Recent advances in the detection of genomic DNA from plasma samples allow us to follow tumor DNA shedding in plasma during systemic treatment. Osimertinib is the standard of care for patients with ...NSCLC with acquired EGFR T790M mutations. We assessed changes in serial plasma cell-free circulating tumor DNA (ctDNA) genomic alterations to predict osimertinib efficacy.
We prospectively collected plasma from patients having EGFR-mutated advanced NSCLC previously treated with EGFR tyrosine kinase inhibitor therapy and with acquired EGFR T790M mutation detected by standard methods. Plasma samples were collected before starting osimertinib treatment, 4 weeks after osimertinib treatment, and on progression. ctDNA was analyzed using the Guardant360 assay.
A total of 15 eligible patients received osimertinib. Before starting treatment, EGFR-activating mutations were detected in the ctDNA of all patients, and EGFR T790M was detected in 93% of the cases. Osimertinib treatment was associated with an objective response rate of 53% and a median progression-free survival of 7.3 months. A total of 12 of the 15 patients had undetectable plasma T790M and decreased activating mutation allelic frequency (AF) at week 4. None of the 12 patients had disease progression within 16 weeks. For the remaining three patients, with detectable plasma T790M (n = 2) or increased activating mutation AF (n = 1) at week 4, two had progressive disease within 16 weeks (p = 0.03).
In patients with EGFR-mutated advanced NSCLC, persistent EGFR T790M or increasing activating mutation AF as detected in ctDNA 4 weeks after the start of osimertinib treatment may predict disease progression within 16 weeks.
Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is ...the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.
Clinical Trial Registration: NCT04342949
The impact of smoking in primary spontaneous pneumothorax Cheng, Yeung-Leung, MD, PhD; Huang, Tsai-Wang, MD; Lin, Chih-Kung, MD ...
The Journal of thoracic and cardiovascular surgery,
07/2009, Letnik:
138, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background The crucial role of cigarette smoking in the development of pneumothorax is unclear because nonsmokers can also develop primary spontaneous pneumothorax. The purpose of this study was to ...clarify the pathophysiologic effects of cigarette smoking and its clinical correlations in primary spontaneous pneumothorax. Methods Included were 115 specimens of lung tissue from patients with primary spontaneous pneumothorax who underwent video-assisted thoracoscopic surgery from January 2001 to December 2002. We reviewed the clinical features of 56 smokers and 59 nonsmokers with an average follow-up of 67 months. The pathologic findings of resected lung specimens were analyzed retrospectively. Results There were no statistical differences in sex, age, body height, body weight, body mass index, or the presence of blebs/bullae on computed tomography scans of the lung or under thoracoscopy between the 2 groups. In the smoking group, patients had more extensive respiratory bronchiolitis ( P < .001), a high prevalence of tobacco pigmentation ( P < .001), and a higher recurrence rate without or after surgery than the nonsmoking group (57% vs 22%, P = .001 and 8.9% vs 1.7%, P = .02, respectively). Patients with extensive respiratory bronchiolitis had significantly higher nonoperative and postoperative recurrences than patients with nonextensive respiratory bronchiolitis ( P = .004 and P < .001, respectively). Conclusion Cigarette smoking is associated with the pathophysiologic consequences of extensive respiratory bronchiolitis, which had a significant impact on the recurrence rates of primary spontaneous pneumothorax.
Background Endoscopic papillary balloon dilation (EPBD) has a lower risk of hemorrhage than sphincterotomy and is easier to perform in altered/difficult anatomy. However, the sphincter of Oddi (SO) ...is only stretched but not cut after EPBD. Therefore, the biliary orifice is less opened, and failed stone extraction with EPBD alone occurs in up to 20% of patients. An uncut SO also may exacerbate pancreatic duct compression from edema after EPBD, and it increases the risk of pancreatitis. Objective To determine whether a longer duration for EPBD (5-minute vs conventional 1-minute) can further weaken the SO and reduce the rates of failed stone extraction and pancreatitis. Design Prospective, randomized trial. Setting Two tertiary-care referral centers. Patients This study involved 170 consecutive patients with common bile duct stones. Intervention EPBD for 1 minute (n = 86) or 5 minutes (n = 84). Main Outcome Measurements Failed stone extraction with EPBD alone and post-ERCP pancreatitis. Results Failed stone extraction with EPBD alone was less frequent with 5-minute EPBD (6 of 84, 7.1%) than with 1-minute EPBD (17 of 86, 19.8%), with a relative risk (RR) of 0.36 ( P = .024). The risk of pancreatitis was also lower with 5-minute EPBD (4 of 84, 4.8%) than with 1-minute EPBD (13 of 86, 15.1%), with an RR of 0.32 ( P = .038). Multivariable logistic regression analyses reaffirmed that 5-minute EPBD reduced the risk of failure with EPBD alone (odds ratio OR 0.19, P = .010) and pancreatitis (OR 0.28, P = .035). Limitations Endoscopists could not be blinded after the dilation durations were randomly assigned. Conclusion Compared with conventional 1-minute EPBD, 5-minute EPBD improves efficacy of stone extraction and reduces the risk of pancreatitis. ( Clinical trial registration number: NCT00451581 )
To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy ...plus induction/concurrent chemotherapy.
The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group.
Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001).
Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.
To characterize the patient demographics, clinical features, and antibiotic susceptibility of ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA), including ...community-associated (CA) and healthcare-associated (HA) isolates.
Retrospective, observational study.
Patients (n = 519) with culture-proven S. aureus ocular infections seen between January 1, 1999, and December 31, 2008, in Chang Gung Memorial Hospital.
