Improving pulse oximetry accuracy in dark-skinned patients: technical aspects and current regulations.

Recent concerns regarding the clinical accuracy of pulse oximetry in dark-skinned patients, specifically in detecting occult hypoxaemia, have motivated research on this topic and recently reported in this journal. We provide an overview of the technical aspects of the issue, the sources of inaccuracy, and the current regulations and limitations. These insights offer perspectives on how pulse oximetry can be improved to address these potential limitations.

Skin Pigmentation Influence on Pulse Oximetry Accuracy: A Systematic Review and Bibliometric Analysis.

Nowadays, pulse oximetry has become the standard in primary and intensive care units, especially as a triage tool during the current COVID-19 pandemic. Hence, a deeper understanding of the measurement errors that can affect precise readings is a key element in clinical decision-making. Several factors may influence the accuracy of pulse oximetry, such as skin color, body temperature, altitude, or patient movement. The skin pigmentation effect on pulse oximetry accuracy has long been studied reporting some contradictory conclusions. Recent studies have shown a positive bias in oxygen saturation measurements in patients with darkly pigmented skin, particularly under low saturation conditions. This review aims to study the literature that assesses the influence of skin pigmentation on the accuracy of these devices. We employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to conduct a systematic review retrospectively since February 2022 using WOS, PubMed, and Scopus databases. We found 99 unique references, of which only 41 satisfied the established inclusion criteria. A bibliometric and scientometrics approach was performed to examine the outcomes of an exhaustive survey of the thematic content and trending topics.

Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results.

BACKGROUND: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The "Tratamiento de Tumores Digestivos" group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. METHODS: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). RESULTS: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). CONCLUSIONS: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. TRIAL REGISTRATION: EudraCT number: 2009-010192-24 . Clinicaltrials.gov number: NCT01043484 .

Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?

PURPOSE: To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. METHODS: Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. RESULTS: A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). TOXICITY: Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. CONCLUSIONS: The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02).

BACKGROUND: RAS testing is used to select patients with anti-epidermal growth factor receptor (EGFR) therapies sensitivity in metastatic colorectal cancer (mCRC). However, other biomarkers such as BRAF, PIK3CA/PTEN, and p-IGF-1R+/MMP7+ (double positive [DP] phenotype) have not been prospectively assessed to predict anti-EGFR resistance. MATERIALS AND METHODS: We designed a multicenter prospective trial (NCT01276379) to evaluate whether the biomarkers BRAF mutation, PIK3CA mutation/PTEN loss, and DP phenotype can improve the prediction for 12-months progression-free survival (PFS) over the use of clinical variables exclusively in patients with RAS wild-type (WT) mCRC treated with standard chemotherapy plus biweekly cetuximab as first-line therapy. The planned sample size was 170 RAS WT patients to detect a 20% difference in 12-month PFS based on the analysis of clinical and selected biomarkers (α = .05, ß = .2). The discriminatory capacity of the biomarkers was evaluated using receiver operating characteristic curves. RESULTS: We included 181 RAS WT patients. The biomarker distribution was as follows: BRAF mutant, 20 patients (11%); PIK3CA mutated/PTEN loss, 98 patients (58%); DP, 23 patients (12.7%). The clinical variables in the clinical score were progression status >0, left-sided tumor, and resectable liver metastasis as the only metastatic site. The area under the curve (AUC) of the score containing the clinical variables was 0.67 (95% confidence interval [CI], 0.60-0.75). The AUC of the score with clinical variables and BRAF mutational status was 0.68 (0.61-0.75, p = .37). The AUC of the score with clinical variables and PI3KCA mutation/PTEN status was 0.69 (0.61-0.76, p = .32). The AUC of the score with clinical variables and DP phenotype was 0.66 (0.58-0.73, p = .09). CONCLUSION: The addition of BRAF, PIK3CA/PTEN, and DP to a clinical score does not improve the discrimination of 12-month PFS. IMPLICATIONS FOR PRACTICE: This prospective biomarker design study has important clinical implications because many prospective clinical trials are designed with the hypothesis that BRAF mutation per se and MEK and PIK3CA downstream pathways are critical for colorectal tumor survival. The results lead to the question of whether these pathways should be considered as passengers instead of drivers.

Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer.

