Transplanting Microglia for Treating CNS Injuries and Neurological Diseases and Disorders, and Prospects for Generating Exogenic Microglia.

Microglia are associated with a wide range of both neuroprotective and neuroinflammatory functions in the central nervous system (CNS) during development and throughout lifespan. Chronically activated and dysfunctional microglia are found in many diseases and disorders, such as Alzheimer's disease, Parkinson's disease, and CNS-related injuries, and can accelerate or worsen the condition. Transplantation studies designed to replace and supplement dysfunctional microglia with healthy microglia offer a promising strategy for addressing microglia-mediated neuroinflammation and pathologies. This review will cover microglial involvement in neurological diseases and disorders and CNS-related injuries, current microglial transplantation strategies, and different approaches and considerations for generating exogenic microglia.

Reconstrucción mamaria diferida con expansor-implante y matriz dérmica autóloga. Una alternativa terapéutica aplicable en tejidos no irradiados. / Delayed breast reconstruction with expander-implant and autologous dermal matrix. An alternative applicable therapeutic in non irradiated tissues.

INTRODUCCIÓN Y OBJETIVO: la reconstrucción mamaria diferida o post mastectomía tiene una importancia trascendental en la vida de la mujer así también como parte del tratamiento integral y multidisciplinario del cáncer mamario, ya que tamaña agresión impacta en la autoestima y funcionalidad social en aquellas mujeres que por algún motivo no fueron sometidas a reconstrucción inmediata. El objetivo es describir a través de la técnica expansor-implante, matriz dérmica autóloga, injerto de grasa y reconstrucción del complejo areola pezón con tejidos autólogos, los resultados alcanzados en pacientes mastectomizadas y reconstruidas de manera diferida. MATERIAL Y MÉTODO: es un estudio retrospectivo, longitudinal, observacional y descriptivo de una serie pequeña de 5 pacientes privadas mastectomizadas no irradiadas que no fueron sometidas por algún motivo a reconstrucción inmediata en otros centros médicos y que acudieron al consultorio privado derivadas por médicos cirujanos mastólogos-oncólogos para ser sometidas en forma diferida a reconstrucción con expansor implante en una secuencia técnica de 3 tiempos quirúrgicos en un periodo comprendido entre abril del 2015 y octubre del 2020. RESULTADOS: la reconstrucción diferida habitualmente la realizamos con expansor-implante y optamos por la utilización de colgajos autólogos siempre cuando se hubiera irradiado la mama enferma. En 4 de 5 pacientes realizamos la reconstrucción del complejo areola pezón (CAP), 3 pacientes fueron de reconstrucción unilateral y 2 de bilateral, en 2 mujeres ocupamos prótesis de doble lumen tipo anatómicos y en 3 mujeres expansor con puerto a distancia, utilizando en 2 pacientes, prótesis de forma redonda y en un implante expansor anatómico. Presentamos un caso de deflación del implante a los 3 años post reconstrucción no reportamos casos de necrosis grasa, ni cuadros infecciosos, no presentamos casos de contractura capsular y reportamos un solo caso de seroma tardío de origen traumático en una paciente de reconstrucción unilateral a los 7 meses post implante. CONCLUSIÓN: la técnica reconstructiva diferida de expansor-implante, matriz dérmica autóloga, y tejidos propios para la reconstrucción del CAP, representan una buena opción terapéutica de baja morbilidad en pacientes que no han sido sometidas a irradiación post mastectomía. Creemos que a nivel nacional aún faltan políticas en salud y conductas que beneficien a las mujeres con cáncer mamario en el camino largo del tratamiento integral de la enfermedad hasta la reconstrucción mamaria y su re inserción con funcionalidad social, laboral y emocional, para unificar criterios y protocolos entre servicios públicos, privados, ministerio de salud, secretarias regionales de salud y sociedades científicas de Mastologia y Cirugía Plástica apoyando a los pocos equipos en reconstrucción mamaria , optimizando protocolos médicos que beneficien a las pacientes enfermos.

