Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Healing Effect of a Nano-Functionalized Medical-Grade Honey for the Treatment of Infected Wounds.

Based on the qualities of Ulmo honey (Eucryphia cordifolia), a medical-grade honey (Ulmoplus®) has been developed. Relevant to this, the use of copper represents an emerging therapy for the treatment of wounds. Therefore, the aim of this study was to see how this medical-grade honey with copper nanoparticles (CuNPs) helped to heal infected or non-infected wounds. Twenty-four guinea pigs (Cavia porcellus) were divided into four groups for phase 1 (without and with infection, U + F1 and U + F2), and two groups for phase 2 (selected formulation, without and with infection, U + F2NI and U + F2I). Bacteriological and histopathological studies, collagen fibers content evaluation, and stereological analysis were performed. The selected formulation displayed the same antibacterial potency as Ulmoplus®, indicating that this medical-grade honey by itself can be used as an antibacterial agent. However, the evaluation of collagen content demonstrated a significant increase in fibroblast and type III collagen fibers for infected and uninfected groups, which correlated with the histopathological study. Therefore, it is correct to affirm that adding CuNPs to Ulmoplus® improved the maturation of collagen fibers. Finally, polymorphonuclear cells presented similar values between experimental groups, which would indicate that the formulation under study was able to regulate the inflammatory process despite their infectious condition.

Thermal Injury Protocol to Study Healing, With and Without Infection, in Guinea Pig (Cavia porcellus) Model / Protocolo de Lesión Térmica, para Estudio de Cicatrización, en Modelo Animal Cobayo (Cavia porcellus)

SUMMARY: Experimental healing studies in humans are complex and difficult to replicate in vitro. Hence, animal models are needed to study the different stages involved. The guinea pig (Cavia porcellus) is a model close to human physiology, including the lack of vitamin C synthesis, a precursor of collagen fibers for healing. The thermal injury in this animal makes it possible to study all the stages of healing, taking few days to show tissue repair in the processes with and without localized infection. The aim of this work was to systematize an experimental guinea pig (Cavia porcellus) animal model protocol for studies on healing with and without localized infection.

Los estudios experimentales de cicatrización en humanos son complejos, difícilmente replicables in vitro, por lo que se hace necesarias modelos animales que permitan el estudio de las distintas etapas que ella implica. El cobayo (Cavia porcellus) resulta ser un modelo cercano a la fisiología humana, incluyendo la falta síntesis de vitamina C precursora de fibras colágenas para la cicatrización. La lesión térmica en este animal, permite estudiar todas las etapas de la cicatrización, mostrando pocos días en la reparación tisular, tanto en proceso con y sin infección localizada. El objetivo de este trabajo fue sistematizar un protocolo de modelo animal experimental en cobayo (Cavia porcellus) para estudios de cicatrización con y sin infección localizada.

Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options.

Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus.

Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study.

Background. Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). Methods. The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. Results. 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9−22 days). Cox's multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan−Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. Conclusion. This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.

Effectiveness of Copper Nanoparticles in Wound Healing Process Using In Vivo and In Vitro Studies: A Systematic Review.

Chronic wounds are defined as wounds that do not heal in an orderly and timely manner through the various stages of the healing process. Copper nanoparticles are essential in dressings for wound healing because they promote angiogenesis and skin regeneration, which hasten the healing process. This systematic investigation sought to explain how copper nanoparticles affect chronic wound healing in vivo and in vitro. We realized a systematic review of original articles studying the effectiveness of copper nanoparticles in the healing process of chronic wounds. The protocol was registered in the PROSPERO database. Several databases were searched between 2012 and January 2022 for English-language papers using MeSH terms and text related to chronic wounds, copper nanoparticles, and wound healing. Quality was evaluated using National Institute for Health and Care Excellence methodology and PRISMA guidelines. We looked at a total of 12 primary studies. Quantitative data were gathered and presented in all studies. Our results suggest that copper nanoparticles could have an excellent healing property, facilitating the liberation of growth factors that help the anti-inflammatory process of the wound and significantly improving antibacterial and antioxidant activities. In addition, copper presents a higher biocompatibility than other metallic ions, promoting regeneration and increasing skin quality.

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.

Role of copper nanoparticles in wound healing for chronic wounds: literature review.

Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing in an orderly and timely manner. The most common and inevitable impairment to wound healing is the installation of an infection, usually in the case of chronic wounds. Therefore, the objective of the present review was to identify the importance of copper nanoparticles in dressings for wound healing. Nanoparticles such as silver, gold and copper combat infectious processes through the inhibition of protein synthesis, peroxidation of the cell membrane and destroying the nucleic acids of bacteria and viruses. Among bioactive nanoparticles, copper plays a complex role in various cells, it modulates several cytokines and growth factor mechanisms of action and is essentially involved in all stages of the wound healing process. More importantly, copper plays a key role in skin regeneration and angiogenesis and accelerates the healing process through induction of vascular endothelial growth factor (VEGF) and angiogenesis by hypoxia-induced factor-1-alpha (HIF-1α) action where copper enhances HIF-1α expression and HIF-1α binding to the critical motifs in the promoter and putative enhancer regions of HIF-1-regulated genes.

Depresión, ansiedad y estrés en estudiantes de enfermería / Depression, anxiety and stress in nursing students

Los estudiantes universitarios, pueden presentar cambios de salud mental compatibles con estrés, ansiedad o depresión, causadas por la evolución propia de la edad y las exigencias académicas, especialmente en carreras de salud, como enfermería. La última Encuesta Nacional de Salud, indicó que el 78 % de los universitarios sufren algún síntoma de depresión. El objetivo del estudio fue determinar características psicométricas de depresión, ansiedad y estrés, en estudiantes de enfermería de la Universidad Mayor, sede Temuco, Chile. El enfoque fue cuantitativo, diseño no experimental, corte transversal, en una muestra de 244 estudiantes de primer a quinto año. Se aplicó la escala de Depresión, Ansiedad y Estrés (DASS-21), validado en Chile por Vinet, Rehbein, Román y Saiz (Antúnez, 2012; Román, 2016). Los aspectos éticos fueron aprobados por el Comité Ético Científico de Universidad Mayor. El análisis y presentación de resultados fueron por estadística descriptiva e inferencial con Software STATA®15. Los resultados indicaron que el 42,6 % de la muestra obtuvo características compatibles con depresión, 48,0 % con ansiedad y 61,1 % con estrés. El rango de edad más afectado fue entre 19 y 21 años, correspondientes a los niveles académicos de primero a tercero. Las tres variables estudiadas, se asociaron significativamente en segundo año académico de la carrera, destacando las características de estrés, y la menor predominancia de las tres variables fue en quinto año. Se concluyó que los estudiantes de enfermería de la Universidad Mayor sede Temuco, mostraron altos porcentajes de estas variables compatibles con alteraciones de la salud mental en los primeros años de estudio, específicamente en estrés y ansiedad por sobre la depresión, con diferencias significativas entre los niveles académicos de ingreso y egreso, lo que abre la oportunidad de apoyo estudiantil por parte de las entidades universitarias involucradas en estos aspectos.

University students can present mental health changes compatible with stress, anxiety or depression, due to the evolution of age and academic demands, especially in health careers, such as nursing. The latest National Health Survey indicated that 78% of university students suffer from some symptoms of depression. The objective of the study was to determine psychometric characteristics of depression, anxiety and stress, in nursing students of the Universidad Mayor, Temuco, Chile. The approach was quantitative, nonexperimental design, cross-sectional, in a sample of 244 students from first to fifth year. The Depression, Anxiety and Stress scale (DASS-21), validated in Chile by Vinet, Rehbein, Román and Saiz (Antúnez, 2012; Román, 2016), and was applied. The ethical aspects were approved by the Scientific Ethics Committee of Universidad Mayor campus Temuco. The analysis and presentation of results were by descriptive and inferential statistics with STATA®15 Software. The results indicated that 42.6% of the sample obtained characteristics compatible with depression, 48.0% with anxiety and 61.1% with stress. The most affected age range was between 19 and 21 years, corresponding to the academic levels from first to third. The three variables studied were significantly associated in the second year of the degree, highlighting the stress characteristics, and the lowest predominance of the three variables was in the fifth year. It was concluded that nursing students from the Universidad Mayor showed high percentages of these variables compatible with alterations in mental health in the first years of study, specifically in stress and anxiety over depression, with significant differences between the academic levels of entry and exit, which opens the opportunity for student support from the university entities involved in these aspects.

