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Globally, small- and medium-sized enterprises (SMEs) are engines of economic growth and job creation. After the pandemic, innovation activities have become more critical than ever as a generator of competitiveness. Therefore, we need to better understand the factors that lead to innovation in SMEs. This study aims to analyze the role of relational capital and technology orientation in innovation to appreciate its final impact on firm performance. The main results reveal a strong positive effect of relational capital on innovation, but the effect is not so strong as firm performance. We also found a strong positive effect of relational capital on technology orientation. Finally, we offer some clues in the debate on technology as a source of innovation and how relational capital and technology orientation are related to a firm’s performance. The results reveal significant implications for innovation policies and relational capital strategies for SMEs.

Over the past few years, neuroimaging studies have been performed in young adults with perinatally acquired HIV (PHIV) to study the impact of HIV infection on the central nervous system (CNS), but no recent review have been published. This review aims to identify brain areas where PHIV eems to have greater impact taking into account demographic, behavioral, and clinical characteristics in PHIV infected patients. For this purpose, PubMed and Medline searches were carried out which included studies from 2010 to April 2020. We performed a systematic review and included 26 articles using structural (brain morphometry and diffusion tensor imaging) and functional magnetic resonance imaging methods involving 1182 PHIV-infected participants. Ample evidence has been provided of HIV effects on underlying brain structure. However, information recorded in the studies is commonly incomplete and results sometimes contradictory. In addition to future improvements and dissemination of tools for the developing brain MRI processing and analysis, the inclusion of data related to HIV infection itself (including clinical and immunovirological characteristics as well as detailed information about antiretroviral treatment such as age at ART initiation) may be of vital importance to the better understanding of the impact of the disease on CNS.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

Objetive To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. Method Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014–2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer–Lemeshow and a bootstrapping analysis with 1000 re-samples respectively. Results 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78–0.91) and Hosmer–Lemeshow p = 0.71. The developed score detected well those patients who were going to need an early DC (first 24 h) after a TBI (2.5 ± 0.5) but not those who would need it in a later stage of their disease (1.7 ± 0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24 h vs. do not require DC, 1.7 ± 0.8 vs. 1 ± 0.7; p = 0.002). Conclusion We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC.

Resumen Objetivo Realizar una escala con parametros clinicos y radiologicos precoces tras un TCE que identifique a los enfermos que en su evolucion posterior van a someterse a una CD. Metodo Estudio observacional de una cohorte retrospectiva de pacientes que tras un TCE ingresan en la Seccion de Neurocriticos del Servicio de Medicina Intensiva de nuestro hospital durante un periodo de 5 anos (2014-2018). Deteccion de variables clinicas y radiologicas y creacion de todos los modelos posibles con las variables significativas, clinicamente relevantes y de facil deteccion precoz. Seleccion del que presentaba valores mas bajos de criterios de informacion bayesiano y de Akaike para la creacion de la escala. Calibracion y validacion interna mediante la prueba de bondad de ajuste de Hosmer-Lemeshow y analisis bootstrapping con 1.000 re-muestreos. Resultados Se realizaron 37 CD en 153 enfermos que ingresaron tras un TCE. El modelo final resultante incluia desviacion de linea media, GCS y colapso ventricular con un area bajo la curva ROC de 0,84 (IC95% 0,78-0,91) y Hosmer-Lemeshow p = 0,71. La escala desarrollada detectaba bien a los enfermos que iban a precisar una CD precoz (en las primeras 24 horas) tras un TCE (2,5 ± 0,5) pero no a aquellos que la necesitarian en una fase mas tardia de su enfermedad (1,7 ± 0,8). Sin embargo, parece prevenirnos sobre los enfermos que si bien no precisan inicialmente una CD si tienen probabilidades de necesitarla posteriormente en su evolucion (CD tardia vs. no precisan CD, 1,7 ± 0,8 vs. 1 ± 0,7; p = 0,002). Conclusion Hemos desarrollado una escala pronostica que permite detectar en nuestro medio, con una buena sensibilidad y especificidad y usando criterios clinico-radiologicos precoces, aquellos pacientes que tras un TCE van a precisar una CD.

A new combustion regime identification methodology using the neural networks as supervised classifiers is proposed and validated. As a first proof of concept, a binary classifier is trained with la...

Summary Molecular findings in ovarian, fallopian tube, and peritoneal high-grade serous carcinoma (HGSCa) are emerging as potential prognostic indicators. The chemotherapy response score (CRS) has been proposed as a histologic-based prognostic factor in patients with HGSCa treated with neoadjuvant chemotherapy (NACT). No study details the relationship between the mutational landscape of HGSCa and the CRS. This study addresses this issue using next-generation sequencing (NGS). We retrospectively identified 25 HGSCas treated with NACT and pathology material available to calculate the CRS. All cases had NGS on the primary debulking specimen post-NACT. The three-tier Bohm CRS was applied to the omentum or adnexa and calculated as a combined score. Tumor mutation burden (TMB) and TP53 variant allele frequency (VAF) were calculated and used in correlative analysis. All cases had at least one mutation, most commonly TP53 (25 cases, 100%). Other mutations were BRCA2 (one case, 4%), ARID1A (two cases, 8%), and 1 (4%) of each of the following: ERBB2, NTRK3, STK11, NTRK2, TSC1, PIK3CA, NF1, NOTCH3, CDK2, SMAD4, and PMS2. TMB ranged from 2.58 to 7.75 (median 3.84). There was no statistically significant relationship between the TMB and omental CRS, R-squared = 0.011 (P = 0.62); adnexal CRS, R-squared = 0.005 (P = 0.74); or with the combined CRS, R-squared = 0.009 (P = 0.65). Statistically significant correlation was found between the TP53 VAF and the omental CRS (R-squared = 0.28, P = 0.007), adnexal CRS (R-squared = 0.26, P = 0.01), and the combined CRS (R-squared = 0.33, P = 0.0026). The TP53 VAF was adjusted for percent of tumor present on the slide resulting in an average per cell TP53 mutational load, resulting in similar results with a statistically significant correlation between the average per cell TP53 mutational load and the omental CRS (R-squared = 0.27, P = 0.02), adnexal CRS (R-squared = 0.16, P = 0.05), and the combined CRS (R-squared = 0.23, P = 0.02). In summary, NGS confirmed TP53 mutations in all cases of HGSCa. TMB showed no correlation with the CRS. TP53 VAF and average per cell TP53 mutational load showed significant correlation with the CRS, whether graded on the adnexa or omentum or as a combined score, indicating concordance between molecular and histological findings following NACT.

