To investigate the clinical effects of laser acupuncture therapy for temporomandibular disorders (TMD) after ineffective previous treatments.2 in total. The visual analog scale (VAS) and maximal mouth opening (MMO) were evaluated before and after treatment.A retrospective observational study was conducted in 29 treatment-resistant TMD patients . Subjects were treated 3 times per week for 4 weeks with the Handylaser Trion , which delivered 0.375 J of energy (5 s) to ST7, ST6, and LI4 and 3 J (40 s) to each Ashi point, 7.5–26.25 J/cmp = 0.005) and to 0.47±0.84 for those with chronic TMD (p<0.001). The MMO significantly increased in patients with acute TMD  and in patients with chronic TMD .VAS analysis showed that the patients were free of pain at rest (endpoint) after 5.90±6.08 sessions of laser acupuncture for acute TMD and after 16.21±17.98 sessions for chronic TMD. The VAS score on palpation of the temporomandibular joint reduced to 0.30±0.67 for patients with acute TMD (Our study shows that laser acupuncture therapy improves the symptoms of treatment-resistant TMD. Further studies with a more appropriate design, involving long-term follow-up examinations in a larger patient sample, are needed to evaluate its efficacy. Temporomandibular disorder (TMD) is a collective term traditionally used to describe multiple disorders, including intracapsular disorders, true abnormalities of the temporomandibular joint (TMJ), and muscular disorders or myofascial pain dysfunction (MPD) syndrome The roles of electrophysical modalities and surgery in the management of TMD have not been fully elucidated Among the therapeutic procedures, low-level laser therapy (LLLT) has recently been proposed to reduce pain intensity and improve maximal mouth opening (MMO) in both acute and chronic TMD patients who had received no previous TMD treatment  The study was approved by the Human Ethics Committee of our hospital . This is a retrospective observational study in general practice. The patient's verbal informed consent for treatment was recorded on the medical chart. Our ethics committee approved the verbal consent procedure. Furthermore, the individual in this manuscript  has give2 in total.The patients were treated 3 times per week for 4 weeks  with the Handylaser Trion , ST6  was used to measure the pain intensity at rest  and upon digital palpation ; in contrast, chronic TMD patients required 16.21±17.98 therapeutic sessions before they could report a similar outcome . After 8Before treatment, all 29 patients reported a VASS score of 6.24±1.52, and VASP score of 7.45±0.94. The mean VASS score before LAT was 5.70±1.62 for acute TMD patients and 6.53±1.43 for chronic TMD patients. The mean VASP score before LAT was 7.10±0.97 for acute TMD patients and 7.63±0.90 for chronic TMD patients.p<0.001), and a VASP score of 0.41±0.78 upon palpation of the TMJ . The mean VASP score was 0.30±0.67 for acute TMD patients  and 0.47±0.84 for chronic TMD patients . The MMO for patients with acute TMD was 40.70±2.67 mm , whereas the MMO for patients with chronic TMD was 39.32±2.29 mm  qi to relieve pain. The combined use of these acupoints is therefore effective in activating blood and moving qi, anti-inflammation, and analgesia. In addition to stimulating Ashi points , pain results from blood stasis due to LAT is a noninvasive technique involving the stimulation of traditional acupoints, with low-intensity, non-thermal laser irradiation. The clinical application of LAT is widespread, although its mechanism is not well understood. LLLT has biologic effects, such as increased pain tolerance, due to changes in the potency of the cellular membrane; vasodilatation; reduction of edema; increase in intracellular metabolism; and acceleration of wound healing qi, LAT is not associated with somatosensation and has the advantage of being noninvasive and aseptic. Moreover, LAT is painless and safe because no heat is generated during the procedure. It is also more effective and requires less time than needle-based acupuncture Analgesia induced by LLLT is mediated by peripheral opioid receptors TMDs occur disproportionately in women of childbearing age in a female to male ratio of between 4:1 and 6:1; the prevalence decreases significantly in men and women above 55 years of age We found that TMD symptoms improved with LAT. Given the relative scarcity of research on this topic, long-term follow-up of these cases and further studies with a larger patient sample and an appropriate design are needed to elucidate the efficacy of LAT in treatment-resistant TMD patients.


ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population.Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K.Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the p = 8.99 × 10−13). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls . The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) . In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk . Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls : 1.77–2.74, ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.The  The rolonfirmed . Human gonfirmed . Sequencriations , severalype gene . In addiactivity . ABCG2 1al drugs . The assABCG2 gene have recently been recognized as clinical biomarkers to assess hyperuricemia and gout. Thus, a rapid method for detecting these mutations would be highly desirable.Furthermore, the SNPs Q141K and Q126X in the human ABCG2 gene with gout to investigate the association between ABCG2 dysfunction and gout risk in a Han Chinese male population.High-resolution melting (HRM) is used as a simple and reliable technology for genotyping. This method enables researchers to rapidly detect and categorize genetic mutations, such as SNPs, and to identify new genetic variants without sequencing. In the present study, we developed an HRM assay to detect three functional SNPs  and then assessed the genetic association of those SNPs in the 2.2.1.The genotype assignments of the three SNPs were determined via HRM curves using the sequenced samples as control genotypes. The studied SNPs were successfully genotyped using HRM analysis, as shown in p = 8.99 × 10−13). Regarding Q126X, the T allele was found on 4.7% of the chromosomes from the gout patients compared with 1.7% of the chromosomes from the controls . The results of the association study, shown in The genotype and allelic frequencies of the three SNPs  among the cases and controls were in Hardy-Weinberg equilibrium for all of the polymorphisms analyzed. For Q141K, the A allele was found on 49.6% of the chromosomes from the gout patients compared with 30.9% of the chromosomes from the controls . The haplotype frequencies in the gout group were compared with the control population and all of the frequencies <0.03 were ignored in the analysis. We found that the frequencies of the GCA, GTC, GCC and ACC haplotypes were 0.481, 0.044, 0.292 and 0.165, respectively, among the gout patients and 0.289, 0.017, 0.404 and 0.271, respectively, among the controls. The GCA and GTC haplotypes were more frequently present in cases than in controls and could be regarded as risk haplotypes  .2.3.Recently, it has been shown that genotyping for only the two dysfunctional variants, 126X and 141K, is sufficient to estimate the severity of ABCG2 dysfunction ,18,19, wp = 1.00 × 10−6) in the 3/4 ABCG2 transport function group and 5.51  in the 1/2 function group. A modest increase in gout risk was observed in genotype combinations with ≤1/4 function , and up to 6.2% of gout patients had this genotype. In contrast, only 2.3% of the normal males had the same genotype combinations  conferred an increased risk of gout (OR 2.40).This study is the first to examine the possible role of SLC22A12, SLC2A9 and ABCG2 are the most strongly associated with regulating the serum urate concentration [SLC22A12 and SLC2A9, and their associations with gout or hyperuricemia in different Chinese populations [Genome-wide association studies have identified several new and common genetic factors that affect serum uric acid levels. Most of these genetic factors are involved with the urate transporters located in the epithelial cells of the renal proximal tubules ,20,21. Aulations –26. HoweSLC22A12 and SLC2A9, ABCG2 is a secretory urate transporter gene. ABCG2 is expressed in the brush border membrane of the proximal tubules of the kidneys and plays a role in the apical secretion of urate [In addition to the absorptive transporter genes of urate . Additioof urate  and enhaABCG2 were associated with an increased risk for gout, whereas the minor A allele in V12M had a protective effect on susceptibility to gout. The Q141K SNP has been extensively studied; it has been found to impair protein-nucleotide binding stability [Consistent with the genetic susceptibility identified in gout patients in a cohort of Japanese individuals , we obsetability , which htability . This vatability . In thistability . These fThe other nonfunctional variant, Q126X, is consistently observed in certain Japanese and Korean cohorts ,32. Howen = 33) mutations were found that revealed that non-functional 126X dramatically increased gout risk (OR 2.91). The half-functional 141K also increased gout risk (OR 2.20). Matsuo et al. [Among the 352 patients with gout, Q126X heterozygous . The clinical features of the individuals enrolled in the study are summarized in 4.2.ABCG2 SNPs: V12M, Q126X and Q141K. ABCG2 SNP genotyping was performed via HRM. The primer sequences are shown in 2, 200 nM each primer, 200 μM dNTPs, 5 μM SYTO 9, 0.5 U of HotStarTaq polymerase  and PCR grade water in a 20 μL volume. PCR cycling and HRM were performed on a Rotor-Gene 6000™ . All of the reactions were performed under the following conditions: one cycle of 95 °C for 15 min; 40 cycles of 95 °C for 30 s, 55 °C for 30 s and 72 °C for 30 s; a melt from 75 to 90 °C was also performed at intervals (ramps) of 0.1 °C/s. An HRM curve analysis was performed using the Rotor-Gene 6000 1.7 software (Corbett Research).Genomic DNA was isolated from the peripheral blood lymphocytes of each patient using a QIAamp DNA Blood Kit  according to the manufacturer’s instructions. Primer sequences were designed to amplify a small fragment surrounding the polymorphism and to avoid amplifying other sequence variations. All of the oligonucleotide primers were obtained from Sango Biotech Co. . We selected three functional 4.3.To confirm the genotyping results, PCR-amplified DNA samples were selected and examined via DNA sequencing. The sequencing primers were the same primers that were used in the HRM assay. The amplicons were gel purified using a QIAquick gel purification kit . The DNA sequencing analysis was performed in an ABI PRISM 3130 genetic analyzer .4.4.http://analysis.bio-x.cn/myAnalysis.php). p Values less than 0.05 were considered statistically significant.The chi-squared test was used to analyze categorical data and compare the genotypes and allele frequency distributions. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Haplotype frequency analyses were performed using the SHEsis online software (5.ABCG2 gene for protein dysfunction will help implement risk-management systems for gout. Developing an understanding of renal transporters will provide interesting targets for the development of future gout therapies. The function of some ABC transporter mutants has reportedly been rescued by pharmacological chaperones [ABCG2 Q141K and Q126X polymorphism in gout may pave the way for pharmacological chaperones targeting ABCG2 as a potential new therapeutic target for gout. Moreover, risk assessment through genotyping only two SNPs with molecular technologies will provide a cost-effective screening strategy for personalized gout treatment that includes adequate prevention and effective therapy.Because gout leads to a significantly impaired quality of life and imposes high life-long medical costs, early genetic testing of the aperones ,36. The


