Caracterización metabólica de los cambios pulmonares estructurales en pacientes con hallazgos incidentales sugestivos de neumonía por COVID-19 en estudios 18F-FDG PET/CT. Perspectivas fisiopatológicas de imágenes multimodales obtenidas durante la pandemia / Metabolic characterization of structural lung changes in patients with findings suggestive of incidental COVID-19 pneumonia on 18F-FDG PET/CT: Pathophysiological insights from multimodal images obtained during the pandemic

Objetivo Evaluar la captación metabólica de diferentes signos tomográficos observados en pacientes con hallazgos estructurales incidentales sugestivos de neumonía por COVID-19 mediante PET/TC con 18F-FDG. Material y métodos Se analizaron retrospectivamente 596 estudios PET/TC realizados desde el 21 de febrero de 2020 hasta el 17 de abril de 2020. Tras excluir 37 exploraciones (trazadores PET diferentes a la 18F-FDG y estudios cerebrales), se evaluó la actividad metabólica de varios cambios estructurales integrados en la puntuación CO-RADS mediante el SUVmáx de estudios multimodales con 18F-FDG. Resultados Se incluyeron 43 pacientes r COVID-19 en la 18F-FDG PET/TC (edad media: 68±12,3 años, 22 varones). Los valores de SUVmáx fueron mayores en los pacientes con categorías CO-RADS 5-6 respecto a los de categorías CO-RADS inferiores (6,1±3,0 vs. 3,6±2,1, p=0,004). En los pacientes con CO-RADS 5-6, las opacidades en vidrio deslustrado, la bilateralidad y las consolidaciones mostraron valores de SUVmáx más elevados (valores de la p de 0,01, 0,02 y 0,01, respectivamente). La distribución parcheada y el patrón crazy paving también se asociaron a valores de SUVmáx más elevados (valores de p de 0,002 y 0,01). Tras el análisis multivariable, el SUVmáx se asoció significativamente con un diagnóstico estructural positivo de neumonía por COVID-19 (odds ratio=0,63, intervalo de confianza del 95%=0,41-0,90; p=0,02). La curva ROC del modelo de regresión destinado a confirmar o descartar el diagnóstico estructural de neumonía por COVID-19 mostró un AUC de 0,77 (error estándar=0,072; p=0,003). Conclusiones En aquellos pacientes remitidos a 18F-FDG PET/TC por indicaciones oncológicas y no oncológicas estándar (43/559; 7,7%) durante la pandemia, la obtención de imágenes multimodales es una herramienta útil durante la detección incidental de neumonía (AU)

Purpose To evaluate the metabolic uptake of different tomographic signs observed in patients with incidental structural findings suggestive of COVID-19 pneumonia through 18F-FDG PET/CT. Material and methods We retrospectively analyzed 596 PET/CT studies performed from February 21, 2020 to April 17, 2020. After excluding 37 scans (non-18F-FDG PET tracers and brain studies), we analyzed the metabolic activity of several structural changes integrated in the CO-RADS score using the SUVmax of multimodal studies with 18F-FDG. Results Forty-three patients with 18F-FDG PET/CT findings suggestive of COVID-19 pneumonia were included (mean age: 68±12.3 years, 22 male). SUVmax values were higher in patients with CO-RADS categories 5–6 than in those with lower CO-RADS categories (6.1±3.0 vs. 3.6±2.1, p=0.004). In patients with CO-RADS 5–6, ground-glass opacities, bilaterality and consolidations exhibited higher SUVmax values (p-values of 0.01, 0.02 and 0.01, respectively). Patchy distribution and crazy paving pattern were also associated with higher SUVmax (p-values of 0.002 and 0.01). After multivariate analysis, SUVmax was significantly associated with a positive structural diagnosis of COVID-19 pneumonia (odds ratio=0.63, 95% confidence interval=0.41–0.90; p=0.02). The ROC curve of the regression model intended to confirm or rule out the structural diagnosis of COVID-19 pneumonia showed an AUC of 0.77 (standard error=0.072, p=0.003). Conclusions In those patients referred for standard oncologic and non-oncologic indications (43/559; 7.7%) during pandemic, imaging with 18F-FDG PET/CT is a useful tool during incidental detection of COVID-19 pneumonia. Several CT findings characteristic of COVID-19 pneumonia, specifically those included in diagnostic CO-RADS scores (5–6), were associated with higher SUVmax values (AU)

Metabolic characterization of structural lung changes in patients with findings suggestive of incidental COVID-19 pneumonia on 18F-FDG PET/CT. Pathophysiological insights from multimodal images obtained during the pandemic.

