Sustained Hyperglycemia and Its Relationship with the Outcome of Hospitalized Patients with Severe COVID-19: Potential Role of ACE2 Upregulation.

Chronic hyperglycemia increases the risk of developing severe COVID-19 symptoms, but the related mechanisms are unclear. A mean glucose level upon hospital admission >166 mg/dl correlates positively with acute respiratory distress syndrome in patients with hyperglycemia. The objective of this study was to evaluate the relationship between sustained hyperglycemia and the outcome of hospitalized patients with severe COVID-19. We also evaluated the effect of high glucose concentrations on the expression of angiotensin-converting enzyme 2 (ACE2). We carried out a case-control study with hospitalized patients with severe COVID-19 with and without sustained hyperglycemia. In a second stage, we performed in vitro assays evaluating the effects of high glucose concentrations on ACE2 gene expression. Fifty hospitalized patients with severe COVID-19 were included, of which 28 (56%) died and 22 (44%) recovered. Patients who died due to COVID-19 and COVID-19 survivors had a high prevalence of hyperglycemia (96.4% versus 90.9%), with elevated central glucose upon admission (197.7 mg/dl versus 155.9 mg/dl, p = 0.089) and at discharge (185.2 mg/dl versus 134 mg/dl, p = 0.038). The mean hypoxemia level upon hospital admission was 81% in patients who died due to COVID-19 complications and 88% in patients who survived (p = 0.026); at the time of discharge, hypoxemia levels were also different between the groups (68% versus 92%, p ≤ 0.001). In vitro assays showed that the viability of A549 cells decreased (76.41%) as the glucose concentration increased, and the ACE2 gene was overexpressed 9.91-fold after 72 h (p ≤ 0.001). The relationship between hyperglycemia and COVID-19 in hospitalized patients with COVID-19 plays an important role in COVID-19-related complications and the outcome for these patients. In patients with chronic and/or sustained hyperglycemia, the upregulation of ACE2, and its potential glycation and malfunction, could be related to complications observed in patients with COVID-19.

A Systematic Stepwise Method to Perform a Supermicrosurgical Lymphovenous Anastomosis.

BACKGROUND: Lymphovenous anastomosis (LVA) has become an increasingly common treatment for patients with extremity lymphedema. In this article, we present our current strategy for patient selection, preoperative planning, and a series of intraoperative clues that may help to perform a supermicrosurgical LVA. Technical considerations are presented using a systematic step-by-step method to make this procedure more reproducible and straightforward. PATIENTS AND METHODS: We conducted a review of patients operated between January 2015 and June 2018 using the aforementioned approach. Data were collected prospectively, and all procedures were performed by the senior author. Preoperative assessment included lymphoscintigraphy, indocyanine green lymphography, noncontrast magnetic resonance lymphography and high-frequency ultrasonography. Lymphovenous anastomosis was decomposed into a sequential 6-step approach considering the main aspects that determine a successful anastomosis. RESULTS: Lymphovenous anastomosis was performed in 229 patients, including 677 anastomoses. Median follow-up was 33 months (range, 13-51 months). A median of 3.1 (range, 1-7) LVA were performed on 2.7 (range, 1-6) incision sites per patient. Median time for dissection of lymphatic(s) and vein(s) was 8.7 minutes (1-18 minutes) with a median time of 27.2 minutes (range, 13-51 minutes) for a complete LVA. Lymphatic detection rate was 100% (677 of 677) and vein detection rate was 99.7% (675 of 677), with 31.0% (210 of 677) of reflux-free veins. For upper-extremity lymphedema (47 of 229; 20.6%), volume reduction was achieved in 100% (47 of 47) of the cases, with a median volume reduction rate of 67% (range, 7-93%). In lower-extremity lymphedema (182 of 229; 79.4%), volume reduction was achieved in 86.8% (158 of 182) of the cases, with a median volume reduction rate of 41% (range, 7-81%). Cellulitis episodes decreased from 2.1 to 0.2 episodes/year after LVA (P < 0.05). CONCLUSIONS: Acceptable success rates were obtained using a sequential strategy for planning and execution of supermicrosurgical LVA for secondary extremity lymphedema. We believe including a stepwise approach may help to simplify this procedure, especially for surgeons in their early practice.

