Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

A phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamics of PF-06939999 (PRMT5 inhibitor) in patients with selected advanced or metastatic tumors with high incidence of splicing factor gene mutations.

BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor. PATIENTS AND METHODS: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors. PF-06939999 was administered orally once or twice a day (q.d./b.i.d.) in 28-day cycles. The objectives were to evaluate PF-06939999 safety and tolerability to identify maximum tolerated dose (MTD) and recommended part 2 dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics [changes in plasma symmetric dimethylarginine (SDMA) levels], and antitumor activities. RESULTS: In part 1 dose escalation, 28 patients received PF-06939999 (0.5 mg q.d. to 6 mg b.i.d.). Four of 24 (17%) patients reported dose-limiting toxicities: thrombocytopenia (n = 2, 6 mg b.i.d.), anemia (n = 1, 8 mg q.d.), and neutropenia (n = 1, 6 mg q.d.). PF-06939999 exposure increased with dose. Steady-state PK was achieved by day 15. Plasma SDMA was reduced at steady state (58%-88%). Modulation of plasma SDMA was dose dependent. No MTD was determined. In part 2 dose expansion, 26 patients received PF-06939999 6 mg q.d. (RP2D). Overall (part 1 + part 2), the most common grade ≥3 treatment-related adverse events included anemia (28%), thrombocytopenia/platelet count decreased (22%), fatigue (6%), and neutropenia (4%). Three patients (6.8%) had confirmed partial response (head and neck squamous cell carcinoma, n = 1; non-small-cell lung cancer, n = 2), and 19 (43.2%) had stable disease. No predictive biomarkers were identified. CONCLUSIONS: PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients (the Alantel study).

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

Robust identification of interactions between heat-stress responsive genes in the chicken brain using Bayesian networks and augmented expression data.

Bayesian networks represent a useful tool to explore interactions within biological systems. The aims of this study were to identify a reduced number of genes associated with a stress condition in chickens (Gallus gallus) and to unravel their interactions by implementing a Bayesian network approach. Initially, one publicly available dataset (3 control vs. 3 heat-stressed chickens) was used to identify the stress signal, represented by 25 differentially expressed genes (DEGs). The dataset was augmented by looking for the 25 DEGs in other four publicly available databases. Bayesian network algorithms were used to discover the informative relationships between the DEGs. Only ten out of the 25 DEGs displayed interactions. Four of them were Heat Shock Proteins that could be playing a key role, especially under stress conditions, where maintaining the correct functioning of the cell machinery might be crucial. One of the DEGs is an open reading frame whose function is yet unknown, highlighting the power of Bayesian networks in knowledge discovery. Identifying an initial stress signal, augmenting it by combining other databases, and finally learning the structure of Bayesian networks allowed us to find genes closely related to stress, with the possibility of further exploring the system in future studies.

Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Childhood-onset Huntignton´s disease. A rare presentation. / Enfermedad de Huntington de inicio en la infancia. Una presentación poco frecuente.

INTRODUCTION: Huntington's disease (HD) is a rare autosomal dominant disease caused by the expansion of CAG triplets in the gene that encodes huntingtin. There are earlier symptoms' onset in offspring due to the phenomenon of anticipation. The clinical features of childhood-onset HD, before age 10 years, differs from adult-onset form. It is characterized by motor impairment, behavioral difficulties and delay or regression in areas of development; while chorea is rarely seen. In this case we describe clinical aspects of a patient with childhood-onset Huntington's disease. CASE REPORT: A 5-year-old girl with a family history of HD and typical development up to 3 years of age. She progressively acquired language impairment with skills that were below her age in expressive and receptive areas, without deficits in pragmatic and social skills. Regarding motor skills, she manifested instability at walking and standing, with rigidity, dystonia and choreic movements. Atrophy of the basal ganglia was evident on MRI, EEG was normal, and molecular confirmation of CAG triplet revealed repeat length of 51 copies. CONCLUSION: Childhood-onset HD differs from adult-form´s clinical manifestations. It should be considered in patients with progressive motor and cognitive impairment. Due to family inheritance, it is important to carefully examine family history and take it into account even without relatives affected, considering the anticipation phenomenon.

