Genomic landscape of extraordinary responses in metastatic breast cancer.

Extreme responders to anticancer therapy are rare among advanced breast cancer patients. Researchers, however, have yet to investigate treatment responses therein on the whole exome level. We performed whole exome analysis to characterize the genomic landscape of extreme responders among metastatic breast cancer patients. Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 30 responders and 15 non-responders. Whole exome sequencing using Illumina HiSeq2500 was performed for all 45 patients (90 samples). Somatic single nucleotide variants (SNVs), indels, and copy number variants (CNVs) were identified for the genomes of each patient. Group-specific somatic variants and mutational burden were statistically analyzed. Sequencing of cancer exomes for all patients revealed 1839 somatic SNVs (1661 missense, 120 nonsense, 43 splice-site, 15 start/stop-lost) and 368 insertions/deletions (273 frameshift, 95 in-frame), with a median of 0.7 mutations per megabase (range, 0.08 to 4.2 mutations per megabase). Responders harbored a significantly lower nonsynonymous mutational burden (median, 26 vs. 59, P = 0.02) and fewer CNVs (median 13.6 vs. 97.7, P = 0.05) than non-responders. Multivariate analyses of factors influencing progression-free survival showed that a high mutational burden and visceral metastases were significantly related with disease progression. Extreme responders to treatment for metastatic breast cancer are characterized by fewer nonsynonymous mutations and CNVs.

Effect of hydroxyapatite on critical-sized defect.

BACKGROUND: Xenologous or synthetic graft materials are commonly used as an alternative for autografts for guided bone regeneration. The purpose of this study was to evaluate effectiveness of carbonate apatite on the critical-size bone defect of rat's calvarium. METHODS: Thirty-six critical-size defects were created on 18 adult male Sprague-Dawley rat calvaria under general anesthesia. Calvarial bones were grinded with 8 mm in daimeter bilaterally and then filled with (1) no grafts (control, n = 10 defects), (2) bovine bone mineral (Bio-Oss®, Geistlich Pharma Ag. Swiss, n = 11 defects), and (3) hydroxyapatite (Bongros®, Bio@ Inc., Seongnam, Korea, n = 15 defects). At 4 and 8 weeks after surgery, the rats were sacrificed and all samples were processed for histological and histomorphometric analysis. RESULTS: At 4 weeks after surgery, group 3 (42.90 ± 9.33 %) showed a significant difference (p < 0.05) compared to the control (30.50 ± 6.05 %) and group 2 (28.53 ± 8.62 %). At 8 weeks after surgery, group 1 (50.21 ± 6.23 %), group 2 (54.12 ± 10.54 %), and group 3 (50.92 ± 6.05 %) showed no significant difference in the new bone formation. CONCLUSIONS: Bongros®-HA was thought to be the available material for regenerating the new bone formation.

Treatment of Traumatic Esophagopleural Fistula Using the Over-the-Scope-Clip System.

Esophagopleural fistula (EPF) is a rare condition that is usually accompanied by severe infection and life-threatening morbidity. Here, we report the successful treatment of an EPF by closing an esophageal orifice using the over-the-scope-clip (OTSC) system without postprocedural complications. A 41-year-old man had serious thoracic and abdominal trauma due to a traffic accident. Computed tomography revealed findings suggestive of esophageal rupture due to Boerhaave syndrome. An emergent explorative operation was performed for primary repair with the insertion of a vacuum-assisted closure device. A postoperative upper gastrointestinal series revealed an EPF tract connecting the left pleural space and distal esophagus. We performed an endoscopic procedure using the "traumatic-type"OTSC to seal the EPF, and the esophageal orifice was completely healed 2 weeks postoperatively. The OTSC system might represent a safe and feasible modality for the treatment of EPF.

Attribution of aerosol light absorption to black carbon and volatile aerosols.

We investigated the contribution of volatile aerosols in light-absorption measurement by three filter-based optical instruments [aethalometer, continuous light-absorption photometer (CLAP), and continuous soot monitoring system (COSMOS)] at Gosan Climate Observatory (GCO) from February to June 2012. The aerosol absorption coefficient (σ abs) and the equivalent black carbon (BC) mass concentration (M BC) measured by the aethalometer and CLAP showed good agreement with a difference of 9 %, which is likely due to the instrumental uncertainty. However, σ abs and M BC measured by the COSMOS with a heated inlet were found to be approximately 44 and 49 % lower than those measured by the aethalometer and CLAP under ambient conditions, respectively. This difference can be attributed to the light absorption by the volatile aerosols coexisting with the BC. Even considering inherent observational uncertainty, it suggests that approximately 35-40 % difference in the σ abs and M BC can be contributed by volatile aerosols. Increase in the difference of M BC measured by the aethalometer and COSMOS with the increasing thermal organic carbon (OC) measured by Sunset OC/EC analyzer further suggests that the filter-based optical instruments without the use of a heater are likely to enhance the value of σ abs and M BC, because this sample air may contain both BC and volatile aerosols.

Recurrent pneumothorax after etanercept therapy in a rheumatoid arthritis patient: a case report.

The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is gradually increasing. Etanercept is the first anti-TNF agent to be approved for RA treatment and is also the most widely used. However, aggravation of interstitial lung disease after etanercept treatment in RA patients has been reported recently. We report the first case of recurrent spontaneous pneumothorax with progression of interstitial lung disease after initiating etanercept therapy. The withdrawal of etanercept and a change to adalimumab, a different class of TNF inhibitor, achieved clinical stabilization.

Amniotic fluid embolism that took place during an emergent Cesarean section -A case report-.

Amniotic fluid embolism (AFE) is a rare but fatal obstetric emergency, characterized by sudden cardiovascular collapse, dyspnea or respiratory arrest and altered mentality, disseminated intravascular coagulation (DIC). It can lead to severe maternal morbidity and mortality, but the prediction of its occurrence and treatment are very difficult. We experienced a case of AFE during emergent Cesarean section in a 40(+6) weeks healthy pregnant woman, age 33. Sudden dyspnea, hypotension, signs of pulmonary edema and DIC were developed during Cesarean section, and cardiac arrest followed after these events. The course of these events was so rapid and catastrophic, which was consistent with AFE. Thus, we report this case precisely and review pathophysiology, diagnosis, treatment of AFE by referring to up-to-date literatures.