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Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subset of B-cell ALL with a poor prognosis with conventional therapies. Diagnostic challenges and lack of standardized treatment protocols contribute to suboptimal outcomes. Additionally, while allogeneic hematopoietic cell transplantation (HCT) is frequently recommended in adults with Ph-like ALL given its high-risk nature, data supporting its role remains limited., Objective: We conducted a multicenter retrospective study evaluating outcomes of adult patients undergoing HCT in first complete remission (CR1) for Ph-like ALL compared to Philadelphia chromosome positive ALL (Ph-pos) and other B-cell Philadelphia negative (Ph-neg) ALL., Study Design: Data was collected from from five academic centers across the US, focusing on HCT outcomes for patients with ALL. Patients undergoing HCT in CR1 between 2006 and 2021 were included., Results: Among 673 patients, 83 (12.3%) had Ph-like ALL, while 271 (40.3%) had Ph-pos and 319 (47.4%) had Ph-neg ALL. Outcomes following HCT in CR1 for Ph-like ALL were comparable to Ph-neg ALL, with no significant differences in 3-year overall survival (66% vs 59%, p=0.1), progression-free survival (59% and 54%, p=0.1), or relapse rates (22% vs 20%, p=0.7). In contrast, Ph-pos ALL had superior outcomes; 3-year OS (75%, p<0.001), PFS (70%, p=0.001) and relapse (12%, p=0.003), this is likely attributed to tyrosine kinase inhibitor therapy., Conclusion: Our study suggests that HCT, coupled with effective 2 nd line therapies can possibly mitigate the poor prognosis associated with Ph-like ALL and offers promising outcomes for patients with Ph-like ALL., Competing Interests: Declaration of competing interest Ibahim Aldoss serves on advisory boards for Amgen, Kite, AbbVie, and Agios, is a consultant for Autolus Therapeutics and Amgen, and has received research support from MacroGenics and AbbVie. Mohammed Kharfan-Dabaja received Research/grant support from Bristol Myers Squibb, Novartis and Pharmacyclics and Honoraria from Kite Pharma. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK)., Methods: A prospective cohort study was conducted on people with HIV (PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB+RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma HIV-1 viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes., Results: Among 173 patients with a median (IQR) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL≥20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in two cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis [AHR: 1.49 per log10 VL, 95% CI: 1.04-2.12, P =.027], detectable viremia on oral ART [AHR: 2.45, 95% CI: 1.29-4.65, P =.006], and the level of viral suppression at transition [AHR: 0.38, 95% CI: 0.19-0.75, P =.004]. We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models., Conclusion: Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB+RPV LA was linked to pre-existing factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Anthracnose, the most critical disease affecting olive fruits, is caused by Colletotrichum species. While developing olive fruits are immune to the pathogen regardless of the cultivar, the resistance level varies once the fruit ripens. The defense mechanisms responsible for this difference in resistance are not well understood. To explore this, we analyzed the phenolic metabolic pathways occurring in olive fruits and their susceptibility to the pathogen during ripening in two resistant cultivars ('Empeltre' and 'Frantoio') and two susceptible cultivars ('Hojiblanca' and 'Picudo'). Overall, resistant cultivars induced the synthesis of aldehydic and demethylated forms of phenols, which highly inhibited fungal spore germination. In contrast, susceptible cultivars promoted the synthesis of hydroxytyrosol 4-O-glucoside during ripening, a compound with no antifungal effect. This study showed that the distinct phenolic profiles between resistant and susceptible cultivars play a key role in determining olive fruit resistance to Colletotrichum species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

This prospective study aimed to determine the prevalence of long COVID in patients hospitalized for SARS-CoV-2 infection from March 2020 to July 2022 and assess the impact of different viral lineages. A total of 2,524 patients were followed up for 12 months, with persistent symptoms reported in 35.2% at one month, decreasing thereafter. Omicron variant patients initially showed higher symptom intensity, but this trend diminished over time. Certain viral lineages, notably Delta lineages AY.126 and AY.43, and Omicron sublineages BA.1.17, BA.2.56, and BA.5.1, consistently correlated with more severe symptoms. Overall, long COVID prevalence and severity were similar across SARS-CoV-2 variants. Specific lineages may influence post-COVID sequelae persistence and severity., Competing Interests: None to declare., (© 2024 Published by Elsevier Inc.)

