Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol.

Injuries to the peripheral nerves represent a frequent cause of permanent disability in adults. The repair of large nerve lesions involves the use of autografts, but they have several inherent limitations. Overcoming these limitations, the use of decellularized nerve matrix has emerged as a promising treatment in tissue regenerative medicine. Here, we generate longer human decellularized nerve segments with a novel decellularization method, using nonionic, zwitterionic, and enzymatic incubations. Efficiency of decellularization was measured by DNA quantification and cell remnant analysis (myelin, S100, neurofilament). The evaluation of the extracellular matrix (collagen, laminin, and glycosaminoglycans) preservation was carried out by enzyme-linked immunosorbent assay (ELISA) or biochemical methods, along with histological and immunofluorescence analysis. Moreover, biomechanical properties and cytocompatibility were tested. Results showed that the decellularized nerves generated with this protocol have a concentration of DNA below the threshold of 50 ng/mg of dry tissue. Furthermore, myelin, S100, and MHCII proteins were absent, although some neurofilament remnants could be observed. Moreover, extracellular matrix proteins were well maintained, as well as the biomechanical properties, and the decellularized nerve matrix did not generate cytotoxicity. These results show that our method is effective for the generation of decellularized human nerve grafts. The generation of longer decellularized nerve segments would allow the understanding of the regenerative neurobiology after nerve injuries in both clinical assays and bigger animal models. Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol. Combination of zwitterionic, non-ionic detergents, hyperosmotic solution and nuclease enzyme treatment remove cell remnants, maintain collagen, laminin and biomechanics without generating cytotoxic leachables.

Population data of 23 STR loci (PowerPlex® Fusion System) in Mexican Mestizos from the West Region.

We analyzed 238 unrelated Mestizo (admixed) individuals from the West region of Mexico with the PowerPlex® Fusion System (Promega Corp.). Allele frequencies and forensic parameters were estimated for the 23 STRs included in this kit. Hardy-Weinberg equilibrium by locus and non-association between pair of loci were demonstrated by exact tests in this population. The combined PE and PD offered by this HID kit were ≥0.9999999986, representing a substantial improvement with respect to those previously offered by 15 STR systems. Interpopulation comparison by AMOVA tests demonstrated low but significant differences among Mexican Mestizos from West, Center, and Northeast regions (Fst = 0.01558; p = 0.0000), similar to the observed among three main ethnic groups from USA (Fst = 0.02048; p = 0.0000). This finding is consistent with the contrary clines of European and Amerindian ancestries described throughout the Mexican territory for Mestizos, the largest population (~90 %) in this country.

Reliability and accuracy of quantitative sensory testing for oxaliplatin-induced neurotoxicity.

OBJECTIVES: Thermal quantitative sensory testing (QST) is a non-invasive procedure helpful in the assessment of the function of small Aδ and C nerve sensory fibres. Oxaliplatin (OXA) is an effective chemotherapeutic agent, but is frequently associated with neurotoxic dose-limiting side effects. This controlled clinical trial evaluated the reliability and accuracy of thermal QST for assessing the OXA-induced acute neuropathic syndrome, whose clinical hallmark is cold-triggered painful paraesthesia. MATERIALS & METHODS: A testing protocol with the Thermal Sensory Analyzer (Medoc) was carried out in 20 colorectal cancer patients during the initial four cycles of OXA-based chemotherapy and in 20 age- and sex-matched healthy volunteers. Testing was carried out on the hands and included the determination of thermal detection and pain thresholds and the intensity of pain evoked by cold stimuli. Calculations were made of: coefficients of test-retest and inter-rater reliability, indices of responsiveness and parameters that quantify diagnostic accuracy. RESULTS: Thermal thresholds showed moderate to good reliability (ρ ≥ 0.383), but were not consistently responsive to the effects of chemotherapy (cold pain thresholds decreased in both groups, although almost twice in patients compared to healthy volunteers). Conversely, the intensity of pain evoked by suprathreshold cold stimuli was reliable (ρ ≥ 0.822), responsive (detected changes over time) and discriminated between patients and healthy volunteers (area under the ROC curve = 0.700). CONCLUSIONS: The procedure was reliable and accurate to evaluate cold hyperalgesia resulting from OXA administration. The data provided may be used to define efficacy endpoints for future clinical trials of therapies for OXA-induced neuropathies and calculate appropriate sample sizes.

