Resolution of acenocoumarol-associated calciphylaxis with drug withdrawal.

Calciphylaxis is a syndrome of cutaneous ischaemic necrosis and ulceration due to arteriolar calcification with subsequent thrombosis, which rarely presents in patients without terminal kidney disease. Recently, several reports of coumarins-associated calciphylaxis have stressed the relevance of anticoagulant therapy as an important risk factor for the development of this condition. We report five cases of acenocoumarol-associated, biopsy-proven calciphylaxis in women aged between 64 and 92 years. The drug had been prescribed for atrial fibrillation and was taken without interruption from 14 to 224 months. Lesions were present for months in all cases and were resistant to multiple therapeutic options, but they resolved only with simple wound care measures 6-14 months after changing the anticoagulant therapy.

Validation of a Comprehensive Early Childhood Allergy Questionnaire.

BACKGROUND: Parental questionnaires to assess incidence of pediatric allergic disease have been validated for use in school-aged children. Currently, there is no validated questionnaire-based assessment of food allergy, atopic dermatitis (AD), and asthma for infants and young children. METHODS: The Comprehensive Early Childhood Allergy Questionnaire was designed for detecting AD, asthma, and IgE-mediated food allergies in children aged 1-5 years. A nested case-control design was applied. Parents of 150 children attending pediatric outpatient clinics completed the questionnaire before being clinically assessed by a pediatrician for allergies. Sensitivity, specificity, and reproducibility of the questionnaire were assessed. RESULTS: Seventy-seven children were diagnosed with one or more current allergic diseases. The questionnaire demonstrated high overall sensitivity of 0.93 (95% CI 0.86-0.98) with a specificity of 0.79 (95% CI 0.68-0.88). Questionnaire reproducibility was good with a kappa agreement rate for symptom-related questions of 0.45-0.90. CONCLUSIONS: Comprehensive Early Childhood Allergy Questionnaire accurately and reliably reflects the presence of allergies in children aged 1-5 years. Its use is warranted as a tool for determining prevalence of allergies in this pediatric age group.

OUTCOMES OF CONTROLLED DCDD LUNG TRANSPLANTATION AFTER THORACO-ABDOMINAL VS ABDOMINAL NORMOTHERMIC REGIONAL PERFUSION: THE SPANISH EXPERIENCE.

OBJECTIVE: Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. METHODS: This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in two groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart versus abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, ICU and hospital length of stay, early survival rates, and mid-term outcomes. RESULTS: 283 cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs. 7.6%; p=0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3%% vs. 41.5%; p=0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. CONCLUSIONS: TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

Neurosteroid vitamin D system as a nontraditional drug target in neuropsychopharmacology.

Vitamin D is becoming increasingly recognized as a nontraditional drug target for different brain pathologies. Although widely known for their role in calcium metabolism, vitamin D and its receptor have been linked to several brain disorders, including cognitive decline, epilepsy, affective disorders, and schizophrenia. Here we discuss mounting evidence, and parallel recent clinical and animal behavioral, genetic and pharmacological data to emphasize the emerging role of the neurosteroid vitamin D system in brain function.

Uniportal VATS for non-small cell lung cancer.

The video-assisted thoracic surgery (VATS) technique has evolved from its multiport origins to even less invasive approaches grounded in its proven benefits over open surgery for the treatment of early stage lung cancer. In this evolution process, the Uniportal VATS (UniVATS) strategy emerged. This technique is giving some evidence of benefits when compared to the multiport VATS and has been embraced by the surgical community spreading its geographical and surgical boundaries. Moreover, UniVATS has proven its feasibility for numerous and more complex procedures for lung cancer diagnosis and treatment, which are reviewed in this document as well as its current and future development.

Current role of uniportal video-assisted thoracic surgery for lung cancer treatment.

