Tislelizumab versus chemotherapy as second-line treatment for European and North American patients with advanced or metastatic esophageal squamous cell carcinoma: a subgroup analysis of the randomized phase III RATIONALE-302 study.

BACKGROUND: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup). PATIENTS AND METHODS: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan). RESULTS: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores. CONCLUSIONS: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study.

COVID-19 vaccine safety in Scotland - background rates of adverse events of special interest.

OBJECTIVES: Mass COVID-19 vaccination commenced in December 2020 in Scotland. Monitoring vaccine safety relies on accurate background incidence rates (IRs) for health outcomes potentially associated with vaccination. This study aimed to quantify IRs in Scotland of adverse events of special interest (AESI) potentially associated with COVID-19 vaccination. STUDY DESIGN AND METHODS: IRs and 95% confidence intervals (CIs) for 36 AESI were calculated retrospectively for the pre-COVID-19 pandemic period (01 January 2015-31 December 2019) and the COVID-19 pandemic period (01 April 2020-30 November 2020), with age-sex stratification, and separately by calendar month and year. Incident cases were determined using International Classification of Diseases-10th Revision (ICD-10)-coded hospitalisations. RESULTS: Prepandemic population-wide IRs ranged from 0.4 (0.3-0.5 CIs) cases per 100,000 person-years (PYRS) for neuromyelitis optica to 478.4 (475.8-481.0 CIs) cases per 100,000 PYRS for acute renal failure. Pandemic population-wide IRs ranged from 0.3 (0.2-0.5 CIs) cases per 100,000 PYRS for Kawasaki disease to 483.4 (473.2-493.7 CIs) cases per 100,000 PYRS for acute coronary syndrome. All AESI IRs varied by age and sex. Ten AESI (acute coronary syndrome, acute myocardial infarction, angina pectoris, heart failure, multiple sclerosis, polyneuropathies and peripheral neuropathies, respiratory failure, rheumatoid arthritis and polyarthritis, seizures and vasculitis) had lower pandemic than prepandemic period IRs overall. Only deep vein thrombosis and pulmonary embolism had a higher pandemic IR. CONCLUSION: Lower pandemic IRs likely resulted from reduced health-seeking behaviours and healthcare provision. Higher IRs may be associated with SARS-CoV-2 infections. AESI IRs will facilitate future vaccine safety studies in Scotland.

Post-processed data and graphical tools for a CONUS-wide eddy flux evapotranspiration dataset.

Large sample datasets of in situ evapotranspiration (ET) measurements with well documented data provenance and quality assurance are critical for water management and many fields of earth science research. We present a post-processed ET oriented dataset at daily and monthly timesteps, from 161 stations, including 148 eddy covariance flux towers, that were chosen based on their data quality from nearly 350 stations across the contiguous United States. In addition to ET, the data includes energy and heat fluxes, meteorological measurements, and reference ET downloaded from gridMET for each flux station. Data processing techniques were conducted in a reproducible manner using open-source software. Most data initially came from the public AmeriFlux network, however, several different networks (e.g., the USDA-Agricultural Research Service) and university partners provided data that was not yet public. Initial half-hourly energy balance data were gap-filled and aggregated to daily frequency, and turbulent fluxes were corrected for energy balance closure error using the FLUXNET2015/ONEFlux energy balance ratio approach. Metadata, diagnostics of energy balance, and interactive graphs of time series data are included for each station. Although the dataset was developed primarily to benchmark satellite-based remote sensing ET models of the OpenET initiative, there are many other potential uses, such as validation for a range of regional hydrologic and atmospheric models.

Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Inter-annual variability of land surface fluxes across vineyards: the role of climate, phenology, and irrigation management.

Irrigation and other agricultural management practices play a key role in land surface fluxes and their interactions with atmospheric processes. California's Central Valley agricultural productivity is strongly linked to water availability associated with conveyance infrastructure and groundwater, but greater scrutiny over agricultural water use requires better practices particularly during extended and severe drought conditions. The future of irrigated agriculture in California is expected to be characterized neither by perpetual scarcity nor by widespread abundance. Thus, further advancing irrigation technologies and improving management practices will be key for California's agriculture sustainability. In this study, we present micrometeorological observations from the Grape Remote Sensing Atmospheric Profile and Evapotranspiration eXperiment (GRAPEX) project. Daily, seasonal, and inter-seasonal surface flux patterns and relationships across five vineyards over three distinct California wine production regions were investigated. Vineyard actual evapotranspiration showed significant differences at the sub-daily and daily scale when comparisons across wine production regions and varieties were performed. Water use in vineyards in the Central Valley was about 70% greater in comparison to the vineyards at the North Coast area due to canopy size, atmospheric demand, and irrigation inputs. Inter-annual variability of surface fluxes was also significant, even though, overall weather conditions (i.e., air temperature, vapor pressure deficit, wind speed, and solar radiation) were not significantly different. Thus, not only irrigation but also other management practices played a key role in seasonal water use, and given these differences, we conclude that further advancing ground-based techniques to quantify crop water use at an operational scale will be key to facing California's agriculture present and future water challenges. Supplementary Information: The online version contains supplementary material available at 10.1007/s00271-022-00784-0.

