The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of ...surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported.
In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination.
On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling.
Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.
FIGO grade 3 endometrioid endometrial carcinoma (EEC) is a heterogenous group of tumors with variable molecular and clinicopathologic characteristics but is treated clinically as a single entity. ...There is a need for additional objective markers to help guide management. The aim of this study was to evaluate a cohort of FIGO grade 3 EEC to validate the prognostic impact of molecular classification using POLE mutation (POLE-mut) analysis and immunohistochemistry for p53 and mismatch repair proteins. A secondary aim was to assess for any morphologic or immunophenotypic correlates among the molecular groups. Ninety-five cases of FIGO grade 3 EEC who underwent a hysterectomy at our institution were identified. Ten tumors (11%) harbored POLE-mut, 35 tumors (37%) showed mismatch repair deficiency, 18 tumors (19%) showed aberrant p53 staining (p53-ab), and 26 cases (27%) lacked all of these findings and were classified as no specific molecular profile. Six separate cases harbored >1 abnormality (multiple classifier), 5 of which had POLE-mut. The POLE-mut group and multiple classifier group showed excellent clinical outcomes, the p53-ab group showed the worst clinical outcomes and the 2 remaining groups showed intermediate prognosis. While the POLE-mut tumors showed a statistically significant enrichment for morphologic features including serous-like atypia and lymphocytic infiltrates, these findings were seen across all 4 molecular groups. There was no correlation between molecular grouping and tumor immunophenotypic findings, but overall 18% and 24% of tumors were completely negative for PAX-8 and estrogen receptor, respectively. Five CTNNB1 mutations were identified, 3 of which occurred in the context of a POLE-mut (including 1 multiple classifier case with MLH1/PMS2 loss). Thus our study corroborates the prognostic impact of molecular classification of high-grade endometrioid carcinoma of the uterus, achieved by readily available immunohistochemical stains in addition to POLE-mut analysis.
This study was aimed to examine the relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus (PDA) shunt and the risk of developing bronchopulmonary dysplasia ...(BPD) or death before 36 weeks (BPD/death).
Infants <28 weeks' gestation who survived ≥7 days (
= 423) had echocardiograms performed on day 7 and at planned intervals.
In multivariable regression models, BPD/death did not appear to be increased until infants had been exposed to a moderate-to-large PDA for at least 7-13 days: OR (95%CI) (referent = closed or small PDA): moderate-to-large PDA exposure for <7 days: 0.38 (range, 0.10-1.46); for 7 to 13 days = 2.12 (range, 1.04-4.32); for ≥14 days = 3.86 (range, 2.15-6.96). Once the threshold of 7 to 13 days had been reached, additional exposure (≥14 days) did not significantly add to the increased incidence of BPD/death: (referent exposure = 7-13 days) exposure for 14 to 27 days = 1.34 (range, 0.52-3.45); for 28 to 48 days = 2.34 (range, 0.88-6.19); for ≥49 days = 1.80 (range. 0.59-5.47). A similar relationship was found for the outcome of BPD-alone.
Infants < 28 weeks' gestation required at least 7 to 13 days of exposure to a moderate-to-large PDA before a significant increase in the incidence of BPD/death was apparent. Once this threshold was reached additional exposure to a moderate-to-large PDA did not significantly add to the increased incidence of BPD/death.
Summary Background Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive ...lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects. Methods This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. Findings Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR–0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (−0·03 T/S units, −0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02–0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (–2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (–3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72–1·20, p=0·57). Interpretation Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding. Funding US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.
Adolescents and young adults are a diverse patient population with unique healthcare needs including sensitive and confidential services. Many clinics serving this population began offering ...telemedicine during the Covid-19 pandemic. Little is known regarding patient and parent experiences accessing these services via telemedicine.
To assess for trends and disparities in telemedicine utilization in the first year of the pandemic, we used the electronic health record to obtain patient demographic data from an adolescent and young adult medicine clinic in a large urban academic institution. Characteristics of patients who had accessed telemedicine were compared to those who were only seen in person. Mean age was compared using t-test, while other demographic variables were compared using chi-squared test or Fisher's exact test. We performed qualitative semi-structured interviews with patients and parents of patients in order to characterize their experiences and preferences related to accessing adolescent medicine services via telemedicine compared to in-person care.
Patients that identified as female, white race, Hispanic/Latinx ethnicity were more likely to have utilized telemedicine. Telemedicine use was also more prevalent among patients who were privately insured and who live farther from the clinic. Although interview participants acknowledged the convenience of telemedicine and its ability to improve access to care for people with geographic or transportation barriers, many expressed preferences for in-person visits. This was based on desire for face-to-face interactions with their providers, and perception of decreased patient and parent engagement in telemedicine visits compared to in-person visits. Participants also expressed concern that telemedicine does not afford as much confidentiality for patients.
More work is needed to address patient and parent preferences for telemedicine as an adjunct modality to in-person adolescent and young adult medicine services. Optimizing quality and access to telemedicine for this patient population can improve overall healthcare for this patient population.
To analyze the clinical presentation and optical coherence tomography (OCT) findings in indirect traumatic optic neuropathy (ITON) in veterans with chronic mild traumatic brain injury (mTBI).
This ...retrospective study is the first to describe the OCT pattern of subclinical to mild ITON in veterans with chronic mTBI. The thicknesses of the macular ganglion cell layer (mGCL), peripapillary retinal nerve fiber layer (pRNFL), and subfoveal choroidal layer were analyzed in young veterans who had mTBI of >6 months' duration and either blunt head injury or improvised explosive device (IED) concussions.
Three major OCT findings were demonstrated: (1) temporal pRNFL thinning was associated with subclinical TON in the eyes of chronic mTBI patients compared with controls; within mTBI subjects, nasal mGCL thinning at the 3-mm modified Early Treatment Diabetic Retinopathy Study circle diameter distance from the fovea correlated with the corresponding temporal retinal nerve fiber layer thinning; (2) inner (1 mm) superior thinning was greater than that of the temporal mGCL in blunt head injury and could potentially distinguish it from IED concussive head trauma; and (3) subfoveal choroidal thinning was significantly worse in eyes of mTBI patients compared with those of controls.
These OCT findings may contribute to the understanding of the spectrum of visual injuries resulting from head trauma.
A persistent left-to-right shunt through a patent ductus arteriosus (PDA) increases the rate of pulmonary hydrostatic fluid filtration, impairs pulmonary mechanics, and prolongs the need for ...respiratory support. Infants with a moderate/large PDA shunt that persists for more than 7-14 days are at increased risk for developing bronchopulmonary dysplasia (BPD) if they also require invasive ventilation for more than 10 days. In contrast, infants who require invasive ventilation for less than 10 days have similar rates of BPD no matter how long they are exposed to a moderate/large PDA shunt. Although pharmacologic PDA closure decreases the risk of abnormal early alveolar development in preterm baboons that are ventilated for 2 weeks, the findings from recent randomized controlled trials, as well as a quality improvement project, suggest that routine early targeted pharmacologic treatments, as currently employed, do not appear to alter the incidence of BPD in human infants.
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