Real-world dosing patterns of regorafenib for patients with metastatic colorectal cancer in Spain: the RE-SEARCH study.

PURPOSE: To describe the dosing patterns of regorafenib in a real-world population of patients with metastatic colorectal cancer (mCRC) in a routine clinical practice setting in Spain, focusing on the starting dose of regorafenib. METHODS: An observational, retrospective, multicenter study that included patients ≥ 18 years old who had histologically documented mCRC and who had initiated treatment with regorafenib since January 2017. Post hoc categorization of dosing patterns revealed the following: initial dose < 160 mg and dose escalation, initial dose < 160 mg and maintenance, initial dose equal to 160 mg and maintenance, and initial dose equal to 160 mg and dose reduction. RESULTS: Most patients (152/241, 63.8%) initiated treatment with regorafenib at doses < 160 mg. There was large variation in the starting dose of regorafenib over time: in 2017, most patients (59%) initiated regorafenib at a dose of 160 mg, this proportion decreased to 6% in 2021. There were no significant differences in the median progression-free survival according to the regorafenib dose patterns during the first two cycles. The proportion of patients who reported at least one adverse event (AE), had a grade 3-4 AE or had an AE leading to dose reduction was greater in the group of patients who received an initial dose equal to 160 and reduction. CONCLUSIONS: Our results indicate that physicians in Spain have gradually adopted a dose-escalation approach during cycle 1, which is a common practice for starting treatment with a reduced dose (< 160 mg/day), a strategy that seems to improve tolerability while maintaining efficacy. TRIAL REGISTRATION: Not applicable.

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Síndrome de Rapunzel: atadura sicológica y simulación orgánica / Rapunzel syndrome: psychological bondage and organic simulation

Introducción. El síndrome de Rapunzel es una entidad infrecuente, que se presenta como un tricobezoar a causa de una aglomeración de cabello acumulado dentro del tracto gastrointestinal, por lo que simula otras patologías quirúrgicas. Caso clínico. Paciente femenina de 10 años de edad, con tricotilomanía y tricofagia, dolor abdominal y síntomas inespecíficos de obstrucción intestinal de ocho meses de evolución. Al examen físico se encontró abdomen con distensión y masa palpable en epigastrio y mesogastrio. La ecografía permitió hacer el diagnóstico de tricobezoar gástrico extendido hasta el intestino delgado, por lo que se llevó a cirugía para gastrotomía y se extrajo el tricobezoar, con evolución satisfactoria de la paciente. El abordaje integral permitió conocer la atadura sicológica por posible maltrato infantil. Resultado. La paciente tuvo una evolución satisfactoria y se dio egreso al quinto día de hospitalización. Actualmente se encuentra en seguimiento por sicología, siquiatría infantil y pediatría. Discusión. El caso clínico denota la importancia en reconocer situaciones de presentación infrecuente en pediatría, que puedan estar asociadas a alteraciones sicológicas o presunción de maltrato infantil y que se presenten como una condición orgánica recurrente que simule otras patologías abdominales frecuentes en la infancia. El retraso diagnóstico puede conducir a un desenlace no deseado con complicaciones. Conclusión. Se hace mandatorio el manejo integral del paciente pediátrico y aumentar la sensibilidad para reconocer situaciones de presunción de maltrato infantil, sobre todo en pacientes con una condición orgánica quirúrgica recurrente.

Introduction. Rapunzel syndrome is an uncommon condition that manifests as trichobezoars, which are hair bundles in the stomach or small intestine that can mimics other surgical illnesses. Multiple complications can arise from delayed diagnosis and treatment. Clinical case. A 10-year-old female patient with trichotillomania and trichophagia, with abdominal pain and nonspecific symptoms of intestinal obstruction of eight months of evolution. Physical examination revealed epigastric tenderness and a solid mass was palpable in the mesogastric and epigastric region. An abdominal ultrasound showed gastric trichobezoar that extended into the small intestine. A gastrotomy was performed and the trichobezoar was extracted with satisfactory evolution of the patient. The comprehensive approach allowed knowing the psychological bond due to possible child abuse. Results. The patient had a satisfactory evolution and was discharged on the fifth day of hospitalization. He is currently being monitored by psychology, child psychiatry and pediatrics. Discussion. This clinical case highlights the importance of recognizing situations that seldom present in pediatrics, which may have a psychological aspect due to the presumption of child abuse, and which present as a recurrent organic condition simulating other frequent abdominal pathologies in childhood; all of which may lead to an unwanted outcome due to diagnostic delay. Conclusion. The comprehensive management of the pediatric patient is mandatory to recognize situations of presumed child abuse, in the face of a recurrent surgical conditions.

Usefulness of an Easy, Structured, and Home-Based Exercise Program to Improve Physical Performance and Quality of Life in a Patient's Cohort with Obesity.

INTRODUCTION: The benefits of exercise in patients with obesity are clear; physical performance and quality of life improve after exercise programs in patients with obesity. Our aim was to evaluate the usefulness of an easy, structured, and home-based exercise program to improve physical performance and quality-of-life in patients with obesity. METHODS: A cohort of patients with obesity (BMI ≥30 kg/m2) was recruited during 2017-2020. Patients who met the inclusion criteria were invited and those who accepted signed informed consent. Patients were evaluated by the same team of physicians who performed the 6-min walking test and collected the clinical and biochemical variables, also applied quality-of-life questionnaire at baseline and 3 months after starting the exercise program that was divided in two levels: level 1: active mobilization of four limbs (15 min) + cardiovascular exercise (15 min walking), 5 days/week; level 2: eight strengthening exercises for upper and lower limbs with an elastic band + cardiovascular exercise (15 min walking), 5 days/week. This study used means (SD), frequencies (percent), Student's t test, and Pearson correlation test. RESULTS: We included 151 patients, mostly women (81.5%), age 46.3 ± 9.8 years old, BMI 40.3 ± 8.56 kg/m2, 34.4% performed some type of exercise, and the most frequents comorbidities were dyslipidemia and diabetes. After 3 months, 86 patients (57%) remained in the study and attended the final evaluation. Evident changes in physical performance were reported (distance traveled, speed walking and VO2max); however, improvement in quality of life was remarkable. CONCLUSION: An easy, structured, and home-based exercise program improves physical performance and quality of life in patients with obesity, without losing its benefits for the health.

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part II: prostate cancer and colorectal cancer.

Oligometastatic disease (OMD) defines a status of cancer that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While imaging diagnostic tools have considerably improved in recent years, unidentified micrometastases can still escape from current detection techniques allowing disease to progress. The variety of OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of an early disease control. Based on increasing detection rates of OMD in the current real clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies may translate into promising treatment options. This experts' review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of Non-Small Cell Lung Cancer and Breast Cancer (Part I), and Prostate Cancer and Colorectal Cancer (Part II), aiming to offer specialists a pragmatic framework that might contribute to the improved management of patients.

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part I: non-small cell lung cancer and breast cancer.

Oligometastatic disease (OMD) defines a cancer status that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While diagnostic imaging tools have considerably improved in recent years, unidentified micrometastases can still evade current detection techniques, allowing the disease to progress. The various OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of early disease control. In view of increasing OMD detection rates in current real-world clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies might translate into promising treatment options. This expert review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of non-small cell lung cancer and breast cancer (Part I), and prostate cancer and colorectal cancer (Part II), aiming to offer specialists a pragmatic framework to help improve patient management.

Peripheral neuropathies in rheumatic diseases: More diverse and frequent than expected. A cross-sectional study.

BACKGROUND/OBJECTIVE: Peripheral neuropathies (PN) are heterogeneous nerve disorders; frequently rheumatic patients have neuropathic symptoms. In some rheumatic diseases (RD) PN are secondary to nerve compression while others are related to metabolic abnormalities, inflammation or vasculitis. Our aim was to explore the frequency of neuropathic symptoms with three neuropathy questionnaires (NQ) and nerve conduction studies (NCS) in RD. METHODS: This is a cross-sectional study in patients with any RD attending for the first time to a rheumatology outpatient clinic. We included all patients who accepted to participate and who answered three NQ and received a physical evaluation. Twenty patients were randomly selected to perform NCS and 10 healthy subjects were included as controls. The topographic diagnoses were: mononeuropathy, multiplex mononeuropathy, and/or polyneuropathy. STATISTICAL ANALYSIS: descriptive statistics (mean, median, standard deviation, interquartile range and frequency, odds ratios and Pearson correlation test). RESULTS: One hundred patients and 10 healthy subjects were included. Sixty-nine were female, mean age 40.6 ± 15.7 years. Rheumatic diagnoses were: systemic lupus erythematosus (26%), rheumatoid arthritis (16%), gout (14%), and osteoarthritis (11%). Fifty-two patients had neuropathic signs during physical examination and 67% had positive questionnaires with variable scores among several RD. Abnormal NCS was reported in 14 patients (70%): 6 (42.8%) median nerve mononeuropathies, 4 (28.5%) multiplex mononeuropathies and 4 (28.5%) polyneuropathies. None of the healthy subjects had neuropathy (NQ, physical evaluation, or NCS). Risk of being NCS positive is higher when the patients were NQ positive. CONCLUSION: PN has variable distribution and high frequency in patients with RD; NQ+ increases the risk of presenting NCS+ for PN.

Are Target Urate and Remission Possible in Severe Gout? A Five-year Cohort Study.

OBJECTIVE: Determine the proportion of patients achieving target serum urate (SU), defined as < 6 mg/dl for patients with non-severe gout and < 5 mg/dl for patients with severe gout, as well as the proportion of patients achieving remission after 5 years of followup. METHODS: Patients from the Gout Study Group (GRESGO) cohort were evaluated at 6-month intervals. Demographic and clinical data were obtained at baseline. Visits included assessments of serum urate, flares, tophus burden, health-related quality of life using the EQ-5D, activity limitations using the Health Assessment Questionnaire adapted for gout, and pain level and patient's global assessment using visual analog scales. Treatment for gout and associated diseases was prescribed according to guidelines and available drugs. RESULTS: Of 500 patients studied, 221 had severe gout (44%) and 279 had non-severe gout (56%) at baseline. No significant differences were observed across the study in percentages of severe gout versus non-severe gout patients achieving SU 6 mg/dl or 5 mg/dl. The highest proportion of patients achieving target SU (50-70%) and remission (39%) were found after 3-4 years of followup. In the fifth year, these proportions decreased and 28% of the patients were in remission, but only 40 patients remained in the study. None of the patients with severe gout achieved remission. CONCLUSION: In patients with severe gout, target SU was hard to achieve and remission was not possible. The main obstacles for target SU and gout remission include poor medication adherence, persistent tophi, and loss to followup.

