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Objectives
Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.Methods
A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.Results
The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.Conclusions
Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells. 相似文献Background
Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.Objectives
The purpose of this study is to provide an update on the authors’ Australian clinical program and discuss lessons learned since performing the world’s first series of distantly procured DCD heart transplants.Methods
The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent’s Hospital.Results
Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function.Conclusions
DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors. 相似文献Context
Do-not-resuscitate (DNR) orders are common among children receiving palliative care, who may nevertheless benefit from surgery and other procedures. Although anesthesia, surgery, and pediatric guidelines recommend systematic reconsideration of DNR orders in the perioperative period, data regarding how clinicians evaluate and manage DNR orders in the perioperative period are limited.Objectives
To evaluate perioperative management of DNR orders at a tertiary care children's hospital.Methods
We reviewed electronic medical records for all children with DNR orders in place within 30 days of surgery at a tertiary care pediatric hospital from February 1, 2016, to August 1, 2017. Using standardized case report forms, we abstracted the following from physician notes: 1) patient/family wishes with respect to the DNR, 2) whether preoperative DNR orders were continued, modified, or suspended during the perioperative period, and 3) whether life-threatening events occurred in the perioperative period. Based on data from these reports, we created a process flow diagram regarding DNR order decision-making in the perioperative period.Results
Twenty-three patients aged six days to 17 years had a DNR order in place within 30 days of 29 procedures. No documented systematic reconsideration took place for 41% of procedures. DNR orders were modified for two (7%) procedures and suspended for 15 (51%). Three children (13%) suffered life-threatening events. We identified four time points in the perioperative period where systematic reconsideration should be documented in the medical record, and identified recommended personnel involved and important discussion points at each time point.Conclusion
Opportunities exist to improve how DNR orders are managed during the perioperative period. 相似文献Background
Critical hand ischemia owing to below-the-elbow atherosclerotic occlusive disease is relatively uncommon. The aim of this study was to examine the outcomes in patients presenting with critical ischemia owing to below-the-elbow arterial atherosclerotic disease who underwent nonoperative and operative management.Methods
A database of patients undergoing operative and nonoperative management for symptomatic below-the-elbow atherosclerotic disease between 2006 and 2016 was retrospectively queried. Patients with critical ischemia (tissue loss and rest pain) were identified. Three management groups were identified: no revascularization (None), endovascular revascularization (Endo), and open revascularization by bypass (Bypass). Patients with acute embolism, active vasculitis, end-stage renal disease, ipsilateral dialysis access complications of steal, and ipsilateral trauma were excluded.Results
One hundred eight patients (56% male; average age, 59 years) presented with symptomatic below-the-elbow disease: 93% presented with digital ulceration and the remainder with rest pain. Eighty-one percent had diabetes and 41% had chronic renal insufficiency (not on dialysis). All underwent catheter-based angiography. Fifty-three patients (49%) had no intervention and subsequently were committed to wound care; 26 of these required no further intervention, 10 had an interval palmar sympathectomy, and 17 underwent either a phalanx or digital amputation. Thirty-four patients (31%) underwent an endovascular intervention with a median of 1.5 vessels (ulnar, radial, or interosseous arteries) intervened on. Technical success was achieved in 29 patients (85%). Of the five technical failures, two went on to bypass, one had a focal endarterectomy and patch angioplasty, and one was treated conservatively. Ten patients in the Endo group required either a phalanx or digital amputation. Twenty-one patients (19%) underwent a saphenous vein bypass (reversed or nonreserved) to the radial in 12 and the ulnar in 11 limbs. In follow-up, 11 patients underwent open or endovascular intervention to maintain patency of the bypass. There were nine phalanx or digital amputations in the Bypass group. No below-the-elbow or above-the-elbow amputations were performed within 30 days. The wound healing rate without amputation was 78% (85 of 108). The predictors of wound healing were technical success of the revascularization, intact palmar arch and presence of digital run-off. The presence of an incomplete arch and poor digital run-off were associated with a phalanx or digital amputation.Conclusions
Upper extremity interventions for critical ischemia are associated with a high rate of success. Major amputations are rare and the many can be treated nonoperatively. In appropriately selected patients, both endovascular and open interventions have a high rate of success. 相似文献Methods: We analyzed data from the Participatory Research in Ottawa: Understanding Drugs study, a cross-sectional, peer-administered survey of people who use drugs from 2012 to 2013. We linked responses to population-based health administrative databases and used multivariable Poisson regression to identify factors independently associated with self-reported HCV testing, self-reported positive HCV status, and database-determined engagement in HCV treatment. Results: Among 663 participants, 562 (84.8%) reported testing for HCV and 258 (45.9%) reported HCV-positive status. In multivariable analysis, HCV-positive status was associated with female gender (RR 1.27; 95%CI 1.04 to 1.55), advancing age (RR 1.03/year; 95%CI 1.02 to 1.04), receiving disability payments (RR 1.42; 95%CI 1.06 to 1.91), injecting drugs (RR 5.11; 95%CI 2.64 to 9.91), ever injecting with a used needle (RR 1.30; 95%CI 1.12 to 1.52), and ever having taken methadone (RR 1.26; 95%CI 1.05 to 1.52). Of HCV positive participants, 196 (76%) were engaged in primary care but only 23 (8.9%) had received HCV therapy. Conclusions/Importance: Although HCV testing and positive status rates are high among PWID in our study, few have received HCV treatment. Innovative initiatives to increase access to HCV treatment for PWID are urgently needed. 相似文献
CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH. 相似文献
Method: Minimum Data Set 3.0 records of 8,300 residents of Department of Veterans Affairs Community Living Centers were used to determine statistically unadjusted and adjusted cross-sectional associations between residents' mental health diagnoses and their pain and pain treatments.
Results: Residents diagnosed with dementia and serious mental illness (SMI) were less likely, and those diagnosed with depressive disorder, post-traumatic stress disorder (PTSD), and substance use disorder (SUD) were more likely, to report recent, severe, and debilitating pain. Among residents affirming recent pain, those with dementia or SMI diagnoses were twice as likely to obtain no treatment for their pain and significantly less likely to receive as-needed pain medication and non-pharmacological pain treatments than were other residents. Those with either depressive disorder or PTSD were more likely, and those with SUD less likely, to obtain scheduled pain medication. In general, these associations remained even after statistically adjusting for residents' demographic characteristics, other mental health disorder diagnoses, and functioning.
Conclusion: Long-term care residents with mental health disorders experience disparities in pain and pain treatment that are not well-explained by their functioning deficits. They may benefit from more frequent, thorough pain assessments and from more varied and closely tailored pain treatment approaches. 相似文献