Deficiency of mannose-binding lectin-associated serine protease-2 associated with increased risk of fever and neutropenia in pediatric cancer patients

BACKGROUND: Mannose-binding lectin-associated serine protease-2 (MASP-2) is an essential component of the lectin pathway of complement activation. MASP-2 deficiency is common because of genetic polymorphisms, but its impact on susceptibility to infection is largely unknown. The aim of the present study was to determine whether children with cancer and MASP-2 deficiency develop more frequent or more severe episodes of fever and severe chemotherapy-induced neutropenia (FN). METHODS: Serum MASP-2 was measured by enzyme-linked immunosorbent assay at the time of diagnosis in children treated with chemotherapy for cancer. Association of FN episodes with MASP-2 concentration was analyzed using Poisson regression accounting for chemotherapy intensity and duration. RESULTS: Median MASP-2 in 94 children was 527 ng/mL (interquartile range, 367-686). Nine (10%) children had MASP-2 deficiency (<200 ng/mL). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded. MASP-2 deficient children had a significantly increased risk of developing FN (multivariate risk ratio, 2.08; 95% confidence interval, 1.31-3.21; P = 0.002), translating into significantly prolonged cumulative duration of hospitalization and of intravenous antimicrobial therapy. They experienced significantly more episodes of FN without a microbiologically defined etiology, and there was a trend toward more frequent episodes of FN with bacteremia. CONCLUSION: In this study, MASP-2 deficiency was associated with an increased risk of FN in children treated with chemotherapy for cancer. MASP-2 deficiency represents a novel risk factor for chemotherapy-related infections.

Stability of the hard and soft tissue profile after mandibular advancement in sagittal split osteotomies: a longitudinal and long-term follow-up study

The aim of the study was to conduct a long-term follow-up investigation of the stability of hard and soft tissues after bilateral sagittal split osteotomy (BSSO) with rigid internal (RIF) fixation to advance the mandible. Sixteen consecutive patients (12 females and 4 males, mean age 21.4 years) were available for re-examination 12.7 years (T5) after surgery. The preceding follow-ups were before (T1), and 5 days (T2), 7.3 months (T3), and 13.9 months (T4) after surgery. Lateral cephalograms were traced by hand, digitized, and evaluated with the Dentofacial Planner program. The x-axis for the system of co-ordinates ran through sella (point zero) and the line NSL -7 degrees. Thus, the program determined the x- and y-values of each variable and the usual angles and distances. Statistical analysis was carried out using Wilcoxon's matched-pair signed-ranks test with Bonferroni adjustments. The relationships between the examined variables were analysed by Spearman rank correlation coefficients. The backward relapse at point B (T5) was 2.42 mm, or 50 per cent, and at pogonion 3.21 mm, or 60 per cent of the initial advancement. The mean net effect at T5 on the labial fold (soft tissue point B) was 94 per cent of the advancement at point B. For the soft tissue chin (soft tissue pogonion), it was 119 per cent of the advancement at pogonion. The net effect on the lower lip (labrale inferior) was 55 per cent of the advancement at incision inferior. The amount of the surgical advancement of the mandible was correlated with the long-term relapse in point B. Among possible reasons for this relapse are the initial soft tissue profile, the initial growth direction, and the remodelling processes of the hard tissue.

Diversity of the basic defect of homozygous CFTR mutation genotypes in humans

BACKGROUND: Knowledge of how CFTR mutations other than F508del translate into the basic defect in cystic fibrosis (CF) is scarce due to the low incidence of homozygous index cases. METHODS: 17 individuals who are homozygous for deletions, missense, stop or splice site mutations in the CFTR gene were investigated for clinical symptoms of CF and assessed in CFTR function by sweat test, nasal potential difference and intestinal current measurement. RESULTS: CFTR activity in sweat gland, upper airways and distal intestine was normal for homozygous carriers of G314E or L997F and in the range of F508del homozygotes for homozygous carriers of E92K, W1098L, R553X, R1162X, CFTRdele2(ins186) or CFTRdele2,3(21 kb). Homozygotes for M1101K, 1898+3 A-G or 3849+10 kb C-T were not consistent CF or non-CF in the three bioassays. 14 individuals exhibited some chloride conductance in the airways and/or in the intestine which was identified by the differential response to cAMP and DIDS as being caused by CFTR or at least two other chloride conductances. DISCUSSION: CFTR mutations may lead to unusual electrophysiological or clinical manifestations. In vivo and ex vivo functional assessment of CFTR function and in-depth clinical examination of the index cases are indicated to classify yet uncharacterised CFTR mutations as either disease-causing lesions, risk factors, modifiers or neutral variants.