Objective: To assess the degree of implementation of cancer screening recommendations in people living with HIV (PLHIV) in Spain., Methods: A self-administered questionnaire was designed on the strategies used for early detection of the main types of cancer in PLHIV. The survey was distributed electronically to HIV physicians participating in the Spanish CoRIS cohort., Results: 106 questionnaires were received from 12 different Spanish Autonomous Communities, with an overall response rate among those who accessed the questionnaire of 60.2%. The majority responded that they followed the CPGs recommendations for the early detection of liver (94.3%), cervical (93.2%) and breast (85.8%) cancers. In colorectal and anal cancer, the proportion was 68.9% and 63.2%, and in prostate and lung cancer of 46.2% and 19.8%, respectively. In hospitals with a greater number of beds, a tendency to perform more cancer screening and greater participation of the Infectious Diseases/HIV Services in the screening programmes was observed. Significant differences were observed in the frequency of colorectal and anal cancer screening among the different Autonomous Communities. The most frequent reasons for not performing screening were the scarcity of material and/or human resources and not being aware of what is recommended in the CPGs., Conclusions: There are barriers and opportunities to expand cancer screening programmes in PLHIV, especially in colorectal, anal and lung cancers. It is necessary to allocate resources for the early detection of cancer in PLHIV, but also to disseminate CPGs screening recommendations among medical specialists., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Alzheimer's disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aβ) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aβ aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise's potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.

(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.

DNA vaccines have inherent advantages compared to other vaccine types, including safety, rapid design and construction, ease and speed to manufacture, and thermostability. However, a major drawback of candidate DNA vaccines delivered by needle and syringe is the poor immunogenicity associated with inefficient cellular uptake of the DNA. This uptake is essential because the target vaccine antigen is produced within cells and then presented to the immune system. Multiple techniques have been employed to boost the immunogenicity and protective efficacy of DNA vaccines, including physical delivery methods, molecular and traditional adjuvants, and genetic sequence enhancements. Needle-free injection systems (NFIS) are an attractive alternative due to the induction of potent immunogenicity, enhanced protective efficacy, and elimination of needles. These advantages led to a milestone achievement in the field with the approval for Restricted Use in Emergency Situation of a DNA vaccine against COVID-19, delivered exclusively with NFIS. In this review, we discuss physical delivery methods for DNA vaccines with an emphasis on commercially available NFIS and their resulting safety, immunogenic effectiveness, and protective efficacy. As is discussed, prophylactic DNA vaccines delivered by NFIS tend to induce non-inferior immunogenicity to electroporation and enhanced responses compared to needle and syringe.

Conditioning regimens play a major role in determining disease outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of i.v. busulfan (Bu) as part of conditioning chemotherapy has been shown to be effective in controlling disease relapse; however, disease relapse remains a major cause of death following allo-HSCT. This study was conducted to determine the long-term outcomes of vorinostat with i.v. Bu plus dual nucleoside analogs clofarabine (Clo) and fludarabine (Flu) in the conditioning regimen for patients undergoing allo-HSCT. This was a rapid dose escalation phase I/II study designed to determine whether the addition of vorinostat would improve the efficacy of standard i.v. Bu/Flu/Clo conditioning regimen. This report presents the long-term disease outcomes of this combination in 68 patients with high-risk leukemia, including 31 (46%) with acute lymphoblastic leukemia (ALL) and 37 (54%) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Fifty-eight patients (85%) were in morphologic complete remission at time of transplantation, and 38 (56%) received a matched unrelated donor graft. Over the median follow-up of 37.6 months, 29 of the 68 patients died (43%), and the nonrelapse mortality (NRM) rate was 22% (n = 15). The median overall survival and median NRM were not reached. Nineteen patients (28%) experienced disease progression. The median progression-free survival was 36.8 months. Thirty-seven patients (57%) developed grade II-IV acute graft-versus-host disease (GVHD), and 20 patients (31%) developed chronic GVHD. Our results suggest a lack of benefit from adding a short course of vorinostat to i.v. Bu/Flu/Clo conditioning regimens for leukemia patients undergoing allo- HSCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

We aimed to study the risks of graft-versus-host disease (GVHD), non-relapse mortality (NRM) and survival outcomes of allogeneic stem cell transplantation (alloSCT) in patients with chronic lymphocytic leukemia ( n  = 17), Richter's syndrome ( n  = 14), or lymphoma ( n  = 18) after small molecule inhibitors (SMIs). Patients had a median of 4 prior therapies, including ibrutinib ( n  = 46; 94%), venetoclax ( n  = 19; 39%), and idelalisib ( n  = 6; 12%). Twenty-one (43%) had >1 SMI. P53 mutation was detected in 58% of patients. The 3-year overall and progression-free survival rates were 68% and 59%, respectively. The rates of grade II-IV and III-IV acute GVHD were 33% and 7%. The 1-year rates of chronic GVHD, NRM and relapse were 19%, 10% and 21%, respectively. Results were comparable to a historical control of patients who received alloSCT without a prior exposure to SMI. We conclude that a prior use of SMI does not impair the outcomes after alloSCT.

