Diagnostic and Prognostic Value of Thrombocytopenia in Severe Burn Injuries.

BACKGROUND AND OBJECTIVES: Burn injuries are the most severe type of trauma, with complex biological consequences associated with high rates of morbidity and mortality. Prompt recognition and management of burn-related complications are imperative for improving the vital and functional prognosis of the patient. Changes in biological parameters can be essential determinants in the prognosis of the burned patient. Thrombocytopenia in critically ill patients is linked to an elevated risk of mortality. We sought to investigate the significance of thrombocytopenia in severely burned patients while considering the limited available data in the literature. MATERIALS AND METHODS: A two-year retrospective study was conducted on 90 patients with severe burns admitted to our Burn Centre. Demographic data, burn lesion characteristics, and daily total blood counts, including platelet assessment, complications, and mortality, were recorded and analyzed. RESULTS: Patients with extensive burns in our study had a poor prognosis based on their Abbreviated Burn Severity Index score (ABSI), age, percentage of total body surface area (TBSA) burned, presence of third-degree burns, and inhalation injuries. Regardless of the moment, patients with thrombocytopenia in our study died significantly more frequently. Compared with the survivors, the platelet count was significantly lower at any given time in the non-survivors group. Significant statistical associations between thrombocytopenia and ABSI score, burn surface area, presence of third-degree burns, and inhalation injuries were identified at different timeframes post-burn injury. Sepsis was encountered in one-third of the patients. Thrombocytopenia was more frequent in patients with sepsis who did not survive compared to survivors and did not normalize until the time of death. CONCLUSIONS: Thrombocytopenia represents an early indicator of severe complications and outcome predictor in severely burned patients. It is correlated with recognized negative prognostic factors and also with sepsis occurrence. Future research efforts should focus on refining early detection parameters and interventions to improve the prognosis of burn patients.

Venous Thromboembolism in Burn Patients: A 5-Year Retrospective Study.

Background and Objectives: Burn patients manifest all components of Virchow's triad, amplifying the concern for venous thromboembolism (VTE). Routine prophylaxis for VTE remains a subject of debate, with the central concern being the occurrence of associated adverse events. Materials and Methods: We conducted a five-year retrospective study on burn patients admitted to our burn center. Demographic data, comorbidities, burn lesions characteristics, surgical interventions, anticoagulant medication, the need for transfusions, the presence of a central venous catheter, length of stay, complications, and mortality were recorded. Results: Of the overall number of patients (494), 2.63% (13 patients) developed venous thromboembolic complications documented through paraclinical investigations. In 70% of cases, thrombosis occurred in a limb with central venous catether (CVC). Every patient with VTE had a Caprini score above 8, with a mean score of 12 points in our study group. Conclusions: Considering each patient's particularities and burn injury characteristics, individualized approaches may be necessary to optimize thromboprophylaxis effectiveness. We suggest routinely using the Caprini Risk Assessment Model in burn patients. We recommend the administration of pharmacologic thromboprophylaxis in all patients and careful monitoring of patients with Caprini scores above 8, due to the increased risk of VTE. Additionally, ongoing research in this field may provide insights into new strategies for managing thrombotic risk in burn patients.

System of Implantable Electrodes for Neural Signal Acquisition and Stimulation for Wirelessly Connected Forearm Prosthesis.

There is great interest in the development of prosthetic limbs capable of complex activities that are wirelessly connected to the patient's neural system. Although some progress has been achieved in this area, one of the main problems encountered is the selective acquisition of nerve impulses and the closing of the automation loop through the selective stimulation of the sensitive branches of the patient. Large-scale research and development have achieved so-called "cuff electrodes"; however, they present a big disadvantage: they are not selective. In this article, we present the progress made in the development of an implantable system of plug neural microelectrodes that relate to the biological nerve tissue and can be used for the selective acquisition of neuronal signals and for the stimulation of specific nerve fascicles. The developed plug electrodes are also advantageous due to their small thickness, as they do not trigger nerve inflammation. In addition, the results of the conducted tests on a sous scrofa subject are presented.

Toxic Epidermal Necrolysis, A Serious Side Effect of Tenoxicam Use: A Case Report.

