Association between F2-isoprostanes and self-reported stressors in pregnant americans of African and European ancestry.

Background: Poor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited. Methods: We used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography-tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth. Results: After adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (ß = 0.16, se = 1.07, p-value = 0.024) and depression scores (ß = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (ß = -0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05). Conclusion: While the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.

Childhood and Adulthood Trauma Associate With Cognitive Aging Among Black and White Older Adults.

Sociocontextual factors powerfully shape risk for age-related cognitive impairment, including excess risk burdening medically underserved populations. Lifecourse adversity associates with cognitive aging, but harms are likely mitigable. Understanding population-salient relationships and sensitive periods for exposure is crucial for targeting clinical interventions. OBJECTIVE: The authors examined childhood and adulthood traumatic events in relation to cognition among Black and White older adults in the Health and Retirement Study (HRS). PARTICIPANTS: Participants (N = 13,952) aged 55+ had complete lifetime trauma and cognitive testing data at the 2006/08, 2010/12, and/or 2014/16 waves. MEASURES: Trauma indices comprised childhood and adulthood event counts. Outcomes included baseline performance and trajectories on the Telephone Interview for Cognitive Status. DESIGN: Main and nonlinear trauma effects were modeled via linear regression, and overall contributions assessed with omnibus likelihood ratio tests. RESULTS: Black participants (N = 2,345) reported marginally lower adulthood trauma exposure than White participants (N = 11,607) with no other exposure differentials observed. In White participants only, greater childhood trauma exposure predicted worse baseline cognition but slower change over time. Across race, adulthood trauma robustly associated with baseline cognition. Relationships were frequently nonlinear: low but nonzero trauma predicted highest cognitive scores, with much poorer cognition observed as trauma exposure increased. Relationships between adulthood trauma and trajectory were limited to the White sample. CONCLUSION: Traumatic experiences, particularly in adulthood, may impact late-life cognitive health if not addressed. Findings highlight foci for clinical researchers and providers: adverse life events as a source of cognitive risk, and identification of community-specific resources that buffer behavioral, physical, and mental health sequelae of previous and incident trauma.

Efficient viral expression of a chemogenetic receptor in the old-world monkey amygdala.

Genetically encoded synthetic receptors, such as the chemogenetic and optogenetic proteins, are powerful tools for functional brain studies in animals. In the primate brain, with its comparatively large, intricate anatomical structures, it can be challenging to express transgenes, such as the hM4Di chemogenetic receptor, in a defined anatomical structure with high penetrance. Here, we compare parameters for lentivirus vector injections in the rhesus monkey amygdala. We find that four injections of 20 µl, infused at 0.5 µl/min, can achieve neuronal hM4Di expression in 50-100% of neurons within a 60 mm3 volume, without observable damage from overexpression. Increasing the number of hM4Di_CFP lentivirus injections to up to 12 sites per hemisphere, resulted in 30%-40% neuronal coverage of the overall amygdala volume, with coverage reaching 60% in some subnuclei. Manganese Chloride was mixed with lentivirus and used as an MRI marker to verify targeting accuracy and correct unsuccessful injections in these experiments. In a separate monkey we visualized, in vivo, viral expression of the hM4Di receptor protein in the amygdala, using Positron Emission Tomography. Together, these data show efficient and verifiable expression of a chemogenetic receptor in old-world monkey amygdala.

Complications of Intravenous Tenecteplase Versus Alteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. METHODS: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www. CLINICALTRIALS: gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. RESULTS: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I2=0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I2=0%), 0.77 ([95% CI, 0.53-1.14]; I2=0%), and 2.31 ([95% CI, 0.69-7.75]; I2=40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I2=0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I2=1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I2=52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. CONCLUSIONS: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.

Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee's success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor's awareness of systemic barriers along with active allyship are foundational for their role.

The financial impact of COVID-19 on a surgical department: The effects of surgical shutdowns and the impact on a health system.

