Long-term recurrence of Dupuytren's disease treated with clostridium histolitycum collagenase. Surgical treatment and anatomopathological study.

OBJECTIVE: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase. MATERIALS AND METHODS: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment. RESULTS: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy. CONCLUSIONS: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection. LEVEL OF EVIDENCE: III.

Gastric GDF15 levels are regulated by age, sex, and nutritional status in rodents and humans.

AIM: Growth differentiation factor 15 (GDF15) is a stress response cytokine that has been proposed as a relevant metabolic hormone. Descriptive studies have shown that plasma GDF15 levels are regulated by short term changes in nutritional status, such as fasting, or in obesity. However, few data exist regarding how GDF15 levels are regulated in peripheral tissues. The aim of the present work was to study the variations on gastric levels of GDF15 and its precursor under different physiological conditions, such as short-term changes in nutritional status or overfeeding achieved by HFD. Moreover, we also address the sex- and age-dependent alterations in GDF15 physiology. METHODS: The levels of gastric and plasma GDF15 and its precursor were measured in lean and obese mice, rats and humans by western blot, RT-PCR, ELISA, immunohistochemistry and by an in vitro organ culture system. RESULTS: Our results show a robust regulation of gastric GDF15 production by fasting in rodents. In obesity an increase in GDF15 secretion from the stomach is reflected with an increase in circulating levels of GDF15 in rats and humans. Moreover, gastric GDF15 levels increase with age in both rats and humans. Finally, gastric GDF15 levels display sexual dimorphism, which could explain the difference in circulating GFD15 levels between males and females, observed in both humans and rodents. CONCLUSIONS: Our results provide clear evidence that gastric GDF15 is a critical contributor of circulating GDF15 levels and can explain some of the metabolic effects induced by GDF15.

Can COVID-19 pandemic worsen previous neurological/psychiatric diseases?

Introduction: The SARS-CoV-2 pandemic has been affecting the world since January 2020. Although its pathogenesis is primarily directed to the respiratory tract, other organs may be affected, including the nervous system. It has also been shown that the social context (confinement, lack of treatment) has affected neurological patients during this period. The aim of the study it was to assess the subjective worsening of neurological/psychiatric diseases in the context of the SARS-Cov-2 pandemic. Methods: Three groups of neurological/psychiatric patients were included: Patients who had symptomatic COVID-19 (n = 89), patients who had asymptomatic COVID-19 (n = 40), and a control group (n = 47), consisting of neurological/psychiatric patients without a history of SARS-Cov-2 infection. Results: 30.7% of the included individuals considered that their basal pathology had worsened during the study period. This feeling was significantly more frequent (P = 0.01) in patients with symptomatic COVID-19 (39.3%) than in patients of the other 2 groups (21.8%). Worsening was not related to the severity of COVID-19. The neurological conditions that significantly worsened after COVID-19, comparing symptomatic COVID-19 with the other 2 groups, were demyelinating and degenerative diseases. Conclusions: These results confirmed the impact of the SARS-Cov-2 pandemic on patients with neurological/psychiatric diseases. Confinement, lack of medical care, and the threat of diagnosis are surely contributing factors. Although the finding of a higher frequency of worsening in symptomatic COVID-19 patients may be related to greater anxiety/depression in this group of patients, we cannot exclude the role of direct affectation of the nervous system by the virus or damage due to neuroinflammation.

Introducción: La pandemia por SARS-CoV-2 afecta al mundo desde enero de 2020. Aunque su patogenia se dirige principalmente a las vías respiratorias, otros órganos pueden verse afectados, incluido el sistema nervioso. También se ha demostrado que el contexto social (confinamiento, falta de tratamiento) ha afectado a los pacientes neurológicos durante este periodo. El objetivo del estudio fue evaluar el empeoramiento subjetivo de enfermedades neurológicas/psiquiátricas en el contexto de la pandemia por SARS-Cov-2. Métodos: Se incluyeron tres grupos de pacientes neurológicos/psiquiátricos: pacientes que tenían COVID-19 sintomático (n = 89), pacientes que tenían COVID-19 asintomático (n = 40) y un grupo control (n = 47), formado por pacientes neurológicos/psiquiátricos sin antecedentes de infección por SARS-Cov-2. Resultados: El 30,7% de los individuos incluidos consideró que su patología basal había empeorado durante el período de estudio. Este sentimiento fue significativamente más frecuente (p = 0,01) en pacientes con COVID-19 sintomático (39,3%) que en pacientes de los otros 2 grupos (21,8%). El empeoramiento no estuvo relacionado con la gravedad de COVID-19. Las condiciones neurológicas que empeoraron significativamente después de la COVID-19, comparando la COVID-19 sintomática con los otros 2 grupos, fueron las enfermedades desmielinizantes y degenerativas. Conclusiones: estos resultados confirmaron el impacto de la pandemia del SARS-Cov-2 en pacientes con enfermedades neurológicas/psiquiátricas. El encierro, la falta de atención médica y la amenaza del diagnóstico son seguramente factores contribuyentes. Aunque el hallazgo de una mayor frecuencia de empeoramiento en pacientes sintomáticos de COVID-19 puede estar relacionado con una mayor ansiedad/depresión en este grupo de pacientes, no podemos excluir el papel de la afectación directa del sistema nervioso por el virus o el daño por neuroinflamación.

