Machine learning in the differentiation of follicular lymphoma from diffuse large B-cell lymphoma with radiomic [18F]FDG PET/CT features.

BACKGROUND: One of the challenges in the management of patients with follicular lymphoma (FL) is the identification of individuals with histological transformation, most commonly into diffuse large B-cell lymphoma (DLBCL). [18F]FDG-PET/CT is used for staging of patients with lymphoma, but visual interpretation cannot reliably discern FL from DLBCL. This study evaluated whether radiomic features extracted from clinical baseline [18F]FDG PET/CT and analyzed by machine learning algorithms may help discriminate FL from DLBCL. MATERIALS AND METHODS: Patients were selected based on confirmed histopathological diagnosis of primary FL (n=44) or DLBCL (n=76) and available [18F]FDG PET/CT with EARL reconstruction parameters within 6 months of diagnosis. Radiomic features were extracted from the volume of interest on co-registered [18F]FDG PET and CT images. Analysis of selected radiomic features was performed with machine learning classifiers based on logistic regression and tree-based ensemble classifiers (AdaBoosting, Gradient Boosting, and XG Boosting). The performance of radiomic features was compared with a SUVmax-based logistic regression model. RESULTS: From the segmented lesions, 121 FL and 227 DLBCL lesions were included for radiomic feature extraction. In total, 79 radiomic features were extracted from the SUVmap, 51 from CT, and 6 shape features. Machine learning classifier Gradient Boosting achieved the best discrimination performance using 136 radiomic features (AUC of 0.86 and accuracy of 80%). SUVmax-based logistic regression model achieved an AUC of 0.79 and an accuracy of 70%. Gradient Boosting classifier had a significantly greater AUC and accuracy compared to the SUVmax-based logistic regression (p≤0.01). CONCLUSION: Machine learning analysis of radiomic features may be of diagnostic value for discriminating FL from DLBCL tumor lesions, beyond that of the SUVmax alone.

Prognostic superiority of International Prognostic Index over [18F]FDG PET/CT volumetric parameters in post-transplant lymphoproliferative disorder.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLDs) are a spectrum of hematological malignancies occurring after solid organ and hematopoietic stem cell transplantation. [18F]FDG PET/CT is routinely performed at PTLD diagnosis, allowing for both staging of the disease and quantification of volumetric parameters, such as whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). In this retrospective study, we aimed to determine the prognostic value of MTV and TLG in PTLD patients, together with other variables of interest, such as the International Prognostic Index (IPI), organ transplant type, EBV tumor status, time after transplant, albumin levels and PTLD morphology. RESULTS: A total of 88 patients were included. The 1-, 3-, 5- year overall survival rates were 67%, 58% and 43% respectively. Multivariable analysis indicated that a high IPI (HR: 1.56, 95% CI: 1.13-2.16) and an EBV-negative tumor (HR: 2.71, 95% CI: 1.38-5.32) were associated with poor overall survival. Patients with a kidney transplant had a longer overall survival than any other organ recipients (HR: 0.38 95% CI: 0.16-0.89). IPI was found to be the best predicting parameter of overall survival in our cohort. Whole-body MTV, TLG, time after transplant, hypoalbuminemia and PTLD morphology were not associated with overall survival. CONCLUSION: [18F]FDG PET/CT whole-body volumetric quantitative parameters were not predictive of overall survival in PTLD. In our cohort, high IPI and an EBV-negative tumor were found to predictors of worse overall survival while kidney transplant patients had a longer overall survival compared to other organ transplant recipients.

Short communication: Algicide activity of antimicrobial peptides compounds against Prototheca bovis.

This study evaluated the in vitro activity of antimicrobial peptides pexiganan (MSI-78), h-Lf1-11, LL-37, cecropin B, magainin-2, and fengycin B against the veterinary mastitis agent Prototheca bovis. The results showed that pexiganan, h-Lf1-11, LL-37, and cecropin B were able to inhibit the growth and had effect on algicide P. bovis isolates (n = 32). The minimum inhibitory concentration ranged from 5 to 10 µg/mL for pexiganan, and algicide effect was detected from 5 to 20 µg/mL. The minimum inhibitory concentration ranged from 10 to 80 µg/mL for h-Lf1-11, 20 to 80 µg/mL for LL-37, and 40 to 160 µg/mL for cecropin B. These findings present a promising and novel alternative for P. bovis treatment and growth control.

Efficacy of miltefosine therapy against subcutaneous experimental pythiosis in rabbits.

