Consolidative chemotherapy after definitive concurrent chemoradiotherapy for esophageal squamous cell carcinoma patients: a population based cohort study.

BACKGROUND: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach. METHODS: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches. RESULTS: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses. CONCLUSIONS: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding.

Exploring the influence of gender, seniority and specialty on paper and computer-based feedback provision during mini-CEX assessments in a busy emergency department.

The mini-clinical evaluation exercise (mini-CEX) is a well-established method of assessing trainees' clinical competence in the workplace. In order to improve the quality of clinical learning, factors that influence the provision of feedback are worthy of further investigation. A retrospective data analysis of documented feedback provided by assessors using the mini-CEX in a busy emergency department (ED) was conducted. The assessors comprised emergency physicians (EPs) and trauma surgeons. The trainees were all postgraduate year one (PGY1) residents. The completion rate and word count for each of three feedback components (positive feedback, suggestions for development, and an agreed action plan) were recorded. Other variables included observation time, feedback time, the format used (paper versus computer-based), the seniority of the assessor, the gender of the assessor and the specialty of the assessor. The components of feedback provided by the assessors and the influence of these contextual and demographic factors were also analyzed. During a 26-month study period, 1101 mini-CEX assessments (from 273 PGY1 residents and 67 assessors) were collected. The overall completion rate for the feedback components was 85.3 % (positive feedback), 54.8 % (suggestions for development), and 29.5 % (agreed action plan). In only 22.9 % of the total mini-CEX assessments were all three aspects of feedback completed, and 7.4 % contained no feedback. In the univariate analysis, the mini-CEX format, the seniority of the assessor and the specialty of the assessor were identified as influencing the completion of all three components of feedback. In the multivariate analysis, only the mini-CEX format and the seniority of the assessor were statistically significant. In a subgroup analysis, the feedback-facilitating effect of the computer-based format was uneven across junior and senior EPs. In addition, feedback provision showed a primacy effect: assessors tended to provide only the first or second feedback components in a busy ED setting. In summary, the authors explored the influence of gender, seniority and specialty on paper and computer-based feedback provision during mini-CEX assessments for PGY1 residency training in a busy ED. It was shown that junior assessors were more likely to provide all three aspects of written feedback in the mini-CEX than were senior assessors. The computer-based format facilitated the completion of feedback among EPs.

Evaluation of the necessity for chest drain placement following thoracoscopic wedge resection.

PURPOSE: To evaluate the outcomes of patients who underwent thoracoscopic wedge resection without chest drain placement. METHODS: The subjects of this retrospective study were 89 patients, who underwent thoracoscopic wedge resection at our hospital between January, 2013 and July, 2015. A total of 45 patients whose underlying condition did not meet the following criteria were assigned to the "chest drain placement group" (group A): peripheral lesions, healthy lung parenchyma, no intraoperative air leaks, hemorrhage or effusion accumulation, and no pleural adhesion. The other 44 patients whose underlying condition met the criteria were assigned to the "no chest drain placement group" (group B). Patient characteristics, specimen data, and postoperative conditions were analyzed and compared between the groups. RESULTS: Group A patients had poorer forced expiratory volume in one second (FEV1) values, less normal spirometric results, significantly higher resected lung volume, a greater maximum tumor-pleura distance, and a larger maximum tumor size. They also had a longer postoperative hospital stay. There was no difference between the two groups in postoperative complications. CONCLUSIONS: Avoiding chest drain placement after a thoracoscopic wedge resection appears to be safe and beneficial for patients who have small peripheral lesions and healthy lung parenchyma.

Metabolites of antroquinonol found in rat urine following oral administration.

Four metabolites (1-4) of antroquinonol from rat urine, collected within 24 h after oral administration of antroquinonol, were characterized by HPLC-SPE-NMR. Compounds 1-4 were further isolated by semipreparative HPLC for structure confirmation. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic analyses and HRESIMS data.

Overexpression of matrix metalloproteinases in lung tissue of patients with primary spontaneous pneumothorax.

BACKGROUND: Although blebs and bullae are frequently found in the apexes of lungs of patients with primary spontaneous pneumothorax (PSP), its pathogens remain unclear. OBJECTIVES: To examine the role of proteases [matrix metalloproteinase (MMP)-2, MMP-7 and MMP-9] and antiproteases [tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4] in the pathogenesis of PSP. METHOD: Fifty consecutive PSP patients who received standard surgical care were enrolled in the study. Lung tissues from 20 patients with stage I non-small cell lung cancer were used as a control. Immunohistochemistry (IHC), reverse transcription-polymerase chain reaction (RT-PCR) and gelatin zymography were used to evaluate the expression of MMP and TIMP in the lung tissue of patients with PSP. RESULTS: Overexpression of MMP-2, MMP-7 and MMP-9 was found in the afflicted lung by IHC, zymography and RT-PCR. By IHC, higher expression of MMP-2 and MMP-9 in PSP patients was identified in alveolar macrophages and type II pneumocytes (88 and 92% of patients in macrophages, and 72 and 70% of patients in type II pneumocytes, respectively). MMP-2, MMP-7 and MMP-9 expression in patients was higher in mesothelial cells (66, 76 and 76%). Overexpression of TIMP-2 was detected in the extracellular matrix around bullae and blebs. Expression levels of TIMP-1, TIMP-3 and TIMP-4 were negligible (<10% of cells) in both PSP patients and controls. CONCLUSIONS: MMP-2, MMP-9, MMP-7 and TIMP-2 were upregulated in PSP lesions. These results suggest that an imbalance between the expression of proteases and antiproteases may be involved in the pathogeneses of PSP.

Analysis and identification of phenolic compounds with antiproliferative activity from Chinese olive (Canarium album L.) fruit extract by HPLC-DAD-SPE-TT-NMR.

Chinese olives (Canarium album L.) are rich in phenolic compounds, exhibiting a broad spectrum of potential clinical applications. This study is the first report on the isolation and elucidation of bioactive compounds with high antiproliferative activity from the ethyl acetate fraction of a Chinese olive fruit methanolic extract (CO-EtOAc). We used the WST-1 assay to determine which subfractions of CO-EtOAc had significant antiproliferative activity using the murine colon cancer cell line CT26. Subsequently, the functional compounds were characterized by the hyphenated technique and high-performance liquid chromatography-diode array detector-solid phase extraction-transfer tube-nuclear magnetic resonance (HPLC-DAD-SPE-TT-NMR). Thirteen phenolic constituents were identified from the antiproliferation-enhancing subfractions of CO-EtOAc, including two new compounds, 2,4-didehydrochebulic acid 1,7-dimethyl ester (5) and 1-hydroxybrevifolin (7), which were further purified and found to exhibit marked antiproliferative activity. Chebulic acid dimethyl ester (2), which was isolated from C. album for the first time, also possessed antiproliferative activity.

Metabolism of (2S)-pterosin A: identification of the phase I and phase II metabolites in rat urine.

The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (±)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ∼71% 1 was excreted as metabolites in rat urine.

Catamenial pneumothorax due to bilateral pulmonary endometriosis.

Co-existence of catamenial pneumothorax and hemoptysis is rare. We present a case of catamenial pneumothorax due to bilateral pulmonary endometriosis in a 45-year-old woman. The patient presented with a 3-year history of intermittent productive cough with blood-tinged sputum, chronic anemia, loss of appetite, and general weakness associated with menstruation. Three years prior to this presentation the patient had undergone a sigmoidectomy as treatment for endometriosis of the sigmoid colon with bleeding. Chest radiographs and computed tomography (CT) scan revealed multiple nodules in both lung parenchyma and recurrent pneumothorax. CT-guided biopsy revealed chronic inflammation of those pulmonary nodules, and laboratory studies disclosed elevated serum levels of carbohydrate antigen 19-9 (CA 19-9) and CA 125. Thoracoscopic wedge resection of the pulmonary nodules was performed, and histopathological examination of the resected nodules revealed endometriosis. At one-year follow-up there was no evidence of recurrence of gastrointestinal bleeding or pneumothorax.

Press tack needle stimulation for blunt chest trauma: a randomized double-blind control trial.

OBJECTIVES: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design. METHODS: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups. RESULTS: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05). CONCLUSIONS: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltirl.gov: NCT04318496.

Effectiveness evaluation of adjuvant concurrent chemoradiotherapy for patients with positron emission tomography-staged esophageal squamous cell carcinoma after complete resection: A population-based cohort study.

BACKGROUND: The role of adjuvant concurrent chemoradiotherapy (ACCRT) is unclear for patients with esophageal squamous cell carcinoma (ESCC) who receive esophagectomy with clean margins. We compared the survival of the ACCRT versus observation groups for these patients staged with positron emission tomography (PET) via a population-based approach. METHODS: Eligible patients with locally advanced ESCC diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratios (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between the ACCRT and observation groups. We also evaluated overall survival (OS) in subgroups of either with or without lymph node metastases. RESULTS: Our primary analysis consisted of 105 patients in whom the covariates were well balanced after PS weighting. The HR for death when ACCRT was compared with observation was 0.58 (95% confidence interval 0.28-1.21, p = 0.15). The results were also not significantly different for IECM or in the subgroup analyses. CONCLUSION: We found that for patients with PET-staged ESCC who received esophagectomy with clean margins, the survival was not statistically different between ACCRT and observation. Further studies (randomized or larger sample size) are needed to clarify this issue.