Tubulization with chitosan guides for the repair of long gap peripheral nerve injury in the rat.

Biosynthetic guides can be an alternative to nerve grafts for reconstructing severely injured peripheral nerves. The aim of this study was to evaluate the regenerative capability of chitosan tubes to bridge critical nerve gaps (15 mm long) in the rat sciatic nerve compared with silicone (SIL) tubes and nerve autografts (AGs). A total of 28 Wistar Hannover rats were randomly distributed into four groups (n = 7 each), in which the nerve was repaired by SIL tube, chitosan guides of low (∼2%, DAI) and medium (∼5%, DAII) degree of acetylation, and AG. Electrophysiological and algesimetry tests were performed serially along 4 months follow-up, and histomorphometric analysis was performed at the end of the study. Both groups with chitosan tubes showed similar degree of functional recovery, and similar number of myelinated nerve fibers at mid tube after 4 months of implantation. The results with chitosan tubes were significantly better compared to SIL tubes (P < 0.01), but lower than with AG (P < 0.01). In contrast to AG, in which all the rats had effective regeneration and target reinnervation, chitosan tubes from DAI and DAII achieved 43 and 57% success, respectively, whereas regeneration failed in all the animals repaired with SIL tubes. This study suggests that chitosan guides are promising conduits to construct artificial nerve grafts.

Peripheral nerve alterations after spinal cord injury in the adult rat.

OBJECTIVE: To assess if spinal cord injury (SCI) can produce alterations in axons of peripheral nerves emerging caudal to the injury. METHODS: Mild/severe contusion or complete transection was performed at T8 in adult rats. The function and morphology of the sciatic nerve were assessed 3 months after the lesion. RESULTS: There was a decrease in the amplitudes of muscle responses in nerve conduction tests. The number of myelinated fibers was maintained, but some of them presented structural abnormalities. CONCLUSION: SCIs cause alterations in peripheral axons not affected by the injury. Preservation of the peripheral components is essential for potential regenerative and rehabilitation therapies. Thus, special care has to be taken to avoid secondary complications, due to compressions or immobility, in SCI humans.

Aberrant perineuronal nets alter spinal circuits, impair motor function, and increase plasticity.

Perineuronal nets (PNNs) are a specialized extracellular matrix that have been extensively studied in the brain. Cortical PNNs are implicated in synaptic stabilization, plasticity inhibition, neuroprotection, and ionic buffering. However, the role of spinal PNNs, mainly found around motoneurons, is still unclear. Thus, the goal of this study is to elucidate the role of spinal PNNs on motor function and plasticity in both intact and spinal cord injured mice. We used transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice), which is implicated in PNN assembly. Crtl1 KO mice showed disorganized PNNs with an altered proportion of their components in both motor cortex and spinal cord. Behavioral and electrophysiological tests revealed motor impairments and hyperexcitability of spinal reflexes in Crtl1 KO compared to WT mice. These functional outcomes were accompanied by an increase in excitatory synapses around spinal motoneurons. Moreover, following spinal lesions of the corticospinal tract, Crtl1 KO mice showed increased contralateral sprouting compared to WT mice. Altogether, the lack of Crtl1 generates aberrant PNNs that alter excitatory synapses and change the physiological properties of motoneurons, overall altering spinal circuits and producing motor impairment. This disorganization generates a permissive scenario for contralateral axons to sprout after injury.

Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration.

