Therapy free of cells vs human mesenchymal stem cells from umbilical cord stroma to treat the inflammation in OA.

Osteoarthritis (OA) is closely linked to the increase in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) is implicated in cartilage degradation. In the last decade, extracellular vesicles (EV) in combination with the use of miRNAs to modify post-transcriptional expressions of multiple genes have shown their utility in new therapies to treat inflammatory diseases. This work delves into the anti-inflammatory effect of extracellular vesicles derived from mesenchymal stem cells (MSC) previously modified to inhibit the expression of miR-21. We compare the efficacy of two treatments, MSC with their miR-21 inhibited through lentiviral transfection and their EV, against inflammation in a new OA animal model. The modified MSC and their EV were intraperitoneally injected in an OA animal model twice. One month after treatment, we checked which therapy was the most effective to reduce inflammation compared with animals untreated. Treated OA model sera were analyzed for cytokines and chemokines. Subsequently, different organs were analyzed to validate the results obtained. EV were the most effective treatment to reduce chemokines and cytokines in serum of OA animals as well as SASP, in their organs checked by proteomic and genomic techniques, compared with MSC alone in a statistically significant way. In conclusion, MSC-miR-21--derived EV showed a higher therapeutic potential in comparison with MSCs-miR-21-. They ameliorate the systemic inflammation through inactivation of ERK1/2 pathway in OA in vivo model. Workflow of the realization of the animal model of OA by injecting cells into the joint cavity of the left knee of the animals, which produces an increase in serum cytokines and chemokines in the animals in addition to the increase in SASP and markers of inflammation. Inhibition of miR-21 in MSCs, from the stroma of the human umbilical cord, by lentivirus and extraction of their EVs by ultracentrifugation. Finally, application of MSC therapy with its miR-21 inhibited or its EVs produces a decrease in serum cytokines and chemokines in the treated animals, in addition to an increase in SASP and markers of inflammation. The cell-free therapy being the one that produces a greater decrease in the parameters studied.

Acellular nerve graft enriched with mesenchymal stem cells in the transfer of the phrenic nerve to the musculocutaneous nerve in a C5-C6 brachial plexus avulsion in a rat model.

INTRODUCTION: Phrenic nerve transfer has been shown to achieve good nerve regeneration in brachial plexus avulsion. Acellular nerve allografts (ANAs) showed inferior results to autografts, which is why its use with mesenchymal stem cells (MSCs) is currently being studied. The aim is to study the effect of BM-MSCs associated with ANAs in a rat model of phrenic nerve transfer to the musculocutaneous nerve in a C5-C6 avulsion. MATERIAL AND METHODS: 42 Wistar-Lewis rats underwent a C5-C6 lesion in the right forelimb by excising a 3 mm segment from both roots, followed by a phrenic nerve transfer to the musculocutaneous nerve associated with the interposition of a three types of nerve graft (randomly distributed): control (autograft) group (n = 12), ANAs group (n = 12), and ANAs + BM-MSCs group (n = 18) After 12 weeks, amplitude and latency of the NAP and the compound motor action potential (CMAP) were measured. Biceps muscles were studied by histological analysis and nerve grafts by electron microscopy and fluorescence analysis. RESULTS: Statistically significant reductions were found in latency of the CMAP between groups control (2.48 ± 0.47 ms) and experimental (ANAs: 4.38 ± 0.78 ms, ANAs + BM-MSCs: 4.08 ± 0.85 ms) and increases in the amplitude of the CMAP between groups control (0.04388 ± 0.02 V) and ANAs + BM-MSCs (0.02275 ± 0.02 V), as well as in the thickness of the myelin sheath between groups control (0.81 ± 0.07 µm) and experimental (ANAs: 0.72 ± 0.08 µm, ANAs + BM-MSCs: 0.72 ± 0.07 µm) and in the area of the myelin sheath between groups control (13.09 ± 2.67 µm2 ) and ANAs (10.01 ± 2.97 µm2 ) (p < .05). No statistically significant differences have been found between groups ANAs and ANAs + BM-MSCs. CONCLUSIONS: This study presents a model for the study of lesions of the upper trunk and validates the autologous graft as the gold standard.

The addition of albumin improves Schwann cells viability in nerve cryopreservation.

The purpose of the current study was to establish a valid protocol for nerve cryopreservation, and to evaluate if the addition of albumin supposed any advantage in the procedure. We compared a traditional cryopreservation method that uses dimethyl sulfoxide (DMSO) as cryoprotectant, to an alternative method that uses DMSO and albumin. Six Wistar Lewis rats were used to obtain twelve 20 mm fragments of sciatic nerve. In the first group, six fragments were cryopreserved in 199 media with 10% DMSO, with a temperature decreasing rate of 1 °C per minute. In the second group, six fragments were cryopreserved adding 4% human albumin. The unfreezing process consisted of sequential washings with saline in the first group, and saline and 20% albumin in the second group at 37 °C until the crioprotectant was removed. Structural evaluation was performed through histological analysis and electronic microscopy. The viability was assessed with the calcein-AM (CAM) and 4',6-diamino-2-fenilindol (DAPI) staining. Histological results showed a correct preservation of peripheral nerve architecture and no significant differences were found between the two groups. However, Schwann cells viability showed in the CAM-DAPI staining was significantly superior in the albumin group. The viability of Schwann cells was significantly increased when albumin was added to the nerve cryopreservation protocol. However, no significant structural differences were found between groups. Further studies need to be performed to assess the cryopreserved nerve functionality using this new method.