INTRODUCTION AND OBJECTIVE: delayed breast reconstruction or post mastectomy has a transcendental importance in women ́s life as well as part of the comprehensive and multidisciplinary treatment of breast cancer. Such aggression impacts on self-esteem and social functionality in women who for some reason were not undergoing immediate reconstruction. The objective is to describe the results achieved in mastectomized patients, through the expander-implant technique, autologous dermal matrix, fat graft and reconstruction of the nipple areola complex (NAC) with autologous tissues MATERIAL AND METHOD: it is a retrospective, longitudinal, observational and descriptive study of a small group of 5 non-irradiated mastectomized private patients who were not subjected to an immediate reconstruction at other medical centers. They came to the private practice referred by other mastologists-oncologists medical surgeons to be submitted to a delayed breast reconstruction with expander prosthesis in a 3 surgical times technique between April 2015 and October 2018. RESULTS: the delayed breast reconstruction is usually performed with expander prosthesis and for those injured breasts that had been irradiated, we use autologous flaps. In 4 out of 5 patients we performed the reconstruction of the NAC, 3 were submitted to unilateral reconstruction and 2 were bilateral, 2 women had anatomical double lumen prosthesis, 3 had expander implant with remote port at which 2 were round and one anatomical. We presented only one case of deflation 3 years later after reconstruction. We didn ́t report cases of fat necrosis nor infectious symptoms. We didn ́t have any case of capsular contracture but only a single case of late seroma after 7 months' post implant in a patient with unilateral reconstruction due to a traumatic incident. CONCLUSION: the delayed breast reconstructive technique with expander-implant, uses of autologous dermal matrix or own tissues for reconstructing the NAC, represents a good therapeutic option of low morbidity to patients who have not undergone post-mastectomy irradiation. We briefly believe that at a National level there is a lack of health policies and therapeutic behaviors that could benefit women with breast cancer on this long path from a complete treatment of this disease to breast reconstruction and its social, labor and emotional reintegration, to unify criteria and protocols between public services, private services, ministry of health, regional secretaries of health and scientific societies such as Mastology and Plastic Surgery to support the few teams in breast reconstruction and optimize medical protocols to benefits the sick patient.

Creatine Supply Attenuates Ischemia-Reperfusion Injury in Lung Transplantation in Rats.

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Nódulo proliferativo en nevus melanocítico congénito gigante / Proliferative nodule in giant congenital melanocytic nevus

El nevus melanocítico gigante es una entidad poco frecuente. En los primeros meses o años de vida, pueden aparecer nódulos dérmicos pequeños o grandes, muy pigmentados, que pueden crecer rápidamente o incluso ulcerarse. Esto obliga a realizar diagnóstico diferencial con el melanoma. Se presenta el caso de una paciente de 3 años de edad, con gran lesión pigmentada en pierna izquierda, con nódulos de rápido crecimiento, compatibles con nódulo proliferativo.

Giant melanocytic nevi are rare. In the fi rst few months or even years of life, they may develop small or large dermic nodules, very pigmented, with rapid growth o even ulcer formation. This forces the diff erential diagnosis with melanoma. We present a case of a 3 year old female patient, with a large pigmented lesion on the left leg, with nodules compatible with proliferative nodules.

Evaluación de la calidad de vida relacionada con la salud pre y post trasplante hepático, en pacientes de un hospital de alta complejidad / Health- related quality of life evaluation pre and post liver transplant in patients of a high complexity hospital

Resumen El trasplante hepático es la alternativa terapéutica indicada en pacientes con enfermedad hepática terminal para mejorar su sobrevida y calidad de vida. El objetivo de este estudio fue evaluar la calidad de vida relacionada con la salud (CVRS) de pacientes con cirrosis hepática antes y después de trasplante hepático. Se incluyeron 33 personas adultas que estaban en lista de espera para trasplante en la institución, se aplicó una serie de cuestionarios antes y después del trasplante: para evaluar la calidad de vida se utilizaron el LDQOL-1 (específico para enfermedad y trasplante hepático) y SF36 (para población general); para evaluar los síntomas depresivos y ansiosos, se utilizaron el BDI y STAI, respectivamente. Los resultados señalan una mejoría en la CVRS, así como disminución de los síntomas ansiosos y depresivos posterior al trasplante.

