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1.
Sarina A. Piha-Paul Do-Youn Oh Makoto Ueno David Malka Hyun Cheol Chung Adnan Nagrial Robin K. Kelley Willeke Ros Antoine Italiano Kazuhiko Nakagawa Hope S. Rugo Filippo de Braud Andrea Iolanda Varga Aaron Hansen Hui Wang Suba Krishnan Kevin G. Norwood Toshihiko Doi 《International journal of cancer. Journal international du cancer》2020,147(8):2190-2198
We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity. 相似文献
2.
C.Z. Simonsen S. Schnenberger P.L. Hendn A.J. Yoo L. Uhlmann A. Rentzos J. Bsel J. Valentin M. Rasmussen 《AJNR. American journal of neuroradiology》2020,41(12):2298
BACKGROUND AND PURPOSE:Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion.MATERIALS AND METHODS:Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia.RESULTS:Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3 ± 13.8 years for conscious sedation versus 71.6 ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group.CONCLUSIONS:Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.Five studies published in 2015 proved the efficacy of endovascular therapy (EVT) for acute ischemic stroke caused by a large-vessel occlusion.1 However, numerous questions remain regarding how to best deliver this treatment, including evaluation of the optimal thrombectomy technique,2 the most effective method of patient triage,3 or whether EVT should be performed with the patient under either general anesthesia (GA) or conscious sedation (CS).Observational studies have suggested that EVT with the patient under CS is associated with better neurologic outcome and lower mortality compared with GA.4 However, 3 randomized trials reported similar outcomes between CS and GA.5-7 Proposed benefits of CS include stable hemodynamics, clinical monitoring, and a potentially shorter procedure. The disadvantages are an unprotected airway and patient movement, which sometimes may require emergent conversion to GA. Patients who need conversion might be sicker (larger strokes, more medical complications), but the conversion procedure itself may also have a potentially deleterious influence on outcome due to the emergent anesthetic induction, associated hypotension, and added time delay before reperfusion.Although most patients can be treated under the less complex CS, it is of interest to identify factors that can predict the risk of conversion and hence the requirement for GA. We undertook a detailed analysis of the patients who were converted from CS to GA in our individual patient data base from the 3 randomized trials to examine the outcome of the converted patients compared with patients who remained in CS. We also aimed to identify possible predictors associated with a need for GA with EVT. 相似文献
3.
Ho-Chul Jung Sung-Bin Chon Won Sup Oh Dong-Hyun Lee Ho-Jin Lee 《The American journal of tropical medicine and hygiene》2015,92(2):256-261
Scrub typhus usually presents as acute undifferentiated fever. This cross-sectional study included adult patients presenting with acute undifferentiated fever defined as any febrile illness for ≤ 14 days without evidence of localized infection. Scrub typhus cases were defined by an antibody titer of a ≥ fourfold increase in paired sera, a ≥ 1:160 in a single serum using indirect immunofluorescence assay, or a positive result of the immunochromatographic test. Multiple regression analysis identified predictors associated with scrub typhus to develop a prediction rule. Of 250 cases with known etiology of acute undifferentiated fever, influenza (28.0%), hepatitis A (25.2%), and scrub typhus (16.4%) were major causes. A prediction rule for identifying suspected cases of scrub typhus consisted of age ≥ 65 years (two points), recent fieldwork/outdoor activities (one point), onset of illness during an outbreak period (two points), myalgia (one point), and eschar (two points). The c statistic was 0.977 (95% confidence interval = 0.960–0.994). At a cutoff value ≥ 4, the sensitivity and specificity were 92.7% (79.0–98.1%) and 90.9% (86.0–94.3%), respectively. Scrub typhus, the third leading cause of acute undifferentiated fever in our region, can be identified early using the prediction rule. 相似文献
4.
This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. 相似文献
5.
6.
Yoo Min Han Su Jin Chung Seokha Yoo Jong In Yang Ji Min Choi Jooyoung Lee Joo Sung Kim 《World journal of gastroenterology : WJG》2022,28(8):853-867
BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD. 相似文献
7.
Rationale:Tarlov or perineurial cysts are nerve root lesions often found in the sacral region. Most perineural cysts (PCs) remain asymptomatic throughout a patient''s life. While their pathogenesis is still unclear, trauma resulting in hemorrhaging into subarachnoid space has been put forward as a possible cause of these cysts. Recently, we worked with a patient experiencing symptomatic PCs after spontaneous subarachnoid hemorrhage.Patient concerns:A 45-year-old man had a coil embolization procedure performed after being diagnosed with a subarachnoid hemorrhage from a ruptured anterior communicating artery. His symptoms were relieved after the procedure, but 7 days later he reported worsening pain in the left perineal area. The pain was intermittent at its onset and exacerbated by sitting, walking, and coughing.Diagnoses:Two weeks after the embolization procedure, a lumbar spine MRI revealed 2 PCs at the S1 and S2 level affecting the left S2 root with high signal intensity in T2 and T1 images, suggestive of bleeding within the cyst.Interventions:We operated using a posterior approach. Cyst fenestration was done after S1 laminectomy. We aspirated approximately 1 cc of old blood.Outcomes:His pain was relieved immediately after cyst removal and no neurologic deterioration occurred during the postoperative period.Lessons:Subarachnoid hemorrhage can be the source of the development of pain from asymptomatic PCs, making them symptomatic. Surgical extirpation is 1 treatment option for these symptomatic PCs. 相似文献
8.
Background
Many patients undergoing below knee amputations (BKA) return for subsequent unplanned operations, hospital readmission, or postoperative complications. This unplanned medical management negatively impacts both patient outcomes and our healthcare system. This study primarily investigates the risk factors for unplanned reoperation following BKA.Methods
Below knee amputations from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from the years 2012–2014 were identified by CPT code 27880 for amputation through the tibia and fibula. Our query identified 4631 BKA cases, including 30 day complications. Multivariate logistic regression modeling was performed on several patient demographic and disease factors to assess for independent predictors of unplanned reoperation. Secondary outcomes of unplanned and related readmissions (related to the procedure), major complications, minor complications, and mortality were also included in the analysis.Results
Of 4631 BKAs identified, 9.63% (446/4631) underwent unplanned reoperations and 8.75% (405/4631) had unplanned and related readmissions. Major complications were experienced by 12.8% (593/4631) and minor complications by 8.7% (401/4631). Thirty day mortality rate was 5.14% (238/4631). The most common procedures for unplanned operations were thigh amputations (128/446, 28.7%), debridement/secondary closure (114/446, 25.6%), and revision leg amputations (46/446, 10.32%). Factors associated with an increased risk of unplanned reoperation included patients transferred from another facility (Adjusted Odds Ratio [AOR]?=?1.28; p?=?.04), recent smokers (AOR?=?1.34; p?=?.02), bleeding disorder (AOR?=?1.30; p?=?.02), and preoperative ventilator use (AOR?=?2.38; p?=?.01).Conclusion
Patients that were ongoing/recent smokers, had diagnosed bleeding disorders, required preoperative ventilator use, or were transferred in from another facility were associated with the highest risks of reoperation following BKA. This patient population experiences high rates of reoperation, readmission, complication, and mortality. 相似文献9.
Leyi Wang Saraswathi Lanka Debbie Cassout Nohra E. Mateus‐Pinilla Ganwu Li William C. Wilson Dongwan Yoo Paul Shelton Richard L. Fredrickson 《Transboundary and Emerging Diseases》2019,66(5):1809-1820
First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year. 相似文献
10.