BACKGROUND: Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving. METHODS: We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients. The effect of IGF-1R activation and distribution was also assessed using cellular models of CRC and RNAi for functional validation. RESULTS: Nuclear IGF-1R increased in metastatic tumours compared to paired untreated primary tumours, and significantly correlated with poor overall survival in mCRC patients. In vitro, chemo-resistant cell lines presented significantly higher levels of IGF-1R expression within the nuclear compartment, and PIAS3, a protein implicated also in the sumoylation process of intranuclear proteins, contributed to IGF-1R nuclear sequestration, highlighting the essential role of PIAS3 in this process. Intriguingly, we observed that ganitumab, an IGF-1R blocking-antibody used in several clinical trials, and dasatinib, an SRC inhibitor, increased the nuclear localisation of IGF-1R. CONCLUSIONS: Our study demonstrates that IGF-1R nuclear location might lead to chemotherapy and targeted agent resistance.

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features.

BACKGROUND: Perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging. METHODS: Patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m(2) twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0). RESULTS: Ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02). CONCLUSIONS: The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies. TRIAL REGISTRY: Clinicaltrials.gov identifier NCT01043484. Trial registration date: 12/30/2009.

Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review.

Free radicals generated within subcellular compartments damage macromolecules which lead to severe structural changes and functional alterations of cellular organelles. A manifestation of free radical injury to biological membranes is the process of lipid peroxidation, an autooxidative chain reaction in which polyunsaturated fatty acids in the membrane are the substrate. There is considerable evidence that damage to polyunsaturated fatty acids tends to reduce membrane fluidity. However, adequate levels of fluidity are essential for the proper functioning of biological membranes. Thus, there is considerable interest in antioxidant molecules which are able to stabilize membranes because of their protective effects against lipid peroxidation. Melatonin is an indoleamine that modulates a wide variety of endocrine, neural and immune functions. Over the last two decades, intensive research has proven this molecule, as well as its metabolites, to possess substantial antioxidant activity. In addition to their ability to scavenge several reactive oxygen and nitrogen species, melatonin increases the activity of the glutathione redox enzymes, that is, glutathione peroxidase and reductase, as well as other antioxidant enzymes. These beneficial effects of melatonin are more significant because of its small molecular size and its amphipathic behaviour, which facilitates ease of melatonin penetration into every subcellular compartment. In the present work, we review the current information related to the beneficial effects of melatonin in maintaining the fluidity of biological membranes against free radical attack, and further, we discuss its implications for ageing and disease.

Exploring the Hidden Complexity: Entropy Analysis in Pulse Oximetry of Female Athletes.

This study examines the relationship between physiological complexity, as measured by Approximate Entropy (ApEn) and Sample Entropy (SampEn), and fitness levels in female athletes. Our focus is on their association with maximal oxygen consumption (VO2,max). Our findings reveal a complex relationship between entropy metrics and fitness levels, indicating that higher fitness typically, though not invariably, correlates with greater entropy in physiological time series data; however, this is not consistent for all individuals. For Heart Rate (HR), entropy measures suggest stable patterns across fitness categories, while pulse oximetry (SpO2) data shows greater variability. For instance, the medium fitness group displayed an ApEn(HR) = 0.57±0.13 with a coefficient of variation (CV) of 22.17 and ApEn(SpO2) = 0.96±0.49 with a CV of 46.08%, compared to the excellent fitness group with ApEn(HR) = 0.60±0.09 with a CV of 15.19% and ApEn(SpO2) =0.85±0.42 with a CV of 49.46%, suggesting broader physiological responses among more fit individuals. The larger standard deviations and CVs for SpO2 entropy may indicate the body's proficient oxygen utilization at higher levels of physical demand. Our findings advocate for combining entropy metrics with wearable sensor technology for improved biomedical analysis and personalized healthcare.

Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.

Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5'fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

Are Activity Wrist-Worn Devices Accurate for Determining Heart Rate during Intense Exercise?

The market for wrist-worn devices is growing at previously unheard-of speeds. A consequence of their fast commercialization is a lack of adequate studies testing their accuracy on varied populations and pursuits. To provide an understanding of wearable sensors for sports medicine, the present study examined heart rate (HR) measurements of four popular wrist-worn devices, the (Fitbit Charge (FB), Apple Watch (AW), Tomtom runner Cardio (TT), and Samsung G2 (G2)), and compared them with gold standard measurements derived by continuous electrocardiogram examination (ECG). Eight athletes participated in a comparative study undergoing maximal stress testing on a cycle ergometer or a treadmill. We analyzed 1,286 simultaneous HR data pairs between the tested devices and the ECG. The four devices were reasonably accurate at the lowest activity level. However, at higher levels of exercise intensity the FB and G2 tended to underestimate HR values during intense physical effort, while the TT and AW devices were fairly reliable. Our results suggest that HR estimations should be considered cautiously at specific intensities. Indeed, an effective intervention is required to register accurate HR readings at high-intensity levels (above 150 bpm). It is important to consider that even though none of these devices are certified or sold as medical or safety devices, researchers must nonetheless evaluate wrist-worn wearable technology in order to fully understand how HR affects psychological and physical health, especially under conditions of more intense exercise.