Hipótesis: un paso central en el pensamiento clínico y la generación de evidencia científica / Hypothesis: an important step in the clinical thinking and the development of scientific evidence

Resumen: El entrenamiento en metodologías de la investigación refuerza diversas habilidades críticas para los profesionales de la salud. El planteamiento de hipótesis, lejos de ser un proceso trivial, constituye un paso fundamental para adquirir un adecuado razonamiento clínico. En el presente artículo, los conceptos de conjetura, hipótesis, teorías y pregunta de investigación son revisados y se enfatiza la importancia del criterio científico en la formación de las escuelas de salud.

Abstract: The training in research methods enhance several abilities that are critical for the health professionals. The adequate proposition of hypothesis, far from being a trivial process, constitutes a fundamental step for acquiring an adequate clinical reasoning. In this article, the concepts of conjecture, hypothesis theories and research question are reviewed and the relevance of the scientific criteria for health professionals is emphasized.

Basic Skin Care and Topical Therapies for Atopic Dermatitis: Essential Approaches and Beyond.

Atopic dermatitis (AD) is a recurrent and chronic skin disease characterized by dysfunction of the epithelial barrier, skin inflammation, and immune dysregulation, with changes in the skin microbiota and colonization by Staphylococcus aureus being common. For this reason, the therapeutic approach to AD is complex and should be directed at restoring skin barrier function, reducing dehydration, maintaining acidic pH, and avoiding superinfection and exposure to possible allergens. There is no curative treatment for AD. However, a series of measures are recommended to alleviate the disease and enable patients to improve their quality of life. These include adequate skin hydration and restoration of the skin barrier with the use of emollients, antibacterial measures, specific approaches to reduce pruritus and scratching, wet wrap applications, avoidance of typical AD triggers, and topical anti-inflammatory drugs. Anti-inflammatory treatment is generally recommended during acute flares or, more recently, for preventive management. Nevertheless, the selection of the pharmacologic agent, as well as its potency, duration, and frequency of application must be in accordance with the severity of the disease and the distribution and type of the lesion. The objectives of this review are to emphasize the importance of basic skin care and to describe current and novel topical therapies for AD.

Glaucoma melanomalítico secundario a melanoma de iris / Melanomalytic glaucoma secondary to iris melanoma

Caso clínico: Varón de 35 años con hipertensión ocular en el ojo derecho (OD). En segmento anterior se observó una masa melanótica. La presión intraocular (PIO) fue de 40mmHg en el OD. En la gonioscopia se observó una masa iridiana con extensión camerular. Se realizó biopsia escisional confirmando el diagnóstico de melanoma de iris y glaucoma melanomalítico. Se asoció tratamiento con braquiterapia epiescleral adyuvante. Discusión: A los pacientes que presentan glaucoma unilateral, con aumento de pigmentación en malla trabecular, es esencial realizar pruebas de imagen. La resección mediante iridectomía junto con braquiterapia adyuvante es eficaz en el control de la enfermedad (AU)

Clinical case: A 35-year-old male with unilateral ocular hypertension in the right eye (RE). Anterior segment examination of the RE showed a melanotic lesion. Intraocular pressure (IOP) was 40mmHg in RE. Gonioscopy revealed extension into the anterior chamber angle. Excisional biopsy was performed and consistent with iris melanoma and secondary melanomalytic glaucoma. Brachytherapy was performed as adjuvant therapy. Discussion: In patients presenting with unilateral glaucoma and increased pigmentation in the trabecular meshwork, it is crucial to perform imaging studies. Resection by iridectomy with adjuvant episcleral brachytherapy is effective in controlling the disease (AU)

Melanomalytic glaucoma secondary to iris melanoma. / Glaucoma melanomalítico secundario a melanoma de iris.

CLINICAL CASE: A 35-year-old male with unilateral ocular hypertension in the right eye (RE). Anterior segment examination of the RE showed a melanotic lesion. Intraocular pressure (IOP) was 40mmHg in RE. Gonioscopy revealed extension into the anterior chamber angle. Excisional biopsy was performed and consistent with iris melanoma and secondary melanomalytic glaucoma. Brachytherapy was performed as adjuvant therapy. DISCUSSION: In patients presenting with unilateral glaucoma and increased pigmentation in the trabecular meshwork, it is crucial to perform imaging studies. Resection by iridectomy with adjuvant episcleral brachytherapy is effective in controlling the disease.

