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991.
N. Kramkimel A. Thomas-Schoemann L. Sakji JL. Golmard G. Noe E. Regnier-Rosencher N. Chapuis E. Maubec M. Vidal MF. Avril F. Goldwasser L. Mortier N. Dupin B. Blanchet 《Targeted oncology》2016,11(1):59-69
Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF V600 -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n?=?159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0–6.0) and 11.0 (95% CI 7.0–16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p?=?0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21–1.08; p?=?0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG ?≥?1 (odds ratio 4.67; 95 % CI 1.39–15.70; p?=?0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5–5.5] vs. 4.5 [2–undetermined] months, p?=?0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7?±?25.0 vs. 36.3?±?17.9 mg/L, p?<?0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥?2 skin rash. 相似文献
992.
993.
994.
Groome M Lindsay J Ross PE Cotton JP Hupp TR Dillon JF 《European journal of gastroenterology & hepatology》2008,20(10):961-965
INTRODUCTION: Oesophageal adenocarcinoma is an increasingly common diagnosis and cause of death; risk factors include 'Barrett's epithelium' (BE). Endoscopic surveillance is most commonly used but is expensive. Other methods of surveillance have been suggested including nonendoscopic balloon cytology, but are handicapped by relying on cytological techniques; hence the need for a partner technology such as a biomarker. From earlier work we know the most commonly expressed oesophageal stress response proteins are SEP 53, SEP70 and anterior gradient-2 (AG-2). We set out to map the expression of these stress response proteins and explore their potential as prototype biomarkers of BE. METHODS: Patients (n=192) presenting to the endoscopy unit of a large teaching hospital with symptoms of gastro-oesophageal reflux disease or a known BE were recruited, endoscopically examined and the biopsies obtained were examined for heat shock protein expression. RESULTS AND DISCUSSION: Normal controls and those with oesophagitis predominantly expressed SEP 53 (76.9/91.95%) and SEP 70 (79.48/89.65%). Although those with BE expressed AG-2; using this expression as a marker for BE, gives a sensitivity of 65.15% and specificity of 89.68% (positive predictive value of 76.78% and negative predictive value of 84.9%) and in gastro-oesophageal reflux disease a sensitivity of 65.15% and specificity of 90.80% (positive predictive value of 84.31% and negative predictive value of 77.45%). We confirmed that AG-2 is preferentially expressed in BE; suggesting its use would allow a screening tool with specificity of around 90%. 相似文献
995.
We examined 99 endotracheal tubes removed from 81 pediatric patients to determine the incidence of partial endotracheal tube obstruction and predisposing factors. The overall incidence of obstruction was 20.2% (20/99); 14 of the 20 obstructed tubes were occluded less than 50%. General anesthesia during the period of intubation was the only factor significantly associated with an increased incidence of obstruction (p less than 0.05). There was no correlation of obstruction with duration of intubation, the presence of a Murphy-eye side hole, or small tube size. Among the 71 tubes from patients who received general anesthesia, a tube size of 4 mm or less was associated with an increased incidence of obstruction (p less than 0.05). Pressure-flow curves for three different sizes of endotracheal tubes were constructed to determine the increase in resistance produced by different degrees of obstruction. At flow rates that approximated those found in children during quiet breathing, the resistance of tubes that were 50% obstructed was 4 times greater than that found in unobstructed tubes. 相似文献
996.
Dor Yoeli Ruth L Ackah Rohini R Sigireddi Michael L Kueht N Thao N Galvan Ronald T Cotton Abbas Rana Christine A OMahony John A Goss 《Journal of pediatric surgery》2018,53(11):2240-2244
Background
The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications.Methods
All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30?days or the same hospital admission as the transplant operation, excluding retransplantation.Results
Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p?=?0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39?days vs. 11?days, p?=?0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression.Conclusion
At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model.Type of study
Prognosis Study.Level of evidence
Level III. 相似文献997.