First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study.

PURPOSE: The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. RESULTS: The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0-53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. CONCLUSION: Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.

A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens.

OBJECTIVES: To assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) in patients with metastatic colorectal cancer who had failed one or two previous chemotherapeutic regimens that included oxaliplatin and/or irinotecan. METHODS: This was a Phase II, multicentre, open-label, randomised, two-arm, parallel-group study comparing AZD6244 with capecitabine monotherapy. Patients received either 100 mg twice daily oral AZD6244 free-base suspension every day or 1,250 mg/m(2) twice daily oral capecitabine, for 2 weeks, followed by a 1-week rest period, in 3-weekly cycles. The primary endpoint was the number of patients experiencing disease progression events. RESULTS: Sixty-nine patients were randomised in the study (34 and 35 patients in the AZD6244 and capecitabine groups, respectively). Disease progression events were experienced by 28 patients (~80%) in both the AZD6244 and capecitabine treatment groups. Median progression-free survival was 81 days and 88 days in the AZD6244 and capecitabine groups, respectively. Ten patients in the AZD6244 treatment arm had a best response of stable disease. For capecitabine, best response was a partial response in one patient, with stable disease in a further 15 patients. The most frequently observed adverse events reported with AZD6244 were acneiform dermatitis, diarrhoea, asthenia and peripheral oedema, compared with hand-foot syndrome, diarrhoea, nausea and abdominal pain with capecitabine. CONCLUSIONS: AZD6244 showed similar efficacy to capecitabine in terms of the number of patients with a disease progression event and of progression-free survival. AZD6244 is currently undergoing evaluation in Phase II trials in combination with other chemotherapeutic agents.

Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab.

The purpose of the study was to prospectively explore the role of serum MMP-7 as a predictive and prognostic marker of anti-epidermal growth factor receptor (EGFR) therapy and irinotecan efficacy in third-line advanced colorectal cancer therapy. One hundred patients were recruited prospectively from six Spanish hospitals. Patients were treated with biweekly irinotecan 180 mg/m(2) and cetuximab 400 mg/m(2) (loading dose) and weekly cetuximab 250 mg/m(2) until progressive disease or unacceptable toxicity. Baseline MMP-7 was determined using a quantitative solid-phase sandwich ELISA. KRAS and BRAF mutational status were also assessed. The clinical endpoints examined were overall survival (OS), progression-free survival (PFS), and response rate. No association between serum MMP-7 and neither KRAS nor BRAF mutational status was found. The multivariate analysis revealed that MMP-7 predicts PFS both in wild-type (WT) KRAS patients (HR 1.03, 95% CI 1.00-1.06; p = 0.046) and in mutant KRAS patients (HR 1.18, 95% CI 1.01-1.35; p = 0.036). The presence of mutant BRAF was associated with shorter PFS (HR 8.49, 95% CI 2.88-25.0; p < 0.001) and worse OS (HR 3.55, 95% CI 1.39-9.09; p = 0.008) in the subset of WT KRAS patients. Serum MMP-7 is associated with PFS in colorectal patients treated with anti-EGFR therapy as third-line treatment independently of KRAS status.

Transanal endoscopic microsurgery for rectal cancer. Long-term oncologic results.

