Fluorescence Lifetime Imaging Microcopy of Extravasating Cancer Cells in the Mouse Microenvironment

Objective. To determine (i) whether early viral kinetics or other markers during a modified treatment regimen are predictors of treatment outcome and (ii) whether fast responders can be treated for 24 weeks, without compromising the sustained virologic response (SVR) rate. Material and methods. One hundred "difficult-to-treat'' chronic hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naive patients genotypes 1 and 4) were treated with triple antiviral induction therapy: amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa-2b induction (weeks 1-2: 18 MU/day, weeks 3-4: 9 MU/day, weeks 5-6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b. Fast responders (>= 3 log(10) HCV RNA decline at week 4) were randomized to 24 or 48 weeks. Slow responders (= or = 5 IU/mL at week 16 became non-SVR. In previous non-responders/relapsers, the predictive value for SVR was 83% if HCV RNA was = 5 IU/mL at week 8 became non-SVR. Conclusions. With high-dose interferon induction, SVR and non-SVR can be predicted reliably within 16 weeks. Fast responders can be treated for 24 weeks, and SVR is independent of baseline viral load in fast responders

Quantitative assessment of cardiac load-responsiveness during extracorporeal life support: case and rationale

We describe a case of a patient assisted by extracorporeal life support, in which we obtained the dynamic filling index, a measure for venous volume during extracorporeal life support, and used this index to assess cardiac load-responsiveness during acute reloading. While reloading, the obtained findings on cardiac pump function by the dynamic filling index were supported by trans-esophageal echocardiography and standard pressure measurement. This suggests that the dynamic filling index can be used to assess cardiac load-responsiveness during extracorporeal life support

Deep learning based correction of RF field induced inhomogeneities for T2w prostate imaging at 7 T

At ultrahigh field strengths images of the body are hampered by B 1 -field inhomogeneities. These present themselves as inhomogeneous signal intensity and contrast, which is regarded as a "bias field" to the ideal image. Current bias field correction methods, such as the N4 algorithm, assume a low frequency bias field, which is not sufficiently valid for T2w images at 7 T. In this work we propose a deep learning based bias field correction method to address this issue for T2w prostate images at 7 T. By combining simulated B 1 -field distributions of a multi-transmit setup at 7 T with T2w prostate images at 1.5 T, we generated artificial 7 T images for which the homogeneous counterpart was available. Using these paired data, we trained a neural network to correct the bias field. We predicted either a homogeneous image (t-Image neural network) or the bias field (t-Biasf neural network). In addition, we experimented with the single-channel images of the receive array and the corresponding sum of magnitudes of this array as the input image. Testing was carried out on four datasets: the test split of the synthetic training dataset, volunteer and patient images at 7 T, and patient images at 3 T. For the test split, the performance was evaluated using the structural similarity index measure, Wasserstein distance, and root mean squared error. For all other test data, the features Homogeneity and Energy derived from the gray level co-occurrence matrix (GLCM) were used to quantify the improvement. For each test dataset, the proposed method was compared with the current gold standard: the N4 algorithm. Additionally, a questionnaire was filled out by two clinical experts to assess the homogeneity and contrast preservation of the 7 T datasets. All four proposed neural networks were able to substantially reduce the B 1 -field induced inhomogeneities in T2w 7 T prostate images. By visual inspection, the images clearly look more homogeneous, which is confirmed by the increase in Homogeneity and Energy in the GLCM, and the questionnaire scores from two clinical experts. Occasionally, changes in contrast within the prostate were observed, although much less for the t-Biasf network than for the t-Image network. Further, results on the 3 T dataset demonstrate that the proposed learning based approach is on par with the N4 algorithm. The results demonstrate that the trained networks were capable of reducing the B 1 -field induced inhomogeneities for prostate imaging at 7 T. The quantitative evaluation showed that all proposed learning based correction techniques outperformed the N4 algorithm. Of the investigated methods, the single-channel t-Biasf neural network proves most reliable for bias field correction

Effect of surgical volume on short-term outcomes of cytoreductive surgery for advanced-stage ovarian cancer:A population-based study from the Dutch Gynecological Oncology Audit