The use of video-assisted thoracic surgery (VATS) as an approach for early-stage lung cancer treatment has revealed benefits compared to open surgery by minimizing trauma to the patients. This trend has brought the evolution of VATS to less and less invasive methods, eventually leading to the development of Uniportal VATS (UniVATS) technique. This new approach has shown to be resourceful, proving its feasibility even for complex oncological procedures. Furthermore, data is starting to express some benefits over multiport VATS, thus spurring on its development towards newer and more complex procedures. It is also been adopted by the surgical community achieving fast evolution and worldwide diffusion. Here, we review the evolution of UniVATS, its current state of evidence, some basic technical aspects, the present role it has in lung cancer treatment and the ongoing development of the technique. RELEVANCE FOR PATIENTS: This article could help patients to understand how the UniVATS technique developed as part of the evolution of VATS, sharing its benefits and indications. Furthermore, patients would be able to understand technical aspects and the current applications of UniVATS for lung cancer treatment.

Standardized surgical technique for uniportal video-assisted thoracoscopic lobectomy.

SUMMARY: Uniportal video-assisted thoracoscopic surgery may be the approach for any thoracic procedure, from minor resections to complex reconstructive surgery. However, anatomical lobectomy represents its most common and clinically proven usage. A wide variety of information about uniportal video-assisted thoracoscopic lobectomies can be found in the literature and multimedia sources. This article focuses on updating the surgical technique and includes important aspects such as the geometric approach, anaesthesia considerations, operating room set-up, tips about the incision, instrumentation management and the operative technique to perform the 5 lobectomies. The following issues are explained for each lobectomy: anatomical considerations, surgical steps and technical advice. Medical illustrations and videos are included to clarify the text with the goal of describing a standard surgical practice.

Progressive hearing loss in mice with a mutated vitamin D receptor gene.

BACKGROUND: Both hypo- and hypervitaminosis D can cause sensorineural hearing loss, and aural symptoms due to vitamin D insufficiency are especially common during gravidity. Hormonal forms of vitamin D regulate transcription by binding with the high-affinity vitamin D receptor (VDR). OBJECTIVE: To assess the effects of impaired vitamin D action in VDR knockout (KO) mice on hearing, cochlear morphology, and cochlear gene expression. MATERIALS AND METHODS: Eighteen young male and female mice (10 VDR KO and 8 wild type, WT, < or =6 months old), 33 adult male and female mice (16 VDR KO and 17 WT, between 7 and 14 months old), and 11 aged male and female mice (5 VDR KO and 6 WT, > or =15 months old) on 129S1 genetic background were studied. Auditory thresholds were evaluated by auditory brain stem response. Morphological changes were analyzed using plastic embedding and light microscopy. The expression of key genes (known to play a role in the regulation of cochlear function), and caspase 3 activity, were assessed using immunofluorescent confocal microscopy. RESULTS: There was a statistically significant difference between the young and the adult groups, and between the adult and aged groups of WT mice. There was also a statistically significant difference between the adult and aged groups in VDR KO mice, and between the young WT group and the young VDR KO group. Spiral ganglion cell loss was observed in the basal turn of adult VDR KO mice, a phenomenon infrequently found in WT mice. Expression of connexin 26, KCNJ10, and transient receptor potential channel vanilloid subfamily 4/6 was not affected by VDR KO-mediated hearing loss. Caspase 3 activation was detected in the spiral ganglion cell and its satellite cells, stria vascularis, spiral ligament fibrocytes, and the organ of Corti in both genotypes. However, the percentage of positive cells and the staining intensity were lower in the VDR KO (compared to the WT) mice. CONCLUSION: These data suggest that sensorineural hearing loss progressively developed at an earlier age in VDR KO mice. While the fundamental gene expressions in the cochlea were not influenced by VDR mutation, it resulted in decrease of caspase 3 activation, which may be one of the factors underlying accelerating age-related hearing loss observed in VDR KO mice.

Neophobia, sensory and cognitive functions, and hedonic responses in vitamin D receptor mutant mice.