Dysbiotic bacteria translocate in progressive SIV infection.

Infection of gut-resident CD4(+) memory T cells during acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is associated with rapid loss of these cells and damage to the epithelial barrier. Damage to the epithelial barrier allows translocation of microbial products from the intestinal lumen into the body. Immune activation caused by these microbial products has been associated with disease progression. Although microbial translocation has been demonstrated in SIV-infected nonhuman primates, the identity of translocating bacteria has not been determined. In this study we examined the communities of bacteria both within the gastrointestinal (GI) tract and systemic tissues of both healthy and experimentally SIV-infected Asian macaques. Although there were only modest changes in the GI tract-associated microbiome resulting from infection, there is substantial dysbiosis after administration of antiretrovirals. Analysis of bacterial DNA isolated from tissues of infected animals revealed a preference for the phylum Proteobacteria, suggesting that they preferentially translocate. Consistent with this finding, we observed increased metabolic activity of Proteobacterial species within the colonic lumen of SIV-infected animals. Overall, these data provide insights into disease progression and suggest that therapies aimed at altering the composition and metabolic activity of the GI tract microbiome could benefit chronically HIV-infected individuals, particularly those on antiretroviral therapies.

Plasmodium genetic loci linked to host cytokine and chemokine responses.

Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1ß, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1ß, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

The brain: a new organ for the metabolic actions of SIRT1.

The sirtuins are a family of highly conserved nicotine adenine dinucleotide (NAD+)-dependent deacetylases that act as cellular sensors to detect energy availability and regulate metabolic processes. Sirtuin 1 (SIRT1) is one of the family members that is activated in response to caloric restriction, acting on multiple targets in a wide range of tissues. Recent studies have shown that SIRT1 controls glucose and lipid metabolism in both liver and muscle, promotes fat mobilization, stimulates remodeling of white to brown fat, controls insulin secretion in the pancreas, and senses nutrient availability in the hypothalamus. SIRT1 is located in several areas of the brain and its central metabolic actions have attracted much attention in the last decade. In this short review, we summarize the main actions and molecular pathways triggered by SIRT1 that control feeding behavior, energy expenditure, glucose metabolism, and insulin sensitivity, with an emphasis on the emerging role of SIRT1 in the brain.

Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo-controlled maintenance treatment for bipolar depression.

OBJECTIVE: To compare the maintenance efficacy of lamotrigine (Lam) to combination therapy of Lam+divalproex ER (Div) in recently depressed patients with bipolar disorder (BD). METHOD: We randomized 86 BD I or II patients in a major depressive episode to 8 months of double-blind treatment with Lam+placebo or Lam+Div. To be eligible for randomization, patients had to achieve control of both depressive and manic symptoms during an open phase that included both Lam and Div. RESULTS: Time to depressive episode did not differ significantly by Kaplan-Maier survival analysis (χ2=1.82, df=1, P=0.18). However, several secondary outcomes did show significant differences. The proportion of Lam+placebo patients who had at least one Montgomery-Asberg Depression Rating Scale (MADRS) score≥15 during the maintenance phase was 67% (30/45) compared with 44% (18/41) for the Lam+Div group (χ2=4.51, P=0.03). Among BD I patients assigned to Lam+placebo, 71.4% (25/35) had at least one visit with MADRS score≥15 compared with 36.7% (11/30) among Lam+Div patients (χ2=7.89, df=1, P=0.005). CONCLUSION: Lam+Div generally provided greater maintenance efficacy than Lam alone for depressive indices in recently depressed BD patients.

[The polyphenols, naturally occurring compounds with beneficial effects on cardiovascular disease]. / Los polifenoles, compuestos de origen natural con efectos saludables sobre el sistema cardiovascular.

In recent years, a number of studies have endorsed the beneficial effects of polyphenols intake on health, especially on the cardiovascular system. This is important since cardiovascular diseases are the main death cause worldwide. The effects of polyphenols are mainly due to their antioxidant properties. These compounds present vasodilating effects, and they can improve the lipid profile and lessen the oxidation of low-density lipoproteins (LDL). They show clear antiinflammatory effects and they can modulate the apoptotic pathways in the vascular endothelium. This review defines from the structural viewpoint the different groups of polyphenols that may occur in vegetables, and updates the knowledge on their bioavailability. Some of the recent studies establishing their beneficial properties at a cardiovascular level are also included.

