To identify predictors of ocular surface squamous neoplasm (OSSN) recurrence after operative resection.
Retrospective case series.
Three hundred eighty-nine consecutive patients who underwent ...excisional biopsy for OSSN lesions at the Bascom Palmer Eye Institute from January 1, 2001, to September 20, 2010.
Review of pathology records and patient charts.
Identification of factors predictive of OSSN recurrence.
Of 389 excised OSSN lesions, 44 recurred during follow-up. The 1-year recurrence rate was 10% and the 5-year recurrence rate was 21%, with a mean time to recurrence in those with a recurrence of 2.5 years (standard deviation, 3.4). Using the American Joint Committee on Cancer (AJCC) clinical staging system, T3 and T2 lesions portended a higher risk of recurrence compared with T1 (T2/T1 hazard ratio HR, 2.05 P = 0.04; T3/T1 HR, 2.31 P = 0.07). In addition, a location characteristic that increased the risk of tumor recurrence was tarsal involvement (AJCC T3 stage lesion; HR, 4.12; P = 0.007). Nasal location was associated with a decreased risk of tumor recurrence (HR, 0.41; P = 0.008). Pathologic characteristics significantly associated with tumor recurrence were the presence of positive margins (HR, 2.73; P = 0.008) and higher grade lesions (carcinoma in situ and squamous cell carcinoma versus dysplasia; HR, 2.55; P = 0.02). Treatment with adjuvant cryotherapy significantly decreased the risk of tumor recurrence (HR, 0.51; P = 0.03). In those patients with positive margins, the use of postoperative topical interferon therapy lowered the recurrence rate to a level similar to that of patients with negative margins.
Certain patient and tumor factors are associated with a higher risk of OSSN recurrence after operative excision, such as tarsal tumor location and positive surgical margins. Postoperative adjuvant therapy should be considered in patients with high-risk OSSN characteristics.
Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this ...dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay.
A large multicenter study in a broad heart transplant surveillance population demonstrates the ability of standardized donor‐ derived cell‐free DNA testing to identify both T cell–mediated and antibody‐mediated acute rejection with a high negative predictive value.
Summary Background Central sleep apnoea is a serious breathing disorder associated with poor outcomes. The remedé system (Respicardia Inc, Minnetonka, MN, USA) is an implantable device which ...transvenously stimulates a nerve causing diaphragmatic contraction similar to normal breathing. We evaluated the safety and effectiveness of unilateral neurostimulation in patients with central sleep apnoea. Methods We recruited patients from 31 hospital-based centres in Germany, Poland, and the USA in this prospective, multicentre, randomised trial. Participants had to have been medically stable for at least 30 days and have received appropriate guideline recommended therapy, be aged at least 18 years, be expected to tolerate study procedures, and willing and able to comply with study requirements. Eligible patients with an apnoea-hypopnoea index (AHI) of at least 20 events per h, tested by a polysomnography, underwent device implantation and were randomly assigned (1:1) by a computer-generated method stratified by site to either stimulation (treatment) or no stimulation (control) for 6 months. The primary effectiveness endpoint in the intention-to-treat population was the comparison of the proportions of patients in the treatment versus control groups achieving a 50% or greater AHI reduction from baseline to 6 months, measured by a full-night polysomnography assessed by masked investigators in a core laboratory. The primary safety endpoint of 12-month freedom from serious adverse events related to the procedure, system, or therapy was evaluated in all patients. This trial is active, but not recruiting, and is registered with ClinicalTrials.gov ( NCT01816776 ). Findings Between April 17, 2013, and May 28, 2015, we randomly assigned 151 eligible patients to the treatment (n=73) or control (n=78) groups. In the analysis of the intention-to-treat population, significantly more patients in the treatment group (35 51% of 68) had an AHI reduction from baseline of 50% or greater at 6 months than had those in the control group (eight 11% of 73; difference between groups 41%, 95% CI 25–54, p<0·0001). 138 (91%) of 151 patients had no serious-related adverse events at 12 months. Seven (9%) cases of related-serious adverse events occurred in the control group and six (8%) cases were reported in the treatment group. Seven patients died (unrelated to implant, system, or therapy), four deaths (two in treatment group and two in control group) during the 6-month randomisation period when neurostimulation was delivered to only the treatment group and was off in the control group, and three deaths between 6 months and 12 months of follow-up when all patients received neurostimulation. 27 (37%) of 73 patients in the treatment group reported non-serious therapy-related discomfort that was resolved with simple system reprogramming in 26 (36%) patients, but was unresolved in one (1%) patient. Interpretation Transvenous neurostimulation significantly reduced the severity of central sleep apnoea, including improvements in sleep metrics, and was well tolerated. The clinically meaningful effects of the therapy are supported by the concordant improvements in oxygenation and quality of life, making transvenous neurostimulation a promising therapeutic approach for central sleep apnoea. Funding Respicardia Inc.
