First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular / Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle

Introducción: El objetivo de este estudio es analizar la relación existente entre la inervación del músculo subescapular y los pasos quirúrgicos de la técnica de Latarjet. Material y método: Se realizó un estudio anatómico mediante disección de 12 hombros fijados en formol, y se analizó el patrón de inervación del músculo subescapular. Se midió el tamaño del tendón en la interlínea articular, la distancia craneocaudal desde el borde superior al borde inferior del subescapular, en la entrada de los nervios, y la distancia mediolateral, desde los nervios hasta la interlínea articular. Se realizó la técnica de Latarjet y se midieron las distancias horizontales de los nervios subescapulares a la interlínea articular y de los nervios a la división del subescapular. Se describió la zona de seguridad por la que transcurre la división del subescapular sin dañar los nervios. Resultados: El músculo subescapular está inervado por 3 ramas del nervio subescapular: superior, medio e inferior, que siguen una distribución constante. No se encontraron diferencias estadísticamente significativas en las distancias de los nervios medidas antes y después de la técnica de Latarjet. Para evitar lesionar los nervios, es preciso realizar la división del subescapular entre los dos tercios superiores y el tercio inferior a lo largo del músculo. Conclusión: El músculo subescapular presenta una triple inervación constante. No hemos apreciado cambios estadísticamente significativos en la inervación tras la cirugía de Latarjet. Por tanto, la técnica de Latarjet parece respetar esta inervación al realizar la división del subescapular en su zona de seguridad.

Introduction: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. Materials and methods: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. Results: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds’ proportions throughout all the split must be maintained. Conclusions: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.(AU)

[Translated article] Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle / Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular

Introducción: El objetivo de este estudio es analizar la relación existente entre la inervación del músculo subescapular y los pasos quirúrgicos de la técnica de Latarjet. Material y método: Se realizó un estudio anatómico mediante disección de 12 hombros fijados en formol, y se analizó el patrón de inervación del músculo subescapular. Se midió el tamaño del tendón en la interlínea articular, la distancia craneocaudal desde el borde superior al borde inferior del subescapular, en la entrada de los nervios, y la distancia mediolateral, desde los nervios hasta la interlínea articular. Se realizó la técnica de Latarjet y se midieron las distancias horizontales de los nervios subescapulares a la interlínea articular y de los nervios a la división del subescapular. Se describió la zona de seguridad por la que transcurre la división del subescapular sin dañar los nervios. Resultados: El músculo subescapular está inervado por 3 ramas del nervio subescapular: superior, medio e inferior, que siguen una distribución constante. No se encontraron diferencias estadísticamente significativas en las distancias de los nervios medidas antes y después de la técnica de Latarjet. Para evitar lesionar los nervios, es preciso realizar la división del subescapular entre los dos tercios superiores y el tercio inferior a lo largo del músculo. Conclusión: El músculo subescapular presenta una triple inervación constante. No hemos apreciado cambios estadísticamente significativos en la inervación tras la cirugía de Latarjet. Por tanto, la técnica de Latarjet parece respetar esta inervación al realizar la división del subescapular en su zona de seguridad.

Introduction: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. Materials and methods: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. Results: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds’ proportions throughout all the split must be maintained. Conclusions: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.(AU)

COPD patient profiles in primary care. Referral criteria.

COPD is a disease with a high prevalence that diminishes the quality of life of many patients. Despite this, there are still high rates of under-diagnosis in Spain, partly due to a lack of recognition of the pathology by patients. In this context, the role played by primary care teams becomes fundamental, as they are one of the first lines of entry into the health system. In this paper we explain the different COPD profiles that may be present, and update the tools for diagnosis and treatment, which, together with an attitude of active suspicion of the disease, can help in the correct management of patients, whether they are undiagnosed or have subsequent complications.

[Translated article] Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle.

INTRODUCTION: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. MATERIALS AND METHODS: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. RESULTS: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds' proportions throughout all the split must be maintained. CONCLUSIONS: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.