Febrile seizures (FSs) are the most common neurological disorder observed in the pediatric age group. The present study provides information about epidemiological and clinical characteristics as well as risk factors associated with FS among Iranian children.On the computerized literature valid databases, the FS prevalence and 95% confidence intervals were calculated using a random effects model. A metaregression analysis was introduced to explore heterogeneity between studies. Data manipulation and statistical analyses were performed using Stata10. The important viral or bacterial infection causes of FSs were; recent upper respiratory infection 42.3% (95% CI: 37.2%–47.4%), gastroenteritis21.5% (95% CI: 13.6%–29.4%), and otitis media nfections15.2% (95% CI: 9.8%- 20.7%) respectively. The pooled prevalence rate of FS among other childhood convulsions was 47.9% (95% CI: 38.8–59.9%). The meta–regression analysis showed that the sample size does not significantly affect heterogeneity for the factor ‘prevalence FS’.Almost half of all childhood convulsions among Iranian children are associated with Febrile seizure. Febrile seizure (FS) is the most common neurological disorder observed in the pediatric age group. It has been reported that one in every 25 children in the population will experience at least one FS during their childhood . The IntThe direct cause of FS is unknown, but the most important associated factors are fever, epilepsy, hypoglycemia, hypocalcaemia, head injury, poisoning and drug overuse, respiratory infection, or gastroenteritis –5. The aChildren who have focal or lateralized FS, prolonged (particularly lasting more than an hour) or seizures that affect only a part of the body, or that recur within 24 hours, are more hazardous .Many studies have already revealed etiology, prevalence, and geographical variation of apparent FSs among Iranian children across the country –13. EvenThe search strategy, selection of publications, and the reporting of results for the review were conducted in accordance with the PRISMA guidelines. Literatures related to FS characteristics in Iranian children were acquired through searching Scientific Information Databases (SID), Global Medical Article Limberly (Medlib), Iranian Biomedical Journal (Iran Medex), Iranian Journal Database (Magiran) as well as international databases including PubMed/Medline and ISI Web of Knowledge were searched for published data related to FS in Iran. The search strategy was limited to the Persian and/or English languages and articles published until Feb 2012 were considered. All publications with medical subject headings (MeSH) and keywords in the title, abstract, and text for words including febrile seizure were investigated. Iranian scientific databases were searched only using the keyword ‘febrile seizure’, as these databases do not distinguish synonyms from each other and do not allow sensitive search operations using linked terms such as ‘AND’, ‘OR’, or ‘NOT’. Consequently, single keywords were searched in inner databases. MeSh keywords including seizures, pediatrics and Iran were assessed combined with the operator “OR” vs “AND” for outer databases. The search string in PubMed was (Seizures [Title]) OR Pediatrics [Title]) AND Iran [Affiliation]) Selection and quality assessment of articlesAll identified papers were critically appraised independently by two independent reviewers.Disagreements were resolved through discussion. Appraisal was guided by a checklist assessing clarity of aims and research questions. The inclusion criteria were as follows: 1. Studies in the mentioned databases with full text, despite the language of original text; 2. Hospital– based data; 3. Reporting among Iranian children; and 4. Studies with overlapping time and sample collection from the same origin. The following exclusion criteria were also applied: 1. inappropriate design; 2. Inadequate reporting of results, i.e., studies not reporting prevalence data for relevant outcomes.Data extractionData were extracted using a standardized and pre–piloted data extraction form. Data extraction was undertaken by the first reviewer and checked by a second reviewer. However, the process was discussed and piloted by both reviewers. All identified papers were critically appraised independently by both reviewers. Disagreements were resolved through discussion. Appraisal was guided by a checklist assessing clarity of aims and research questions. Information was extracted from author, title, year, setting of study, sample selection, sample size, study type, seizure types, age, and prevalence. Therefore, risk of bias for inadequate reporting was reduced. All data– abstraction forms were reviewed and eligible papers were entered into the meta–analysis.Statistical analysisThe random effects model was used for combining results of studies in meta–analysis. Variance for each study was calculated using the binomial distribution formula. The presence of heterogeneity was determined by the Der Simonian–Laird (DL) approach .Significance level was <0.1 and I2 statistic for estimates of inconsistency within the meta–analyses. The I2 statistic estimates the percent of observed between–study variability due to heterogeneity rather than to chance and ranges from 0 to 100% . A value of 0% indicates no observed heterogeneity while100% indicates significant heterogeneity . For thiOverall, 115 studies  were identified. Of them, 94 studies were excluded based on the inclusion and exclusion criteria . FinallyEtiology and prevalence of febrile seizuresThe important viral or bacterial infection causes of FSs were recent upper respiratory infection42.3% (95% CI: 37.2%–47.4%), gastroenteritis21.5% (95% CI: 13.6%–29.4%), otitis media infections15.2% (95% CI: 9.8%–20.7%), pneumonia8.7% (95% CI: 5.4%–11.9%), urinary infections3.2% (95% CI: 1.3%–5.0%), rosella 2.0% (95% CI: 0.02%–3.8%), and other infections12.8% (9.8%–15.8%). The pooled prevalence rate of childhood febrile seizure compared to other childhood seizures in Iran was 47.9 %(95% CI 12.3–29.5%) .Prevalence of simple and complex febrile seizure were 69.3% (95% CI: 19.6–31.0) and 28.3% (95% CI: 59.5– 79.0), respectively. Generalized seizures are classified into a number of categories depending on their behavioral effects. Tonic–colonic seizures the prevalence rate among other types of generalized seizures was 78.9% (95%CI: 68.8%–89.2%).. Geographical variation of febrile seizuresA significant geographic discrepancy on prevalence of FS was also observed in different parts of the country.Subgroup analysis based on the type of climate showed no interaction with prevalent of FS. Prevalence rate of FS among other childhood convulsions in central Iran was 40.03% (95% CI: 37.09%–42.07%), in the east it was 59.4% (95%CI: 38.2%–80.7%), 44.1% (95% CI: 37.4%–50.8%) in the south, and 57.5% (95% CI: 49.1%–65.9%) in western of Iran. According to the data, the lowest prevalence was observed in north of the country 33.0% (95% CI: 24.5%–41.5%).Meta–regression analysisMeta–regression, thus, helps explore several possible reasons for the observed heterogeneity among the studies Meta–regression showed an association between year of study and prevalence rate of FS as well as it shows causes of the variability in the results of studies. Meta- regression showed variability in prevalence of FS a non significant effect for sample . Therefore studies with large sample size show prevalence rate of FS high in comparison with studies with small sample size. Meta-regression analysis found that year conducted of the studies significantly affects heterogeneity for the factor ‘prevalence rate FS’ . Publication bias is the term for what occurs whenever the research that appears in the published literature is systematically unrepresentative of the population of completed studies. There was no evidence of publication bias  so we tried considered the most of published articles in this subject.This systematic review aimed to provide epidemiological characteristics of FSs based on 21 separate samples (from 115 publications) based on 4599 neonates. The pooled prevalence of childhood febrile seizures (among other convolutions) in Iran was 47.9% . Complex FSs was seen in 28.3% (95% CI: 59.5–79.0) of patients in this study, although other studies have reported a range of prevalence 6.7%–35% , 34. ThiAccording to the national epidemiological survey, the prevalence rate of FSs rate has been decreasing from childhood to adulthood in community trials .This is Tonic-colonic seizures the prevalence rate among other types of generalized seizures was 78.9% (95%CI: 68.8%–89.2%).Generalized seizures are classified into a number of categories depending on their behavioral effects. Tonic-colonic seizures are most commonly associated with epilepsy and seizures in general , 37. In Our study is the first systematic review and meta-analysis that preformed to measure the risk of bacterial infection causes in children with FSs in fewer than for six–year age group. According to the results, urinary infections were 3.2 %( 95% CI: 1.3%–5.0%) in the previous study conducted by Lee et al (1991) and Bauchner (1987).There were some considerations for bacterial infection playing a role in incidence of FSs, frequency of urinary tract infection was5%, and 1.7%, respectively , 7. Bacterial meningitis was very uncommon in children diagnosed with FSs inconsistent with our results. Results in this systematic review showed that 8.7% (95% CI: 5.4%–11.9%) were positive, for Streptococcus pneumonia in comparison with Teach et al (1999) whom reported 2.9% (95%CI 0.6–5.2) in children with FSs .Some limitations in the present study need to be addressed. It was an observational study and patients were not randomly selected. Therefore, selection bias and confounding seems to be expected. Meanwhile, the authors’ ability to assess the quality of studies was limited by the fact that many studies failed to offer detailed information of selected subjects or valid data on important factors. Our analysis also suggests the need for large population-based incidence studies of febrile seizure, particularly in children under six year age, to generate more accurate estimates as well as provide a reasonably robust assessment of heterogeneity.