Efficient transduction of the peripheral nervous system (PNS) is required for gene therapy of acquired and inherited neuropathies, neuromuscular diseases and for pain treatment. We have characterized the tropism and transduction efficiency of different adeno-associated vectors (AAV) pseudotypes after sciatic nerve injection in the mouse. Among the pseudotypes tested, AAV2/1 transduced both Schwann cells and neurons, AAV2/2 infected only sensory neurons and AAV2/8 preferentially transduced Schwann cells. AAV2/8 expression in the sciatic nerve was detected up to 10 weeks after administration, the latest time point analyzed. The injected mice developed neutralizing antibodies against all AAVs tested; the titers were higher against AAV2/1 than AAV2/2 and were the lowest for AAV2/8, correlating with a higher transgene expression overtime. AAV2/8 coding for ciliary neurotrophic factor (CNTF) led to an upregulation of P0 and PMP22 myelin proteins, four weeks after transduction of injured sciatic nerves. Importantly, CNTF-transduced mice showed a significant increase in both GAP43 expression in sensory neurons, a marker of axonal regeneration, and the compound muscle action potential. These results prove the utility of AAV8 as a gene therapy vector for Schwann cells to treat myelin disorders or to improve nerve regeneration.

Efalizumab treatment of psoriasis vulgaris: a cohort study in outpatient clinical practice.

BACKGROUND: Efalizumab is approved by the European Medicines Evaluation Agency for the treatment of adult patients with moderate to severe plaque psoriasis who fail to respond to, have a contraindication for, or cannot tolerate other systemic therapies. OBJECTIVES: To evaluate the efficacy and safety of efalizumab treatment in daily practice at a dermatology department in a teaching hospital in Barcelona, Spain. METHODS: A cohort study was carried out for patients treated with efalizumab for at least 3 months between May 2005 and July 2007. In total, 31 patients [21 men, 10 women; mean psoriasis and severity index (PASI) 12.9] were treated with efalizumab. Data were collected prospectively, including PASI, and recorded at the start of treatment and at follow-up visits with a frequency of at least every 3 months. RESULTS: At the end of the study period, efalizumab treatment was ongoing in 18 of the 31 patients (58.1%), and 7 of these patients had been treated for > or = 24 months. At week 12, 67.7% of the patients treated with efalizumab had achieved an improvement of 50% in PASI (PASI 50), 41.9% reached PASI 75, and 16.1% reached PASI 90 (intention to treat and as-treated analyses). In all, 19 patients (61.3%) received treatment for > or = 24 weeks. At week 24, 89.5% of these patients reached PASI 75, and 26.3% reached PASI 90 (as-treated analysis). During efalizumab treatment, mainly mild adverse effects were reported, including transient papular or circinate exacerbations of psoriasis, which were seen in five patients (16.1%). Rebounds (defined as PASI > or = 125% of baseline, leading to erythroderma in two patients) occurred in 7/31 patients (22.6%); this occurred while on treatment in 5/11 nonresponding patients (45.5%) and after discontinuation of treatment in 2/20 patients with good response (10.0%). CONCLUSION: Efalizumab is an effective and safe treatment for psoriasis in most patients of a high need population in routine practice, and provides maintained improvement in 'responders'. Combination treatment was transiently used in 48.4% of patients to optimize therapeutic results. Special consideration must be given to possible rebound in patients with an inadequate response or after discontinuation of treatment.

Neural plasticity after peripheral nerve injury and regeneration.

