only logically be tackled by correcting the primary lesion/s by gene therapy or genome editing, or through the development of drugs that stimulate innate immunity.

[Clinical features of inflammatory bowel disease (ulcerative colitis and Crohn's disease) in geriatric practice in Saint Petersburg.]

Objective - to identify the clinical features of inflammatory bowel disease (IBD) in elderly and senile patients in St. Petersburg. A retrospective analysis of medical charts of 208 patients over 60 years old with inflammatory bowel diseases (IBD) was carried out: 60% of them with ulcerative colitis (UC), 40% with Crohn's disease (CD). The control group consisted of 867 patients aged up to 60 years (UC- 524 patients, 60,4%; CD - 343 patients, 29,6%). Concomitant cardiovascular diseases were detected in 87% of patients, broncho-pulmonary - in 25%, diseases of the bones and joints - in 35%, pathology of the kidneys and urinary tract - in 26,5%, and liver - in 44%. Debut and recurrent IBD were often accompanied (33,6%) by a worsening of somatic pathology (versus 8,7% in other age groups of patients). It's took longer to verify diagnosis of IBD in older patients, than in patients of young and middle ages. Patients with distal localization of the pathological process (proctitis and left-sided colitis) prevailed among patients with UC, the inflammatory form of the disease dominated in patients with CD.

Coping strategies, satisfaction with life, and quality of life in Crohn's disease: A gender perspective using structural equation modeling analysis.

OBJECTIVE: To identify coping strategies and socio-demographics impacting satisfaction with life and quality of life in Crohn's disease (CD). METHODS: 402 patients completed the Patient Harvey-Bradshaw Index, Brief COPE Inventory, Satisfaction with Life Scale (SWLS), Short Inflammatory Bowel Disease Questionnaire (SIBDQ). We performed structural equation modeling (SEM) of mediators of quality of life and satisfaction with life. RESULTS: The cohort comprised: men 39.3%, women 60.1%; P-HBI 4.75 and 5.74 (p = 0.01). In inactive CD (P-HBI≤4), both genders had SWLS score 23.8; men had SIBDQ score 57.4, women 52.6 (p = 0.001); women reported more use of emotion-focused, problem-focused and dysfunctional coping than men. In active CD, SWLS and SIBDQ scores were reduced, without gender differences; men and women used coping strategies equally. A SEM model (all patients) had a very good fit (X2(6) = 6.68, p = 0.351, X2/df = 1.114, SRMR = 0.045, RMSEA = 0.023, CFI = 0.965). In direct paths, economic status impacted SWLS (ß = 0.39) and SIBDQ (ß = 0.12), number of children impacted SWLS (ß = 0.10), emotion-focused coping impacted SWLS (ß = 0.11), dysfunctional coping impacted SWLS (ß = -0.25). In an indirect path, economic status impacted dysfunctional coping (ß = -0.26), dysfunctional coping impacted SIBDQ (ß = -0.36). A model split by gender and disease activity showed that in active CD economic status impacted SIBDQ in men (ß = 0.43) more than women (ß = 0.26); emotional coping impacted SWLS in women (ß = 0.36) more than men (ß = 0.14). CONCLUSIONS: Gender differences in coping and the impacts of economic status and emotion-focused coping vary with activity of CD. Psychological treatment in the clinic setting might improve satisfaction with life and quality of life in CD patients.

Effects of Radiation Exposure on the Cost-Effectiveness of CT Angiography and Perfusion Imaging in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: CT angiography and perfusion imaging is an important prognostic tool in the management of patients with aneurysmal subarachnoid hemorrhage. The purpose of this study was to perform a cost-effectiveness analysis of advanced imaging in patients with SAH, incorporating the risks of radiation exposure from CT angiography and CT perfusion imaging. MATERIALS AND METHODS: The risks of radiation-induced brain cancer and cataracts were incorporated into our established decision model comparing the cost-effectiveness of CT angiography and CT perfusion imaging and transcranial Doppler sonography in SAH. Cancer risk was calculated by using National Cancer Institute methodology. The remaining input probabilities were based on literature data and a cohort at our institution. Outcomes were expected quality-adjusted life years gained, costs, and incremental cost-effectiveness ratios. One-way, 2-way, and probabilistic sensitivity analyses were performed. RESULTS: CT angiography and CT perfusion imaging were the dominant strategies, resulting in both better health outcomes and lower costs, even when incorporating brain cancer and cataract risks. Our results remained robust in 2-way sensitivity analyses varying the prolonged latency period up to 30 years, with either brain cancer risk up to 50 times higher than the upper 95% CI limit or the probability of cataracts from 0 to 1. Results were consistent for scenarios that considered either symptomatic or asymptomatic patients with SAH. Probabilistic sensitivity analysis confirmed our findings over a broad range of selected input parameters. CONCLUSIONS: While risks of radiation exposure represent an important consideration, CT angiography and CT perfusion imaging remained the preferred imaging compared with transcranial Doppler sonography in both asymptomatic and symptomatic patients with SAH, with improved health outcomes and lower health care costs, even when modeling a significantly higher risk and shorter latency period for both cataract and brain cancer than that currently known.

