Evaluating the impact of a rigid and a deformable registration method of pre-treatment images for hypoxia-based dose painting.

PURPOSE: To assess the impact of rigid and deformable image registration methods (RIR, DIR) on the outcome of a hypoxia-based dose painting strategy. MATERIALS AND METHODS: Thirty head and neck cancer patients were imaged with [18F]FMISO-PET/CT before radiotherapy. [18F]FMISO-PET/CT images were registered to the planning-CT by RIR or DIR. The [18F]FMISO uptake was converted into oxygen partial pressure (pO2) maps. Hypoxic Target Volumes were contoured on pO2 maps for the deformed (HTVdef) and non-deformed (HTV) cases. A dose escalation strategy by contours, aiming at 95 % tumour control probability (TCP), was applied. HTVs were characterised based on geometry-related metrics, the underlying pO2 distribution, and the dose boost level. A dosimetric and radiobiological evaluation of selected treatment plans made considering RIR and DIR was performed. Moreover, the TCP of the RIR dose distribution was evaluated when considering the deformed [18F]FMISO-PET image as an indicator of the actual target radiosensitivity to determine the potential impact of an unalignment. RESULTS: Statistically significant differences were found between HTV and HTVdef for volume-based metrics and underlying pO2 distribution. Eight out of nine treatment plans for HTV and HTVdef showed differences on the level 10 %/3 mm on a gamma analysis. The TCP difference, however, between RIR and the case when the RIR dose distribution was used with the deformed radiosensitivity map was below 2 pp. CONCLUSIONS: Although the choice of the CTplan-to-PET registration method pre-treatment impacts the HTV localisation and morphology and the corresponding dose distribution, it negligibly affects the TCP in the proposed dose escalation strategy by contours.

Adherence to metformin and the onset of rheumatoid arthritis: a population-based cohort study.

Objective: The aim of this retrospective cohort study was to examine whether adherence to metformin treatment may be associated with lower onset of rheumatoid arthritis (RA).Method: Using the computerized databases of a 2.3-million state-mandated health services organization in Israel, we identified incident RA cases among a cohort of 113 749 adult patients who initiated metformin therapy between 1998 and 2014. Adherence was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin.Results: During the 18 year study period, there were 558 incident RA cases (61 per 100 000 person-years). Adherence to metformin treatment was associated with a lower risk of developing RA, with the lowest risk recorded among patients with a PDC of 40-59% [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.84] compared with non-adherent patients (PDC < 20%). A mean daily metformin dose of 2550 mg or more was also associated with a lower risk of developing RA (adjusted HR 0.62, 95% CI 0.46-0.84) compared to a daily dose of 850 mg or less. In stratified analyses by gender, the negative association between adherence and the risk of RA was limited to women alone.Conclusions: Adherence to metformin treatment is associated with a reduced risk of developing RA in women. Further studies are needed to assess the effect of metformin on RA development in other patient populations.

High serum carbonic anhydrase IX predicts shorter survival in head and neck cancer.

OBJECTIVES: The objective of the study was to investigate prognostic and predictive value of pretreatment soluble carbonic anhydrase IX (CA IX) blood serum concentration in patients with locally advanced head and neck cancer. BACKGROUND: Increased expression of CA IX in tumor tissues has been associated with treatment resistance and worth prognosis. Soluble form of CA IX, released from tumor cells, is detectable in blood serum and could be a convenient predictive factor of treatment effectiveness that would enable treatment individualization. METHODS: The prospective study evaluated 48 patients with locally advanced squamous cell carcinomas of head and neck, treated by radiotherapy or chemo-radiotherapy. Pretreatment soluble CA IX serum concentrations were examined using enzyme-linked immunosorbent assay. RESULTS: Soluble CA IX serum concentration failed to predict radiotherapy effectiveness in the studied patient population (p = 0.26). However, high CA IX serum concentrations have been associated with shorter overall survival (p = 0.035) CONCLUSION: High pretreatment CA IX serum concentration is a negative prognostic factor in locally advanced head and neck cancer patients (Tab. 1, Fig. 2, Ref. 23).

[Relation between carbonic anhydrase IX serum level, hypoxia and radiation resistance of head and neck cancers]. / Vztah medzi sérovou hladinou karboanhydrázy IX, hypoxiou a rádiorezistenciou nádorov hlavy a krku.

BACKGROUND: Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy. MATERIALS AND METHODS: The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion. RESULTS: We found a substantial variability in the CA IX levels measured in the examined population, ranging 0- 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pretreatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). CONCLUSION: The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients.

Pathomorphological peculiarities of coronary artery ectasias and their role in the pathogenesis of sudden cardiac death.

Polypositional postmortem contrast coronarography and pathomorphological analysis were used to study 400 cases of atherosclerotic, postinfarction, arrhythmogenic, and hypertensive heart. High incidence of sudden cardiac death was established in patients with coronary artery ectasia in atherosclerotic heart. In most cases, ectasias were observed in the anterior interventricular branch of the left coronary artery with dominant localization in the second and forth segments. Correlation was found between the maximum incidence of ectasia in the anterior interventricular branch of the left coronary artery and their maximal length, diameter, and bag-shaped appearance. We determined characteristic alterations in cardiac angioarchitectonics reflecting segmentary location of ectasia reflecting inadequacy of coronary circulation and myocardial ischemia leading to ventricular fibrillation and sudden cardiac death.

Effect of clozapine on physical and verbal aggression.

OBJECTIVE: The hypothesis that clozapine reduced serious physically and verbally aggressive behavior of persons with schizophrenia whose symptoms did not respond to typical neuroleptic treatment was tested. METHOD: Incident reports of aggression and restraint of 75 such inpatients were reviewed for 3 months before clozapine treatment and for 6 months of clozapine treatment. BPRS scores were also examined. Twenty-eight patients with no incidents were removed from study. RESULTS: There were significantly fewer incidents of physical aggression per month per patient on clozapine than before clozapine (mean +/- S.D. = 0.13 +/- 0.25 vs. 0.54 +/- 0.93; t = 3.4, df = 46, p < 0.002) and a similar decline in verbal aggression (0.21 +/- 0.31 vs. 0.73 +/- 0.83; t = 4.3, df = 46, p < 0.000). On clozapine, 49% (n = 23) of patients had fewer incidents of physical aggression, 36% (n = 17) showed no change and 15% (n = 7) showed more. Seventy percent (n = 33) of patients had fewer incidents of verbal aggression, 4% (n = 2) showed no change and 25% (n = 12) had more. During the 3 months before clozapine, 14 patients (30%) were restrained a total of 40 times. During the first 6 months of clozapine treatment, three patients (6%) were restrained a total of six times. There were significant decreases in BPRS hostility, positive, negative and psychosis scores. CONCLUSION: Clozapine appears to reduce serious aggression among some patients.

Pro-Search, Biblio-Links and Pro-Cite: software to gather and manage scientific and technical information.

Pro-Search, Biblio-Links and Pro-Cite combine to form a system for managing scientific information on the desktop. Pro-Search provides access to over 400 databases (500 on the IBM PC), Biblio-Links converts records downloaded from online, CD-ROM and diskette information services into Pro-Cite records. Pro-Cite is a full-featured bibliographic database for managing scientific literature.

Hodgkin's lymphoma in an adolescent with systemic lupus erythematosus.

An adolescent female with systemic lupus erythematosus (SLE) with diffuse proliferative lupus nephritis subsequently contracted Hodgkin's lymphoma, mixed cellularity type. Prior to the diagnosis of Hodgkin's lymphoma, hypogammaglobulinemia developed with IgG deficiency. The nephritis, which improved on steroid therapy, remitted entirely after nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) therapy. The hypogammaglobulinemia also remitted after chemotherapy for Hodgkin's lymphoma. The literature concerning the association of SLE and Hodgkin's lymphoma is reviewed. The significance of this concurrence is discussed in regard to the possible pathophysiology and the clinical management.

Malignant melanoma of the external ear. Review of 102 cases.

The medical records of 102 patients with a diagnosis of melanoma of the external ear seen at The M.D. Anderson Hospital over approximately a 30 year period were reviewed. Survival was correlated with the sex, the clinical appearance of the lesion, the anatomic site of origin, the microscopic thickness and level of invasion, the absence or presence of clinical and pathologic nodal metastasis, the type of neck dissection and the type of definitive surgical treatment to the ear. The thickness and nodal metastasis adversely affected prognosis. Proper surgical treatment usually involves less than total amputation of the ear. A randomized prospective study should answer the question of whether elective neck dissection of the periauricular, parotid and upper posterior cervical and jugulodigastric nodes is justified. The use of chemoimmunotherapy offers a negligible therapeutic benefits for disseminated disease but may be of prophylactic value in a planned, adjunctive protocol for poor risk patients.