Los polifenoles, compuestos de origen natural con efectos saludables sobre el sistema cardiovascular / The polyphenols, naturally occurring compounds with beneficial effects

En los últimos años numerosos estudios han avalado los efectos beneficiosos de la ingesta de polifenoles sobre la salud, especialmente sobre el sistema cardiovascular. Esto es importante, porque las enfermedades cardiovasculares son la principal causa de muerte en el mundo. Los efectos de los polifenoles son fundamentalmente consecuencia de sus propiedades antioxidantes. Estos compuestos presentan efectos vasodilatadores, son capaces además de mejorar el perfil lipídico y atenúan la oxidación de las lipoproteínas de baja densidad (LDL). Presentan claros efectos antiinflamatorios y estos compuestos son a su vez capaces de modular los procesos de apoptosis en el endotelio vascular. Esta revisión define desde el punto de vista estructural, los distintos grupos de polifenoles que pueden formarse en los vegetales y actualiza los conocimientos sobre su biodisponibilidad. En ella se recopilan asimismo algunos de los estudios recientes que establecen sus propiedades beneficiosas a nivel cardiovascular (AU)

In recent years, a number of studies have endorsed the beneficial effects of polyphenols intake on health, especially on the cardiovascular system. This is important since cardiovascular diseases are the main death cause worldwide. The effects of polyphenols are mainly due to their antioxidant properties. These compounds present vasodilating effects, and they can improve the lipid profile and lessen the oxidation of low-density lipoproteins(LDL). They show clear anti inflammatory effects and they can modulate the apoptotic pathways in the vascular endothelium. This review defines from the structural viewpoint the different groups of polyphenols that may occur in vegetables, and updates the knowledge on their bioavailability. Some of the recent studies establishing their beneficial properties at a cardiovascular level are also included (AU)

Effect of a cocoa polyphenol extract in spontaneously hypertensive rats.

In this study, we evaluated the short-term effect of a cocoa polyphenol extract (CPE), in spontaneously hypertensive rats (SHR). Male 17-22-week-old SHR were administered by intragastric gavage water, 50 mg kg(-1) Captopril or CPE at different doses (13, 26, 80 and 160 mg kg(-1)). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by the tail cuff method before the administration and also 2, 4, 6, 8, 24, 48 and 72 h post-administration. Highly significant decreases in the SBP and in the DBP were observed when captopril or CPE was administered to SHR. The cocoa extract produced a dose dependent effect in the SBP of the SHR up to the dose of 80 mg kg(-1). Nevertheless this dose of CPE did not decrease the arterial blood pressure in the normotensive Wistar Kyoto rats. The decrease in the SBP caused by 80 mg kg(-1) of CPE in the SHR (-39.1 ± 3.7 mm Hg) was maximum 6 h post-administration, and the initial values of SBP were recovered 72 h post-administration of this extract. Paradoxically, 160 mg kg(-1) of the cocoa extract caused a decreased antihypertensive effect than lower doses of CPE. In addition, the decrease in DBP was always more accentuated when the dose of CPE administered was lower. Our results suggest that CPE may be used as a functional food ingredient with beneficial effects for controlling arterial blood pressure.

Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy + Apoe -/- mouse model of the metabolic syndrome.

AIMS/HYPOTHESIS: Chemokines and their receptors such as chemokine (C-C motif) receptor 2 (CCR2) may contribute to the pathogenesis of the metabolic syndrome via their effects on inflammatory monocytes. Increased accumulation of CCR2-driven inflammatory monocytes in epididymal fat pads is thought to favour the development of insulin resistance. Ultimately, the resulting hyperglycaemia and dyslipidaemia contribute to development of the metabolic syndrome complications such as cardiovascular disease and diabetic nephropathy. Our goal was to elucidate the role of CCR2 and inflammatory monocytes in a mouse model that resembles the human metabolic syndrome. METHODS: We generated a model of the metabolic syndrome by backcrossing KKAy ( + ) with Apoe ( -/- ) mice (KKAy ( + ) Apoe ( -/- )) and studied the role of CCR2 in this model system. RESULTS: KKAy ( + ) Apoe ( -/- ) mice were characterised by the presence of obesity, insulin resistance, dyslipidaemia and increased systemic inflammation. This model also manifested two complications of the metabolic syndrome: atherosclerosis and diabetic nephropathy. Inactivation of Ccr2 in KKAy (+) Apoe ( -/- ) mice protected against the metabolic syndrome, as well as atherosclerosis and diabetic nephropathy. This protective phenotype was associated with a reduced number of inflammatory monocytes in the liver and muscle, but not in the epididymal fat pads; circulating levels of adipokines such as leptin, resistin and adiponectin were also not reduced. Interestingly, the proportion of inflammatory monocytes in the liver, pancreas and muscle, but not in the epididymal fat pads, correlated significantly with peripheral glucose levels. CONCLUSIONS/INTERPRETATION: CCR2-driven inflammatory monocyte accumulation in the liver and muscle may be a critical pathogenic factor in the development of the metabolic syndrome.