Abstract Liver transplantation is the therapeutic intervention of choice in patients with terminal liver disease to improve survival rate and quality of life. The aim of this study was to assess health related quality of life (HRQOL) in liver cirrhosis patients before and after liver transplantation. Thirty-three patients in waiting list for transplant in the institution were included; some questionnaires were applied before and after transplantation: to assess HRQOL were used LDQOL-1 (specific for liver disease and transplant) and SF36 (for general population); to assess depressive and anxious symptoms, BDI and STAI were used, respectively. Results showed an improvement in HRQOL and reduction in depressive and anxious symptoms after transplantation.

Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospective evaluation.

OBJECTIVE: To evaluate the potential benefit of an intact fish skin graft rich in omega-3 (Kerecis Omega3), in the management of postoperative diabetic foot wounds. METHOD: Prospective evaluation in eight patients with diabetes following forefoot surgery. The dressing was applied weekly for a period of six weeks in the diabetic foot clinic. At each visit the wound was photographed and independently measured using ImageJ software to calculate wound area. Secondary outcome measures were pain, infection, odour, discharge and irritation. RESULTS: The wound area range was 0.94 to 29.55cm². In wounds of less than three months duration, regardless of size, the median percentage wound area reduction was over 84.9% at six weeks (n=6, range: 71.3 to 100%). There were two wounds over three months duration, in these the wound area reduction was <42% at six weeks (n=2, range: 41.2 to 41.1%). No patients developed infection or skin reactions. None reported odour, discharge or itching. CONCLUSION: Our initial results demonstrate that the trend towards healing is more marked in wounds less than three months duration. This would suggest that the fish skin graft has potential to decrease time to healing in this patient group when used early on in the healing process, perhaps as a routine adjunct to postoperative diabetic foot wound management. CONCLUSION: Postoperative diabetic foot wounds are difficult to heal. In this series, fish skin grafts show promise as an agent to accelerate wound healing. We suggest larger randomised trials to further evaluate its use in acute and chronic wounds.

Vitamin D deficiency in solid-organ transplant recipients from a Spanish Mediterranean population.

BACKGROUND: Solid-organ transplant recipients (SOTRs) are at risk of developing vitamin D deficiency, mainly caused by reduced sunlight exposure with subsequent low vitamin D synthesis in the skin. AIM: To analyse whether SOTRs from a Spanish Mediterranean region were vitamin D-deficient. METHODS: This was a cross-sectional, descriptive and observational study in a transplantation-specialized Dermatological Unit from a Mediterranean area to determine the calcidiol levels of a cohort of 78 consecutively attending patients not receiving vitamin D supplements. Serum 25(OH)D3 levels were determined and clinical characteristics were collected. Logistic regression analysis was used to analyse variables associated with dichotomized 25(OH)D3 levels (≤ or > 10 ng/mL). RESULTS: The cohort comprised 30 lung, 29 kidney and 19 liver transplant recipients. Mean calcidiol was 18 ± 9 ng/mL. Deficiency of 25(OH)D3 was present in 19% of patients, while 68% had insufficient levels and 13% had sufficient levels. Following multivariate logistic regression analysis, the season of blood sampling remained the only predictor of deficient 25(OH)D3 levels. CONCLUSION: Despite living in a mid-latitude country with sunny weather, our SOTR population was at high risk of developing hypovitaminosis D, especially in autumn/winter. Avoiding sun exposure is important to prevent skin cancer, but careful monitoring of vitamin D status is recommended, with supplementation if hypovitaminosis D is detected.

Arteriovenous Graft for Hemodialysis: Effect of Cryotherapy on Postoperative Pain and Edema.