Vitamin D is a seco-steroid hormone with multiple actions in the brain, mediated through the nuclear vitamin D receptor (VDR). We have recently shown that mutant mice lacking functional VDR demonstrate altered emotional behavior and specific motor deficits. Here we further examine phenotype of these mice, testing their novelty responses, as well as cognitive and sensory (olfactory and gustatory) functions in the novel food, two-trial Y-maze and tastant consumption tests. In addition, we study depression-like behavior in these mice, using anhedonia-based sucrose preference test. Overall, VDR mutant mice showed neophobic response in several different tests, but displayed unimpaired olfactory and gustatory functions, spatial memory and baseline hedonic responses. Collectively, these data confirm that mutation of VDR in mice leads to altering emotional/anxiety states, but does not play a major role in depression, as well as in the regulation of some sensory and cognitive processes. These results support the role of the vitamin D/VDR neuroendocrine system in the regulation of behavior, and may have clinical relevance, enabling a better focus on psychiatric and behavioral disorders associated with dysfunctions in this neuroendocrine system.

Aberrant nest building and prolactin secretion in vitamin D receptor mutant mice.

1Alpha,25(OH)2D3, the hormonal form of vitamin D, is a neuroactive seco-steroid hormone with multiple functions in the brain. Most of these effects are mediated through the nuclear vitamin D receptor (VDR), widely distributed in the central nervous system. Our earlier studies showed that mutant mice lacking functional VDR have specific behavioural abnormalities, including anxiety and aberrant maternal behaviour, which may be hormonally regulated. Here we describe impaired nest building behaviour in VDR mutant mice. Since prolactin plays a key role in the regulation of nest building in both sexes, we also examine whether VDR mutant mice have altered prolactin levels. Overall, serum prolactin levels were increased in VDR mutant mice, accompanied by marked impairments in their nest building activity. In contrast, there were no differences in prolactin mRNA expression levels between wildtype control mice and VDR mutant mice. Collectively, these data suggest that partial genetic ablation of VDR affects prolactin system in mice, and that altered serum prolactin levels in VDR mutants may underlie some of their behavioural abnormalities, such as impaired nest building.

Influence of paternal genotypes on F1 behaviors: lessons from several mouse strains.

F1 and F2 mouse hybrids derived from different parental strains are becoming a useful tool in behavioral research, underlining the importance of their in-depth behavioral phenotyping. 129S1/SvImJ (S1), C57BL/6 (B6), NMRI (N) and BALB/c (BC) mice are commonly used in behavioral neuroscience, demonstrating marked behavioral differences. Here, we assess behavioral phenotypes of male mice of S1 and several hybrid strains (S1B6, S1N, S1BC) in a battery of behavioral tests, including the open field, novel odor exposure, novelty-induced grooming, horizontal rod (Suok) and the elevated plus maze tests. In addition, we assessed aggression and social barbering in these strains. Overall, the substantial differences observed here between these strains allow us to determine the influence of different genetic backgrounds on mouse behaviors, and more fully understand how different strain-specific behaviors overlap in the F1 progeny. Our results imply complex interplay between parental genotypes in anxiety, activity, grooming, aggression and barbering of their F1 progeny, further confirming the utility of F1 hybrids in behavioral neurogenetics.

Fístula arteriovenosa pulmonar tratada mediante lobectomía por VATS uniportal / Pulmonary Arteriovenous Fistula Treated by Uniportal VATS Lobectomy

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[Translated article] Pulmonary Arteriovenous Fistula Treated by Uniportal Vats Lobectomy / Fístula arteriovenosa pulmonar tratada mediante lobectomía por VATS uniportal

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Thalamic calcification in vitamin D receptor knockout mice.

Vitamin D is a steroid hormone with many important functions in the brain, mediated through the nuclear vitamin D receptor. Here, we report that aging nuclear vitamin D receptor knockout mice demonstrate a symmetric thalamic calcification with numerous Ca/P-containing laminated bodies. These results are consistent with clinical findings showing brain calcification in patients with vitamin D deficiency. Our results suggest that nuclear vitamin D receptor deficiency leads to brain mineralization in vitamin D receptor knockout mice, which may represent an experimental model of intracranial calcification.

Behavioural anomalies in mice evoked by "Tokyo" disruption of the Vitamin D receptor gene.