ESMO Congress 2021: highlights from the EORTC gastrointestinal tract cancer group's perspective.

There has been no major change of practice in gastrointestinal oncology at the European Society for Medical Oncology (ESMO) symposium 2021, but confirmation that immunotherapy in combination with chemotherapy has become standard of care in several indications. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Track Cancer Group has selected important phase II and III trials presented during the symposium across all gastrointestinal cancers as well as early reports on new drugs or new combinations that may change practice in the future.

Quality of life with first-line pembrolizumab for PD-L1-positive advanced gastric/gastroesophageal junction adenocarcinoma: results from the randomised phase III KEYNOTE-062 study.

BACKGROUND: In the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population. MATERIALS AND METHODS: HRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated. RESULTS: The HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [-0.16; 95% confidence interval (CI) -5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003). CONCLUSIONS: HRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1-positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population.

Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study.

BACKGROUND: Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth- or later-line (4L+) treatment. PATIENTS AND METHODS: Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4L+ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to ≥2, and safety. RESULTS: Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4L+ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] = 0.68 (0.47-0.97), P = 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P = 0.0192] in the 4L+ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P = 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4L+ group. Time to deterioration of ECOG PS to ≥2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) = 0.60 (0.42-0.86), P = 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P = 0.0329] in the 4L+ group. The safety of FTD/TPI was consistent in all subgroups. CONCLUSIONS: This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months.

Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm / Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry

ANTECEDENTES Y OBJETIVOS: Las guías sobre el tratamiento de la psoriasis habitualmente no incluyen las recomendaciones acerca de cuál debe ser la primera línea de tratamiento sistémico o biológico. Los objetivos de este estudio fueron describir las tendencias en la prescripción del primer fármaco biológico y comparar la retirada de los fármacos y las tasas de efectos adversos a lo largo de los 10 años de seguimiento. MATERIAL Y MÉTODOS: Se utilizó el registro Biobadaderm para determinar cuál fue el primer fármaco biológico indicado en pacientes con psoriasis naïve para biológicos, así como cuál es la tasa de efectos adversos y los motivos de suspensión de los fármacos. Los resultados obtenidos se compararon en tres periodos distintos de tiempo (2008-2010, 2011-2014, 2015-2018). RESULTADOS: Los fármacos anti-TNF fueron los biológicos prescritos con mayor frecuencia entre los años 2008 y 2010. Ustekinumab se convirtió en el tratamiento biológico más indicado a partir de 2014. El motivo principal de suspensión de los tratamientos fueron los efectos adversos, la falta de eficacia y la remisión de la enfermedad. La probabilidad de suspender los fármacos por uno de estos motivos fue cada vez menor si se compara con el periodo de tiempo previo. CONCLUSIONES: El presente estudio identifica cuáles fueron las tendencias en la prescripción del primer fármaco biológico en la práctica clínica habitual entre los años 2008 y 2018. Sugiere que los dermatólogos estamos cada vez más seguros en cuanto al perfil de seguridad y somos cada vez más exigentes en cuanto a la eficacia de los fármacos

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs

Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

Effect of season on the in vitro fertilizing ability of frozen-thawed Spanish bovine spermatozoa.

The purpose of the present study was to evaluate the effects of season on the in vitro fertilizing ability of bovine spermatozoa and subsequent embryo development. Bovine oocytes were matured and fertilized in vitro with Holstein dairy bull sperm cells collected and frozen in different seasons (winter, spring, and summer). On d 2 and 8 postinsemination, cleavage and blastocyst rates, respectively, were recorded; the blastocysts were graded for morphology. The number of sperm cells binding to the zona pellucida of oocytes, together with the number of nuclei in the developing blastocysts, were assessed after staining with Hoechst. No significant differences were observed among seasons in cleavage and embryo development rate. However, the proportion of "advanced blastocysts" was significantly higher in spring compared with winter and summer, with a corresponding decrease in the proportion of early blastocysts in spring compared with winter and summer. The number of sperm cells binding per oocyte was significantly lower in the oocytes inseminated with sperm samples collected in summer compared with winter or spring. Moreover, a significant interaction was observed in the number of sperm cells binding per oocyte between bull and season. Although no significant differences were observed among seasons in the number of nuclei per blastocyst, a significant interaction was observed between bull and season for this variable. Embryo development rate in in vitro fertilization appeared to be affected by season of semen collection, with sperm samples collected in spring being associated with a higher proportion of advanced blastocysts and better morphology than those collected at other times of the year.

SEOM clinical guideline for the diagnosis and treatment of gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA) (2019).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians.

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER).