TITLE: Enfermedad de Huntington de inicio en la infancia. Una presentación poco frecuente.Introducción. La enfermedad de Huntington (EH) es una enfermedad de herencia autosómica dominante caracterizada por la expansión de tripletes de citosina-adenina-guanina (CAG) en el gen que codifica la huntingtina. Los síntomas en la descendencia suelen ser más tempranos por el fenómeno de anticipación. La clínica de inicio en la infancia, antes de los 10 años, difiere de la observada en la adultez. Se manifiesta por afectación motora, dificultades conductuales y retraso o regresión del desarrollo. La corea es infrecuente. El objetivo del caso es describir aspectos clínicos de una paciente con EH de inicio infantil. Caso clínico. Niña de 5 años con antecedentes familiares de EH y desarrollo típico hasta los 3 años. Presentó progresivamente afectación del lenguaje con habilidades descendidas para su edad en aspectos expresivos y comprensivos, sin afectación en las habilidades pragmáticas y sociales. En cuanto a la motricidad, la marcha y la bipedestación eran inestables, y mostraba rigidez, distonía y movimientos coreicos. Presentó atrofia de los núcleos lenticulares y caudados en la resonancia magnética, y posteriormente se realizó el diagnóstico molecular con la expansión de tripletes CAG (51 copias). Conclusión. La EH de inicio en la infancia presenta manifestaciones clínicas distintas a la forma del adulto. Debe considerarse en pacientes con afectación motora y cognitiva progresiva. Por la herencia familiar, es importante interrogar cuidadosamente sobre los antecedentes familiares y tenerla en cuenta aun sin familiares afectados por el fenómeno de anticipación.

[Translated article] Type III acromioclavicular dislocation: Mid term results after operative and non-operative treatment.

INTRODUCTION: Controversy exists in the literature about the best treatment for type III acromioclavicular dislocations. The aim of this study is to compare functional results between surgical and conservative treatment in type III acromioclavicular joint dislocations. MATERIAL AND METHOD: We retrospectively evaluated the records of 30 patients from our area with acute type III acromioclavicular dislocations that were treated from January 1st, 2016 to December 31st, 2020. Fifteen patients were treated surgically and 15 conservatively. Follow-up mean time was 37.93 months in operative group and 35.73 months in non-operative group. Results obtained on the Constant score was the main variable analysed and results obtained on the Oxford score and the Visual Analogue Scale for pain were the secondary variables. Epidemiological variables were analysed, as well as range of mobility in injured shoulder and subjective and radiological variables (distance between the superior border of the acromion and the superior border of the clavicle's distal end and presence of osteoarthritis in the acromioclavicular joint). RESULTS: Functional evaluation scores did not show differences between the two groups (Constant: operative 82/non-operative 86.38, p 0.412; Oxford: operative 42/non-operative 44.80, p 0.126) nor did Visual Analogue Scale (operative 1/non-operative 0.20, p 0.345). Subjective evaluation of the injured shoulder was excellent or good in 80% of the patients in both groups. Measurement of the distance between the superior border of the acromion and the superior border of the clavicle's distal end were significantly higher in non-operative group (operative 8.95/non-operative 14.21, p 0.008). CONCLUSIONS: Although radiographic results were better in the surgical treatment group, functional evaluation scores did not show significant differences between the two groups. These results do not support the routine use of surgical treatment for grade III acromioclavicular dislocations.

Relationship between dietary characteristics and heel quantitative ultrasound parameters in postmenopausal women from the OsteoLaus cohort.

The role of dietary patterns in the development of osteoporosis is unclear. The heel quantitative ultrasound (QUS) is a potential alternative to Dual X-Ray Absorptiometry. Nutrients, foods, dietary patterns and compliance to dietary guidelines were compared between the lowest and the highest tertiles of QUS parameters [Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS), Stiffness Index (SI)], using data from the OsteoLaus cohort. Participants in the highest tertiles of QUS parameters (385 for BUA, 397 for SOS, 386 for SI) were younger, of higher body weight, and had less major osteoporotic fractures. Women in the highest tertiles of SI and BUA consumed more fat (35.1 ± 0.4 vs 33.9 ± 0.4 and 34.9 ± 0.4 vs 33.8 ± 0.4 gr/day for SI and BUA, respectively, p < 0.05), and complied less frequently with dairy intake guidelines [odds ratio (95% confidence interval): 0.70 (0.53-0.92) and 0.72 (0.55-0.95) for SI and BUA, respectively, p < 0.05] than women in the lowest tertile. No differences were found regarding dietary patterns, healthy dietary scores, or compliance to dietary guidelines. Postmenopausal women in the highest QUS tertiles were younger, of higher weight and BMI, consumed more monounsaturated fatty acids and less dairy and calcium than women in the lowest tertiles. No differences were found between QUS tertiles regarding dietary patterns.

[Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain]. / Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6.ª onda epidémica COVID-19 en España.

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.

Factores asociados al diagnóstico tardío del Trastorno del Espectro Autista / Factors associated with delayed diagnosis of Autism Spectrum Disorder

El trastorno del espectro autista (TEA) es una condición crónica del neurodesarrollo caracterizada por déficits persistentes en la comunicación e interacción social y un patrón de intereses restringidos y/o comportamientos repetitivos que pueden afectar el funcionamiento del individuo en la vida diaria familiar y comunitaria. El diagnóstico oportuno intenta mejorar la trayectoria, reducir el impacto funcional y disminuir los efectos de condiciones médicas asociadas. El diagnóstico tardío de TEA es considerado como aquel realizado luego de los 6 años de edad, en coincidencia con el fin de la escolaridad inicial. Si bien esta edad puede resultar arbitraria lo que se busca es una generalización de aquellos casos en los que probablemente hubo múltiples pérdidas de oportunidades diagnósticas y terapéuticas. Objetivo: Reflexionar sobre los determinantes del diagnóstico tardío del TEA con el fin de proponer posibles soluciones a esta problemática. Desarrollo: A partir de tres viñetas clínicas de pacientes que recibieron el diagnóstico en nuestro servicio, luego de los 6 años de edad, nos proponemos identificar y analizar aquellos factores (motivos sociodemográficos, problemas organizacionales, en la etapa de evaluación diagnóstica, respecto al género, cuidadores/ familiares y características clínicas) que determinan la demora diagnóstica. Conclusiones: El diagnóstico tardío del TEA es una problemática compleja y multifactorial, que implica desafíos significativos en el desarrollo de los NNyA con esta condición, sus familias y su entorno. Es importante considerar las causas que demoran el diagnóstico, desde el ámbito clínico, familiar y socio-ambiental para poder intervenir oportunamente (AU)

Autism spectrum disorder (ASD) is a chronic neurodevelopmental condition characterized by persistent deficits in communication and social interaction and a pattern of restricted interests and/or repetitive behaviors that can affect the individual's daily functioning both at home and in the community. Early diagnosis is important to improve the developmental trajectory, reduce functional impairment, and decrease the impact of comorbid medical conditions. Delayed diagnosis of ASD is defined as a diagnosis made after the age of 6 years, coinciding with the end of preschool. Although this age may be arbitrary, it serves to encompass cases in which there were probably multiple missed diagnostic and therapeutic opportunities. Objective: To explore the causes of late diagnosis of ASD in order to propose possible solutions to this problem. Development: Based on three clinical vignettes of patients who were diagnosed at our department after 6 years of age, we aimed to identify and analyze factors influencing diagnostic delays. These factors included sociodemographic causes, organizational challenges, issues during the diagnostic workup, considerations related to gender, caregivers/families, and clinical characteristics. Conclusions: Delayed diagnosis of ASD is a complex and multifactorial problem leading to significant challenges in the development of children and adolescents with this condition as well as their families and their environment. Identification of the causes of diagnostic delay is important from the clinical, family and socio-environmental point of view, in order to start timely interventions (AU)

Oxidative stress and histopathological effects by microplastic beads, in the crayfish Procambarus clarkii, and fiddler crab Leptuca pugilator.

The present study was aimed at evaluating the in vivo effects of microplastics (MP), in terms of oxidative stress and histopathological effects, in two crustacean species: Procambarus clarkii and Leptuca pugilator. In addition, MP accumulation in the hepatopancreas (HP) of both species was also determined. Adults of both crayfish and crabs were exposed for one month to fluorescent polystyrene beads (size: 1 µm) at nominal concentrations of 1000 or 5000 particles/mL. During the exposure, animals were maintained under controlled feeding, aeration, temperature, and photoperiod conditions. At the end of the exposure, HP and hemolymph (HL) samples were harvested for analysis of oxidative damage and total antioxidant levels. Additionally, the presence of MPs in both tissues was confirmed. Significant differences with the control groups were observed in lipid peroxidation levels in HP in animals exposed to the lowest concentration in P. clarkii and to the highest concentration in L. pugilator. A marked increase in antioxidant levels was also observed in the HL at both concentrations in P. clarkii, and at the highest MPs concentration in L. pugilator. Moreover, several histopathological changes were detected in both gills and HP, including hypertrophied lamellae, lifting or collapse of gill epithelia, loss of normal shape of hepatopancreatic tubules, and epithelial atrophy in the HP tissue. We conclude that exposure to MP beads at selected concentrations results in oxidative damage, induces histopathological changes in gills and HP, and triggers an antioxidant response in two crustacean species.

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.

Polarized thermal emission from dust in a galaxy at redshift 2.6.

Magnetic fields are fundamental to the evolution of galaxies, playing a key role in the astrophysics of the interstellar medium and star formation. Large-scale ordered magnetic fields have been mapped in the Milky Way and nearby galaxies1,2, but it is not known how early in the Universe such structures formed3. Here we report the detection of linearly polarized thermal emission from dust grains in a strongly lensed, intrinsically luminous galaxy that is forming stars at a rate more than 1,000 times that of the Milky Way at redshift 2.6, within 2.5 Gyr of the Big Bang4,5. The polarized emission arises from the alignment of dust grains with the local magnetic field6,7. The median polarization fraction is of the order of 1%, similar to nearby spiral galaxies8. Our observations support the presence of a 5-kiloparsec-scale ordered magnetic field with a strength of around 500 µG or lower, oriented parallel to the molecular gas disk. This confirms that such structures can be rapidly formed in galaxies, early in cosmic history.

Pd2 and CoPd dimers/N-doped graphene sensors with enhanced sensitivity for CO detection: A first-principles study.

CONTEXT: The detection and monitoring of CO gas are essential to avoid human health problems. Therefore, the CO adsorption on Pd2 and PdCo dimers deposited on pyridinic Nx-doped graphene (PNxG; x = 1 - 3) was investigated employing the auxiliary density functional theory. In the most stable arrangements for the Pd2 dimer supported on PNxG, a Pd atom is in the PNxG vacancy, and the other Pd atom is placed on C atoms. For the PdCo dimer deposited on PNxG, the most stable interaction is like Pd2 dimer supported on PNxG, but with the Co atom centered over the vacancy site. Concerning the stability of the Pd2 and PdCo dimers supported on PNxG, the interaction energies (Eint) of the PdCo dimer deposited on PNxG are higher than those obtained with the Pd2 dimer. Also, the Eint of Pd2 and PdCo dimers deposited on PNxG are higher than those supported on pristine graphene. The CO adsorption energies on Pd2/PNxG and PdCo/PNxG composites are higher than those reported in the literature for pristine graphene, showing that the Pd2/PNxG and PdCo/PNxG composites have a good sensitivity toward the CO molecule. METHODS: All electronic structure calculations were performed using the auxiliary density functional theory implemented in the deMon2k program. For exchange and correlation functional, the revised PBE was used. The Pd atoms were treated with an 18-electron QECP|SD basis set, while the remaining atoms were subjected to a DZVP-GGA basis set. The GEN-A2* auxiliary-function-set was used for all computations.

Age-associated systemic factors change central and peripheral immunity in adult male mice.

