Cardiac and pericardial fistulae associated with esophageal or gastric neoplasms: a literature review

Pericardial and cardiac fistulae secondary to esophageal or gastric tumors are considered exceptional. They have never been the object of a literature review. We reviewed the medical literature between 1881 and 2001, searching for all published cases of pericardial or cardiac fistulae developed from esophageal and gastric tumors or favored by the applied therapy to these tumors. The cases of metastasization, tumor spread, and neoplasic pericardial effusion without fistula were excluded. Fifty patients were identified, with one original case. More than half the cases (56%) occurred in the last 25 years. Substernal pain is the main symptom. The majority of patients present at least one condition favoring fistula formation. The auscultation of a water-wheel murmur may suggest a pneumopericardium and therefore a pericardial fistula, as does a purulent pericarditis. Arrhythmias, signs of ischemia, and hematemesis point toward a ventricular fistula. Neurological and hemostasis disorders may be suspect of an atrial lesion. Diagnosis should be made by the association of a scanner and a transit. Prognosis is bad: 76% of the patients die in the first month. Pericardial or cardiac fistulae are part of the differential diagnosis of thoracic pain in patients with esophageal or gastric tumors and in patients who were treated for these pathologies. The diagnosis must be as quick as possible. An operation (patients with a good prognosis) or the placement of a stent (patients with a bad prognosis) is the only chance of survival

Die Behandlung von Acetabulumfrakturen bei geriatrischen Patienten mittels modifizierter Kabelcerclage und primärer Hüfttotalprothese. Erste Ergebnisse [Treatment of acetabular fractures in the elderly with primary total hip arthroplasty and modified cerclage. Early results]

This prospective study addresses early results of the treatment of acute acetabular fractures in elderly patients by total hip arthroplasty and cerclage wiring.Fifteen patients with an average age of 81 years were treated at our institution between February 1998 and December 2000. There were two transverse fractures, eight T-shaped fractures, two transverse fractures with associated posterior wall fracture, two posterior column fractures with associated posterior wall fracture, and one fracture of both columns. Treatment consisted of cerclage wiring of the fracture and primary non-cemented total hip replacement.All of the patients were followed for a mean of 36 months. Although there was one patient with three hip dislocations during the first 10 months after the operation, we found an excellent or good result for the entire group. During this relatively short follow-up period, we have not found a radiological loss of fracture reduction of more than 1 mm or a cup migration of more than 3.2 mm. All of the fractures healed and no loosening of the implant was evident.Primary total hip arthroplasty combined with internal fixation is a valid treatment option for acetabular fractures in the elderly. Preliminary results are convincing, but a bigger patient population and a longer follow-up time are necessary before we are able to draw final conclusions.

First aid in burn injuries with counterintuitive warm water improves outcome

Objective: Cooling is considered a panacea in burn injury. However, burn injuries are characterized by an ischemic zone prone to progression, a phenomenon that can substantially increase morbidity. Cold-induced vasoconstriction potentially aggravates ischemia and promotes progression. Therefore we compared the effect of warm (37°C) and cold (17°C) water on burn progression. Methods: The comb burn model creates 4 rectangular burned surfaces separated by 3 unburned interspaces that become necrotic if untreated. After heating in boiling water the template was applied for 60 seconds on 24 Wistar rats randomized into 3 groups: no treatment (CON); treatment for 20 minutes with cold water (17°C: CW) or warm water (37°C: WW). Burn progression in surface (planimetry) and Departmenth (histology), as well as microcirculatory perfusion (laser Doppler flowmetry) were assessed after 1h, as well as 1, 4, and 7 days. Results: Both CW and WW delayed burn progression without reducing the final burn Departmenth (deep dermis). In contrast, only WW but not CW increased dermal perfusion (81 ± 2% (WW) vs. 62 ± 2% (CW) and 63 ± 1% (CON), p< 0·05) already 1 hour after burn induction. The difference observed after one hour led to a complete flow recovery during the observation period and translated into increased interspace survival, respectively less necrosis with WW(65 ± 4% vs. 81 + 4% (CW) and 91 ± 2% (CON), p< 0·05) after 7 days. Conclusions: Application of warm water significantly improved dermal perfusion, increased interspace survival, and delayed burn progression.However it didn't alter the ultimate burn Departmenth of the actually burned area. Therefore, warm water can create a therapeutic window for targeted nonsurgical treatment of burn progression.

Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department.

BACKGROUND: Legionella species cause severe forms of pneumonia with high mortality and complication rates. Accurate clinical predictors to assess the likelihood of Legionella community-acquired pneumonia (CAP) in patients presenting to the emergency department are lacking. METHODS: We retrospectively compared clinical and laboratory data of 82 consecutive patients with Legionella CAP with 368 consecutive patients with non-Legionella CAP included in two studies at the same institution. RESULTS: In multivariate logistic regression analysis we identified six parameters, namely high body temperature (OR 1.67, p < 0.0001), absence of sputum production (OR 3.67, p < 0.0001), low serum sodium concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR 1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using optimal cut off values of these six parameters, we calculated a diagnostic score for Legionella CAP. The median score was significantly higher in Legionella CAP as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p < 0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001). Receiver operating characteristics showed a high diagnostic accuracy of this diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point, only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or =4 points, 66% of patients had Legionella CAP. CONCLUSION: Six clinical and laboratory parameters embedded in a simple diagnostic score accurately identified patients with Legionella CAP. If validated in future studies, this score might aid in the management of suspected Legionella CAP.

Motivational intervention to reduce cannabis use in young people with psychosis: a randomized controlled trial.

Background: Cannabis use has a negative impact on psychosis. Studies are needed to explore the efficacy of psychological interventions to reduce cannabis use in psychosis. Our aim is to study the efficacy of a specific motivational intervention on young cannabis users suffering from psychosis. Methods: Participants (aged less than 35 years) were randomly assigned to treatment as usual (TAU) alone, or treatment as usual plus motivational intervention (MI + TAU). TAU was comprehensive and included case management, early intervention and mobile team when needed. Assessments were completed at baseline and at 3, 6 and12 months follow-up. Results: Sixty-two participants (32 TAU and 30 MI + TAU) were included in the study. Cannabis use decreased in both groups at follow-up. Participants who received MI in addition to TAU displayed both a greater reduction in number of joints smoked per week and greater confidence to change cannabis use at 3 and 6 months follow-up, but differences between groups were nonsignificant at 12 months. Conclusions: MI is well accepted by patients suffering from psychosis and has a short-term impact on cannabis use when added to standard care. However, the differential effect was not maintained at 1-year follow-up. MI appears to be a useful active component to reduce cannabis use which should be integrated in routine clinical practice.

Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles.

INTRODUCTION: Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC. METHODS: We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples. RESULTS: HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified. CONCLUSIONS: This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population.

Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis.

Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function.

Specific delineation of BK polyomavirus in kidney tissue with a digoxigenin-labeled DNA probe.

The detection of BK polyomavirus (BK virus, BKV) in kidney tissue is hampered by nonspecificity of antibodies suited to immunohistochemistry, and nonspecific background with in situ hybridization. The biotin-labeled DNA probe that is commercially available (Enzo Life Sciences, Inc.) shows good signal, but the intrinsic background in kidney tissue is high. We determined that the intrinsic background is due to endogenous biotin or biotin-binding activity in the renal tubular epithelium. Neither antibody blocking procedures nor an avidin/biotin block were entirely satisfactory for eliminating this background staining. We developed a digoxigenin-labeled DNA probe, and protocol, for detecting BK virus in formalin-fixed, paraffin embedded, kidney tissue obtained at autopsy. The hybridization signal is strong and there is no perceptible background staining. Eleven negative control kidneys all failed to hybridize. Conditions for low stringency hybridization may be employed, detecting both the related JC polyomavirus and BKV. Alternatively, high stringency hybridization conditions may be utilized, detecting BKV only. BK associated tubular necrosis is clearly demonstrated in two cases of BK nephritis.

Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

Purpose To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim). Patients and Methods From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 μg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled. Results The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest. Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.

