Role of Helicobacter pylori infection in pathogenesis of atherosclerosis

Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

Background

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival.

Methods

A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan–Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival.

Results

At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5–5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3–5.4, p = .01).

Conclusions

Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.     

The Role of Smoking in Breast Cancer Development: An Analysis of a Mayo Clinic Cohort

Abstract:  The purpose of this study was to assess the predictive value of smoking history on breast cancer diagnosis in a referral clinic population. We conducted a case–control study using clinical data collected on 8,097 female patients (1,225 breast cancer cases and 6,872 controls) seen in the Mayo Clinic Breast Clinic between August 1, 1993 and November 31, 2003. Breast cancer patients and noncancer patients significantly differed with respect to age at time of the index visit (p < 0.001), number of pregnancies (p = 0.006), number of live births (p = 0.002), vital status at last known follow-up (p < 0.001), current menstruation (p < 0.001), age at menopause (p < 0.001), history of hysterectomy (p < 0.001), use of oral contraception (p = 0.05), duration of oral contraception use (p = 0.001), use of other exogenous hormones (p < 0.001), duration of exogenous hormone use (p = 0.05), breast pain at time of index visit (p = 0.002), smoking status (p < 0.001), and use of five or more alcoholic beverages per week (p = 0.002). After adjustment for these baseline characteristics, having a personal history of smoking was found to be predictive of breast cancer diagnosis (odds ratios [OR] = 1.25, p = 0.004). Other positive predictors for breast cancer diagnosis were: age (OR = 1.02, p < 0.001), history of hysterectomy (OR = 0.66, p < 0.001), prior use of oral contraception for more than 11 years (OR = 2.10, p < 0.001), and prior use of other exogenous hormones/estrogen (OR = 1.81, p < 0.001). In this referral practice having a personal history of smoking is predictive of breast cancer diagnosis. Further studies are needed to further explore this relationship.     

Bisphosphonate‐associated osteonecrosis of the jaw: does it occur in children?

Background  Bisphosphonate use in adult patients has been linked to osteonecrosis of the jaw (ONJ). This complication has not been systematically assessed in a paediatric population receiving bisphosphonates.
Objective  To assess our cohort of paediatric patients treated with intravenous bisphosphonate for occurrence of ONJ.
Design  Observational study at a tertiary children's hospital.
Patients  A total of 42 paediatric patients with osteoporosis who received bisphosphonate infusions for a mean of 6·5 years (SD 2·7 years) were assessed clinically and radiographically for possible ONJ. Among 42, 37 patients had received disodium pamidronate 1 mg/kg/dose at a mean cumulative dose of 19·8 mg/kg and zoledronic acid (ZA) 0·05 mg/kg/dose at a mean cumulative dose of 0·49 mg/kg; four had received ZA and one received pamidronate alone. Invasive dental treatment during bisphosphonate treatment, a known risk factor for osteonecrosis, was specifically assessed.
Results  In all patients assessed, including 11 who had invasive dental treatment, there were no cases of osteonecrosis.
Conclusion  ONJ has so far not been demonstrated in this patient group.     

Chemotherapeutic activity of liposomal SJA-95: A new polyene macrolide antibiotic in experimental aspergillosis and cryptococcosis

The incidence of systemic fungal infections that has risen dramatically over the past three decades has propelled a continuous need for more potent antifungal drugs. The purpose of this research was to evaluate the chemotherapeutic activity of a new heptaene polyene macrolide antibiotic (SJA-95) and liposomal incorporated SJA-95 (lip. SJA-95) in a mouse model of aspergillosis and cryptococcosis respectively. Lip. SJA-95 was prepared in our laboratory by the proliposome method involving incorporation of the antifungal into the proliposome mixture and its subsequent conversion into a liposomal dispersion by a simple dilution step. Treatment with free SJA-95 and lip. SJA-95, both in aspergillosis and cryptococcosis, progressively prolonged the survival time and decreased the fungal loads in vital organs respectively. A higher LD₅₀ value of lip. SJA as compared to that of free SJA-95 was indicative of reduced toxicity of lip. SJA-95. Our findings suggest lip. SJA-95 treatment results in prolonged survival time, effective microbiological clearance and reduced toxicity that might help to establish its usefulness as a chemotherapeutic agent in systemic fungal infections with fewer adverse reactions.     

Cross‐Imaging Platform Comparison of Ultrasonic Backscatter Coefficient Measurements of Live Rat Tumors

Objective. To translate quantitative ultrasound (QUS) from the laboratory into the clinic, it is necessary to demonstrate that the measurements are platform independent. Because the backscatter coefficient (BSC) is the fundamental estimate from which additional QUS estimates are calculated, agreement between BSC results using different systems must be demonstrated. This study was an intercomparison of BSCs from in vivo spontaneous rat mammary tumors acquired by different groups using 3 clinical array systems and a single‐element laboratory scanner system. Methods. Radio frequency data spanning the 1‐ to 14‐MHz frequency range were acquired in 3 dimensions from all animals using each system. Each group processed their radio frequency data independently, and the resulting BSCs were compared. The rat tumors were diagnosed as either carcinoma or fibroadenoma. Results. Carcinoma BSC results exhibited small variations between the multiple slices acquired with each transducer, with similar slopes of BSC versus frequency for all systems. Somewhat larger variations were observed in fibroadenomas, although BSC variations between slices of the same tumor were of comparable magnitude to variations between transducers and systems. The root mean squared (RMS) errors between different transducers and imaging platforms were highly variable. The lowest RMS errors were observed for the fibroadenomas between 4 and 5 MHz, with an average RMS error of 4 × 10^?5 cm^?1Sr^?1 and an average BSC value of 7.1 × 10^?4 cm^?1Sr^?1, or approximately 5% error. The highest errors were observed for the carcinoma between 7 and 8 MHz, with an RMS error of 1.1 × 10^?1 cm^?1Sr^?1 and an average BSC value of 3.5 × 10^?2 cm^?1Sr^?1, or approximately 300% error. Conclusions. This technical advance shows the potential for QUS technology to function with different imaging platforms.