Predicting abdominal adipose tissue in overweight Latino youth.

OBJECTIVES: 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. STUDY DESIGN: Cross-sectional. PARTICIPANTS: 196 overweight 8-13-year-old Latino youth. Two-thirds (n = 131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n = 65) was used as a cross-validation group. METHODS AND PROCEDURES: Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). RESULTS: The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p < 0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p < 0.001). Regression analyses showed approximately 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. CONCLUSIONS: Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level.     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Effects of radiotherapy planning with a dedicated combined PET-CT-simulator of patients with non-small cell lung cancer on dose limiting normal tissues and radiation dose-escalation: a planning study.

BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints.     

Expression of BAG-1 and BcL-2 Proteins Before and After Neoadjuvant Chemotherapy of Locally Advanced Breast Cancer

It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.     

Dental anomalies in cleft lip and palate: A case–control comparison of total and outside the cleft prevalence

This study’s objective was to compare the total and outside the cleft prevalence of dental anomalies (DA) between patients with cleft lip and palate (CLP) and a control group. This retrospective cross-sectional study was done under a case–control design. The case group consisted of 192 non-syndromic patients with complete CLP, while the control group included 411 patients. All subjects had orthopantomography, intra, and extraoral photographs. The prevalence of dental agenesis, supernumerary teeth, impacted teeth, dental transposition, and microdontia were compared using a chi-squared test (P < .05). Next, a second test was made, but only the anomalies outside the cleft were considered for this study. Total prevalence was 89.1% for cases, and 20.9% for controls (P < .01). The prevalence of each DA was significantly higher for the case group. In the analysis of DAs outside the cleft, the total prevalence was still significantly associated (P < .01); however, only dental agenesis was statistically significant (P < .01). Further analysis found that a high rate of upper premolar absence (P < .01) could explain this event. Patients with CLP have a higher prevalence of DAs compared to controls. After considering only the DAs outside the cleft, the total prevalence remains significantly higher. However, this phenomenon is explained mainly by the elevated prevalence of upper premolars’ agenesis. This study’s results suggest that environmental factors are behind the high prevalence of DAs in subjects with CLP.     

Pulmonary artery-bronchus fistula treated with coil embolization

Bronchopulmonary arterial fistula consists of an abnormal connection between the bronchus and the vascular tree and is a rare but serious complication associated with a variety of lung interventions. We present a case of a 61-year-old female with a history of metastatic breast cancer treated with lumpectomy and radiation 20 years prior, who was found to have a fistula between the right pulmonary artery and the right mainstem bronchus. Our patient was treated endovascularly with coil embolization in the setting of massive hemoptysis flooding the trachea, which was successful in controlling the acute bleed, although care was withdrawn in the following days following a discussion with the family given the presence of advanced metastatic disease. This case illustrates the use of endovascular techniques to treat an actively bleeding bronchopulmonary arterial fistulae, including a review of the existing literature regarding the optimal endovascular management strategy. Although our patient did not achieve the best outcome, endovascular intervention with stent-placement or embolization can serve to temporarily halt blood flow through the fistula, stabilizing the patient and allowing for more radical therapy after improvement.     

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication

Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.     

Genome-wide linkage analysis combined with genome sequencing in large families with intracranial aneurysms

Rupture of an intracranial aneurysm (IA) leads to aneurysmal subarachnoid haemorrhage (ASAH), a severe type of stroke. Some rare variants that cause IA in families have been identified, but still, the majority of genetic causes, as well as the biological mechanisms of IA development and rupture, remain unknown. We aimed to identify rare, damaging variants for IA in three large Dutch families with multiple affected members with IA (N = 9, 11, and 6). By combining linkage analysis and genome sequencing (GS), we identified six rare and damaging variants for which all cases within one of the families were heterozygous. These variants were p.Tyr87Cys in SYCP1, p.Phe1077Leu in FMNL2, p.Thr754Lys in TBC1D2, p.Arg321His in ZNF782, p.Arg979Trp in CCDC180, and p.Val125Met in NCBP1. None of the variants showed association with IA status in a large cohort of 937 patients from the general IA patient population and 1046 controls. Gene expression in IA and cerebral artery tissue further prioritized FMNL2 and TBC1D2 as potential important players in IA pathophysiology. Further studies are needed to characterize the functional consequences of the identified variants and their role in the biological mechanisms of IA.Subject terms: Stroke, Aneurysm, Genetic linkage study, Next-generation sequencing