An interview with five experts on AIDS therapy, Dr. Robert Coombs, Dr. Scott Hammer, Dr. Michael Saag, Dr. Charles van der Horst, and Dr. Deborah Cotton, explores their impressions of the results from three large clinical trials. The trials--ACTG 175, Delta 1, and Delta 2--analyzed the efficacy of treatment with AZT alone compared to AZT combined with ddI or ddC, and ddI alone. Coombs states that the ACTG 175 results are the first convincing evidence of overall survival benefit with ddI compared with AZT alone. According to Hammer, the results suggest that AZT monotherapy may no longer be the optimal approach. Van der Horst said the results show that treatment outweighs no treatment, even at the beginning when CD4 counts are higher. Cotton observed that although the results show a benefit, she would not start therapy in an asymptomatic person. The experts also detailed what data they use to determine the best treatment to use for patients. Coombs said he uses the patient's CD4 cell count and clinical status, along with their viral load. Saag said his decision to treat asymptomatic patients is based on his understanding of how the virus causes disease and the pathogenesis of HIV infection. 相似文献
998.
Decrements in platelet function and recovery are known to accumulate during the 5-day storage period, and the clinical response to platelets transfused after several days' storage has been suggested by some researchers to be less than that seen with platelets stored for shorter periods. The clinical response to single-donor platelet (SDP) units (as measured by corrected count increments [CCIs] and intertransfusion intervals) was investigated in autologous bone marrow transplant patients. Twenty-seven consecutive autologous bone marrow transplant patients with a variety of hematologic and solid organ malignancies were evaluated for posttransfusion CCIs after 419 SDP transfusions of units stored for 1 to 5 days. Patients were not excluded from the study because of clinical condition, such as fever or sepsis. The mean 15- minute posttransfusion CCI for SDP units stored for only 1 day (11,006 +/− 5,157) was no different than that for units stored for 5 days (10,225 +/− 4,481; p > 0.05); 24-hour posttransfusion CCIs were also not different if the SDP unit had been stored for 1 day or 5 days (6229 +/− 4489 vs. 4786 +/− 2759; p > 0.05) or for any intermediate period. Nor were intertransfusion intervals affected by storage time. While platelets may exhibit a progressive lesion during the 5-day storage period, these changes do not result in a decreased clinical response. 相似文献
999.
The Institute of Medicine's (IOM) Committee on Perinatal Transmission of HIV released its report in October 1998. Universal and routine HIV testing with the right of refusal for all pregnant women in the United States was recommended. This recommendation differed from the CDC guidelines in 1995 that recommended universal counseling but only voluntary testing for all pregnant women. Dr. Nancy Kass from the IOM committee and Dr. Howard Minkoff of the Maimonides Medical Center discuss the policy and its implications with Dr. Deborah Cotton, editor of AIDS Clinical Care and IOM committee member. Medical and social advantages of the policy are described, and steps are detailed for implementing IOM's recommendations. 相似文献
1000.
M E Edmonds M P Blundell M E Morris E M Thomas L T Cotton P J Watkins 《The Quarterly journal of medicine》1986,60(232):763-771
A specialized foot clinic for diabetic patients has made a detailed analysis of the presentation of diabetic foot ulcers and from this a new, organised approach to treatment has been derived. Over three years it has achieved a high rate of ulcer healing and reduced the number of major amputations. It has brought together the skills of chiropodist, shoe-fitter, nurse, physician and surgeon to manage the distinctive lesions of the neuropathic and ischaemic diabetic foot. The neuropathic ulcer was invariably associated with callus, whereas the ischaemic ulcer presented as areas of necrosis often from localised pressure of tight shoes. Essential aspects of management are specially constructed shoes, intensive chiropody and precise antibiotic treatment. Healing was achieved in 204 out of 238 (86 per cent) neuropathic ulcers and 107 out of 148 (72 per cent) ischaemic ulcers. Relapse rate in special shoes was 26 per cent compared with 83 per cent who preferred to wear their own shoes. In the two years before the establishment of the clinic, there were 11 and 12 major amputations yearly. This rate has now been reduced to seven, seven and five amputations yearly. 相似文献