Injuries to the peripheral nerves result in partial or total loss of motor, sensory and autonomic functions conveyed by the lesioned nerves to the denervated segments of the body, due to the interruption of axons continuity, degeneration of nerve fibers distal to the lesion and eventual death of axotomized neurons. Injuries to the peripheral nervous system may thus result in considerable disability. After axotomy, neuronal phenotype switches from a transmitter to a regenerative state, inducing the down- and up-regulation of numerous cellular components as well as the synthesis de novo of some molecules normally not expressed in adult neurons. These changes in gene expression activate and regulate the pathways responsible for neuronal survival and axonal regeneration. Functional deficits caused by nerve injuries can be compensated by three neural mechanisms: the reinnervation of denervated targets by regeneration of injured axons, the reinnervation by collateral branching of undamaged axons, and the remodeling of nervous system circuitry related to the lost functions. Plasticity of central connections may compensate functionally for the lack of specificity in target reinnervation; plasticity in human has, however, limited effects on disturbed sensory localization or fine motor control after injuries, and may even result in maladaptive changes, such as neuropathic pain, hyperreflexia and dystonia. Recent research has uncovered that peripheral nerve injuries induce a concurrent cascade of events, at the systemic, cellular and molecular levels, initiated by the nerve injury and progressing throughout plastic changes at the spinal cord, brainstem relay nuclei, thalamus and brain cortex. Mechanisms for these changes are ubiquitous in central substrates and include neurochemical changes, functional alterations of excitatory and inhibitory connections, atrophy and degeneration of normal substrates, sprouting of new connections, and reorganization of somatosensory and motor maps. An important direction for ongoing research is the development of therapeutic strategies that enhance axonal regeneration, promote selective target reinnervation, but are also able to modulate central nervous system reorganization, amplifying those positive adaptive changes that help to improve functional recovery but also diminishing undesirable consequences.

Spanish Consensus Document on the Treatment Algorithm for Rosacea. / Documento de consenso español para el algoritmo de tratamiento de la rosácea.

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea.

Analysis of FK506-mediated protection in an organotypic model of spinal cord damage: heat shock protein 70 levels are modulated in microglial cells.

Functional loss after spinal cord injuries is originated by primary and secondary injury phases whose underlying mechanisms include massive release of excitatory amino acids to cytotoxic levels that contribute to neural death. Attenuation of this excitotoxicity is a key point for improving the functional outcome after injury. One of the drugs with potential neuroprotective actions is FK506, a molecule widely used as an immunosuppressant. FK506 may exert neuroprotection via inhibition of calcineurin by binding the FKBP12, or by binding other immunophilins such as FKBP52, leading to modulation of heat shock proteins (Hsp) 90 and 70. In the present study, we used an in vitro model of organotypic culture of rat spinal cord slices to assess whether FK506 is able to protect them against glutamate excitotoxicity. The results showed that FK506 promoted a significant protective effect on the spinal cord tissue at concentrations of 50 and 100 nM. Hsp70 induction was restricted to microglial cells in spinal cord slices treated with either glutamate or FK506. In contrast, the combination of both agents led to a transient reduction in Hsp70 levels in parallel to a marked reduction in IL-1beta precursor production by glial cells. The use of geldanamycin, which promotes persistent induction of Hsp70 in these cells as well as in motoneurons, did not produce tissue neuroprotection. These observations suggest that FK506 might protect spinal cord tissue by targeting on microglial cells and that transient downregulation of Hsp70 on these cells after excitotoxicity is a relevant mechanism of action of FK506.

[Tacrolimus in diseases other than atopic dermatitis]. / Tacrolimus en enfermedades diferentes a la dermatitis atópica.

Topical tacrolimus is an immunosuppressant that acts through the inhibition of calcineurin and thus of the T cells. This causes a decrease in the production of interleukins, the granulocyte colony stimulating factor, alpha interferon and tumor necrosis factor. Although the use of topical tacrolimus is only indicated for the treatment of moderate or severe atopic dermatitis, its immunosuppressant effect and fewer side effects regarding topical corticosteroids have lead to the increase of its use in other types of inflammatory skin diseases. The purpose of this article is to review the use of tacrolimus in this group of diseases other than atopic dermatitis, this use not being authorized within the data sheet of the drug.

Paternity tests in Mexico: Results obtained in 3005 cases.

National and international reports regarding the paternity testing activity scarcely include information from Mexico and other Latin American countries. Therefore, we report different results from the analysis of 3005 paternity cases analyzed during a period of five years in a Mexican paternity testing laboratory. Motherless tests were the most frequent (77.27%), followed by trio cases (20.70%); the remaining 2.04% included different cases of kinship reconstruction. The paternity exclusion rate was 29.58%, higher but into the range reported by the American Association of Blood Banks (average 24.12%). We detected 65 mutations, most of them involving one-step (93.8% and the remaining were two-step mutations (6.2%) thus, we were able to estimate the paternal mutation rate for 17 different STR loci: 0.0018 (95% CI 0.0005-0.0047). Five triallelic patterns and 12 suspected null alleles were detected during this period; however, re-amplification of these samples with a different Human Identification (HID) kit confirmed the homozygous genotypes, which suggests that most of these exclusions actually are one-step mutations. HID kits with ≥20 STRs detected more exclusions, diminishing the rate of inconclusive results with isolated exclusions (<3 loci), and leading to higher paternity indexes (PI). However, the Powerplex 21 kit (20 STRs) and Powerplex Fusion kit (22 STRs) offered similar PI (p = 0.379) and average number of exclusions (PE) (p = 0.339) when a daughter was involved in motherless tests. In brief, besides to report forensic parameters from paternity tests in Mexico, results describe improvements to solve motherless paternity tests using HID kits with ≥20 STRs instead of one including 15 STRs.

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Influence of the substrate's hydrophilicity on the in vitro Schwann cells viability.

A series of polymeric biomaterials including poly (methyl acrylate) (PMA), chitosan (CHT), poly(ethyl acrylate) (PEA), poly(hydroxyethyl acrylate) (PHEA), and a series of random copolymers containing ethyl acrylate and hydroxyethyl acrylate monomeric units were tested in vitro as culture substrates and compared for their impact on the proliferation and expansion of Schwann cells (SCs). Immunocytochemical staining assay and scanning electron microscopy techniques were applied to perform a quantitative analysis to determine the correct maintenance of the cultured glial cells on the different biomaterials. The results strongly suggest that cell attachment and proliferation is influenced by the substrate's surface chemistry, and that hydrophobic biomaterials based on PMA, PEA, and the copolymers PEA and PHEA in a narrow composition window are suitable substrates to promote cell attachment and proliferation of SCs in vitro.

Multi-feature classifiers for burst detection in single EEG channels from preterm infants.

OBJECTIVE: The study of electroencephalographic (EEG) bursts in preterm infants provides valuable information about maturation or prognostication after perinatal asphyxia. Over the last two decades, a number of works proposed algorithms to automatically detect EEG bursts in preterm infants, but they were designed for populations under 35 weeks of post menstrual age (PMA). However, as the brain activity evolves rapidly during postnatal life, these solutions might be under-performing with increasing PMA. In this work we focused on preterm infants reaching term ages (PMA ⩾36 weeks) using multi-feature classification on a single EEG channel. APPROACH: Five EEG burst detectors relying on different machine learning approaches were compared: logistic regression (LR), linear discriminant analysis (LDA), k-nearest neighbors (kNN), support vector machines (SVM) and thresholding (Th). Classifiers were trained by visually labeled EEG recordings from 14 very preterm infants (born after 28 weeks of gestation) with 36-41 weeks PMA. MAIN RESULTS: The most performing classifiers reached about 95% accuracy (kNN, SVM and LR) whereas Th obtained 84%. Compared to human-automatic agreements, LR provided the highest scores (Cohen's kappa = 0.71) using only three EEG features. Applying this classifier in an unlabeled database of 21 infants ⩾36 weeks PMA, we found that long EEG bursts and short inter-burst periods are characteristic of infants with the highest PMA and weights. SIGNIFICANCE: In view of these results, LR-based burst detection could be a suitable tool to study maturation in monitoring or portable devices using a single EEG channel.