BACKGROUND: The COVID-19 pandemic resulted in sweeping shutdowns of surgical operations to increase hospital capacity and conserve resources. Our institution, following national and state guidelines, suspended nonessential surgeries from March 16 to May 4, 2020. This study examines the financial impact of this decision on our institution's health system by comparing 2 waves of COVID-19 cases. METHODS: The total revenue was obtained for surgical cases occurring during the first wave of the pandemic between March 1, 2020 and July 31, 2020 and the second wave between October 1, 2020 and February 29, 2021 for all surgical departments. During the same time intervals, in the prepandemic year 2019, total revenue was also obtained for comparison. Net revenue and work relative value units per month were compared to each respective month for all surgical divisions within the department of surgery. RESULTS: Comparing the 5-month first wave period in 2020 to prepandemic 2019 for all surgical departments, there was a net revenue loss of $99,674,376, which reflected 42% of the health system's revenue loss during this period. The department of surgery contributed to a net revenue loss of $58,368,951, which was 24.9% of the health system's revenue loss. Within the department of surgery, there was a significant difference between the net revenue loss per month per division of the first and second wave: first wave median -$636,952 [interquartile range: -1,432,627; 26,111] and second wave median -$274,626 [-781,124; 396,570] (P = .04). A similar difference was detected when comparing percent change in work relative value units between the 2 waves (wave 1: median -13.2% [interquartile range: -41.3%, -1.8%], wave 2: median -7.8% [interquartile range: -13.0%, 1.8%], P = .003). CONCLUSION: Stopping elective surgeries significantly decreased revenue for a health system. Losses for the health system totaled $234,839,990 during the first wave, with lost surgical revenue comprising 42% of that amount. With elective surgeries continuing during the second wave of COVID-19 cases, the health system losses were substantially lower. The contribution surgery has to a hospital's cash flow is essential in maintaining financial solvency. It is important for hospital systems to develop innovative and alternative solutions to increase capacity, offer comprehensive care to medical and surgical patients, and prevent shutdowns of surgical activity through a pandemic to maintain financial security.

Moyamoya syndrome in a young person with Down syndrome: diagnostic and therapeutic considerations.

An 18-year-old woman with a history of Down syndrome (DS) presented with left upper extremity weakness. Neurological examination revealed moderate hypotonia throughout, with mild spasticity of the left ankle. She had 2/5 left upper and lower extremity strength, mild pronation with drift in the left arm and 3+ deep tendon reflexes in the left biceps, brachioradialis, patellar and Achilles. Strength was 5/5 in the right upper and lower extremities. A CT angiography of the head and neck with contrast demonstrated severe narrowing of the bilateral supraclinoid internal carotid arteries (ICAs), suggestive of moyamoya pattern. A diagnostic angiography confirmed stenosis in the right and left supraclinoid ICAs. The patient was started on aspirin therapy and underwent an indirect bypass procedure via encephaloduroarteriosynangiosis 6 weeks after initial presentation. DS is associated with a high risk of congenital heart disease, which in turn increases risk of stroke, namely cardioembolic events, including moyamoya disease. Intellectual disability is nearly ubiquitous in DS, thus adding to the challenges of making a diagnosis of moyamoya in this population.

A case of fatal familial insomnia: diagnostic and therapeutic approaches.

Fatal Familial Insomnia (FFI) is an uncommon but fatal genetic condition that is characterized by severe progressive insomnia, dysautonomia, neuropsychiatric changes, and gait instability. Diagnostic workup includes genetic testing, EEG, MRI imaging of the brain, polysomnography, and CSF analysis. MRI brain imaging may be notable for areas of restricted diffusion in the thalamus. Therapeutic approaches are centered on symptom management, predominantly for insomnia. It is important for clinicians to consider FFI in patients presenting with progressive insomnia, cognitive deficits, and gait instability, and to direct patients and families toward genetic counseling and palliative care services.

Development of a peer-led, network mapping intervention to improve the health of individuals with severe mental illnesses: protocol for a pilot study.