Attenuation correction remains a challenge in pelvic PET/MRI. In addition to the segmentation/model-based approaches, deep learning methods have shown promise in synthesizing accurate pelvic attenuation maps (μ-maps). However, these methods often misclassify air pockets in the digestive tract, potentially introducing bias in the reconstructed PET images. The aims of this work were to develop deep learning–based methods to automatically segment air pockets and generate pseudo-CT images from CAIPIRINHA-accelerated MR Dixon images. Methods: A convolutional neural network (CNN) was trained to segment air pockets using 3-dimensional CAIPIRINHA-accelerated MR Dixon datasets from 35 subjects and was evaluated against semiautomated segmentations. A separate CNN was trained to synthesize pseudo-CT μ-maps from the Dixon images. Its accuracy was evaluated by comparing the deep learning–, model-, and CT-based μ-maps using data from 30 of the subjects. Finally, the impact of different μ-maps and air pocket segmentation methods on the PET quantification was investigated. Results: Air pockets segmented using the CNN agreed well with semiautomated segmentations, with a mean Dice similarity coefficient of 0.75. The volumetric similarity score between 2 segmentations was 0.85 ± 0.14. The mean absolute relative changes with respect to the CT-based μ-maps were 2.6% and 5.1% in the whole pelvis for the deep learning–based and model-based μ-maps, respectively. The average relative change between PET images reconstructed with deep learning–based and CT-based μ-maps was 2.6%. Conclusion: We developed a deep learning–based method to automatically segment air pockets from CAIPIRINHA-accelerated Dixon images, with accuracy comparable to that of semiautomatic segmentations. The μ-maps synthesized using a deep learning–based method from CAIPIRINHA-accelerated Dixon images were more accurate than those generated with the model-based approach available on integrated PET/MRI scanners.

Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare CD20-negative aggressive lymphoma. Given its rarity, data on ALK + LBCL are scarce and limited to case reports and small case series. Our systematic review included 184 unique cases published in the literature and shows that ALK + LBCL can affect individuals at any age, has a male predominance and is not associated with chronic viral infections. The malignant cells express ALK, VS38c, BLIMP-1, EMA, c-MYC, and BOB-1. The STAT3/STAT5, PI3K/AKT, PLCG2, and ERK pathways are important in the pathophysiology of ALK + LBCL. The prognosis of ALK + LBCL is poor with a 5-year survival rate of 28%. Early disease stage is associated with better outcomes. ALK inhibitors and other targeted agents could be of value in the treatment of ALK + LBCL. Additional research is needed to better understand, diagnose and treat ALK + LBCL.

The experience with uterine inflammatory myofibroblastic neoplasms with an unfavorable outcome is limited. We present the clinicopathologic features of 9 such cases, including 8 inflammatory myofibroblastic tumors (IMTs) and 1 epithelioid inflammatory myofibroblastic sarcoma (EIMS). Median patient age for the IMT group was 50.5 years; the patient with EIMS was 43 years old. Patients presented with abnormal uterine bleeding, presumed fibroids, pelvic pain, arthralgia and low-grade fever, as well as an incidental finding. Median tumor size for the IMTs was 8.5 cm. The borders were either infiltrative or well-circumscribed. Histologically, IMTs were purely fascicular or myxoid or showed predominance of one or the other pattern. Seven tumors were spindled, and 1 was both spindled and epithelioid. Tumors had variable nuclear atypia, ranging from grade 1 to 3. All tumors had an inflammatory infiltrate-predominantly lymphocytic, majority had necrosis (62.5%) and none had lymphovascular invasion. 7/8 (87.5%) tumors were positive for ALK-1 by immunohistochemistry (IHC). One tumor was negative for ALK-1 by IHC but was positive for ALK fusion by fluorescence in situ hybridization and had TNS1-ALK fusion by next-generation sequencing (NGS). Three other tumors with NGS testing showed one of the following ALK-fusion partners: FN1, DCTN1, and IGFBP5. The EIMS had infiltrative borders, myxoid and hyalinized patterns, epithelioid cells, and no lymphovascular invasion. This tumor was ALK-1 positive by IHC, had ALK rearrangement by fluorescence in situ hybridization and RANBP2-ALK fusion by NGS. Extrauterine disease at time of diagnosis was noted in 2/8 (25%) of IMTs, and in the single case of EIMS. Seven patients had surgery as primary treatment, 1 patient had neoadjuvant chemotherapy and 1 patient declined treatment. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, radiotherapy or hormonal therapy. Most patients (71.4%) recurred within 24 months (mos). Two thirds of patients were alive with disease at last follow up (mean 43.6 mos). The patient with EIMS was alive with disease at 22 mos. IMT referral cases were initially diagnosed as smooth muscle tumors in 87.5% of cases; while the EIMS was diagnosed as high-grade endometrial stromal sarcoma. Lack of consideration of IMT in the differential diagnosis of smooth muscle tumors with myxoid features can result in misdiagnosis and under-utilization of targeted therapy in these patients.