Radical reduction and reconstruction for male genital elephantiasis: Superficial circumflex iliac artery perforator (SCIP) lymphatic flap transfer after elephantiasis tissue resection.

BACKGROUND: Treatment of elephantiasis, the most severe lymphedema, is challenging. Management of male genital elephantiasis (MGE) is even more challenging than extremity elephantiasis due to its complicated shape and high risk of lymphorrhea and cellulitis. Complete resection of fibrous tissue and lymphatic reconstruction is considered to be ideal for the treatment of MGE. The aim of this study was to evaluate the feasibility of radical reduction and reconstruction (3R) for isolated MGE. METHODS: Medical charts of patients who underwent 3R were reviewed. The 3R operation consisted of genital fibrous tissue resection and reconstruction of soft tissue and lymphatic structure using superficial circumflex iliac artery perforator (SCIP) lymphatic flap transfer (LFT). No compression was applied postoperatively. Patient and flap characteristics, intraoperative findings, and postoperative results were evaluated. RESULTS: Seven patients were included. MGE included isolated scrotal elephantiasis in 4 cases, and scrotal and penile elephantiasis in 3 cases. Resected tissue volume ranged from 609 to 2304 grams (average, 1511.0 grams). SCIP-LFT was performed in all cases; pedicled full-thickness SCIP-LFT for scrotal reconstruction in all cases, and SCIP pure-skin-perforator flap transfer for penile reconstruction in 3 cases. There was no postoperative genital complication or evidence of genital lymphedema recurrence in the mean follow-up period of 22.7 months. Genital lymphedema scores significantly improved postoperatively (6.7 ± 1.8 vs. 0.3 ± 0.5, P <0.001). CONCLUSIONS: 3R operation allowed one-stage curative treatment for MGE. LFT has the potential to play an essential role in the prevention of postoperative wound complications and lymphedema recurrence after radical resection of fibrotic tissue.

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19.

Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. Vitamin C (ascorbic acid, AA) is an essential nutrient with many biological roles that have been proven to play an important part in immune function; it serves as an antioxidant, an anti-viral, and exerts anti-thrombotic effects among many other physiological benefits. Research has proven that AA at pharmacological doses can be beneficial to patients with acute respiratory distress syndrome (ARDS) and other respiratory illnesses, including sepsis. In addition, High-Dose Intravenous Vitamin C (HDIVC) has proven to be effective in patients with different viral diseases, such as influenza, chikungunya, Zika, and dengue. Moreover, HDIVC has been demonstrated to be very safe. Regarding COVID-19, vitamin C can suppress the cytokine storm, reduce thrombotic complications, and diminish alveolar and vascular damage, among other benefits. Due to these reasons, the use of HDIVC should be seriously considered in complicated COVID-19 patients. In this article, we will emphasize vitamin C's multiple roles in the most prominent pathophysiological processes presented by the COVID-19 disease.

Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19.

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

Effect of dietary inclusion of winter brassica crops on milk production, feeding behavior, rumen fermentation, and plasma fatty acid profile in dairy cows.

This study determined feeding behavior, dry matter (DM) intake (DMI), rumen fermentation, and milk production responses of lactating dairy cows fed with kale (Brassica oleracea) or swede (Brassica napus ssp. napobrassica). Twelve multiparous lactating dairy cows (560 ± 22 kg of body weight, 30 ± 4 kg of milk/d, and 60 ± 11 d in milk at the beginning of the experiment; mean ± standard deviation) were randomly allocated to 3 dietary treatments in a replicated 3 × 3 Latin square design. The control diet comprised 10 kg of grass silage DM/d, 4 kg of ryegrass herbage DM/d, and 8.8 kg of concentrate DM/d. Then, 25% of herbage, silage, and concentrate (DM basis) was replaced with either kale or swede. Cows offered kale had decreased total DMI compared with cows fed the control and swede diets, whereas inclusion of swede increased eating time. Milk production, composition, and energy-corrected milk:DMI ratio were not affected. Cows fed with kale had a greater rumen acetate:propionate ratio, whereas swede inclusion increased the relative percentage of butyrate. Estimated microbial N was not affected by dietary treatments, but N excretion was reduced with inclusion of kale, improving N utilization. Cows fed kale tended to have increased nonesterified fatty acids and showed presence of Heinz-Ehrlich bodies, whereas hepatic enzymes such as aspartate aminotransferase, γ-glutamyl transferase, and glutamate dehydrogenase were not affected by dietary treatments. In plasma, compared with the control, swede and kale reduced total saturated fatty acids and increased total polyunsaturated fatty acids and total n-3 fatty acids. Overall, feeding cows with winter brassicas had no negative effect on production responses. However, mechanisms to maintain milk production were different. Inclusion of swede increased the time spent eating and maintained DMI with a greater relative rumen percentage of butyrate and propionate, whereas kale reduced DMI but increased triacylglycerides mobilization, which can negatively affect reproductive performance. Thus, the inclusion of swede may be more suitable for feeding early-lactating dairy cows during winter.