Comprehensive study of alkaloids from Crinum asiaticum var. sinicum assisted by HPLC-DAD-SPE-NMR.

A comprehensive study of the alkaloids presentin the leaves of Crinum asiaticum var. sinicum, assisted by HPLC-SPE-NMR, led to the characterization of 21 compounds of similar polarity on an analytical scale. Thirteen of these were isolated for further structural confirmation. Seven are proved to be new, namely, (+)-siculine (4), 1-epijosephinine (11), 7-methoxycrinamabine (10), 2-O-acetylcrinamabine (16), 3-O-acetyl-8-O-demethylmaritidine (17), 2-O-acetylbulbisine (18), and 1-O-acetylbulbisine (19). In addition, dihydrovittatine (6) and 8-O-demethyloxomaritidine (21) were isolated for the first time from Nature, although they have been prepared previously as synthetic products. Their structures were established by spectroscopic analysis.

Two new morphinane alkaloids from Sinomenium acutum.

Two new morphinane alkaloids, 1-hydroxy-10-oxo-sinomenine (1) and 4,5-epoxy-14-hydroxy sinomenine N-oxide (2), have been isolated from the stems of Sinomenium acutum. Their structures were established by various spectral analyses, especially 2D NMR experiments. The structure of 2 was confirmed by single crystal X-ray diffraction. The absolute configurations of 1 and 2 were deduced by comparison of CD spectra with the known alkaloid sinomenine (3). Compound 1 was tested for DPPH inhibition and gave IC(50) of 27.9 µM. Compound 2 was tested for neuroprotective effect and showed significant activity against ß-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 µM in PC-12 cells.

Acupuncture for blunt chest trauma: A protocol for a double-blind randomized control trial.

INTRODUCTION: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients. METHODS: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months. EXPECTED OUTCOME: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture. OTHER INFORMATION: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022. PROTOCOL REGISTRATION: (CMUH109-REC1-002), (NCT04318496).

Metabolism of dicentrine: identification of the phase I and phase II metabolites in miniature pig urine.

The metabolic profile of dicentrine, a selective α(1)-adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities, in miniature pig urine via oral administration was investigated for the first time. The urine, collected after a single oral administration of dicentrine, was pretreated using solvent extraction and column chromatographic methods to identify the metabolites containing fractions. Twenty-four metabolites (MI-1-9 and MII-1-15), of which 21 compounds are new, were identified by mass spectrometry and high-performance liquid chromatography-diode array detector solid-phase extraction-NMR techniques. Of these, 14 metabolites (MI-5, MII-1 and 2, and MII-5-15) were further isolated for structure confirmation. The phase I metabolic transformations of dicentrine were found to be N-demethylation, N-oxidation, O-demethylation (9,10-OMe), O,O-demethylenation (1-OCH(2)O-2), and hydroxylation at the benzylic (C-4) and the aromatic (C-3) positions, whereas those for the phase II were O-glucuronidation and O-glucosylation of the phenolic group of the phase I metabolites.

Arisanschinins A-E, lignans from Schisandra arisanensis hay.

Four new oxygenated dibenzocyclooctadiene lignans, arisanschinins A-D ( 1- 4), and a new 1,4-bis(phenyl)-2,3-dimethylbutane lignan, arisanschinin E ( 5), together with 15 known compounds, were isolated from the EtOAc-soluble fraction of the aerial parts of SCHISANDRA ARISANENSIS Hay. The structures of 1- 5 were elucidated on the basis of extensive spectroscopic analyses, including 2D NMR (HMQC, HMBC, and NOESY) experiments. The configurations of the biphenyl and octadiene moieties were deduced from circular dichroism (CD) and NOESY spectra, respectively. Compound 1 showed significant inhibition of α-glucosidase IN VITRO. The radical-scavenging activities of these compounds were evaluated using DPPH.

Patients with spontaneous pneumothorax have a higher risk of developing lung cancer: A STROBE-compliant article.