Severe tophaceous gout and disability: changes in the past 15 years.

Epidemiologic data from recent decades show a significant increase in the prevalence and incidence of gout worldwide, in addition to changes in its clinical expression. Our objective was to compare the frequency of the severity of gout and disability in two patient groups at our clinic during different periods. We included and compared data of two groups: group A (1995-2000), patients from previous report, and group B (2010-2014), the baseline data of current patients participating in a cohort (GRESGO). This evaluation included data of socioeconomic and educational levels, demographics, associated diseases, previous treatment, clinical and biochemical data, and disability evaluated using the Health Assessment Questionnaire (HAQ). We included data of 564 gout patients. Participants were 35.7 ± 12.7 years old at onset and had 12.0 ± 9.2-years disease duration at their first evaluation in our department. Group B patients were younger, had higher educational and socioeconomic levels, and had more severe disease. However, this group had less frequency of some associated diseases and significantly higher HAQ scores. With increased HAQ score, a higher number of acute flares and tender, limited-to-motion, and swollen joints were seen. The spectrum of gout has changed over the past decade. A higher percentage of our patients had a severe form of disease, were younger, had earlier disease onset, and had more disability reflected in higher HAQ scores. In our current patient group, the variable most associated with disability was limited-to-motion joints; however, the number of acute flares and tender and swollen joints was also higher in patients with greater disability.

Defensin production by human limbo-corneal fibroblasts infected with mycobacteria.

Epithelial cells of the cornea and the conjunctiva constitutively produce antimicrobial peptides; however, the production of defensins by other cell types located around the eye has not been investigated. We analyzed the production of beta-defensins (hBD) and cathelicidin LL-37 during the infection of primary limbo-corneal fibroblasts with M. tuberculosis (MTB), M. abscessus (MAB), and M. smegmatis (MSM). The intracellular survival of each mycobacterium, the production of cytokines and the changes on the distribution of the actin filaments during the infection were also analyzed. Fibroblasts produce basal levels of hBD1 and LL-37 and under PMA stimulation they produce hBD2, hBD3 and overexpress hBD1 and LL-37. MAB induced the highest levels of hBD1 and LL-37 and intermediate levels of IL-6; however, MAB was not eliminated. In addition, MAB induced the greatest change to the distribution of the actin filaments. MTB also produced changes in the structure of the cytoskeleton and induced low levels of hBD1 and IL-6, and intermediate levels of LL-37. The balance of these molecules induced by MTB appeared to contribute to the non-replicative state observed in the limbo-corneal cells. MSM induced the lowest levels of hBD1 and LL-37 but the highest levels of IL-6; MSM was eliminated. The results suggest that mycobacterial infections regulate the production of antimicrobial peptides and cytokines, which in conjunction can contribute to the control of the bacilli.

Evaluation of hand function in rheumatic disease. Validation and usefulness of the Spanish version AUSCAN, m-SACRAH and Cochin questionnaires.

INTRODUCTION: Questionnaires to evaluate hand function are variable in the number of items, domains and diseases in which they had been previously used. OBJECTIVES: a) To translate to Spanish and validate the m-SACRAH and AUSCAN questionnaires; b) to do a transcultural adaptation of DASHe, previously validated in Spain), and c) to compare them and the Cochin questionnaire (previously validated in México), in rheumatic patients with variable impairment of hand function. MATERIAL AND METHODS: m-SACRAH, AUSCAN and DASH were translated/retro-translated and adapted. The final version was revised to determine content validity and them, plus Cochin were applied to 10 healthy subjects (pilot study) with a variable educational level and in 16 rheumatic patients with variable diagnoses and degrees of hand function impairment; all patients answered 4 questionnaires and were evaluated clinically by blinded investigators. RESULTS: Seventy six percent were women, mean age 45.7±11.4 years. Cronbach́s alpha >0.90; time to answer went from 2.3±0.087 (AUSCAN) to 3.5±0.36 minutes (DASH). There was good correlation among them (r=0.0683 AUSCAN-m-SACRAH to r=0.889 AUSCAN-DASH) and good capability for discrimination between patients with mild VS moderate to severe impairment was also demonstrated; patients with mild impairment needed less time to answer them and there were no significant differences among questionnaire scores. Patients prefered AUSCAN (10/16), Cochin (4/16) and m-SACRAH (2/16). CONCLUSION: The 4 questionnaires are useful to evaluate hand function in rheumatic patients and have good discrimination capability. More patients preferred AUSCAN.