INTRODUCTION: Adults with severe mental illness (SMI) have reduced life expectancy and many have comorbid physical health conditions. Primary care providers are experiencing increased demands for care for people with SMI. Barriers to accessing physical healthcare have been identified which negatively affect quality of care. We propose that peer support workers (PSWs) could deliver an intervention to service users to promote their physical health by drawing on existing social support. The aim of this research was to pilot a novel PSW-led intervention, including personal well-being network mapping, to improve access to primary care for physical health needs. METHODS AND ANALYSIS: Twenty-four participants will be recruited from community-based mental health teams in two boroughs of London. Each participant will be offered a six-session intervention. Quantitative data will be collected before and after intervention (at 4-month follow-up). Qualitative interviews will be conducted with PSWs after completion of the intervention and with participants at a 4-month follow-up. Some intervention sessions will be observed by a member of the research team. This is a pilot study with a small sample aiming to assess acceptability and feasibility of an intervention. We aim to use the results to refine the existing theory of change and to optimise the intervention and its evaluation in a future randomised controlled trial. This study is strengthened by its potential clinical importance and origin in previous research where service users engaged with well-being network mapping. ETHICS AND DISSEMINATION: This study has been approved by the London-Chelsea Regional Ethics Committee (ref: 17/LO/0585). The findings will be disseminated to participants, the National Health Service trusts that we recruited from, primary care mental health leads, commissioners and in peer-reviewed journals and academic conferences.

Direct Oral Anticoagulant Agents: Pharmacologic Profile, Indications, Coagulation Monitoring, and Reversal Agents.

Vitamin K antagonists (VKAs), such as warfarin, have been used for thromboprophylaxis and for the treatment of thromboembolic events in patients with nonvalvular atrial fibrillation for over 60 years. The increasing use of direct oral anticoagulants (DOACs) in recent years has shown greater advantages and safer use over VKA, including reduced bleeding, fewer drug interactions, no food interactions, a quick onset and offset of activity, and predictable dose-response properties. Despite their advantages, there are a couple of major limitations that raise concerns among clinicians, including the need for more coagulation assays to monitor their effects and more specific reversal antidotes in life-threatening circumstances of bleeding. This review will discuss the important characteristics of the 5 Food and Drug Administration-approved DOACs (including anticoagulation monitoring for each) and the specific and nonspecific reversal agents to DOAC-associated bleeding.

Taking the Initiative: Risk-Reduction Strategies and Decreased Malpractice Costs.

BACKGROUND: To heighten awareness of attending and resident surgeons regarding strategies for defense against malpractice claims, a series of risk reduction initiatives have been carried out in our Department of Surgery. We hypothesized that emphasis on certain aspects of risk might be associated with decreased malpractice costs. The relative impact of Department of Surgery initiatives was assessed when compared with malpractice experience for the rest of the Clinical Practices of the University of Pennsylvania (CPUP). STUDY DESIGN: Surgery and CPUP malpractice claims, indemnity, and expenses were obtained from the Office of General Counsel. Malpractice premium data were obtained from CPUP finance. The Department of Surgery was assessed in comparison with all other CPUP departments. Cost data (yearly indemnity and expenses), and malpractice premiums (total and per physician) were expressed as a percentage of the 5-year mean value preceding implementation of the initiative program. RESULTS: Surgery implemented 38 risk reduction initiatives. Faculty participated in 27 initiatives; house staff participated in 10 initiatives; and advanced practitioners in 1 initiative. Department of Surgery claims were significantly less than CPUP (74.07% vs 81.07%; p < 0.05). The mean yearly indemnity paid by the Department of Surgery was significantly less than that of the other CPUP departments (84.08% vs 122.14%; p < 0.05). Department of Surgery-paid expenses were also significantly less (83.17% vs 104.96%; p < 0.05), and surgical malpractice premiums declined from baseline, but remained significantly higher than CPUP premiums. CONCLUSIONS: The data suggest that educating surgeons on malpractice and risk reduction may play a role in decreasing malpractice costs. Additional extrinsic factors may also affect cost data. Emphasis on risk reduction appears to be cumulative and should be part of an ongoing program.