The International Society of Gynecological Pathologists (ISGyP) Endocervical Adenocarcinoma Project aims to provide evidence-based guidance for the pathologic evaluation, classification, and reporting of endocervical adenocarcinoma. This review presents the recommendations pertaining to gross evaluation and intraoperative consultation of specimens obtained from patients in the setting of cervical cancer. The recommendations are the product of review of published peer-reviewed evidence, international guidelines and institutional grossing manuals, as well as deliberation within this working group. The discussion presented herein details the approach to the different specimen types encountered in practice: loop electrosurgical excision procedure, cone, trachelectomy, radical hysterectomy, pelvic exenteration, and lymphadenectomy specimens. Guidelines for intraoperative evaluation of trachelectomy and sentinel lymph node specimens are also addressed. Correlation with ISGyP recommendations on cancer staging, which appear as a separate review in this issue, is also included when appropriate. While conceived in the framework of endocervical adenocarcinoma, most of the discussion and recommendations can also be applied to other cervical malignancies.

Summary Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.

INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America, and Western Africa. In Latin America (LA), Peru and Brazil have the highest prevalence of HTLV-1-related diseases, however, data on ATLL in other LA countries is scarce. ATLL carries a dismal prognosis and is essentially incurable by conventional drugs. We describe the epidemiology, clinical features, treatment, and disease outcome of ATLL encountered in 11 countries in LA. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL cases were classified according to the Shimoyama criteria into acute (A), lymphomatous (L), chronic (C) and smoldering (S). Treatment approaches used as first-line therapy were: 1) chemotherapy alone; 2) combined chemotherapy with zidovudine/interferon-alpha (AZT-IFN); and 3) AZT-IFN alone, as previously done with Miami cohort (Malpica and Ramos et al. Blood Advances 2018). Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response and stable disease, these had to persist for a period of at least 4 weeks. Survival curves were estimated using the Kaplan-Meier method and Log rank test. RESULTS: A total of 253 pts with ATLL were identified. Two hundred twenty six pts (L=122, A=73, C=26, S=5) had sufficient data for analysis. Demographic and clinical features are shown in Figure 1 and Table 1. Median age at diagnosis was 57 years, with a female predominance in A (58%) and S (100%) types. Most ATLL pts were from Peru (n=159, 63%) followed by Chile (n=44, 17%), Argentina (n=20, 8%) and Colombia (n=17, 7%). B symptoms were high present in A, L and C types (73%, 72%, 58% vs. 8% S type, respectively, p=0.011). Hypercalcemia was highly associated with A type (57% vs. L 27%, p=0.014). The PIT score yielded to a more aggressive risk classification compared to the IPI score (high-risk: 55% vs. 29%, respectively, p CONCLUSION: ATLL continues to carry a dismal outcome with conventional therapies thus urging the development of novel approaches. Our study found that Latin American ATLL variant presents at a younger age, has a female predominance, high incidence of L type, low incidence of indolent types and lower survival rates, suggesting that Latin American ATLL variant presents earlier and more aggressively than in Japanese pts. AZT-IFN produced durable responses in A type patients who achieved CR as compared to chemotherapy alone. Chemotherapy responses were more durable in L types who achieved CR as compared to A type. In conclusion, in the management of aggressive ATLL, chemotherapy remains the preferred choice for L type (with consideration of allo-HSCT upfront), while AZT-IFN is a good option to attempt for A type upfront. Figure Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Janssen: Consultancy, Research Funding; Abbvie: Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:Roche: Other: advisory board, Speakers Bureau; amgen: Speakers Bureau.

INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, Western Africa, the Caribbean basin and South America. Cutaneous signs of ATLL are varied and may consist of macules (M), plaques (P), multiple papules (MP), tumoral nodules (TN), erythroderma (E) or mixed-lesions (≥2 predominant lesions, ML). M and P forms are believed to carry a better prognosis. However, data on cutaneous presentation of ATLL remains scarce. Herein, we report cases of ATLL with cutaneous involvement diagnosed in 4 Latin American countries over the last 3 decades. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL subtypes were classified according to the Shimoyama criteria into acute, lymphomatous, chronic and smoldering. Primary cutaneous tumoral (PCT) variant was classified according to the 2019 International Revised ATLL Consensus. We designed 2 cohorts: the first, ATLL pts with cutaneous involvement, and the second, matched cases without cutaneous involvement. We determined the type of skin lesion as well as the survival associated with the various types of skin lesions. We compared the frequency of clinical features using Fisher's exact test. Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response, and stable disease, these had to persist for a period of at least 4 weeks. We analyzed survival data according to ATLL subtype, cutaneous involvement status, and type of skin lesion using the Kaplan-Meier method and Log rank test. RESULTS: A total of 169 pts with ATLL were identified; 63 had cutaneous involvement and 106 did not. Clinical features are shown in Table 1. In both groups the median age was 57 years with a female predominance. Cutaneous involvement was most frequently found in acute (41%) and lymphomatous (37%) ATLL pts. The E (24%) and P (22 %) types were the most frequent skin lesions. Disease stage, presence of B symptoms, hypercalcemia, ECOG ≥2, elevated LDH, and IPI/ PIT score were not different among groups. Table 2 and Table 3 summarize the first-line therapy used and response rates. The use of first-line zidovudine plus interferon alpha (AZT-IFN), regardless of the type of skin lesion, resulted in relatively high response rates [overall response (OR) 100%, n=8; CR 62.5%] as compared to multi agent-chemotherapy (OR 33.3%, n=12). Overall, the presence of cutaneous involvement was associated with better overall survival (OS) compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p CONCLUSION: In Latin American pts with aggressive ATLL, cutaneous involvement appears to be associated with better survival compared to non-cutaneous involvement. PCT subtype, an ATLL variant characterized by isolated skin lesions with no organ involvement and poor outcome, appeared to have a better prognosis compared to acute and lymphomatous ATLL forms. P and MP skin lesions were both associated with better survival. Hypercalcemia was found as an independent prognostic factor for survival in pts with cutaneous involvement. Finally, AZT-IFN appears to be reasonable first-line option for aggressive ATLL subtypes with cutaneous involvement regardless of the type of skin lesion at diagnosis, based on the relatively high response rates observed in this subset; further investigation in randomized clinical trials is needed. Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Takeda: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Research Funding; Kymera: Consultancy; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau.

Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management.

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.

OBJECTIVE: To determine the frequency of the main risk factors for heart failure in a hospital in the Peruvian Andes during the period 2018. CONCLUSIONS: The most frequent risk factors that are present in HF in the high altitude hospital in 2018 were: valvular heart disease, arterial hypertension, pulmonary hypertension, atrial fibrillation and cor-pulmonale. MATERIALS AND METHODS: The study design was quantitative, descriptive, observational and cross-sectional. A data collection sheet was applied, descriptive statistics were used, and frequency tables were used for the presentation of qualitative variables. RESULTS: The study population of 124 cases had a mean age of 69 ± 15 years. The female sex was present in 58.87% of the chaos, 90% were older than 65 years, the occupation of housewife had a frequency of 41.60% and the place of residence was Huancayo in 72.58%. The frequency of the main risk factors was: valvular disease (73.39%), HTN (62.10%), PHT (58.06%), atrial fibrillation (33.87%) and cor-pulmonale (25.81%). CONCLUSIONS: The most frequent risk factors that are present in HF in the high altitude hospital in 2018 were: valvular heart disease, arterial hypertension, pulmonary hypertension, atrial fibrillation and cor-pulmonale.

Resumen El Grupo de Trabajo de Metabolismo y Nutricion de la Sociedad Espanola de Medicina Intensiva, Critica y Unidades Coronarias (SEMICYUC) ha revisado y actualizado las recomendaciones del tratamiento nutrometabolico en el paciente critico (previamente publicadas por el grupo en el ano 2011) con la finalidad de ayudar a la toma de decisiones en la practica clinica diaria. Para su elaboracion, llevada a cabo entre marzo de 2016 y febrero de 2019, se ha contado con un panel de expertos dedicados a la Medicina Intensiva con amplia experiencia en el tratamiento nutricional de los pacientes criticos. Para cada una de las recomendaciones se ha establecido un nivel de evidencia basado en la metodologia del grupo GRADE (Grading of Recommendations Assessment, Development and Evaluation Working Group) y un grado de recomendacion que ha tenido en cuenta el impacto clinico de la recomendacion, independientemente del nivel de evidencia establecido por la escala GRADE.

The Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) has reviewed and updated the recommendations for specialized nutritional and metabolic support in critically ill patients published by the Group in 2011, with the primary aim of helping decision making in daily clinical practice. The recommendations have been formulated by an expert panel with broad experience in nutritional and metabolic support in critically ill patients, and were drafted between March 2016 and February 2019. A level of evidence has been provided for each of the recommendations, based on the GRADE methodology (Grading of Recommendations Assessment, Development and Evaluation Working Group). A grade of recommendation has also been produced, taking into account the clinical impact of the recommendation, regardless of the level of evidence established by the GRADE scale.

A 62-year-old woman presented in December 2016 with 1 year of vaginal bleeding. At that time, the pelvic examination was unremarkable. Past medical history was significant for gastric reflux, mixed hyperlipidemia, and hypertension. Past surgical history was significant for salpingostomy for

Sedation is necessary in the management of critically ill patients, both to alleviate suffering and to cure patients with diseases that require admission to the intensive care unit. Such sedation should be appropriate to the patient needs at each timepoint during clinical evolution, and neither too low (undersedation) nor too high (oversedation). Adequate sedation influences patient comfort, safety, survival, subsequent quality of life, bed rotation of critical care units and costs. Undersedation is detected and quickly corrected. In contrast, oversedation is silent and difficult to prevent in the absence of management guidelines, collective awareness and teamwork. The Zero Oversedation Project of the Sedation, Analgesia and Delirium Working Group of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units aims to offer a practical teaching and collective awareness tool for ensuring patient comfort, safety and management with a view to optimizing the clinical outcomes and minimizing the deleterious effects of excessive sedation. The tool is based on a package of measures that include monitoring pain, analgesia, agitation, sedation, delirium and neuromuscular block, keeping patients pain-free, performing dynamic sedation according to clinical objectives, agreeing upon the multidisciplinary protocol to be followed, and avoiding deep sedation where not clinically indicated.