A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.

BACKGROUND: Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry. RESULTS: Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P < 0.001) with a concomitant increase in the proportion of CD27+ memory B cells (P < 0.001) and activated CD86+CD27+ memory B cells (P < 0.001), as an immunopharmacodynamic marker of CD40 activation. CONCLUSIONS: CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY NUMBER: ACTRN12609000294257.

Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

[A new system of specialized gastroenterological care to patients with inflammatory bowel diseases in St. Petersburg].

AIM: To substantiate the effectiveness of the set-up center in the early detection of patients with inflammatory bowel diseases (IBD) and in its organization and implementation of current therapeutic programs. MATERIALS AND METHODS: The therapeutic activity of the specialized medical care system set up in St. Petersburg for patients with IBD (ulcerative colitis (UC) and Crohn's disease (CD)), which is based on a multifunctional inflammatory bowel disease center at City Clinical Hospital Thirty-One, was analyzed. RESULTS: The effective work of the center could reduce time for verification of the diagnosis of UC from 6.4 +/- 1.4 to 3.6 +/- 0.8 months and CD from 28.6 +/- 6.7 to 15.3 +/- 4.2 months, respectively; decline the annual number of patients with moderate and severe UC from 73.4 to 53.6 and CD from 66.7 to 47%, and also set up a centralized system for all required types of current therapeutic and diagnostic care for these patients. CONCLUSION: The establishment of the St. Petersburg Center for the diagnosis and treatment of inflammatory bowel diseases could develop and realize in practice a new closed-loop urban system for the early detection and notification of IBD patients, the organization and rendering of individual effective therapeutic-and-prophylactic care.

Intracerebral and subarachnoid hemorrhage in patients with cancer.

OBJECTIVE: To analyze the risk factors, presentation, etiologies, and outcomes of adult cancer patients with intracranial hemorrhage (IH). METHODS: We analyzed 208 patients retrospectively with the diagnosis of IH from the Memorial Sloan-Kettering neurology database from January 2000 through December 2007. Charts were examined for clinical and radiographic data. Survival was calculated using the Kaplan-Meier method. Survival between groups was compared via the log-rank test. Logistic regression models were used to assess for prognostic indicators of 30- and 90-day mortality. RESULTS: There were 181 intracerebral and 46 subarachnoid hemorrhages. Sixty-eight percent of patients had solid tumors, 16% had primary brain tumors, and 16% had hematopoietic tumors. Hemiparesis and headache were the most common symptoms. Intratumoral hemorrhage (61%) and coagulopathy (46%) accounted for the majority of hemorrhages, whereas hypertension (5%) was rare. Median survival was 3 months (95% confidence interval [CI] 2-4), and 30-day mortality was 31%. However, nearly one-half of patients were completely or partially independent at the time of discharge. Patients with primary brain tumors had the longest median survival (5.9 months, 95% CI 2.9-11.8, p = 0.05). Independent predictors of 30-day mortality were not having a primary brain tumor, impaired consciousness, multiple foci of hemorrhage, hydrocephalus, no ventriculostomy, and treatment of increased intracranial pressure. CONCLUSIONS: Intracranial hemorrhage in patients with cancer is often due to unique mechanisms. Prognosis is poor, but comparable to intracranial hemorrhage in the general population. Aggressive care is recommended despite high mortality, because many patients have good functional outcomes.

[Palpebral and lacrimal system injuries in children]. / Plaies palpébro-lacrymales de l'enfant.

The authors report the different palpebral and lacrimal wounds found in children and their treatment. Early microscopic surgery is important for good prognosis. The eyelids must be thoroughly examined searching for a marginal injury, superior palpebral levator muscle resection, and lacrimal system injury after ocular injuries have been investigated. The treatment is microscopic surgery of the eyelid and the canaliculus with most often a monocanalicular intubation. The authors present two clinical studies conducted in the Reims Hospital that show the frequency of this traumatology and the main characteristics. In children, most injuries come from dog bites with canalicular laceration in the left lower eyelid. In palpebral injuries without canalicular section, the injury was most often located on the right lower eyelid. Preliminary treatment of childhood palpebral and lacrimal injuries is necessary with microscopic surgery. It is important to repair the canaliculus with or without canalicular intubation and the eyelid margin.

Overexpression and altered glycosylation of MUC1 in malignant mesothelioma.

Current interest in the MUC1/EMA mucin relates to its role in malignancy, and its potential as a therapeutic target. MUC1/EMA expression has been observed in the majority of epithelioid mesotheliomas. However, little is known of the characteristics of MUC1/EMA in mesothelioma. Herein, we studied the cell surface and soluble expression of the MUC1/EMA glycoprotein, and determined the mRNA and genomic expression profiles in mesothelioma. We found that the anti-MUC1 antibody, E29, was the most diagnostically useful of seven antibody clones examined with a sensitivity of 84% (16 out of 19 cases) and no false positive results. MUC1 mRNA expression was significantly higher in mesothelioma samples than in benign mesothelial cells. No amplification of the MUC1 gene was observed by FISH. Seven of 9 mesothelioma samples expressed MUC1-secreted mRNA isoform in addition to the archetypal MUC1/transmembrane form. CA15.3 (soluble MUC1) levels were significantly higher in the serum of mesothelioma patients than in healthy controls but were not significantly different to levels in patients with benign asbestos-related disease. CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target.