Latarjet procedure for shoulder instability: Implications in the innervation of the subscapularis muscle. / Técnica de Latarjet para la inestabilidad anterior de hombro: implicaciones en la inervación del músculo subescapular.

INTRODUCTION: Our aim was to describe whether Latarjet's technique affects subscapularis muscle innervation. MATERIALS AND METHODS: We studied 12 embalmed shoulders. Subscapularis muscle innervation pattern was registered. Dimensions of the subscapularis at the glenohumeral joint line and the nerves entry point were measured. Horizontal distances from the nerves to the glenohumeral joint line as well as vertical ones to the split were measured before and after Latarjet procedure. A safe zone for the split was designed to avoid damage to subscapularis innervation. RESULTS: Subscapularis muscle is innervated by three principal branches: upper, middle, and inferior subscapularis nerves. No statistical differences were found between innervation distances before and after Latarjet procedure. To perform subscapularis split along the muscle safe zone, two thirds' proportions throughout all the split must be maintained. CONCLUSIONS: Subscapularis muscle has a triple innervation and was not altered after Latarjet procedure. Therefore, Latarjet technique seems to respect subscapularis muscle innervation if its split is placed through the subscapularis muscle safe zone.

Interobserver reliability of classifying shoulder calcific tendinopathy on plain radiography and ultrasound.

INTRODUCTION: Shoulder calcific tendinopathy is a frequent cause of shoulder pain. Diagnosis is usually based on ultrasound (US) and/or X-ray. US is considered an inherently operator-dependent imaging modality and, interobserver variability has previously been described by experts in the musculoskeletal US. The main objective of this study is to assess the interobserver agreement for shoulder calcific tendinopathy attending to the size, type, and location of calcium analyzed in plain film and ultrasound among trained musculoskeletal radiologists. MATERIAL AND METHODS: From June 2018 to May 2019, we conducted a prospective study. Patients diagnosed with shoulder pain related to calcific tendinopathy were included. Two different experienced musculoskeletal radiologists evaluated independently the plain film and the US. RESULTS: Forty patients, with a mean age of 54.6 years, were included. Cohen's kappa coefficient of 0.721 and 0.761 was obtained for the type of calcium encountered in plain film and the US, respectively. The location of calcification obtained a coefficient of 0.927 and 0.760 in plain film and US, respectively. The size of the calcification presented an intraclass correlation coefficient (ICC) of 0.891 and 0.86 in plain film and US respectively. No statistically significant differences were found in either measurement. CONCLUSION: This study shows very good interobserver reliability of type and size measurement (plain film and US) of shoulder calcifying tendinopathy in experienced musculoskeletal radiologists.

Implementation of a hybrid healthcare model in rheumatic musculoskeletal diseases: 6-months results of the multicenter Digireuma study.

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMDs) require a tailored follow-up that can be enhanced by the implementation of innovative tools. The Digireuma study aimed to test the feasibility of a hybrid follow-up utilizing an electronic patient reported outcomes (ePROs)-based monitoring strategy in patients with RMDs. METHODS: Adult patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) were recruited for a 6-month bicentric prospective follow-up consisting of face-to-face and digital assessments. Patients were asked to report disease-specific ePROs on a pre-established basis, and could also report flares, medication changes, and recent infections at any time. Four rheumatologists monitored these outcomes and contacted patients for interventions when deemed necessary. Results from face-to-face and digital assessments were described. RESULTS: Of 56 recruited patients, 47 (84%) submitted any ePROs to the digital platform. Most patients with RA were female (74%, median age of 47 years), while 48% of patients with SpA were female (median age 40.4 years). A total of 3,800 platform visits were completed, with a median of 57 and 29 visits in patients with RA and SpA, respectively. Among 52 reported alerts, 47 (90%) needed contact, of which 36 (77%) were managed remotely. Adherence rates declined throughout the study, with around half of patients dropping out during the 6 months follow-up. CONCLUSION: The implementation of a hybrid follow-up in clinical practice is feasible. Digital health solutions can provide granular knowledge of disease evolution and enable more informed clinical decision making, leading to improved patient outcomes. Further research is needed to identify target patient populations and engagement strategies.

Estudio biomecánico comparativo de dos configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados / Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate

Introducción: La utilización de tornillos cementados en la fijación interna de fracturas de húmero proximal con placas bloqueadas parece mejorar la estabilidad del implante y disminuir las complicaciones asociadas al fracaso de síntesis. Sin embargo, la combinación óptima de tornillos cementados se desconoce. El objetivo de este estudio fue analizar la estabilidad relativa de dos configuraciones de tornillos cementados sometidos a una fuerza de compresión axial en una fractura simulada de húmero proximal. Material y métodos: Se realizó una osteotomía del cuello quirúrgico en cinco pares de húmeros embalsamados con una edad media de 74 años (rango 46-93), fijados con una placa de acero inoxidable con tornillos bloqueados. En cada par de húmeros, en el húmero derecho se cementaron los tornillos A y E, y en el lado contralateral se cementaron los tornillos B y D. Cada espécimen fue testado inicialmente mediante una carga cíclica de compresión axial durante 6.000 ciclos para evaluar el movimiento interfragmentario (estudio dinámico). Al final de la prueba, los especímenes se sometieron a una carga de compresión axial progresiva para medir la rigidez de la construcción (estudio estático). Resultados: No se encontraron diferencias estadísticamente significativas en la movilidad interfragmentaria entre las dos configuraciones de tornillos cementados en el estudio dinámico (p=0,463). Cuando se sometieron a rotura, los especímenes con tornillos cementados en las hileras B y D presentaron una carga de rotura mayor (2218N vs. 2105, p=0,901) y una mayor rigidez (125N/mm vs. 106N/mm, p=0,672); sin embargo, ninguna de estas diferencias fue estadísticamente significativa. Conclusiones: La configuración de los tornillos cementados utilizadas en este estudio no influyen en la estabilidad del implante cuando se aplica una carga cíclica de baja energía. La cementación de los tornillos de las hileras B y D proporciona una resistencia similar a la cementación de los tornillos...(AU)

Introduction: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. Material and methods: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46–93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). Results: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. Conclusions: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.(AU)

[Translated article] Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate / Estudio biomecánico comparativo de 2 configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados

Introducción: La utilización de tornillos cementados en la fijación interna de fracturas de húmero proximal con placas bloqueadas parece mejorar la estabilidad del implante y disminuir las complicaciones asociadas al fracaso de síntesis. Sin embargo, la combinación óptima de tornillos cementados se desconoce. El objetivo de este estudio fue analizar la estabilidad relativa de dos configuraciones de tornillos cementados sometidos a una fuerza de compresión axial en una fractura simulada de húmero proximal. Material y métodos: Se realizó una osteotomía del cuello quirúrgico en cinco pares de húmeros embalsamados con una edad media de 74 años (rango 46-93), fijados con una placa de acero inoxidable con tornillos bloqueados. En cada par de húmeros, en el húmero derecho se cementaron los tornillos A y E, y en el lado contralateral se cementaron los tornillos B y D. Cada espécimen fue testado inicialmente mediante una carga cíclica de compresión axial durante 6.000 ciclos para evaluar el movimiento interfragmentario (estudio dinámico). Al final de la prueba, los especímenes se sometieron a una carga de compresión axial progresiva para medir la rigidez de la construcción (estudio estático). Resultados: No se encontraron diferencias estadísticamente significativas en la movilidad interfragmentaria entre las dos configuraciones de tornillos cementados en el estudio dinámico (p=0,463). Cuando se sometieron a rotura, los especímenes con tornillos cementados en las hileras B y D presentaron una carga de rotura mayor (2218N vs. 2105, p=0,901) y una mayor rigidez (125N/mm vs. 106N/mm, p=0,672); sin embargo, ninguna de estas diferencias fue estadísticamente significativa. Conclusiones: La configuración de los tornillos cementados utilizadas en este estudio no influyen en la estabilidad del implante cuando se aplica una carga cíclica de baja energía. La cementación de los tornillos de las hileras B y D proporciona una resistencia similar a la cementación de los tornillos...(AU)

Introduction: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. Material and methods: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46–93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). Results: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. Conclusions: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.(AU)

Dietary muramidase increases ileal amino acid digestibility of wheat and corn-based broiler diets without affecting endogenous amino acid losses.

The objective of these studies was to evaluate the impact of dietary muramidase (MUR) on endogenous amino acids (AA) losses and digestibility of nutrients in wheat and corn-based broiler diets. In experiment 1, the effect of dietary MUR on the flow of endogenous AA (EAA) at the jejunum and terminal ileum of broilers were assessed using either the nitrogen (N) free diet method (NFD) or the highly digestible protein diet method (HDP; 100 g casein/kg diet). Sialic acid and muramic acid concentrations were measured in the jejunal content. In experiment 2, a 2x2x2 factorial arrangement of treatments with 2 base grains (wheat or corn), with low or high metabolizable energy (ME) levels, and without or with MUR supplementation was implemented. All diets contained phytase, xylanase, and cellulase. Apparent ileal digestibility (AID) of dry matter (DM), protein (CP), amino acids (AA), crude fat, and energy, as well as the apparent total tract metabolizability (ATTM) of DM, CP, and gross energy (GE) were determined. The standardized ileal digestibility (SID) of AA was obtained by correcting AID values for basal ileal EAA obtained from chicks fed with NFD or HDP in experiment 1, jejunal EAA flow of all AA was higher (P < 0.001) compared to the ileum, but this effect was method dependent. Jejunal, but not ileal, EAA flow measured with HDP was higher compared to NFD, as well as sialic acid (P < 0.001) and muramic acid (P < 0.004) concentrations. Muramidase inclusion had no effect on basal EAA flow, independently of the segment and the method used. In experiment 2, dietary MUR supplementation increased the AID of CP (P < 0.05), all AA, and tended (P = 0.07) to increase the AID of GE, independently of the cereal type used. However, ATTM of DM and GE, but not CP, increased with MUR inclusion compared with the control treatments, especially in wheat and low ME diets (P < 0.05). In conclusion, MUR supplementation improved AID of CP and AA without affecting EAA losses and increases energy utilization.

[Translated article] Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate.

INTRODUCTION: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. MATERIAL AND METHODS: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46-93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). RESULTS: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. CONCLUSIONS: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.

Dolor abdominal inespecífico, un cuadro a vigilar / Non-specific abdominal pain, a case to keep under observation

El dolor abdominal es un síntoma inespecífico, común a múltiples procesos, con una alta prevalencia en la población general. Representa el 15-20% de los motivos de consulta en los servicios de urgencias.1 La mayoría de estos dolores tienen una etiología benigna, por lo que el objetivo inicial de la asistencia médica es identificar a aquellos pacientes cuyo dolor abdominal sea debido a una patología grave2. En ocasiones, puede tener una evolución tanto rápida como tórpida pudiendo provocar un abdomen agudo. El abdomen agudo se define como un dolor abdominal de instauración reciente, que requiere de un diagnóstico rápido y preciso debido a la posibilidad de que derive en un tratamiento quirúrgico urgente. Para ello es importante una buena anamnesis y exploración, enfocado a detectar signos y síntomas de alarma. Si no es diagnosticado y tratado de forma adecuada y precoz, puede originar consecuencia como sepsis, shock, insuficiencia renal, con elevada mortalidad3. A continuación presentamos el caso de una paciente con dolor abdominal inespecífico y pruebas complementarias anodinas en el inicio del cuadro, que evoluciona en las siguientes horas, obligando a la paciente a consultar de nuevo, llegando a precisar una intervención quirúrgica de urgencia. Se trata de un caso que nos obliga a determinar múltiples diagnósticos diferenciales y cómo abordar esta clínica tan frecuente como cambiante. (AU)