Swiss-cheese atrial septal defect (ASD) is a malformation characterized by multi-fenestrated interatrial defects. Here, we describe a vignette of a 23-year-old man with Swiss-Cheese ASD characterized ...by two defects with areas of 0.74 cm
and 0.44 cm
, complicated with an atrial septal aneurysm successfully repaired with a cribriform amplatzer septal occluder (ASO) via the percutaneous transcatheter approach. This case emphasizes the importance of attaining a clear view of three-dimensional structures for proper device selection and deployment in repair as additional structural defects such as concomitant aneurysms impose significant challenges.
To describe the clinical and histologic characteristics of ocular surface squamous neoplasia (OSSN) lesions and provide clinicopathologic correlation to determine clinical features that may indicate ...higher-grade lesions.
Retrospective case series.
A total of 612 consecutive OSSN lesions sent to the Bascom Palmer ocular pathology laboratory from January 1, 2001 to September 20, 2010.
Pathologic examination of lesions by a single experienced ocular pathologist (S.R.D.). Review of pathology records and patient charts.
Correlation of clinical factors and histology of higher-grade OSSN.
Over the studied period, 33% of submitted specimens were characterized as mild, moderate, or severe dysplasia; 52% were classified as carcinoma in situ; and 11% were graded as squamous cell carcinoma. Characteristics associated with higher-grade OSSN lesions included male gender, biopsy at Bascom Palmer Eye Institute, temporal and superior locations, lack of corneal involvement, papillomatous and nodular appearance, microscopic multifocality, and positive margins on biopsy.
Certain clinical factors are associated with higher-grade histologic lesions. These findings may help clinicians more accurately evaluate and anticipate the pathologic grade of conjunctival and corneal lesions suspected to be OSSN.
The purpose of this study was to determine the prevalence of ocular surface squamous neoplasia (OSSN) coexisting with pterygia in South Florida and to study the treatment and related outcomes.
...Noninterventional retrospective study.
A total of 2005 patients with surgically excised pterygia at the Bascom Palmer Eye Institute from 2000 to 2010.
Pathology reports of patients with pterygia were reviewed for evidence of OSSN. Patients were divided into the following groups: pterygium and no OSSN (group 1), clinically suspected OSSN with pterygium (group 2), and unexpected OSSN with pterygium found on histopathology (group 3). Clinical charts of patients in groups 2 and 3 were reviewed.
Period prevalence, treatment, and outcome.
In surgically excised pterygia, the prevalence of coexistent OSSN was 1.7% (n = 34), of which 41% (n = 14) were clinically suspected preoperatively (group 2) and 59% (n = 20) were unexpectedly found on histopathology (group 3). Clinically suspected OSSN with pterygia was generally treated with wide surgical margins and cryotherapy, whereas unexpected OSSN with pterygia was treated with simple excision, followed by adjuvant interferon treatment in 30% (n = 6). After a mean follow-up of 2 years, there were no recurrences in the suspected OSSN group and 2 recurrences in the unexpected OSSN group. The recurrence rate in the latter group was 11% at 1 year and 24% at 2 years.
Ocular surface squamous neoplasia is uncommonly found to coexist with pterygium. The prognosis in suspected OSSN cases is excellent, with no recurrences noted despite positive margins in 50% of cases. The recurrence rates of unexpected OSSN mirrors that of OSSN not associated with pterygium, and thus vigilance for recurrence is important.
This article presents a novel coupling of numerical techniques that enable three-dimensional convection-driven microstructure simulations to be conducted on practical time scales appropriate for ...small-size components or experiments. On the microstructure side, the cellular automata method is efficient for relatively large-scale simulations, while the lattice Boltzmann method provides one of the fastest transient computational fluid dynamics solvers. Both of these methods have been parallelized and coupled in a single code, allowing resolution of large-scale convection-driven solidification problems. The numerical model is validated against benchmark cases, extended to capture solute plumes in directional solidification and finally used to model alloy solidification of an entire differentially heated cavity capturing both microstructural and meso-/macroscale phenomena.
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