Data collected included patient demographics and clinical information. Antibiotic susceptibility was verified by disc diffusion method.
Proportion of MRSA in S. aureus ocular infections and the clinical characteristics, diagnoses, and antibiotic susceptibility patterns of CA-MRSA versus HA-MRSA ocular infections.
We identified 274 patients with MRSA ocular infections, which comprised 181 CA-MRSA and 93 HA-MRSA isolates. The average rate of MRSA in S. aureus infections was 52.8% with a stable trend, whereas the annual ratio of CA-MRSA in ocular MRSA infections averaged 66.1% and tended to increase over the 10-year interval. Patients with ocular CA-MRSA were younger. Lid and lacrimal system disorders were more common, but keratitis, endophthalmitis, and wound infection were less common among CA-MRSA cases than HA-MRSA cases. Both CA-MRSA and HA-MRSA isolates were resistant to clindamycin and erythromycin, but CA-MRSA was more susceptible to sulfamethoxazole/trimethoprim.
Community-associated MRSA is an important pathogen of ocular infections; CA-MRSA and HA-MRSA ocular infections differ demographically and clinically, but both strains were multi-resistant in Chang Gung Memorial Hospital, one of the biggest referral centers in Taiwan. In a country with a high prevalence of MRSA, ophthalmologists should be aware of such epidemiologic information.
Background Malfunction of the arteriovenous fistula (AVF) is an important cause of morbidity and hospitalization in hemodialysis (HD) patients. The aim of this study is to evaluate the effect of far ...infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5. Study Design Randomized controlled study. Setting & Participants Patients with estimated glomerular filtration rate of 5-20 mL/min/1.73 m2. Intervention 40 minutes of far infrared therapy 3 times weekly for a year. Outcomes The primary outcome is the rate of AVF malfunction within 12 months, with malfunction defined as either: (1) thrombosis without thrill for AVFs not undergoing HD or (2) receiving any type of interventional procedure due to a lower Kt/V (<1.2) for patients undergoing HD. Secondary outcomes include: (1) cumulative primary unassisted AVF patency, defined as time from creation of the AVF to the first episode of AVF malfunction; (2) physiologic maturation of the AVF by the definition of AVF access blood flow (Qa) ≥500 mL/min and AVF diameter ≥4 mm at 3 months; and (3) clinical maturation of the AVF suitable for HD at 1 year. Measurements AVF Qa was measured by Doppler ultrasonography at 2 days and 1, 2, 3, and 12 months. Results We enrolled 122 patients who were randomly allocated to the intervention (n = 60) and control (n = 62) groups. In comparison to controls, patients in the intervention group had higher Qa values at 1, 2, 3, and 12 months; a higher rate of physiologic maturation (90% vs 76%; P = 0.04) at 3 months; and a lower rate of AVF malfunction (12% vs 29%; P = 0.02) but higher rates of AVF cumulative unassisted patency (87% vs 70%; P = 0.01) and clinical maturation (82% vs 60%; P = 0.008) within 12 months. Limitations This is a single-center nonblinded study. Conclusions Far infrared therapy improves the access flow, maturation, and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5.
Background The association between chronic hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) has been widely debated. Study Design National population-based cohort study. Setting & ...Participants Insurance claims data from the Taiwan National Health Insurance Research Database in 2000-2005. Predictor Chronic HCV infection as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. Outcomes ESRD as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. Results We identified 6,291 adults with chronic HCV infection. The control group included 31,455 sex- and age-matched individuals without evidence of chronic hepatitis. The incidence of ESRD was 2.14-fold higher in patients with chronic HCV infection (HR, 1.53; 95% CI, 1.17-2.01; P = 0.002) than in patients without HCV infection. Age stratification analysis showed that patients aged 50-59 years with chronic HCV infection (HR, 7.77; 95% CI, 4.23-14.3; P < 0.001) had the highest risk of developing ESRD relative to patients aged 20-49 years without chronic HCV infection (interaction P < 0.001). Limitations Lack of clinical data. Conclusions Patients with chronic HCV infection are at greater risk of developing ESRD than individuals without chronic HCV infection. In addition, the risk of developing ESRD is highest in younger patients with HCV infection. Early renal screening programs should be initiated for this high-risk group of young individuals with chronic HCV infection.
Background Hand hygiene (HH) is considered to be the most simple, rapid, and economic way to prevent health care–associated infection (HAI). However, poor HH compliance has been repeatedly reported. ...Our objective was to evaluate the impact of implementing the updated World Health Organization (WHO) multimodal HH guidelines on HH compliance and HAI in a tertiary hospital in Taiwan. Methods We conducted a before-and-after interventional study during 2010-2011. A multimodal HH promotion campaign was initiated. Key strategies included providing alcohol-based handrub dispensers at points of care, designing educational programs tailored to the needs of different health care workers, placement of general and individual reminders in the workplace, and establishment of evaluation and feedback for HH compliance and infection rates. Results Overall HH compliance increased from 62.3% to 73.3% after 1 year of intervention ( P < .001). The rate of overall HAI decreased from 3.7% to 3.1% ( P < .05), urinary tract infection rate decreased from 1.5% to 1.2% ( P < .05), and respiratory tract infection rate decreased from 0.53% to 0.35% ( P < .05). This campaign saved an estimated $940,000 and 3,564 admission patient days per year. Conclusion The WHO multimodal HH guidelines are feasible and effective for the promotion of HH compliance and are associated with the reduction of HAIs.
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