Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis.

Background: Breast cancer is the most common cancer type that affects women. In hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population. Methodology: This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment. Results: PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR-/HER2+ subtype and 42% of patients with HR+/HER2- postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2- premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort. Conclusion: A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.

Different duration of high-altitude pre-exposure associated with the incidence of acute mountain sickness on Jade Mountain.

OBJECTIVE: The objective of this study is to determine the association between the duration of high-altitude (>3000 m) pre-exposure and acute mountain sickness (AMS) incidence. METHODS: A prospective observational study was conducted on 2 random days each month from April 2007 to March 2008 at Paiyun Lodge (3402 m), Jade Mountain, Taiwan. Demographic data, prior AMS history, symptoms, and scores and the days and times of high-altitude pre-exposure within the preceding 2 months were obtained from lowland (<1500 m) trekkers. RESULTS: Totally, 1010 questionnaires were analyzed; 106, 76, and 828 trekkers had pre-exposure lasting at least 3 days (group 1), less than 3 days (group 2), and 0 days (group 3), respectively. Acute mountain sickness incidence was significantly higher in groups 2 and 3 than in group 1 (21.70%, 35.53%, 37.08%, respectively; P = .008). Logistic regression analysis indicated a significantly lower AMS risk in group 1 (group 1, P = .004; odds ratio [OR], 0.479; 95% confidence interval [CI], 0.290-0.791; group 2, P = .226; OR, 0.725; 95% CI, 0.430-1.221). In group 1, 28 and 78 trekkers had single and intermittent multiple pre-exposure, respectively. There was no difference in the incidence or severity of AMS symptoms between single and intermittent multiple pre-exposure (AMS, P = .838; headache, P = .891; dizziness or lightheadedness, P = .414; fatigue and/or weakness, P = .957; gastrointestinal symptoms, P = .257; difficulty sleeping, P = .804; AMS score, P = .796). CONCLUSIONS: High-altitude pre-exposure lasting at least 3 days within the preceding 2 months was associated with a significant lower AMS incidence during a subsequent ascent among Jade Mountain trekkers.

Risk factors associated with complications in patients with chemotherapy-induced febrile neutropenia in emergency department.

Febrile neutropenia caused by chemotherapy is a frequent medical emergency associated with severe complications in the emergency department (ED). Timely administration of antibiotics is believed to improve patient outcomes for several infectious diseases such as pneumonia and sepsis but has not been thoroughly evaluated for reducing risk of complications in chemotherapy-induced febrile neutropenia. The aim of this study was to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia. We reviewed the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008. Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included. Serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization. Univariate and multivariate logistic regression analysis was performed to determine potential factors associated with serious complications. We further use decision tree approach to help analyze variables. Among a total of 81 febrile neutropenic episodes in 78 patients, 25 (30.8%) episodes of serious complications were identified. Latency of the first dose of antibiotics, pneumonia and platelet counts ≤ 50,000/mm(3) were identified as independent factors associated with serious complications of febrile neutropenia. Earlier administration of antibiotics is associated with fewer complications in patients presenting to the ED with febrile neutropenia.

Perforated peptic ulcer associated with abdominal compartment syndrome.

Abdominal compartment syndrome (ACS) is defined as an increased intra-abdominal pressure with adverse physiologic consequences. Abdominal compartment syndrome caused by perforated peptic ulcer is rare owing to early diagnosis and management. Delayed recognition of perforated peptic ulcer with pneumoperitoneum, bowel distension, and decreased abdominal wall compliance can make up a vicious circle and lead to ACS. We report a case of perforated peptic ulcer associated with ACS. A 74-year-old man with old stroke and dementia history was found to have distended abdomen, edema of bilateral legs, and cyanosis. Laboratory tests revealed deterioration of liver and kidney function. Abdominal compartment syndrome was suspected, and image study was arranged to find the cause. The study showed pneumoperitoneum, contrast stasis in heart with decreased caliber of vessels below the abdominal aortic level, and diffuse lymphedema at the abdominal walls. Emergent laparotomy was performed. Perforated peptic ulcer was noted and the gastrorrhaphy was done. The symptoms, and liver and kidney function improved right after emergent operation.