School-Based Work Capacity Evaluation in Young People With Intellectual Disabilities: 2 Case Reports.

PURPOSE: These case reports examine the application of a work capacity/work-hardening model to increase work capacity in young people with disabilities. KEY POINTS: Examination, evaluation, interventions, and outcomes are described for 2 teenagers with intellectual disability. This approach is novel in that it uses functional capacity evaluation concepts used in ergonomic/occupational health contexts and applies them to youth with disabilities in educational settings. CONCLUSION: These concepts expand the scope of practice for physical therapists in school settings and potentially increase work opportunities for youth with disabilities.

Morningness/eveningness chronotype, poor sleep quality, and daytime sleepiness in relation to common mental disorders among Peruvian college students.

The study was designed to investigate the association between sleep disturbances and common mental disorders (CMDs) among Peruvian college students. A total of 2538 undergraduate students completed a self-administered questionnaire to gather information about sleep characteristics, sociodemographic, and lifestyle data. Evening chronotype, sleep quality, and daytime sleepiness were assessed using the Horne and Ostberg morningness-eveningness questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, respectivelty. Presence of CMDs was evaluated using the General Health Questionnaire. Logistic regression procedures were used to examine the associations of sleep disturbances with CMDs while accounting for possible confounding factors. Overall, 32.9% of the participants had prevalent CMDs (39.3% among females and 24.4% among males). In multivariable-adjusted logistic models, those with evening chronotype (odds ratios (OR) = 1.43; 95% CI 1.00-2.05), poor sleep quality (OR = 4.50; 95% CI 3.69-5.49), and excessive daytime sleepiness (OR = 1.68; 95% CI 1.41-2.01) were at a relative increased odds of CMDs compared with those without sleep disturbances. In conclusion, we found strong associations between sleep disturbances and CMDs among Peruvian college students. Early education and preventative interventions designed to improve sleep habits may effectively alter the possibility of developing CMDs among young adults.

Mind the sustainability gap.

Despite increasing efforts to reach sustainability, key global biophysical indicators such as climate change and biodiversity loss continue to deteriorate rather than improve. Ongoing failure to move towards sustainability calls into question the focus of current research and policy. We recommend two strategies for progress. First, sustainability must be conceptualized as a hierarchy of considerations, with the biophysical limits of the Earth setting the ultimate boundaries within which social and economic goals must be achieved. Second, transdisciplinary research programs must confront key normative questions facing modern consumer societies. The humanities should have a key role in such programs. Assisted by these strategies, ambitious targets that realistically reflect the biophysical limits of the life-support system of the Earth must be set and relentlessly worked towards.

Asthma prevalence among US adults, 1998-2000: role of Puerto Rican ethnicity and behavioral and geographic factors.

OBJECTIVES: We analyzed asthma prevalence among US adults by age, gender, race, Puerto Rican ethnicity, and other demographic, behavioral, health, and geographic variables. We hypothesized that high prevalences would be observed among Puerto Ricans and in the Northeast census region. METHODS: We used data from the 1998 through 2000 US National Health Interview Surveys. Information on lifetime history of asthma and asthma in the past year was collected from 95615 adults. We calculated weighted prevalence estimates and odds ratios from logistic regression. RESULTS: Of US adults, 8.9% had ever been diagnosed with asthma, and 3.4% had experienced an episode in the past 12 months. Asthma diagnosis rates were highest among Puerto Ricans (17.0%) and lowest among Mexican Americans (3.9%); rates were 9.6% and 9.2% among non-Hispanic Blacks and non-Hispanic Whites, respectively. Geographically, asthma prevalence was highest in the West (10.5%) and lowest in the Northeast (8.6%). Puerto Ricans in all regions had high asthma rates. CONCLUSIONS: final logistic regression model included race/ethnicity, obesity, poverty, female gender, and cigarette smoking. Higher asthma rates were confirmed among Puerto Ricans but not in the Northeast region.

Summary health statistics for u.s. Adults: national health interview survey, 2004.