BACKGROUND: Arteriovenous grafting offers an alternative for patients whose vessels are unsuitable for arteriovenous fistula. However, as a result of subcutaneous tunnel dissection, postoperative pain and edema of the operated limb present early after surgery. As a traditional therapeutic approach, cryotherapy has the ability to suppress postoperative pain and edema. AIMS: The purpose of the study was to investigate the feasibility of cryotherapy after arteriovenous graft surgery to decrease perioperative medication usage. DESIGN: This study was a randomized controlled trial. SETTING: A large integrated health care facility in South China. PARTICIPANTS/SUBJECTS: A total of 85 hemodialysis patients who received arteriovenous graft surgery from March 2011 to February 2017 were enrolled. METHODS: The participants were divided into an intervention group and a control group according to the postoperative management. Ice packs were applied covering the operative forearm for 120 minutes after wound closure in the intervention group. General information, pain score, analgesic consumption, wound inflammation, forearm edema, and participant satisfaction were compared between the two groups. RESULTS: Cryotherapy-treated patients required less analgesia (26.19% vs. 48.84%, p < .05), reported lower pain score from 30 minutes to 48 hours postoperative (p < .05), less wound inflammation (11.90% vs. 25.58%, p < .05), and higher participant satisfaction (8.92 ± 0.57 vs. 6.52 ± 0.63, p < .05), whereas the incidence of forearm edema was equivalent (p > .05). No adverse events were reported in either group. CONCLUSIONS: Cryotherapy is a preferable intervention for patients after arteriovenous graft implantation as a result of its favorable cost, convenience, and fewer side effects.

Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds.

The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone kidney tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-ε-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 106 proximal tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.

Adjunctive hyperbaric oxygen therapy for irradiated rat calvarial defects

PURPOSE: The aim of this study was to conduct a histologic evaluation of irradiated calvarial defects in rats 4 weeks after applying fibroblast growth factor-2 (FGF-2) with hyaluronan or biphasic calcium phosphate (BCP) block in the presence or absence of adjunctive hyperbaric oxygen (HBO) therapy. METHODS: Twenty rats were divided into HBO and non-HBO (NHBO) groups, each of which was divided into FGF-2 and BCP-block subgroups according to the grafted material. Localized radiation with a single 12-Gy dose was applied to the calvaria of rats to simulate radiotherapy. Four weeks after applying this radiation, 2 symmetrical circular defects with a diameter of 6 mm were created in the parietal bones of each animal. The right-side defect was filled with the materials mentioned above and the left-side defect was not filled (as a control). All defects were covered with a resorbable barrier membrane. During 4 weeks of healing, 1 hour of HBO therapy was applied to the rats in the HBO groups 5 times a week. The rats were then killed, and the calvarial specimens were harvested for radiographic and histologic analyses. RESULTS: New bone formation was greatest in the FGF-2 subgroup, and improvement was not found in the BCP subgroup. HBO seemed to have a minimal effect on new bone formation. There was tendency for more angiogenesis in the HBO groups than the NHBO groups, but the group with HBO and FGF-2 did not show significantly better outcomes than the HBO-only group or the NHBO group with FGF-2. CONCLUSIONS: HBO exerted beneficial effects on angiogenesis in calvarial defects of irradiated rats over a 4-week healing period, but it appeared to have minimal effects on bone regeneration. FGF-2 seemed to enhance new bone formation and angiogenesis, but its efficacy appeared to be reduced when HBO was applied.

Eight-week healing of grafted calvarial bone defects with hyperbaric oxygen therapy in rats

PURPOSE: The purpose of this study was to evaluate the synergistic effect of adjunctive hyperbaric oxygen (HBO) therapy on new bone formation and angiogenesis after 8 weeks of healing. METHODS: Sprague-Dawley rats (n=28) were split into 2 groups according to the application of adjunctive HBO therapy: a group that received HBO therapy (HBO group [n=14]) and another group that did not receive HBO therapy (NHBO group [n=14]). Each group was divided into 2 subgroups according to the type of bone graft material: a biphasic calcium phosphate (BCP) subgroup and an Escherichia coli-derived recombinant human bone morphogenetic protein-2-/epigallocatechin-3-gallate-coated BCP (mBCP) subgroup. Two identical circular defects with a 6-mm diameter were made in the right and left parietal bones of each rat. One defect was grafted with bone graft material (BCP or mBCP). The other defect was not grafted. The HBO group received 2 weeks of adjunctive HBO therapy (1 hour, 5 times a week). The rats were euthanized 8 weeks after surgery. The specimens were prepared for histologic analysis. RESULTS: New bone (%) was higher in the NHBO-mBCP group than in the NHBO-BCP and control groups (P<0.05). Blood vessel count (%) and vascular endothelial growth factor staining (%) were higher in the HBO-mBCP group than in the NHBO-mBCP group (P<0.05). CONCLUSIONS: HBO therapy did not have a positive influence on bone formation irrespective of the type of bone graft material applied after 8 weeks of healing. HBO therapy had a positive effect on angiogenic activity.