We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial.Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 13 (35.1%) patients, respectively. The most frequent adverse events were asthenia (36.8% vs. 37.8%), dehydration (5.3% vs. 2.7%), diarrhea (71% vs. 81.1%), hyperglycemia (13.1% vs.18.9%), and skin-related toxicities (92.1% vs. 86.4%).The addition of dalotuzumab to erlotinib did not improve efficacy outcome in patients with refractory advanced NSCLC. Insulin-like growth factor 1 receptor (IGF1R) is overexpressed in a wide variety of human malignances, including non-small-cell lung cancer (NSCLC). Additioin vitro and down-regulation of cell surface receptors by 75% to 90%. According to previous phase I trials, dalotuzumab reached a biologically optimal concentration when a dose of 10 mg/kg/week was administered and plasma IGF1R levels increased after dalotuzumab administration independently of the administered dose[Dalotuzumab, formerly MK-0646, is a humanized IgG1 anti-IGF1R monoclonal antibody (MoAb) that selectively binds to IGF1R without binding to insulin receptor (IR). By binding to the extracellular domain of the receptor, dalotuzumab blocks ligand binding and inhibits receptor autophosphorylation by up to 90%, leading to a block in IGF1- and IGF2-mediated cell proliferation We hypothesized that dual inhibition of the EGFR and IGF1R pathways could prove beneficial in NSCLC patients. We therefore performed a phase I/II trial testing the combination of erlotinib and dalotuzumab in unselected, advanced NSCLC patients who were refractory to previous chemotherapy.This study was designed as a phase I/II trial. Patients were recruited from five centers for the phase I trial and 20 centers for the phase II trial from Europe, the United States and Canada Figure . PatientThe phase I trial consisted of a safety and tolerability run-in study testing dalotuzumab at two dose levels that had previously been demonstrated as safe with an adequate pharmacodymamic profile (5 and 10 mg/kg). Erlotinib was administered as a daily oral dose of 150 mg and dalotuzumab as a 60-minute weekly intravenous infusion. Dalotuzumab was administered following a "3 + 6" escalation scheme design, with an anticipated intermediate dose level of 7.5 mg/kg in the event of intolerable toxicity at the higher dose level.In the phase II trial, patients were randomized to the control or experimental arm. Patients in the control arm received erlotinib alone, and those in the experimental arm received erlotinib plus dalotuzumab at the dose level determined by the phase I trial. Both dalotuzumab and erlotinib were provided by the sponsor of the trial, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc., Whitehouse Station, NJ, USA.9/L). Non-hematologic DLT were defined as any ≥ grade 3 non-hematologic toxicity, with the specific exception of grade 3 skin toxicity, nausea and/or vomiting, diarrhea, dehydration or hyperglycemia that in the opinion of the investigator occurred in the setting of inadequate compliance with supportive care measures and lasted less than 48 hours.For the phase I trial, the primary objective was to determine the safety and tolerability of erlotinib in combination with dalotuzumab in patients with advanced NSCLC. For clinical assessment of toxicity, patients were evaluated weekly and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. For theFor the phase II trial, the primary efficacy endpoint was progression-free survival (PFS); secondary endpoints were response rate, overall survival (OS) and safety and tolerability. PFS was defined as the time from randomization until either radiographic evidence of disease progression or death due to any cause, whichever occurred first. OS was defined as the time from randomization to death due to any cause. Response was graded according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 guidelines. RadiogrFrom 19 Mar 2008 to 5 Jun 2009, 23 patients were enrolled in the phase I trial. Four patients were included in the first dose cohort  and sixteen in the second dose cohort . From 11 Aug 2010 to 24 Mar 2011, 83 patients were enrolled in the phase II trial. Eight were excluded from the analysis leaving 75 patients, 38 in the control arm and 37 in the experimental arm. Clinical characteristics for patients in both phases are summarized in Table In the phase I trial, the most common toxicities were those related to erlotinib. Thirteen patients (65%) developed diarrhea (two grade 3), and 50% suffered ≤ grade 2 rash or acneiform dermatitis  in 35 92.1%) patients in the control arm and 32 (86.4%) patients in the experimental arm, asthenia in 14 (36.8%) and 14 (37.8%) patients, dehydration in 2 (5.3%) and 1 (2.7%), and diarrhea in 27 (71%) and 30 (81.1%), respectively. Hyperglycemia was seen in 5 (13.1%) patients in the control arm and 7 (18.9%) in the experimental arm. Grade 3-5 hyperglycemia was observed in 4 (10.52%) and 4 (10.81%) patients, respectively. Although grade 3 to 5 adverse events are reported together, no grade 5 hyperglycemia was observed. One death, probably related to interstitial lung disease, was reported in the erlotinib arm (2.63%) (Table .1% patiep =0.268). OS was 10.2 months in the control arm and 6.6 months in the experimental arm  were observed in the control arm (7.9%) and one (2.8%) in the experimental arm, and there were no complete responses in either arm. All four patients with PR had adenocarcinomas. Twenty-one 55.3%) patients in the control arm and 21 (56.7%) in the experimental arm had stable disease (SD) as best response. Stable disease between 3 and 12 months was attained by seven patients in each arm , and SD lasted longer than 12 months in three and two patients, respectively . At the time of the first evaluation after crossover, six patients had progressed and no response assessment was done in four patients. None of the patients who crossed over harbored Although the present study has confirmed the general safety and tolerability of the combination of erlotinib plus dalotuzumab in patients with advanced NSCLC, no benefit was observed in terms of efficacy. In fact, the RR for the combination of erlotinib and dalotuzumab was lower than the 8-10% obtained with standard therapies in recurrent advanced NSCLC, including not only chemotherapy but also EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. Even thAs expected from previous dose-escalation studies, toxicity was mild and mainly related to erlotinib–14.The major concern regarding IGF1R inhibition is the risk of hyperglycemia. In a previous trial of figitumumab, 15% of patients previously had been diagnosed with diabetes, and grade 3-5 hyperglycemia rates were almost 20% in both arms of the trial[The cumulative experience of using MoAbs directed against IGF1R in combination with different therapies in unselected NSCLC patients raises the question of why promising evidence in the laboratory has failed repeatedly when translated into the clinical setting. One reason could be the excessive toxicity of the combinations. For example, when anti-IGF1R MoAbs were combined with chemotherapy or erlotinib, toxicity may well have prevented the optimum synergistic effect. Conversely, and similar to our findings, the toxicity profile was quite acceptable with erlotinib plus R1507. In factKRAS or EGFR mutations. Patients with KRAS mutations had a higher 12-week PFS rate than those with wild-type KRAS (36% vs. 0%) when treated with erlotinib plus R1507[KRAS mutations had progressive disease. EGFR mutations did not correlate with outcome to erlotinib plus R1507[EGFR mutations was allocated to the experimental arm. Although this patient had stable disease lasting seven months, it is impossible to draw any conclusions from this individual case.A second explanation for the failure of dual IGF1R and EGFR inhibition may lie in the influence of us R1507. In the us R1507. In the In conclusion, the present study has shown that although the combination of dalotuzumab plus erlotinib is generally tolerable, it does not confer greater benefit than erlotinib alone in advanced NSCLC patients who are EGFR-TKI naïve. The cumulative results of this and other studies of dual IGF1R and EGFR inhibition indicate that further investigation of such combinations is not warranted in unselected NSCLC patients.Written inform consent form included the patient authorization for publication of data obtained from the present trial.Teresa Moran: Presented in part at the 100th Annual Meeting of the American Association for Cancer Research (April 2009) and at the IASLC 14th World Conference on Lung Cancer (July 2011).


Chronic hepatitis is a major public health problem. Hepatitis B virus is the primary cause, and Hepatitis B and C together are responsible for 60% of cirrhosis and 80% of hepatocellular carcinomas. This study measured the prevalence of HBsAg among Senegalese military to develop an appropriate strategy to prevent cirrhosis and hepatocellular carcinoma.We conducted a descriptive cross-sectional study among Senegalese military aged 25 to 60 years. A sample of 1224 participants was selected following a two-level-stratification. The mark of surface HBs antigen using chemiluminescence concerned 1195 participants. The presence of HBsAg was analyzed according to age, marital status, alcohol consumption and glomerular filtration rate. Epi-info6fr and R software were used, respectively, for data capture and analyses. A Chi-square test was performed to compare proportions considering a significance level of 5% and a confidence interval of 95%.The average age was 39.8 ± 9.2 years. Participants in the age groups of 25–34 years, 45–60 years and 35–44 years were respectively 30.7%, 34.4% and 34.9% of the sample. Married persons represented 82.6% of participants and 17.08% were single. Most participants were educated (99%), and 56% had reached at least secondary school level. Alcohol consumption was at 11.5%. The HBsAg prevalence rate was 10.8% [9.1% to 12.7%] with a significant difference between age groups (P < 0.001), which ranged from 5.6% for 45–60 years, 9.62% for 25–34 years to 16.9% for 35–44 years. Marital status and alcohol consumption did not affect the carriage of HBsAg. HBsAg prevalence was more common among participants who had a glomerular filtration rate greater than 90 ml/min. Transaminases rate exceeded the normal threshold for 43 participants (3.6%); the increase was 6.6% [2.7% to 11.8%] for HBsAg carriers and 3.2% [1.2% to 6.7%] for alcohol users.The high prevalence of HBsAg in the military requires the implementation of an effective prevention and care program to reduce the risk of cirrhosis and hepatocellular carcinoma and contribute to reducing the burden of communicable diseases, such as hepatitis and HIV/AIDS, and non-communicable diseases. Chronic viral hepatitis is a worldwide major public health problem, particularly in developing countries that are facing a range of barriers to contain the epidemic -5. ApproThis high prevalence justifies the implementation of a national program against hepatitis and the integration of the vaccine in the Expanded Immunization Program.The fight against viral hepatitis B is not well structured in the army. The current situation of infection prevalence is unknown. Therefore, one of the objectives of this study was to determine the prevalence of HBsAg in the military to develop strategies for cirrhosis and hepatocellular carcinoma prevention.We performed a descriptive and analytical cross-sectional study in the Senegalese military in the period from May 2013 to February 2014.Military aged men 25 to 60 years who were present in the country during the survey were included in the study.Soldiers who had less than 2 years of duty in the military or were unable to answer the questions were excluded.The enrolled population was divided into three (3) age groups: 25–34, 35–44 and 45–60 years. The survey was conducted in all Senegalese regions.The sample size was calculated in the framework of STEPS investigation in the military, which provided an estimate of 1,296 men who were divided into three strata. Each