Antiviral strategies that target host systems needed for SARS-CoV-2 replication and pathogenesis may have therapeutic potential and help mitigate resistance development. Here, we evaluate nafamostat mesylate, a potent broad-spectrum serine protease inhibitor that blocks host protease activation of the viral spike protein. SARS-CoV-2 is used to infect human polarized mucociliated primary bronchiolar epithelia reconstituted with cells derived from healthy donors, smokers and subjects with chronic obstructive pulmonary disease. Nafamostat markedly inhibits apical shedding of SARS-CoV-2 from all donors (log 10 reduction). We also observe, for the first-time, anti-inflammatory effects of nafamostat on airway epithelia independent of its antiviral effects, suggesting a dual therapeutic advantage in the treatment of COVID-19. Nafamostat also exhibits antiviral properties against the seasonal human coronaviruses 229E and NL6. These findings suggest therapeutic promise for nafamostat in treating SARS-CoV-2 and other human coronaviruses., Competing Interests: K.H.B. is founder and holds equity in Pneumax, LLC., (© 2021 The Authors. Nano Select published by Wiley‐VCH GmbH.)

Introduction: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19., Methodology: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured., Results: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients., Conclusions: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Roberto Ovilla-Martinez, Xochitl Cota-Rangel, Jose De La Pena-Celaya, Mariana Alejandra Alvarado-Zepeda, Alejandro Jimenez Sastre, Humberto Azuara Forcelledo, Bernardino Ordonez Rodriguez, Juan Pulido Broca, Aaron Molina Jaimes, Alejandro Muniz-Carvajal, Maria Magdalena Bahena Garcia, Eduardo Cervera Ceballos, Nidia Paulina Zapata Canto, Jorge Oscar Garcia Mendez, Omar Noel Garcia Jimenez, Jesus Alberto Salas Heredia, Javier Solis Soto, Ruben Alberto Villalobos Mendez, Gregorio Ignacio Ibarra, Cindy Ledesma de la Cruz, Nora Araujo Martinez, Jessi Juarez Lara, Cecilio Omar Ceballos Zuniga, Felipe Vicente Villasenor Perez, Jose Carlos Herrera Garcia, Patricia Nuche Salazar, Alfredo Dominguez Paregrina, Bertha Arizpe Bravo, Gabriela Enciso Figueroa, Teresita Trujillo, Adriana Miguel Alvarez, Diego de Jesus Garcia Gallegos, Alejandro Ortiz Arroyo, Claudia Ivette Solorzano Soto, Hiram Javier Jaramillo Ramirez, Ibis De la Cruz Hernandez, Sergio De Gante Martinez, Guadalupe Esmeralda Montesinos Gomez, Silvia Martinez Velasco, Roberto Garcia Graullera, Miguel Angel Vazquez Lopez, Victor Itai Urbalejo Ceniceros, Yolanda Lugo Garcia, Ana Itamar Gonzalez Avila, Jorge Duque Rodriguez, Rodolfo Ruiz Lujan, Violeta I Rodriguez Rivera, Lucio Soberanes Ramirez, Pamela Elena Baez-Islas.)

Background: COVID-19 has been associated with negative results in patients with A blood group and with a better evolution in O blood group individuals., Aim: Because the evidence regarding ABO blood groups and COVID was empirically not that clear in our country, we tested the association regarding COVID-19 and blood groups., Material and Methods: Adult patients were enrolled in this prospective, case-control, observational multicenter study. Patients with a confirmed diagnosis of COVID-19 were assigned to one of three groups based on the clinical presentation of the infection. Age, gender, ABO and Rh blood groups, body mass index, history of diabetes mellitus or high blood pressure, and smoking were recorded directly or from their clinical charts. ABO blood group was obtained from 5,000 blood donors (50% each gender). Atherothrombotic variables were compared with a nation-wide data collection., Results: A total of 2,416 patients with COVID-19 were included (women:39.6%; men:60.4%). There were no significant differences between cases and controls in terms of age. O blood group was the most frequently found in healthy donors and COVID-19 patients, but this blood group was significantly higher in COVID-19 patients vs. healthy donors. ABO blood group was not associated with the final health status in COVID-19 patients. Obesity, diabetes mellitus, hypertension and smoking were significantly more frequent among COVID-19 patients., Conclusion: The proposed protective effect of the O blood group in COVID-19 patients could not be reproduced in the Mexican population while some atherothrombotic risk factors had a significant effect on the clinical evolution., Competing Interests: Conflict of Interests None declared., (Copyright © 2021. Published by Elsevier Inc.)

With over 4.8 million deaths within 2 years, time is of the essence in combating COVID-19. The infection now shows devastating impacts on the younger population, who were not previously predicted to be vulnerable, such as in the older population. COVID-19-related complications have been reported in neonates whose mothers were infected with SARS-CoV-2 during pregnancy, and in children who get infected. Hence, a deeper understanding of the pathophysiology of COVID-19 during various developmental stages and placental transmission is essential. Although a connection has not yet been established between exosomal trafficking and the placental transmission of COVID-19, reports indicate that SARS-CoV-2 components may be trafficked between cells through exosomes. As the infection spreads, the transcriptome of cells is drastically perturbed, e.g., through the severe upregulation of several immune-related genes. Consequently, a major outcome of COVID-19 is an elevated immune response and the detection of viral RNA transcripts in host tissue. In this direction, this review focuses on SARS-CoV-2 virology, its in utero transmission from infected pregnant mothers to fetuses, SARS-CoV-2 and exosomal cellular trafficking, transcriptomic impacts, and RNA-mediated therapeutics against COVID-19. Future research will establish stronger connections between the above processes to develop diagnostic and therapeutic solutions towards COVID-19 and similar viral outbreaks.

Purpose: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT)., Patients and Methods: We evaluated 194 patients with follicular lymphoma who received an alloSCT ( n = 98) or autoSCT ( n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan)., Results: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT ( P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively ( P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27)., Conclusions: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma., (©2021 American Association for Cancer Research.)

The development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell-mediated immune responses. Here, we asked whether combination adjuvants based on delta inulin (Advax) formulated with Toll-like receptor (TLR) agonists could improve vaccine protection mediated by a fungal recombinant protein, Bl-Eng2 (i.e., Blastomyces endoglucanase 2), which itself harbors an immunodominant antigen and dectin-2 agonist/adjuvant. We found that Bl-Eng2 formulated with Advax3 containing TLR9 agonist or Advax8 containing TLR4 agonist provided the best protection against pulmonary infection with Blastomyces dermatitidis, being more effective than complete Freund's adjuvant or Adjuplex. Advax3 was most efficient in inducing gamma interferon (IFN-γ)- and interleukin-17 (IL-17)-producing antigen-specific T cells that migrated to the lung upon Blastomyces dermatitidis infection. Mechanistic studies revealed Bl-Eng2/Advax3 protection was tempered by neutralization of IL-17 and particularly IFN-γ. Likewise, greater numbers of lung-resident T cells producing IFN-γ, IL-17, or both IFN-γ and IL-17 correlated with fewer fungi recovered from lung. Protection was maintained after depletion of CD4 + T cells, partially reduced by depletion of CD8 + T cells, and completely eliminated after depletion of both CD4 + and CD8 + T cells. We conclude that Bl-Eng2 formulated with Advax3 is promising for eliciting vaccine-induced antifungal immunity, through a previously uncharacterized mechanism involving CD8 + and also CD4 + T cells producing IFN-γ and/or IL-17. Although no licensed vaccine exists as yet against any fungal disease, these findings indicate the importance of adjuvant selection for the development of effective fungal vaccines. IMPORTANCE Fungal disease remains a challenging clinical and public health problem. Despite medical advances, invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immunocompetent and -deficient hosts, with worldwide mortality rates ranking 7th, even ahead of tuberculosis. The development of safe, effective vaccines remains a major hurdle for fungi. Critical barriers to progress include the lack of defined fungal antigens and suitable adjuvants. Our research is significant in identifying adjuvant combinations that elicit optimal vaccine-induced protection when formulated with a recombinant protective antigen and uncovering the mechanistic bases of the underlaying vaccine protection, which will foster the strategic development of antifungal vaccines.

Fluid overload (FO) grade ≥2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L] × creatinine [mg/dL]/platelets [10 9 cells/L]) correlates with grade ≥2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade ≥2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade ≥2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log 2 -transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade ≥2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log 2 EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade ≥2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P < .001) and in the validation (cutoff: 4.3, HR = 4.8, P < .001) cohorts. The significant effect of EASIX persisted in multivariate CART analysis in the study (HR = 6.3, P < .001) and the validation (HR = 28, P = .002) cohorts. Additional predictors in multivariate analysis included body weight below 80 kg in recipients older than 55 years (HR = 4.5, P < .001) in the study cohort and diabetes (HR = 34, P = .001) and age >60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade ≥2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade ≥2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: Our study aim was to document the seroprevalence and associated risk factors of feline foamy virus (FFV) infection in domestic cat populations presented to animal shelters located in Southern California, Colorado and Florida, USA., Methods: We used a glutathione S-transferase capture ELISA targeting the FFV Gag antigen to screen domestic cat serum collected from cats with unknown owners at eight different animal shelters from Colorado (n = 105, three shelters), Southern California (n = 172, three shelters) and Florida (n = 31, two shelters). χ 2 statistics determined location effect on seroprevalence. Bayesian generalized linear models were used to explore age and sex as potential risk factors for infection., Results: FFV seroprevalence was 64.0% across all locations. Seroprevalence by location was as follows: Southern California 75.0%, Colorado 52.4% and Florida 41.9%, with Southern California's seroprevalence being significantly higher. Age had a significant effect on model fit for all locations, with adults having a higher probability of being infected. In Colorado, sex also had a significant effect on model fit, with males having a higher probability of being infected., Conclusions and Relevance: We have documented that FFV is extremely common in stray domestic cat populations across varied geographic and ecological niches throughout the USA. Adult cats are at a higher FFV infection risk than young cats. FFV has been associated with a higher risk of other retroviral infections and has been implicated in several chronic diseases of cats. Additional epidemiological and clinical studies are warranted to investigate the potential impacts of FFV on domestic cat health., Competing Interests: Conflict of interest: There are no conflicts of interest at play in this research. Funding sources had no hand in the study design, data collection, analysis of data or conclusions of the results.