Innate immunity in inflammatory bowel disease: a disease hypothesis.

Crohn's disease arises from a defective interaction between the highly concentrated mass of bacteria in the gastrointestinal tract and the underlying tissues. It has generally been believed to result from an excessively exuberant inflammatory response or from 'autoimmunity'. Recent evidence has emerged that the problem is instead a failure of the way in which the body responds to the penetration of bacteria and other bowel contents through the intestinal mucosal barrier. Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency. Failure of inflammatory mediator production leads to insufficient recruitment of neutrophils, resulting in inadequate removal of bacteria and other debris. This impairment of acute inflammation can be compensated in some circumstances by signalling through NOD2. If not cleared, the foreign material in the bowel wall is taken up within macrophages, eliciting a granulomatous reaction and the local and systemic sequelae so characteristic of Crohn's disease.

Modified skin window technique for the extended characterisation of acute inflammation in humans.

OBJECTIVE: To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. SUBJECTS: 15 healthy subjects and 5 Crohn's patients. TREATMENT: Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 microg/ml interleukin-8 (IL-8). METHODS: Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. RESULTS: Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn's patients, notably PKC alpha/beta hyperphosphorylation (11.3 +/- 3.1 vs 1.2 +/- 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. CONCLUSIONS: The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators.

Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor.

BACKGROUND: Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured. AIMS: To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.

Can unresolved infection precipitate autoimmune disease?

Autoimmune diseases are frequently postulated to arise as post-infectious phenomena. Here we survey the evidence supporting these theories, with particular emphasis on Crohn's disease and ankylosing spondylitis. Direct proof that infection establishes persistent autoimmunity remains lacking, although it may provoke a prolonged inflammatory response when occurring on a susceptible immunological background. The argument of infective causality is by no means trivial, since it carries important consequences for the safety of vaccine development.

Stroke in patients with cancer: incidence and etiology.

OBJECTIVE: To assess the incidence and type of strokes in patients with cancer at Memorial Sloan-Kettering Cancer Center. METHODS: Retrospective review of all ischemic strokes diagnosed by a neurologist and confirmed by neuroimaging between February 1997 and April 2001 was conducted. Age, gender, cancer diagnosis and stage, and vascular risk factors were recorded. NIH Stroke Scale and modified Rankin Scale scores were calculated retrospectively. Stroke etiology was assigned independently by two neurologists using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Ninety-six patients with a confirmed stroke were identified. The median age was 67, and 61.5% were men. The distribution of vascular risk factors was comparable with that seen in large stroke trials. Lung cancer (30%) was the most common primary tumor followed by brain and prostate cancer (9% each). Strokes were embolic in 52 (54%) and nonembolic in 44 (46%). Eleven of 12 tested patients had an elevated D-dimer level, but in only 3 patients could a definitive diagnosis of nonbacterial thrombotic endocarditis be made. The median survival was 4.5 months (95% CI 2.8 to 9.5) from the diagnosis of stroke; 25% of patients died within 30 days. Treatment had no effect on survival. CONCLUSIONS: Embolic strokes are the commonest cause of stroke in patients with cancer, due partially to hypercoagulability, whereas atherosclerosis accounted for only 22% of stroke in this population. Outcome was primarily determined by the underlying malignancy and the patient's neurologic condition.

[Retinal vein occlusion and carotid Doppler imaging]. / Occlusions veineuses rétiniennes et échographie-Doppler carotidienne.

PURPOSE: To investigate retinal vein occlusion with B-mode ultrasonography carotid and color Doppler imaging. METHODS: In 223 patients (225 eyes) presenting with retinal vein occlusion, we retrospectively investigated vascular risk factors (hypertension, diabetes, hyperlipidemia, cardiovascular history, smoking, and glaucoma), standard laboratory tests, and color Doppler imaging of the carotid artery. RESULTS: The data from 106 women (47.54%) and 117 men (52.46%), with a mean age of 65 years, were studied, with 169 patients presenting a central retinal vein occlusion (CRVO) and 56 a branch retinal vein occlusion (BRVO). Thirteen patients (6%) had significant carotid artery stenosis (>=70%), which was the single etiology. Forty patients (18%) had nonsignificant carotid artery stenosis (<70%) with a risk of embolism production. Such carotid artery lesions found in color Doppler imaging in the RVO investigations were significantly more frequent in older patients (>65 years) who presented at least two RVO risk factors (p<0.001). CONCLUSION: This study has shown the the advantages of carotid Doppler imaging in retinal vein occlusion.