Objective: Despite lacking clinical data, the Dutch government is considering increasing the minimum annual surgical volume per center from twenty to fifty cytoreductive surgeries (CRS) for advanced-stage ovarian cancer (OC). This study aims to evaluate whether this increase is warranted. Methods: This population-based study included all CRS for FIGO-stage IIB-IVB OC registered in eighteen Dutch hospitals between 2019 and 2022. Short-term outcomes included result of CRS, length of stay, severe complications, 30-day mortality, time to adjuvant chemotherapy, and textbook outcome. Patients were stratified by annual volume: low-volume (nine hospitals, &lt;25), medium-volume (four hospitals, 29–37), and high-volume (five hospitals, 54–84). Descriptive statistics and multilevel logistic regressions were used to assess the (case-mix adjusted) associations of surgical volume and outcomes. Results: A total of 1646 interval CRS (iCRS) and 789 primary CRS (pCRS) were included. No associations were found between surgical volume and different outcomes in the iCRS cohort. In the pCRS cohort, high-volume was associated with increased complete CRS rates (aOR 1.9, 95%-CI 1.2–3.1, p = 0.010). Furthermore, high-volume was associated with increased severe complication rates (aOR 2.3, 1.1–4.6, 95%-CI 1.3–4.2, p = 0.022) and prolonged length of stay (aOR 2.3, 95%-CI 1.3–4.2, p = 0.005). 30-day mortality, time to adjuvant chemotherapy, and textbook outcome were not associated with surgical volume in the pCRS cohort. Subgroup analyses (FIGO-stage IIIC-IVB) showed similar results. Various case-mix factors significantly impacted outcomes, warranting case-mix adjustment. Conclusions: Our analyses do not support further centralization of iCRS for advanced-stage OC. High-volume was associated with higher complete pCRS, suggesting either a more accurate selection in these hospitals or a more aggressive approach. The higher completeness rates were at the expense of higher severe complications and prolonged admissions.</p

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands

Background: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be “complete” in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Methods: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery Discussion: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void

Feasibility of clinical studies of chemical exchange saturation transfer magnetic resonance imaging of prostate cancer at 7 T

Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours

External Financial Aid to Blood Transfusion Services in Sub-Saharan Africa: A Need for Reflection

Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid provided for blood transfusion services in sub-Saharan Africa has resulted in serious negative outcomes, which requires reflection and rethinking

Sofosbuvir and ribavirin in HCV genotypes 2 and 3

BACKGROUND: In clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection. METHODS: We conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4:1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus. CONCLUSIONS: Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.)

Inquérito sorológico para a detecção de anticorpos contra o vírus da Imunodeficiência Humana (VIH) em crianças internadas em enfermaria geral

São apresentados os resultados de um inquérito sorológico para a detecção de anticorpos contra o Vírus da Imunodeficiência Humana (VIH), em grupo não selecionado de crianças, internadas numa enfermaria geral de pediatria. Foram testados 441 pacientes pelo método ELISA, com uma positividade de 1,1 %, cujos resultados foram confirmados pelos testes de Western-Blot e/ou ImunoBlot. Nenhum dos cinco pacientes com teste positivo apresentou história de transfusão anterior, enquanto que 4,3% dos pacientes estudados apresentaram história transfusional. Todas as mães apresentaram também testes ELISA positivos. Em quatro casos, pelo menos um dos genitores referiu uso de drogas por via endovenosa. Em todas as crianças, o modo de transmissão foi vertical. A partir desses achados sugere-se a necessidade de a equipe de saúde tomar precauções quando da manipulação de sangue ou secreções. Recomenda-se a realização de inquéritos anônimos em enfermarias de hospitais gerais para auxiliar na determinação da real prevalência das infecções pelo VIH

Grambank reveals the importance of genealogical constraints on linguistic diversity and highlights the impact of language loss

While global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here we outline the Grambank database. With over 400,000 data points and 2,400 languages, Grambank is the largest comparative grammatical database available. The comprehensiveness of Grambank allows us to quantify the relative effects of genealogical inheritance and geographic proximity on the structural diversity of the world's languages, evaluate constraints on linguistic diversity, and identify the world's most unusual languages. An analysis of the consequences of language loss reveals that the reduction in diversity will be strikingly uneven across the major linguistic regions of the world. Without sustained efforts to document and revitalize endangered languages, our linguistic window into human history, cognition and culture will be seriously fragmented.Genealogy versus geography Constraints on grammar Unusual languages Language loss Conclusio