Influence of deep sternal wound infection on long-term survival after cardiac surgery

BACKGROUND: This study aimed to investigate the influence of deep sternal wound infection on long-term survival following cardiac surgery. MATERIAL AND METHODS: In our institutional database we retrospectively evaluated medical records of 4732 adult patients who received open-heart surgery from January 1995 through December 2005. The predictive factors for DSWI were determined using logistic regression analysis. Then, each patient with deep sternal wound infection (DSWI) was matched with 2 controls without DSWI, according to the risk factors identified previously. After checking balance resulting from matching, short-term mortality was compared between groups using a paired test, and long-term survival was compared using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Overall, 4732 records were analyzed. The mean age of the investigated population was 69.3±12.8 years. DSWI occurred in 74 (1.56%) patients. Significant independent predictive factors for deep sternal infections were active smoking (OR 2.19, CI95 1.35-3.53, p=0.001), obesity (OR 1.96, CI95 1.20-3.21, p=0.007), and insulin-dependent diabetes mellitus (OR 2.09, CI95 1.05-10.06, p=0.016). Mean follow-up in the matched set was 125 months, IQR 99-162. After matching, in-hospital mortality was higher in the DSWI group (8.1% vs. 2.7% p=0.03), but DSWI was not an independent predictor of long-term survival (adjusted HR 1.5, CI95 0.7-3.2, p=0.33). CONCLUSIONS: The results presented in this report clearly show that post-sternotomy deep wound infection does not influence long-term survival in an adult general cardio-surgical patient population.

The short-term treatment effects on the microbiota at the dorsum of the tongue in intra-oral halitosis patients-a randomized clinical trial

OBJECTIVES This study aims to assess the effects of rinsing with zinc- and chlorhexidine-containing mouth rinse with or without adjunct tongue scraping on volatile sulfur compounds (VSCs) in breath air, and the microbiota at the dorsum of the tongue. MATERIAL AND METHODS A randomized single-masked controlled clinical trial with a cross-over study design over 14 days including 21 subjects was performed. Bacterial samples from the dorsum of the tongue were assayed by checkerboard DNA-DNA hybridization. RESULTS No halitosis (identified by VSC assessments) at day 14 was identified in 12/21 subjects with active rinse alone, in 10/21 with adjunct use of tongue scraper, in 1/21 for negative control rinse alone, and in 3/21 in the control and tongue scraping sequence. At day 14, significantly lower counts were identified only in the active rinse sequence (p < 0.001) for 15/78 species including, Fusobacterium sp., Porphyromonas gingivalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Tannerella forsythia. A decrease in bacteria from baseline to day 14 was found in successfully treated subjects for 9/74 species including: P. gingivalis, Prevotella melaninogenica, S. aureus, and Treponema denticola. Baseline VSC scores were correlated with several bacterial species. The use of a tongue scraper combined with active rinse did not change the levels of VSC compared to rinsing alone. CONCLUSIONS VSC scores were not associated with bacterial counts in samples taken from the dorsum of the tongue. The active rinse alone containing zinc and chlorhexidine had effects on intra-oral halitosis and reduced bacterial counts of species associated with malodor. Tongue scraping provided no beneficial effects on the microbiota studied. CLINICAL RELEVANCE Periodontally healthy subjects with intra-oral halitosis benefit from daily rinsing with zinc- and chlorhexidine-containing mouth rinse.

Randomised in situ study on the efficacy of a tin/chitosan toothpaste on erosive-abrasive enamel loss

Tin is a notable anti-erosive agent, and the biopolymer chitosan has also shown demineralisation-inhibiting properties. Therefore, the anti-erosive/anti-abrasive efficacy of the combination of both compounds was tested under in situ conditions. Twenty-seven volunteers were included in a randomised, double-blind, three-cell crossover in situ trial. Enamel specimens were recessed on the buccal aspects of mandibular appliances, extraorally demineralised (6 × 2 min/day) and intraorally treated with toothpaste slurries (2 × 2 min/day). Within the slurry treatment time, one-half of the specimens received additional intraoral brushing (5 s, 2.5 N). The tested toothpastes included a placebo toothpaste, an experimental NaF toothpaste (1,400 ppm F(-)) and an experimental F/Sn/chitosan toothpaste (1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5% chitosan). The percentage reduction of tissue loss (slurry exposure/slurry exposure + brushing) compared to placebo was 19.0 ± 47.3/21.3 ± 22.4 after use of NaF and 52.5 ± 30.9/50.2 ± 34.3 after use of F/Sn/chitosan. F/Sn/chitosan was significantly more effective than NaF (p ≤ 0.001) and showed good efficacy against erosive and erosive-abrasive tissue loss. This study suggests that the F/Sn/chitosan toothpaste could provide good protection for patients who frequently consume acidic foodstuffs.

Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico.

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.

Maternal and neonatal outcomes by labor onset type and gestational age.

OBJECTIVE: We sought to determine maternal and neonatal outcomes by labor onset type and gestational age. STUDY DESIGN: We used electronic medical records data from 10 US institutions in the Consortium on Safe Labor on 115,528 deliveries from 2002 through 2008. Deliveries were divided by labor onset type (spontaneous, elective induction, indicated induction, unlabored cesarean). Neonatal and maternal outcomes were calculated by labor onset type and gestational age. RESULTS: Neonatal intensive care unit admissions and sepsis improved with each week of gestational age until 39 weeks (P < .001). After adjusting for complications, elective induction of labor was associated with a lower risk of ventilator use (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.28-0.53), sepsis (OR, 0.36; 95% CI, 0.26-0.49), and neonatal intensive care unit admissions (OR, 0.52; 95% CI, 0.48-0.57) compared to spontaneous labor. The relative risk of hysterectomy at term was 3.21 (95% CI, 1.08-9.54) with elective induction, 1.16 (95% CI, 0.24-5.58) with indicated induction, and 6.57 (95% CI, 1.78-24.30) with cesarean without labor compared to spontaneous labor. CONCLUSION: Some neonatal outcomes improved until 39 weeks. Babies born with elective induction are associated with better neonatal outcomes compared to spontaneous labor. Elective induction may be associated with an increased hysterectomy risk.

Incidence of second malignancies for prostate cancer

INTRODUCTION There is a need to assess risk of second primary cancers in prostate cancer (PCa) patients, especially since PCa treatment may be associated with increased risk of second primary tumours. METHODS We calculated standardized incidence ratios (SIRs) for second primary tumours comparing men diagnosed with PCa between 1980 and 2010 in the Canton of Zurich, Switzerland (n = 20,559), and the general male population in the Canton. RESULTS A total of 1,718 men developed a second primary tumour after PCa diagnosis, with lung and colon cancer being the most common (15 and 13% respectively). The SIR for overall second primary cancer was 1.11 (95%CI: 1.06-1.17). Site-specific SIRs varied from 1.19 (1.05-1.34) to 2.89 (2.62-4.77) for lung and thyroid cancer, respectively. When stratified by treatment, the highest SIR was observed for thyroid cancer (3.57 (1.30-7.76)) when undergoing surgery, whereas liver cancer was common when treated with radiotherapy (3.21 (1.54-5.90)) and kidney bladder was most prevalent for those on hormonal treatment (3.15 (1.93-4.87)). Stratification by time since PCa diagnosis showed a lower risk of cancer for men with PCa compared to the general population for the first four years, but then a steep increase in risk was observed. CONCLUSION In the Canton of Zurich, there was an increased risk of second primary cancers among men with PCa compared to the general population. Increased diagnostic activity after PCa diagnosis may partly explain increased risks within the first years of diagnosis, but time-stratified analyses indicated that increased risks remained and even increased over time.

Outcome study of real-time MR-guided cervical periradicular injection therapy in an open 1.0 Tesla MRI system

PURPOSE To evaluate the accuracy, safety, and efficacy of cervical nerve root injection therapy using magnetic resonance guidance in an open 1.0 T MRI system. METHODS Between September 2009 and April 2012, a total of 21 patients (9 men, 12 women; mean age 47.1 ± 11.1 years) underwent MR-guided cervical periradicular injection for cervical radicular pain in an open 1.0 T system. An interactive proton density-weighted turbo spin echo (PDw TSE) sequence was used for real-time guidance of the MR-compatible 20-gauge injection needle. Clinical outcome was evaluated on a verbal numeric rating scale (VNRS) before injection therapy (baseline) and at 1 week and 1, 3, and 6 months during follow-up. RESULTS All procedures were technically successful and there were no major complications. The mean preinterventional VNRS score was 7.42 and exhibited a statistically significant decrease (P < 0.001) at all follow-up time points: 3.86 ± 1.53 at 1 week, 3.21 ± 2.19 at 1 month, 2.58 ± 2.54 at 3 months, and 2.76 ± 2.63 at 6 months. At 6 months, 14.3 % of the patients reported complete resolution of radicular pain and 38.1 % each had either significant (4-8 VNRS score points) or mild (1-3 VNRS score points) relief of pain; 9.5 % experienced no pain relief. CONCLUSION Magnetic resonance fluoroscopy-guided periradicular cervical spine injection is an accurate, safe, and efficacious treatment option for patients with cervical radicular pain. The technique may be a promising alternative to fluoroscopy- or CT-guided injections of the cervical spine, especially in young patients and in patients requiring repeat injections.