member was consistently linked to only one training unit. Therefore, we proceeded with a first selection to determine the number of respondents in each training unit using the human resources central database. A second simple random sampling was performed from the local unit file to identify participants for each stratum.Information regarding the socio-demographic  and behavioral characteristics  of the subjects were collected using a revised STEPS questionnaire .For each participant, 5 ml of venous blood taken from the elbow crease were collected in a dry test tube and centrifuged. Sera were decanted and maintained at 4°C if the analyses were not performed within 4 hours.HBsAg was initially detected using the DETERMINE HBs Agkit ® (Alere) and ARCHITECT HBsAg QUANTITATIVE II (Abbott Diagnostics) ®. In a second step, measurement of transaminases (AST and ALT) was performed using the controller from Biochemistry Cobas400 ® of Roche Diagnostic laboratories and the Spectrophotometer CYPRESS diagnostic ®.Chronic renal disease was defined by a glomerular filtration rate expressed in ml per min. The assessment of the glomerular filtration rate (GFR) was performed using the Modification of Diet in Renal Disease (MDRD) formula . Two staBiochemical results were reported on the questionnaire.Data were entered in Epi-info6 software and analyzed using R software. The Chi-square test was performed to compare proportions with 5% for the significance level and 95% for the confidence interval (CI).Participation was voluntary. Each participant signed a consent letter at the beginning of the investigation and had the opportunity to stop participating at any stage of the process. All results were returned to the subjects, and participants who were detected as HBs antigen carriers were referred to specialists for treatments.Instead of the 1,296 participants who were planned to be involved in the survey, 1,224 soldiers were enrolled, and 1,195 were tested for HBsAg and transaminase levels. The lack of HBsAg research for 29 participants was related to the mobility of soldiers and stock out of test, while not their status.The mean age was 39.8 years, and it was equal to the median . The sample consisted mostly of men with a sex ratio of 31.2, which followed the personnel structure in the armed forces. Soldiers were more represented (48.0%), followed by non-commissioned officers (45.6%) and officers (6.4%). Most participants were married (82.6%), singles represented 17.08% and other 0.32% of the sample. Serere (25.0%) and Ouolof (24.3%) ethnic groups were more frequent, followed by Diola (18.3%) and Pulaar (16.3%). Almost all respondents were literate (99.1%), and 56.0% had at least achieved secondary level at school (See Table The GFR identified two stages of chronic kidney disease (CKD) among participants: it was higher than 90 ml per min for 68% of participants (CKD stage 1) and between 60 and 90 ml per min for 32% (CKD stage 2).The prevalence of HBsAg was estimated at 10.8% [9.1% to 12.7%], and it varied significantly between the different age groups (P < 0.001). It was 9.62% [6.8% to 13.1%], 16.90% [13.4% to 20.8%] and 5.60% [3.6% to 8.3%] for the age groups 25–34, 35–44 and 45–60 years, respectively ; it was 6.6% [2.7% to 11.8%] among carriers of HBsAg and 3.2% [1.2% to 6.7%] among drinkers. However, an increase two times greater than normal was exceptional.HBsAg prevalence is a public health problem, especially in sub-Saharan Africa ,19. An aA study in Nigeria estimated an HBV seroprevalence 14.6% with a higher frequency in the 20-30-year-old age group [The military is considered a gateway group for sexually transmitted diseases (STDs) and HIV/AIDS. The observed prevalence of HBsAg in this study confirms the results of the national survey of combined HIV surveillance in the military, which had shown prevalence figures identical to the general population .HBsAg seroprevalence was 12.3% and 7.7% in participants with CKD stage 1 and stage 2, respectively. Diouf et al.  reportedSome authors attempted to link the carrying of HBsAg and CKD -30. In oThis study was conducted among soldiers who were selected through incorporation screening based on comprehensive clinical data that satisfied medical fitness criteria to serve in the armed forces. However, this medical screening did not include liver function tests. Accordingly, symptomatic carriers should have been eliminated. In addition, the sample was essentially composed of men. The cross-sectional nature of the study did not allow a demonstration of a causal relationshipThe highly endemic HBsAg prevalence mentioned in this study is similar to the prevalence in the general population. This finding makes sense because no specific measures were taken to expect a different situation until now. The detection of HBsAg is not yet introduced into the army incorporation screening.The interest of this work was to promote the introduction of Hepatitis B prevention in the overall fight against non-communicable diseases in the army program and communicable diseases, such as HIV/AIDS and hepatitis. Conducting awareness campaigns among the military, periodic screening, improving access to treatment and the training of health personnel will be the major components of this program, which seeks to reduce cirrhosis and hepatocellular carcinoma morbidity and mortality and the burden of non-communicable diseases.


Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. It is unclear why this dual relationship is observed. We here study whether body mass index (BMI) affects (a) age at breast cancer diagnosis and (b) the probability of being diagnosed with a specific breast cancer phenotype, taking menopausal status into account.All patients with non-metastatic operable breast cancer from UZ Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n=7020). For statistical analysis, linear models and logistic regression were used to study respectively the association between BMI and age at diagnosis and BMI and breast cancer phenotype by menopausal status. Where necessary, a correction for the relation between BMI and age will be applied, based on publicly available data from the Belgian Health Interview Surveys.There was a quadratic relationship between BMI and age at breast cancer diagnosis studying the overall population (p<0.0001). A 5kg/m2 increase in BMI was associated with the following increases in age at diagnosis: +1.8y (95% CI 1.4-2.3y) at BMI=18, +1.2y (95% CI 0.95-1.5y) at BMI=23 and +0.6y (95% CI 0.4-0.9y) at BMI=28 (corrected for menopause). Correction for the relation BMI with age are ongoing and not yet available in this abstract.The relationship between BMI and the probability of being diagnosed with specific breast cancer phenotypes will be presented during the congress.The relation between BMI and age at diagnosis and between BMI and the chance of being diagnosed with specific breast cancers is complex. New analyses taking into account the relation between BMI and age are ongoing. We look forward to present the final results on the congress.


Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13).The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate.P =  0.0046) whereas VES-13 was more specific . Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival.Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy. Cancer occurs predominantly in the older population, yet patients over 60 years are significantly under-represented in clinical trials in oncology Several recent reports have strongly suggested that different components of comprehensive (CGA) or multidimensional geriatric assessment (MGA) can be useful in oncology to predict early death In response to a French National Cancer Institute (INCa) call for proposal, and following escalating appeals for validated geriatric screening tools We subsequently launched the national ONCODAGE multicenter study to validate the G8 tool prospectively. The primary objective was to validate the G8 instrument as a screening tool to identify older cancer patients (>70 years) requiring geriatric assessment by comparing with a reference test of MGA. Secondary objectives included assessing the diagnostic accuracy of G8 in specific sub-populations, the diagnostic accuracy of VES-13 and comparing it to that of G8, the within-patient reproducibility of both tests, and the prognostic value of both tests in terms of 1-year survival. Additional exploratory analyses included the assessment of the diagnostic accuracy of G8 and VES-13 using a modified reference test , and sensitivity analyses to assess the impact of missing questionnaires in the definition of the reference test.We recruited patients from 23 health care facilities, including the 15 INCa-accredited Regional Coordination Units for Geriatric Oncology. Patients eligible were older than 70 years and were included either before any first-line treatment, or between any two steps of a pre-defined first-line treatment sequence  for various types of histologically-confirmed cancer /head and neck, breast, prostate, and non-Hodgkin's lymphomas (NHL)). Patients with known central nervous system metastases were excluded. Patients were informed of the study and provided their signed informed consent prior to enrollment and G8/MGA assessment. The protocol was approved by the regional ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre Mer III), and was conducted in accordance with the Declaration of Helsinki, Good Clinical Practices .At the first visit after enrollment, patients received a full clinical examination and completed the G8 test with a nurse, a clinical research assistant (CRA), or a physician. The G8 consists of eight items: patient age , and seven items from the original 18-item MNA . The total score ranges from 0 to 17, with lower scores indicating a higher risk of impairments.VES-13 is a self-administered questionnaire that was completed during the first visit after enrollment. For three pre-identified centers, patients also filled in the questionnaire at the following geriatric visit. VES-13 consisted of four groups of questions: age, self-perceived health, difficulties to perform six specific activities, and difficulties to perform daily living tasks due to health concerns. The score ranged from 0 to 10 and a score ≥3 was considered to show impairment.Patients underwent a geriatric evaluation in the month following the completion of G8 and VES-13 (+/- seven days) before treatment began. The nurse completed six of the seven instruments of the MGA as already described Abnormal scores for each instrument were established according to the following published cut-offs The reference test was defined as normal if scores for the seven instruments were available and normal. In a subsequent exploratory analysis, the reference test was modified and we considered the reference test to be ‘impaired’ if the seven instruments were available with two or more abnormal scores, or if the score for two or more instruments could not be calculated due to one or more missing items or unavailable instruments.We defined the following populations: the included population, the eligible population, and the eligible and evaluable population. The included population corresponded to all patients included, regardless of eligibility and availability of G8 and MGA results. The eligible population included all patients who did not violate any eligibility criteria. The eligible and evaluable population for diagnostic accuracy assessment was defined as all eligible patients, for whom G8 as well as at least one instrument of MGA were available and were administered less than one month apart (± one week).Diagnostic accuracy was measured by the classification probabilities (sensitivity and specificity), positive and negative predictive values (PPV and NPV), and positive and negative diagnostic likelihood ratios (+/-DLR). The McNemar test was applied to compare the sensitivity of G8 and VES-13, as well as their specificity.The required sample size was estimated based on our preliminary work The study population was described in terms of clinical and demographic