Objectives-This report presents health statistics from the 2004 National Health Interview Survey for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, family income, poverty status, health insurance coverage, marital status, place of residence, and region of residence for chronic condition prevalence, health status, functional limitations, health care access and utilization, health behaviors, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. Source of Data-The NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2004, data were collected for 31,326 adults for the Sample Adult questionnaire. The conditional response rate was 83.8%, and the final response rate was 72.5%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for him or herself, a proxy was allowed. Highlights-In 2004, 62% of adults 18 years of age or over reported excellent or very good health. Sixty-two percent of adults never participated in any type of vigorous leisure-time physical activity, and 15% of adults did not have a usual place of health care. Twelve percent of adults had been told by a doctor or health professional that they had heart disease, and 22% had been told on two or more visits that they had hypertension. Twenty-one percent of all adults were current smokers, and 21% were former smokers. Based on estimates of body mass index, 35% of adults were overweight and 24% were obese.

Microsatellite status and cell cycle associated markers in rectal cancer patients undergoing a combined regimen of 5-FU and CPT-11 chemotherapy and radiotherapy.

BACKGROUND: Microsatellite instability (MSI) and expression of cell cycle-related markers may predict a favorable outcome in colorectal cancer patients. The aim of this study was to elucidate the molecular profiles of patients with rectal cancers treated with neoadjuvant chemotherapy (5-Fluorouracil and CPT-11), radiotherapy and surgery that correlate with response to therapy. PATIENTS AND METHODS: Fifty-seven patients with rectal cancer were treated with the same preoperative chemotherapy regimen, radiotherapy (45 to 54 Gy) followed by surgery. The microsatellite status, the expression of the mismatch repair proteins MLH1 and MSH2 and p21WAF1/C1PI, p27, bcl-2, topoisomerase II (topo II) and Ki-67 were assessed in the pretreatment biopsies. The response to adjuvant therapy was categorized in the resected specimens as complete response (CR, no microscopic residual tumor present) and partial response (PR, tumor present). RESULTS: p21WAF1/C1PI, expression characterized the CR with 12 out of 30 tumors (40%) positive for this marker. None of the patients whose tumors did not express p21WAFI/C1PI (10 patients) was a CR (p=0.011). Overall, the tumors with CR also showed higher expression of bcl-2, Ki-67, topo II and p27. However, p53 was more frequently expressed in the PR tumors. Tumors with high microsatellite instability showed CR (3/5, 60%) more often than PR, whereas tumors with stable microsatellites showed PR (26/36, 80%) more often than CR (p=0.099). CONCLUSION: We conclude that a molecular profile characterized by high microsatellite instability with loss of mismatch repair protein expression and p21WAF1/C1PI is predictive of an improved response to neoadjuvant treatment with 5-FU, CPT-11 and radiation therapy.

Skin cancer screening among U.S. adults from 1992, 1998, and 2000 National Health Interview Surveys.

BACKGROUND: Relatively little is known about the prevalence of skin cancer screening in the context of inconsistent skin cancer screening recommendations. METHODS: To determine the prevalence and predictors of skin cancer screening rates in the U.S. adult population, we used self-reported data from the 1992, 1998, and 2000 National Health Interview Surveys, a nationally representative survey of civilian noninstitutionalized adults. RESULTS: The percentage of the U.S. adult population who had ever had a skin examination conducted by a doctor was 20.6% in 1992, 20.9% in 1998, and 14.5% in 2000. The percentage with a recent skin examination was 10.3% in 1992, 11.0% in 1998, and 8.0% in 2000. White non-Hispanics reported being screened more frequently than persons in other racial or ethnic groups. Recent skin cancer screening exams were more common among white persons who had a family history of melanoma, had higher education, had usual place of care, and were older (> or =50 years). Frequent use of sunscreen and hats was associated with a recent skin cancer exam. CONCLUSIONS: In the past decade, skin cancer screening rates have been consistently low. Continued monitoring of skin cancer examination is important given conflicting current research results and potentially evolving science.

Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.

PURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.