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection.

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.

Introduction: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome. Methods: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene. Results: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/µl ± 0.30) and controls (3.3 ng/µl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/µl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/µl) were also observed (p = 0.037). Conclusion: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.

The role of close contacts of COVID-19 patients in the SARS-CoV-2 transmission: an emphasis on the percentage of nonevaluated positivity in Mexico.

OBJECTIVES: To determine the percentage of positivity of close contacts of coronavirus disease 19 (COVID-19) patients to depict the importance of asymptomatic infections in the patient-to-patient transmission of COVID-19. METHODS: One hundred subjects were included. Nineteen index COVID-19 cases and 81 traced close contacts were screened for coronavirus 2 of severe acute respiratory syndrome (SARS-CoV-2) using real-time reverse transcription-polymerase chain reaction. Immunoglobulin M and G against SARS-CoV-2 were evaluated by rapid test. RESULTS: Thirty-four (42%) contacts in the study were positive for SARS-CoV-2. Twenty-three (67.6%) manifested less than 2 respiratory symptoms, and 5 (14.7%) remained asymptomatic. The average of positive contacts by index COVID-19 case (R0) was 4.3 and the mean of time of positive COVID-19 test at sampling time was 18.9 days. Positive antibody test against SARS-CoV-2 was observed in 16% of the participants. CONCLUSION: The proportion of close contacts of COVID-19 patients infected with SARS-CoV-2 (42%) and with less than 2 or with no respiratory symptoms (82.4%) was high in the study population. A low proportion of COVID-19 patients had a positive test for antibodies against SARS-CoV-2. The screening for SARS-CoV-2 in close contacts of COVID-19 positive patients should be encouraged to avoid spreading the infection and the expansion of the disease.

Cognitive Functioning and Cortical Brain Thickness in Acromegaly Patients: A Pilot study.

OBJECTIVE: Cognitive effects in acromegaly patients are poorly understood and the mechanisms involved are still unclear. The aim of this study was to evaluate the cognitive function, depression, and quality of life of acromegaly patients treated with pegvisomant versus somatostatin analogues (SRLs) and to analyze the effect of the different treatments on cognition and possible structural brain changes. METHODS: This cross-sectional study involved 23 acromegaly patients divided into two groups according to treatment modality: One group of 9 patients treated with pegvisomant and another group of 14 patients treated with SRLs. All participants underwent blood analysis, neuropsychological tests, depression tests, quality of life assessment, and 3-Tesla magnetic resonance imaging. RESULTS: We found no significant differences between groups in the neuropsychological tests, depression or quality of life; nor in the whole-brain cortical thickness. In the SRL group, the volume of the thalamus correlated positively with executive function, a correlation not found in the pegvisomant group. In addition, the pegvisomant group had significantly higher levels of insulin than the SRL group. CONCLUSIONS: In conclusion, in this pilot study, the type of pharmacological treatment in patients with acromegaly and good glycemic control did not influence the cognitive function and cortical brain thickness. However, pegvisomant could play a neuroprotective role on the thalamus that will have to be demonstrated with larger samples in future studies.

Clinical features, microbiological epidemiology and recommendations for management of cellulitis in extremity lymphedema.