Efecto cicatrizante de la miel de ulmo (Eucryphia cordifolia) suplementada con ácido ascórbico como tratamiento en quemaduras / Healing effect of ulmo honey (Eucryphia cordifolia) supplemented with ascorbic acid as treatment in burns

Debido al daño de la piel producto de quemaduras, los microorganismos encuentran condiciones favorables para su desarrollo, produciéndose desnaturalización, necrosis, exudado, congestión y edema. La miel posee actividad antioxidante, antiinflamatoria y antibacteriana. A su vez, el ácido ascórbico mejora la barrera epidérmica y reduce la contracción de heridas, entre otros. El objetivo de esta investigación fue evaluar morfológicamente la cicatrización de heridas con un tratamiento en base a miel de ulmo (Eucryphia cordifolia) suplementada con ácido ascórbico, comparando su efecto con miel de ulmo no suplementada, en heridas causadas por quemaduras de tipo B. La investigación fue aprobada por el Comité Ético Científico de la Universidad de La Frontera. Se trabajó con 15 cobayos (Cavia porcellus) distribuidos en tres grupos: MS (miel suplementada), M (miel), y Control+ (Hidrogel-Tull). Se provocó una quemadura en seco en el dorso del tórax de 1 cm de diámetro, que abarcó hasta el límite de la fascia profunda. Al día 10 de tratamiento, se extrajeron las biopsias y se depositaron en PBS. Posteriormente, fueron fijadas en formalina tamponada y procesadas para fines histológicos, realizándose las técnicas de VGE, VGC, PAS, y Sirius Red. El cobayo se utilizó como modelo animal por tener un metabolismo dependiente de ácido ascórbico. El grupo MS mostró un rápido debridamiento en comparación a los grupos control, con cierre epidermal en el 60% de las muestras, observándose una fase proliferativa avanzada. El grupo M no regeneró la capa epidérmica y presentó una fase proliferativa inicial. Los resultados de este estudio evidenciaron que al suplementar la miel de ulmo con ácido ascórbico se logra una cicatrización más rápida, con respecto a la miel de ulmo no suplementada, en heridas causadas por quemaduras.

Skin damage from burns creates favorable conditions for microorganism development, producing denaturation, necrosis, discharge, congestion and edema. Honey contains antioxidant, anti-inflammatory and antibacterial properties. At the same time ascorbic acid reduces the epidermal barrier and wound contraction, among others. The objective of this research was to morphologically evaluate wound healing with treatment based on Ulmo honey (E. cordifolia) supplemented with ascorbic acid, comparing its effect with unsupplemented Ulmo honey, in wounds caused by type B burns. The research was approved by the Scientific Ethics Committee of the Universidad de La Frontera. We worked with 15 guinea pigs (Cavia porcellus) divided into three groups: SH (supplemented honey), H (honey), and Control + (Hydrogel-Tulle). A 1 cm diameter dry burn was caused on the back of the chest and covered the extent of the deep fascia. At day 10 of treatment, biopsies were removed and placed in PBS. They were subsequently fixed in buffered formalin and processed for histological purposes, with VGE, VGC, PAS, and Sirius Red techniques. The guinea pig was used as an animal model for having a metabolism dependent on ascorbic acid. The SH group showed a rapid debridement compared to control groups, with epidermal closure in 60% of the samples, and advanced proliferative phase was observed. The H group did not regenerate epidermal layer and showed an initial proliferative phase. The results of this study showed that supplementing Ulmo honey with ascorbic acid achieves faster healing when compared to unsupplemented Ulmo honey in wounds caused by burns.

Estudio comparativo de la cicatrización en quemaduras con tratamiento en base a miel de ulmo (eucryphia cordifolia) y vitamina C oral versus hidrogel en cobayos (cavia porcellus) / Comparative study of healing in burns treatment based on ulmo honey (eucryphia cordifolia) and oral vitamin C in guinea pig (cavia porcellus) versus hydrogel

La quemadura es una herida traumática que resulta en un daño local y sistémico, con cambios oxidativos. La miel posee actividad antioxidante, antiinflamatoria y antibacteriana. A su vez, la vitamina C mejora la barrera epidérmica y reduce la contracción de heridas, entre otros. El objetivo de este estudio fue evaluar morfológicamente el efecto del tratamiento con miel de ulmo + vitamina C en cobayo y comparar su capacidad cicatrizante y debridante con hydrogel+tull en heridas causadas por quemaduras tipo B al día 10 post-injuria. Se utilizaron 15 cobayos (Cavia porcellus) distribuidos en los grupos A (miel de ulmo tópica y vitamina C oral), B (hidrogel-tull), y Control (suero fisiológico al 0,9 por ciento). Se observó el debridamiento de las heridas, y se realizaron curaciones diarias hasta la obtención de biopsias al día 10 post-injuria. Secciones de 4 um fueron teñidas con HE, Tricrómico de Masson y PAS. En el grupo A se produjo un rápido debridamiento respecto al grupo B y Control. El tratamiento en estudio presentó una fase proliferativa avanzada al día 10 post-injuria, con tejido vascularizado, presencia de fibras colágenas y fibroblastos. La epidermis se regeneró por completo, presentando una lámina basal visible mediante la tinción PAS. El grupo B presentó una etapa fibroblástica proliferativa inicial, observándose elementos agudos a nivel dérmico. La fase de epitelización se completó solo en el 50 por ciento de las muestras. La miel ulmo + vitamina C mostraron ser sustanciasefectivas como material de tratamiento en la cicatrización de quemaduras tipo B de piel en cobayo.

A burn is a traumatic injury resulting in local and systemic injury with oxidative changes. Honey has antioxidant, anti-inflammatory and antibacterial properties. At the same time, among other benefits vitamin C improves the epidermal barrier and reduces wound contraction. The aim of this study was to evaluate morphologically the effect of regimen with Ulmo honey + vitamin C in guinea pigs and compare its healing and debriding potential with Hydrogel + tull in injuries caused by type B burns at day 10 post-injury. We used 15 guinea pigs (Cavia porcellus) distributed in groups A (Ulmo honey and vitamin C topical, oral), B (hydrogel-tull), and control (0.9 percent saline). Wound debridement was observed daily and wound treatment was performed daily until biopsies were obtained at day 10 post-injury. Four 4 um sections were stained with HE, Masson's trichrome and PAS. In group A there was rapid debridement when compared with groups B and Control. Treatment study presented advanced proliferative phase at day 10 post-injury with vascularized tissue, and presence of collagen fibers and fibroblasts. The epidermis was completely regenerated, presenting a visible basal lamina by PAS staining. Group B presented an initial proliferative fibroblastic phase, showing acute dermal elements. Epithelialization phase was completed in only 50 percent of the samples. Ulmo honey + vitamin C substances have been shown to be effective as treatment material in healing of type B burns in guinea pig skin.

Cicatrización en quemaduras tipo AB-B en conejillo de indias (Cavia porcellus) utilizando miel de ulmo asociada a vitamina C oral / Healing of burns type AB-B in guinea pig (Cavia Porcellus) using ulmo honey associated with oral vitamin C

En los últimos años se ha incrementado el interés por el uso de terapias alternativas para la curación de heridas. La miel de abeja es una antigua medicina natural que ha sido utilizada en el tratamiento de heridas y úlceras, mientras la vitamina C mejora la barrera epidérmica y reduce la contracción de heridas. Este estudio pretende avalar el tratamiento con miel asociada a vitamina C oral como curación alternativa y eficiente en quemaduras tipo AB-B. Se utilizaron 12 cuyes (Cavia porcellus). Los animales se distribuyeron en grupos A (sin Vitamina C) y B (con Vitamina C). Bajo efectos anestésicos se provocó una quemadura de 1.7 mm de diámetro en la región dorsal derecha, que fue tratada con curaciones con miel. Al mismo tiempo, se provocó una quemadura de similares características en la región dorsal izquierda, tratada con suero Ringer, siendo utilizada como control. De ambas lesiones se obtuvieron biopsias a los 6, 10 y 14 días post injuria. Nuestros resultados muestran que la formación de tejido granular, activación de fibroblastos, y reepitelización es más rápida en el grupo B, donde se observó un tejido vascularizado y fibras colágenas organizadas en el día 14 post injuria, similar al control (biopsia de animal sano). Estos datos confirman que la utilización de la miel de ulmo asociada a Vitamina C oral mejora la regenaración de este tipo de heridas, logrando una cicatrización efectiva, rápida y de buena calidad.

In recent years there has been increasing interest in the use of alternative therapies for healing wounds. Bee honey is an ancient natural medicine that has been used in the treatment of wounds and ulcers, while Vitamin C improves the epidermal barrier and reduces wound contraction. The aim of this study is to support treatment with honey associated with oral vitamin C as an alternative and efficient healing treatment, in type AB-B burns. For this study, twelve guinea pigs (Cavia porcellus) were used. The animals were distributed in groups A (without Vitamin C) and B (with Vitamin C). While under anesthetic effect burn of 1.7 mm in diameter was caused in the right dorsal region, subsequent healing was treated with honey. At the same time a burn of similar characteristics was caused in the left dorsal region, treated with Ringer serum being used as control. Biopsies were obtained from both lesions at days 6, 10 and 14 post injury. Results showed granular tissue formation, fibroblast activation, and reepitalization is more rapid in group B, where vascularized tissue and organized collagen fibers were observed at day 14 post injury similar to control (biopsy in healthy animal). These results confirm that the use of Ulmo honey associated with oral Vitamin C improves regeneration in this type of wound, achieving effective, rapid and good quality healing.