Commentary on the 2008 WHO classification of mature T- and NK-cell neoplasms

In 2008, the World Health Organization (WHO) published a revised and updated edition of the classification of tumors of the hematopoietic and lymphoid tissues. The aims of the fourth edition of the WHO classification was to incorporate new scientific and clinical information in order to refine diagnostic criteria for previously described neoplasms and to introduce newly recognized disease entities. The recognition that T-cell lymphomas are related to the innate and adaptive immune system, as well as enhanced understanding of other T-cell subsets, such as the regulatory T-cell and follicular helper T-cells, has contributed to our understanding of the morphologic, histologic, and immunophenotypic features of T- and NK-cell neoplasms. The purpose of this review is to highlight major changes in the classification of T- and NK-cell neoplasms and to explain the rationale for these changes

Effect of dispase denudation on amniotic membrane

Molecular Vision151962-197

0357: Two-dimensional speckle-tracking imaging for the left atrial and ventricular function in patients undergoing atrial fibrillation ablation

IntroductionLeft atrium (LA) structural remodeling associated with atrial fibrillation (AF) contributes to recurrence after AF catheter ablation (CA). Characterizing LA function may be useful to identify patients with higher risk of recurrence and could guide ablation strategy in term of substrate modification. We aimed to identify predictors of recurrence and atrial remodeling by assessing LA and left ventricle (LV) deformation properties using two-dimensional speckle-tracking imaging before and after AF CA.Methods62 patients (age 54±10 years, 90% male) with AF (45 paroxysmal (PAF), 17 persistent (PsAF)) underwent an echocardiography before CA, 3 and 6 months after CA to assess LA strain (S total (S-tot), positive peak (S-pos), negative peak (S-neg)), LA strain rate (SR positive peak (SRs), early (SRe) and late negative peak (SRa)) and LV strain (LV longitudinal and radial S).ResultsPsAF patients baseline had significantly larger LA volumes (41±8 vs 32±10ml/m2), decreased S-tot (10±5 vs 20±6%; p<0.001), SR-LAs (0.6±0.2 vs 1±0.3s−1; p<0.001) and LV strain (−12±3 vs −16±3%; p<0.001) compared to PAF group. After 6 month follow-up, 69% of the patients remained in sinus rhythm. Baseline LA active emptying, reservoir function and LA S-tot (13.2±6.2 vs 20.1±7%, p<0.001), S-neg (−7.2±3.5 vs –10.6±3.3%, p<0.009), SR-s (0.71±0.3 vs 1.01±0.35 s−1, <0.004), SR-a (–0.89±0.56 vs −1.37±0.48 s−1, p<0.01) and LV strain (−13.5±4.8 vs −17.1±3.5%, p<0.003) were significantly decreased in patients with AF recurrence. At multivariate analysis, the unique independent predictor of sinus rhythm maintenance was LA S-tot (HR 0.819 (0.685–0.979), p=0.028). In the overall cohort, LA volumes decreased from baseline to 3 and 6 months but there was no significant change in LA S, LA SR nor LV strain. At multivariate analysis, the unique independent predictor of LA reverse remodeling after CA was the duration of AF history (HR 0.84 (0.73–0.96), p=0.013).ConclusionsAltered global LA and LV strain before CA is associated with AF recurrence. Echocardiographic LA function characterization before ablation procedures may be helpful to guide AF ablation strategy and drug management after CA

Deep Learning-Based Dose Prediction To Improve the Plan Quality of Volumetric Modulated Arc Therapy for Gynecologic Cancers

Background: In recent years, deep‐learning models have been used to predict entire three‐dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. Purpose: To develop a deep‐learning model to predict high‐quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. Methods: A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U‐Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5‐point scale (5, acceptable as‐is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. Results: The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel‐wise dose difference was −0.14 ± 0.46 Gy. The percentage dose differences in the predicted target metrics of D1% and D98% were −1.05% ± 0.59% and 0.21% ± 0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were −0.30 ± 1.66 Gy and −0.42 ± 2.07 Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. Conclusions: Deep‐learning dose prediction can be used to predict high‐quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization

Taste evaluation of a novel midazolam tablet for pediatric patients: In vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles

Harmonized methodologies are urgently required for the taste evaluation of novel pediatric medicines. This study utilized in vitro, in vivo and clinical data to evaluate the palatability of a novel midazolam chocolate tablet. In vitro dissolution experiments showed the crushed tablet to release within 5 min 1.68 mg of midazolam into simulated saliva. This translated to a drug level of 0.84 mg/ml in the oral cavity, which would be higher than the midazolam bitterness detection threshold concentration of 0.03 mg/ml determined in a rat 'brief access taste aversion' (BATA) model. The visual analogue scale scores of patients aged 4-16 years prescribed with midazolam pre-surgery showed a clear preference for the midazolam chocolate tablets (3.35 ± 1.04, n = 20) compared to the control midazolam solution (1.47 ± 0.62, n = 17). The clinical data was in agreement with the in vivo rodent data in showing the novel chocolate tablet matrix to be effective at taste-masking the bitter midazolam

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

International audiencePURPOSE: Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. METHODS: Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. RESULTS: Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. CONCLUSION: SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind

Deep Learning-Based Dose Prediction for Automated, Individualized Quality Assurance of Head and Neck Radiation Therapy Plans

PURPOSE: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. METHODS AND MATERIALS: A total of 245 volumetric modulated arc therapy HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included computed tomography images, target prescriptions, and contours for targets and organs at risk (OARs). The model\u27s performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared with manual flags by 3 HN radiation oncologists. RESULTS: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D CONCLUSIONS: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab

Background: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. Methods: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. Results: In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). Conclusion: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept

Klebsiella pneumoniae related community-acquired acute lower respiratory infections in CAMBODIA: clinical characteristics and treatment

<p>Abstract</p> <p>Background</p> <p>In many Asian countries, <it>Klebsiella pneumoniae </it>(KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very little is known about <it>KP </it>etiology in ALRI in Cambodia, a country that has one of the weakest medical infrastructures in the region. We present here the first clinico-radiological description of <it>KP </it>community-acquired ALRI in hospitalized Cambodian patients.</p> <p>Methods</p> <p>Through ALRI surveillance in two provincial hospitals, <it>KP </it>was isolated from sputum and blood cultures, and identified by API20E gallery from patients ≥ 5 years-old with fever and respiratory symptoms onset ≤14 days. Antibiotics susceptibility testing was provided systematically to clinicians when bacteria were isolated. We collected patients' clinical, radiological and microbiological data and their outcome 3 months after discharge. We also compared <it>KP</it>-related with other bacteria-related ALRI to determine risk factors for <it>KP </it>infection.</p> <p>Results</p> <p>From April 2007 to December 2009, 2315 ALRI patients ≥ 5 years-old were enrolled including 587 whose bacterial etiology could be assigned. Of these, 47 (8.0%) had <it>KP </it>infection; their median age was 55 years and 68.1% were females. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including 39% that were necrotizing), preexisting parenchyma lesions (29.5%) and pleural effusions alone (4.5%) and normal parenchyma (4.5%). Five patients had severe conditions on admission and one patient died during hospitalization. Of the 39 patients that were hospital discharged, 14 died including 12 within 1 month after discharge. Only 13 patients (28%) received an appropriate antibiotherapy. Extended-spectrum beta-lactamases (ESBL) - producing strains were found in 8 (17.0%) patients. Female gender (Odds ratio (OR) 2.1; <it>p </it>= 0.04) and diabetes mellitus (OR 3.1; <it>p </it>= 0.03) were independent risk factors for <it>KP</it>-related ALRI.</p> <p>Conclusions</p> <p><it>KP </it>ALRI in Cambodia has high fatality rate, are more frequently found in women, and should be considered in diabetic patients. The extremely high frequency of ESBL-producing strains in the study is alarming in the context of uncontrolled antibiotic consumption and in absence of microbiology capacity in most public-sector hospitals.</p

Mapping Site-Specific Changes that Affect Stability of the NTerminal Domain of Calmodulin

Biophysical tools have been invaluable in formulating therapeutic proteins. These tools characterize protein stability rapidly in a variety of solution conditions, but in general, the techniques lack the ability to discern site-specific information to probe how solution environment acts to stabilize or destabilize the protein. NMR spectroscopy can provide site-specific information about subtle structural changes of a protein under different conditions, enabling one to assess the mechanism of protein stabilization. In this study, NMR was employed to detect structural perturbations at individual residues as a result of altering pH and ionic strength. The N-terminal domain of calmodulin (N-CaM) was used as a model system, and the 1H-15N heteronuclear single quantum coherence (HSQC) experiment was used to investigate effects of pH and ionic strength on individual residues. NMR analysis revealed that different solution conditions affect individual residues differently, even when the amino acid sequence and structure are highly similar. This study shows that addition of NMR to the formulation toolbox has the ability to extend understanding of the relationship between site-specific changes and overall protein stability