BACKGROUND: This high volume, single center study investigated the prevalence, bacterial epidemiology, and responsiveness to antibiotic therapy of cellulitis in extremity lymphedema. METHODS: From 2003 to 2018, cellulitis events from a cohort of 420 patients with extremity lymphedema were reviewed. Demographics, lymphedema grading, symptoms, inflammatory markers, cultures and antibiotic therapy regimens were compiled from cellulitis episodes data. Univariate and multivariate analyses were performed for detailed analysis. RESULTS: A total of 131 separate episodes of cellulitis were recorded from 43 (81.1%) lower limb and 10 (19.9%) upper limb lymphedema patients. The prevalence and recurrence rates for cellulitis in lymphedema patients were 12.6% (53 of 420) and 56.6% (30 of 53), respectively. The most common findings were increased limb circumference (127 of 131; 96.9%) and abnormal C-reactive protein (CRP) level (86 of 113; 76.1%). Blood cultures were obtained in 79 (60.3%) incidents, with 9 (11.4%) returning positive. Streptococcus agalactiae was the most isolated bacterium (5 of 9; 55.5%). CONCLUSIONS: The cellulitis prevalence and recurrence rate in extremity lymphedema were 12.6%, and 56.6%, respectively. Strongest indicators of cellulitis were increased affected limb circumference and elevated CRP level. Empiric antibiotic therapy began with coverage for Steptococcus species before broadening to anti-Methicillin-resistant Staphylococcus aureus and anti-Gram negatives if needed for effective treatment of extremity lymphedema cellulitis.

Diaphragmatic Hernia Associated With Absent Ductus Venosus and Anomalous Connection of an Obliterated Umbilical Vein to the Coronary Sinus.

Umbilical vein anomalies are a rare congenital defect, which have been associated with absent ductus venosus, with few cases also involving a congenital diaphragmatic hernia. We describe a case of postnatal development of an anterior diaphragmatic hernia of Morgagni in a four-year-old patient diagnosed prenatally with mesocardia, absent ductus venosus with a large umbilical vein, a large secundum atrial septal defect, and patent ductus arteriosus.

Polifarmacia en adulto mayor, impacto en su calidad de vida: revision de literatura / Polypharmacy in older adults and impact on their quality of life: literature review / Polifarmácia em idosos, impacto em sua qualidade de vida: revisão da literatura

RESUMEN: Objetivo: Conocer mediante el análisis del estado del conocimiento, el impacto de polifarmacia en calidad de vida de adultos mayores y cuál ha sido el rol de enfermería frente a esta problemática de salud. Métodos: Revisión descriptiva de 62 artículos originales de diversos diseños metodológicos, en bases de datos: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS y Dialnet. Resultados: La polifarmacia en adultos mayores se presenta con mayor frecuencia en el sexo femenino, en personas con bajo nivel de escolaridad, sumados a factores socioeconómico. Un gran porcentaje de adultos mayores presenta efecto cascada en consumo de fármacos, por cantidad de medicamentos consumidos y número de médicos consultados, produciendo interacciones farmacológicas, afectando funcionalidad y calidad de vida. Conclusiones: Es necesario mayor control de medicamentos consumidos por adultos mayores, para evitar efectos nocivos. Los profesionales de enfermería deben tener un rol educativo en este grupo etario, para disminuir polifarmacia e impulsar estilos de vida que fomenten el envejecimiento saludable.(AU)

ABSTRACT: Objective: To know, by analyzing the state of knowledge, the impact of the polypharmacy on the quality of life of older adults and the role of nursing when dealing with this health problem. Materials and Methods: Descriptive review of 62 original articles with multiple methodological designs, in the databases EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS and Dialnet. Results: Polypharmacy in older adults is more frequent in the female sex and people with low level of education, and is associated with socioeconomic factors. A large percentage of older adults present with prescription cascade due to the amount of drugs consumed and the number of doctors consulted, leading to pharmacological interactions that affect functionality and quality of life. Conclusions: More control of drugs consumed by older adults is needed to avoid harmful effects. Nursing professionals should have an educational role in this age group to reduce polypharmacy and promote lifestyles that foster healthy ageing.(AU)

RESUMO: Objetivo: Conhecer, através da análise do estado do conhecimento, o impacto da polifarmácia na qualidade de vida do idoso e qual o papel da enfermagem diante desse problema de saúde. Métodos: Revisão descritiva de 62 artigos originais de vários desenhos metodológicos, nas bases de dados: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS e Dialnet. Resultados: A polifarmácia em idosos ocorre mais frequentemente no sexo feminino, em pessoas com baixa escolaridade, somada a fatores socioeconômicos. Uma grande porcentagem de idosos apresenta efeito cascata no consumo de medicamentos, pela quantidade de medicamentos consumidos e número de médicos consultados, produzindo interações farmacológicas, afetando a funcionalidade e a qualidade de vida. Conclusões: É necessário um maior controle dos medicamentos consumidos por idosos para evitar efeitos nocivos. Os profissionais de enfermagem devem ter papel educativo nessa faixa etária, para diminuir a polifarmácia e promover estilos de vida que promovam o envelhecimento saudável.(AU)

[Polypharmacy in older adults and impact on their quality of life. Literature review]. / Polifarmacia en adulto mayor, impacto en su calidad de vida. Revision de literatura.

OBJECTIVE: To know, by analyzing the state of knowledge, the impact of the polypharmacy on the quality of life of older adults and the role of nursing when dealing with this health problem. MATERIALS AND METHODS: Descriptive review of 62 original articles with multiple methodological designs, in the databases EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS and Dialnet. RESULTS: Polypharmacy in older adults is more frequent in the female sex and people with low level of education, and is associated with socioeconomic factors. A large percentage of older adults present with prescription cascade due to the amount of drugs consumed and the number of doctors consulted, leading to pharmacological interactions that affect functionality and quality of life. CONCLUSIONS: More control of drugs consumed by older adults is needed to avoid harmful effects. Nursing professionals should have an educational role in this age group to reduce polypharmacy and promote lifestyles that foster healthy ageing.

OBJETIVO: Conocer mediante el análisis del estado del conocimiento, el impacto de polifarmacia en calidad de vida de adultos mayores y cuál ha sido el rol de enfermería frente a esta problemática de salud. MÉTODOS: Revisión descriptiva de 62 artículos originales de diversos diseños metodológicos, en bases de datos: EBSCO, PubMed, Web of Science, SciELO, Elsevier, SCOPUS y Dialnet. RESULTADOS: La polifarmacia en adultos mayores se presenta con mayor frecuencia en el sexo femenino, en personas con bajo nivel de escolaridad, sumados a factores socioeconómico. Un gran porcentaje de adultos mayores presenta efecto cascada en consumo de fármacos, por cantidad de medicamentos consumidos y número de médicos consultados, produciendo interacciones farmacológicas, afectando funcionalidad y calidad de vida. CONCLUSIONES: Es necesario mayor control de medicamentos consumidos por adultos mayores, para evitar efectos nocivos. Los profesionales de enfermería deben tener un rol educativo en este grupo etario, para disminuir polifarmacia e impulsar estilos de vida que fomenten el envejecimiento saludable.

In Vitro Evaluation of BacT/Alert FA Blood Culture Bottles and T2Candida Assay for Detection of Candida in the Presence of Antifungals.

The T2Candida assay is a novel, non-culture-based assay for the diagnosis of candidemia directly from whole blood. The impact of antifungals on the performance of the T2Candida assay and blood culture bottles has not been well described. In this study, the performance of the T2Candida assay was compared to that of blood culture in detecting Candida spp. in spiked blood cultures with or without the presence of antifungals. Clinical bloodstream isolates of Candida spp. were inoculated into human whole blood at low (1 to 5 cells/ml) and high (10 to 50 cells/ml) concentrations with or without the presence of caspofungin and fluconazole. Time to detection (TTD) was assessed for prepared samples using BacT/Alert FA aerobic blood culture bottles or the T2Candida assay. In the absence of antifungals, T2Candida assay sensitivity was comparable to that of blood culture at both the low inoculum and the high inoculum (95% versus 97.5% and 100% versus 100%, respectively) and the assay had an average TTD that was significantly shorter (5.1 h versus 27.2 to 30 h, respectively). Neither caspofungin nor fluconazole was observed to impact the sensitivity or TTD of the T2Candida assay, while fluconazole reduced the overall blood culture sensitivity by 7.5% to 12.5% (at the low inoculum and high inoculum, respectively) and significantly increased the TTD of Candida albicans, C. tropicalis, and C. parapsilosis by 14.8 to 67 h. Neither caspofungin nor fluconazole impacted the performance of the T2Candida assay in vitro, and the assay may be useful for the diagnosis of candidemia in patients receiving antifungal therapy.

Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients.

INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP.

Uso de colgajos perforantes para el tratamiento de hidradenitis supurativa axilar y esternal graves / Use of perforator flaps for treatment of severe axillary and sternal hidradenitis suppurativa

Resumen Objetivo: Presentar una serie de reconstrucciones con colgajos perforantes en pacientes con casos severos de hidradenitis supurativa y sus resultados. Pacientes y métodos: Se realizaron 7 reconstrucciones axilares y un caso de reconstrucción esternal en 5 pacientes. Todos los pacientes correspondieron a la clasificación II o III de Hurley, y fueron derivados a nuestro servicio después de por lo menos un año de tratamiento médico sin obtener resultados. El equipo de cirugía plástica realizó tanto la resección como la reconstrucción en todos los casos. Los vasos perforantes fueron marcados con un dispositivo Doppler sonido. Resultados: Se obtuvo cobertura en todos los casos, con solo una pérdida parcial de colgajo que fue resuelta con curaciones. Tras un seguimiento de 26 meses, no hubo recidiva de hidradenitis supurativa. Todas las reconstrucciones evolucionaron con resultados funcionales óptimos. Conclusión: Los colgajos perforantes son una buena alternativa para el tratamiento de casos severos de hidradenitis supurativa, tanto esternal como axilar. Por esta razón, debe ser considerado en el armamento de cirujanos plásticos que traten esta enfermedad, una vez que el tratamiento médico haya fallado.

Abstract Aim: To present a brief series of reconstructions with perforator flaps in severe cases of hidradenitis suppurativa patients and results. Patients and methods: Seven axillary and one sternal case in five patients were operated on. All patients were in stage II or III according to Hurley classification, and were referred after at least one year of medical treatment with no satisfactory result. The plastic surgery team performed both, resection and reconstruction in all cases. Perforator vessels were marked using a handheld Doppler device. Results: One partial flap failure occurred, which healed with standard wound care. After a median follow up of 26 months, no relapse of hidradenitis suppurativa occurred. All reconstructions evolved with full functional results. Conclusion: Perforator flaps are a good choice in the treatment of severe cases of hidradenitis suppurativa, both sternal and axillary. It should be considered in the armamentarium of any plastic surgeon treating patients with this condition, once the medical treatment has failed.

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women.

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m²) was 38.15 ± 4.7 vs. 34.18 ± 4.5 (p < 0.02), and body weight (kg) was 98.5 ± 13.1 vs. 88.28 ± 12.2 (p < 0.03). All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001), left posterior cingulate (p < 0.001), and right posterior cingulate (p < 0.03); decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01); decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025); and decreased connectivity between the left and right posterior cingulate (p < 0.04). Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex) may be modified by a weight loss program including a Mediterranean diet and physical exercise.

SCORE study: quality indicators for rheumatology nursing clinics.

Nursing clinics in rheumatology (NCR) are organizational care models that provide care centred within the scope of nurses abilities. To analyse patients differences in the knowledge of the disease, adherence to the treatment, quality indicators of the Rheumatology Departments included quality perceived by the patients with and without NCR. National multicenter observational prospective cohort study 1 year follow-up, comparing patients attending rheumatology services with and without NCR. NCR was defined by the presence of: (1) office itself; (2) at least one dedicated nurse; (3) its own appointment schedule, and (4) phone. Variables included were (baseline and 12 months) Batalla, Haynes-Sackett, Morisky-Green and quality perceived tests. In addition, another specific questionnaire was drawn up to collect the healthcare, teaching and research activities of each Rheumatology Department. A total of 393 patients were included; 181 NCR and 212 not NCR, corresponding to 39 units, 21 with NCR and 18 without NCR (age 53 ± 11.8 vs 56 ± 13.5 years). Significant differences in favour of the NCR group were found in Haynes-Sackett (p = 0.033) and Morisky-Green (p = 0.03) tests in the basal visit. Significant differences were found in questions about "the courtesy and/or kindness received by the nurse", being "good or very good" in greater proportion in the NCR group. The publications from the last 5 years were significantly higher in the NCR group in both, national (p = 0.04) and international (p = 0.03) journals. A higher research activity and quality perceived by the patients are observed in the Rheumatology Departments with NCR.