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Believing and blaming of alleged victims of child sexual abuse (CSA) was measured in a community sample of 202 adults. Subjects completed a questionnaire consisting of vignettes in which 11-year-old girls reported being sexually abused. A majority of respondents viewed the girl's report of sexual abuse as truthful; however, alleged victim retractions significantly reduced the credibility ratings for those reports. The effect of perpetrator socioeconomic status (SES) did not reach significance on either alleged victim believing or blaming. Females were significantly more likely than males to believe the girl's report of abuse, and more likely to believe children's reports in general. Females were significantly less likely than males to blame the girl for the occurrence of the abuse. Gender differences on believing and blaming remained significant when effects of respondent age and education were removed as covariates. Estimates of the prevalence of CSA varied widely, with no significant gender difference. Over half of the respondents believed that alleged victims aged five years or younger should be allowed to testify in court in CSA cases. [ABSTRACT FROM AUTHOR]

Objective: Despite theorizing that posttraumatic stress disorder (PTSD) symptomatology may be exacerbated during the military-to-civilian transition, little research has delved into the trajectory of trauma-related symptomatology or the impact of diverse factors on timing of PTSD onset. To understand risk and protective factors for PTSD during the transition into civilian life, this study examined demographic, experiential, and psychosocial characteristics that may explain variation in PTSD symptoms and timing of onset., Method: A nationwide sample representing 48,965 U.S. veterans separating from military service in fall 2016 responded to six Web-based surveys over 3 years. Assessments included PTSD symptoms, stress, warfare exposures, military sexual trauma, moral injury events, resilience, and social support. Multivariable models estimated covariates of positive PTSD screen or symptoms., Results: Trauma exposure during military service was high at 59%. Probable PTSD was detected in 26% of the sample at baseline, with additional cases in each survey wave for an overall rate of 30%. Meeting criteria for probable PTSD covaried with current stress, female gender, and minority race/ethnicity; baseline psychological resilience and concurrent social support mitigated the risk. PTSD symptoms correlated positively with stress levels at current and previous time points. Social support was protective but only when contemporaneous with the PTSD symptoms., Conclusions: This study illustrates the need for ongoing social support for veterans coping with symptoms of PTSD, life stressors, and postmilitary trauma, suggesting a countervailing influence of psychological resilience and contemporaneous (but not historical) social support on symptom exacerbation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance., Summary of Background Data: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias., Methods: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores by respondent demographic was evaluated using regression analyses. Inter-rater reliability was assessed using the Cronbach's alpha., Results: 103 cardiothoracic surgeons completed the Checklist (trainee gender: male n=50, female n=53) and 112 completed the GRS (trainee gender: male n=56, female n=56). For the Checklist, male cardiothoracic surgeons who were in practice <10 years ( P = 0.036) and involved in training residents ( P = 0.049) were more likely to score male trainees higher than female trainees. The GRS demonstrated high inter-rater reliability across male and female trainees by years and scope of practice for the respondent (alpha >0.900) when compared to the Checklist assessment tool., Conclusions: Early career male surgeons may exhibit gender bias against women when evaluating trainee performance of coronary anastomoses. The GRS demonstrates higher interrater reliability and robustness against gender bias in the assessment of technical performance than the Checklist, and such scales should be emphasized in educational evaluations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

New antibiotics with unique biological targets are desperately needed to combat the growing number of resistant bacterial pathogens. ATP synthase, a critical protein found in all life, has recently become a target of interest for antibiotic development due to the success of the anti-tuberculosis drug bedaquiline, and while many groups have worked on developing drugs to target bacterial ATP synthase, few have been successful at inhibiting Pseudomonas aeruginosa (PA) ATP synthase specifically. PA is one of the leading causes of resistant nosocomial infections across the world and is extremely challenging to treat due to its various antibiotic resistance mechanisms for most commonly used antibiotics. Herein, we detail the synthesis and evaluation of a series of C1/C2 quinoline analogues for their ability to inhibit PA ATP synthase and act as antibiotics against wild-type PA. From this survey, we found six compounds capable of inhibiting PA ATP synthase in vitro showing that bulky/hydrophobic C1/C2 substitutions are preferred. The strongest inhibitor showed an IC 50 of 10 μg/mL and decreased activity of PA ATP synthase to 24% relative to the control. While none of the compounds were able to inhibit wild-type PA in cell culture, two showed improved inhibition of PA growth when permeability of the outer membrane was increased or efflux was knocked out, thus demonstrating that these compounds could be further developed into efficacious antibiotics., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Purpose: Neoadjuvant chemotherapy prior to definitive surgery has been utilized widely for locally advanced oral squamous cell carcinoma (OSCC). We evaluated neoadjuvant erlotinib with platinum-docetaxel vs. placebo with platinum-docetaxel in stage III-IVB OSCC patients., Experimental Design: Patients with newly diagnosed stage III, IVA, IVB (AJCC 7th) OSCC amenable to surgical resection were included. Patients were randomized to receive up to 3 cycles of chemotherapy with concurrent erlotinib or placebo, followed by surgery. The primary endpoint was major pathologic response (MPR) rate, secondary endpoints included safety, overall (OS) and progression-free survival (PFS)., Results: Fifty-two patients received at least one cycle of treatment and 47 were evaluable with surgical resection. MPR rate was not different between erlotinib (30%, 7/23) and placebo arms (41.7%, 10/24) (p=0.55). At median follow up of 26.5 months, there was no difference on OS or PFS between groups. Patients who received erlotinib with chemotherapy and achieved MPR (n=7) had no recurrence. The treatment-related adverse event rates were not different between the two groups (96% vs. 96%). However, rash, mostly low grade, was more common in the erlotinib arm (79% vs. 50%). Transcriptomic analysis in the pre-treatment samples indicated that genes in protein glycosylation and Wnt signaling pathways were associated with benefit in those treated with erlotinib plus chemotherapy., Conclusions: The addition of erlotinib to platinum-taxane chemotherapy was well-tolerated but did not induce higher rates of MPR or PFS or OS survival benefit. Patients who received chemotherapy with erlotinib and achieved major pathological responses had excellent clinical outcome.

