A Descriptive Study of 103 Primary Cutaneous B-Cell Lymphomas: Clinical and Pathological Characteristics and Treatment from the Spanish Lymphoma Oncology Group (GOTEL).

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

Situs Inversus Totalis in the Critical Care Unit: A Case Report and Literature Review.

Situs inversus is a rare congenital disorder where the reversal of some of the major thoracic or abdominal organs is present. In this disorder, alterations in the fetus's organ lateralization lead to a complete reversal in the arrangement of the internal organs. Most of the time, they are found incidentally when having a procedure or imaging modality. Little has been written regarding the challenges encountered while providing critical care to these patients. Here we present the case of a 68-year-old male patient admitted to the intensive care unit (ICU) with hypoxemic respiratory failure secondary to pneumonia who underwent diagnostic bronchoscopy for organism identification and was confirmed to have situs inversus totalis. Situs inversus totalis represents a challenge at different levels of care to these patients, including in the ICU. Limitations in critical care can be seen upon imaging identification, and during routine procedures performed at the ICU. Confusion might appear while performing bedside point of care ultrasound, obtaining vascular access, performing electrocardiogram, and sample identification, among others. The case brings the relevance of being able to recognize this rare disorder, which can be diagnosed even in advanced age since it might present the clinician with challenges at the time of providing care to patients.

Current Perspective on the Potential Benefits of Smart Insulin Pens on Glycemic Control in Patients With Diabetes: Spanish Delphi Consensus.

INTRODUCTION: Diabetes mellitus (DM) is a chronic disease with high morbidity and mortality, and glycemic control is key to avoiding complications. Technological innovations have led to the development of new tools to help patients with DM manage their condition. OBJECTIVE: This consensus assesses the current perspective of physicians on the potential benefits of using smart insulin pens in the glycemic control of patients with type 1 diabetes (DM1) in Spain. METHODS: The Delphi technique was used by 110 physicians who were experts in managing patients with DM1. The questionnaire consisted of 94 questions. RESULTS: The consensus obtained was 95.74%. The experts recommended using the ambulatory glucose profile report and the different time-in-range (TIR) metrics to assess poor glycemic control. Between 31% and 65% of patients had TIR values less than 70% and were diagnosed based on glycosylated hemoglobin values. They believed that less than 10% of patients needed to remember to administer the basal insulin dose and between 10% and 30% needed to remember the prandial insulin dose. CONCLUSIONS: The perception of physicians in their usual practice leads them to recommend the use of ambulatory glucose profile and time in range for glycemic control. Forgetting to administer insulin is a very common problem and the actual occurrence rate does not correspond with clinicians' perceptions. Technological improvements and the use of smart insulin pens can increase treatment adherence, strengthen the doctor-patient relationship, and help improve patients' education and quality of life.

Soil Microbial Community Responses to Different Management Strategies in Almond Crop.

A comparative study of organic and conventional farming systems was conducted in almond orchards to determine the effect of management practices on their fungal and bacterial communities. Soils from two orchards under organic (OM) and conventional (CM), and nearby nonmanaged (NM) soil were analyzed and compared. Several biochemical and biological parameters were measured (soil pH, electrical conductivity, total nitrogen, organic material, total phosphorous, total DNA, and fungal and bacterial DNA copies). Massive parallel sequencing of regions from fungal ITS rRNA and bacterial 16 S genes was carried out to characterize their diversity in the soil. We report a larger abundance of bacteria and fungi in soils under OM, with a more balanced fungi:bacteria ratio, compared to bacteria-skewed proportions under CM and NM. The fungal phylum Ascomycota corresponded to around the 75% relative abundance in the soil, whereas for bacteria, the phyla Proteobacteria, Acidobacteriota and Bacteroidota integrated around 50% of their diversity. Alpha diversity was similar across practices, but beta diversity was highly clustered by soil management. Linear discriminant analysis effect size (LEfSE) identified bacterial and fungal taxa associated with each type of soil management. Analyses of fungal functional guilds revealed 3-4 times larger abundance of pathogenic fungi under CM compared to OM and NM treatments. Among them, the genus Cylindrocarpon was more abundant under CM, and Fusarium under OM.

Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study.

PURPOSE: Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL. EXPERIMENTAL DESIGN: We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples. RESULTS: Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients. CONCLUSIONS: Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.

Sensing Capacity in Dysprosium Metal-Organic Frameworks Based on 5-Aminoisophthalic Acid Ligand.

Two novel metal-organic frameworks (MOFs), based on dysprosium as the metal and the 5-aminoisophthalic acid (5aip) ligand, have been solvothermally synthesized, with the aim of studying and modulating their luminescence properties according to the variation of solvent in the structure. These materials display intense photo-luminescence properties in the solid state at room temperature. Interestingly, one fascinating sensory capacity of compound 2 regards obtaining a variation of the signal, depending on the solvent to which it is exposed. These results pave the way for a new generation of sensitive chemical sensors.

Molecular and Pathogenic Characterization of Cylindrocarpon-like Anamorphs Causing Root and Basal Rot of Almonds.

Three almond nurseries were prospected in the South of Spain (Sevilla) to evaluate the sanitary status of the nursery plant material. Samples consisted of main roots, secondary roots and six-month-old basal stems 'GxN-15', 'Nemaguard', 'Cadaman', 'Rootpac-40' and 'Rootpac-20' rootstocks planted in the soil, and twigs of mother plants from 'Lauranne', 'Guara', 'Marcona', 'Marta' and 'Ferragnes' almond cultivars. Endophytic and potential pathogenic fungi were identified in mother plants and 70 Cylindrocarpon-like anamorph isolates were detected in the root system and basal stems of analyzed rootstocks. Based on partial sequencing of the his3 gene and multilocus phylogenetic analysis of the concatenated ITS, tub2, his3 and tef1-α partial sequences, seven Cylindrocarpon-like anamorph species were identified as Dactylonectria torresensis, D. novozelandica, D. macrodidyma, Ilyonectria liriodendri, Neonectria sp. 1, N. quercicola and Cylindrocladiella variabilis. Pathogenicity was assessed on young healthy detached twigs of 'Guara' almond cultivar and one-year-old 'Lauranne' potted almonds grafted onto 'GxN-15' rootstocks. Among the seven Cylindrocarpon-like anamorph species, I. liriodendri, Neonectria sp. 1 and N. quercicola were the most aggressive. Inoculated detached shoots developed necrotic lesions 15 days after inoculation. Inoculated trees showed sectorized necrosis in the main and secondary roots and the basal stem of the rootstock 5 months after inoculation. The most aggressive species were able to cause necrosis also in the grafted cultivar, and I. liriodendri, and N. quercicola also reduced the root biomass. This is the first report of Cylindrocarpon-like anamorph species causing root and basal rot of almonds.

Joint position statement of the International Federation of Sports Medicine (FIMS) and European Federation of Sports Medicine Associations (EFSMA) on the IOC framework on fairness, inclusion and non-discrimination based on gender identity and sex variations.

The IOC recently published its framework on fairness, inclusion and non-discrimination based on gender identity and sex variations. This framework is drafted mainly from a human rights perspective, with less consideration for medical/scientific issues. The framework places the onus for gender eligibility and classification entirely on the International Federations (IFs), even though most will not have the capacity to implement the framework. The position of no presumption of advantage is contrary to the 2015 IOC consensus. Implementation of the 2021 framework will be a major challenge for IFs that have already recognised the inclusion of trans and women athletes with differences of sexual development (DSD) using a scientific/medical solution. The potential consequences for sports that need to prioritise fairness or safety could be one of two extremes (1) exclusion of all transgender or DSD athletes on the grounds of advantage or (2) self-identification that essentially equates to no eligibility rules. Exclusion of all transgender or DSD athletes is contrary to the Olympic charter and unlawful in many countries. While having no gender eligibility rules, sport loses its meaning and near-universal support. Athletes should not be under pressure to undergo medical procedures or treatment to meet eligibility criteria. However, if an athlete is fully informed and consents, then it is their free choice to undergo carefully considered or necessary interventions for gender classification for sport to compete fairly and safely in their chosen gender. Free choice is a fundamental human right, but so is the right to fair and safe competition.

Pilot study: genetic distribution of AR, FGF5, SULT1A1 and CYP3A5 polymorphisms in male Mexican population with androgenetic alopecia.

Genetics is responsible for 80% of androgenetic alopecia (AGA) predisposition. Several single nucleotide polymorphisms (SNPs) have been linked to AGA risk and the metabolism of its first-line therapies. Genotypic and allelic frequencies have not been described in Mexican individuals; therefore, the aim of this study was to describe the genetic distribution of SNPs associated with AGA predisposition and drug metabolism. Using Real Time-PCR, we genotyped SNPs rs4827528 (AR), rs7680591 (FGF5), rs1042028, rs1042157, rs788068 and rs6839 (SULT1A1) and rs776746 (CYP3A5) in 125 (controls = 60, cases = 65) male volunteers from Northern and Western Mexico. The SULT1A1 SNPs rs1042028 (C/T) and rs788068 (T/A/C) resulted in a 100% distribution of the ancestral allele C and mutated allele A, respectively; rs1042028 diverges from the previously reported frequency, while the rs788068 ancestral allele was found to be more predominant than the reported frequency. Rs1042028, rs788068 and rs4827528, were not in Hardy-Weinberg (HW) equilibrium; conversely, rs1042157 and rs6839, rs776746, and rs7680591 followed HW principles. A statistically significant difference (P<0.05) was obtained for the rs1042157 allelic frequency between cases and controls in Western Mexico. We reported the genotypic and allelic frequencies of seven polymorphisms in Mexican individuals from Northern and Western Mexico.