As part of the upcoming Mars 2020 rover mission, NASA is planning to include an autonomous helicopter to demonstrate the feasibility and utility of using helicopters for Mars exploration. Helicopte...

Using the first axiom of statics for equilibrium of a two forces system applied to points of a solid body, it was verified, that the pressure in the zone of contact of a tool with a lens during its abrasive processing by the grinding-free method is unevenly distributed. With this in mind, the nature of the distribution of the pressure profile has been presented graphically, showing the equilibrium condition when the tool is rotated around the center of the spherical surface of the lens relative to its axis of symmetry and the clamping force of the unions that are grinded has been recorded. On that base an expression is proposed for determining the current pressure at an arbitrarily chosen point on the surface of the lens. An expression for determining the continuously changing contact area of the instrument and the lens during its processing by grinding-free method is obtained. The calculation of current pressure at different points of the diametrical cross-section of the contact zone of the lapping surfaces of the tool, performing oscillatory motion, and the lens is performed. As a result, the uneven distribution of pressure in the area under study was revealed, with the minimum value of this indicator taking place in the zone of contact of the tool edge with the lens, and the maximum in the zone of contact of the lens edge with the tool. The observed non-uniformity increases with an increase in the angle of deviation of the tool from the axis of symmetry of the lens. Theoretical and experimental studies of the influence of the tool diameter on the polishing process of the lens under conditions of free grinding, which prevents the occurrence of local error in the marginal zone of the latter due to the pressure drop between the grinding surfaces during the instrument movement, are carried out. At the same time it was found that in order to avoid a “blockage of the edge”, it is necessary to use a tool with diameter of at least 0.8 of the diameter of the lens (in case it is the lower link). The obtained results allow assigning the optimal diameter of the tool depending on the size of the processed lens without preliminary laborious experiments and can be used in optical and optoelectronic instrument making.

Se realiza una revisión sobre el riesgo de los pacientes que padecen diabetes mellitus en el contexto de morbimortalidad general y relacionada a infección por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). Así mismo se repasan las recomendaciones generales, de alimentación y de la prevención de las comorbilidades que más frecuentemente padecen dichos enfermos. Finalmente se hace una revisión de las recomendaciones farmacológicas sobre el tratamiento tanto oral como parenteral en el paciente ambulatorio, en la hospitalización y en estados críticos infectados por el SARS-CoV-2.

Questions "Where does innovation initiate in a company?" and "How can a small and medium-sized enterprise (SME) leverage its different resources to enhance its innovation capabilities to outperform its competitors?" remain unanswered to date. Accordingly, this study examined the relationship between the firm's relational capital and fundamental strategic orientations that a firm can adopt and how these different orientations affect innovation and organizational performance. The target sample included 360 Mexican SMEs who completed a pen-and-pencil questionnaire conducted at the four main cities of this country. Structural equation modeling was performed, and results revealed a strong positive effect of relational capital over all four strategic orientations considered in this study. However, mixed findings of strategic orientations and innovation were obtained. Although market and entrepreneurial orientation positively influenced innovation, a negative relationship was found between learning orientation and innovation and a nonsignificant relationship between technology orientation and innovation. As expected, innovation positively influenced the performance of SMEs. This study offers essential academic contributions and interesting managerial insights to improve performance using relational capital through innovation and strategic orientations. Therefore, we propose relational capital as an underexploited resource and a source of innovation for SMEs.

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82]

Background The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with aggressive diseases, such as adult T-cell leukemia/lymphoma (ATLL). However, less is known on the impact of HTLV-1 infection in non-ATLL hematologic malignancies. We aimed to investigate if HTLV-1 carriers with diffuse large B-cell lymphoma (DLBCL) have worse survival outcomes than non-HTLV-1 carriers. Materials and Methods We performed a single-center retrospective cohort study by matching HTLV-1 carriers to non-carriers based on age, sex, Ann Arbor stage, and year of diagnosis. Our outcomes of interest were overall survival (OS) and progression-free survival (PFS). The Kaplan-Meier method was used to estimate OS and PFS between carriers and non-carriers. We fitted multivariate Cox regression models to assess the mortality and recurrence/disease progression risk of HTLV-1 infection. Results A total of 188 patients, 66 with HTLV-1 infection and 122 without HTLV-1, were included in the study. HTLV-1 carriers had higher extranodal involvement than non-carriers (47% vs. 27%, P = .010). With a median follow-up of 78 months (95% CI: 41-90 months), HTLV-1 carriers had a similar 5 year OS (41% vs. 42%, P = .940) and PFS (34% vs. 32%, P = .691) compared to non-carriers. In the multivariate Cox analysis, HTLV-1 infection was not associated with worse OS (aHR: 0.98, 95% CI: 0.64-1.50) or PFS (aHR: 0.90, 95% CI: 0.60-1.34). Conclusion HTLV-1 carriers with DLBCL did not have worse survival outcomes compared to non-carriers. Our results suggest that clinicians should follow standard guidelines for DLBCL management on HTLV-1 seropositive patients.

Introducción: El aborto espontáneo se refiere al fenómeno por el cual un embrión o feto se descarga automáticamente del cuerpo de la madre por alguna razón involuntaria, generalmente a las 20 semanas del embarazo. Entre el 15 % y el 20 % de todos los embarazos tienen riesgo de aborto espontáneo, alrededor de un 10 % terminarán siendo abortos espontáneos. Metodología: Estudio descriptivo transversal con intención analítica. Se tomaron los datos de 207 historias clínicas del archivo del hospital público de Pamplona, Norte de Santander, de mujeres gestantes universitarias, correspondientes a los periodos del año 2007 al 2016. Se consideró aborto espontáneo la variable reportada en la historia clínica. Se estimó la frecuencia de aborto espontáneo y se exploró la asociación con diferentes variables clínicas y sociodemográficas en estudiantes universitarias. Se construyeron modelos de regresión binomial simple y multivariable, para estimar la asociación entre las variables. Resultados: Se reportaron 15 abortos espontáneos (7,5 %), aquellas que no se habían aplicado la vacuna antitetánica y quienes no se realizaron citología durante los 12 meses previos presentaron los mayores porcentajes de abortos espontáneos (16,7 % y 15,2 %, respectivamente). Las mujeres que acusaron haber estado hospitalizadas (RP 4,01 IC 95 % 1,69-9,49), y haber tenido abortos previamente (RP 7,53 IC 95 % 3,02-18,77), mostraron asociación con el aborto espontáneo. Conclusión: Se pudo estimar que la proporción de abortos espontáneos es similar a lo reportado en otros estudios; no obstante, es necesario generar investigaciones adicionales que evalúen la relación entre el aborto espontáneo y factores individuales y contextuales para generar estrategias que disminuyan estas cifras.

Introduction. There are different scoring systems to differentiate risk groups in patients with DLBCL treated with chemoimmunotherapy. Those systems have used the same 5 variables (age, performance status, LDH, stage, extranodal involvement) for 27 years. However, LATAM data have not been included in the development of previous scoring systems. It is important to mention that novel biological variables, such as albumin, beta-2-microglobulin (B2M) and platelet/lymphocyte ratio (PLR), have been reported and could improve discrimination (Villela et al. Blood 2019; 134Suppl_1: 1613). Therefore, we carried out a large, multinational study to develop and validate a LATAM-IPI score. Methods. This is a retrospective cohort of 1030 patients with a diagnosis of DLBCL treated with standard chemoimmunotherapy with curative intent between 2010 and 2018. Data were obtained from 8 LATAM countries: Argentina, Colombia, Chile, Guatemala, Mexico, Paraguay, Peru, and Venezuela. The five classic IPI variables (age, ECOG, extranodal involvement, LDH, stage) were analyzed and albumin and PLR were added (Villela et al. Blood 2019; 134Suppl_1: 1613). B2M was not included because it was not requested regularly in all countries. Development of LATAM-IPI: The training set consisted of 85% of the sample, randomly selected, and the remaining 15% was reserved for internal validation. Using the training set, the univariate and multivariate association between clinical prognostic factors and OS was analyzed fitting Cox proportional-hazard models. Outcomes. Clinical characteristics of the training (n=878) and internal validation (n=151) cohorts are shown in Table 1. There were no statistical differences in baseline characteristics between the cohorts. The median follow-up for the whole cohort was 36 months (IQR: 11-57). When exploring the classic IPI variables on the training set, all variables were associated with high risk of mortality [age 65-74, Hazard Ratio (HR) 1.24, 95% CI 0.96 to 1.58, p=0.08; age ≥75, HR 1.71, 95% CI 1.28 to 2.28, p=0.0003), ECOG (≥ 2, HR=2, 95% CI 1.61 to 2.53; p Conclusions: Using multinational learning and validation cohorts including over 1,000 DLBCL patients treated with standard chemoimmunotherapy in LATAM, we developed a novel LATAM-IPI score using age ≥75 years, ECOG ≥2, advanced stage, LDH ratio (1.1-29 and ≥3) and albumin Disclosures Villela: amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau. Idrobo:Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Castillo:Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

Assessment of pelvic, para-aortic or inguinal lymph nodes (LNs) provides not only important prognostic information, but also determines the need for adjuvant treatment. Sentinel lymph node (SLN) biopsy has the potential to provide this prognostic information, while reducing morbidity compared with extended LN dissection. This review discusses the clinical and pathological aspects of SLN biopsy in gynaecological cancer.

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune-mediated non-malignant hematologic disorders, with infection being the most common non-hematological adverse event from these therapies. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection, including opportunistic infections. Screening and antimicrobial prophylaxis against tuberculosis, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia, are indicated in selected patients on steroids and with certain risk factors for infection. Rituximab is associated with hepatitis B virus reactivation. All patients planned to be started on rituximab should be screened for hepatitis B surface antigen and total core antibody, with antiviral prophylaxis given depending on test results. In eculizumab treated patients, immunization against meningococcal serogroups ACWY and B is recommended. In addition, some guidelines suggest antibiotic prophylaxis for the duration of eculizumab treatment. In splenectomized patients, counseling and immunization are cornerstones of infection prevention. Several federal and society guidelines about immunizations and prophylactic antimicrobial therapies for patients treated with various immunosuppressive agents exist and are summarized in this manuscript in a clinical-focused table. In addition, management suggestions are made where no formal guidelines exist.

Endometrial mesonephric-like carcinomas (MLCa) are uncommon with50 reported cases thus far. Previous studies have characterized the histologic, immunohistochemical, and molecular features of MLCa; however, there is limited information with respect to outcome. This single-institution study of 23 uterine MLCas characterizes the behavior of such a neoplasm. Uterine MLCas (2004-present) had review of histologic features, immunohistochemical results, molecular profile, and clinical information (stage, treatment, follow-up). The behavior of MLCa was compared with low-grade endometrioid carcinomas (ECas) and uterine serous carcinomas (USCs) treated at our institution from 2004 to present. All MLCas had a mixture of previously described architectural and cytologic features most notably ductal and/or tubular architecture (21/23), nuclei resembling those of papillary thyroid carcinoma (18/23), and at least focal intraluminal eosinophilic secretions (20/23). Immunoperoxidase studies facilitated diagnosis in 22 cases: CD10, 10/10; calretinin, 5/15; estrogen receptor (≥10% nuclei), 6/21; progesterone receptor, 1/15; GATA-3, 15/16; TTF-1, 11/16. Fourteen of 17 tested cases had a KRAS mutation (7 as the only alteration; 7 with additional mutations including PIK [n=5]; PTEN [n=2], CTNNB1 [n=1]).One case had mutations in PTEN, PIK, and CTNNB1 without KRAS; 2 cases had no detectable somatic mutation. Overall, 48% of patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage 3 or 4 disease with the following uterine risk factors:50% myometrial invasion, 20/23; lymphovascular space invasion, 16/23; cervical stromal invasion, 7/23. Twenty patients had adjuvant therapy (7 radiation only; 13 chemotherapy±radiation), whereas 3 patients had either unknown or declined therapy. Follow-up was known for 21 patients: 17 patients had recurrences or never achieved remission with the lung being the most common recurrence site (n=9); 7 patients died of disease. The median progression-free survival was 18.2 months for MLCa compared with 183 months for ECa and 67.1 months for USC. The median overall survival for MLCa was 70.6 months compared with 139.1 months for USC (median survival for ECa not reached). Uterine MLCa is uncommon with most tumors recognized by architectural heterogeneity, vesicular, overlapping nuclei with grooves, and eosinophilic luminal secretions. The typical immunoprofile includes low to absent expression of hormone receptors but at least focal expression of GATA-3 and/or TTF-1. Most tested cases had a KRAS mutation although genetic mutations typically associated with ECa are not uncommon. Compared with more commonly encountered types of ECa, MLCa is more aggressive with a tendency towards earlier and distant recurrence.

OBJECTIVE: To estimate whether gastrointestinal-type chemotherapy was associated with improved survival compared to standard gynecologic regimens for women with ovarian mucinous carcinoma. METHODS: We conducted a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers. Demographic and clinical information was abstracted from the medical records. Gastrointestinal-type chemotherapy contained 5-fluorouracil, capecitabine, irinotecan, or oxaliplatin. Gynecologic regimens included standard carboplatin or cisplatin. Bevacizumab treatment was allowed in both groups. Summary statistics were used to compare baseline characteristics; Kaplan-Meier product-limit estimator was used to compare survival outcomes. RESULTS: Fifty-two patients received either gastrointestinal-type chemotherapy (n=26; 50%) or a standard gynecologic regimen (n=26; 50%). Three-quarters of tumors were early-stage (I or II), 68% grade 1 or 2 and 88% of patients had no gross residual disease after surgery. Patients receiving gastrointestinal-type chemotherapy were more likely to receive bevacizumab (50% vs. 4%; P < .001), but there were no other differences in clinical or demographic characteristics. Unadjusted overall survival analyses showed that gastrointestinal-type chemotherapy was associated with better overall survival (HR 0.2, 95% CI 0.1–0.8), as were early stage tumors and having no gross residual disease. CONCLUSION: Gastrointestinal-type chemotherapy with or without bevacizumab was associated with improved survival and should be considered in patients with ovarian mucinous carcinoma requiring adjuvant therapy.

The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Bohm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.

When a seismometer network records an earthquake, operators will manually review the waveforms and identify the wave phases, a task known as phase picking. Manual phase picking is a time-consuming process that can be automated using machine learning; however, automatic methods have not yet achieved human-level performance, and open-source implementations of state-of-the-art algorithms are not always available. Convolutional networks have revolutionized the field of image processing, where the large amounts of readily available data make possible near-human performance in tasks such as classification and segmentation. Fortunately, phase picking is also an area where thousands of phases are manually picked, which makes convolutional networks a good fit for the processing of this type of data. In this paper, we describe Cospy, an open-source convolutional phase picker that uses a two-stage analysis in which the first stage segments a rough area around the phase, and the second stage regresses the precise location. Our approach was evaluated on the Northern California Earthquake Data Center (NCEDC) data set and, when targeting picks closer than 0.1 s, it achieved an $F_{1}$ -score of 93.13% for P phases and 91.07% for S phases. Our results show that convolutional networks are on track to achieve human-level performance on the task of seismic phase picking and can contribute to decreasing the need for manual analysis. An open-source implementation of the proposed approach, pretrained on the NCEDC data set, can be downloaded at https://github.com/stbnps/cospy .

