Long-term efficacy and urological toxicity of low-dose-rate brachytherapy (LDR-BT) as monotherapy in localized prostate cancer

PurposeThe purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa).Methods and MaterialsDuring the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I¹²⁵ and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed.ResultsAll D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores (p = 0.016) and higher initial urine residual volumes (p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively.ConclusionsThe treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.     

Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect

Formation of the palate, the organ that separates the oral cavity from the nasal cavity, is a developmental process characteristic to embryos of higher vertebrates. Failure in this process results in palatal cleft. During the final steps of palatogenesis, two palatal shelves outgrowing from the sides of the embryonic oronasal cavity elevate above the tongue, meet in the midline, and rapidly fuse together. Over the decades, multiple mechanisms have been proposed to explain how the superficial mucous membranes disappear from the contact line, thus allowing for normal midline mesenchymal confluence. A substantial body of experimental evidence exists for cell death, cell migration, epithelial-to-mesenchymal transdifferentiation (EMT), replacement through new tissue intercalation, and other mechanisms. However, the most recent use of gene recombination techniques in cell fate tracking disfavors the EMT concept, and suggests that apoptosis is the major fate of the midline cells during physiological palatal fusion. This article summarizes the benefits and drawbacks of histochemical and molecular tools used to determine the fates of cells within the palatal midline. Mechanisms of normal disintegration of the midline epithelial seam are reviewed together with pathologic processes that prevent this disintegration, thus causing cleft palate.     

Association between dental fear and dental attendance among adults in Finland

OBJECTIVE: Our aim was to evaluate the association between dental attendance and dental fear while considering the simultaneous effects of perceived oral health and treatment need, satisfaction with oral health services, age, gender, marital status, and attained level of education. MATERIAL AND METHODS: The two-stage stratified cluster sample (n=8028) represented Finnish adults aged 30 years and older. The response rate to this nationwide sample was 88%. Dental fear was measured with the question: "How afraid are you of visiting a dentist?" Multiple logistic regression analyses were used to determine the association between dental fear and dental attendance, including the following independent variables: perceived oral health, perceived treatment need, satisfaction with oral health services, age, gender, marital status, and attained level of education. RESULTS: Among all ages, except 30 to 34-year-olds, irregular attenders were more likely to be very afraid of visiting a dentist than regular attenders were. The association was stronger the older the age group. Only age modified the association between dental fear and attendance. Irregular dental attendance can be attributed to high dental fear (etiologic fraction among exposed) in 41% of cases. CONCLUSION: Reducing dental fear would increase the number of regular attenders, especially among older age groups. Individuals for whom oral health services have been provided regularly since childhood seem to continue to use these services regularly despite high dental fear.     

Outcome of Patients with Esophageal Perforations: A Multicenter Study

Background

Recent studies have suggested that stent-grafting may improve the treatment outcome of patients with esophageal perforation, but evidence on this is still lacking.

Methods

Data on 194 patients who underwent conservative (43 patients), endoclip (4 patients) stent-grafting (63 patients) or surgical treatment (84 patients) for esophageal perforation were retrieved from nine medical centers.

Results

In-hospital/30-day mortality was 17.5 %. Three-year survival was 67.1 %. Age, coronary artery disease, and esophageal malignancy were independent predictors of early mortality. Chi squared automatic interaction detection analysis showed that patients without coronary artery disease, without esophageal malignancy and younger than 70 years had the lowest early mortality (4.1 %). Surgery was associated with slightly lower early mortality (conservative 23.3, endoclips 25.0 %, stent-grafting 19.0 %, surgery 13.1 %; p = 0.499). One center reported a series of more than 20 patients treated with stent-grafting which achieved an early mortality of 7.7 % (2/26 patients). Stent-grafting was associated with better survival with salvaged esophagus (conservative 76.7 %, endoclips 75.0 %, stent-grafting 77.8 %, surgery 56.0 %; p = 0.019). Propensity score adjusted analysis showed that stent-grafting achieved similar early mortality (p = 0.946), but significantly higher survival with salvaged esophagus than with surgical treatment (p = 0.001, OR 0.253, 95 % CI 0.110–0.585). Primary surgical repair was associated with somewhat lower early mortality (14.6 vs. 19.0 %; p = 0.561) and better survival with salvaged esophagus (85.4 vs. 77.8 %; p = 0.337) than stent-grafting.

Conclusions

Esophageal perforation was associated with a rather high mortality rate in this all-comers population. Stent-grafting failed to decrease operative mortality, but it improved survival with salvaged esophagus. The results of one of the centers indicate that increasing experience with this less invasive procedure may possibly improve the outcome of these patients.     

Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements

Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle‐induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT‐PCR, the expression of interferon gamma (IFN‐γ), interleukin‐4 (IL‐4), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), IL‐13, and IL‐17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN‐γ or IL‐4 could be identified. IL‐17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up‐regulation of IL‐10, M‐CSF, IL‐8, CCL2‐4, CXCL9‐10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF‐α, IL‐1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri‐implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1241–1246, 2014.     

Homozygosity for a HERG potassium channel mutation causes a severe form of long QT syndrome: identification of an apparent founder mutation in the Finns

OBJECTIVES

We studied the clinical characteristics and molecular background underlying a severe phenotype of long QT syndrome (LQTS).

BACKGROUND

Mutations of cardiac ion channel genes cause LQTS, manifesting as increased risk of ventricular tachycardia and sudden death.

METHODS

We studied two siblings showing prolonged QT intervals corrected for heart rate (QTc), their asymptomatic parents with only marginally prolonged QTc intervals and their family members. The potassium channel gene HERG was screened for mutations by deoxyribonucleic acid sequencing, and the electrophysiologic consequences of the mutation were studied in vitro using the whole-cell patch-clamp technique.

RESULTS

A novel missense mutation (L552S) in the HERG channel, present in the homozygous state in the affected siblings and in the heterozygous state in their parents, as well as in 38 additional subjects from six LQTS families, was identified. One of the homozygous siblings had 2:1 atrioventricular block immediately after birth, and died at the age of four years after experiencing unexplained hypoglycemia. The other sibling had an episode of torsade de pointes at the age of two years. The mean QTc interval differed significantly (p < 0.001) between heterozygous symptomatic mutation carriers (500 ± 59 ms), asymptomatic mutation carriers (452 ± 34 ms) and noncarriers (412 ± 23 ms). When expressed in vitro, the HERG-L552S formed functional channels with increased activation and deactivation rates.

CONCLUSIONS

Our data demonstrate that homozygosity for a HERG mutation can cause a severe cardiac repolarization disorder without other phenotypic abnormalities. Absence of functional HERG channels appears to be one cause for intrauterine and neonatal bradycardia and 2:1 atrioventricular block.     

Seropositivity for Helicobacter pylori antibodies is associated with lower occurrence of venous bypass graft occlusion

Common chronic infections including those caused by cytomegalovirus (CMV), herpes simplex viruses (HSV), Helicobacter pylori and Chlamydia pneumoniae have previously been related to increased risk of coronary heart disease (CHD). We investigated the association between serology of these chronic infections and coronary bypass graft occlusions in 61 patients. As a result, IgG seropositivity rate against H. pylori was higher among patients without occlusion (82%) than in those with occlusion (45%) or apparently healthy controls (57%) (p = 0.004 and p = 0.008, respectively). In conclusion, H. pylori infection, as judged by IgG seropositivity, is associated with lower occurrence of venous bypass graft occlusion in patients with CHD and may thus be connected with better outcome and prognosis of CHD patients after bypass graft surgery.