Neuronal calcium channel mutation in a patient with congenital ataxia and attacks of hemiplegic migraine with cerebral edema

Background: Familial Hemiplegic Migraine (FHM), characterized by a prolonged unilateral hemiparesis, mainly results from mutations in the alpha-1a subunit of the calcium channel gene CACNA1A that can also cause two other dominantly inherited neurological disorders, Episodic Ataxia type 2 (EA2, with sometimes migrainous headaches) and Spinocerebellar Ataxia type 6 (SCA6, late-onset and progressive). A same mutation can have different clinical expression in a family (hemiplegic migraine, migraine-coma, cerebellar ataxia). CACNA1A mutations in FHM are usually missense, leading to gain-of-function, while truncating mutations leading to loss-of-function are usually associated with EA2. Case report: This 9-year-old girl was seen as a baby for hypotonia and transient vertical nystagmus. Her first brain MRI was normal. She evolved as a congenital ataxia, but since the age of two, she had attacks of coma, hemiparesis (either side), partial seizures, dystonic movements and fever. Attacks were initially triggered by minor head bumps, subsequently spontaneous. Brain MRIs in the acute stage always showed transient unilateral hemisphere swelling. Follow-up images revealed atrophic lesions in the temporo-occipital regions and cerebellar atrophy. A prophylactic trial with flunarizine was ineffective. Acetazolamide was recently introduced. Methods: Since our patient shared features of both FHM and EA2, we studied the CACNA1A gene by direct sequencing in the patient's and parents' DNA. Results: We identified an unreported de novo heterozygous deletion of three base pairs (c.4503_4505delCTT) predicting the deletion of one amino acid (p.Phe1502del). The CACNA1A protein contains 4 domains, each formed by six transmembrane segments. The deletion is located in a highly conserved region in segment 6 (S6) of the third domain. Mutations in S6 segments of calcium channels change single-channel conductance and channel selectivity, most resulting in loss-of-function. Outlook: In vitro expression studies of the identified mutation are underway, aiming at understanding its functional consequences and finding an efficient treatment.

Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: a multicentre phase II trial.

BACKGROUND: Stage IIIB non-small-cell lung cancer (NSCLC) is usually thought to be unresectable, and is managed with chemotherapy with or without radiotherapy. However, selected patients might benefit from surgical resection after neoadjuvant chemotherapy and radiotherapy. The aim of this multicentre, phase II trial was to assess the efficacy and toxicity of a neoadjuvant chemotherapy and radiotherapy followed by surgery in patients with technically operable stage IIIB NSCLC. METHODS: Between September, 2001, and May, 2006, patients with pathologically proven and technically resectable stage IIIB NSCLC were sequentially treated with three cycles of neoadjuvant chemotherapy (cisplatin with docetaxel), immediately followed by accelerated concomitant boost radiotherapy (44 Gy in 22 fractions) and definitive surgery. The primary endpoint was event-free survival at 12 months. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030810. FINDINGS: 46 patients were enrolled, with a median age of 60 years (range 28-70). 13 (28%) patients had N3 disease, 36 (78%) had T4 disease. All patients received chemotherapy; 35 (76%) patients received radiotherapy. The main toxicities during chemotherapy were neutropenia (25 patients [54%] at grade 3 or 4) and febrile neutropenia (nine [20%]); the main toxicity after radiotherapy was oesophagitis (ten patients [29%]; nine grade 2, one grade 3). 35 patients (76%) underwent surgery, with pneumonectomy in 17 patients. A complete (R0) resection was achieved in 27 patients. Peri-operative complications occurred in 14 patients, including two deaths (30-day mortality 5.7%). Seven patients required a second surgical intervention. Pathological mediastinal downstaging was seen in 11 of the 28 patients who had lymph-node involvement at enrolment, a complete pathological response was seen in six patients. Event-free survival at 12 months was 54% (95% CI 39-67). After a median follow-up of 58 months, the median overall survival was 29 months (95% CI 16.1-NA), with survival at 1, 3, and 5 years of 67% (95% CI 52-79), 47% (32-61), and 40% (24-55). INTERPRETATION: A treatment strategy of neoadjuvant chemotherapy and radiotherapy followed by surgery is feasible in selected patients. Toxicity is considerable, but manageable. Survival compares favourably with historical results of combined treatment for less advanced stage IIIA disease. FUNDING: Swiss Group for Clinical Cancer Research (SAKK) and an unrestricted educational grant by Sanofi-Aventis (Switzerland).