[Contribution of the occupational health to the COVID-19 pandemic control.] / Contribución de la salud laboral al control de la pandemia por covid-19 en España.

When the World Health Organization declared Covid-19 as a public health emergency of international concern, the Spanish Ministry of Health called the health, labor, social security authorities, Labor and Social Security Inspection, National Institute of Security and Occupational Health, employers, unions, occupational risk prevention services, mutual societies and scientific societies of occupational medicine and nursing, to collaborate in the control of the transmission of SARS-CoV-2 in companies. The Occupational Health Group of the Public Health Commission of the Interterritorial Council of the National Health System, developed the Procedure for the prevention of occupational risks in the face of exposure to SARS-CoV-2, which has been updated 15 times until the date. It contains the prevention measures to be implemented in the workplaces: organizational and collective protection, personal protection, especially vulnerable worker and risk level, study and management of cases and contacts that occurred in the company, collaboration in the management of temporary disability and, more recently, reincorporation and management of vaccinated workers. As a result of these cooperation and collaboration frameworks, a series of activities were deployed in the workplace, which are described in this article.

Cuando la Organización Mundial de la Salud declaró la Covid-19 como una emergencia de salud pública de importancia internacional, el Ministerio de Sanidad convocó a las autoridades sanitarias, laborales, de seguridad social, Inspección de Trabajo y Seguridad Social, Instituto Nacional de Seguridad y Salud en el Trabajo, empresarios, sindicatos, servicios de prevención de riesgos laborales, mutuas y sociedades científicas de la medicina y enfermería del trabajo, para colaborar en el control de la transmisión del SARS-CoV-2 en el ámbito de las empresas. La Ponencia de Salud Laboral de la Comisión de Salud Pública del Consejo Interterritorial del Sistema Nacional de Salud, elaboró el Procedimiento para los servicios de prevención de riesgos laborales frente a la exposición al SARS-CoV-2, que se ha actualizado 15 veces hasta la fecha. En él se recogen las medidas de prevención a implantar en los centros de trabajo: de carácter organizativo y de protección colectiva, de protección personal, de trabajador especialmente vulnerable y nivel de riesgo, de estudio y manejo de casos y contactos ocurridos en la empresa, de colaboración en la gestión de la incapacidad temporal y, más recientemente, de reincorporación y gestión de las y los trabajadores vacunados. Como resultado de esos marcos de cooperación y colaboración se desplegaron una serie de actividades en los lugares de trabajo que son descritas en este artículo.

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

Long-term follow-up of patients with nodular lymphocyte predominant Hodgkin lymphoma: A report from the Spanish Lymphoma Oncology Group.

Nodular lymphocytic predominance Hodgkin lymphoma (NLPHL) is a very uncommon subtype of Hodgkin lymphoma (HL), representing approximately 5% of all HL cases, with an incidence of 0.3/100,000 cases per year and with unique characteristics which distinguish it from classic Hodgkin lymphoma. Given its low frequency, there is a lack of prospective randomized studies to inform practice, the accumulated experience of academic groups being the main source of relevant information for the management of these patients. Eighty-five patients recruited by the Spanish Lymphoma Group (GOTEL) from 12 different hospitals were retrospectively analyzed to describe their sociodemographic and clinical characteristics. The median follow-up was 16 years, with a 10-year overall survive of 92.9% and 81.2% at 20 years. Five patients developed a second malignancy. No transformation to a more aggressive lymphoma was detected. A total of 31% tumor relapses was found: 77% in a single location; most of them at a supra-diaphragmatic level. Patients received different first-line treatments, and progression was observed in 3/4 (75%) of the patients who did not receive any type of treatment, 6/23 (26%) who received both chemotherapy (CH) and radiotherapy (RT), 12/43 (27%) who received RT and 7/15 (47%) that received only CH treatment. The mean time to relapse was 3 years and 47% presented relapses beyond 5 years (higher probability in stage IV p < 0.001). This is one of the longest follow-up series of NLPHL published, confirming its excellent prognosis, and that treatments may be adapted to reduce toxicity. Causes of death in these patients are varied, and the minority due to a primary malignancy relapses.

Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.