We evaluated the in vitro activity of miltefosine against 29 Pythium spp. and the in vivo therapeutic response of 2mg/kg/day of miltefosine given orally to rabbit with pythiosis induced experimentally. The MICs (in µg/mL) of miltefosine was medium-dependent and ranged from 0.5 to 2 and 32-64 on RPMI 1640 and Mueller Hinton broth, respectively. The treatment with miltefosine demonstrated significantly lower subcutaneous lesion areas compared to the control group but was not sufficient for the complete remission of the lesions. This study indicates that miltefosine has limited efficacy against pythiosis and furthers in vitro and in vivo studies are necessary to determine the possible potential of this drug in the treatment of pythiosis.

Diagnostic performance of FDG-PET/CT of post-transplant lymphoproliferative disorder and factors affecting diagnostic yield.

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, requiring a timely and accurate diagnosis. In this study, we evaluated the diagnostic performance of FDG-PET/CT in patients with suspected PTLD and examined if lactate dehydrogenase (LDH) levels, Epstein-Barr virus (EBV) load, or timing of FDG-PET/CT relate to detection performance of FDG-PET/CT. METHODS: This retrospective study included 91 consecutive patients with clinical suspicion of PTLD and a total of 97 FDG-PET/CT scans within an 8-year period. Pathology reports and a 2-year follow-up were used as the reference standard. Diagnostic performance of FDG-PET/CT for detection of PTLD as well as logistic regression analysis for factors expected to affect diagnostic yield were assessed. RESULTS: The diagnosis of PTLD was established in 34 patients (35%). Fifty-seven FDG-PET/CT scans (59%) were true negative, 29 (30%) were true positive, 6 (6%) false positive, and 5 (5%) false negative. Sensitivity of FDG-PET/CT for the detection of PTLD was 85%, specificity 90%, positive predictive value 83%, and negative predictive value 92%, with good inter-observer variability (k = 0.78). Of the parameters hypothesized to be associated with a true positive FDG-PET/CT result for the diagnosis of PTLD, only LDH was statistically significant (OR 1.03, p = 0.04). CONCLUSION: FDG-PET/CT has a good diagnostic performance in patients suspected of PTLD, with a good inter-observer agreement. Only LDH levels seemed to influence the detection performance of FDG-PET/CT. EBV-DNA load and timing of FDG-PET/CT after transplantation did not affect FDG-PET/CT diagnostic yield.

Relationship between semiquantitative 18F-fluorodeoxyglucose positron emission tomography metrics and necrosis in classical Hodgkin lymphoma.

Semiquantitative 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by 18F-FDG PET or computed tomography (CT) (necrosisvisual) correlates with an adverse prognosis. We investigated whether semiquantitative 18F-FDG PET metrics correlate with necrosisvisual, determined the incidence of necrosisvisual and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited 18F-FDG PET and a contrast enhanced CT scan. Semiquantitative 18F-FDG PET parameters were determined using Hermes Hybrid 3D software. Necrosisvisual, defined by photopenic tumor areas on 18F-FDG PET and attenuation values between 10 and 30 Hounsfield units (HUs) on CT, was assessed blinded to outcome. Univariate Cox regression survival analyses of progression free survival (PFS) were performed. Necrosisvisual was observed in 18.3% of cHL patients. Bulky disease (tumor mass >10 cm in any direction) (P = 0.002) and TLG (P = 0.041) but no other semiquantitative parameters were significantly associated with necrosisvisual. In exploratory univariate survival analysis for PFS the covariates IPS, bulky disease, MTV and TLG were prognostic, while necrosisvisual was not.

Susceptibility profile of Candida rugosa (Diutina rugosa) against antifungals and compounds of essential oils.

Candida rugosa (recently reclassified Diutina rugosa) is an emerging pathogen affecting humans and animals. Candida resistance to existing drugs is an important factor to be monitored, as well as the need of researching alternatives to conventional antifungals. Here, we evaluated the in vitro effects of some antifungals and major components of essential oils by the broth microdilution method (CLSI M27-A3) against fifteen C. rugosa strains from animals isolated and molecular identificated. The results showed MIC90 of: 0.125µg/mL to ketoconazole and voriconazole, 0.25µg/mL to micafungin, 0.5µg/mL to anidulafungin, 1µg/mL to caspofungin, 2µg/mL to amphotericin B, itraconazole and flucytosin, 8µg/mL to fluconazole, 16µg/mL to nystatin and >128µg/mL to terbinafine. The compounds carvacrol (MIC90 320µg/mL), thimol (MIC90 320µg/mL) and cinnamaldehyde (MIC90 160µg/mL) demonstrated antifungal activity against the samples tested.

Performance of advanced imaging modalities at diagnosis and treatment response evaluation of patients with post-transplant lymphoproliferative disorder: A systematic review and meta-analysis.

INTRODUCTION AND AIM: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, associated with significant morbidity and mortality. In this systematic review we evaluated the clinical performance of advanced imaging modalities at diagnosis and treatment response evaluation of PTLD patients after solid organ and hematopoietic stem cell transplantation. METHODS: We have carried out a literature search until December 15, 2017 using PubMed/Medline, Embase, "Web of Science" and Cochrane Library databases concerning the performance of computed tomography (CT), magnetic resonance imaging (MRI) and 18F-flurodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) at diagnosis or treatment response evaluation of PTLD patients. RESULTS: A total of 11 studies were included comprising 368 patients, from which FDG-PET(/CT) was the primary imaging modality investigated. The methodological quality according to QUADAS-2 of the reviewed studies was moderate-poor. Subgroup analysis of imaging results for detection and staging in patients with PTLD indicated that FDG-PET/(CT) identified additional lesions not detected by CT and/or MRI in 27.8%, (95% confidence interval [95%CI]) 17.0%-42.0% (I2 = 51.1%), from which extra-nodal sites in 23.6% (95%CI: 7.9%-52.4%) (I2 = 76.6%). False negative results occurred in 11.5% (95%CI: 4.9%-24.5%) (I2 = 73.4%), predominantly in physiological high background activity regions and in early PTLD lesions. False positive results occurred in 4.8% (95%CI: 2.6%-8.6%) (I2 = 0%) predominantly due to inflammatory conditions. Subgroup analysis of imaging results at treatment response evaluation indicated that FDG-PET(/CT) findings altered or guided treatment in 29.0% (95%CI: 14.0%-50.5%) (I2 = 40.1%). False positive results during treatment response evaluation were reported in 20.0% (95%CI: 10.7%-34.2%) (I2 = 0%), predominantly due to inflammatory conditions. CONCLUSION: FDG-PET(/CT) is currently the most frequently investigated imaging modality in PTLD patients. Available studies report promising results in detection, staging and therapy evaluation but suffer from methodological shortcomings. Concerns remain with regard to occurrence of false negatives due to physiological high background activity and early PTLD lesions as well as false positives due to inflammatory conditions.

Sonochemical assisted synthesis of SrFe12O19 nanoparticles.

We present the synthesis of M-type strontium hexaferrite by sonochemistry and annealing. The effects of the sonication time and thermal energy on the crystal structure and magnetic properties of the obtained powders are presented. Strontium hexagonal ferrite (SrFe12O19) was successfully prepared by the ultrasonic cavitation (sonochemistry) of a complexed polyol solution of metallic acetates and diethylene glycol. The obtained materials were subsequently annealed at temperatures from 300 to 900 °C. X-ray diffraction analysis shows that the sonochemical process yields an amorphous phase containing Fe(3+), Fe(2+) and Sr(2+) ions. This amorphous phase transforms into an intermediate phase of maghemite (γ-Fe2O3) at 300 °C. At 500 °C, the intermediate species is converted to hematite (α-Fe2O3) by a topotactic transition. The final product of strontium hexaferrite (SrFe12O19) is generated at 800 °C. The obtained strontium hexaferrite shows a magnetization of 62.3 emu/g, which is consistent with pure hexaferrite obtained by other methods, and a coercivity of 6.25 kOe, which is higher than expected for this hexaferrite. The powder morphology is composed of aggregates of rounded particles with an average particle size of 60 nm.

Mechanical alloying of biocompatible Co-28Cr-6Mo alloy.

We report on an alternative route for the synthesis of crystalline Co-28Cr-6Mo alloy, which could be used for surgical implants. Co, Cr and Mo elemental powders, mixed in an adequate weight relation according to ISO Standard 58342-4 (ISO, 1996), were used for the mechanical alloying (MA) of nano-structured Co-alloy. The process was carried out at room temperature in a shaker mixer mill using hardened steel balls and vials as milling media, with a 1:8 ball:powder weight ratio. Crystalline structure characterization of milled powders was carried out by X-ray diffraction in order to analyze the phase transformations as a function of milling time. The aim of this work was to evaluate the alloying mechanism involved in the mechanical alloying of Co-28Cr-6Mo alloy. The evolution of the phase transformations with milling time is reported for each mixture. Results showed that the resultant alloy is a Co-alpha solid solution, successfully obtained by mechanical alloying after a total of 10 h of milling time: first Cr and Mo are mechanically prealloyed for 7 h, and then Co is mixed in for 3 h. In addition, different methods of premixing were studied. The particle size of the powders is reduced with increasing milling time, reaching about 5 mum at 10 h; a longer time promotes the formation of aggregates. The morphology and crystal structure of milled powders as a function of milling time were analyzed by scanning electron microscopy and XR diffraction.

Diet and physical activity: a healthful binomial.

Individual health status is the result of a combination of different factors such as genetics, dowry, age, nutritional status, physical activity, as well as environmental factors, hygiene, salubrity, stress and tobacco consumption. The existence of bad food habits and other risk factors leads to an increase in the development of chronic diseases, obesity, diabetes, cardiovascular disease, osteoporosis and certain types of cancer. Such diseases occupy greater rates of morbidity and mortality in European countries. This situation seems to justify that in our country defective intervention on different risk factors or, perhaps, a worsening in the control of some of them is taking place where the diet and lifestyle seem clearly implied. It is clear that if we take as bases the angular determinants for cardiovascular health identified in the 'Victory Declaration on Cardiac Health', healthful food habits, free tobacco lifestyle, regular physical activity and positive psycho-social atmosphere, future perspectives in our country do not seem to be very favourable.

Evaluation of a new tablet formulation based on Bacillus thuringiensis sorovar. israelensis for larvicidal control of Aedes aegypti.

The effect of sunlight on the efficacy and persistence of an experimental tablet formulation based on Bacillus thuringiensis sorovar. israelensis (C4P1) was evaluated against Aedes aegypti larvae under simulated field conditions. The initial mortality ranged from 93 to 100%, and the residual activity (> or = 70% mortality) recorded in containers exposed to sunlight or shade were, respectively, 13-35 days and 40-54 days. The results suggest that C4P1 can provide long-term larvicidal effect and operational advantages.

Randomized single-blind trial of topical ketanserin for healing acceleration of diabetic foot ulcers.

The objective of this study was to determine the efficacy of topically applied ketanserin for healing acceleration of diabetic foot ulcers. From August 1993 to September 1994, 140 NIDDM patients entered a randomized single-blind trial of topical ketanserin (Sufrexal, Janssen Pharmaceuticals; n = 69) vs. normal saline (labeled here as placebo; n = 71). All patients were subjected to surgical debridement of necrotic tissue and lavage with normal saline. Wounds were < 100 cm2 in area. Persons with NIDDM and foot ulcers Wagner 2 and 3 with a median of 8 (interquartile range 4-26) weeks duration were included. Ulcer area was measured at 0, 4, 8 and 12 weeks. The groups were similar in age, sex, years of diabetes duration, obesity, ulcer Wagner type, number of previous amputations and surgical debridements during this hospital stay. Average percent reduction in ulcer area at 12 weeks was 87% for ketanserin vs. 63% for placebo (p < 0.001). The regression equations for the least-squares fit to the area (y) against time (x) data points were y = 43.46-3.181x (r = -0.995) for ketanserin and y = 39.46-2.016x (r = -0.999) for placebo (p < 0.01). The 95% confidence limits for slopes were -3.181 +/- 0.98 and -2.016 +/- 0.15. Thus, average daily reduction in ulcer area was 4.5 mm2/day for ketanserin vs. 2.88 mm2/day for placebo. In conclusion, topical ketanserin significantly accelerated wound healing in diabetic neurotrophic foot ulcers when applied as part of a comprehensive healing program.

Clinical stage, age and treatment in tropical pyomyositis: a retrospective study including forty cases.

A comparative and retrospective trial of 40 patients with tropical pyomyositis covering studies done between January 1, 1987 and November 31, 1990, at the General Hospital at Cosamaloapan, Veracruz, IMSS, was undertaken. The objectives were to compare predisposing factors, clinical data, morbidity, mortaity and hospital stay among 1) medical (group I) and surgical treatment (II), 2) adult and pediatric populations and 3) the clinical stage of the disease (invasive, suppurative and late). In group I, the family history of diabetes (56%), fever (66%) and hospital stay (6.5 +/- 1.8 days) were significantly different from group II (19%, 100% and 12.8 +/- 5.5 days), respectively. The mean age in adult and pediatric populations was 38 and 8 years, respectively. Pediatric patients had lowest hemoglobin levels (9.7 +/- 1.3). Upper respiratory antecedent was highest in suppurative stage (65%). In the late stage eosinophilia (5.9 +/- 6.9), fluctuance muscles (100%), complication rate of 57%, surgical drainage (100%) and mortality of 29% were found. Cultures were performed in 20 cases with negative results in 55% and the remaining 45% were positive to Staphylococcus aureus. Pyomyositis appears to be multifactorial in origin, the antecedents of trauma and upper respiratory infection were the major predisposing factors. Septicemia caused high morbidity and mortality in the late stage. Surgical treatment was frequently needed, increasing costs.

Evidence for direct involvement of the sarcoplasmic reticulum Ca(2+)-ATPase in a passive monovalent cation (K+/Na+) exchange.

A specific inhibitor of SERCA-pumps, thapsigargin (TG) was used to demonstrate the direct involvement of the SR Ca(2+)-ATPase in passive K+/Na+ exchange. The K(+)-potential variations across vesicle membranes were measured in the absence of ATP with a fluorescent probe: 3,3'-dipropylthiodicarbocyanine iodide. Addition of EGTA dissipates the K(+)-potential whereas the presence of TG abolishes this effect. Our data prove that the Ca(2+)-ATPase translocates monovalent cations at a rate similar to the E2-->E1 conformational change.

[Delay in hospitalization, diagnosis and surgical intervention in acute appendicitis]. / Retardo en la hospitalización, el diagnóstico y la intervención quirúrgica de la apendicitis aguda.

AIMS: To assess if self-medication delays diagnosis and Surgical Treatment in acute appendicitis and increases morbidity, mortality and hospital stay as well. DESIGN: Retrospective, comparative and observational study. STATISTICS: Chi square, exact Fisher test. SUBJECTS AND STUDY GROUPS: 57 patients were subjected to appendectomy and were stratified in three groups according to the lapse of time between initiation of symptoms and hospitalization: group A less than 24 h (n = 20), group B between 24 and 48 h (n = 17), and group C more than 48 h (n = 20). RESULTS: Groups B and C showed a significant delay for both diagnosis (p < 0.001) and surgical intervention (p < 0.001) in relation to group A. The incidence of acute abdomen presentation showed a positive trend with time of hospitalization (p = 0.03). Self-medication increased from group A to C (p < 0.001). Groups B and C showed a complication rate of 24 and 25%, respectively (p > 0.05). Conversely, group A had not complications (p < 0.05). In addition there was a 5% mortality due to sepsis in group C. Finally, hospital stay was longer in groups B and C (p < 0.001). CONCLUSIONS: Self-medication correlated with delayed hospitalization, diagnosis, treatment and complications. Hospital stay was consequently longer.

Characteristic features of the heterologous functional synthesis in Escherichia coli of a 2[4Fe-4S] ferredoxin.

Different strategies have been used to express synthetic genes all encoding Clostridium pasteurianum 2[4Fe-4S] ferredoxin (Fd) in Escherichia coli. The polypeptide can be produced as the C-terminal addition to a hybrid Cro::Protein A fusion protein lacking the metallic centers. The incorporation of the [4Fe-4S] clusters into the cleaved apoFd cannot be carried out in the same conditions as those affording holoFd from purified C. pasteurianum apoFd. In contrast, fully functional Fds can be produced from non-fused synthetic genes under the dependence of strong promoters. The yields of recombinant Fd, although sufficient to purify significant quantities of protein, are limited by the very short half-life of the 2[4Fe-4S] Fd in E. coli, irrespective of the expression system used. These features are characteristic of 2[4Fe-4S] Fds when compared with the far more stable recombinant rubredoxin, and probably other small iron-sulfur proteins which have already been produced in high yields. The reasons for the high turnover of 2[4Fe-4S] Fds are discussed.

Nephrogenic adenoma with bladder exstrophy and immunosuppression.

Nephrogenic adenoma, an unusual proliferative lesion, often occurs in association with chronic inflammation of the bladder and is rarely found in children. Two cases are reported, one occurring in a young child born with bladder exstrophy, and one in a young female, with both interstitial cystitis and chronic use of immunosuppressive therapy. We believe these are the first case reports of nephrogenic adenoma occurring in this specific clinical setting.