Interobserver and intraobserver variability of apparent diffusion coefficient measurements in treated malignant hepatic lesions: measurements in the whole lesion versus in the area with the most restricted diffusion

Purpose: The increase of apparent diffusion coefficient (ADC) in treated hepatic malignancies compared to pre-therapeutic values has been interpreted as treatment success; however, the variability of ADC measurements remains unknown. Furthermore, ADC has been usually measured in the whole lesion, while measurements should be probably centered on the area with the most restricted diffusion (MRDA) as it represents potential tumoral residue. Our objective was to compare the inter/intraobserver variability of ADC measurements in the whole lesion and in MRDA. Material and methods: Forty patients previously treated with chemoembolization or radiofrequency were evaluated (20 on 1.5T and 20 on 3.0T). After consensual agreement on the best ADC image, two readers measured the ADC values using separate regions of interest that included the whole lesion and the whole MRDA without exceeding their borders. The same measurements were repeated two weeks later. Spearman test and the Bland-Altman method were used. Results: Interobserver correlation in ADC measurements in the whole lesion and MRDA was as follows: 0.962 and 0.884. Intraobserver correlation was, respectively, 0.992 and 0.979. Interobserver limits of variability (mm2/sec*10-3) were between -0.25/+0.28 in the whole lesion and between -0.51/+0.46 in MRDA. Intraobserver limits of variability were, respectively: -0.25/+0.24 and -0.43/+0.47. Conclusion: We observed a good inter/intraobserver correlation in ADC measurements. Nevertheless, a limited variability does exist, and it should be considered when interpreting ADC values of hepatic malignancies.

Cytokines and hs-CRP levels in individuals treated with low-dose aspirin for cardiovascular prevention: a population-based study (CoLaus Study).

Pro-inflammatory cytokines and high-sensitive C-reactive protein (hs-CRP) are associated with increased risk for cardiovascular disease. Low-dose aspirin for CV prevention is reported to have anti-inflammatory effects. The aim of this study was to determine the association between pro-inflammatory cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention in a population-based cohort (CoLaus Study). We assessed blood samples in 6085 participants (3201 women) aged 35-75years. Medications' use and indications were recorded. Among aspirin users (n=1'034; 17%), overall low-dose users (351; 5.8%) and low-dose for cardiovascular prevention users (324; 5.3%) were selected for analysis. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α were assessed by a multiplex particle-based flow cytometric assay and hs-CRP by an immunometric assay. Cytokines and hs-CRP were presented in quartiles. Multivariate analysis adjusting for sex, age, smoking status, body mass index, diabetes mellitus and immunomodulatory drugs showed no association between cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention, either comparing the topmost vs. the three other quartiles (OR 95% CI, 0.84 (0.59-1.18), 1.03 (0.78-1.32), 1.10 (0.83-1.46), 1.00 (0.67-1.69) for IL-1β, IL-6, TNF-α and hs-CRP, respectively), or comparing the topmost quartile vs. the first one (OR 95% CI, 0.87 (0.60-1.26), 1.19 (0.79-1.79), 1.26 (0.86-1.84), 1.06 (0.67-1.69)). Low-dose aspirin use for cardiovascular prevention does not impact plasma pro-inflammatory cytokine and hs-CRP levels in a population-based cohort.

Ultrasound evaluation of synovitis in RA: Correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE: To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS: One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS: In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r=0.41, P<0.0001). The same was true for the PwD score (r=0.41, P<0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r=0.54, P<0.0001 and r=0.46, P<0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS: The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

Plant- and microbe-derived compounds affect the expression of genes encoding antifungal compounds in a pseudomonad with biocontrol activity.

We have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on the in vitro expression of two antifungal biosynthetic genes by the plant-protecting rhizobacterium Pseudomonas fluorescens CHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.