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.

Although bortezomib and rituximab have synergistic activity in patients with lymphoma and both can attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem cell transplantation (alloSCT). In this phase I/II trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 to 1.3 mg/m 2 per dose) was administered i.v. on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results with an historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and matched unrelated donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m 2 . The weighted cumulative incidences of grades II to IV and III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival was not reached in patients age ≤ 50 years and with a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤ 50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Feline foamy virus (FFV) is a retrovirus that has been detected in multiple feline species, including domestic cats ( Felis catus ) and pumas ( Puma concolor ). FFV results in persistent infection but is generally thought to be apathogenic. Sero-prevalence in domestic cat populations has been documented in several countries, but the extent of viral infections in nondomestic felids has not been reported. In this study, we screened sera from 348 individual pumas from Colorado, Southern California and Florida for FFV exposure by assessing sero-reactivity using an FFV anti-Gag ELISA. We documented a sero-prevalence of 78.6% across all sampled subpopulations, representing 69.1% in Southern California, 77.3% in Colorado, and 83.5% in Florida. Age was a significant risk factor for FFV infection when analyzing the combined populations. This high prevalence in geographically distinct populations reveals widespread exposure of puma to FFV and suggests efficient shedding and transmission in wild populations.

Objectives: To test a more complete set of morphometric radiographic parameters to evaluate the idiopathic osteosclerosis (IO) lesions located in the maxillomandibular area and to know their features during routine radiographic evaluation., Materials and Methods: Radiographs from patients attending the oral diagnosis clinic of our institution were reviewed. Evaluated parameters were gender and age of the patients, size, side, homogeneity, morphology, radiodensity, mineralization, borders, relation to roots, affected tooth or teeth and location of the analyzed lesions., Results: Of the 6340 assessed patients, 354 (5.6%) harbored 362 lesions. IOs were more common during 2nd to 4th decades (mean age = 39 years). IO frequency rose from 1st to 3rd decades and then decreased. Size varied from 0.1 to 5.8 cm, and its frequency increased from 7 to 30 years age and then decreased too. The mandible and molar region were more commonly affected. Radiopaque image, radicular location, round shape, homogeneous core and well-defined boundaries were the more frequent IO features., Conclusions: Our method allows to analyze IO lesions with precise parameters. Analysis of the results does not support the previously suggested theories to explain their origin, and these figures suggest that the so-called IOs are developmental alterations of the bone.

Background: The aim of this study was to record and analyze all DDAs associated to dilacerated teeth in patients attending the clinics of the Postgraduate Division, Facultad de Odontología, UNAM in Mexico City., Material and Methods: Orthopantomograms from all patients seeking for stomatological attention in our institution were reviewed and those cases of dilaceration were separated. Age, gender, diagnosis, location, involved teeth and associated DDAs were recorded and analyzed., Results: From 6,340 patients, 99 (1.6%) harbored 125 dilacerated teeth. Of them, 45 (45.5%) showed one or more DDAs. The most frequently detected DDAs were hypodontia, enamel pearls, taurodontism and microdontia., Conclusions: 45.5% is a very high proportion of DDAs in patients with dilacerated roots. Findings from this study strongly suggest that patients with dilacerated teeth should be carefully screened since many of them could present other DDAs. Simultaneous occurrence of dilaceration and DDAs suggests synchronic developmental defects during dental growth.

This study aims to evaluate the clinicopathological features, TNM status, AJCC staging and behavior of squamous cell carcinoma of the tongue (SCCT) in patients older than 45 years. The files of the Department of Pathology of the Hospital General de México were reviewed and all cases of SCCT in patients older than 45 years were selected. Clinicopathological features, treatment, follow-up, microscopic diagnosis, and IJCC and TNM staging were retrieved. Complete data from 60 cases were evaluated. They were more common in males (mean age = 63.9 years). Unexpectedly a high rate of tumors (38.3%) were in the base of the tongue (BT). Moderately and poorly differentiated SCCT were the most common. 16.7% presented lymph node invasion, 15% were recurrent tumors and BT carcinomas recurred more frequently. A high rate (81.7%) were stage II and 48.3% were low-risk patients. SCCTs in the studied population displayed different clinico-pathological and behavioral features compared with worldwide data. Our results suggest that BT tumors should be treated more aggressively than those in the mobile tongue. BT located tumors were more frequent than previously published. Additional frequency studies will define outcomes in age cohorts with a consensus cut-off for young and elderly populations. More population-based studies should be performed in Latin American regions to acquire accurate data on SCC incidence in elder subpopulations and to identify precisely the etiological factors in these patients.