Connective tissue amyloidosis in patients referred for orthopedic surgery. CONNECT-AMY study. / Amiloidosis del tejido conectivo en pacientes referidos a cirugía ortopédica. Estudio CONNECT-AMY.

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

Action Mechanisms of Small Extracellular Vesicles in Inflammaging.

The accumulation process of proinflammatory components in the body due to aging influences intercellular communication and is known as inflammaging. This biological mechanism relates the development of inflammation to the aging process. Recently, it has been reported that small extracellular vesicles (sEVs) are mediators in the transmission of paracrine senescence involved in inflammatory aging. For this reason, their components, as well as mechanisms of action of sEVs, are relevant to develop a new therapy called senodrugs (senolytics and senomorphic) that regulates the intercellular communication of inflammaging. In this review, we include the most recent and relevant studies on the role of sEVs in the inflammatory aging process and in age-related diseases such as cancer and type 2 diabetes.

A Comparative Study of Doppler Ultrasound against Temporal Artery Biopsy in the Diagnosis of Giant Cell Arteritis. / Estudio comparativo de la ecografía Doppler frente a la biopsia de arteria temporal en el diagnóstico de la arteritis de células gigantes.

BACKGROUND: Giant cell arteritis (GCA) is a vasculitis that affects medium- and large-sized arteries. Temporal artery biopsy is the gold standard for diagnosis. In view of the high demand for temporal biopsies, the purpose of this study is to evaluate the usefulness of Doppler ultrasonography in patients with suspected giant cell arteritis, to determine its sensitivity and specificity as a diagnostic test and to determine whether it would be possible to substitute biopsy for ultrasonography. MATERIALS AND METHODS: A prospective study was undertaken including 57 patients from February 2015 to July 2016, who have undergone both ultrasonography and temporal biopsy. RESULTS: A total of 57 patients were included, 3of whom died during the follow-up, and a patient was excluded from the study when she refused to have the biopsy. Another 21 patients were diagnosed with GCA by a rheumatologist after a minimum of 6 months of follow-up and 22 patients had positive ultrasonography, 8 of whom were diagnosed with GCA and 4 with polymyalgia rheumatica. In our study, the sensitivity of ultrasonography was 42.6%, and the specificity was 65.7%. A total of 19 patients had a positive biopsy, all of them were diagnosed with GCA. In our study, the sensitivity of the biopsy was 73.7% and the specificity was 100%. CONCLUSIONS: In view of the data from our study, the usefulness of ultrasonography is questionable, and research about the role of ultrasonography in this disease should be further studied.

EHTIC study: Evaluation of a new hemostatic agent based on tissue factor in skin grafting procedures.

BACKGROUND: Excessive bleeding is a major concern in scar debridement and grafting procedures. TT-173 is a new topical hemostatic agent based on recombinant human tissue factor that has shown promising results in patients who underwent tooth extraction. EHTIC study sought to evaluate the efficacy and safety of TT-173 to reduce the bleeding in donor sites of skin grafting procedures. METHODS: EHTIC study was a phase II, randomized, parallel, double blind, placebo controlled trial. Patients received TT-173 (n=38) or placebo (n=33) sprayed over donor site after graft harvest. Time to hemostasis and incidence of adverse events were recorded. Systemic absorption of the product and its immunogenicity were also measured during the follow up of the subjects. RESULTS: Treatment with TT-173 significantly reduced the bleeding time from 7 to 3min (Log-Rank p<0.0001). Moreover, bleeding stopped within the 10min of evaluation period in all the patients that received TT-173. In contrast, 24.24% of patients from placebo group required additional measures to arrest hemorrhage (Fisher p=0.0013). Product related adverse events, systemic absorption into blood stream, interferences with the healing of the donor site or immunogenic reaction against TT-173 were not observed. CONCLUSION: The new hemostatic agent TT-173 has proven efficacious and safe to reduce the bleeding from donor site. This study paves the way for further investigation of the product as topical hemostatic treatment in plastic surgery and other surgical indications.

Intraneural Venous Malformations of the Median Nerve.

Venous malformations arising from the peripheral nerve are a rare type of vascular malformation. We present the first case of an intraneural venous malformation of the median nerve to be reported in a child and review the previous two cases of median nerve compression due to a venous malformation that have been reported. These cases presented with painless masses in the volar aspect of the wrist or with symptoms suggestive of carpal tunnel syndrome. Clinical suspicion should lead to the use of Doppler ultrasonography as the first-line diagnostic tool. Magnetic resonance imaging and histopathology can confirm the diagnosis, as phleboliths are pathognomonic of venous malformations. Surgical treatment appears to be the only modality capable of successfully controlling the growth of an intraneural malformation. Sclerotherapy and radiotherapy have never been used to treat this type of malformation.

Burn patients during the Summer Solstice festivities: A retrospective analysis in a hospital burn unit from 2005 to 2015.

AIM: San Juan (Summer Solstice) is an annual festival celebrated in many parts of Spain on June 24 by lighting bonfires on beaches and in open air. The aim of this study is to analyse the patient profile of those sustaining burns the night before San Juan. MATERIAL AND METHODS: The data of 179 patients who sustained burns on June 23 and 24 between 2005 and 2015 were collected retrospectively. RESULTS: The average age of the patients involved in this study was 27.33 years, with males constituting a higher proportion. Hands were the most affected area of the body, and the average burn area was 3.39%. No statistically significant relationship was found between the tidal times and the number of patients with burns, although the latter increased at low tide (p=0.177). CONCLUSIONS: The results of this study can guide prevention campaigns during these festivities in the future.