PURPOSE: Local excision of malignant rectal tumors remains controversial due to the lack of prospective studies. The principal aim of this paper is to analyze survival and recurrence of patients with rectal cancer who were operated by transanal endoscopic microsurgery with curative intention. METHODS: In 1997, we started a prospective protocol for patients who had T1/T2 rectal tumors: transanal local full-thickness excision was considered curative in T1 low risk (group A); patients with T1 high-risk and T2 low-risk tumors received postoperative radiotherapy (group B). From 1997 to 2006, 88 patients were enrolled. Sixty eight entered the study after the preoperative workup and 20 patients with an initial diagnosis of adenoma after postoperative definitive pathological assessment. RESULTS: After definitive histological findings, 54 patients were to group A, 28 to group B, and 6 had immediate radical surgery. One patient was lost for follow-up. At a mean follow-up of 71 months, 7 (4 from group A and 3 from group B) out of 81 patients recurred. Five-year overall survival was of 94% and cancer-specific survival of 96%. CONCLUSIONS: Our data support that transanal endoscopic microsurgery is an adequate treatment for T1 low-risk tumor, and no additional measures are required. For T2 low-risk lesions, our study showed a higher local recurrence rate than that reported after radical surgery but a similar survival outcome.

Oxygen Saturation Behavior by Pulse Oximetry in Female Athletes: Breaking Myths.

The myths surrounding women's participation in sport have been reflected in respiratory physiology. This study aims to demonstrate that continuous monitoring of blood oxygen saturation during a maximal exercise test in female athletes is highly correlated with the determination of the second ventilatory threshold (VT2) or anaerobic threshold (AnT). The measurements were performed using a pulse oximeter during a maximum effort test on a treadmill on a population of 27 healthy female athletes. A common behavior of the oxygen saturation evolution during the incremental exercise test characterized by a decrease in saturation before the aerobic threshold (AeT) followed by a second significant drop was observed. Decreases in peripheral oxygen saturation during physical exertion have been related to the athlete's physical fitness condition. However, this drop should not be a limiting factor in women's physical performance. We found statistically significant correlations between the maximum oxygen uptake and the appearance of the ventilatory thresholds (VT1 and VT2), the desaturation time, the total test time, and between the desaturation time and the VT2. We observed a relationship between the desaturation time and the VT2 appearance. Indeed, a linear regression model between the desaturation time and the VT2 appearance can predict 80% of the values in our sample. Besides, we suggest that pulse oximetry is a simple, fairly accurate, and non-invasive technique for studying the physical condition of athletes who perform physical exertion.

Martial arts injuries: a longitudinal study about judo, karate and wushu carried out in the Community of Madrid, Spain.

BACKGROUND: Martial arts are currently being practiced throughout the world by about 100 million people. Considering that sports injuries account for 20% of all emergencies treated in hospitals, this is an issue that should be further studied. Our objective was to determine the prevalence and type of injuries in wushu, judo, and karate practitioners in Community of Madrid, Spain. METHODS: A descriptive epidemiology study was carried out. A questionnaire was used to collect data from 457 men and women practicing karate, judo and/or wushu, including injuries from the past five years, type of injury and occurrence during training or competition. RESULTS: Injuries that disrupted training occurred in 56% of judokas, in 36.7% of karatekas and in 38.9% of wushu practitioners (WP). For judokas, the most common injury site was "shoulder/arm/elbow" (13.43%), for karatekas, it was "lower leg/foot/ankle" (9.95%), and for WP it was "groin/hip/thigh" (9.45%) (P=0.000). The most common injuries in judo and karate were "ankle sprains and joint injuries" (4.98% and 3.98%), while for WP the most common injury were "hamstring strains" (5.47%) (P=0.008). There was no relationship between occurrence of a first injury and sex, age or belt rank. CONCLUSIONS: Judo is the martial art with the highest percentage of injuries, followed by wushu and then karate.

Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer.

BACKGROUND: We gathered data from multiple institutions on the cetuximab regimen of patients with metastatic colorectal cancer. METHODS: 126 patients from 19 centers were included from July 2006 to July 2007 in this prospective non-controlled study. Irinotecan-refractory metastatic colorectal cancer patients with Karnofsky >or=70 received cetuximab 500 mg/m(2) every 2 weeks (q2w) in combination with irinotecan 180 mg/m(2) q2w until disease progression or unacceptable toxicity. The primary endpoint was the progression-free rate at 12 weeks. RESULTS: Median age was 65 years; 65.9% male; colon/rectum 64.3/34.1%; Karnofsky status or=90% in 45.3/54.7% of the patients. The progression-free rate was 42.7 (95% CI 32.8-52.6) and 22.4% (95% CI 14.2-30.7) at 12 and 24 weeks, respectively. The main grade 3 or 4 toxicities were: diarrhea 13.5% and acne-like rash 10.3%. No grade 3 or 4 infusional or allergic reactions were reported. CONCLUSIONS: The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen.

Metastatic Colorectal Cancer. First Line Therapy for Unresectable Disease.

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed.