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La presentación clínica, curso de la enfermedad y resultado de la infección por SARS-CoV-2 en pediatría difieren de los observados en adultos. En una revisión de Hoang et al. se estimó que la prevalencia de las manifestaciones dermatológicas fue de 0.25 % de un total de 2445 niños con COVID-19 confirmada. Según Parri, se documentó 3 % en 100 niños. En la revisión sistemática de Shah et al. se analizaron 13 estudios que incluyeron 149 niños que cumplieron con los criterios de elegibilidad. La lesión maculopapular eritematosa acral fue la más común, también el eritema multiforme, el exantema de la varicela y las presentaciones similares a enfermedad de Kawasaki. La duración de las lesiones cutáneas fue de una a dos semanas en 43 %. La biopsia de piel de 18 casos reveló infiltrado linfocítico perivascular, infiltrado paracrino superficial y profundo y vasculitis linfocítica. La RT-PCR fue positiva en 13.8 %. Los marcadores serológicos analizados de virus de herpes simple y parvovirus B19 fueron negativos, y fueron positivos para Mycoplasma pneumoniae en dos de 20 casos. El mecanismo fisiopatológico de las lesiones en piel secundarias a infección por SARS-CoV-2 aún no se ha podido explicar; es probable que se trate de la combinación de uno o más mecanismos complejos, daños cutáneos directos inducidos por el virus, reacciones vasculíticas o lesiones indirectas o secundarias como consecuencia de una reacción inflamatoria sistemática. Se revisaron las publicaciones de 2019 a 2021 en PubMed como fuente principal de búsqueda, para lo cual se utilizaron palabras clave.

La agricultura urbana contribuye a una alimentación saludable y a la seguridad y soberanía alimentaria, en población de escasos recursos. La pandemia generada por el COVID-19 generó impactos sociales en la ciudad a causa de la disminución en la productividad, lo cual aumentó el desempleo e impactó el ingreso de recursos económicos de las familias para suplir necesidades básicas como la alimentación. La Secretaría Distrital de Salud (SDS) impulso la estrategia de agricultura urbana con el objetivo de desarrollar acciones que permitieran a la población enfrentar los impactos sociales de la pandemia por COVID-19 en Bogotá, diseñando e implementando huertas agroecológicas en los entornos de vida hogar, educativo y comunitario, sin utilización de productos químicos, que brindaron alimentos a la comunidad en la ciudad en el periodo enero a septiembre del 2021. Se evidenció que el entorno de mayor producción de alimentos de manera saludable y sostenible fue el comunitario y las localidades con mayor extensión de vida en área sembrada fueron las que más ruralidad tienen como Sumapaz, Usme y Ciudad Bolívar. Los productos sembrados más relevantes fueron hortalizas y verduras, y en el entorno hogar las plantas medicinales y aromáticas. Se concluyó que hubo una buena recepción y aceptación de las acciones de agricultura urbana por parte de la comunidad, lo que contribuyó de manera integrada a la implementación de las dimensiones de Seguridad Alimentaria y Nutricional, y de Salud Ambiental, del Plan Decenal de Salud Pública.

To calculate the diagnostic performance of [sup18/supF]-FDG PET/MR in colorectal cancer (CRC).This study was designed following the PRISMA-DTA guidelines. To be included, published original articles (until December 31, 2021) that met the following criteria were considered eligible: (1) evaluated [sup18/supF]-FDG PET/MR as the diagnostic method to detect CRC; (2) compared [sup18/supF]-FDG PET/MR with histopathology as the reference standard, or clinical/imaging composite follow-up when pathology was not available; (3) provided adequate crude data for meta-analysis. The diagnostic pooled measurements were calculated at patient and lesion levels. Regarding sub-group analysis, diagnostic measurements were calculated in "TNM staging," "T staging," "N staging," "M staging," and "liver metastasis" sub-groups. Additionally, we calculated the pooled performances in "rectal cancer: patient-level" and "rectal cancer: lesion-level" sub-groups. A hierarchical method was used to pool the performances. The bivariate model was conducted to find the summary points. Analyses were performed using STATA 16.A total of 1534 patients from 18 studies were entered. The pooled sensitivities in CRC lesion detection (tumor, lymph nodes, and metastases) were 0.94 (95%CI: 0.89-0.97) and 0.93 (95%CI: 0.82-0.98) at patient-level and lesion-level, respectively. The pooled specificities were 0.89 (95%CI: 0.84-0.93) and 0.95 (95%CI: 0.90-0.98) at patient-level and lesion-level, respectively. In sub-groups, the highest sensitivity (0.97, 95%CI: 0.86-0.99) and specificity (0.99, 95%CI: 0.84-1.00) were calculated for "M staging" and "rectal cancer: lesion-level," respectively. The lowest sensitivity (0.81, 95%CI: 0.65-0.91) and specificity (0.79, 95%CI: 0.52-0.93) were calculated for "N staging" and "T staging," respectively.This meta-analysis showed an overall high diagnostic performance for [sup18/supF]-FDG PET/MR in detecting CRC lesions/metastases. Thus, this modality can play a significant role in several clinical scenarios in CRC staging and restaging. Specifically, one of the main strengths of this modality is ruling out the existence of CRC lesions/metastases. Finally, the overall diagnostic performance was not found to be affected in the post-treatment setting.

Lung cancer remains the leading cancer-related death across North America. Imaging is fundamental. Recently, healthcare disparities came into research focus. Our aim was to explore disparity from an imaging, genetic, and outcome perspective. We utilized the AACR Project GENIE Biopharma Consortium (BPC) dataset v 1.1 to build a collated NSCLC dataset. Descriptive and analytical statistics were applied according to data characteristics. From 1849 patients, mean age was 64.4 y (±10.5), 58% (n = 1065) were female, 23% (n = 419) never smoked, 84% (n = 1545) were of white race, and 57% (n = 1052) were < stage III. No difference (p > 0.05) was found for baseline imaging by race. White race showed higher 3-month surveillance imaging (p = 0.048) and a baseline stage < IV (OR 0.61). KRAS (33.3 vs. 17.9%), STK11 (14.8 vs. 7.3%), and KEAP1 (13.3 vs. 5.3%) mutations were predominant among white patients while EGFR mutation (19.2 vs. 44.1%) was less predominant. Mutations in TP53 or KEAP1 had worse PFS and OS. The latter was also reduced in STK11, KRAS + STK11, and KRAS + KEAP1 mutations. Meanwhile, EGFR mutation had increased OS. Multivariate analysis showed that progression on imaging at 3 or 6 months (HR 1.69 and 1.43, respectively), TP53 (HR 1.37) and KRAS (HR 1.26) had lower OS while EGFR and LRP1B (HR 0.69 and 0.39, respectively) had higher OS. No racial disparity at baseline imaging was observed. Higher initial stages among non-white patients might reflect inequalities in accessing healthcare. However, race wasn’t associated to OS. Finally, progression in imaging at 3 or 6 months showed the higher hazard ratios for death.

We investigated the prognostic value of sarcopenia measurements and metabolic parameters of primary tumors derived from 18F-FDG-PET/CT among patients with primary, metastatic esophageal and gastroesophageal cancer. A total of 128 patients (26 females; 102 males; mean age 63.5 ± 11.7 years; age range: 29–91 years) with advanced metastatic gastroesophageal cancer who underwent 18F-FDG-PET/CT as part of their initial staging between November 2008 and December 2019 were included. Mean and maximum standardized uptake value (SUV) and SUV normalized by lean body mass (SUL) were measured. Skeletal muscle index (SMI) was measured at the level of L3 on the CT component of the 18F-FDG-PET/CT. Sarcopenia was defined as SMI < 34.4 cm2/m2 in women and

The imaging report is essential for the communication between physicians in patient care. The information it contains must be clear, concise with evidence-based conclusions and sufficient to support clinical decision-making. In recent years, several classification schemes and/or reporting guidelines for PET have been introduced. In this manuscript, we will review the classifications most frequently used in oncology for interpreting and reporting 18F-FDG PET imaging in lymphoma, multiple myeloma, melanoma and head and neck cancers, PSMA-ligand PET imaging for prostate cancer, and 68Ga-DOTA-peptide PET in neuroendocrine tumors (NET).

Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

To determine in a group of patients with progressive metastatic neuroendocrine tumors (PM-NETs) treated with 177Lu-DOTATATE whether a correlation exists between somatostatin receptor (SSTR)-2 expression in various tumors on baseline 68Ga-DOTATATE PET and their response to therapy. A secondary aim was to determine whether an association exists between tumor product of diameter (POD) and PET-derived Krenning score.Patients treated PM-NETs who had SSTR-2 overexpression (SSTR-RADS 5) on screening 68Ga-DOTATATE PET and CT at baseline and 3 months after therapy completion were included. Marker lesions on baseline CT were reassessed on CT after therapy using adapted Southwest Oncology Group solid tumor evaluation criteria. For each lesion, bidimensional diameter on CT and SSTR expression on PET (SSTR-RADS uptake scorePET-derived Krenning score) were recorded. Logistic regression models fitted through generalized estimating equations were used to assess for an association between SSTR expression and response to therapy, or lesion's POD.Forty-one patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE were included. There were 135 marker lesions (mean 3.2 lesions/patient) with Krenning score of 4 (n = 74), 3 (n = 44) or 2 (n = 17). There was no association found between SSTR-2 expression, as determined by SSTR-RADS uptake score or PET-derived Krenning score, and POD or response to therapy.In patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE, there was similar response to therapy for all lesions with PET-generated Krenning score ≥2. No correlation was found between lesion's POD and level of tracer uptake.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI

Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials &amp, Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT and bone scintigraphy who were candidates for salvage therapy, as determined by a multidisciplinary panel of experts. 18F-DCFPyL PET was assessed for the presence and extent of recurrence: local, oligometastatic (≤4), or extensive. Post-PET management and clinical outcome, including PSA response, was documented. For patients who received PET-directed ablative therapies, response was categorized as “complete” if PSA became undetectable or “favorable” if PSA decreased ≥50%. Results: Forty-seven men with biochemical failure after radical prostatectomy (n = 29), primary radiotherapy (n = 15) or focal tumor ablation (n = 3) were included. PET was positive in (43/47) 91.5%, including local recurrence in (9/47) 19.2%, oligometastatic disease in (16/47) 34%, and extensive metastatic disease in (18/47) 38.3%. PET-directed focal ablative therapies without systemic therapy were given to (13/29) 44.8% of patients without extensive metastases on PET with a mean PSA response of 69% (median, 74.5%, range: 35–100). Favorable biochemical response was observed in (10/13) 76.9% of patients with limited recurrence on PET, and in 23.1% (3/13), there was complete response. Conclusion: 18F-DCFPyL PET was positive in &gt, 90% of patients with biochemical failure. For those with limited recurrence, PSMA PET-directed local ablative therapies resulted in favorable outcome in more than 3 in 4 patients, and in nearly a quarter of them, there was complete biochemical response.

Background: To investigate, whether 18[18F]-FDG PET/CT - derived radiomics combined with sarcopenia measurements improves survival prognostication among patients with advanced, metastatic gastroesophageal cancer. Methods: In this IRB-approved retrospective study, we included 128 consecutive patients with advanced, metastatic esophageal and gastroesophageal cancer (n=128; 26 females; 102 males; mean age 63.5±11.7 years; age range: 29-91 years) undergoing 18[18F]-FDG PET/CT for staging between November 2008 and December 2019. Segmentation of the primary tumor and radiomics analysis derived from PET and CT images was performed semi-automatically with a commonly used open-source software platform (LIFEX, Version 6.30, lifexsoft.org). Patients’ nutritional status was determined by measuring the skeletal muscle index (SMI) at the level of L3 on the CT component. Univariable and multivariable analyses were performed to establish a survival prediction model including radiomics, clinical data, and SMI score. Results: In a univariable Cox proportional hazards model, ECOG (Conclusion: PET and CT radiomics derived from hybrid 18[18F]-FDG PET/CT combined with sarcopenia measurements and clinical parameters may improve survival prediction among patients with advanced, metastatic gastroesophageal cancer.

PurposeRadiomics is an emerging imaging assessment technique that has shown promise in predicting survival among nasopharyngeal carcinoma (NPC) patients. Studies so far have focused on PET or MR-based radiomics independently. The aim of our study was to evaluate the prognostic value of clinical and radiomic parameters derived from both PET/CT and MR.MethodsRetrospective evaluation of 124 NPC patients with PET/CT and radiotherapy planning MR (RP-MR). Primary tumors were segmented using dedicated software (LIFEx version 6.1) from PET, CT, contrast-enhanced T1-weighted (T1-w), and T2-weighted (T2-w) MR sequences with 376 radiomic features extracted. Summary statistics describe patient, disease, and treatment characteristics. The Kaplan–Meier (KM) method estimates overall survival (OS) and progression-free survival (PFS). Clinical factors selected based on univariable analysis and the multivariable Cox model were subsequently constructed with radiomic features added.ResultsThe final models comparing clinical, clinical + RP-MR, clinical + PET/CT and clinical + RP-MR + PET/CT for OS and PFS demonstrated that combined radiomic signatures were significantly associated with improved survival prognostication (AUC 0.62 vs 0.81 vs 0.75 vs 0.86 at 21 months for PFS and 0.56 vs 0.85 vs 0.79 vs 0.96 at 24 months for OS). Clinical + RP-MR features initially outperform clinical + PET/CT for both OS and PFS (42 months).ConclusionOur study demonstrated that PET/CT-based radiomic features may improve survival prognostication among NPC patients when combined with baseline clinical and MR-based radiomic features.

Background/rationalePET/CT plays a crucial role in esophageal (EC) and gastroesophageal junction cancer (GEJ) diagnosis and management. Despite endorsement in clinical guidelines, variation in acceptance of PET/CT exists. The aim of this study was to assess the early use of PET/CT among EC and GEJ patients in a regionalized setting and identify factors contributing to disparity in access.Materials and methodsRetrospective cohort study of adults with EC or GEJ between 2012 and 2014 from the Population Registry of Esophageal and Stomach Tumours of Ontario and Ontario Health (Cancer Care Ontario). Receipt of PET/CT and relevant demographics were collected, and statistical analysis performed. Continuous data were analysed with t-tests and Wilcoxon rank sum test. Categorical data were analysed with chi-square test. Kaplan–Meier methods were used to estimate median survival.ResultsFifty-five percent of patients diagnosed with EC or GEJ between 2012 and 2014 received PET/CT (1321/2390). Eighty-four percent of patients underwent surgical resection (729/870), and 80% receiving radical treatment (496/622) underwent PET/CT. The use of PET/CT increased from 2012 to 2014. Male patients received more PET/CT than females (85% vs.78% p Median survival for the overall cohort was 11.1 months, 17.2 vs. 5.2 months among those who did and did not receive PET/CT and 35 vs. 27 months among the surgical cohort (p = 0.16).ConclusionsWe found that PET/CT use increased from 2012 to 2014 and that the majority of EC/GEJ patients being considered for curative therapy received PET/CT. There were also gender disparities identified. PET/CT appears to confer a potential survival benefit in our study, although our assessment is limited. Our findings may serve as learned lessons for other new imaging modalities, new indications for PET/CT or even for the introduction of new radiopharmaceuticals for PET/CT.

Purpose: We aim determine the value of PET and CT radiomic parameters on survival with serial follow-up PET/CT in patients with nasopharyngeal carcinoma (NPC) for which curative intent therapy is undertaken. Methods: Patients with NPC and available pre-treatment as well as follow up PET/CT were included from 2005 to 2006 and were followed to 2021. Baseline demographic, radiological and outcome data were collected. Univariable Cox proportional hazard models were used to evaluate features from baseline and follow-up time points, and landmark analyses were performed for each time point. Results: Sixty patients were enrolled, and two-hundred and seventy-eight (278) PET/CT were at baseline and during follow-up. Thirty-eight percent (38%) were female, and sixty-two patients were male. All patients underwent curative radiation or chemoradiation therapy. The median follow-up was 11.72 years (1.26–14.86). Five-year and ten-year overall survivals (OSs) were 80.0% and 66.2%, and progression-free survival (PFS) was 90.0% and 74.4%. Time-dependent modelling suggested that, among others, PET gray-level zone length matrix (GLZLM) gray-level non-uniformity (GLNU) (HR 2.74 95% CI 1.06, 7.05) was significantly associated with OS. Landmark analyses suggested that CT parameters were most predictive at 15 month, whereas PET parameters were most predictive at time points 3, 6, 9 and 15 month. Conclusions: This study with long-term follow up data on NPC suggests that mainly PET-derived radiomic features are predictive for OS but not PFS in a time-dependent evaluation. Furthermore, CT radiomic measures may predict OS and PFS best at initial and long-term follow-up time points and PET measures may be more predictive in the interval. These modalities are commonly used in NPC surveillance, and prospective validation should be considered.

The aim of this study was to determine if radiomic features combined with sarcopenia measurements on pretreatment 18 F-FDG PET/CT can improve outcome prediction in surgically treated adenocarcinoma esophagogastric cancer patients.One hundred forty-five esophageal adenocarcinoma patients with curative therapeutic intent and available pretreatment 18 F-FDG PET/CT were included. Textural features from PET and CT images were evaluated using LIFEx software ( lifexsoft.org ). Sarcopenia measurements were done by measuring the Skeletal Muscle Index at L3 level on the CT component. Univariable and multivariable analyses were conducted to create a model including the radiomic parameters, clinical features, and Skeletal Muscle Index score to predict patients' outcome.In multivariable analysis, we combined clinicopathological parameters including ECOG, surgical T, and N staging along with imaging derived sarcopenia measurements and radiomic features to build a predictor model for relapse-free survival and overall survival. Overall, adding sarcopenic status to the model with clinical features only (likelihood ratio test P = 0.03) and CT feature ( P = 0.0037) improved the model fit for overall survival. Similarly, adding sarcopenic status ( P = 0.051), CT feature ( P = 0.042), and PET feature ( P = 0.011) improved the model fit for relapse-free survival.PET and CT radiomics derived from combined PET/CT integrated with clinicopathological parameters and sarcopenia measurement might improve outcome prediction in patients with nonmetastatic esophagogastric adenocarcinoma.

To assess whether 18F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT). This ethics review board–approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received 18F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies. There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p

espanolObjetivo: el objetivo principal de este trabajo es analizar el contenido que las marcas mas vendidas del sector automovilistico en Espana en el ano 2019 estan difundiendo en sus canales propios en YouTube. Diseno/metodologia/enfoque: se sigue la metodologia de analisis de contenido para analizar los videos mas populares de las diez marcas de coches utilitarias mas vendidas en el ano 2019 en Espana. Para ello se identifica, en primer lugar, el canal, suscriptores y los videos mas visualizados desde finales de 2018 y a lo largo de 2019. En segundo lugar, se analiza el contenido de los mensajes y, por ultimo, la interaccion de los publicos a traves del numero de «me gusta» que ha recibido cada uno de los videos analizados. Resultados: los resultados han permitido entender que contenido estan difundiendo las marcas de automoviles a traves de sus canales propios de YouTube en un periodo concreto. Ademas, de poner de manifiesto que, aunque el contenido mas habitual sea el clasico spot publicitario que las marcas utilizan para television y otros medios convencionales, tambien se ha desvelado la utilizacion de YouTube para apoyar la estrategia de Inbound marketing. Limitaciones/implicaciones: se trata de una investigacion descriptiva, cuyo alcance es exploratorio, por lo que su principal aportacion es una revision novedosa sobre el objeto de estudio que supone un punto de partida para investigaciones posteriores. Asimismo, dada la limitada muestra, 50 videos, y que los datos obtenidos a traves del analisis se han acotado a un periodo de tiempo concreto, los resultados no se pueden generalizar, pero si permiten abrir una reflexion acerca del uso de los canales propios de YouTube por parte de las marcas del sector del automovil. Originalidad/contribucion: la originalidad de este estudio radica en el estudio de un sector en concreto, el automovilistico, y por su relevancia como anunciante y como sector empresarial. EnglishPurpose: the main goal of this paper is to analyse the content that the best-selling brands in the automotive sector in Spain during 2019 are broadcasting on their own YouTube channels. Design / Methodology / Approach: the content analisis methodology is followed to analyse the most popular videos of the ten best-selling utility car brands in 2019 in Spain. To do this, firstly, the channel, subscribers and the most viewed videos since the end of 2018 and throughout 2019 are identified. Secondly, the content of the messages is analysed and, finally, the interaction of audience by the number of «likes» received by each of the analysed videos. Results: the results have made possible to understand what content car brands are broadcasting through their own YouTube channels in a specific period. In addition, it is proved that, though the most common content is the classic advertising spot that brands use for television and other conventional media, the use of YouTube has also been revealed to support the Inbound marketing strategy. Limitations / Implications: this is descriptive research, which scope is exploratory, so its main contribution is a new review of the studied object that provides a starting point for further research. In addition, given the limited sample, 50 videos, and that fact obtained through the analysis have been limited to a specific period of time, results cannot be generalised, but they do allow us to reflect on the use of YouTube channels by brands in the automotive sector. Originality / Contribution: the originality of this paper lies in the study of a specific sector, the automotive, and its relevance as an advertiser and as a business sector.

PURPOSE: To determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT (bPET) and interim PET (iPET) performed prior to second cycle of therapy are predictive of therapy response and progression free survival (PFS). PATIENTS & METHODS: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki67, 8.3%) underwent 68Ga-DOTATATE PET/CT (DT- PET) to determine suitability for peptide receptor radionuclide therapy (PRRT) as part of a prospective multicenter study. Mean follow-up was 12.2 months. Of them, 36 patients had iPET. Tumor metrics evaluated: 1. Marker lesion-based measures: mean SUVmax and ratio to liver/spleen; 2. Segmented DT tumor volume (DTTV) measures: DTTV; SUVmax and SUVmean using liver and spleen as thresholds; 3. Heterogeneity parameters (coefficient of variance, kurtosis, and skewness). Wilcoxon rank sum test was used for association between continuous variables and therapy response as determined by clinical response. Univariable and multivariable Cox proportional hazards model were used for association with PFS. RESULTS: There were 71 responders and 20 non-responders. Using marker lesions, higher mean SUVmax and mean SUVmax(Tumor/Liver) were predictors of therapy response (P = 0.018 & 0.024, respectively). For DTTV, higher SUVmax and SUVmean using liver as threshold and lower kurtosis were predictors of favorable response (P = 0.025, 0.0055 & 0.031, respectively. These also correlated with longer PFS. iPET DTTV SUVmean using liver threshold and ratio iPET mean SUVmax using target lesions correlated with therapy response (P = 0.024 & 0.048, respectively) but not PFS. From the multivariable analysis adjusting for age, primary site and Ki67, mean SUVmax (P = 0.019), SUVmax T/L (P = 0.018), SUVmax T/S (P = 0.041), DTTV SUVmean Liver (P = 0.0052) and skewness (P = 0.048) remain significant predictors of PFS. CONCLUSION: Degree of somatostatin receptor expression and tumor heterogeneity as represented by several metrics in our analysis are predictive of therapy response and/or PFS. Change in these parameters after first cycle of PRRT did not correlate with clinical outcomes.

Purpose: The aim of the study is to evaluate the prognostic value of a joint evaluation of PET and CT radiomics combined with standard clinical parameters in patients with HL. Methods: Overall, 88 patients (42 female and 46 male) with a median age of 43.3 (range 21–85 years) were included. Textural analysis of the PET/CT images was performed using freely available software (LIFE X). 65 radiomic features (RF) were evaluated. Univariate and multivariate models were used to determine the value of clinical characteristics and FDG PET/CT radiomics in outcome prediction. In addition, a binary logistic regression model was used to determine potential predictors for radiotherapy treatment and odds ratios (OR), with 95% confidence intervals (CI) reported. Features relevant to survival outcomes were assessed using Cox proportional hazards to calculate hazard ratios with 95% CI. Results: albumin (p = 0.034) + ALP (p = 0.028) + CT radiomic feature GLRLM GLNU mean (p = 0.012) (Area under the curve (AUC): 95% CI (86.9; 100.0)—Brier score: 3.9, 95% CI (0.1; 7.8) remained significant independent predictors for PFS outcome. PET-SHAPE Sphericity (p = 0.033); CT grey-level zone length matrix with high gray-level zone emphasis (GLZLM SZHGE mean (p = 0.028)); PARAMS XSpatial Resampling (p = 0.0091) as well as hemoglobin results (p = 0.016) remained as independent factors in the final model for a binary outcome as predictors of the need for radiotherapy (AUC = 0.79). Conclusion: We evaluated the value of baseline clinical parameters as well as combined PET and CT radiomics in HL patients for survival and the prediction of the need for radiotherapy treatment. We found that different combinations of all three factors/features were independently predictive of the here evaluated endpoints.

PurposeRadiomics is an emerging imaging assessment technique, which has shown promise predicting survival among nasopharyngeal carcinoma (NPC) patients. Studies so far have focused on MR-based radiomic analysis. The aim of our study was to evaluate the prognostic value of clinical and radiomic parameters derived from both PET/CT and MR.MethodsRetrospective evaluation of 124 NPC patients with PET/CT and radiotherapy planning MR (RP-MR). Primary tumors were segmented using dedicated software (LIFEx .version 6.1) from PET, CT, contrast enhanced T1-weighted (T1-w), and T2-weighted (T2-w) MR sequences with 376 radiomic features extracted. Summary statistics described patient, disease and treatment characteristics. Kaplan Meier (KM) method estimated overall survival (OS) and progression free survival (PFS). Clinical factors selected based on univariate analysis and multivariate Cox model were subsequently constructed with radiomic features added.ResultsThe final models comparing clinical, clinical + RP-MR, clinical + PET/CT and clinical + RP-MR + PET/CT for OS and PFS demonstrated that combined radiomics signatures were significantly associated with improved survival prognostication (AUC 0.62 vs 0.81 vs 0.75 vs 0.86 at 21 months for PFS and 0.56 vs 0.85 vs 0.79 vs 0.96 at 24 months for OS). Clinical + RP-MR features initially outperform clinical + PET/CT for both OS and PFS ( 42 months).ConclusionOur study demonstrated that PET/CT-based radiomic features may improve survival prognostication among NPC patients when combined with baseline clinical and MR-based radiomic features.

Background: In many countries, hypertension in the pediatric population is considered a serious risk of mortality and morbidity. In this respect, it is central to design and develop new pharmaceutical forms for pediatric patients with hypertension. The development of Orodispersible Mini-Tablets (ODMTs) for pediatric use has gained importance in recent years. Therefore, regulations for developing suitable and palatable dosage forms for pediatric patients have been established by WHO authorities. Objective: This study aimed to design and develop orodispersible mini tablets of enalapril maleate (EnM ODMTs) for pediatric use. Methods: Five pharmaceutical formulations (A, B, C, D and E, shown in Table 1) were designed. The effects of different co-processed excipients and active pharmaceutical ingredients at different doses were studied. Lactose co-processed excipients selected were the following: Tablettose® 80, Microce- Lac® 100 and StarLac®. The micromeritic properties for all the physical mixtures were examined. The mini tablets were obtained by direct compression. Quality control parameters were determined in accordance with US Pharmacopeia. Results: Three OMDTs with StarLac® showed good results of hardness, flow ability and fast disintegration. The formulation with 0.1 mg of enalapril maleate presented the best results for the official parameters of hardness (4.0 kp), friability (< 1%), disintegration time (28 s), drug content uniformity (103.6 %), and wetting time (23 s). Conclusion: The three OMDTs with StarLac® showed good quality parameters, according to official requirements. Formulation A exhibited the best wetting time, complying with the dose recommended for pediatric patients. This formulation could be considered eligible for being manufactured at industrial scale.

Los medios de comunicación a partir de la implementación de las nuevas Tecnologías de la Información y Comunicación (TIC) se han diversificado conforme a la evolución y adaptación del uso de dispositivos tecnológicos en la vida del hombre. Con la hibridación de los medios surge la ecología mediática en la cual emergen nuevas formas de llevar acabo el acto comunicativo, los medios de comunicación se adaptan a la prácticas comunicativas y en ello se condensan las nuevas formas de comunicar. Estudiar el alcance y los niveles significativos de los modelos convergentes en los procesos de comunicación digital no sólo nos acercan al panorama mediático también nos vislumbra las capacidades de las plataformas y los dispositivos en el contexto social. En el siguiente documento discutiremos como a partir de la implementación de herramientas digitales y las narrativas transmedia podemos generar un aporte significativo a la apropiación del conocimiento por parte de los usuarios. Mediante el reconocimiento de los niveles de significación de todos los actores involucrados en la comunidad, entenderemos como las dinámicas participativas y colaborativas nos acercan a la democratización del conocimiento. Para comprender tanto el proceso apropiación del conocimiento como la relación que existe entre la sociedad y la tecnología es necesario definir de manera conceptual el proceso de apropiación, posteriormente el ecosistema mediático en el que se vinculan la narrativas mediáticas, para así abordar la relación que existe entre la tecnología digital, las narrativas transmedia y los procesos de apropiación del conocimiento en los usuarios.

El presente escrito surge durante la cuarentena, aceptada por el pueblo colombiano desde el mes de marzo y siguientes del año común 2020 por disposición gubernamental, para disminuir el riesgo de contagio y de muerte durante la Pandemia del “Coronavirus”, SARS-CoV-2, Covid19. Todas las epidemias, plagas y pandemias conocidas sobre la faz de la tierra, han formado parte de la evolución y la naturaleza humana. Hoy, en pleno siglo XXI, después de haber viajado al espacio, haber conquistado la Luna, de tener medios de comunicación instantáneos, “casi telepáticos”, una estructura proteica virtualmente invisible, microscópica, “inerte”, nos mantiene confinados en el mismo tiempo, a más de la mitad de los 7.800 millones de Seres Humanos que cohabitamos en el Planeta Azul. Nada ni nadie nos había exhortado a tantas personas juntas a detenernos durante horas, días, quizá semanas o aún meses, a pensar en lo insignificantes que somos ante el implacable poder de la Naturaleza.

Our purpose was to determine the effect of a smoothing filter and partial-volume correction (PVC) on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on molecular imaging PSMA (miPSMA) scoring. Methods: Men who had biochemical recurrence of prostate cancer with negative findings on CT and bone scintigraphy were referred for 18F-DCFPyL (2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl) PET/CT. Examinations were performed on 1 of 2 different brands of PET/CT scanner. All suspected tumor sites were manually contoured on coregistered CT and PET images, and each was assigned an miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomic CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified rule-of-thumb (RoT) correction factor (CF) was derived for lesions at various sizes (

Despite the importance of recombinant protein production in the academy and industrial fields, many issues concerning the expression of soluble and homogeneous products are still unsolved. Several strategies were developed to overcome these obstacles; however, at present, there is no magic bullet that can be applied for all cases. Indeed, several key expression parameters need to be evaluated for each protein. Among the different hosts for protein expression, Escherichia coli is by far the most widely used. In this chapter, we review many of the different tools employed to circumvent protein insolubility problems.