Vitamin D is a steroid hormone with many important functions in the brain, mediated through the nuclear Vitamin D receptor (VDR). Mounting clinical data link VDR mutations to various psychiatric phenotypes. We have reported previously that mutant mice lacking functional VDR ("Tokyo" VDR mutant mice) display several behavioural anomalies, including high anxiety and aberrant grooming. Given the important role of Vitamin D and VDR in brain development and functioning, we hypothesized that several other important behavioural domains may be affected by disruption of the VDR gene in mice. Here we report that VDR mutants display unaffected depressive-like behaviour, but show abnormal social behaviours, reduced social barbering and aggressiveness, impaired nest building and aberrant maternal (pup neglect, cannibalism) behaviours. Taken together, these findings confirm the important role postulated for the VDR in the regulation of behaviour, and suggest the mice lacking functional VDR may be a useful tool to model different brain disorders.

Increased severity of chemically induced seizures in mice with partially deleted Vitamin D receptor gene.

Vitamin D is a neuroactive steroid hormone with multiple functions in the brain. Numerous clinical and experimental data link various Vitamin D-related dysfunctions to epilepsy. Here, we study the role of Vitamin D receptors (VDRs) in experimental epilepsy in mice. To examine this problem, we assessed the seizure profiles in VDR knockout mice following a systemic injection of pentylenetetrazole (70 mg/kg). Overall, compared to the wild-type (WT) 129S1 mice (n=10 in each group), the VDR knockout group significantly demonstrated shorter latencies to the onset, higher Racine scores and increased mortality rates. Our findings suggest that VDRs modulate seizure susceptibility in mice, and that the Vitamin D/VDR endocrine system may be involved in the pathogenesis of epilepsy.

Temporal stability of novelty exploration in mice exposed to different open field tests.

We investigated behavioural activity and temporal distribution (patterning) of mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain were subjected in parallel to three different OF arenas (Experiment 1), two different OF arenas in two trials (Experiment 2) or two trials of the same OF test (Experiment 3). Overall, mice demonstrated a high degree of similarity in the temporal profile of novelty-induced horizontal and vertical exploration (regardless of the size, colour and shape of the OF), which remained stable in subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c-S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic background), again showing strikingly similar temporal patterns of their OF exploration, despite marked behavioural strain differences in anxiety and activity. These results suggest that mice are characterised by stability of temporal organization of their exploration in different OF novelty situations.

Behavioural characterization in rats using the elevated alley Suok test.

Exploration of the long elevated alley (the rat Suok test) enables behavioural characterisation of anxiety, activity and neurological phenotypes in rats. Here we show that this new test is sensitive to different types of anxiety in rats, including drugs (pentylenetetrazole)-induced, light-induced and socially induced (encounter with an unfamiliar male) anxiety, as assessed by reduced Suok test horizontal, vertical, directed exploration and stops. High anxiety also leads to higher motor incoordination (as assessed by the number of falls and hind-paw slips), suggesting that this test may be used for combined profiling of anxiety, motor-vestibular anomalies and anxiety-induced motor incoordination in rats. This new behavioural paradigm may be widely used in neurobehavioural stress research, including modelling of stress-evoked states and pharmacological screening of psychotropic drugs.

Anticonvulsant effects of 1,25-dihydroxyvitamin D in chemically induced seizures in mice.

Here, we study the role of a neurosteroid hormone Vitamin D in epilepsy. To examine this problem, we used 1,25-dihydroxyvitamin D, an active form of Vitamin D, injected subcutaneously to NMRI mice (33 microg/20 microl) 40 min prior to seizures induced by systemic injection of pentylenenetrazole (PTZ, 70 mg/kg). Overall, compared to the vehicle-treated control animals (n=11 in each group), the Vitamin D-treated mice demonstrated reduced severity of PTZ-induced seizures (longer latency, shorter duration and lower mortality). In a separate experiment, we assessed the time-course of antiepileptic effects of 1,25-dihydroxyvitamin D. For this, we injected this compound (33 microg/20 microl) to NMRIx129S1 mice (n=11) 40 min, 3, 6, 12 and 24 h prior to seizures, showing that antiepileptic effects were short-term, almost disappearing 3h after administration. Our findings show that Vitamin D plays a direct anticonvulsant role in the brain and suggest that the Vitamin D endocrine system may represent a new target for the development of anticonvulsant drugs.