Purpose: To assess radiographically the presence of an ossified stylohyoid complex (OSHC) with signs and symptoms of Eagle syndrome or other oro-facial painful diseases in patients attending our institution and to confirm that the important issue for study is to know the length of the ossificated portion of the stylohyoid complex only., Methods: We separated 1000 consecutive files, and after selection, 922 panoramic radiographs were evaluated. Assessed parameters were gender and age of the patients, size, and location of the analyzed OSHCs. In addition, the length parameters of the studied OSHCs were also determined in 100 extra radiographs., Results: Normal length of OSHCs was between 2.83 and 4.16 cm and OSHCs measuring more than 4.17 cm long comprising 23.2% of the sample. Any of the patients with OSHC presented signs or symptoms of the Eagle syndrome or any other orofacial painful disease., Conclusions: This is the first study on OSHCs using the mandatory parameters of normal, short and elongated length in the studied population. Our results suggest that the presence of an OSHC is not an important feature for pain detection in the Eagle syndrome and is not an important risk factor for development of throat pain in this and other painful orofacial diseases. Our results are different from those previously published in other populations and suggest that the widely used lengths of 2 to 4 cm for measuring the OSHCs are not adequate parameter. It is desirable to define first the short, normal and abnormal parameters of OSHCs in each studied population.

Background: The aim of this study was to record the frequency of dilaceration in patients attending our institution and to analyze the possible associated factors., Material and Methods: Orthopantomograms from all patients attended in our institution were reviewed and those cases of dilaceration were selected. Documented data were age, gender, diagnosis, location and involved teeth. Data on possible etiological factors was also recorded., Results: 125 dilacerated teeth in 99 patients were found. Dilacerations were more commonly detected in females and in maxillary teeth. Maxillary 2nd bicuspids and lateral incisors were the more commonly affected teeth and were more common in teeth with predecessors (anterior teeth and bicuspids). Traumatic episodes and caries of the predecessor teeth was mentioned but never were related with affected teeth., Conclusions: Data from the studied population are different compared to previously published studies. Our results support the point of view that the occurrence of dilacerated teeth could be related to limited availability of space to allocate the erupting teeth in the dental arch and perhaps to the possibility of the tooth to rotate, preventing eruption. Key words: Developmental alterations, dental developmental alterations, root dilaceration., Competing Interests: Conflict of interest statement: The authors state that there are no conflicts of interest. The author declares that the human rights of the persons were not violated and that all of them signed an informed consent letter.

The interaction of 3 water sanitizers (sodium hypochlorite, iodine-polyvinylpyrrolidone, and citrate) utilized in poultry production on antibacterial activity and bioavailability of amoxicillin trihydrate (AMX) were studied. Sanitizers were mixed with AMX in prepared water, the resulting substances were regarded as amoxicillin-sanitizer products (ASP). First, the in vitro antibacterial activity of each ASP was compared to that of AMX. Then, pharmacokinetics (PK) of ASP and AMX diluted in prepared water, were carried out in broiler-chickens. Amoxicillin or ASP (20 mg/kg) from different concentrations of sanitizers was directly placed into the chicken's crop and blood samples were taken. Basic PK parameters were obtained. Serum activity/concentrations of AMX were assessed by agar diffusion and corroborated with high performance liquid chromatography. Results show that ASP of AMX/sodium hypochlorite decrease both, the antimicrobial activity of in vitro AMX and its relative bioavailability (Fr) assessed with the maximum serum concentration (Cmax), the area under the concentration-time curve, and the mean residence time (MRT) (3.80 μg/mL, 2.70 μg/mL·h, and 0.59 h, respectively), compared to the AMX administered alone (12.54 μg/mL, 44.02 μg/mL·h, and MRT 2.78 h). ASP from amoxicillin/ionophore, reduced the Cmax (10.62 μg/mL), Fr (94.67%), and MRT (2.07 h), at the highest tested concentrations. In contrast, the 2 highest concentrations of the citrate sanitizer increased the Cmax (15.07 and 15.47 μg/mL), Fr (119 and 132%), and MRT (3.32 and 4.06 h) and their in vitro antimicrobial activity. Interactions between the tested water sanitizers and AMX modify the Cmax, Fr, MRT of the latter, altering the PK/pharmacodymanic ratios for a time-dependent antibiotic. Results also reveal that the use of amoxicillin trihydrate administered through the drinking water does not meet the required PK/pharmacodymanic ratios. Thus, it is here postulated that this antibiotic should be administered at least twice a day and that its interaction with water sanitizers should be considered.