characteristics with counts and percentages for qualitative variables and summary statistics  for quantitative variables. Sensitivity, specificity, PPV, NPV, +/-DLR and area under the ROC curve were estimated with their (two-sided) 95%CI.v abnormal score) Reproducibility analysis was based on estimation of the Kappa agreement statistics for dichotomous data , and the G8 score. Significant factors at the univariate stage (p<5%) were subsequently included in a multivariate model. The final model was based on a manual stepwise backward selection approach with statistical significance set at 5%. An exploratory model was also calculated examining the prognostic value of the reference test MGA score. Hazard ratios (HR) are reported with 95%CIs.The prognostic value of the screening tools was assessed by analyzing one-year overall survivals using a Cox proportional hazards model. Candidate prognostic factors included age, sex, ECOG PS (Eastern Cooperative Oncology Group performance status), stage . A further 162 patients were excluded from analyses due to protocol violations, participation withdrawals, missing G8 or MGA . Delay bAfter the first 779 enrollments, we convened an international independent data monitoring committee to examine recruitment across different tumor sites and discuss initial statistical hypotheses. No modification was proposed by the committee of experts.On average, it took one hour to complete the MGA overall  and it was completed in less than one and a half hours for 75% of patients. Almost all (91.6%) patients completed the seven instruments entirely. Rates of completion varied across instruments from 97.0% for the GDS15 to 99.8% for the ADL and MNA. The proportion of patients with abnormal scores varied from 15.3% for the ADL to 47.8% for the IADL . SimilarOverall, 1151 (80.2%) eligible and evaluable patients were considered to have an impaired reference test. This was determined for the large majority of patients  who had an abnormal score on one or more of any of the seven available instruments. For the remaining 120 patients (10.4%), the score from at least one instrument was missing and could not be determined. For 85 of these patients, although at least one score was missing, the score on one of the remaining instruments was abnormal so their reference test was considered impaired. For the remaining 35 patients with only five or six available scores, all available scores were normal. Their reference test was considered to be impaired for the purposes of the main analyses .Of the 1031 patients overall with altered scores, 306 (29.7%) had an altered score on one instrument, 236 (22.9%) on two, 173 (16.8%) on three, 132 (12.8%) on four, 94 (9.1%) on five, 73 (7.1%) on six and 17 (1.6%) on seven.v 75.1% for non-metastatic (M0)) and across tumor site . At least one geriatric intervention was proposed by the geriatrician at the end of MGA in 72.2% of the cases and between one and four per patient in 64.3% of the population. The most frequently proposed interventions were nutritional support , home assistance , standard treatment adaptation , psychological support  and physiotherapy .Proportions of subjects with at least one impaired score varied across disease stage (93.0% for metastatic patients (M1) In the eligible and evaluable population (n = 1435), G8 was mostly administered by a nurse or CRA (87%) and less frequently by a physician (12.9%). It took an average of 4.4 minutes to complete  with 98.7% completed in ten minutes or less. The final G8 scores ranged from 1.5 to 17, with 68.4% of patients showing impaired scores (≤14). The proportions of patients with impaired G8 scores varied according to disease stage (85.6% for M1 and 63.0% for M0) and tumor site .The diagnostic accuracy of G8 is outlined in G8 was abnormal in 94.4% abnormal MNA (592/627), 93.6% abnormal ADL (205/219), 91.3% abnormal TGUG (293/321), 84.8% abnormal GDS15 (391/461), 84.5% abnormal IADL (580/686), 80.5% abnormal MMSE (235/292) and 77.4% abnormal CIRS-G (466/602). Overall, 136 patients with Grade 3-4 comorbidities had normal G8 scores; this included mainly patients with one severe comorbidity (58.1%) the most prevalent being vascular (49.3%), cardiac (15.4%), respiratory (14%) and metabolic (11.8%).Among false negative results, 53.1% had only one abnormal MGA questionnaire  as compared to 18.4% in the true positive group .v 71.3% (M0); Specificity  =  43.8% (M1) v 65.7% (M0); PPV  =  95.8% (M1) v 86.3% (M0); NPV  =  19.4% (M1) v 43.0% (M0))  0% (M0)) . Sensiti0% (M0)) .A subgroup analysis explored the influence of the presence or absence of at least one treatment in the last three months. G8 sensitivity or specificity did not appear to be particularly affected by this factor.In the eligible and evaluable population (n = 1435), VES-13 was mainly administered with the assistance of a nurse or CRA (78.7%), with 12.1% being completed by the patient alone, and 8.8% with the assistance of the physician. On average, it took 5.7 minutes to complete , with 98% completed in less than 10 minutes.v 65.4% (M0); Specificity = 43.8% (M1) v 75.6% (M0); PPV = 95.1% (M1) v 89.0% (M0); NPV = 10.8% (M1) v 41.9% (M0)).VES-13 showed impaired scores in 60.2% of patients. Sensitivity and specificity were 68.7% and 74.3%, respectively . The AUCVES-13 was abnormal in 94.1% abnormal ADL (206/219), 87.5% abnormal TGUG (281/321), 81.5% abnormal IADL (559/686), 80.9% abnormal GDS15 (373/461), 77.5% abnormal MNA (486/627), 75.3% abnormal MMSE (220/292) and 72.4% abnormal CIRS-G (436/602). Overall, VES-13 was normal in 166 patients with Grade 3–4 comorbidities, which included mainly patients with one severe comorbidity (51.2%), the most prevalent being vascular (45.2%), cardiac (21.7%), respiratory (14.5%) and psychiatric (12.7%) comorbidities.Among false negative results, 45.3% had only one abnormal MGA questionnaire  as compared to 18.1% in the true positive group .The G8 test had a better sensitivity than VES-13  at the expense of a lower specificity .Reproducibility for both G8 (n = 1429) and VES-13 (n = 251) was good: Kappa = 0.65, (95%CI 0.61 to 0.70), and Kappa = 0.64, (95%CI 0.54 to 0.73), respectively. When investigating the items of each instrument, the Kappa coefficient varied from excellent for objective criteria such as age  to poor for subjective criteria such as self-rated health .Among the 1435 patients eligible and evaluable, information on vital status was available for 1365 patients with a median follow-up of 377 days (95%CI 373 to 381). At the univariate level, all candidate prognostic factors were statistically significant . In the In a model including all significant candidate prognostic factors and MGA result, abnormal MGA was found to be significantly associated with poorer survival at one year .Using a modified definition of the reference test , 56.7% of patients (813 cases) were considered abnormal. G8 sensitivity was 86.5% and specificity 55.3% . The AUCFor 35 out of 1435 patients, scores for at least five instruments were available and normal. However, MGA was considered abnormal due to the one or two not fully completed questionnaires despite normality on all other available instruments. To specifically account for these patients with missing questionnaires, we investigated two modified definitions of the reference test. First, if two or less questionnaires were missing but all other MGA instruments had normal scores, then the reference test was considered normal, otherwise the definition of our primary reference test prevailed. Second, the reference test was considered normal as long as all completed questionnaires had a normal score (regardless of the number of missing questionnaires).Using these new definitions of the reference test did not cause changes in the diagnostic performances of G8 , so the primary definition with these 35 patients considered as abnormal reference tests was maintained.This is the first study designed to determine the diagnostic accuracy of the G8 questionnaire and, by far, the largest prospective cohort available to validate a screening tool in geriatric oncology with previously published studies including 41–419 patients v ≥1 abnormal MGA tests − 80% of the population), sensitivity, of foremost importance for a screening tool, was good at 76.5% and specificity was satisfactory at 64.4%. With the modified reference test , sensitivity of G8 was improved to 86.5% while specificity was reduced to 55.3%.The proportion of G8 impaired scores was 68.4%. In the validation against the reference test  needs to be considered when generalizing the results. Consequently, we provide diagnostic accuracy estimations per tumor location in the subgroup analyses. There was a significant proportion of patients (9.1%) with missing metastatic status for whom physicians decided not to perform usual pre-treatment work-up because of low risk of metastasis and age.Our target population is clearly identified with simple, quantitative criteria: at least one or two abnormal questionnaires among seven consensus geriatric tools. However, while MGA appears the best available and most reproducible instrument to identify it, this target population (reference test) has no unbiased definition. Two different thresholds considering one v 57.1% for VES-13), although the AUC was not statistically different While considering sensitivity as the most important criteria , we believe G8 to be the best available tool, although VES-13 remains a good alternative with lower sensitivity but higher specificity. In this study we assessed the performance of VES-13, which is currently the most widely-used screening tool for older cancer patients, although it was originally designed to predict functional decline or death over a two-year period in community-dwelling elders. The higher sensitivity of the G8 screening tool has been reported in the literature. A previous independent report of 113 patients found greater sensitivity for G8  along with male sex , poor ECOG status  and metastatic disease . The definition of the reference test was supported by the association observed between impaired MGA and poorer survival at one year in the exploratory survival analyses . With specificity of 64.4% and NPV of 40.3%, the G8 tool still needs improvement. The somewhat low reproducibility observed for questions such as neuropsychological problems may be an issue for improvement, although part of the explanation may be the delay between the two tests that lasted up to one month.The false negative rate, undetected unfit patients, was lower with G8 than with VES-13: 23.5% Considering these results, the G8 questionnaire may be proposed to cancer patients over 70 years. Given its simplicity, this approach may allow physicians to discriminate fit from unfit patients. In this way, fit patients can benefit from standard treatment without extensive evaluation and efforts can be centered on unfit patients who need careful medical attention. For the latter, if resources are available, management should be multidisciplinary and based on appropriate geriatric assessment. If not, they should be offered at least cautious medical attention and case management when advanced practice nurses can be involved.In summary, no current consensus exists to define target elderly population who may benefit from further medical attention before cancer treatment. Our definition which uses a threshold of one or two abnormal geriatric assessment questionnaires is probably the most reliable up to now and our exploratory survival analyses demonstrated the prognostic value of impaired MGA, but search for a refined reference test remains an issueThis study responds to a critical need for easy and quick-to-use screening tools to identify older patients requiring more detailed assessment and possible geriatric interventions. Screening has been recently encouraged for all patients that may benefit from full CGA in a recent SIOG/EUSOMA publication S1 AppendixThe G8 questionnaire.(DOCX)Click here for additional data file.S2 AppendixONCODAGE abridged protocol (in English).(DOC)Click here for additional data file.


Objective. Human noroviruses (NoVs) of genogroup II are the most common strains detected in sporadic cases of acute nonbacterial gastroenteritis in outpatients in Nanjing. To gain insight into the molecular epidemiology of GII strains, we analyzed 75 positive NoV cases from 2010 to 2013. Methods. The sporadic cases were detected by real-time PCR with specific primers and probes to human NoVs of genogroup I or II, human sapovirus, human rotavirus, human astrovirus, and human enteric adenovirus. Human NoVs of genogroup II were further studied by VP1 amplification (RT- PCR), cloning, sequencing, and phylogenetic analysis. Results. Rotavirus and human NoVs were more frequently detected in all the cases from 2010 to 2013. Human NoVs infection was more frequent since 2011 and more frequent than rotavirus infection after 2012. Out of the 75 NoV cases of genogroup II, there were 5 GII.6, 11 GII.3, and 59 GII.4. Of the 59 GII.4, 27 cases were previous GII.4.2006b strains that circulated between 2010 and 2012; while 32 cases were the newly emerging GII.4 strains GII.4.2012 from 2011 to 2013. Conclusion. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains. Nonbacterial acute gastroenteritis is commonly caused by rotavirus, human calicivirus (HuCV), human astrovirus, or enteric adenovirus –5. Rotav Norovirus of the family Caliciviridae, have a 7.5 kb to 7.7 kb single-stranded genome of positive-sense RNA which contains three open reading frames (ORFs). ORF1 encodes for the nonstructural proteins with high conservation. ORF2 codes for the major capsid protein (VP1) with the highest degree of sequence variability in the genome. ORF3 codes for the minor capsid protein (VP2) with high variability. Similar to other caliciviruses, VP1 of NoVs is most important in strain diversity. According to VP1 sequencing analysis, NoVs are classified into five distinct genogroups (genogroup I [GI] to genogroup V [GV]) with at least 32 genetic clusters [Noroviruses (NoVs), members of the genusclusters –9. Of thclusters . Furtherclusters . As a reclusters . HoweverTo understand the epidemiologic patterns of GII sporadic cases in Nanjing, we analyzed NoV sporadic specimens collected by Nanjing Municipal Center for Disease Control and Prevention from 2010 to 2013.µL and the nucleic acid elution volume was 100 µL. The nucleic acid for detection of enteric adenovirus was treated with ribonuclease at 37°C for 30 mins by RNase cocktail (Ambion (Europe) Ltd., Cambridgeshire, United Kingdom). For detecting human calicivirus (HuCV), rotavirus, human astrovirus, and enteric adenovirus, we applied primers and TaqMan probes described in the literature  in accordance with the manufacturer's instructions. The stool suspension was 200 terature . For NoVA 252-nucleotide (nt) region of the 3′ end of the VP1 gene of 75 strains was amplified with primer set using the Qiagen one-step RT-PCR kit . The sequencing coverage was 1×. The reaction was conducted with an initial RT step at 50°C for 30 mins, followed by PCR activation at 95°C for 5 mins, then 35 cycles of amplification , and a final extension step for 7 mins at 72°C in a GeneAmp PCR system 9700 thermal cycler . The RT-PCR products were purified in 2% agarose gels and cloned into pGEM-T Easy vector . The restricted plasmids of 2011, 2012, and 2013 or PCR products of 2010 were purified by PEG precipitation and washed with 70% ethanol. The restricted plasmids or PCR products were bidirectionally sequenced on an ABI 3730XL DNA sequencer  using the BigDye terminator cycle sequencing ready reaction kit (Applied Biosystems); as a result, one direction sequencing entirely covered another direction except for samples of 2010.All sequences generated in this study were edited with BioEdit 7.0.1  and analhttp://www.ncbi.nlm.nih.gov) were selected for the phylogenetic tree; they are Hu/GII.4/Kobe034/2006/JP, Hu/GII.4/Sydney/NSW0514/2012/AU, and others as show in phylogenetic trees.To compare GII.4, GII.3, and GII.6 sequences from our study with strains that have been detected globally, a GenBank BLAST search , 24 was The VP1 sequences identified in this study were submitted to GenBank under the following accession numbers: KJ528320–KJ528394.Between 2010 and 2013, CDC confirmed 165, 144, 148, and 164 viral positive specimens by real-time RT-PCR, respectively. In these positive strains, the majority (90%) was caused by rotavirus and HuCV each year. Before 2011, there were more cases caused by rotavirus strains than that caused by HuCV strains. During the year 2012, there was almost the same number of cases caused by these two pathogens. After 2012, more cases were caused by HuCV strains than by rotavirus strains . For casThe phylogenetic analysis of 75 NoVs strains of genogroup II showed strain diversities during different years. There were 5 GII.6 and 11 GII.3 and 59 GII.4. For example, the GII.6 strains in 2011 and 2012, both were more similar to strain KC153251.1|_Norovirus_Hu/GII.6/Minsk10620/2012/BY than to strain JX989075.1|_Norovirus_Hu/GII.6/GZ2010-L96/Guangzhou/CHN/2011. Another example, the GII.3 strains of 2012 were more similar to the three strains KF306213.1|_Norovirus_Hu/GII.3/Jingzhou/2013402/CHN, JX984948.1|_Norovirus_Hu/GII.3/GZ2010-L63/Guangzhou/CHN/2010, and KC464329.1|_Norovirus_Hu/ GII.3/537/547/2010/AU than the other GII.3 strains, while the GII.3 strains of 2011 and 2013 were more similar to strain KC464495.1|_Norovirus_Hu/GII.3/CGMH36/2010/TW than the other GII.3 strains. Of the 59 GII.4 strains, there were two groups similar to strain JX459908.1|_Norovirus_Hu/GII.4/Sydney/NSW0514/2012/AU  or strain AB291542.2|_Norovirus_Hu/GII.4/Kobe034/2006/JP , respectively. The 5 GII.4 strains in 2010 were all in group 2. The 20 GII.4 strains in 2011 were 3 in group 1 and 17 in group 2. The 14 GII.4 strains in 2012 were 9 in group 1 and 5 in group 2. The 20 GII.4 strains in 2013 were all in group 1 .Norovirus Hu/GII.4/Kobe034/2006/JP strains were the predominant strains in 2010 and 2011. The newly variant norovirus Hu/GII.4/Sydney/NSW0514/2012/AU emerged in Nanjing in 2011 and became the predominant strain since 2012. To understand the amino acid changes of these strains, we compared the translated amino acid sequences of NoVs. Three characteristic amino acid substitutions were found in Nanjing strains not only for the former strains group of norovirus Hu/GII.4/Kobe034/2006/JP strains, but also for the newly strains group of norovirus Hu/GII.4/Sydney/NSW0514/2012/AU as shown in Our previous studies showed that the incidence rate of viral diarrhea was higher than the bacterial prevalence and increased from 2008 to 2010 in Nanjing, China . In presNoVs of genogroup II are a highly diverse subgroup of NoVs with up to 44% VP1 amino acid diversity within the genogroup . And VP1Comparison of GII.4 sequences circulating in Nanjing with sequences submitted to GenBank demonstrated that all the GII.4 strains might have a worldwide distribution. The 59 GII.4 strains were in 2 groups: 32 in the group of the newly emerging GII.4 strains GII.4.2012  from 2011 to 2013 and 27 in group of the previous strains GII.4.2006b  between 2010 and 2012, respectively. A study in Shanghai showed that the predominant norovirus genotype was GII.4 and the GII.4-2006b variant was the predominant subtype both in inpatients and outpatients between 2006 and 2011 . The newDespite the fact that the studies on NoVs for understanding antigenic sites and immunological functions are hampered by a lack of suitable animal model, some significant advances have been achieved by using virus-like particles  or monoc


Postoperative acute kidney injury (AKI) is an important cause of mortality and morbidity among surgical patients. Less is known about the occurrence of AKI after operations for gynecologic malignancies. The aim of this study was to determine the incidence of AKI in patients who underwent surgery for gynecologic malignancies and to compare patients with and without postoperative AKI.A total of 1,000 patients were enrolled retrospectively from January 2007 through March 2013. Patients under 18 years of age, those with chronic kidney disease and patients who died within the first week after surgery were excluded. AKI was defined according to the KDIGO 2012 Clinical Practice Guideline for Acute Kidney Injury. Perioperative variables of patients were collected from medical charts.P = 0.046), had higher body mass index , higher preoperative C-reactive protein (CRP) levels  and more frequently had history of distant organ metastasis  when compared with those who did not have AKI. When compared with patients who did not develop AKI postoperatively, longer operation times , intraoperative usage of higher amounts of erythrocyte suspension  and fresh frozen plasma  were seen in those who developed AKI.The mean age was 55.4 ± 12.4 years. The incidence of postoperative AKI was 8.8%, stage 1 occurred in 5.9%, stage 2 in 2.4% and stage 3 in 0.5% of the patients. Patients who had AKI were significantly older (57.9 ± 12.8 vs. 55.1 ± 12.3 years, Our results demonstrate that AKI occurs in 8.8% of the patients following surgery for gynecologic malignancies. Patients who had AKI were older, had higher body mass index with higher preoperative CRP levels, more frequent distant organ metastasis and longer operation times and higher amounts of blood transfused intraoperatively.