Background: Salivary duct carcinoma (SDC) and adenocarcinoma, not otherwise specified (adeno-NOS), are rare salivary gland cancers. Data on the efficacy of systemic therapy for these diseases are limited., Methods: Data were retrospectively collected from patients seen at The University of Texas MD Anderson Cancer Center during 1990 to 2020. Objective response rate (ORR) was assessed per RECIST v1.1. Recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were assessed by Kaplan-Meier method. Cox regression model was performed to identify predictors of survival., Results: The analysis included 200 patients (110 with SDC and 90 with adeno-NOS); 77% had androgen-receptor-positive tumors and 47% had HER2-positive (2+-3+) tumors. Most patients without metastasis at diagnosis underwent surgery (98%) and postoperative radiotherapy (87%). Recurrence rate was 55%, and the median RFS was 2 years. Nodal involvement and positive surgical margins were associated with recurrence (P < .005). Among patients with stage IVA-B disease, addition of systemic therapy to local therapy increased OS (P = .049). The most-used palliative-systemic-therapy regimen was platinum doublet ± trastuzumab. For first-line therapy, the ORR and median PFS were 33% and 5.76 months, respectively, and for second-line therapy the ORR and median PFS were 25% and 5.3 months, respectively. ORR and PFS were higher with HER2-targeting agents. Median OS was 5 years overall and 2 years for metastatic disease. Older age and higher stage were associated with worse OS., Conclusion: Adding systemic therapy to local therapy may improve outcomes of patients with locoregionally advanced SDC or adeno-NOS. Except for HER2-targeted therapy, response to palliative systemic therapy is limited. These findings may be used as a benchmark for future drug development., (© 2021 American Cancer Society.)

Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence., Patients and Methods: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response., Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR ( n = 11) or MPR ( n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8 + T-cell cluster enriched in patients with pCR., Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment., (©2021 American Association for Cancer Research.)

Background/aims: To identify prognostic factors for local recurrence, distant metastasis and disease-specific survival (DSS) for lacrimal gland carcinoma., Methods: All consecutive patients with lacrimal gland carcinoma treated from January 1998 through December 2018 were included. Log-rank tests and univariate Cox proportional hazards regression models were used to study risk factors and survival., Results: Overall, 55 patients were included in this study, and 5 patients were excluded from the survival analysis. Median age was 46 years (range: 10-76). 43 patients (78%) had adenoid cystic carcinoma (ACC). 31 patients (56%) had T2 disease at presentation. 28 patients (51%) underwent orbital exenteration with or without adjuvant radiotherapy or chemoradiation, 26 (47%) underwent eye-sparing surgery with or without adjuvant radiotherapy or chemoradiation, and 1 received palliative chemoradiation. 11 patients (22%) experienced local recurrence; 14 (29%) experienced distant metastasis. Five- and 10-year local-recurrence-free survival rates were 0.71 (95% CI 0.58 to 0.88), and 5- and 10-year distant-metastasis-free survival rates were 0.67 (95% CI 0.53 to 0.85) and 0.49 (95% CI 0.30 to 0.81), respectively. There was no significant difference in risks of local recurrence, distant metastasis or DSS between ACC patients who had orbital exenteration and those who had eye-sparing surgery. Perineural invasion was negatively associated with local-recurrence-free survival (p=0.02). Among patients with ACC, basaloid/solid histologic type was associated with significantly worse DSS than non-basaloid/solid histologic type (p<0.01)., Conclusions: For lacrimal gland carcinoma, orbital exenteration with adjuvant therapy and eye-sparing surgery with adjuvant therapy are associated with similar recurrence outcomes. Eye-sparing surgery is associated with better DSS. Perineural invasion is a risk factor for local recurrence. ACC with basaloid/solid subtype correlates with worse DSS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Information regarding risk of metastasis and disease-related death (DD) from conjunctival squamous cell carcinoma (SCC) is relatively scarce. We explored prognostic factors for orbital exenteration, local recurrence, nodal metastasis, and DD in patients with conjunctival SCC., Design: Retrospective cross-sectional study., Methods: All consecutive patients with conjunctival SCC treated by the senior author at MD Anderson Cancer Center during1999-2018 were included. Survival curves were estimated using the Kaplan-Meier method, and survival differences were assessed using 2-sided log-rank tests., Results: The study included 44 patients (24 men, 20 women); median age was 64 years (range, 40-90). T categories at presentation were as follows: Tis, 20 patients; T2, 8; T3, 9; and T4, 7. Eighteen patients (41%) had tumors exclusively in the bulbar conjunctiva; 26(59%) had nonbulbar conjunctival involvement. The median follow-up time was 29.2 months (95% CI: 21.8-44.3). Orbital exenteration was performed in 10 cases (23%) and was associated with T3 or more advanced disease at presentation (p < 0.001). Seven patients developed local recurrence during follow up. History of organ transplant correlated with local recurrence and orbital exenteration (p < 0.01). Nodal metastasis was present in 1 patient at presentation and occurred in 3 patients during follow up, for an overall nodal metastasis rate of 9% (4/44). By end of follow up, 2 patients had died of disease, 4 had died of other causes, and 38 were alive with no evidence of disease. The results suggest that both orbital exenteration and nodal metastasis are independent variables associated with DD., Conclusions: In patients with conjunctival SCC, orbital exenteration and nodal metastasis are associated with DD and organ transplantation is associated with orbital exenteration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations., Methods: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells., Results: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes., Conclusion: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction., (© 2021 Wiley Periodicals LLC.)

Background: We previously demonstrated associations between exercise during pancreatic cancer treatment and quality of life and physical fitness prior to pancreatectomy. In this study, we quantified exercise among survivors following pancreatic tumor resection and characterized concordance with established guidelines., Methods: We quantified exercise frequency, duration, and intensity among survivors who underwent pancreatectomy for adenocarcinoma or a neuroendocrine tumor at our center from 2000 to 2017 and compared them with American College of Sports Medicine Guidelines for Cancer Survivors. Additional surveys measured motivation to exercise, barrier self-efficacy, quality of life, and fatigue. Multivariable models were constructed to evaluate associations between clinicodemographic and psychosocial variables and guideline concordance, and between guideline concordance and quality of life and fatigue., Results: Of 504 eligible survivors, 262 (52%) returned surveys. Only 62 participants (24%) reported meeting both aerobic and strengthening guidelines; 103 (39%) reported meeting neither. Adjusted analyses demonstrated that higher autonomous motivation was associated with higher aerobic and strengthening guideline concordance (both p < 0.01). Higher barrier self-efficacy and older age were associated with higher aerobic guideline concordance (p < 0.01). We identified no significant associations between guideline concordance and tumor type, time since surgery, or recent cancer therapy (all p > 0.05). We found favorable associations between aerobic guideline concordance and both quality of life and fatigue (both p < 0.001)., Conclusions: Less than one-quarter of participants exercised sufficiently to meet national exercise guidelines following pancreatectomy. To maximize exercise and related benefits, interventions should help survivors increase intrinsic motivation and overcome barriers to exercise.

Purpose: Patient travel time can cause treatment delays when providers and families decide to seek proton therapy. We examined whether travel distance or referral pattern (domestic versus international) affects time to radiation therapy and subsequent disease outcomes in patients with medulloblastoma at a large academic proton center., Patients and Methods: Children with medulloblastoma treated at MD Anderson (MDA) with a protocol of proton beam therapy (PBT) between January 4, 2007, and June 25, 2014, were included in the analysis. The Wilcoxon rank-sum test was used to study the association between time to start of radiation and distance. Classification- and regression-tree analyses were used to explore binary thresholds for continuous covariates (ie, distance). Failure-free survival was defined as the time interval between end of radiation and failure or death., Results: 96 patients were included in the analysis: 17 were international (18%); 19 (20%) were from Houston, Texas; 21 were from other cities inside Texas (21%); and 39 (41%) were from other US states. The median time from surgery to start of radiation was not significantly different for international patients (median = 1.45 months) compared with US patients (median = 1.15 months; P  = .13). However, time from surgery to start of radiation was significantly longer for patients residing > 1716 km (> 1066 miles) from MDA (median = 1.31 months) than for patients residing ≤ 1716 km (≤ 1066 miles) from MDA (median = 1.05 months; P  = .01). This 1- to 2-week delay (median = 7.8 days) did not affect failure-free survival (hazard ratio = 1.34; P  = .43)., Conclusion: We found that short delays in proton access can exist for patients traveling long distances to proton centers. However, in this study, treatment delays did not affect outcomes. This highlights the appropriateness of PBT in the face of travel coordination. Investment by proton centers in a rigorous intake process is justified to offer timely access to curative PBT., Competing Interests: Conflicts of Interest: Steven J. Frank, MD, is an Associate Editor of the International Journal of Particle Therapy. Dr Frank discloses leadership and ownership interests in C4 Imaging and National Comprehensive Cancer Network Stock; honoraria from Boston Scientific, Hitachi, and Varian Medical Systems; research funding from Elekta, Hitachi, and Eli Lilly; a consulting or advisory role with Hitachi, Breakthrough Chronic Care, Varian Medical Systems; and patents developed at the University of Texas MD Anderson Cancer Center, which have been licensed to C4 Imaging. Dr Frank also discloses travel, accommodations, and expenses provided by the National Comprehensive Cancer Network and Boston Scientific. The authors have no other conflicts to disclose., (©Copyright 2020 The Author(s).)

Importance: The opioid epidemic has reignited interest in opioid-sparing strategies in managing pain. However, few studies have focused on opioid use during perioperative care in patients undergoing head and neck surgery with free flap reconstruction., Objectives: To examine the association between multimodal analgesia (MMA) administration and perioperative opioid requirements in patients undergoing head and neck surgery with free flap reconstruction and to investigate whether MMA alters the duration of stay in the postanesthesia care unit (PACU)., Design, Setting, and Participants: In this retrospective case-control study, data were collected between April 1, 2016, and December 31, 2017. The study was conducted at a single cancer center in the United States. Participants were 357 patients 18 years or older scheduled for head and neck surgery with free flap reconstruction., Exposures: Patients in the treatment group received oral celecoxib, gabapentin, and/or tramadol hydrochloride before surgery. Control group patients did not receive any of these medications., Main Outcomes and Measures: The amount of opioid administered in the operating room and in the PACU was converted to morphine equivalent daily dose (MEDD) for comparison between the 2 groups. The duration of stay in the PACU was based on the start time and end time of PACU care recorded by nurses in the PACU., Results: In total, 149 patients (mean [SD] age, 60.3 [13.7] years; 104 [69.8%] men) were included in the treatment group, and 208 patients (mean [SD] age, 64.2 [13.6] years; 146 [70.2%] men) were included in the control group. The mean (SD) MEDD of opioid given during surgery was 51.7 (19.8) in the treatment group and 67.9 (24.7) in the control group, for a difference in the means (treatment vs control) of -16.17 (95% CI, -20.81 to -11.52). In the PACU, the mean (SD) MEDD of opioid given was 11.7 (13.3) in the treatment group and 14.9 (15.7) in the control group, for a difference in the means (treatment vs control) of -3.22 (95% CI, -6.40 to -0.03). The MMA treatment remained largely associated with reduced amount of opioid given during surgery, in the PACU, and both combined after controlling for other important factors., Conclusions and Relevance: This case-control study found that the patients who received MMA before head and neck surgery with free flap reconstruction required less opioid medication. The treatment group also had shorter duration of stay in the PACU compared with the control group.

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8 + tumor-infiltrating lymphocyte (CD8 + TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8 + TIL density, safety, and efficacy in patients with OPC., Patients and Methods: Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8 + TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes., Results: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8 + TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment ( P = 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8 + TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8 + TIL change in patients with a MPR was seen ( P = 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence., Conclusions: Durvalumab + tremelimumab did not increase CD8 + TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC., (©2020 American Association for Cancer Research.)

Objectives: Off-label use of prazosin for posttraumatic stress disorder-related sleep disturbances (PTSD-SD) is widespread in Veterans Health Administration (VA) settings, but clinical trials have had mixed results. Trial criteria may exclude significant sub-groups, and therefore a 2018 study may not provide the final evidence of prazosin efficacy for PTSD-SD. This study analyzed correlates of prazosin use in Vietnam era (VNE) and Operations Enduring Freedom/Iraqi Freedom (OEF/OIF) cohorts to illustrate patterns of usage in this heterogeneous population., Method: Data extracted on patients with PTSD-SD prescribed prazosin in 2015 described the proportion of days covered (PDC) ≥ 80% and daily dose ≥ 6 mg (therapeutic target dose) over the next 12 months., Results: Both VNE (n = 41,365) and OEF/OIF (n = 62,984) cohorts had high rates of comorbidity (N = 104,349; 46% hypertension, 22% alcohol use disorder, 14% drug use disorder). Adherence and dosing were low: 19% of veterans achieved PDC ≥ 80%; 7% achieved ≥ 6mg/day (average 2.6 mg/day). In covariate-adjusted models, VNE veterans had better adherence, VNE women had lower rates of therapeutic dosing, and minority race/ethnicity was a strong risk factor for non-adherence. PDC correlated inversely with alcohol/drug disorders., Conclusion: Prazosin is prescribed for PTSD-SD to a diverse clinical population with multiple comorbidities and concurrent medications and is characterized by poor adherence and sub-optimal dosing. Future work should clarify the efficacy of prazosin for subgroups of veterans with PTSD-SD, notably women and racial/ethnic minorities., (Copyright © 1964–2020 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Background: Recently, the concept of persistent postsurgical opioid use has been described for patients undergoing cancer surgery. Our hypothesis was based on the premise that patients with oral tongue cancer require high dosages of opioids before, during, and after surgery, and thus a large percentage of patients might develop persistent postsurgical opioid use., Methods: After institutional review board approval, we conducted a retrospective study that included a cohort of patients with oral tongue cancers who underwent curative-intent surgery in our institution. Multivariable logistic regression models were fit to study the association of the characteristics of several patients with persistent (six months after surgery) and chronic (12 months after surgery) postoperative opioid use., Results: A total of 362 patients with oral tongue malignancies were included in the study. The rate of persistent use of opioids after surgery was 31%. Multivariate analysis showed that patients taking opioids before surgery and those receiving adjuvant therapy were 2.9 and 1.78 times more likely to use opioids six months after surgery. Fifteen percent of the patients were taking opioids 12 months after surgery. After adjusting for clinically relevant covariates, patients complaining of moderate tongue pain before surgery and those taking opioids preoperatively had at least three times higher risk of still using these analgesics one year after surgery., Conclusions: Patients with oral tongue cancers have a high risk of developing persistent and chronic postsurgical opioid use., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: No previous studies to date have validated the American Joint Committee on Cancer (AJCC) 8th edition of the TNM classification for orbital sarcoma., Objectives: To determine the prognostic performance of the most recent TNM classification for orbital sarcoma and to identify other prognostic factors for local recurrence, lymph node metastasis, distant metastasis, and death due to disease., Design, Setting, and Participants: This single-center retrospective cohort study included 73 consecutive patients treated for orbital sarcoma from March 1, 2003, through June 30, 2018. Data were analyzed from November 1 to December 31, 2018., Main Outcomes and Measures: T and N categories at presentation and disease-related outcomes, including local recurrence, lymph node metastasis, distant metastasis (DM), and death due to disease (DD)., Results: The 73 participants included 43 men (59%), and the median age was 21 (range, 0-77) years. The common histologic types were rhabdomyosarcoma (RMS) (35 [48%]), solitary fibrous tumor/hemangiopericytoma (10 [14%]), and Ewing sarcoma (8 [11%]). The most common TNM designations were T2 N0 M0 (26 [36%]) and T4 N0 M0 (24 [33%]). T category was associated with the risk of all disease-related outcomes, including local recurrence (hazard ratio [HR] for T2 vs T4, 0.22 [95% CI, 0.06-0.81]; HR for T3 vs T4, 0.59 [95% CI, 0.13-2.65]; P = .03), lymph node metastasis by the last follow-up (T1, 1 [14%]; T2, 0; T3, 0; T4, 12 [35%]; P = .001), DM (HR for T2 vs T4, 0.29 [95% CI, 0.08-1.07]; P = .04), and DD (HR of T2 vs T4, 0.16 [95% CI, 0.04-0.73]; HR of T3 vs T4, 0.30 [95% CI, 0.04-2.34]; P = .02). Higher risk of DM and higher risk of DD were associated with disease category of at least T3 (HR for DM, 3.24 [95% CI, 0.89-11.72; P = .06]; HR for DD, 6.32 [95% CI, 1.43-27.95; P = .005]), N1 disease (HR for DM, 13.33 [95% CI, 4.07-43.65; P < .001]; HR for DD, 7.07 [95% CI, 2.45-20.44; P < .001]), tumor size larger than 3 cm (HR for DM, 2.72 [95% CI, 0.92-8.05; P = .06]; HR for DD, 5.79 [95% CI, 1.85-18.14; P < .001]), and age of patient with RMS younger than 1 year or 10 years or older (HR for DM, 6.85 [95% CI, 0.83-56.53; P = .04]; HR for DD, 7.03 [95% CI, 0.85-57.83; P = .04]). Higher risk of local recurrence was associated with disease category of at least T3 (HR for3 cm, 0.27 [95% CI, 0.09-0.77]; P = .009). Higher risk of lymph node metastasis was associated with disease category of at least T3 (odds ratio [OR], 13.33 [95% CI, 1.77-602.30]; P = .004), alveolar RMS (OR, 9.98 [95% CI, 2.13-51.55]; P = .001), and age of patient with RMS younger than 1 year or 10 years or older (OR, 9.20 [95% CI, 1.01-458.29] P = .03)., Conclusions and Relevance: In patients with orbital sarcoma, T and N categories at presentation (defined by the AJCC 8th edition classification) correlate with metastasis and survival. These findings appear to support consideration of strict surveillance testing for regional nodal and systemic metastases in patients with orbital sarcoma with disease category of at least T3 and/or N1 disease.

Objectives: Prior reports have demonstrated a potential enhancement in overall response rate (ORR) to chemotherapy after exposure to immunotherapy. The goal of this study was to evaluate the ORR and survival to chemotherapy and/or targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients who progressed on immune checkpoint inhibitors (ICI)., Materials and Methods: We retrospectively collected clinical and pathologic data from patients with recurrent/metastatic HNSCC who progressed on ICI and subsequently received chemotherapy or targeted therapy. ORR was assessed by RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method., Results: A total of 43 patients met criteria for inclusion. The majority were male (91%) and former smokers (60%). Most patients received ICI as first-line (58.14%); the vast majority was platinum exposed (90.7%). The ORR to ICI was 21%. The ORR to systemic therapy before ICI was 47%, and the ORR after ICI failure was 42%. After progression on ICI, the median PFS and OS on the subsequent line of therapy were 4.2 and 8.4 months respectively., Conclusion: In our cohort of recurrent/metastatic HNSCC patients, the ORR and OS to systemic therapy after progression on ICI were higher than historical controls for second-line or beyond. Further investigations are warranted to better characterize optimal sequencing and combination strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Identifying tumor characteristics that correlate with metastasis and survival in patients with conjunctival melanoma can potentially lead to better outcomes through a better selection of patients for adjuvant treatments including potentially life-saving new melanoma therapy. The objective of this study was to validate the conjunctival melanoma staging criteria in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) and explore the prognostic importance of tumor thickness, histologic ulceration, and sentinel lymph node biopsy (SLNB) findings in patients with conjunctival melanoma. This is a case series of 88 consecutive patients with conjunctival melanoma. Clinicopathologic characteristics were analyzed. Associations between pathologic characteristics and outcomes were studied using Kaplan-Meier survival analysis. Local recurrence, lymph node metastasis, distant metastasis, and disease-specific survival (DSS) were the main outcome measures. The study included 56 women and 32 men; the median age was 62 years. At presentation, 41 patients had T1 disease, 23 had T2 disease, 23 had T3, and 1 had T4 disease. Sixty-six patients had invasive conjunctival melanoma (median thickness, 1.56 mm), 17 had conjunctival melanoma in situ, and in 5 patients, tumor thickness could not be determined. Overall, 22 patients had ulceration. In total, 31 patients underwent SLNB, and 4 had a positive sentinel lymph node (SLN). The median follow-up time was 46.6 months. Overall, 12 patients had nodal metastasis at presentation or during follow-up, 19 patients had distant metastasis at last follow-up, and 14 patients died of the disease. Tumor thickness and ulceration were associated with increased risks of nodal metastasis, distant metastasis, and death from the disease. Overall, greater clinical T category at presentation was associated with increased risks of distant metastasis and disease-related death; however, the risks of distant metastasis and disease-related death did not differ between T1 (bulbar) and T2 (nonbulbar) tumors or between T2c,d (caruncular) and T1-T2a,b (noncaruncular) tumors. In patients who underwent SLNB, a positive SLN was associated with worse distant metastasis free survival and DSS. Consideration should be given to adding ulceration and emphasizing tumor thickness as the main determinants of pathologic T category for conjunctival melanoma in future AJCC classifications. The significant association between a positive SLN and worse DSS highlights the importance of SLNB for prognosis in patients with conjunctival melanoma and selecting high-risk patients for adjuvant drug treatment.

Gold standard prognostic models for long-term outcome in patients with severe traumatic brain injury (TBI) use admission characteristics and are considered useful in some areas but not for clinical practice. In this study, we aimed to build prognostic models for 6-month Glasgow Outcome Score (GOS) in patients with severe TBI, combining baseline characteristics with physiological, treatment, and injury severity data collected during the first 24 h after injury. We used a training dataset of 472 TBI subjects and several data mining algorithms to predict the long-term neurological outcome. Performance of these algorithms was assessed in an independent (test) sample of 158 subjects. The least absolute shrinkage and selection operator (LASSO) led to the highest prediction accuracy (area under the receiving operating characteristic curve = 0.86) in the test set. The most important post-baseline predictor of GOS was the best motor Glasgow Coma Scale (GCS) recorded in the first day post-injury. The LASSO model containing the best motor GCS and baseline variables as predictors outperformed a model with baseline data only. TBI patient physiology of the first day-post-injury did not have a major contribution to patient prognosis six months after injury. In conclusion, 6-month GOS in patients with TBI can be predicted with good accuracy by the end of the first day post-injury, using hospital admission data and information on the best motor GCS achieved during those first 24 h post-injury. Passed the first day after injury, important physiological predictors could emerge from landmark analyses, leading to prediction models of higher accuracy than the one proposed in the current research.

Background/aims: To validate the predictive value of the American Joint Committee on Cancer (AJCC) 8th-edition classification for local recurrence, metastasis and survival in patients with eyelid sebaceous carcinoma., Methods: We performed a retrospective review of 100 consecutive patients with eyelid sebaceous carcinoma. Eyelid carcinomas were staged according to the AJCC 7th-edition and 8th-edition criteria. Associations between T and N categories and disease-related outcomes including local recurrence, lymph node metastasis, distant metastasis and survival were evaluated., Results: 60 women and 40 men had a median age of 67 years (range, 41-94 years). The proportions of patients who experienced local recurrence, lymph node metastasis, distant metastasis and death from disease were 6%, 21%, 7% and 6%, respectively. Two-year and 5-year disease-specific survival (DSS) rates were 93.8% and 92.0%, respectively. There were significant correlations between (1) T2c or worse category and lymph node metastasis (p=0.04) and distant metastasis (p=0.01), (2) T3b or worse category and local recurrence (p=0.01) and death from disease (p=0.01) and (3) N1 category at presentation and distant metastasis (p<0.01) and death from disease (p<0.01). The AJCC 8th-edition classification showed a better homogeneity of the T-category distribution (p<0.01) and a slightly higher discrimination ability for lymph node metastasis (C=0.734 vs C=0.728) than the 7th-edition., Conclusions: T and N categories per AJCC 8th-edition classification are predictive of local recurrence, metastasis and DSS outcomes for eyelid sebaceous carcinoma. Surgeons should perform strict surveillance testing for nodal and systemic metastases in patients with T2c or worse T category and/or N1 disease at presentation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Immune checkpoint blockade (ICB) has revolutionized the treatment of NSCLC, but only approximately 15% of patients achieve durable benefit. Understanding mechanisms of resistance to ICB is pivotal in developing more effective treatment strategies. Recent studies showed that human leukocyte antigen (HLA) class I heterozygosity might be important in mediating benefit from ICB. We aimed to investigate the impact of HLA class I genotype on outcomes of patients with NSCLC treated with ICB., Methods: We collected HLA typing, genomic, and clinical data from patients with advanced NSCLC treated with ICB at M. D. Anderson Cancer Center. We compared HLA class I-heterozygous and HLA class I-homozygous patients for progression-free survival (PFS) and overall survival (OS). HLA I supertype/alleles were also analyzed. To validate our findings, we also analyzed two previously published independent cohorts of patients with NSCLC (the CheckMate-012 and Chowell cohorts)., Results: No significant correlations were observed for HLA class I zygosity and PFS or OS in the M. D. Anderson Cancer Center (n = 200), CheckMate-012 (n = 75), or Chowell (n = 371) cohorts. No HLA class I supertype/allele was consistently shown to be correlated with PFS or OS. Predictors of worse outcome across the three cohorts included presence of targetable driver mutation, serine/threonine kinase 11 gene (STK11) mutation, negative programmed death ligand 1 expression, and low tumor mutational burden., Conclusions: HLA class I genotype is not correlated with survival in advanced NSCLC treated with ICB. This suggests that the impact of HLA class I diversity may be disease specific and that tumor genomic and immune markers are more impactful in predicting benefit from ICB in NSCLC., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Importance: To our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma., Objective: To determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma., Design, Setting, and Participants: In this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded., Main Outcomes and Measures: Local recurrence, nodal metastasis, distance metastasis, and DSS., Results: Of the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS., Conclusions and Relevance: These findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.

The use of longitudinal measurements to predict a categorical outcome is an increasingly common goal in research studies. Joint models are commonly used to describe two or more models simultaneously by considering the correlated nature of their outcomes and the random error present in the longitudinal measurements. However, there is limited research on joint models with longitudinal predictors and categorical cross-sectional outcomes. Perhaps the most challenging task is how to model the longitudinal predictor process such that it represents the true biological mechanism that dictates the association with the categorical response. We propose a joint logistic regression and Markov chain model to describe a binary cross-sectional response, where the unobserved transition rates of a two-state continuous-time Markov chain are included as covariates. We use the method of maximum likelihood to estimate the parameters of our model. In a simulation study, coverage probabilities of about 95%, standard deviations close to standard errors, and low biases for the parameter values show that our estimation method is adequate. We apply the proposed joint model to a dataset of patients with traumatic brain injury to describe and predict a 6-month outcome based on physiological data collected post-injury and admission characteristics. Our analysis indicates that the information provided by physiological changes over time may help improve prediction of long-term functional status of these severely ill subjects. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

OBJECT There is limited literature available to guide transfusion practices for patients with severe traumatic brain injury (TBI). Recent studies have shown that maintaining a higher hemoglobin threshold after severe TBI offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. METHODS The authors performed a secondary analysis of data obtained from a recently performed randomized clinical trial studying the effects of erythropoietin and blood transfusions on neurological recovery after severe TBI. Assigned hemoglobin thresholds (10 g/dl vs 7 g/dl) were maintained with packed red blood cell transfusions during the acute phase after injury. PHI was defined as the presence of new or enlarging intracranial hematomas on CT as long as 10 days after injury. A severe PHI was defined as an event that required an escalation of medical management or surgical intervention. Clinical and imaging parameters and transfusion thresholds were used in a multivariate Cox regression analysis to identify independent risk factors for PHI. RESULTS Among 200 patients enrolled in the trial, PHI was detected in 61 patients (30.5%). The majority of patients with PHI had a new, delayed contusion (n = 29) or an increase in contusion size (n = 15). The mean time interval between injury and identification of PHI was 17.2 ± 15.8 hours. The adjusted risk of severe PHI was 2.3 times higher for patients with a transfusion threshold of 10 g/dl (95% confidence interval 1.1-4.7; p = 0.02). Diffuse brain injury was associated with a lower risk of PHI events, whereas higher initial intracranial pressure increased the risk of PHI (p < 0.001). PHI was associated with a longer median length of stay in the intensive care unit (18.3 vs 14.4 days, respectively; p = 0.04) and poorer Glasgow Outcome Scale scores (42.9% vs 25.5%, respectively; p = 0.02) at 6 months. CONCLUSIONS A higher transfusion threshold of 10 g/dl after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher hemoglobin transfusion threshold after severe TBI., Competing Interests: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Background: The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients., Methods: The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score., Results: Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01)., Conclusion: Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings., Level of Evidence: Epidemiologic study, level II.

Background: The effect of red blood cell (RBC) storage on oxygenation in critically ill patients is still unknown. The objective of this study was to determine the association of RBC storage with oxygenation, long-term neurologic recovery, and death after traumatic brain injury., Methods: We used data from a 2 × 2 factorial randomized controlled trial of administration of erythropoietin or placebo and of assignment to transfusion threshold of less than 7g/dL or less than 10 g/dL in neurosurgical intensive care units in two US Level 1 trauma centers. Patients had severe traumatic brain injury with closed head injury, were unable to follow commands, and were enrolled within 6 hours of injury. Blood oxygenation 1 hour after the transfusion as measured by jugular venous oxygen saturation (n = 59) was the primary outcome. Secondary outcomes were brain tissue oxygenation (n = 77), 6-month Glasgow Outcome Scale (GOS) score (n = 122) collected using a structured interview and dichotomized into favorable (good recovery or moderate disability) or unfavorable outcome (severe disability, vegetative state, or dead), and mortality (n = 125). RBC age was defined as the maximum age of RBCs over all units in one transfusion per patient. For long-term outcomes, RBC age was defined as the mean age over all units given., Results: We failed to detect an association of RBC age with jugular venous oxygen saturation (linear regression β = 1.59; 95% confidence interval [CI], -2.99 to 6.18; p = 0.49), brain tissue oxygenation (linear regression β = 0.20; 95% CI, -0.23 to 0.63; p = 0.36), GOS score (odds ratio, 1.37; 95% CI, 0.53-3.57; p = 0.52), and mortality (hazard ratio, 1.35; 95% CI, 0.61-2.98; p = 0.46)., Conclusion: Limitations of this study include the fact that the RBC ages were not randomized, although this was a prospective study. We conclude that older blood does not seem to have adverse effects in severe traumatic brain injury., Level of Evidence: Prognostic study, level III.

Cerebral dysfunction caused by traumatic brain injury may adversely affect cerebral hemodynamics and oxygenation leading to worse outcomes if oxygen capacity is decreased due to anemia. In a randomized clinical trial of 200 patients comparing transfusion thresholds <7 g/dl versus 10 g/dl, where transfusion of leukoreduced packed red blood cells was used to maintain the assigned hemoglobin threshold, no long-term neurological difference was detected. The current study examines secondary outcome measures of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue oxygenation (PbtO2) in patients enrolled in this randomized clinical trial. We observed a lower hazard for death (hazard ratio [HR]=0.12, 95% confidence interval [CI]=0.02-0.99) during the first 3 days post-injury, and a higher hazard for death after three days (HR=2.55, 95% CI=1.00-6.53) in the 10 g/dl threshold group as compared to the 7 g/dL threshold group. No significant differences were observed for ICP and CPP but MAP was slightly lower in the 7 g/dL group, although the decreased MAP did not result in increased hypotension. Overall brain tissue hypoxia events were not significantly different in the two transfusion threshold groups. When the PbtO2 catheter was placed in normal brain, however, tissue hypoxia occurred in 25% of patients in the 7 g/dL threshold group, compared to 10.2% of patients in the 10 g/dL threshold group (p=0.04). Although we observed a few differences in hemodynamic outcomes between the transfusion threshold groups, none were of major clinical significance and did not affect long-term neurological outcome and mortality.