Tenoxicam, a selective cyclooxygenase (COX)-2 inhibitor, has potent analgesic and anti-inflammatory effects and is frequently used for out-of-hospital pain control. Even though other non-steroidal anti-inflammatory drugs were incriminated in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) appearance, the literature is scarce regarding this agent. We report a case of tenoxicam-induced toxic epidermal necrolysis, detailing the multidisciplinary approach in a patient presenting skin detachment of 90% of the total body surface area, with concomitant ocular, oral, nasal, and vaginal mucosae involvement. A skin biopsy confirmed the diagnosis. The immediate cessation of the incriminated drug and rapid initiation of systemic steroids, along with topical therapies, and isolation into a specific environmental condition to limit skin infection were the cornerstones of therapeutic management. The patient was discharged with skin hyperpigmentation area and mild anxiety as long-term sequels. This report emphasized that severe or complicated cases should be transferred to a specialized burn center to reduce mortality risk and long-term morbidity.

Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action.

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.

Emergency Care for Burn Patients-A Single-Center Report.

Burns, one of the main public health problems, lead to significant mortality and morbidity. Epidemiological studies regarding burn patients in Romania are scarce. The aim of this study is to identify the burn etiology, demographics, clinical characteristics, and outcomes in patients requiring treatment in a regional burn unit. DESIGN: We performed a retrospective observational study of 2021. PATIENTS: All patients admitted to our six-bed intensive care unit (ICU) were included. INTERVENTIONS: The following data were collected for further analysis: demographics, burn pattern (etiology, size, depth, affected body region), type of ventilation, ABSI (Abbreviated Burn Severity Index) score, comorbidities, bioumoral parameters, and hospitalization days. RESULTS: There were 93 burned patients included in our study that were divided into two groups: alive patients' group (63.4%) and deceased patients' group (36.6%). The mean age was 55.80 ± 17.16 (SD). There were 65.6% male patients, and 39.8% of the patients were admitted by transfer from another hospital. Further, 59 patients presented third-degree burns, from which 32.3% died. Burns affecting >37% of the total body surface area (TBSA) were noticed in 30 patients. The most vulnerable regions of the body were the trunk (p = 0.003), the legs (p = 0.004), the neck (p = 0.011), and the arms (p = 0.020). Inhalation injury was found in 60.2% of the patients. The risk of death in a patient with an ABSI score > 9 points was 72 times higher. Comorbidities were present in 44.1% of the patients. We observed a median LOS (length of stay) of 23 days and an ICU-LOS of 11 days. Logistic regression analysis showed that admission protein, creatinkinase, and leukocytes were independent risk factors for mortality. The general mortality rate was 36.6%. CONCLUSION: A thermal factor was responsible for the vast majority of burns, 94.6% of cases being accidents. Extensive and full-thickness burns, burns affecting the arms, inhalation injuries, the need for mechanical ventilation, and a high ABSI score represent important risk factors for mortality. Considering the results, it appears that prompt correction of protein, creatinkinase, and leukocytes levels may contribute to improvement in severe burn patients' outcomes.

Cervical intranodal schwannoma - a rare diagnosis.

Intranodal schwannoma is a rare benign tumor, which originates from the peripheral nerve sheath (Schwann cells), fewer cases being reported with lymphatic involvement. We present the case of a middle-aged female patient, with one-year growing mass in the lateral-cervical area, in intimate relation with the vascular package of the neck. Preoperative cervical computed tomography examination showed the tumor features. There was no intraoperative complication, with the piece being completely removed. The morphological examination revealed the structure of a lymph node, and after Hematoxylin-Eosin staining, there were eosinophilic cytoplasm, euchromatic nuclei, with round, elongated or slightly wavy form and reduced pleomorphism, rare degenerative nuclear atypia, and no mitotic activity nor necrosis. The expression of S100 protein on immunohistochemistry, along with negative results for smooth muscle actin and desmin sustained the diagnosis of intranodal schwannoma of the neck. With a low index of cellular proliferation (Ki67), this case is in line with the reported features of schwannoma having extremely rare malignant transformation.

Generation of an Immortalized Human Adipose-Derived Mesenchymal Stromal Cell Line Suitable for Wound Healing Therapy.