Introduction: Giant Osteosclerotic Lesions (GOLs) are a group of rarely reported intraosseous lesions. Their precise diagnosis is important since they can be confused with malignant neoplasms., Objective: This retrospective study aimed to record and analyze the clinical and radiographic Giant Osteosclerotic Lesions (GOLs) detected in the maxillomandibular area of patients attending to our institution. Materials and Methods: Informed consent from the patients was obtained and those cases of 2.5 cm or larger lesions with radiopaque or mixed (radiolucid-radiopaque) appearance located in the maxillofacial bones were selected. Assessed parameters were: age, gender, radiographic aspect, shape, borders, size, location and relations to roots. Lesions were classified as radicular, apical, interradicular, interradicular-apical, radicular-apical or located in a previous teeth extraction area. Additionally, several osseous and dental developmental alterations (DDAs) were assessed., Results: Seventeen radiopacities in 14 patients were found and were located almost exclusively in mandible and were two types: idiopathic osteosclerosis and condensing osteitis. GOLs were more frequent in females, and in the anterior and premolar zones. 94.2% of GOLs were qualified as idiopathic osteosclerosis and one case was condensing osteitis. All studied cases showed different osseous and dental developmental alterations (DDAs). The most common were: Microdontia, hypodontia, pulp stones, macrodontia and variations in the mental foramina., Conclusions: GOLs must be differentiated from other radiopaque benign and malignant tumors. Condensing osteitis, was considered an anomalous osseous response induced by a chronic low-grade inflammatory stimulus. For development of idiopathic osteosclerosis, two possible mechanisms could be related. The first is modification of the normal turnover with excessive osseous deposition. The second mechanism will prevent the normal bone resorption, arresting the osseous breakdown process.

Background: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes. Here we examine the capacity of vif to substitute for bet function in a chimeric FFV to assess the transferability of anti-feA3 factors to allow viral replication., Results: We show that vif can replace bet to yield replication-competent chimeric foamy viruses. An in vitro selection screen revealed that an engineered Bet-Vif fusion protein yields suboptimal protection against feA3. After multiple passages through feA3-expressing cells, however, variants with optimized replication competence emerged. In these variants, Vif was expressed independently from an N-terminal Bet moiety and was stably maintained. Experimental infection of immunocompetent domestic cats with one of the functional chimeras resulted in seroconversion against the FFV backbone and the heterologous FIV Vif protein, but virus could not be detected unambiguously by PCR. Inoculation with chimeric virus followed by wild-type FFV revealed that repeated administration of FVs allowed superinfections with enhanced antiviral antibody production and detection of low level viral genomes, indicating that chimeric virus did not induce protective immunity against wild-type FFV., Conclusions: Unrelated viral antagonists of feA3 cellular restriction factors can be exchanged in FFV, resulting in replication competence in vitro that was attenuated in vivo. Bet therefore may have additional functions other than A3 antagonism that are essential for successful in vivo replication. Immune reactivity was mounted against the heterologous Vif protein. We conclude that Vif-expressing FV vaccine vectors may be an attractive tool to prevent or modulate lentivirus infections with the potential option to induce immunity against additional lentivirus antigens.