In recent years, the scientific discussion has focused on new strategies to enable a torn anterior cruciate ligament (ACL) to heal into mechanically stable scar tissue. Dynamic intraligamentary stabilization (DIS) was first performed in a pilot study of 10 patients. The purpose of the current study was to evaluate whether DIS would lead to similarly sufficient stability and good clinical function in a larger case series.Acute ACL ruptures were treated by using an internal stabilizer, combined with anatomical repositioning of torn bundles and microfracturing to promote self-healing. Clinical assessment  and assessment of knee laxity was performed at 3, 6, 12, and 24 months. A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDS and Lysholm scores.278 patients with a 6:4 male to female ratio were included. Average patient age was 31 years. Preoperative mean IKDC, Lysholm, and Tegner scores were 98.8, 99.3, and 5.1 points, respectively. The mean anteroposterior (AP) translation difference from the healthy contralateral knee was 4.7 mm preoperatively. After DIS treatment, the mean 12-month IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points, respectively, and the mean AP translation difference was 2.3 mm. All these outcomes were significantly non-inferior to the preoperative or healthy contralateral values (p < 0.0001). Mean patient satisfaction was 8.8 (VAS 0–10). Eight ACL reruptures occurred and 3 patients reported insufficient subjective stability of the knee at the end of the study period.Anatomical repositioning, along with DIS and microfracturing, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament. Optimal treatment after anterior cruciate ligament (ACL) rupture is still intensely debated. A conservative treatment approach shows satisfactory results in patients who place low demands on the knee joint -3, but tCurrent techniques of ACL reconstruction have demonstrated biomechanical, three-dimensional reestablishment of knee joint stability, enabling patients to perform pivoting sports, but compared with conservative treatment decreased degeneration of the knee joint could not be demonstrated . Barrackrestitutio ad integrum of the ACL would ideally preserve both the neural and the ligamentous stabilizing functions of the ACL. However, spontaneous recovery of the ACL is probably only possible in partial or completely intrasynovial ruptures. The poor healing capacity of the torn ligament—caused by biological factors, the hostile environment of the synovial fluid [A al fluid ,10, the al fluid ,12, and al fluid -15. In aal fluid . Recent al fluid -19.Dynamic intraligamentary stabilization (DIS) was successfully tested in a biomechanical human cadaver  and in aInclusion criteria: Between February 1, 2011, and January 31, 2014, a total of 278 patients were treated with a dynamic intraligamentary stabilization. Inclusion criteria were as follows: acute ACL injury (time to surgery 21 days or less); closed growth plates; patient not eligible for conservative treatment or not accepting it. Conservative treatment was recommended if all of the following criteria were fulfilled: no more than a 3 mm difference in AP translation when compared with the uninjured contralateral side; no pivoting sports; no meniscal lesions.Operative technique: The operative technique has been described previously . BrieflyIn contrast to the pilot series, the surgical technique has been advanced and the necessary surgical instruments improved. The tibial ACL stump is now augmented with up to 5 (average 3) PDS 2–0 sutures. This allows a more accurate reduction of the remaining tissue even in grossly damaged ligaments. The implant and the tensioning device underwent several evolutionary steps, making the implant easier to handle and the applied tension more accurate and reliable. The recent version of the tibial implant is premounted (monobloc system) and the thread is now self-cutting. In addition, the tensioning device now fits in the inner aperture of the implant, leading to a stable connection during the tensioning process Figure .Figure 1Clinical evaluation: In accordance with the pilot study protocol of the 10 patients, all patients in the current study were evaluated at 6 weeks and at 3, 6, 12, and 24 months after surgery. The same instruments were used for outcome assessment at each follow-up visit: Tegner, Lysholm, International Knee Documentation Committee (IKDC), and visual analogue scale (VAS) for patient satisfaction . Based on the instruments’ outcomes a new combined success definition was applied. Their preoperative scores were assessed as early as possible, but naturally after the trauma. Knee laxity was assessed by measuring anterior translation at 30 degrees flexion with an arthrometer  and comparing it with the contralateral knee. All patients were informed that their treatment and follow-up data would be recorded in a scientific database for evidence generation and postmarket surveillance of Ligamys™ and its outcomes, for which they gave their voluntary written informed consent. The study was approved by the Cantonal Ethics Committee of Berne, Switzerland: Ref.-Nr. KEK-BE: 048/09.ACL rupture classification: A 3-digit ACL rupture classification was introduced on the basis of the model of AO classification for long bones . The firStatistics: A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDC and Lysholm scores. Non-inferiority was declared if the lower margin of the one-sided 95% confidence interval for the difference in the means lied above a clinically defined minimum acceptable threshold. For this study, a threshold of 84 percent/points for the IKDC and Lysholm scores, and of < =3 mm compared with the healthy contralateral side for the anterior translation difference was considered clinically acceptable. All analyses were conducted using SAS 9.4 .A total of 278 patients were treated between February 1, 2011, and January 31, 2014. There were 115 women (41%) and 163 men (59%). Mean (SD) age was 32.4 (11.4) years (range 18–63 years), and mean (SD) body mass index was 24.1 (3.29) (range 16–35.4). The right:left knee ratio was 119:159 (left 57.19%). The mean accident-surgery interval was 18.0 (29.93) days. In 240 patients (86%), there was no preexisting lesion of the injured knee. The other 38 patients had an average of 2 intraoperatively observed preexisting lesions. The most frequent ones were abrasions of the medial femoral cartilage 25 patients, of the lateral one in 11; 8 patients showed degenerative lesions of the medial meniscus, 2 of the lateral one. 173 (62%) patients showed additional trauma related lesions of the injured knee. 127 patients (46%) had 1 additional lesion, 42 patients (15%) had 2 additional lesions, 3 patients (1%) had 3 additional lesions, and 1 patient (0.4%) had 4 additional lesions. 152 patients (55%) had an additional lesion of one or both menisci. In 98 patients (36%), we immediately sutured the torn menisci and in another 25 patients (9%), we partially resected them. In 29 patients, the meniscal lesions were superficial and stable and therefore not suitable for suturing. The mean (SD) operation time was 53.6 (14.2) minutes (range 30–120 minutes), and the mean (SD) hospitalization time was 1.9 (0.9) days (range 1–5 days).Applying the newly introduced rupture classification, the 3 most frequent rupture classes were an A.2.2 rupture  in 58 patients 21%), followed by an A.1.1 rupture  in 56 patients (20%), and an A.1.2 rupture  in 36 patients (13%). Table %, followThere were 148 3-month follow-ups; 197 6-month follow-ups; 204 12-month follow-ups; 69 24-monthfollow-ups; and 2 follow-ups in other intervals. The mean interval of the last follow-up was 14 months; the maximum interval was 3 years.The mean (SD) Lysholm score was 99.3 (2.3) points  before injury, 91.8 (6.9) points  after 3 months, and 97 (5.0) points  after 24 months. The mean (SD) IKDC score was 98.8% (6.4)  before injury, reaching 83.2% (9.6)  after 3 months and 94.8% (6.5)  after 24 months.By improving from a mean (SD) of 3.7 (1) points after 3 months (range 1–10 N = 148) to a mean 5.1 (1.4) points after 24 months (range 3–10 N = 69), the group’s mean Tegner score nearly reached the pre-injury level of 5.1 (1.4) points (range 3–10). The mean (SD) patient satisfaction was 8.1 (1.5)  after 3 months and 8.9 (1.3)  after 24 months. Before surgery, the mean (SD) anterior translation difference between the injured and the healthy contralateral knee was 4.7 (2.0) mm (range 0–11 mm). After 3 months, it was 0.8 (1.4) mm (range −3 to 5 mm) and after 24 months, it was 2.3 (1.7) mm (range −2 to 6 mm) .There was a mean (SD) of 79.9 (29.4) days until 100% return to work (range 4–120 days) for patients who did heavy physical labor; 50.6 (39.4) days (range 1–191 days) for patients who did light physical labor; and 25.1 (19.0) days (range 0–100 days) for patients with a sitting occupation.Three intraoperative complications occurred in 3 patients (1.1%): 1 perforation of the endo button into the femur, 1 second screw tunnel because of insufficient anterior coverage, and 1 Kirschner wire breakage. All situations could be solved without additional damage to the knee. There were 8 complications in 8 patients until hospital discharge (2.9%): 5 hematomas and 3 others .Eight reruptures of the ACL occurred at an average of 338 days after surgery (range 106–740 days). None of the cases had had any intra- or postoperative complications. All were treated with a ligament graft. There were 3 reported mechanical insufficiencies of the ACL (giving way). Figure The implant was removed postoperatively in 67 24.1%) patients, of whom 28 (10.1%) asked for implant removal without any clinical need. In the other cases, the implant was removed because of infection , pain , or joint stiffness ; in the remaining cases , the implant was removed during interventions for meniscal rerupture, a free-floating body in the joint, or crepitations (Figure .1% patieThe most important findings of the current study are that its results corroborate those of the pilot group . This grThe preoperative Tegner activity scale between the pilot group and the current population changed from 6 to 5, reflecting a more sportive patient group in the pilot study. As could be expected with an increasing number of treated patients, the range of results became more widespread, which we consider to be a trend towards normalization rather than one towards worsening. At 6 months after surgery, the median IKDC and Lysholm scores were both above 90, and after 12 months, they had returned to levels of close to 100 with the same Tegner scale as before the ACL rupture. However, there were also some 6-month scores of around 50 points for the Lysholm and IKDC scales, which remained low at 12 months. Nevertheless, overall patient satisfaction was already very high at 6 months, and it further increased with longer follow-up intervals. The 24-months results, despite being at a desirably high level, only represent a 25% follow-up rate, with more patient examinations expected in future.Our main conclusion from the results of the first 10 patients—namely, that DIS of the knee with a freshly ruptured ACL, in combination with anatomical repositioning and biological improvement of the healing environment, can lead to a biomechanically stable ACL with good functional scores and high patient satisfaction—can now be generalized to a much higher degree. A bias towards optimal results was introduced by the motivation and physical fitness of our first 10 patients. However, the desired functional outcomes in the present 278 cases, an AP side-to-side difference ≤3 mm, a Lysholm score >84 points, and an IKDC score >84%, were reached in 86.8%, 95.6%, and 87.6% of patients, respectively, at the last follow-up. In applying our combined success definition, we found that 77.2% presented an excellent outcome.It was surprisingly difficult to compare outcomes with other authors. The initial conservative approach with delayed surgery in case of unsatisfactory results leads to pre-surgery instead of pre-injury reporting of activity levels and scores. Since DIS must be performed within few weeks after ACL rupture, we routinely assess patients’ pre-injury activity levels, even if with a retrospective perspective. Streich et al.  comparedOur findings add further evidence to the paradigm shift that a torn ACL has sufficient healing capacity. We have already presented results of other studies indicating that the injured ACL can produce a stable scar under certain circumstances. Sutures with tissue augmentation , placemeThe essential prerequisites for ACL healing are mainly the same as they are for all biological tissues: stability and integrity of a healing environment. The increased AP translation of the knee with a ruptured ACL leads to a constant disconnection of the 2 ACL stumps and thereby compromises healing by instability . A methoAP translation measurements at 6–12 months after surgery are only a surrogate measure for the reestablished static stability of the knee joint, but its correlation with patient satisfaction scores was reported to be poor, whereas proprioception is a key aspect in measuring the overall outcome of an ACL reconstruction . PatientThe failure rate of DIS, either as a rerupture of the ligament or a clinically unstable knee, was 3.95% until the end of the study period. Following up on 612 patients, Salmon et al.  found a One of the major drawbacks in conservative treatment is the neglect of the concomitant injuries after an ACL injury, mainly the meniscal tears. A missed unstable meniscus, combined with knee instability, will destroy the meniscal tissue and consequently end in surgical removal ,52. In tLimitations of the study: The current study has weaknesses that need to be considered. Being a case series, the study can only generate level-four-evidence. We had initially designed a randomized trial for the first ten patients, but a 100% cross over rate of patients allocated to conventional ACL reconstruction made it impossible to conduct the trial. Despite reaching a 2-years maximum follow-up in 22% of reported cases, the average follow-up time is only 14 months and the topic of ACL repair or reconstruction and their long-term outcomes needs much longer follow-up intervals. Further, it is unclear when the internal brace fails and what the consequences for ap-translation of the affected knee are. First analyses revealed a minimal translation increase if the monobloc was removed, but without any clinical or functional consequences. Finally, restoration of knee proprioception after DIS is a clinical hypothesis that cannot yet be proven.Anatomical repositioning, along with DIS and microfracturing of the notch, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament.