Abdominal pain is a nonspecific symptom, common to multiple processes, with a high prevalence in the general population. It represents 15-20% of the reasons for consultation in the Emergency Department1. Most of these pains have a benign etiology, so the initial objective of medical care is to identify those patients whose abdominal pain is due to a serious pathology2. Sometimes, it can have both a fast and torpid evolution and can cause an acute abdomen. Acute abdomen is defined as abdominal pain of recent onset, which requires a rapid and accurate diagnosis due to the possibility that it may lead to urgent surgical treatment. For this, a good history and examination is important, focused on detecting alarm signs and symptoms. If it is not diagnosed and treated properly and early, it can cause consequences such as sepsis, shock, kidney failure, with high mortality3. Below we present the case of a patient with nonspecific abdominal pain and anodyne complementary tests at the beginning of the condition, which evolves in the following hours, forcing the patient to consult again, eventually requiring an emergency surgical intervention. This is a case that forces us to determine multiple differential diagnoses and how to approach this clinic that is as frequent as it is changing. (AU)

A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma.

BACKGROUND: Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. METHODS: This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100-1000 mg once daily (QD; n = 38) and 200-400 mg twice daily (BID; n = 30). RESULTS: First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81-15.28) for QD and 4.6 months (range: 0.33-58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99-41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. CONCLUSION: These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM.

Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022.

In 2021, the Food and Drug Administration Oncology Center of Excellence announced Project Optimus focusing on dose optimization for oncology drugs. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce met to review and discuss the optimization of dosage for oncology trials and to develop a practical guide for oncology phase I trials. Defining a single recommended phase II dose based on toxicity may define doses that are neither the most effective nor the best tolerated. MDICT recommendations address the need for robust non-clinical data which are needed to inform trial design, as well as an expert team including statisticians and pharmacologists. The protocol must be flexible and adaptive, with clear definition of all endpoints. Health authorities should be consulted early and regularly. Strategies such as randomization, intrapatient dose escalation, and real-world eligibility criteria are encouraged whereas serial tumor sampling is discouraged in the absence of a strong rationale and appropriately validated assay. Endpoints should include consideration of all longitudinal toxicity. The phase I dose escalation trial should define the recommended dose range for later testing in randomized phase II trials, rather than a single recommended phase II dose, and consider scenarios where different populations may require different dosages. The adoption of these recommendations will improve dosage selection in early clinical trials of new anticancer treatments and ultimately, outcomes for patients.

Comparative biomechanical study of two configurations of cemented screws in a simulated proximal humerus fracture fixed with locking plate. / Estudio biomecánico comparativo de dos configuraciones de tornillos cementados en una fractura simulada de húmero proximal fijada con placa y tornillos bloqueados.

INTRODUCTION: Screw tip augmentation with bone cement for fixation of osteoporotic proximal humerus fractures seems to improve stability and to decrease the rate of complications related to implant failure. However, the optimal augmentation combinations are unknown. The aim of this study was to assess the relative stability of two augmentations combinations under axial compression load in a simulated proximal humerus fractures fixed with locking plate. MATERIAL AND METHODS: A surgical neck osteotomy was created in five pairs of embalmed humeri with a mean age of 74 years (range 46-93 years), secured with a stainless-steel locking-compression plate. In each pair of humeri, on the right humerus were cemented the screws A and E, and in the contralateral side were cemented screws B and D of the locking plate. The specimens were first tested cyclically in axial compression for 6,000 cycles to evaluate interfragmentary motion (dynamic study). At the end of the cycling test, the specimens were loaded in compression force simulating varus bending with increasing load magnitude until failure of the construct (static study). RESULTS: There were no significant differences in interfragmentary motion between the two configurations of cemented screws in the dynamic study (p=0.463). When tested to failure, the configuration of cemented screws in lines B and D demonstrated higher compression load to failure (2218N vs. 2105, p=0.901) and higher stiffness (125N/mm vs. 106N/mm, p=0.672). However, no statistically significant differences were reported in any of these variables. CONCLUSIONS: In simulated proximal humerus fractures, the configuration of the cemented screws does not influence the implant stability when a low-energy cyclical load is applied. Cementing the screws in rows B and D provides similar strength to the previously proposed cemented screws configuration and could avoid complications observed in clinical studies.

Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials.

BACKGROUND: During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. METHODS: A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. RESULTS: The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. CONCLUSIONS: This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients.