Experience with the use of intravitreal bevacizumab in cases with type I retinopathy of prematurity in a Latin American country.

In retinopathy of prematurity (ROP) type I, the use of intravitreal bevacizumab (IVB), which is an inhibitor of endothelial growth factor (VEGF), has become popular despite not being a therapy approved by regulatory agencies. However, IVB has shown positive effects in halting disease progression at lower costs compared to other anti-VEGF therapies (ranibizumab or aflibercept). In this report, we present the experience during the treatment with IVB of 102 Colombian children with ROP type I, with a success rate of 98% (100). Complications occurred in 3.9% (4). Finally, we conclude that a single dose of IVB is an effective therapy for the management of ROP type I, with a lower risk of complications and retreatment.

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test.

OBJECTIVE: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. METHODS: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years). RESULTS: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. CONCLUSION: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population.

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task.

INTRODUCTION: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. METHODS: The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). RESULTS: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. CONCLUSIONS: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population.

The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure.

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal-ligand complexes, especially with repeated use, should be studied further.

The CORCOBIA study: Cut-off points of Alzheimer's disease CSF biomarkers in a clinical cohort.

INTRODUCTION: The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya). METHODS: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aß42, Aß40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups. RESULTS: The resulting cut-offs and their AUC were the following: Aß42 750 pg/mL (AUC 0.809); Aß42/Aß40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aß42/tTau 1.76 (AUC 0.86); Aß42/pTau181 10.25 (AUC 0.86). CONCLUSIONS: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aß42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.

Gadolinium Deposition Disease: A Case Report and the Prevalence of Enhanced MRI Procedures Within the Veterans Health Administration.

Background: Gadolinium (Gd) usage in the Veterans Health Administration is increasing and patients with renal disease are frequently exposed. Gd is not entirely eliminated within 24 hours after administration, which may pose long-term adverse effects. Case Presentation: A Vietnam-era veteran aged > 70 years presented for evaluation of Gd-based contrast agent-induced chronic multisymptom illness. In the course of his routine clinical care, he was exposed to repeated Gd-enhanced magnetic resonance imaging studies. After his second Gd-based contrast agent exposure, he noted rash, pain, headaches, and hoarseness. Years after the exposure to the contrast agents, he continued to have detectable Gd in urine and serum. Conclusions: Practitioners should be aware of long-term intracellular Gd retention (including the brain) as patients increasingly turn to consultants with concerns about Gd deposition disease. Data from patient advocates demonstrate that Gd is eliminated in intermediate and long phases, which may represent a multicompartment model. The commercialization of Gd use in imaging studies is outpacing the science addressing the long-term consequences of harboring this alien, toxic, nonphysiologic rare earth metal.

Dysnatremia in Gastrointestinal Disorders.

The primary solute of the milieu intérieur is sodium and accompanying anions. The solvent is water. The kidneys acutely regulate homeostasis in filtration, secretion, and resorption of electrolytes, non-electrolytes, and minerals while balancing water retention and clearance. The gastrointestinal absorptive and secretory functions enable food digestion and water absorption needed to sustain life. Gastrointestinal perturbations including vomiting and diarrhea can lead to significant volume and electrolyte losses, overwhelming the renal homeostatic compensatory mechanisms. Dysnatremia, potassium and acid-base disturbances can result from gastrointestinal pathophysiologic processes. Understanding the renal and gastrointestinal contributions to homeostatis are important for the clinical evaluation of perturbed volume disturbances.

Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

Peritonealized urachal remnant and obstructive congenital peritoneal band. A case report. / Remanente uracal peritonizado y banda peritoneal congénita obstructiva. Reporte de caso.

INTRODUCTION: Intestinal obstruction as a result of congenital peritoneal bands is rare in surgical practice. It typically compromises the small bowel, and it also has been reported to involve the appendix or a Meckel's diverticulum. However, peritonealized urachal remnant as part of a congenital band is highly infrequent. CASE REPORT: 5-year-old boy presenting with intestinal obstruction related to a peritoneal band from the mesentery to the appendix and a peritonealized urachal remnant, associated with an incidental finding of a Meckel's diverticulum. Diagnosis was achieved laparoscopically. The peritoneal band, the urachal remnant, and the Meckel's diverticulum were resected. DISCUSSION: Kerkeni's congenital band classification consists of 4 independent groups. This case combines both a band stemming from an embryological remnant and an idiopathic band.

