Preservación de la fertilidad en personas transgénero del espectro masculino. Revisión narrativa de la literatura / Fertility preservation in transmasculine people: Narrative review

La terapia hormonal de afirmación de género con testosterona (GAHT, por sus siglas en inglés) permite, a las personas transgénero del espectro masculino, modificar las características sexuales secundarias del sexo asignado al nacer, aliviando así los síntomas de la disforia de género durante el proceso denominado transición. Sin embargo, se debe tener presente que se desconoce, en la actualidad, el efecto de la GAHT sobre la fertilidad a largo plazo, y el potencial efecto gonadotóxico de la misma. La demanda de un correcto asesoramiento reproductivo y la opción de realizar técnicas de preservación de la fertilidad (PF) han aumentado de forma exponencial en los últimos años, comportando cambios profundos en el manejo clínico de estas personas. En este artículo se realiza una revisión bibliográfica sobre el efecto de la GAHT a nivel reproductivo y en la fertilidad, junto con las técnicas de PF disponibles en este colectivo, principalmente la vitrificación de ovocitos. Además, realizamos un análisis de los resultados reproductivos publicados hasta la fecha tras el uso de técnicas de preservación, y exponemos los últimos avances de laboratorio en relación con la criopreservación de tejido ovárico y la maduración in vitro de ovocitos, junto con las opciones de futuro en población transgénero del espectro masculino.(AU)

Gender affirming hormone therapy (GAHT) in transmasculine people (individuals who identify as men or on the masculine spectrum and were assigned female sex at birth) makes it possible to modify the secondary sexual characteristics of the sex assigned at birth, thus alleviating the symptoms of gender dysphoria, during the process called transition. However, it is necessary to highlight that the effect of GAHT on long-term fertility and its potential gonadotoxic effects are currently unknown. Knowledge of the effects of testosterone on fertility and reproduction has increased recently, whilst the request for comprehensive reproductive counselling and the option of performing fertility preservation (FP) techniques have increased exponentially in recent years, leading to profound changes in the clinical management of this population. In this review, we analyzed all the information published regarding the effect of GAHT on reproduction and the FP techniques available in this group, mainly oocyte vitrification. In addition, we carry out an exhaustive analysis of the reproductive results published to date after the use of preservation techniques and present the latest laboratory advances concerning ovarian tissue cryopreservation and in vitro oocyte maturation, together with future options in the transmasculine people.(AU)

Recanalization of portal vein thrombosis after pediatric liver transplantation: Efficacy and safety of the transsplenic access.

BACKGROUND: Endovascular management of portal vein thrombosis (PVT) is challenging. Transsplenic access (TSA) is growing as an access option to the portal system but with higher rates of bleeding complications. The aim of this article is to evaluate the efficacy and safety of transsplenic portal vein recanalization (PVR) using a metallic stent after pediatric liver transplantation. MATERIALS AND METHODS: This is a retrospective review of 15 patients with chronic PVT who underwent PVR via TSA between February 2016 and December 2020. Two children who had undergone catheterization of a mesenteric vein tributary by minilaparotomy were excluded from the patency analysis but included in the splenic access analysis. The technical and clinical success of PVR and complications related to the procedure via TSA were evaluated. RESULTS: Thirteen children with PVT were treated primarily using the TSA. The mean age was 4.1 years (range, 1.5-13.7 years), and the most common clinical presentation was hypersplenism (60%). Technically successful PVR was performed in 11/13 (84.6%) children, and clinical success was achieved in 9/11 (81.8%) children. No major complications were observed, and one child presented moderate pain in the TSA (from a total of 17 TSA). The median follow-up was 48.2 months. The median primary patency was 9.9 months. Primary patency in the first 4 years was 75%, and primary assisted patency was 100% in the follow-up period. CONCLUSIONS: Transsplenic PVR is a safe and effective method for the treatment of PVT after pediatric liver transplantation.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Anomalous location of intracranial vessels in adults.

Anomalous intracranial vessels are not uncommon, and this finding is not always associated with arteriovenous malformations. Other conditions such as anomalous connections between arteries or phlebitc patterns can also present as vessels with abnormal intracranial locations. Noninvasive diagnosis is important to determine whether to do more invasive tests such as cerebral digital subtraction angiography or to estimate the risk of bleeding in arteriovenous malformations and therefore to evaluate the need for endovascular/surgical treatment. In this paper, we present an algorithm for the differential diagnosis of anomalous intracranial vessels according to their location (intra/extra-axial) and function (whether the vessels are arterialized). Moreover, we analyze the important points of the angioarchitecture of the principal arteriovenous malformations with risk of intracranial bleeding, such as pial arteriovenous malformations and dural fistulas.

Vasos intracraneales en localización anómala en adultos / Anomalous location of intracranial vessels in adults

La detección de vasos anómalos a nivel intracraneal no es un hallazgo infrecuente y no siempre está asociada a la presencia de malformaciones arteriovenosas. Otras entidades como las conexiones arterioarteriales o un patrón flebítico también pueden presentarse como unos vasos en localización intracraneal anómala. El diagnóstico mediante pruebas no invasivas es importante para determinar la necesidad de realizar pruebas más cruentas como una angiografía cerebral por sustracción digital o para estimar el riesgo de sangrado en malformaciones arteriovenosas y, por tanto, evaluar la necesidad de tratamiento endovascular/quirúrgico. En este manuscrito presentamos un algoritmo de diagnóstico diferencial de la presencia de vasos anómalos intracraneales de acuerdo con su localización (intra/extraaxiales) y su funcionalidad (arterialización o no de dichos vasos). Asimismo, analizaremos los puntos importantes de la angioarquitectura de las principales malformaciones arteriovenosas con riesgo de sangrado intracraneal, como son las malformaciones arteriovenosas piales y las fístulas durales.(AU)

Anomalous intracranial vessels are not uncommon, and this finding is not always associated with arteriovenous malformations. Other conditions such as anomalous connections between arteries or phlebitc patterns can also present as vessels with abnormal intracranial locations. Noninvasive diagnosis is important to determine whether to do more invasive tests such as cerebral digital subtraction angiography or to estimate the risk of bleeding in arteriovenous malformations and therefore to evaluate the need for endovascular/surgical treatment. In this paper, we present an algorithm for the differential diagnosis of anomalous intracranial vessels according to their location (intra/extra-axial) and function (whether the vessels are arterialized). Moreover, we analyze the important points of the angioarchitecture of the principal arteriovenous malformations with risk of intracranial bleeding, such as pial arteriovenous malformations and dural fistulas.(AU)

Characterization of hand forces exerted during non-powered hospital bed pushing and pulling tasks.

Accurate assessment of biomechanical risk associated with pushing/pulling tasks represents a challenging issue, especially in the health system where personnel are often required to maneuver beds and carts. Most studies in this field have been carried out in the laboratory, while few data have been collected under actual working conditions. This study aims to characterize the forces exerted during non-powered hospital bed maneuvering. Twenty participants were required to move a bed (equipped with a customized handlebar to measure exerted forces) along an actual hospital path including straight, turn and maneuver phases. The results show that higher forces are associated with the initial phase (peak and mean values 222 and 68 N) while the straight, turn and maneuvering phases required similar (lower) efforts. The combined effect of left, right and transversal forces suggests that the trunk of the operator might experience axial rotation, thus calling for further investigations of this aspect.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

A continuous-time Markov model approach for modeling myelodysplastic syndromes progression from cross-sectional data.

The integration of both genomics and clinical data to model disease progression is now possible, thanks to the increasing availability of molecular patients' profiles. This may lead to the definition of novel decision support tools, able to tailor therapeutic interventions on the basis of a "precise" patients' risk stratification, given their health status evolution. However, longitudinal analysis requires long-term data collection and curation, which can be time demanding, expensive and sometimes unfeasible. Here we present a clinical decision support framework that combines the simulation of disease progression from cross-sectional data with a Markov model that exploits continuous-time transition probabilities derived from Cox regression. Trajectories between patients at different disease stages are stochastically built according to a measure of patient similarity, computed with a matrix tri-factorization technique. Such trajectories are seen as realizations drawn from the stochastic process driving the transitions between the disease stages. Eventually, Markov models applied to the resulting longitudinal dataset highlight potentially relevant clinical information. We applied our method to cross-sectional genomic and clinical data from a cohort of Myelodysplastic syndromes (MDS) patients. MDS are heterogeneous clonal hematopoietic disorders whose patients are characterized by different risks of Acute Myeloid Leukemia (AML) development, defined by an international score. We computed patients' trajectories across increasing and subsequent levels of risk of developing AML, and we applied a Cox model to the simulated longitudinal dataset to assess whether genomic characteristics could be associated with a higher or lower probability of disease progression. We then used the learned parameters of such Cox model to calculate the transition probabilities of a continuous-time Markov model that describes the patients' evolution across stages. Our results are in most cases confirmed by previous studies, thus demonstrating that simulated longitudinal data represent a valuable resource to investigate disease progression of MDS patients.

Endoscopic submucosal dissection for superficial premalignant and malignant epithelial neoplasms of the digestive tract: a real-life experience in Italy.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is a technique for en bloc resection of neoplastic lesions of the digestive tract. Endoscopic submucosal dissection was developed in Asia, and data from Western countries are scarce. Our study aimed to assess the efficacy and safety of ESD for resection of superficial premalignant and malignant epithelial neoplasms in a tertiary center in Italy. PATIENTS AND METHODS: All patients with gastrointestinal lesions who underwent ESD between January 2013 and December 2018 in our center were retrospectively evaluated. Technical success, en bloc, R0, curative resection, and complication rates were assessed. RESULTS: A total of 107 lesions (stomach, no.=41; rectum, no.=32; colon, no.=28; esophagus, no.=5; duodenum, no.=1) were resected by ESD in 93 patients. Endoscopic submucosal dissection was technically successful in 99.1% (106/107) of lesions. Among the 90 superficial premalignant and malignant epithelial neoplasms, en bloc, and R0 resection rates were 97.8% (no.=88) and 75.6% (no.=68), respectively. Major complications occurred in 9.3% (10/107) of cases: 4 (3.7%) were perforations and 6 (5.6%) were major bleedings. All complications, but two which needed surgery, were managed endoscopically. CONCLUSIONS: Our study shows that ESD is a feasible, effective, and safe technique in a Western country.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.

'Timed up and go' and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis.

Motor and cognitive disabilities are related to brain atrophy in multiple sclerosis (MS). 'Timed up and go' (TUG) has been recently tested in MS as functional mobility test, as it is able to evaluate ambulation/coordination-related tasks, as well as cognitive function related to mobility. The objective of this study is to evaluate the relationship between brain volumes and TUG performances. Inclusion criteria were a diagnosis of MS and the ability to walk at least 20 m. TUG was performed using a wearable inertial sensor. Times and velocities of TUG sub-phases were calculated by processing trunk acceleration data. Patients underwent to a brain MRI, and volumes of whole brain, white matter (WM), grey matter (GM), and cortical GM (C) were estimated with SIENAX. Sixty patients were enrolled. Mean age was 41.5 ± 11.6 years and mean EDSS 2.3 ± 1.2. Total TUG duration was correlated to lower WM (ρ = 0.358, p = 0.005) and GM (ρ = 0.309, p = 0.017) volumes. A stronger association with lower GM volume was observed for intermediate (ρ = 0.427, p = 0.001) and final turning (ρ = 0.390, p = 0.002). TUG is a useful tool in a clinical setting as it can not only evaluate patients' disability in terms of impaired functional mobility, but also estimate pathological features, such as grey atrophy.

Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Cochlear, auditory brainstem responses in Type 1 diabetes: relationship with metabolic variables and diabetic complications.

AIMS: Few studies have analysed the presence of hearing abnormalities in diabetes. We assessed the presence of subclinical auditory alterations and their possible association with early vascular and neurological dysfunction in young adults with Type 1 diabetes of long duration. METHODS: Thirty-one patients with Type 1 diabetes (mean age 33 ± 2.3 years, disease duration 25.7 ± 4.2 years) and 10 healthy controls underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) analyses. Associations with metabolic variables and chronic complications were explored. RESULTS: Compared with healthy controls, patients with diabetes had significantly higher mean hearing thresholds, although still within the normoacusic range. DPOAE intensities at medium frequencies (2.8-4 kHz) were significantly lower in patients with diabetes. In ABR, in addition to waves I, III and V, we observed the appearance of a visible wave IV in patients with diabetes compared with controls (prevalence 61% vs. 10%, P < 0.05), and its appearance was related to a prolonged I-V interval (4.40 ± 0.62 ms vs. 4.19 ± 0.58 ms, P < 0.05). Diastolic blood pressure was higher in people with abnormal DPOAE (P < 0.05), whereas systolic blood pressure correlated with wave V and interpeak I-V interval latencies. A trend towards an association between evidence of wave IV and the presence of somatic neuropathy or abnormal cardiovascular autonomic tests was observed. CONCLUSIONS: Young adults with long-term Type 1 diabetes have subclinical abnormalities in qualitative auditory perception, despite normal hearing thresholds, which might reflect neuropathic and/or vascular alterations.

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM).

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.

Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

Feasibility of a preventive mass vaccination campaign with two doses of oral cholera vaccine during a humanitarian emergency in South Sudan.

BACKGROUND: As an adjunct to cholera prevention measures, WHO advises the use of oral cholera vaccine through mass vaccination campaigns in high-risk areas and for vulnerable population groups. We assessed the feasibility and acceptability of a mass vaccination campaign using 1) a predominantly fixed and 2) a mobile door-to-door strategy. METHODS: Vaccination included administration of two doses (given 2 weeks apart) of oral cholera vaccine to individuals older than 1 year of age, in four refugee camps: Jamam, Doro, Batil and Gendrassa, and the host population in Maban County, South Sudan, from December 2012 to February 2013. RESULTS: A total of 258 832 doses were administered to a population of 166 000 (126 000 refugees and 40 000 host population). The first round coverage for the refugees was above 84% for Doro, Jamam and Batil and 104% for Gendrassa. The second dose reached the same coverage as the first dose. For the host population, the coverage for the first dose was above 90% in Doro and Jamam and 53% in Gendrassa and Batil. For the second round, the coverage was above 79% in Doro and Jamam and above 70% in Batil and Gendrassa. CONCLUSIONS: The vaccination of a large population in an emergency context proved to be feasible and acceptable and achieved high coverage. This is encouraging and is a way forward for reducing cholera related morbidity and mortality among vulnerable populations.