BACKGROUND: Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. PATIENTS AND METHODS: Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m2 i.v., days 1-4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m2 to 80 mg/m2. RESULTS: The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06-2.98; P = 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79-1.75; P = 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. CONCLUSION: EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).

Relationships between climate and sperm quality in dairy bull semen: A retrospective analysis.

The aim of the present study was to make a retrospective analysis of the relationship between climatic factors and sperm quality of frozen-thawed semen from bulls kept in temperate climates. Semen samples from 21 European dairy bulls from 2 countries were collected and cryopreserved in winter, spring, and summer. Sperm quality parameters such as kinematics, morphology, plasma membrane integrity, mitochondrial membrane potential, sperm chromatin structure assay, and reactive oxygen species were analyzed and correlated retrospectively with climate factors recorded by the local meteorological office. This study demonstrated that sperm quality parameters are more likely to be correlated with climate factors 1 or 2 mo before semen collection than in the month of semen collection. During the month of sperm collection, sperm kinematics, DNA fragmentation, and hydrogen peroxide production were the only sperm quality parameters related to climate factors, whereas 1 and 2 mo before sperm collection, normal morphology and additional sperm kinematics, in addition to DNA fragmentation and hydrogen peroxide production, were correlated with climate factors. In conclusion, dairy bull sperm quality is affected by climatic conditions, even in so-called temperate zones. The timing of heat stress during spermatogenesis determines which aspects of sperm quality are likely to be affected. Husbandry conditions for bulls used for semen collection should be adapted to allow the animals' physiological responses for temperature regulation within the scrotum to operate fully, to mitigate the effects of increased temperature and humidity. Extremes of temperature should be avoided.

Leiomiosarcoma y sarcoma pleomórfico dérmico: directrices para el diagnóstico y tratamiento / Leiomyosarcoma and Pleomorphic Dermal Sarcoma: Guidelines for Diagnosis and Treatment

El leiomiosarcoma de la piel se clasifica en tres grupos: dérmico, hipodérmico y cutáneo metastásico. El dérmico se origina de las fibras musculares lisas del músculo erector del pelo, dartos genital o de la areola mamaria. Se considera un tumor de malignidad intermedia, con tendencia a la recidiva local (24%) y un bajo riesgo de metástasis (4%). El leiomiosarcoma hipodérmico se origina de las paredes musculares de los vasos, y se caracteriza por presentar una mayor tasa de recidiva local (37%) y metástasis (43%). El sarcoma pelomórfico dérmico aparece habitualmente en pacientes ancianos y se localiza característicamente en zonas de piel fotoexpuesta (cuero cabelludo). Comparte características histológicas e inmunohistoquímicas con el fibroxantoma atípico, pero con un comportamiento más agresivo (metástasis en el 10-20%). Los criterios histológicos que lo diferencian son la infiltración del tejido celular subcutáneo, la infiltración perineural y la presencia de focos de necrosis

There are 3 types of leiomyosarcoma of the skin: dermal, subcutaneous, and metastatic cutaneous. Dermal leiomyosarcoma arises from smooth muscle fibers in arrector pili muscles, genital dartos muscles, and the nipple-areola complex. It is an intermediate-grade tumor associated with a tendency for local recurrence (24%) and low metastatic potential (4%). Subcutaneous leiomyosarcoma originates from smooth muscle in blood vessel walls and has higher rates of local recurrence (37%) and metastasis (43%). Plemorphic dermal sarcoma typically affects elderly patients and arises in sun-exposed areas (e.g., the scalp). Its histologic and immunohistochemical characteristics are similar to those of atypical fibroxanthoma, but it is more aggressive (metastasis rate of 10-20%). Histologically, it can be distinguished from atypical fibroxanthoma by the observation of subcutaneous tissue invasion, perineural invasion, and foci of necrosis

Leiomyosarcoma and Pleomorphic Dermal Sarcoma: Guidelines for Diagnosis and Treatment. / Leiomiosarcoma y sarcoma pleomórfico dérmico: directrices para el diagnóstico y tratamiento.

There are 3 types of leiomyosarcoma of the skin: dermal, subcutaneous, and metastatic cutaneous. Dermal leiomyosarcoma arises from smooth muscle fibers in arrector pili muscles, genital dartos muscles, and the nipple-areola complex. It is an intermediate-grade tumor associated with a tendency for local recurrence (24%) and low metastatic potential (4%). Subcutaneous leiomyosarcoma originates from smooth muscle in blood vessel walls and has higher rates of local recurrence (37%) and metastasis (43%). Plemorphic dermal sarcoma typically affects elderly patients and arises in sun-exposed areas (e.g., the scalp). Its histologic and immunohistochemical characteristics are similar to those of atypical fibroxanthoma, but it is more aggressive (metastasis rate of 10-20%). Histologically, it can be distinguished from atypical fibroxanthoma by the observation of subcutaneous tissue invasion, perineural invasion, and foci of necrosis.