Adipose-derived mesenchymal stromal cells (ADSC) are a promising source for cellular therapy of chronic wounds. However, the limited life span during in vitro expansion impedes their extensive use in clinical applications and basic research. We hypothesize that by introduction of an ectopic expression of telomerase into ADSC, the cells' lifespans could be significantly extended. To test this hypothesis, we aimed at engineering an immortalized human ADSC line using a lentiviral transduction with human telomerase (hTERT). ADSC were transduced with a third-generation lentiviral system and a hTERT codifying plasmid (pLV-hTERT-IRES-hygro). A population characterized by increased hTERT expression, extensive proliferative potential and remarkable (potent) multilineage differentiation capacity was selected. The properties for wound healing of this immortalized ADSC line were assessed after 17 passages. Their secretome induced the proliferation and migration of keratinocytes, dermal fibroblasts, and endothelial cells similarly to untransduced ADSC. Moreover, they sustained the complete re-epithelialization of a full thickness wound performed on a skin organotypic model. In summary, the engineered immortalized ADSC maintain the beneficial properties of parent cells and could represent a valuable and suitable tool for wound healing in particular, and for skin regenerative therapy in general.

Burn-Induced Acute Kidney Injury-Two-Lane Road: From Molecular to Clinical Aspects.

Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28-100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.

Remote Sensing System for Motor Nerve Impulse.

In this article, we present our research achievements regarding the development of a remote sensing system for motor pulse acquisition, as a first step towards a complete neuroprosthetic arm. We present the fabrication process of an implantable electrode for nerve impulse acquisition, together with an innovative wirelessly controlled system. In our study, these were combined into an implantable device for attachment to peripheral nerves. Mechanical and biocompatibility tests were performed, as well as in vivo testing on pigs using the developed system. This testing and the experimental results are presented in a comprehensive manner, demonstrating that the system is capable of accomplishing the requirements of its designed application. Most significantly, neural electrical signals were acquired and transmitted out of the body during animal experiments, which were conducted according to ethical regulations in the field.

Magnesium-A More Important Role in CKD-MBD than We Thought.

Chronic kidney disease (CKD) is associated with different complications, including chronic kidney disease-mineral and bone disorder (CKD-MBD), which represents a systemic disorder that involves the presence of different mineral or bone structure abnormalities (i.e., modification of bone turnover, strength, volume, etc.), including even vascular calcification development. Even if, over the years, different pathophysiological theories have been developed to explain the onset and progression of CKD-MBD, the influence and importance of serum magnesium level on the evolution of CKD have only recently been highlighted. So far, data are inconclusive and conflicting; therefore, further studies are necessary to validate these findings, which could be useful in developing a better, more adequate, and personalized management of CKD patients.

Uric Acid and Oxidative Stress-Relationship with Cardiovascular, Metabolic, and Renal Impairment.

BACKGROUND: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin-angiotensin-aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. CONCLUSIONS: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients' long-term prognosis and their quality of life.

Overview of Renal Replacement Therapy Use in a General Intensive Care Unit.

OBJECTIVES: Population-based studies regarding renal replacement therapy (RRT) used in critical care populations are useful to understand the trend and impact of medical care interventions. We describe the use of RRT and associated outcomes (mortality and length of intensive care stay) in a level 1 hospital. DESIGN: A retrospective descriptive observational study. PATIENTS: Critically ill patients admitted to the ICU from 1 January to 31 December 2018. INTERVENTIONS: Age, gender, ward of admission, primary organ dysfunction at admission, length of hospital stay (LOS), mechanical ventilation, APACHE, SOFA and ISS scores, the use of vasopressors, transfusion, RRT and the number of RRT sessions were extracted. RESULTS: 1703 critically ill patients were divided into two groups: the RRT-group (238 patients) and the non-RRT group (1465 patients). The mean age was 63.58 ± 17.52 (SD) in the final ICU studied patients (64.72 ± 16.64 SD in the RRT-group), 60.5% being male. Patients admitted from general surgery ward needing RRT were 41.4%. The specific scores, the use of vasopressors, transfusions and mortality were higher in the RRT-group. The ICU LOS was superior in the RRT-group, regardless of the primary organ dysfunction. CONCLUSIONS: RRT was practiced in 13.9% of patients (especially after age of 61), with mortality being the outcome for 66.8% of the RRT-group patients. All analyzed data were higher in the RRT group, especially for multiple trauma and surgical patients, or patients presenting cardiac or renal dysfunctions at admission. We found significant increased ISS scores in the RRT-group, a significant association between the need of vasopressors or transfusion requirement and RRT use, and an association in the number of RRT sessions and LOS (p < 0.001).

The Ideal Time for Iron Administration in Anemia Secondary to Blood Loss-An Experimental Animal Model.

BACKGROUND: Anemia and iron deficiency are two of the main public health problems worldwide, associated with negative outcomes in surgical patients. This experimental study aimed to create a model of acute iron deficiency with anemia through blood loss and extensive surgery. Afterwards, intravenous iron was administered to correct the iron deficiency and to improve the hematological parameters in distinct moments regarding the surgical time. To assess the optimum time for therapeutic intervention, experimental subjects were compared, performing clinical, paraclinical, and histological examinations, as well. METHODS: Male rats (n = 35), aged 11-13 months, were randomly designated into six groups. Anemia and iron deficiency were obtained through a 15% blood volume loss, followed by major surgical intervention (femur fracture and osteosynthesis using Kirschner wire). Therapeutic intervention was obtained with an intravenous ferric carboxymaltose infusion, as follows: group II: intraoperative (n = 7), group III: 48 h after surgery (n = 7), group IV: 48 h before surgery (n = 5), and group V: seven days before surgery (n = 6). Group I (n = 5) was left anemic, while group 0 (n = 5) was nonanemic without therapeutic intervention. RESULTS AND DISCUSSION: In group I, serum iron lower than in group 0 (27.04 ± 6.92 µg/dL versus 60.5 ± 2.34 µg/dL), as well as hemoglobin (10.4 ± 0.54 g/dL versus 14.32 ± 2.01 g/dL) and ferritin values (22.52 ± 0.53 ng/mL versus 29.86 ± 3.97 ng/mL), validated the experimental model. Regarding wound healing after surgical trauma, we observed that neovascularization was more significant in group III, followed by group V, with fewer neutrophils, a well-represented and rich in lymphomonocytes inflammatory infiltrate associated with the biggest collagen fiber dimensions. The periosteal reaction and callus area presented thicker trabeculae in groups II and III compared to the anemic group. CONCLUSIONS: This original experimental study assessed the effect of perioperative intravenous iron administration at a specific time by comparing the weight, hematological, and iron status-defining parameters, as well as histological characteristics of the included subjects. The present findings highlight that correcting the iron deficiency in emergency settings through intravenous iron administration intraoperatively or 48 h postoperatively could determine the improved bioumoral parameters, as well as a better evolution of the postoperative wound and bone healing compared to the anemic group or subjects that received therapeutic intervention 48 h before surgery.

Rhabdomyolysis-Induced Acute Renal Injury in a Schizophrenic Patient.

Nowadays, schizophrenia is treated with atypical antipsychotics that can determine neuroleptic malignant syndrome or rhabdomyolysis appearance. In addition to trauma and muscular hypoxia, there are some drugs and toxins associated with rhabdomyolysis development, among which olanzapine. A case of severe rhabdomyolysis syndrome, with extremely high levels of serum creatine kinase (CK), followed by acute kidney failure, secondary to olanzapine overdose and prolonged immobilization is outlined. Continuous renal replacement therapy was performed, with a slow clearance of serum CK levels. Under supportive therapy, systemic alkalinisation with volume resuscitation and corticotherapy, patient's general condition was improved, as well as his lower limb paresis. He followed frequent psychiatric evaluations and psychotherapies, before and after being transferred to a medical service. Rhabdomyolysis diagnosis is difficult in mild cases due to non-specific signs and symptoms, but it also has some typical manifestation, generically called "the rhabdomyolysis syndrome triad". The treatment is usually supportive; renal replacement therapy is required in the presence of acute kidney injury unresponsive to aggressive volume resuscitation. The systemic myoglobin release is responsible for renal injury. Olanzapine muscle toxicity can lead to severe rhabdomyolysis syndrome complicated with acute kidney injury and multiple organ dysfunction syndrome. Rapid identification and aggressive therapeutic management are essential for improving patients' outcome and prevent the occurrence of irreversible injuries.

Incidence of Iron Deficiency and the Role of Intravenous Iron Use in Perioperative Periods.

Iron deficiency is a major problem in worldwide populations, being more alarming in surgical patients. In the presence of absolute iron deficiency (depletion of body iron), functional iron deficiency (during intense bone marrow stimulation by endogenous or exogenous factors), or iron sequestration (acute or chronic inflammatory conditions), iron-restricted erythropoiesis can develop. This systemic review was conducted to draw attention to the delicate problem of perioperative anemia, and to provide solutions to optimize the management of anemic surgical patients. Systemic reviews and meta-analyses, clinical studies and trials, case reports and international guidelines were studied, from a database of 50 articles. Bone marrow biopsy, serum ferritin levels, transferrin saturation, the mean corpuscular volume, and mean corpuscular hemoglobin concentration were used in the diagnosis of iron deficiency. There are various intravenous iron formulations, with different pharmacological profiles used for restoring iron. In surgical patients, anemia is an independent risk factor for morbidity and mortality. Therefore, anemia correction should be rapid, with parenteral iron formulations-the oral ones-being inefficient. Various studies showed the safety and efficacy of parenteral iron formulations in correcting hemoglobin levels and decreasing the blood transfusion rate, the overall mortality, the postoperative infections incidence, hospitalization days, and the general costs.

Mesenchymal stromal cell-derived factors promote the colonization of collagen 3D scaffolds with human skin cells.

The development of stem cell technology in combination with advances in biomaterials has opened new ways of producing engineered tissue substitutes. In this study, we investigated whether the therapeutic potential of an acellular porous scaffold made of type I collagen can be improved by the addition of a powerful trophic agent in the form of mesenchymal stromal cells conditioned medium (MSC-CM) in order to be used as an acellular scaffold for skin wound healing treatment. Our experiments showed that MSC-CM sustained the adherence of keratinocytes and fibroblasts as well as the proliferation of keratinocytes. Moreover, MSC-CM had chemoattractant properties for keratinocytes and endothelial cells, attributable to the content of trophic and pro-angiogenic factors. Also, for the dermal fibroblasts cultured on collagen scaffold in the presence of MSC-CM versus serum control, the ratio between collagen III and I mRNAs increased by 2-fold. Furthermore, the gene expression for α-smooth muscle actin, tissue inhibitor of metalloproteinase-1 and 2 and matrix metalloproteinase-14 was significantly increased by approximately 2-fold. In conclusion, factors existing in MSC-CM improve the colonization of collagen 3D scaffolds, by sustaining the adherence and proliferation of keratinocytes and by inducing a pro-healing phenotype in fibroblasts.

Histopathological features of low-dose organophosphate exposure.

Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose exposure. The systemic dysfunction appears partly due to acetylcholinesterase inhibition, exhibiting a primary toxic effect on the endocrine system but also on the liver and kidneys, which are responsible for products metabolization and elimination. Prolonged OP exposure can be responsible for histopathological (HP) changes that can either evolve or worsen pre-existing conditions. We conducted an experimental study including six male Wistar rats divided into two groups (four rats in the study group and two in the control group). The subjects in the first group were administered 100 mg∕kg Chlorpyrifos half median lethal dose (LD50) at baseline and at 48 hours, under general anesthesia. Organ harvesting was achieved after one week. HP modifications were discovered in all kidney samples, with dystrophic changes and vacuolization of mesangial cells, dilation of renal tubules and epithelial atrophy. Congestion of vascular structures also occurred. The liver samples showed severe alteration in both vessels and hepatocytes. Adrenal gland impairment was confirmed through an increase in vacuole number in all areas, while a decrease in colloid content was noted in the thyroid gland simultaneously with a modified foamy aspect. This study is the first to certify the extent of organ injury induced by OP exposure, describing both glomerular and tubular involvement in the kidneys, liver necrosis and endocrine disturbances.

Heterogeneity of human fibroblasts isolated from hypertrophic scar.

Pathological wound healing states, such as hypertrophic scarring and keloids, represent a huge clinical and financial burden on healthcare system. The complex biological mechanisms occurring in hypertrophic scarring are still barely understood. To date, there is no satisfactory description of hypertrophic fibroblasts. Therefore, in the present study we focused on the comparatively characterization of the fibroblasts residing in different regions of hypertrophic scars. To achieve this aim, fibroblasts were isolated from normal skin samples (n=4) and hypertrophic scars (n=4). These cell populations were further were used for the evaluation of proliferation and migration capacity, for the gene and protein expression of extracellular matrix protein type I collagen and fibronectin and for the presence of myofibroblasts. Our results demonstrated that perilesional and intralesional fibroblasts isolated from hypertrophic scars could be considered as distinct populations, having different properties. Thus, the intralesional fibroblasts had an increased proliferation capacity and increased gene and protein expression of collagen I and fibronectin. However, the perilesional fibroblasts had augmented mobility as revealed by in vitro scratch test and contained a higher percentage of myofibroblasts [alpha-smooth muscle actin (α-SMA)high cells], in comparison to the intralesional population. In conclusion, our data could provide an explanation regarding the inconsistent efficacy of topic therapies for hypertrophic scars.