Importance: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury., Objective: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury., Design, Setting, and Participants: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL., Interventions: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells., Main Outcomes and Measures: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury., Results: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009)., Conclusions and Relevance: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting., Trial Registration: clinicaltrials.gov Identifier: NCT00313716.

Background: The Final Rule regulations were developed to allow exception from informed consent (EFIC) to enable clinical trial research in emergency settings where major barriers exist for informed consent. There is little known evidence of the effect of the Final Rule in minority enrollment in clinical trials, particularly in traumatic brain injury (TBI) trials. A clinical trial funded by the National Institute of Neurological Disorders and Stroke was conducted to study the effects of erythropoietin on cerebral vascular dysfunction and anemia in subjects with TBI. There were periods of time when EFIC was and was not available for enrollment into the study., Purpose: To explore the effect of EFIC availability on TBI trial enrollment of minority versus non-minority subjects., Methods: Minority status of screened (n = 289) and enrolled (n = 191) TBI subjects was determined for this study. We tested for the presence of a minority and EFIC availability interaction in a multiple logistic regression model after controlling for EFIC and minority group main effects and other covariates., Results: An interaction between the availability of EFIC minority and non-minority enrollment was not detected (odds ratio = 1.22; 95% confidence interval (CI) = 0.29-5.16)., Limitations: Our study was conducted at a single site, and the CI for the EFIC and minority interaction term was wide. Therefore, a small interaction effect cannot be ruled out., Conclusion: EFIC increased the odds of being enrolled regardless of minority status.

After having a radial keratotomy, a physician developed binocular diplopia. The differential diagnosis and management of symptoms by appropriate spectacles is described.

Why would a patient without ocular pathology and with carefully prescribed glasses have "fuzzy" vision in one eye except when the left lens is twisted upward? The answer may be simpler than you think.

A contentious middle-age patient inadvertently obstructs the management of a simple presbyopic problem related to asymmetric accommodative loss.

Diabetic retinopathy is a common cause of blindness in the adult population in the United States. Ophthalmologists now have laser and surgical treatment modalities available that can significantly decrease the risk of blindness in the diabetic population. The American Academy of Ophthalmology, through its Diabetes 2000 program, is making a national effort to educate all physicians who care for diabetic patients to recognize the problem and to be aware of the therapies available to prevent blindness.

A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema.

This case presentation reviews the refractive options facing a myopic patient who chose to remain myopic after cataract extraction. The factors leading to this choice are explained.

We observed two patients who had unilateral posterior vitreous cysts; one patient had been observed for 17 years. Both patients were young females who reported transient, infrequent obscurations of vision that were not disabling. One involved eye was emmetropic, and the other was highly myopic. No other ocular abnormalities were present. In the patient observed for 17 years, the physical characteristics of the posterior vitreous cyst remained unchanged. With this stable clinical course, posterior vitreous cyst that does not visually disable the patient may be managed by periodic observation.

Distributions of elements above the atomic number of sodium were mapped in the retinal pigment epithelia of eight human eyes. X-ray energy spectra and maps were collected from cryofixed, freeze-dried, and epoxy-embedded tissues using energy-dispersive x-ray microanalysis. All eyes had high concentrations of phosphorus in the nuclei of retinal pigment epithelial cells. Melanosomes were rich in sulfur, zinc, calcium, and iron. Lipofuscin and cytoplasm contained only phosphorus and sulfur in detectable amounts. Drusen, when present, contained phosphorus and calcium. Six eyes had a prominent aluminum peak recorded from melanosomes, nuclei, and Bruch's membrane. In one pair of 90-year-old eyes, small, electron-dense deposits surrounded many melanosomes and contained mercury and selenium. Retinal pigment epithelial melanosomes may bind and accumulate metals and other potentially toxic ions over time, preventing them from reaching the neural retina.

While refractive surgery such as radial keratotomy, epikeratophakia, and corneal relaxing incisions offer many potential benefits to patients, they can also generate optical problems such as overcorrection or undercorrection of the prior refractive error and variable vision. The authors offer suggestions for avoiding problems through proper patient selection; candid preoperative communication with the patient about possible difficulties and limitations; understanding of the physiological changes that may occur; and optical techniques for alleviating postoperative vision problems.

Electrical signals in response to both diffuse flashes of light and phase-alternating spatial patterns were recorded from the eyes and from the occipital scalp of a subject with a traumatic unilateral (right) optic nerve section. Clinical examination disclosed a grossly normal right eye with no light perception, a Marcus Gunn pupil, and an atrophic optic disc. The left eye was normal. The electroretinogram responses on the lesioned side (OD) were normal, but there was no pattern-evoked retinal response (PERR) and no recordable visual-evoked response present. The conclusion is that the optic nerve and ganglion cells appear to be selectively responsible for the PERR potential.

A good visual result after cataract surgery and intraocular lens implantation depends on preoperative determination of an "ideal" postoperative refraction. This will depend on the refractive error in the other eye and whether the cataract is monocular or binocular. Methods are outlined for calculating the postoperative refraction and refracting the pseudophakic patient after surgery.

The authors cite various information and misinformation regarding proposed treatments (atropinization, contact lenses, orthokeratology, wearing glasses, not wearing glasses) for the progression of myopia. They conclude that there is insufficient evidence to support the more vigorous approaches to treatment of myopia, and provide some useful explantations for patients and their parents who question the ophthalmologist's decision to treat conservatively.