106 research outputs found

    How to tie dangerous surgical knots: easily. Can we avoid this?

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    ObjectiveSecure knots are essential in all areas of surgical, medical and veterinary practice. Our hypothesis was that technique of formation of each layer of a surgical knot was important to its security.DesignEqual numbers of knots were tied, by each of three groups, using three techniques, for each of four suture materials; a standard flat reef knot (FRK), knots tied under tension (TK) and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and tested by distraction with increasing force, till each material broke or the knot separated completely.SettingTemporary knot tying laboratory.MaterialsThe suture materials were, 2/0 polyglactin 910 (Vicryl), 3/0 polydioxanone, 4/0 poliglecaprone 25 (Monocryl) and 1 nylon (Ethilon).ParticipantsThree groups comprised, a senior surgeon, a resident surgeon and three medical students.Outcome measuresProportion of each knot type that slipped, degree of slippage and length of suture held in loop secured by each knot type.Results20% of FRK tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip was significantly less for FRK (mean 6.3%–, 95% CI 2.2% to 10.4%) than for TK (mean 312%, 95% CI 280.0% to 344.0%) and NHCK (mean 113.0%, –95% CI 94.3% to 131.0%).The mean length of suture in loops held within (FRK mean 25.1 mm 95% CI 24.2 to 26.0 mm) was significantly greater than mean lengths held by the other techniques (TK mean 17.0 mm, 95% CI 16.3 to 17.7 mm), (NHCK mean 16.3 mm, 95% CI 15.9 to 16.7 mm). The latter two types of knot may have tightened more than anticipated, in comparison to FRK, with potential undue tissue tension.ConclusionMeticulous technique of knot tying is essential for secure knots, appropriate tissue tension and the security of anastomoses and haemostasis effected.</jats:sec

    Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort.

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    Objectives To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours.Methods Paediatric patients (-2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians.Results The values for ADC, D, DDCα, α, and DDCK gave CV 30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083).Conclusion Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data.Key points • ADC has good repeatability as low 5th centile of the histogram distribution. • High CV was observed for all parameters at extremes of histogram. • Parameters from the stretched exponential model showed low coefficients of variation. • The median ADC, D, DDC α , and DDC K are highly correlated and repeatable. • Perfusion/kurtosis parameters showed high CV variations across their histogram distributions

    Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

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    Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 +/- A 11 vs 64 +/- A 18 %; p = 0.03) and overall survival (58 +/- A 12 vs 83 +/- A 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.Canadian Institutes of Health Research [MOP 82727]info:eu-repo/semantics/publishedVersio

    Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

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    We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

    Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

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    PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

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    PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

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    The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

    Laparoscopic ventral hernia repair under spinal anesthesia: a feasibility study

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    BACKGROUND: Regional anesthesia has not been used as the sole anesthetic procedure in laparoscopic ventral hernia repair due to the fear of potential adverse effects of the pneumoperitoneum. However, there are recent reports on the feasibility of performing laparoscopic procedures, such as cholecystectomy, in fit patients, under spinal anesthesia alone. The current study aimed to detect the feasibility of performing laparoscopic ventral hernia repair under spinal anesthesia. METHODS: Twenty-five American Society of Anesthesiologists (ASA) I or II patients underwent laparoscopic ventral hernia repair with low-pressure Co-2 pneumoperitoneum under spinal anesthesia. In 9 cases the hernia: was umbilical/para-umbilical, in 5 cases epigastric, and in II cases incisional. Intraoperative incidents, complications, postoperative pain, and recovery in general, as well as patient satisfaction at follow-up examination, were prospectively recorded. RESULTS: All operations were completed laparoscopically and conversion from spinal to general anesthesia was not required in any of the cases. Median pain score at 4 hours postoperatively was .5 (range 0-5), at 8 hours 1.5 (range 0-6), and at 24 hours 1.5 (range 0-4). Most patients were discharged 24 hours after the operation; the median hospital stay was 1 day (range 1-3 days). At 2-weeks follow-up, no late complications were detected and all patients reported being satisfied with the anesthetic procedure. CONCLUSION: Laparoscopic ventral hernia repair with low-pressure Co-2 pneumoperitoneum can be successfully and safely performed under spinal anesthesia. Furthermore, it seems that spinal anesthesia is associated with minimal postoperative pain and smooth recovery. (c) 2008 Elsevier Inc. All rights reserved

    Impact of Uncomplicated Total Thyroidectomy on Voice and Swallowing Symptoms: a Prospective Clinical Trial

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    Voice and swallowing alterations are frequently reported after thyroidectomy, even in absence of nerve injury. The symptoms impair the quality of life. Aim of the study was to evaluate prospectively vocal function and swallowing symptom changes after total thyroidectomy in the early and late postoperative period. Prospective observational study. All consecutive patients scheduled for total thyroidectomy were included. Subjective voice evaluation using the Greek version of Voice Handicap Index (VHI) was performed preoperatively and at 2nd postoperative day, 1 month, 12 months postoperatively to assess the functional outcome. Laryngoscopy was performed at the same timing. Subjective swallowing evaluation using the Swallowing Impairment score (SIS) evaluated the swallowing symptoms. The study population included 125 patients. Total VHI score differed significantly between preoperative values and at 48 h and 1 year postoperatively (p = 0.000). Significant changes were observed for the functional and emotional domain of VHI between preoperative and 48 h postoperatively (p = 0.001, 0.003, respectively). There were statistically significant changes for physical domain of VHI between preoperative values and values at 48 h and 1 year (p = 0.000, 0.001, respectively). Regarding the swallowing symptoms, the mean postoperative score at 1 month did not differ significantly from the mean preoperative score (p = 0.103). Swallowing alterations showed a tendency to increase 48 h postoperatively and decreased thereafter. Swallowing score at 1 year postoperatively was statistical significant lower compared to preoperative values. Even with intact laryngeal nerves, transient voice and swallowing alterations may occur after total thyroidectomy. Patients should be informed about these mild changes to lower anxiety following the operation. © 2019, Association of Surgeons of India
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