Background: Extra-Nodal natural killer/T-cell lymphoma (ENKL) is a rare lymphoma representing approximately 5-10% of T-cell non-Hodgkin lymphomas diagnosed in the United States each year. Patients with advanced stage III/IV ENKL and relapsed refractory ENKL have a poor prognosis even despite aggressive therapy and stem cell transplantation (SCT). We conducted a review of the management of 37 patients with advanced-stage and relapsed/refractory ENKL in a predominantly non-Asian cohort evaluating both chemotherapy and SCT outcomes., Patients and Methods: We evaluated clinical outcomes in all patients treated for advanced stage III/IV or relapsed/refractory ENKL at MD Anderson cancer center between 2000-2014. Next, we collected stem cell transplant data from four transplant institutions to further evaluate outcomes of both allogeneic (allo-SCT) and autologous (auto-SCT) stem cell transplantation in ENKL., Results: OS and PFS were 73% and 45% at one year, and 30% and 19% at 3-years, respectively. SMILE chemotherapy was more effective in maintaining a CR compared to CHOP (83% vs 17%). Only achievement of CR was prognostic for OS (HR 0.245, p=0.002) and PFS (HR 0.072, p) CONCLUSION: Our results suggest that achievement of a CR is imperative in patients with advanced ENKL, and is desirable for any patient for whom auto-SCT is utilized. SMILE-based chemotherapy appeared effective in attaining a CR, and was also an effective salvage regimen. For patients attaining a first CR, auto-SCT should be strongly considered, but should definitely be utilized in patients attaining CR2. For patients with refractory disease, allo-SCT can be considered in a selected group of patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic stem cell transplantation. We hypothesized that FO is associated with transplantation outcomes and evaluated this complication in 2 cohorts of patients. FO was graded based on post-transplantation weight gain, symptoms, and need for treatment, scored in real time by an independent team. The first cohort (study cohort; n = 145) underwent haploidentical transplantation for hematologic malignancies following a melphalan-based conditioning regimen. In univariate analysis, factors associated with day +100 nonrelapse mortality (NRM) were FO grade ≥2 (hazard ratio [HR], 15; 95% confidence interval [CI], 4.2 to 55; P < .001), creatinine >1 mg/dL (HR, 4.7; 95% CI, 1.6 to 14; P = .005), and age >55 years (HR, 4.5; 95% CI, 1.5 to 13; P = .008). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 13.1; 95% CI, 3.4 to 50; P < .001) and serum creatinine level >1 mg/dL at transplantation admission (HR, 3.5; 95% CI, 1.1 to 11; P = .03). These findings were verified in a separate cohort (validation cohort) of patients with acute myelogenous leukemia/myelodysplastic syndrome who underwent HLA-matched transplantation with busulfan-based conditioning (n = 449). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 34; 95% CI, 7.2 to 158; P < .001) and, in patients with FO grade <2, advanced disease status (HR, 5; 95% CI, 1.1 to 22; P = .03). A higher NRM translated to significantly poorer 1-year overall survival rates for patients with FO ≥2 than for patients without FO (70% versus 42%, P < .001 in the study cohort and 64% versus 38%, P < .001 in the validation cohort). In conclusion, FO grade ≥2 is strongly associated with higher NRM and shorter survival and should be considered an important prognostic factor in transplantation., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Multifocal epithelial hyperplasia is an uncommon disease of the oral mucosa caused by the human papilloma virus., Aim: To study the clinical and pathological findings of multifocal epithelial hyperplasia detected during an oral examination of 343 Mexican Nahuatl children from a single primary school in El Paso de Cupilco, Mexico., Methods: A thorough oral examination was performed in all children and clinical data (age, gender, location and number of lesions) were documented and analyzed., Results: Multifocal epithelial hyperplasia was diagnosed in 110 of the 343 children (32.3%). The ages of the children varied from 5 to 15 years, and of these, 56.3% were girls. The lesions were asymptomatic, 0.2 to 3.0 cm in diameter, soft, round to oval, smooth surfaced, sessile papulonodules, similar in colour to that of the surrounding mucosa. The lesions were commonly seen on the buccal mucosa and tongue, and most affected children (85%) had less than 5 lesions. Children in the 7 to 10 years age group were most often affected., Limitations: Human papillomavirus typing was not done owing to a lack of facilities., Conclusions: There is a high incidence of multifocal epithelial hyperplasia in Nahuatl children with a predilection for females.

Mite diversity of selected citrus orchards in Andalusia (southern Spain) was studied during 2002-2007. The following species were found: Eutetranychus orientalis, Tetranychus urticae, Panonychus citri (Tetranychidae), Tydeus californicus, Lorryia formosa (Tydeidae), Pronematus ubiquitus (Iolinidae), Euseius stipulatus, Typhlodromus phialatus, Neoseiulus californicus, Euseius scutalis, Phytoseiulus persimilis, Paraseiulus talbii and Neoseiulus cucumeris (Phytoseiidae). Eutetranychus orientalis was the dominant tetranychid species in orange and lemon trees, whereas T. urticae was slightly more abundant in mandarines. The most abundant tydeid in clementine and orange was Tydeus californicus, in lemon it was L. formosa. The iolinid P. ubiquitus was found in very low numbers. With respect to phytoseiids, E. stipulatus was dominant in the three citrus species. Eutetranychus orientalis had a unimodal phenology, peaking only in autumn, whereas the other two tetranychids had two maxima. Tydeus californicus showed one or two peaks depending upon the citrus species, and E. stipulatus also had two peaks, one in spring and one in autumn. The mites displayed a non-random distribution in the tree. Eutetranychus orientalis preferred the outer and upper leaves. On the contrary, tydeids (mainly T. californicus) and phytoseiids (mainly E. stipulatus) preferred inner and lower leaves. These preferences had not been sufficiently described previously, and they are important for sampling plans.

In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide therapy. Five (62%) patients had to stop taking the drug because of toxicity. The main reason for drug discontinuation was acute GVHD in 43% of patients. This incidence was 11% in the patients who were randomized to not receive lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4 years for those receiving lenalidomide. This was not reached in patients randomized to not receive lenalidomide and in patients in complete remission who were not randomized. These results suggested that treatments other than lenalidomide are needed for persistent CLL after alloSCT., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)