Type 2 Diabetes is a condition characterized by blood glucose levels caused by any lack of insulin or the body's inability to utilize insulin effectively. It develops most often in middle-aged and older adults, but may appear in children, adolescents and youth.To evaluate the response of functional capacity and level of physical activity in women with type 2 diabetes.This cross-sectional study consisted of 34 women from the city of Londrina, with age range from 44 to 55 yrs., were divided into two groups: I.DM  and II.Control . The diagnosis of diabetes was made through a clinical and laboratory evaluation. To assess the level of physical activity was applied the International Physical Activity Questionnaire [IPAQ] and conducted a functional test: Step Test (ST) 2 min to assess the functional status and strength of the lower limbs. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS-2.0). Statistical significance was accepted for p <0.05. The data numerical correlation of Spearman and Mann-Whitney and chi-square were performed.No significant difference between groups I and II in ST (p=0.379) and in the questionnaire (p=0.868). In Group I, 41.7% are inactive and Group II, 56.5% are minimally active (p=0.360). ST was found in a performance at the Group I of 49  repetitions and Group II 45  repetitions (p=0.379). There was a difference between the diastolic blood pressure immediately after the TS groups (p=0.027) and the Borg scale according to claim even after fatigue test (p=0.043). The Results of the IPAQ questionnaire in Group I/Group II respectively were: Active 0%/7.4%; minimally active 57.1%/66.7% and 42.9%/29.4% inactive (p=0.556) and METs 2070/1680 (p=0.868). There was no significant correlation TD and IPAQ (rs=-0.236/p=0.180). In Group I all have the diagnosis of metabolic syndrome in Group II 63%.Type 2 Diabetes is strongly related to metabolic risk, we found that although not significant was no difference in performance between groups. Physical activity brings metabolic and cardiovascular benefits and should be encouraged to minimize risk factors.


There is no advantage in maintaining patients on oral fasting aftergastrointestinal elective resection. The early feeding up to 48 h can bebeneficial, because it reduces infectious complications and hospital stay.  Evaluate the evolution and tolerance of early oral diet in postoperative periodafter gastrectomy for gastric cancer. Anthropometric assessment was performed on the day of surgery, weight, height,body mass index and weight loss were measured. Acceptance of diet was evaluated asfood intake (amount accepted) and gastrointestinal symptoms such as nausea,vomiting, constipation, diarrhea, abdominal distension, postoperativecomplications and hospital stay. The sample consisted of 23 patients, 17 with partial gastrectomy and six withtotal gastrectomy. In the assessment of nutritional status 9% were malnourished,54.5% normal weight, 9% overweight and 27.2% obese, but 54% had weight loss. Therewas good acceptance of the diet in 96,9% of the sample. Nausea and abdominaldistension were present in 4,3% and 65.2% constipation. Surgical complicationsaccording to the Clavien scalle, 13% had grade V, 4.3% grade IIIA, 8.7% grade Iand 73% did not have complications. The length of hospital stay was 5±2.2 days.Early postoperative re-feeding in total and partial gastrectomy was well toleratedby patients. Stomach cancer is the fourth most incident in Brazil for men and the fifth for womenFor gastric cancer the most effective treatment is surgery Patients undergoing gastric resection are generally able to initiate the oral intakefrom three to seven days postoperatively Studies show, however, that there is no advantage in maintaining patients on oralfasting after the gastrointestinal elective resection. The early feeding up to 48 h canbe beneficial because it reduces infectious complications and hospital stay The operations with presence of gastrointestinal anastomoses, enteroenteric, enterocolicor colorectal can start a liquid diet routine on the first day after surgery. Oliveirastudy showed that 74% n=14) of the patients tolerated the volume of 300 ml by liquiddiet meal 4 of the The objective of this study was to evaluate the progress and tolerance the start ofearly oral diet (up to 48 h) in patients in the postoperative period of total andpartial gastrectomy demonstrating its applicability in hospital practiceThis study was submitted to the Research Ethics Committee of the institution beingapproved in accordance with the Protocol. 2270, 2013. It is a prospective, descriptiveand transversal study. The research was conducted between the months July to December2013 involving 41 patients of the Abdominal Surgery Department of Erastus GaertnerHospital, Curitiba, PR, Brazil. The sample was of patients who underwent partial ortotal gastrectomy in the research period. Patients unable to perform anthropometric andwith late-onset diet (more than 48 h) were excluded.nd day after surgery, because on the 1st daywere fasted) when they were asked about the acceptance and tolerance of the diet byvolume ingested per meal and symptoms , until hospital discharge; 3) up to 30 days after surgery to evaluatepossible complications , which classifies surgical complications within seven classes  the dayof the surgical procedure was checked for weight, height, body mass index (BMI), usualweight reported by the patient and the time lost weight (one week to six months) whencompared to the current, percentage of weight loss (% WLP) involuntary dividing thesample into two groups, adults (less than 60 years) and seniors; 2) on the first day ofearly oral feeding /height (m²) and classifiedby the World Health Organization The data were tabulated in Microsoft Excel® 2007 version, with descriptive analysis and used software used was the SPSS 19.0.In the six-month period was included 41 patients, 18 were excluded because they realizedother concomitant surgical procedures , or because they started late diet, totaling 23 patients inthe final sample. The age ranged from 48 to 84 years (mean 61 and median 60), in bothgenders. Seventeen (73.9%) underwent partial gastrectomy, eight with lymphadenectomy,and six (26.1%) to total gastrectomy with lymphadenectomy. According to clinical orpathological staging of the tumor, it was noted that almost half of the patients were inIII   .To evaluate nutritional status patients were divided into adults and the elderly. Inadults 9% (n=1) of patients were malnourished, 54.5% (n=6) in eutrophic, 9% (n=1) wereoverweight and 27.2% (n=3) obesity, however, another data evaluated was the percentageof weight loss, which found that 54.5% (n=6) of adults have had this weight loss, with27.2% (n=3) in a serious way. In the elderly 41.6% (n=5) of patients were underweight,41.6% (n=5) in eutrophic and 16.6% (n=2) overweight according to body mass index (BMI).Regarding weight loss 100% (n=12) showed that loss considering 58.3% were severelyaffected.nd postoperative period(1st day of diet); 95.2% in the complete-liquid diet on 3rdpostoperative period (2nd day of diet) and 100% in the pasty-liquid diet onthe 4th postoperative period (3rd day of diet). Overall there wasgood acceptance of the diet (average 96.9%) at all stages.In assessing the evolution and acceptance of the diet protocol there was good acceptancein 95.6% on the restrict-liquid diet on the 2When analyzing the symptoms after starting the diet, no patients presented vomiting ordiarrhea in the relocation period, 4.3% had nausea and/or abdominal distension and 65,2had constipation. The length of stay ranged from 3 to 14 days (average 5±2.2).Complications within 30 days of postoperative fistulas were 13% (n=3) and 17.2% (n=4)other complications . There were noother researched complications such as dehiscence, pneumonia, stroke, respiratoryfailure and wound infection.In assessing the degree of postoperative complications according to Clavien's Scale, itwas noted that not all grades were present in the sample. They were reported in gradeI8.7%, grade III A 4.3%, grade V 13% and without complications 73.9%.The main complication, if compared with nutritional status, was the presence of fistula.Of the 13% (n=3) found 8.6% (n=2) were elderly with low weight and 4.3% (n=1) adultswith some degree of obesity and mild weight loss. Among found fistulas, 8.6% (n=2) werein the esophagojejunal anastomosis and 4.3% (n=1) in duodenal stump.In this study it is clear that the majority of patients  was admitted withadvanced disease according to clinical staging or pathological TNM The displayed weight loss can be justified by food intake presented by patientsaccording to tumor location. According IBNO  6.5% (n=13) of patients with gastric cancer increased food intake,71.7% (n=142) decreased and 21.7% (n=43) remained preserved. Another information weightrelated referred to the weight loss at 60.1% (n=80) on adults and 56.9% (n=37) on theelderly In Oliveira study the early diet for patients with gastrectomy was accepted in 74% ofcases, with low incidence of gastrointestinal symptoms. In 2011 Jo regards acceptance by89% and only 8% with gastrointestinal symptoms Studies evaluating patients undergoing gastrectomy for gastric cancer claim that oralfeeding on the first postoperative day is safe Early feeding after operations involving resection and intestinal anastomosis can beconducted without risks and benefits as early discharge, lower incidence of infectiouscomplications and lower hospital costs Regarding vomiting - which did not occur in this study - it is controversial; waspresent in 13% in Nascimento (2002) paper, related to intestinal anastomoses Another symptom found more frequently was constipation, taken after a period of overthree days without stool. Approximately 65.2% of patients were constipatedpostoperatively, but it must be considered the preoperative fasting time andapproximately 48 h postoperatively and therefore no sufficient training of waste toevacuate, even with starting the diet. Another possible cause is the decrease inintestinal transit caused by the use of anesthetics, opioids and impaired mobilitypostoperatively.The hospital stay was 5±2.2 days in these patients. According to Hur it was 8.03±1.43days in early feeding group and 9.9±2 in the control group Early feeding in total or partial gastrectomy postoperative period was well tolerated bypatients.