Treatment of Facial Neuralgia Developed after Inferior Meatal Antrostomy by Narrowing of the Inlet with Endoscopic Cartilage Graft

Inferior meatal antrostomy (IMA) is a widely performed surgical technique to treat postoperative maxillary mucocele. The method is safe and easy to perform, without major complications compared with other approaches. Facial pain after IMA is a rare clinical entity that can be challenging to diagnose and treat. The authors present an unusual case of acute facial neuralgia triggered by cold air that developed after IMA. The antrostomy was located at the anterior-most part of the inferior meatus, and the inlet size was relatively large compared with the size of the remaining sinus. Surgical narrowing of the antrostomy inlet using endoscopy dramatically reduced the symptoms, and symptom relief was maintained for up to one year after surgery.

The analgesic efficacy of the transversalis fascia plane block in iliac crest bone graft harvesting: a randomized controlled trial / 대한마취과학회지

BACKGROUND: Iliac crest bone graft (ICBG) harvesting is associated with significant perioperative pain and opioid consumption. This randomized controlled trial sought to determine if the transversalis fascia plane (TFP) block provides effective analgesia for anterior ICBG harvesting. METHODS: Fifty patients undergoing wrist fusion surgery with anterior ICBG harvesting were randomized to receive a TFP block with either 20 ml of 0.5% ropivacaine or 5% dextrose. Patients additionally received a brachial plexus block for primary surgical-site anesthesia and either a general or spinal anesthetic depending on patient preference. Primary outcomes of interest were perioperative opioid consumption (measured as intravenous morphine equivalents [IME]), pain intensity at the ICBG harvest site for up to 48 h postoperatively, and the incidence of persistent postoperative pain at 6 and 12 months after surgery. RESULTS: The TFP group used less opioid in the post-anesthetic care unit (PACU) (median 0 vs. 2.5 mg IME, P = 0.01) and in the first 8 h following PACU discharge (median 2.5 vs. 13.0 mg IME, P = 0.02). The patients who received a TFP block also had lower pain scores in PACU (median 0 vs. 4.0 out of 10, P < 0.001). Although opioid consumption and pain scores were lower in the TFP group at later timepoints, this difference was not statistically significant. Persistent pain at the ICBG site was reported in only 4.3% and 6.5% of all patients at 6 and 12 months, respectively. CONCLUSIONS: The TFP block provides effective early analgesia for anterior ICBG harvesting. The incidence of persistent postoperative pain was low.

Efficacy of parenteral glutamine supplementation in adult hematopoietic stem cell transplantation patients

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients. METHODS: In this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group. RESULTS: Regarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group. CONCLUSION: Results showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.

Biodegradable Magnesium Alloy Stents as a Treatment for Vein Graft Restenosis

PURPOSE: To explore the effects of biodegradable magnesium alloy stents (BMAS) on remodeling of vein graft (VG) anastomotic restenosis. MATERIALS AND METHODS: To establish a VG restenosis model, seventy two New Zealand rabbits were randomly divided into three groups according to whether a stent was implanted in the graft vein or not. BMASs and 316L stainless steel stents were implanted in BMAS and 316L groups, respectively, while no stent was implanted in the no-treatment control group (NC group). Loss of lumen diameter in the graft vein was measured in all three groups. Upon harvesting VG segments to evaluate intimal proliferation and re-endothelization, the degradation and biological safety of the stents were observed to explore the effects of BMAS on VG remodeling. RESULTS: Model establishment and stent implantation were successful. The BMAS reduced lumen loss, compared with the control group (0.05±0.34 mm vs. 0.90±0.39 mm, p=0.001), in the early stage. The neointimal area was smaller in the BMAS group than the 316L group after 4 months (4.96±0.66 mm2 vs. 6.80±0.69 mm2, p=0.017). Re-endothelialization in the BMAS group was better than that in the 316L group (p=0.001). Within 4 months, the BMAS had degraded, and the magnesium was converted to phosphorus and calcium. The support force of the BMAS began to reduce at 2–3 months after implantation, without significant toxic effects. CONCLUSION: BMAS promotes positive remodeling of VG anastomosis and has advantages over the conventional 316L stents in the treatment of venous diseases.