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Background: Intra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models. Methods: Forty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5). Results: There were significant changes (p<0.05) noted in all organ systems, most notably systolic blood pressure (SBP) (p<0.001), cardiac index (CI) (p = 0.003), stroke volume index (SVI) (p<0.001), mean pulmonary airway pressure (MPP) (p<0.001), compliance (p<0.001), pO2 (p = 0.003), bicarbonate (p = 0.041), hemoglobin (p = 0.012), lipase (p = 0.041), total bilirubin (p = 0.041), gastric pH (p<0.001), calculated glomerular filtration rate (GFR) (p<0.001), and urine output (p<0.001). SVV increased progressively as the IAP increased with no obvious changes in intravascular volume status. There were no significant differences between the models regarding their impact on cardiovascular, respiratory, renal and gastrointestinal systems. However, significant differences were noted between the two models at 30mmHg, with MIO30 showing worse metabolic and hematological parameters, and Pn30 and Pn40 showing a more rapid rise in creatinine. Conclusions: This study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear. [ABSTRACT FROM AUTHOR]

The main contribution of this paper is the assets of the current and voltage ripples in a buck converter with an LED load. The results indicate that the ripples are different and that it is possible to reduce the passive filter concerning the model of the LED as a simple resistance. The paper presents the design and simulation of a buck converter as a power supply for an LED lamp. Modeling the LED as a resistor and a voltage source (SVRM), the equations to calculate the components of the circuit using the SVRM model are presented, where the Fourier series and phasors are used to calculate the output filter. The equations are validated with SPICE simulations. The results indicate that the SVRM model for the LED load affects the calculation of the output filter of the buck converter as well as the voltage and current ripples, making it a more precise design alternative to the proposed development. [ABSTRACT FROM AUTHOR]

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-β (TFG-β) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-β1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-β chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-β chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-β might play a key role in wound chronification and postulate the validity of our TGF-β chronified HaCaT in vitro model for the study of chronic wound physiology. [ABSTRACT FROM AUTHOR]

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Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization.Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales.Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future.Trial Registration: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol. [ABSTRACT FROM AUTHOR]

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI. [ABSTRACT FROM AUTHOR]

Objective: The amniotic membrane (AM) is a tissue with low immunogenity and high therapeutic potential due to its anti-inflammatory, anti-fibrotic and antimicrobial effects. This paper describes the use of cryopreserved amniotic membrane allografts to treat diabetic foot ulcers (DFUs) in patients with diabetes. Method: In this case series, AM was processed to obtain a final medicinal product: cryopreserved amniotic membrane. cryopreserved AM was applied every 7–10 days until total epithelialisation of the DFUs. Results: A total of 14 patients with DFUs (median size: 12.30cm, (range: 0.52–42.5cm2) were treated and followed up until complete closure (median time: 20 weeks, range: 7–56 weeks). Patients received 4–40 AM applications. All patients in this study achieved complete epithelialisation of the wound. No adverse events were observed. Conclusion: AM is a feasible and safe treatment in complex DFUs. Furthermore, the treatment is successful in achieving epithelialisation of long-evolution, unhealed wounds resistant to conventional therapies. [ABSTRACT FROM AUTHOR]

Background: Low splanchnic perfusion is an immediate effect of pneumoperitoneum-induced intra-abdominal hypertension (IAH). Anatomical structure results in the intestinal mucosa being the area most sensitive to hypoperfusion. The relationship between intestinal injury and clinical parameters of tissue perfusion [abdominal perfusion pressure (APP), gastric intramucosal pH (pHi) and lactic acid (Lc)] has not been previously studied. This study aimed to monitorize intestinal pathogenesis through sequential ileal biopsies and to measure APP, pHi, and Lc levels at different pneumoperitoneum-induced intra-abdominal pressures (20, 30, and 40 mmHg) to evaluate the potential relationships between them.Materials and Methods: Fifty pigs were divided into four groups; a control group (C) and three experimental groups with different pneumoperitoneum-induced levels [20 mmHg (G20), 30 mmHg (G30), and 40 mmHg (G40)], that were maintained for 3 and 5 h. APP, pHi, and Lc were measured and ileal biopsies taken laparoscopically every 30 min. The mucosal damage was graded using the standardized Park's Score and animals were classified as injured (I+) or uninjured (I-).Results: Different histopathological lesions were observed in groups G20, G30, and G40 but no damage observed in group C. A 33.3% of animals in G20 and G30 were I+ after 3 h, while 93.3% were injured in G40. After 5 h, histopathological lesions were no longer seen in some animals in G20 and only 10% were I+. Conversely, in G30 I+ pigs increased to 80% while those in G40 remained at 93.3% I+. The I+ animals had significantly lower APP and pHi than those I-. Lc was the clinical parameter that showed the earliest differences, with significantly higher figures in I+ animals.Conclusions: The evolution of intestinal injuries from pneumoperitoneum-induced IAH depends on the degree of IAP. These damages may be associated with decreases in APP and pHi, and increases in Lc. [ABSTRACT FROM AUTHOR]

Background: A mechanical intestinal obstruction (MIO) can generate intraabdominal hypertension (IAH) that is life threatening. The intestines are very sensitive to IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis and bacterial translocations. This may lead to acute intestinal distress syndrome (AIDS). The identification of intestinal injuries during IAH and its correlation with clinical parameters as the abdominal perfusion pressure (APP), the gastric intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to evaluate the sequence of intestinal histopathological findings in an MIO model and to analyze potential relationships with parameters currently used in clinical practice (APP, pHi and Lc). Material and methods: Twenty pigs were divided into three groups: a control group (n = 5) and two experimental groups with 20 mmHg (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every 30 minutes in all groups. The intestinal damage was graded according to the Park Score. Results: Intestinal injuries were found in 42.9% of pigs in the experimental groups. The lesions were independent of the level and duration of IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and G2, there were no significant differences among those uninjured (I-). Lc was significantly increased in all I+ pigs from the onset of IAH. Conclusion: The IAH by MIO causes intestinal lesions from the first 30 minutes with concurrent decreases in APP and pHi and increases in Lc. Lc could be the best clinical parameter related to intestinal damages with a clear difference between I + and I- animals. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. Methods and Findings: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. Conclusions: The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation. [ABSTRACT FROM AUTHOR]

Epithelial and mesenchymal cells isolated from the amniotic membrane (AM) possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases. [ABSTRACT FROM AUTHOR]

Background: This study was designed to provide our experience in the management of infected and drained pancreatic necrosis using the retroperitoneal approach. Methods: This was a prospective observational study in a tertiary care university hospital. Thirty-two patients with confirmed infected pancreatic necrosis were studied. Superficial necrosectomy was performed with lavage and aspiration of debris. This was achieved though a retroperitoneal approach of the pancreatic area and under the direct vision of a flexible endoscope. The follow-up procedure using retroperitoneal endoscopy did not require taking the patient to the operating room. The main outcome measures were infection control, morbidity, and mortality related to technique, reintervention, and long-term follow-up. Results: No significant morbidity or mortality related to the technique was observed in all of the patients with infected pancreatic necrosis treated with this retroperitoneal approach compared with published data using other approaches. Reinterventions were not required and patients are currently asymptomatic. Conclusions: Retroperitoneal access of the pancreatic area is a good approach for drainage and debridement of infected pancreatic necrosis. Translumbar retroperitoneal endoscopy allows exploration under direct visual guidance avoiding open transabdominal reintervention and the risk of contamination of the abdominal cavity. This technique does not increase morbidity and mortality, can be performed at the patients' bedside as many times as necessary, and has advantages over other retroperitoneal approaches. [ABSTRACT FROM AUTHOR]

Large-surface or deep wounds often become senescent in the inflammatory or proliferation stages and cannot progress to reepithelialization. This failure makes intervention necessary to provide the final sealing epithelial layer. The best current treatment is autologous skin graft, although there are other choices such as allogenic or autologous skin substitutes and synthetic dressings. Amniotic membrane (AM) is a tissue of interest as a biological dressing due to its biological properties and immunologic characteristics. It has low immunogenicity and beneficial reepithelialization effects, with antiinflammatory, antifibrotic, antimicrobial, and nontumorigenic properties. These properties are related to its capacity to synthesize and release cytokines and growth factors. We report the use of AM as a wound dressing in two patients with large and deep traumatic wounds. Negative pressure wound therapy followed by AM application was capable of restoring skin integrity avoiding the need for skin graft reconstruction. AM induced the formation of a well-structured epidermis. To understand this effect, we designed some assays on human keratinocyte-derived HaCaT cells. AM treatment of HaCaT induced ERK1/2 and SAP/JNK kinases phosphorylation and c-jun expression, a gene critical for keratinocytes migration; however, it did not affect cell cycle distribution. These data suggest that AM substantially modifies the behavior of keratinocytes in chronic wounds, thereby allowing effective reepithelialization. [ABSTRACT FROM AUTHOR]

Background The follow-up of drained infected pancreatic necrosis (IPN) is usually done with data on the patient’s clinical evolution and information obtained from serial helical computed tomographic scans. Management often requires necrosectomies and periodic debridements. Hypothesis Translumbar retroperitoneal endoscopy is effective in the management of drained IPN. Design A prospective observational study. Setting University tertiary care hospital. Patients A series of 11 consecutive patients with drained IPN undergoing postoperative follow-up with translumbar retroperitoneal endoscopy. Interventions Initially, the IPN was drained via the posterior extraperitoneal translumbar approach; then, a superficial necrosectomy was performed during the same surgical intervention by flushing and endoscopic aspiration; and, finally, a lavage and drainage system was fitted. In the immediate postoperative period, for management of the IPN, we removed the drainage tube and inserted a flexible endoscope as far as the pancreatic area to eliminate the infected necrotic material by flushing and aspiration. Main Outcome Measures In these patients, we studied control of the infection of the pancreatic area, quantification variables of the necrosectomy, technique-related morbidity and mortality, and the need for subsequent operations. Results The 11 patients studied showed good results regarding the control and complete elimination of the infected necrosis. There was no technique-related morbidity or mortality or need for subsequent operations. Conclusion Translumbar retroperitoneal endoscopy allows exploration of the retroperitoneal space under direct visual guidance, facilitates lavage and aspiration, avoids subsequent surgical operations for debridement, decreases the need for repeated computed tomographic scans to evaluate the evolution of the IPN, and has no added morbidity or mortality. [ABSTRACT FROM AUTHOR]

Hypothesis: The extraperitoneal translumbar approach and retroperitoneoscopy are useful in the treatment and follow-up of patients with infected pancreatic necrosis. Design: Descriptive study. Setting: University hospital. Patients: Fifteen consecutive patients with infected and drained pancreatic necrosis. Interventions: Extraperitoneal translumbar approach to drain and retroperitoneoscopy as a method to propose evolutive control. Main Outcome Measures: Morbidity and mortality. Results: Four (27%) of 15 patients died, and 3 (20%) of 15 patients experienced complications during hospital admission. Conclusions: The retroperitoneal access to infected pancreatic necrosis has low rates of mortality and morbidity and a low percentage of repeated surgeries, and retroperitoneoscopy facilitates evolutive control of treated infected pancreatic necrosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 47-year-old man with chronic alcoholism that complains of severe abdominal pain with vomiting and nausea after taking large amount of food and alcohol. The patient was diagnosed with intra-abdominal hypertension (IAH) with compression of the inferior vena cava caused by pancreatic pseudocyst (PP). The PP was decompressed and controlled through computed tomography (CT) by inserting two drainage tubes obtaining 2700 milliliter (ml) of gray liquid.