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.

Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group.

Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice. This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.

Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. CONCLUSION: Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, especially the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

[Type 3 c diabetes: Approach from the first level doctor]. / La diabetes tipo 3c. Abordaje desde el médico del primer nivel.

DM3c is diabetes (DM) of the exocrine pancreas that must be suspected whenever there is a history of chronic pancreatitis (CP), acute pancreatitis (AP) or recurrence (80% of cases) or new-onset DM in individuals from over 50 years of age without any other justification (negative autoimmunity tests, Glutamic Acid Decarboxylase antibodies). It is an entity misdiagnosed as type 2 diabetes (DM2) (90%) and therefore, if it is not suspected, it can go unnoticed. For its diagnosis, abdominal ultrasound, determination of the CA 19.9 tumor antigen (carbohydrate antigen 19-9), nuclear magnetic resonance (NMR) or computerized axial tomography (CT) are useful. The treatment is the same as DM2, although certain specifications depend on the type of drugs and with the particularity that in dealing with «fragile diabetes¼ greater caution must be taken with hypoglycemia (monitoring). Likewise, as it is a disease of the exocrine pancreas, it will have to be specifically treated to avoid metabolic, malabsorptive and/or nutritional alterations.

[Translated article] Tumor ablation and vertebral augmentation in the treatment of vertebral metastases: A multicenter study.

INTRODUCTION: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. MATERIAL: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. RESULTS: In group A pain improvement in VAS was 7.7-2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8 to 1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. CONCLUSION: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.

Tumor ablation and vertebral augmentation in the treatment of vertebral metastases: A multicenter study. / Ablación tumoral y cementación en el tratamiento de las metástasis vertebrales. Estudio multicéntrico.

INTRODUCTION: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. MATERIAL: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. RESULTS: In group A pain improvement in VAS was 7.7-2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8-1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. CONCLUSION: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.

Common laboratory reagents: Are they a double-edged sword in microplastics research?

Understanding and communicating instances of microplastic contamination is critical for enabling plastic-free transitions. While microplastics research uses a variety of commercial chemicals and laboratory liquids, the impact of microplastics on these materials remains unknown. To fill this knowledge gap, the current study investigated microplastics abundance and their characteristics in laboratory waters (distilled, deionized, and Milli-Q), salts (NaCl and CaCl2), chemical solutions (H2O2, KOH and NaOH), and ethanol from various research laboratories and commercial brands. The mean abundance of microplastics in water, salt, chemical solutions, and ethanol samples was 30.21 ± 30.40 (L-1), 24.00 ± 19.00 (10 g-1), 187.00 ± 45.00 (L-1), and 27.63 ± 9.53 (L-1), respectively. Data comparisons revealed significant discrepancies between the samples in terms of microplastic abundance. Fibers (81 %) were the most common microplastics, followed by fragments (16 %) and films (3 %); 95 % of them were <500 µm, with the smallest and largest particle sizes recorded being 26 µm and 2.30 mm, respectively. Microplastic polymers discovered included polyethylene, polypropylene, polyester, nylon, acrylic, paint chips, cellophane, and viscose. These findings lay the groundwork for identifying common laboratory reagents as a potential contributor to microplastic contamination in samples, and we offer solutions that should be integrated into data processing to produce accurate results. Taken together, this study shows that commonly used reagents not only play a key role in the microplastic separation process but also contain microplastic contamination themselves, requiring the attention of researchers to promote quality control during microplastic analysis and commercial suppliers in formulating novel prevention strategies.

Perioperative neuromuscular blockade. 2020 update of the SEDAR (Sociedad Española de Anestesiología y Reanimación) recommendations.

We present an update of the 2020 Recommendations on neuromuscular blockade of the SEDAR. The previous ones dated 2009. A modified Delphi consensus analysis (experts, working group, and previous extensive bibliographic revision) 10 recommendations were produced1: neuromuscular blocking agents were recommended for endotracheal intubation and to avoid faringo-laryngeal and tracheal lesions, including critical care patients.2 We recommend not to use neuromuscular blocking agents for routine insertion of supraglotic airway devices, and to use it only in cases of airway obstruction or endotracheal intubation through the device.3 We recommend to use a rapid action neuromuscular blocking agent with an hypnotic in rapid sequence induction of anesthesia.4 We recommend profound neuromuscular block in laparoscopic surgery.5 We recommend quantitative monitoring of neuromuscular blockade during the whole surgical procedure, provided neuromuscular blocking agents have been used.6 We recommend quantitative monitoring through ulnar nerve stimulation and response evaluation of the adductor pollicis brevis, acceleromyography being the clinical standard.7 We recommend a recovery of neuromuscular block of at least TOFr ≥ 0.9 to avoid postoperative residual neuromuscular blockade.8 We recommend drug reversal of neuromuscular block at the end of general anesthetic, before extubation, provided a TOFr ≥ 0.9 has not been reached.9 We recommend to choose anticholinesterases for neuromuscular block reversal only if TOF≥2 and a TOFr ≥ 0.9 has not been attained.10 We recommend to choose sugammadex instead of anticholinesterases for reversal of neuromuscular blockade induced with rocuronium.