Lung cancer is a common malignancy worldwide, and risk factors include bronchitis, asthma, tuberculosis, smoking, and air pollution. These are also risk factors for spontaneous pneumothorax, a benign disease. We hypothesized that patients who experience a spontaneous pneumothorax have a greater risk to develop lung cancer, and designed a study to determine if this is so.We used the population-based Taiwan Health Insurance Research Database to perform a retrospective cohort study. The database includes more than 99% of the population of Taiwan. We established a 27,405-person pneumothorax cohort and a 109,620 person comparison cohort with data from 2000 to 2009 to evaluate the relationship between spontaneous pneumothorax and lung cancer.Multivariable analysis showed that patients who have had a spontaneous pneumothorax have a greater relative risk to develop lung cancer. The overall hazard ratio was 2.09 (95% confidence interval 1.69-2.58) adjusted by age, gender, hypertension, diabetes mellitus, and chronic lung diseases such as chronic obstructive pulmonary disease, tuberculosis, asthma, bronchitis, and emphysema. A dose effect was present; a high frequency of spontaneous pneumothorax was associated with a greater relative risk to develop lung cancer. If the spontaneous pneumothorax frequency was greater than 2 times per year, the hazard ratio was 34.09 (95% confidence interval 22.74-51.10)Patients with spontaneous pneumothorax have an increased relative risk to develop lung cancer, especially among patients 35 to 49 years of age. The more frequent the occurrence of spontaneous pneumothorax, the greater the relative risk of lung cancer. If the spontaneous pneumothorax frequency was greater than 2 times per year, the increase in risk of lung cancer was more than 30-fold.

Diastereomeric identification of neolignan rhamnosides from Trochodendron aralioides leaves by LC-SPE-NMR and circular dichroism.

Trochodendron aralioides is an old-existing relic plant with limited availability and only a few identified compounds. Accumulative analysis on the methanolic extract from its leaf part by LC-SPE-NMR resulted in the identification of seven new compounds, including three neolignan α-rhamnosides [(7R,8S)-dihydrodehydrodiconiferyl alcohol- 9-O-α-rhamnopyranoside (2) and 9'-O-α-rhamnopyranoside (3), and (7S,8R)-dehydrodiconiferyl alcohol-9'-O-α-rhamnopyranoside (4)], two isomeric oxyneolignan α-rhamnosides [(7R,8S)- (5) and (7R,8R)-icariside E8 (6)), and (7R,8S)- (10) and (7R,8R)-icariside E9 (11)], and two isomeric acylated fructofuranosyl mevalonolactones (13, 14), along with five known compounds (1, 7-9 and 12). The absolute configuration of the C-7 and C-8 positions for the new compounds 2-6 and 10-11 was assigned by comparison of the reported ECD spectra. Compounds 2, 3, 4, and 6 were further isolated by semi-preparative column chromatography for structure confirmation by 2D NMR spectroscopic analysis.

Three adducts of butenolide and apigenin glycoside from the leaves of Machilus japonica.

Chemical investigation of the EtOH extract of the leaves of Machilus japonica var. kusanoi resulted in the isolation of three compounds with a unique skeleton, i.e., apigenosylides A-C (4-6), together with five known flavonoid glycosides. Some of these compounds possess moderate inhibitory activity against alpha-glucosidase. The structures of the new compounds were elucidated on the basis of spectrometric analyses. They possess an unprecedented skeleton comprising the adduct of a butenolide moiety and apigenin glycoside linked via a 1,2-dioxane moiety.

Acylated flavonol monorhamnosides, alpha-glucosidase inhibitors, from Machilus philippinensis.

Bioassay-guided fractionation and isolation of the active constituents from the leaf extract of Machilusphilippinense Merr. yielded two active compounds, kaempferol-3-O-alpha-L-rhamnopyranoside 3'',4''-di-E-P-coumaroic acid ester (1) and 3''-E,4''-Z-di-p-coumaroic acid ester (2) when tested against a Bacillus stearothermophilus, a alpha-glucosidase type IV. The IC50 values of 1 and 2 were 6.10 and 1.00microM, respectively. Further application of the HPLC-SPE-NMR hyphenated technique in the on-line characterization of other active ingredients present in the CH2Cl2 - soluble fraction led to identification of luteolin (3) and seven additional 3-O-(coumaroyl-rhamnopyranosyl)-flavonols (4-10). Their structures were determined mainly by 1H NMR spectroscopic analyses. Among the compounds identified, compounds 2, 4, 5, and 7 were hitherto unknown natural products.

Pulmonary Tumor Thrombotic Microangiopathy: Case Report and Literature Review.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive pulmonary disease complicated by malignancy. It manifests clinically as respiratory distress with pulmonary hypertension, progressive right sided heart failure, and sudden death. We describe a case of PTTM associated with metastatic gastric carcinoma. This case demonstrates the diagnostic diffi culties in such a rare and rapidly fatal oncological complication. More awareness among clinicians may help make a right diagnosis in the short time available. We also review the literatures to demonstrate the clinical characteristics that might provide clues towards an antemortem diagnosis, and may provide the key in treating PTTM.