We investigate whether computed tomography (CT) derived radiomics may correlate with driver gene mutations in patients with pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, 47 patients (mean age 64 ± 11 years; range: 42–86 years) with PDAC, who were treated surgically and who underwent preoperative CT imaging at our institution were included in the study. Image segmentation and feature extraction was performed semi-automatically with a commonly used open-source software platform. Genomic data from whole genome sequencing (WGS) were collected from our institution’s web-based resource. Two statistical models were then built, in order to evaluate the predictive ability of CT-derived radiomics feature for driver gene mutations in PDAC. 30/47 of all tumor samples harbored 2 or more gene mutations. Overall, 81% of tumor samples demonstrated mutations in KRAS, 68% of samples had alterations in TP53, 26% in SMAD4 and 19% in CDKN2A. Extended statistical analysis revealed acceptable predictive ability for KRAS and TP53 (Youden Index 0.56 and 0.67, respectively) and mild to acceptable predictive signal for SMAD4 and CDKN2A (Youden Index 0.5, respectively). Our study establishes acceptable correlation of radiomics features and driver gene mutations in PDAC, indicating an acceptable prognostication of genomic profiles using CT-derived radiomics. A larger and more homogenous cohort may further enhance the predictive ability.

Many recombinant proteins are products of great value in biomedical and industrial fields. The use of solubility and affinity tags are commonly used to increase yields and facilitate the purification process. However, it is of paramount importance in several applications to remove the fusion tag from the final product. In this regard, the Tobacco Etch Virus protease (TEV) is one of the most widely used for tag removal. The presence in the TEV of the same tag to be removed facilitates the separation of TEV and the tag from the cleaved recombinant protein in a single purification step. We generated a double-tagged (StrepTagII and HisTag) TEV variant with reported mutations that improve the activity, the expression yield in E. coli, and that decrease the auto-proteolysis. This TEV can be easily purified by two consecutive affinity chromatography steps with high yields and purity. The cleavage reaction can be done to almost completeness in as fast as 15 min at room temperature and the removal of the protease and tags is performed in a single purification step, independent of the previous presence of a StrepTagII or a HisTag on the target.

Una de las funciones de Twitter es el etiquetado digital denominado: hashtag. A través de las etiquetas, ordena y clasifica los mensajes de esta plataforma de redes sociales. El objetivo de esta investigación es estudiar el fenómeno del etiquetado social conocido como hashtag activism (activismo de etiquetas) como impulsores de la participación cívica, respondiendo la pregunta: ¿cómo entender la participación cívica online a través del etiquetado social en redes socio digitales? Nuestra metodología hace un análisis cualitativo de 33 casos representativos de las etiquetas #Ladies y #Lords utilizadas en México que realizan un escrutinio social desde el 2011. Concluimos que el etiquetado digital impacta en la participación cívica y la comunicación en la sociedad de la información.

Purpose To determine the prognostic value of sarcopenia measurements done on staging [18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Methods Patients with early stage, surgically treated esophageal adenocarcinoma and available pre-treatment PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI 2/m2 in women and 2/m2 in men. Results Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, Lymphovascular Invasion (LVI) positive lymph nodes and sarcopenia were significant prognostic factors concerning RFS, and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Conclusion Combining the patients’ imaging derived sarcopenic status with standard clinical data, but not metabolic parameters offered an overall improved prognostic value concerning OS and RFS.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment.Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI 34.4cmOf the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS.Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Artificial intelligence (AI) algorithms based on deep convolutional networks have demonstrated remarkable success for image transformation tasks. State-of-the-art results have been achieved by generative adversarial networks (GANs) and training approaches which do not require paired data. Recently, these techniques have been applied in the medical field for cross-domain image translation. This study investigated deep learning transformation in medical imaging. It was motivated to identify generalizable methods which would satisfy the simultaneous requirements of quality and anatomical accuracy across the entire human body. Specifically, whole-body MR patient data acquired on a PET/MR system were used to generate synthetic CT image volumes. The capacity of these synthetic CT data for use in PET attenuation correction (AC) was evaluated and compared to current MR-based attenuation correction (MR-AC) methods, which typically use multiphase Dixon sequences to segment various tissue types. This work aimed to investigate the technical performance of a GAN system for general MR-to-CT volumetric transformation and to evaluate the performance of the generated images for PET AC. A dataset comprising matched, same-day PET/MR and PET/CT patient scans was used for validation. A combination of training techniques was used to produce synthetic images which were of high-quality and anatomically accurate. Higher correlation was found between the values of mu maps calculated directly from CT data and those derived from the synthetic CT images than those from the default segmented Dixon approach. Over the entire body, the total amounts of reconstructed PET activities were similar between the two MR-AC methods, but the synthetic CT method yielded higher accuracy for quantifying the tracer uptake in specific regions. The findings reported here demonstrate the feasibility of this technique and its potential to improve certain aspects of attenuation correction for PET/MR systems. Moreover, this work may have larger implications for establishing generalized methods for inter-modality, whole-body transformation in medical imaging. Unsupervised deep learning techniques can produce high-quality synthetic images, but additional constraints may be needed to maintain medical integrity in the generated data.

The detection of small molecules in living cells using genetically encoded FRET sensors has revolutionized our understanding of signaling pathways at the sub-cellular level. However, engineering fluorescent proteins and specific binding domains to create new sensors remains challenging because of the difficulties associated with the large size of the polypeptides involved, and their intrinsically huge conformational variability. Indeed, FRET sensors’ design still relies on vague structural notions, and trial and error combinations of linkers and protein modules. We recently designed a FRET sensor for the second messenger cAMP named CUTie (Cyclic nucleotide Universal Tag for imaging experiments), which granted sub-micrometer resolution in living cells. Here we apply a combination of sequence/structure analysis to produce a new-generation FRET sensor for the second messenger cGMP based on Protein kinase G I (PKGI), which we named CUTie2. Coarse-grained molecular dynamics simulations achieved an exhaustive sampling of the relevant spatio-temporal coordinates providing a quasi-quantitative prediction of the FRET efficiency, as confirmed by in vitro experiments. Moreover, biochemical characterization showed that the cGMP binding module maintains virtually the same affinity and selectivity for its ligand thant the full-length protein. The computational approach proposed here is easily generalizable to other allosteric protein modules, providing a cost effective-strategy for the custom design of FRET sensors.

Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28D/E, P45S, E55Q, and S64I changes (p0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

To assess whetherThis ethics review board-approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who receivedThere were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p 0.001]). The performance of MR and PET/MR was comparable. For identification of csPCa in PI-RADS ≥ 3 lesions, the AUC (95% CI) for PET, mpMR, and PET/MR was 0.75 (0.65-0.86), 0.69 (0.56-0.82), and 0.78 (0.67-0.89), respectively. The AUC for PET/MR was significantly larger than that of mpMR (p = 0.04).PSMA PET detects more csPCa than mpMR, but at low specificity. The performance PET/MR is better than mpMR for detection of csPCa in PI-RADS ≥ 3 lesions.NCT03149861.

Autoimmune encephalitis occurs as a subacute condition with a strong infectious association in children. In the last 20 years, the frequency of non-infectious cases has increased significantly.A previously healthy eight-year-old male child with normal neurodevelopment, without a history of consanguinity, manifested progressive neurological deterioration with autoimmune encephalitis-limbic encephalitis up to hypothalamic dysfunction.In the mentioned case, it was documented that an inborn error of the immune system generated a severe neurological clinical picture, with permanent and irreversible damage, secondary to lack of immunological memory in the broad clinical context of a common variable immunodeficiency.Antecedentes: La encefalitis autoinmune se presenta como un cuadro subagudo con fuerte asociación infecciosa en los niños. En los últimos 20 años, la frecuencia de casos no infecciosos ha aumentado de manera significativa Caso clínico: Niño del sexo masculino de ocho años de edad previamente sano con neurodesarrollo normal, sin antecedente de consanguinidad, en quien se manifestó deterioro neurológico progresivo, desde encefalitis autoinmune-encefalitis límbica hasta disfunción hipotalámica. Conclusión: En el caso referido se documentó un error innato del sistema inmunológico que generó cuadro clínico neurológico severo, con daño permanente e irreversible secundario a falta de memoria inmunológica en el contexto clínico amplio de una inmunodeficiencia común variable.

Background: Autoimmune encephalitis occurs as a subacute condition with a strong infectious association in children. In the last 20 years, the frequency of non-infectious cases has increased significantly Clinical case: A previously healthy eight-year-old male child with normal neurodevelopment, without a history of consanguinity, manifested progressive neurological deterioration with autoimmune encephalitis-limbic encephalitis up to hypothalamic dysfunction. Conclusion: In the mentioned case, it was documented that an inborn error of the immune system generated a severe neurological clinical picture, with permanent and irreversible damage, secondary to lack of immunological memory in the broad clinical context of a common variable immunodeficiency.

The aim of this work was to evaluate the physicochemical and biological properties of docetaxel (DCX) loaded chitosan nanocapsules (CS Nc) functionalized with the monoclonal antibody Chi-Tn (CS-PEG-ChiTn mAb Nc) as a potential improvement treatment for cancer therapy. The Tn antigen is highly specific for carcinomas, and this is the first time that such structure is targeted for drug delivery. The nanocapsules (Ncs), formed as a polymeric shell around an oily core, allowed a 99.9% encapsulation efficiency of DCX with a monodispersity particle size in the range of 200 nm and a high positive surface charge that provide substantial stability to the nanosystems. Release profile of DCX from Ncs showed a sustained and pH dependent behavior with a faster release at acidic pH, which could be favorable in the intracellular drug delivery. We have designed PEGylated CS Nc modified with a monoclonal antibody which recognize Tn antigen, one of the most specific tumor associated antigen. A biotin-avidin approach achieved the successful attachment of the antibody to the nanocapsules. Uptake studies and viability assay conducted in A549 human lung cancer cell line in vitro demonstrate that ChiTn mAb enhance nanoparticles internalization and cell viability reduction. Consequently, these ChiTn functionalized nanocapsules are promising carriers for the active targeting of DCX to Tn expressing carcinomas.

Goal PET is a relatively noisy process compared to other imaging modalities, and sparsity of acquisition data leads to noise in the images. Recent work has focused on machine learning techniques to improve PET images, and this study investigates a deep learning approach to improve the quality of reconstructed image volumes through denoising by a 3D convolution neural network. Potential improvements were evaluated within a clinical context by physician performance in a reading task. Methods A wide range of controlled noise levels was emulated from a set of chest PET data in patients with lung cancer, and a convolutional neural network was trained to denoise the reconstructed images using the full-count reconstructions as the ground truth. The benefits, over conventional Gaussian smoothing, were quantified across all noise levels by observer performance in an image ranking and lesion detection task. Results The CNN-denoised images were generally ranked by the physicians equal to or better than the Gaussian-smoothed images for all count levels, with the largest effects observed in the lowest-count image sets. For the CNN-denoised images, overall lesion contrast recovery was 60% and 90% at the 1 and 20 million count levels, respectively. Notwithstanding the reduced lesion contrast recovery in noisy data, the CNN-denoised images also yielded better lesion detectability in low count levels. For example, at 1 million true counts, the average true positive detection rate was around 40% for the CNN-denoised images and 30% for the smoothed images. Conclusion Significant improvements were found for CNN-denoising for very noisy images, and to some degree for all noise levels. The technique presented here offered however limited benefit for detection performance for images at the count levels routinely encountered in the clinic.

The aim of this study was to determine whether quantitative PET parameters on baseline (68)Ga-DOTATATE PET/CT and interim PET (iPET) performed before the second cycle of therapy are predictive of the therapy response and progression-free survival (PFS). Methods: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki-67 index, 8.3%) underwent (68)Ga-DOTATATE PET/CT to determine suitability for peptide receptor radionuclide therapy as part of a prospective multicenter study. The mean follow-up was 12.2 mo. Of the 91 patients, 36 had iPET. The tumor metrics evaluated were marker lesion–based measures (mean SUV(max) and ratio of the mean lesion SUV(max) to the SUV(max) in the liver or the SUV(max) in the spleen), segmented (68)Ga-DOTATATE tumor volumes (DTTVs), SUV(max) and SUV(mean) obtained with the liver and spleen as thresholds, and heterogeneity parameters (coefficient of variation, kurtosis, and skewness). The Wilcoxon rank sum test was used for the association between continuous variables and the therapy response, as determined by the clinical response. Univariable and multivariable Cox proportional hazards models were used for the association with PFS. Results: There were 71 responders and 20 nonresponders. When marker lesions were used, higher mean SUV(max) and ratio of the mean lesion SUV(max) to the SUV(max) in the liver were predictors of the therapy response (P = 0.018 and 0.024, respectively). For DTTV parameters, higher SUV(max) and SUV(mean) obtained with the liver as a threshold and lower kurtosis were predictors of a favorable response (P = 0.025, 0.0055, and 0.031, respectively). The latter also correlated with a longer PFS. The iPET DTTV SUV(mean) obtained with the liver as a threshold and the ratio of mean SUV(max) obtained from target lesions at iPET to baseline PET correlated with the therapy response (P = 0.024 and 0.048, respectively) but not PFS. From the multivariable analysis with adjustment for age, primary site, and Ki-67 index, the mean SUV(max) (P = 0.019), ratio of the mean lesion SUV(max) to the SUV(max) in the liver (P = 0.018), ratio of the mean lesion SUV(max) to the SUV(max) in the spleen (P = 0.041), DTTV SUV(mean) obtained with the liver (P = 0.0052), and skewness (P = 0.048) remained significant predictors of PFS. Conclusion: The degree of somatostatin receptor expression and tumor heterogeneity, as represented by several metrics in our analysis, were predictive of the therapy response or PFS. Changes in these parameters after the first cycle of peptide receptor radionuclide therapy did not correlate with clinical outcomes.

En medicina popular, Silybum marianum se usa como agente hepatoprotector. La silimarina es su componente principal. El presente trabajo trata de la formulación y evaluación de tabletas de S. marianum a partir de extracto etanólico por compresión directa. El extracto etanólico se obtuvo de las semillas mediante extracción con soxhlet. Se prepararon dos formulaciones farmacéuticas usando extracto fluido como principio activo y Aeroperl® 300 Pharma como vehículo. Para mejorar la capacidad de flujo y la compresibilidad, se emplearon excipientes coprocesados MicroceLac® 100 y FlowLac® 90. Los parámetros de precompresión y postcompresión se evaluaron de acuerdo con USP 34-NF 29. Además, la silimarina se determinó mediante datos espectrales de RMN. Ambas formulaciones mostraron excelentes propiedades reológicas y los mejores parámetros biofarmacéuticos se observaron en F2 (S. marianum ethanolic extract, aeroperl® 300 Pharma, flowLac® 90, glicolado de almidón y estearato de magnesio) en términos de friabilidad (0,82%) y el tiempo de desintegración (8,05 min). In popular medicine Silybum marianum is used as a hepatoprotective agent. Silymarin is the major constituent. The present work deals with the formulation and evaluation of S. marianum tablets from ethanolic extract by direct compression. The ethanolic extract was obtained from seeds by soxhlet extraction. Two pharmaceutical formulations were prepared using fluid extract as an active principle, and Aeroperl® 300 Pharma as a carrier. In order to improve flow ability and compressibility, co-processed excipients MicroceLac® 100 and FlowLac® 90 were employed. Pre-compression and post-compression parameters were evaluated according to USP 34-NF 29. Besides, silymarin was determined by NMR spectral data. Both formulations showed excellent rheological properties and the best biopharmaceutical parameters were observed in F2 (S. marianum ethanolic extract, aeroperl® 300 Pharma, flowLac® 90, glycolate starch and magnesium stearate) in terms of the friability (0.82 %) and the disintegration time (8.05 min). Fil: Cianchino, Valeria Andrea. Universidad Nacional de San Luis; Argentina Fil: Favier, Laura Silvina. Universidad Nacional de San Luis; Argentina Fil: Ortega, Claudia Alicia. Universidad Nacional de San Luis; Argentina Fil: Peralta, Cecilia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina Fil: Cifuente, Diego Alberto. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina

Las inmunoglobulinas son proteínas heterodiméricas compuestas de 2 cadenas pesadas y 2 cadenas ligeras. La inmunoglobulina G humana es un derivado del plasma y contiene más de 95 % de IgG. La composición de las subclases de IgG es similar a la del plasma humano normal. El tratamiento con inmunoglobulina comenzó hace más de 50 años y su uso se ha descrito en numerosas enfermedades. En Colombia, la importancia de este recurso inmunomodulador condujo a la necesidad de contar con una guía de práctica clínica para su uso, para lo cual se reunió un grupo multidisciplinario de expertos, quienes se distribuyeron en mesas de trabajo, por especialidad, para redactar un texto base. Se llevaron a cabo búsquedas bibliográficas sistemáticas; las evidencias identificadas se valoraron y clasificaron para sustentar un texto preliminar que fue discutido, analizado y corregido. Se emitieron recomendaciones de uso de la inmunoglobulina intravenosa en patologías que abarcan inmunodeficiencias primarias y secundarias, enfermedades autoinmunes, alteraciones neurológicas, infecciones, trasplantes y enfermedades misceláneas; se asignaron calificaciones según el sistema GRADE para cada una. El resultado final se tradujo en las recomendaciones que se presentan con la finalidad de informar, orientar y apoyar en el uso óptimo de dicho recurso inmunomodulador.

The advent of new DNA sequencing technologies leads to a dramatic increase in the number of available genome sequences and therefore of target genes with potential for functional analysis. The insertion of these sequences into proper expression vectors requires a simple an efficient cloning method. In addition, when expressing a target protein, quite often it is necessary to evaluate different DNA constructs to achieve a soluble and homogeneous expression of the target with satisfactory yields. The development of new molecular methods made possible the cloning of a huge number of DNA sequences in a high-throughput manner, necessary for meeting the increasing demands for soluble protein expression and characterization. In this chapter several molecular methods suitable for high-throughput cloning are reviewed.

Treatment of hyper IgE syndrome (HIES) is directed towards prevention and management of infections by using sustained systemic antibiotics and antifungals