First evidence of microplastic contamination in ready-to-use packaged food ice cubes.

Concern over microplastics has grown tremendously, and they have been found in all environmental compartments; yet, much remains unknown regarding their impact on a variety of human-consuming food products. Here, we contribute to ongoing research by screening the 15 most popular commercial brands of packaged food ice cubes in Mexico City for microplastics. Microplastics were detected in 100% of the samples evaluated, with concentrations ranging from 19 ± 4 to 178 ± 78 L-1. There was a significant difference in the microplastic concentration across samples. The mean microplastic concentration was 79 ± 47 L-1, and the main types were polypropylene, polyethylene, polyvinyl alcohol, tygon polymer, sealing ring gardena 2824 large, polyamide 6, and cellophane. Moreover, microplastics that are fibrous (87%), non-colored (54%), and less than 300 µm in size (63%), were found to be more prevalent. The SEM-EDX analysis showed heterogeneous structural and morphological characteristics of microplastics, as well as traces of Si, S, Ti, Ca, Al, and Na. Furthermore, we estimate that ice cube consumption in Mexico City can result in the inadvertent ingestion of 4.9 × 102 ± 3.4 × 102-1 × 104 ± 7.2 × 103 microplastics annually. The findings of the study revealed that microplastics were identified in ice cubes and can be conveyed to humans, stressing the need of managing and eradicating such contamination from our food.

Implementation of an enhanced recovery after surgery program including a patient school: Impact on quality of life results.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) protocols and educational programmes have been shown to accelerate orthopaedic surgery recovery with fewer complications, and improve patient-reported outcomes (PROs) for different types of surgery. The objective was to evaluate the impact of an ERAS programme including a patient school on health outcomes and PROs for Total Knee Replacement (TKR) surgery. MATERIAL AND METHODS: A multidisciplinary group created the programme and the patient school (preoperative consultations where the patients' surgical processes are explained and are also given instructions for an appropriate perioperative care management). An observational, prospective study was conducted on all patients operated for TKR from March 2021 to March 2022. Main health outcomes were: hospital stay length, surgical complications and surgery cancellations due to a wrong preoperative medication management. PROs evaluated were: patient satisfaction with pain management, the school, and quality of life before and after surgery (EQ-5D). RESULTS: One hundred thirty-three patients were included. Median hospital stay length was 3 days (IQR 3-5). Rate of surgical complications was 25.6%. No surgery was cancelled. Patient satisfaction rates with pain management and with the school were 8.10/10 and 9.89/10, respectively. Concerning quality of life, mean improvement in mobility and knee pain after the surgery was 0.66 (p < 0.05) and 0.84 (p < 0.05), respectively. CONCLUSIONS: The ERAS programme including a patient school was highly successful with a fast recovery, a short hospital stay length, no surgery cancellations, and improved PROs.

Clinical and genetical diagnosis of a case of Meretoja syndrome and frontotemporal lifting procedure.

A 56-year-old male with family background of corneal dystrophy presents with poor subjective vision. Biomicroscopy reveals bilateral reticular stromal dystrophy and facial inspection shows signs of muscle dysfunction, such as eyebrow ptosis, weakness and sagging of the frontal muscles, redundant skin on the forehead and skin hyperelasticity. The patient is referred to Plastic Surgery for evaluation of the frontal muscle involvement, undergoing a frontotemporal lifting procedure. On the other hand, genetics confirms the pathogenic variant c.640G>A (p.Asp214Asn) in the GSN gene, encoding gelsolin, a mutation associated with Finnish-type familial amyloidosis or Meretoja syndrome.

Ultrasound-guided bilateral erector spinae plane block in dogs undergoing sternotomies anaesthetised with propofol-dexmedetomidine continuous infusion.

BACKGROUND: To describe the use of a bilateral thoracic (T5 - T9) ultrasound-guided erector spinae plane block (UG-ESPB) in dogs undergoing sternotomy anaesthetised with propofol and dexmedetomidine continuous infusions. METHODS: Demographic information, perioperative anaesthetic and analgesic drugs, the prevalence of hypotension and nociceptive events, and their treatment, were recorded and analysed. Local anaesthetic injection point, volume and concentration were reported for each dog. In attempt to differentiate somatic nociception from visceral nociception, the surgery was divided into three timeframes: from the skin incision to the thoracic cavity opening; from the latter to the beginning of its closure; from thoracic cavity closure to the end of surgery. RESULTS: Overall, 10 dogs were included and four experienced nociception: somatic nociception was recorded in one dog, whereas visceral nociception was recorded in four dogs. The overall fentanyl consumption to control nociception was 0.3 µg/kg/h. No adverse events associated with the UG-ESPB were reported. CONCLUSION: The bilateral UG-ESPB could be used as a part of a multimodal analgesic technique in dogs undergoing sternotomies. However, more clinical studies are warranted to assess its safety and effects.

Free, but not microplastic-free, drinking water from outdoor refill kiosks: A challenge and a wake-up call for urban management.

Free refill drinking water kiosks are an essential sustainable water supply system for people in metropolitan areas worldwide. Despite their importance in urban settings, the impact of microplastic contamination remains elusive. Here, we investigated the occurrence and characteristics of microplastics in drinking-water samples collected from 22 self-distributed refill kiosks located in 14 multiuse urban parks spread across nine municipalities in Mexico City (Mexico). The results showed that microplastics were detected in all the samples, with an overall mean concentration of 74.18 ± 48.76 microplastics L-1. The abundance of microplastics was significantly different between sampled kiosks, ranging from 23 ± 11.31 to 202 ± 28.39 microplastics L-1. There were more fibrous microplastics (88%) than fragments (9%) and films (3%), with the majority (56%) being <200 µm in length. They were predominantly transparent (85%), with only a few being colored (15%; blue, red, green, and brown). Attenuated Total Reflection-Fourier-transform infrared spectroscopy further revealed microplastics of various polymer types, including polyvinyl alcohol, high-density polyethylene, polypropylene, polyvinyl acetate, ethylene vinyl alcohol, acrylic, alkyd resin, and viscose. Based on our findings, drinking water from urban refill kiosks exposes children more than adults to microplastics. Furthermore, the steps that should be taken at urban refill kiosks to prevent microplastic pollution while offering recreational services to people have been highlighted. Therefore, this first study serves as a wake-up call to urban water management to improve the safety of water from emerging pollutants like microplastics in the infrastructure of refill kiosks.

[Infantile hepatic cholestatis: An unusual case of Langerhans cells histiocytosis associated with advanced fibrosis]. / Colestasis hepática infantil: presentación de un caso inusual de histiocitosis de células de Langerhans asociado a fibrosis avanzada.

Neonatal cholestasis is a clinical metabolic alteration requiring investigation of its eitiology. It is characterized by elevation of liver enzymes with cholestasis pattern and, in some cases, with acute liver failure. Its etiology is variable although the most frequent cause is atresia of extrahepatic bile ducts. We present a case of a 23-month-old boy who presented with cholestasis and was finally diagnosed with systemic Langerhans cell histiocytosis.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Long-term outcomes of spinal SBRT. Is it important to select the treatment time?

PURPOSE: SBRT (stereotactic body radiation therapy) is widely used as a curative treatment in tumoral lesions and has become a fundamental tool for the treatment of spine metastasis. In this study, we present survival and toxicity outcomes of spine SBRT after a 2-year follow-up. METHODS/PATIENTS: Data from spine SBRT treatments performed at our institution between March 2012 and February 2020 was collected. Medical records, including demographic, primary tumor, and treatment characteristics were reviewed. Patient follow-up included clinical evaluation, imaging, and blood tests. Toxicity was recorded according to CTCAE v4.0. RESULTS: We analyzed 73 consecutive spine SBRT treatments in 60 patients. 39.7% of the cases had primary breast cancer and 23.3% had prostate cancer. Most cases (87.7%) were treated with a single SBRT fraction of 16 Gy. Median follow-up was 26.1 months (range 1.7-78.6), and 1- and 2-year overall survival (OS) rates were 96.9% and 84.2%, respectively. Local control (LC) rates at 1- and 2-years were 76.3% and 70.6%, respectively. Multivariate analysis identified histology as a prognostic factor for both OS and LC. Patients who underwent spine SBRT 6 months after the spinal lesion diagnosis had LC at 2 years of 88%, vs 61.7% for those who underwent SBRT before this period. No grade III or higher toxicity was reported. The vertebral compression fracture (VCF) rate was 4.1%. CONCLUSION: Spine SBRT at our institution showed a 2-year LC of 70.6%, without G3 toxicities. Delaying SBRT at least 6 months to administer systemic treatment was related to an improvement in local control.

Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments.

PURPOSE: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. METHODS: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. RESULTS: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).