Objective: The purpose of this paper is to prove that computer-vision techniques allow synthesizing water-fat separation maps for local specific absorption rate (SAR) estimation, when patient-specific water-fat images are not available. Methods: We obtained ground truth head models by using patient-specific water-fat images. We obtained two different label-fusion water-fat models generating a water-fat multiatlas and applying the STAPLE and local-MAP-STAPLE label-fusion methods. We also obtained patch-based water-fat models applying a local group-wise weighted combination of the multiatlas. Electromagnetic (EM) simulations were performed, and B1+ magnitude and 10 g averaged SAR maps were generated. Results: We found local approaches provide a high DICE overlap (72.6 ± 10.2% fat and 91.6 ± 1.5% water in local-MAP-STAPLE, and 68.8 ± 8.2% fat and 91.1 ± 1.0% water in patch-based), low Hausdorff distances (18.6 ± 7.7 mm fat and 7.4 ± 11.2 mm water in local-MAP-STAPLE, and 16.4 ± 8.5 mm fat and 7.2 ± 11.8 mm water in patch-based) and a low error in volume estimation (15.6 ± 34.4% fat and 5.6 ± 4.1% water in the local-MAP-STAPLE, and 14.0 ± 17.7% fat and 4.7 ± 2.8% water in patch-based). The positions of the peak 10 g-averaged local SAR hotspots were the same for every model. Conclusion: We have created patient-specific head models using three different computer-vision-based water-fat separation approaches and compared the predictions of B1+ field and SAR distributions generated by simulating these models. Our results prove that a computer-vision approach can be used for patient-specific water-fat separation, and utilized for local SAR estimation in high-field MRI. Significance: Computer-vision approaches can be used for patient-specific water-fat separation and for patient specific local SAR estimation, when water-fat images of the patient are not available.

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

In most cases of suspected endometrial neoplasia tumor origin can be correctly assigned according to a combination of clinical, radiologic, and pathologic features, even when the latter are based upon the examination of relatively small biopsy samples. However there are well-recognized exceptions to this rule which continue to create diagnostic difficulty, and sometimes difficulties persist even after the detailed examination of resection specimens. Among the most common problems encountered in practice are the distinction of primary endometrial and primary endocervical adenocarcinomas, and the determination of tumor origin when there is synchronous, multifocal involvement of gynecologic tract sites, for example the endometrium and the ovary. However, accurate diagnosis in these cases is important because this has significant staging, management and prognostic implications. In this review we discuss the value and limitations of key morphologic, immunophenotypic and molecular findings in these diagnostic scenarios.

This article provides practical recommendations developed from the International Society of Gynecological Pathologists Endometrial Carcinoma Project to address 4 issues that may arise in the diagnosis of uterine corpus low-grade endometrioid carcinoma: (1) The distinction between atypical hyperplasia and low-grade endometrioid carcinoma. (2) The distinction between low-grade endometrioid carcinoma and serous carcinoma. (3) The distinction between corded and hyalinized or spindle cell variants of low-grade endometrioid carcinoma and carcinosarcoma. (4) The diagnostic criteria for mixed endometrial carcinomas, a rare entity that should be diagnosed only after exclusion of a spectrum of tumors including morphologic variants of endometrioid carcinoma, dedifferentiated endometrial carcinoma, carcinosarcoma, and endometrial carcinomas with ambiguous morphology.

This paper presents an original methodology to design a financial product that could enhance the demand side participation in ancillary services, especially for industrial consumers. The financial product consists in an American option on the Spanish secondary reserve market for the following day, where the buyer has the right, but not the obligation to offer part of their capacity to the system operator. Considering this approach, an industrial consumer would receive an economic incentive to offer its flexibility to the system without changing its production planning, paying an upfront premium. The computation of the American option is based on a Monte Carlo simulation approach where the random paths are obtained from a machine learning model. The machine learning model attempts to forecast the 24 hour secondary band prices of the following day using a combination of different algorithms; the output and the error of the model are used as a baseline to perform the Monte Carlo simulation that computes the option value.

In this review, we sought to address 2 important issues in the diagnosis of endometrial carcinoma: how to grade endometrial endometrioid carcinomas and how to incorporate the 4 genomic subcategories of endometrial carcinoma, as identified through The Cancer Genome Atlas, into clinical practice. The current International Federation of Gynecology and Obstetrics grading scheme provides prognostic information that can be used to guide the extent of surgery and use of adjuvant chemotherapy or radiation therapy. We recommend moving toward a binary scheme to grade endometrial endometrioid carcinomas by considering International Federation of Gynecology and Obstetrics defined grades 1 and 2 tumors as "low grade" and grade 3 tumors as "high grade." The current evidence base does not support the use of a 3-tiered grading system, although this is considered standard by International Federation of Gynecology and Obstetrics, the American College of Obstetricians and Gynecologists, and the College of American Pathologists. As for the 4 genomic subtypes of endometrial carcinoma (copy number low/p53 wild-type, copy number high/p53 abnormal, polymerase E mutant, and mismatch repair deficient), which only recently have been identified, there is accumulating evidence showing these categories can be reproducibly diagnosed and accurately assessed based on biopsy/curettage specimens as well as hysterectomy specimens. Furthermore, this subclassification system can be adapted for current clinical practice and is of prognostic significance independent of conventional variables used for risk assessment in patients with endometrial carcinoma (eg, stage). It is too soon to recommend the routine use of genomic classification in this setting; however, with further evidence, this system may become the basis for the subclassification of all endometrial carcinomas, supplanting (partially or completely) histotype, and grade. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project.

PURPOSE The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research. METHODS Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse (Health and Research Informatics). Seven different sequencing experiment types were included in the warehouse, with data from institutional research studies and clinical sequencing. RESULTS The implementation of the molecular warehouse involved the close collaboration of many teams with different expertise and a use case–focused approach. Cornerstones of project success included project planning, open communication, institutional buy-in, piloting the implementation, implementing custom solutions to address specific problems, data quality improvement, and data governance, unique aspects of which are featured here. We describe our experience in selecting, configuring, and loading molecular data into the molecular data warehouse. Specifically, we developed solutions for heterogeneous genomic sequencing cohorts (many different platforms) and integration with our existing clinical data warehouse. CONCLUSION The implementation was ultimately successful despite challenges encountered, many of which can be generalized to other research cancer centers.