INTRODUCCION: La obstrucción intestinal por bandas peritoneales congénitas es poco común en la práctica quirúrgica. Su ubicación más frecuente compromete el intestino delgado y existen reportes que involucran el apéndice y el divertículo de Meckel, pero que un remanente uracal peritonizado haga parte de una banda congénita es verdaderamente singular. CASO CLINICO: Niño de 5 años de edad con cuadro de obstrucción intestinal en el que confluyen una banda peritoneal, que va del mesenterio al apéndice y que se une a un remanente uracal peritonizado, asociado al hallazgo incidental de un divertículo de Meckel. El diagnóstico se definió por medio de una laparoscopia y como tratamiento se realizó la resección de la banda peritoneal, del remanente uracal y del divertículo de Meckel. DISCUSION: La clasificación de bandas congénitas de Kerkeni comprende 4 grupos independientes, en este caso confluyen una banda derivada de un remanente embriológico junto con el tipo idiopático.

Development, equivalence study, and normative data of version B of the Spanish-language Free and Cued Selective Reminding Test.

INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is widely used for the assessment of verbal episodic memory, mainly in patients with Alzheimer disease. A Spanish-language version of the FCSRT and normative data were developed within the NEURONORMA project. Availability of alternative, equivalent versions is useful for following patients up in clinical settings. This study aimed to develop an alternative version of the original FCSRT (version B) and to study its equivalence to the original Spanish-language test (version A), and its performance in a sample of healthy individuals, in order to develop reference data. METHODS: We evaluated 232 healthy participants of the NEURONORMA-Plus project, aged between 18 and 90. Thirty-three participants were assessed with both test versions using a counterbalanced design. RESULTS: High intra-class correlation coefficients (between 0.8 and 0.9) were observed in the equivalence study. While no significant differences in performance were observed in total recall scores, free recall scores were significantly lower for version B. CONCLUSIONS: These preliminary results suggest that the newly developed FCSRT version B is equivalent to version A in the main variables tested. Further studies are necessary to ensure interchangeability between versions. We provide normative data for the new version.

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test. / Estudios normativos españoles (proyecto NEURONORMA-Plus): Normas para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT).

OBJECTIVE: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. METHODS: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (<50 and ≥50 years). RESULTS: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (<50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. CONCLUSION: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population.

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task. / Estudios normativos españoles (Proyecto NEURONORMA Plus): normas para las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT).

INTRODUCTION: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. METHODS: The sample included 308 cognitively healthy individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). RESULTS: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. CONCLUSIONS: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Overlapping roles of NADPH oxidase 4 for diabetic and gadolinium-based contrast agent-induced systemic fibrosis.

Dozens of millions of people are exposed to gadolinium-based contrast agents annually for enhanced magnetic resonance imaging. Gadolinium-based contrast agents are known nephrotoxins and can trigger the potentially fatal condition of systemic fibrosis. Risk factors are practically entirely undefined. We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control groups followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogated both skin and renal pathology, whether from diabetes or gadolinium-based contrast agent treatment. These discoveries demonstrate the importance of Nox4 in gadolinium-based contrast agent- and diabetes-induced fibrosis.NEW & NOTEWORTHY A mouse model of gadolinium-based contrast agent- and diabetes-induced fibrosis was used to demonstrate the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Using these models, we established the role of Nox4 as a mediator of reactive oxygen species generation and subsequent skin and kidney fibrosis. These novel findings have defined Nox-4-mediated mechanisms by which gadolinium-based contrast agents induce systemic diseases.

Rosuvastatin-Induced Rhabdomyolysis, Pancreatitis, Transaminitis, and Acute Kidney Injury.

Changing medications within a drug class requires considering the indication and dosage, possible adverse effects, and drug-drug interactions.

Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution.

Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.

[Massive rotator cuff injury: arthroscopic treatment with upper capsular reconstruction]. / Lesión masiva del manguito rotador: tratamiento artroscópico con reconstrucción capsular superior.

Massive rotator cuff injuries (LMMRs) are those breaks of more than 5 cm either the anteroposterior plane, or lateromedial plane. Some authors consider them to be complete ruptures of at least two rotator cuff tendons. The clinical case of a 63-year-old man with this type of injury that was resolved by the superior capsule reconstruction technique is presented, technical details and some of the literature review to carry out the procedure are shown.

Las lesiones masivas del manguito rotador (LMMR) son aquellas roturas de más de 5 cm ya sea el plano anteroposterior o lateromedial. Algunos autores las consideran como roturas completas de al menos dos tendones del maguito rotador. Se presenta el caso clínico de un varón de 63 años con este tipo de lesión que se resolvió mediante la técnica de reconstrucción de cápsula superior, se muestran detalles técnicos y un poco de la revisión de la literatura para llevar a cabo el procedimiento.