Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Underutilization of gene expression profiling for early-stage breast cancer in California

PURPOSE: To describe the utilization of gene expression profiling (GEP) among California breast cancer patients, identify predictors of use of GEP, and evaluate how utilization of GEP influenced treatment of early stage breast cancer. METHODS: All women diagnosed with hormone receptor positive, node-negative breast cancer reported to the California Cancer Registry between January 2008 and December 2010 were linked to Oncotype DX (ODX) assay results. RESULTS: Overall, 26.7% of 23,789 eligible patients underwent the assay during the study period. Women age 65 or older were much less likely than women under age 50 to be tested (15.1% versus 41.4%, p<0.001). Black women were slightly less likely and Asian women slightly more likely than non-Hispanic white women to undergo GEP with the ODX assay (22.2% and 28.9% versus 26.9% respectively, p<0.001). Patients residing in low SES census tracts had the lowest use of the test (8.9%), with the proportion increasing with higher SES category. Women with Medicaid health insurance were less likely than other women to be tested (17.7% versus 27.5%, p<0.001). Receipt of adjuvant chemotherapy (ACT) was associated with the ODX recurrence score, although only 63% of patients whose recurrence scores indicated a high benefit received ACT. Of patients not tested, 15% received ACT. CONCLUSIONS: Nearly three-fourths of eligible breast cancer patients in California during the 3-year period 2008 through 2010 did not undergo GEP. As a result, it is likely that many women unnecessarily received ACT and suffered associated morbidity. In addition, some high risk women who would have benefited most from ACT were not identified

Educational review: measurement of GFR in special populations.

Importance Changes in kidney function are typically followed by the sequential estimation of glomerular filtration rate (eGFR). Formulae for eGFR work well on a population basis, but there are well-known conditions where they do not work. Objective The purpose of this review is to summarize the existing literature on special populations in the pediatric age range and provide recommendations on how to estimate GFR in these populations. Findings The reliability of creatinine depends on muscle mass, while cystatin C (not widely available) is limited by inflammation and changes in protein catabolism. Various dietary factors can alter eGFR. Renal function in neonates changes drastically every day, and there are currently no satisfactory reference intervals for routine pediatric use. Gender effects and conditions such as wasting disease and obesity require alternative ways to obtain eGFR. In oncology patients, chemotherapy may negatively affect renal function, and nuclear GFR measurements may be necessary. For body builders, high muscle mass may lead to underestimation of eGFR using creatinine. Conclusions and Relevance Clinicians should be aware of special populations that may yield misleading eGFRs with conventional creatinine-based formulae, and that the alternative methods may be more appropriate for some populations