Aging coincides with major changes in brain immunity that aid in a decline in neuronal function. Here, we postulate that systemic, pro-aging factors contribute to immunological changes that occur within the brain during aging. To investigate this hypothesis, we comprehensively characterized the central and peripheral immune landscape of 20-month-old male mice using cytometry by time-of-flight (CyTOF) and investigated the role of age-associated circulating factors. We found that CD8+ T cells expressing programmed cell death protein 1 (PD1) and tissue-resident memory CD8+ T cells accumulated in the aged brain while levels of memory T cells rose in the periphery. Injections of plasma derived from 20-month-old mice into 5-month-old receiving mice decreased the frequency of splenic and circulating naïve T cells, increased memory CD8+ T cells, and non-classical, patrolling monocytes in the spleen, and elevated levels of regulatory T cells and non-classical monocytes in the blood. Notably, CD8+ T cells accumulated within white matter areas of plasma-treated mice, which coincided with the expression of vascular cell adhesion molecule 1 (VCAM-1), a mediator of immune cell trafficking, on the brain vasculature. Taken together, we here describe age-related immune cell changes in the mouse brain and circulation and show that age-associated systemic factors induce the expansion of CD8+ T cells in the aged brain.

Type III acromioclavicular dislocation: Mid term results after operative and non-operative treatment. / Luxación acromioclavicular grado III. Resultados a medio plazo tras tratamiento conservador y quirúrgico.

INTRODUCTION: Controversy exists in the literature about the best treatment for type III acromioclavicular dislocations. The aim of this study is to compare functional results between surgical and conservative treatment in type III acromioclavicular joint dislocations. MATERIAL AND METHOD: We retrospectively evaluated the records of 30 patients from our area with acute type III acromioclavicular dislocations that were treated from January 1st, 2016 to December 31st, 2020. Fifteen patients were treated surgically and 15 conservatively. Follow up mean time was 37.93 months in operative group and 35.73 months in non-operative group. Results obtained on the Constant score was the main variable analysed and results obtained on the Oxford score and the Visual Analogue Scale for pain were the secondary variables. Epidemiological variables were analysed, as well as range of mobility in injured shoulder and subjective and radiological variables (distance between the superior border of the acromion and the superior border of the clavicle's distal end and presence of osteoarthritis in the acromioclavicular joint). RESULTS: Functional evaluation scores did not show differences between the two groups (Constant: operative 82/non-operative 86.38, p 0.412; Oxford: operative 42/non-operative 44.80, p 0.126) nor did Visual Analogue Scale (operative 1/non-operative 0.20, p 0.345). Subjective evaluation of the injured shoulder was excellent or good in 80% of the patients in both groups. Measurement of the distance between the superior border of the acromion and the superior border of the clavicle's distal end were significantly higher in non-operative group (operative 8.95/non-operative 14.21, p 0.008). CONCLUSIONS: Although radiographic results were better in the surgical treatment group, functional evaluation scores did not show significant differences between the two groups. These results do not support the routine use of surgical treatment for grade III acromioclavicular dislocations.

Cannabis use frequency and pain interference among people with HIV.

Cannabis is often used by people with HIV (PWH) for pain, yet study results are inconsistent regarding whether and how it affects pain. This study examines whether greater cannabis use frequency is associated with lower pain interference and whether cannabis use modifies the association of pain severity and pain interference among 134 PWH with substance dependence or a lifetime history of injection drug use. Multi-variable linear regression models examined the association between past 30-day cannabis use frequency and pain interference. Additional models evaluated whether cannabis use modified the association between pain severity and pain interference. Cannabis use frequency was not significantly associated with pain interference. However, in a model with interaction between cannabis use frequency and pain severity, greater cannabis use frequency attenuated the strength of the association between pain severity and pain interference (p = 0.049). The adjusted mean difference (AMD) in pain interference was +1.13, + 0.81, and +0.05 points for each 1-point increase in pain severity for those with no cannabis use, 15 days of use, and daily use, respectively. These findings suggest that attenuating the impact of pain severity on pain-related functional impairment is a potential mechanism for a beneficial role of cannabis for PWH.

Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer.

Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.