PURPOSE: To evaluate the metabolic uptake of different tomographic signs observed in patients with incidental structural findings suggestive of COVID-19 pneumonia through 18F-FDG PET/CT. MATERIALS AND METHODS: We retrospectively analyzed 596 PET/CT studies performed from February 21, 2020 to April 17, 2020. After excluding 37 scans (non-18F-FDG PET tracers and brain studies), we analyzed the metabolic activity of several structural changes integrated in the CO-RADS score using the SUVmax of multimodal studies with 18F-FDG. RESULTS: Forty-three patients with 18F-FDG PET/CT findings suggestive of COVID-19 pneumonia were included (mean age: 68±12.3 years, 22 male). SUVmax values were higher in patients with CO-RADS categories 5-6 than in those with lower CO-RADS categories (6.1±3.0 vs. 3.6±2.1, p=0.004). In patients with CO-RADS 5-6, ground-glass opacities, bilaterality and consolidations exhibited higher SUVmax values (p-values of 0.01, 0.02 and 0.01, respectively). Patchy distribution and crazy paving pattern were also associated with higher SUVmax (p-values of 0.002 and 0.01). After multivariate analysis, SUVmax was significantly associated with a positive structural diagnosis of COVID-19 pneumonia (odds ratio=0.63, 95% confidence interval=0.41-0.90; p=0.02). The ROC curve of the regression model intended to confirm or rule out the structural diagnosis of COVID-19 pneumonia showed an AUC of 0.77 (standard error=0.072, p=0.003). CONCLUSIONS: In those patients referred for standard oncologic and non-oncologic indications (43/559; 7.7%) during pandemic, imaging with 18F-FDG PET/CT is a useful tool during incidental detection of COVID-19 pneumonia. Several CT findings characteristic of COVID-19 pneumonia, specifically those included in diagnostic CO-RADS scores (5-6), were associated with higher SUVmax values.

Anthropogenic impacts on threatened species erode functional diversity in chelonians and crocodilians.

The Anthropocene is tightly associated with a drastic loss of species worldwide and the disappearance of their key ecosystem functions. The orders Testudines (turtles and tortoises) and Crocodilia (crocodiles, alligators, and gharials) contain numerous threatened, long-lived species for which the functional diversity and potential erosion by anthropogenic impacts remains unknown. Here, we examine 259 (69%) of the existing 375 species of Testudines and Crocodilia, quantifying their life history strategies (i.e., trade-offs in survival, development, and reproduction) from open-access data on demography, ancestry, and threats. We find that the loss of functional diversity in simulated extinction scenarios of threatened species is greater than expected by chance. Moreover, the effects of unsustainable local consumption, diseases, and pollution are associated with life history strategies. In contrast, climate change, habitat disturbance, and global trade affect species independent of their life history strategy. Importantly, the loss of functional diversity for threatened species by habitat degradation is twice that for all other threats. Our findings highlight the importance of conservation programmes focused on preserving the functional diversity of life history strategies jointly with the phylogenetic representativity of these highly threatened groups.

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.

BACKGROUND: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival. PATIENTS AND METHODS: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed. RESULTS: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population. CONCLUSION: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

Assessing DESS solution for the long-term preservation of nematodes from faecal samples.

Preservation of biological samples is a relevant issue for many scientific disciplines. Although traditional preservers, such as formaldehyde or ethanol, imply major disadvantages related to health risks, DNA degradation and distortion of structures, they are widely used. Hence, the search for viable alternatives preserving morphometry and genetics seems necessary. Here we assess the suitability of DESS solution to preserve adult nematodes and their eggs in faeces. Concretely, faecal samples of terrestrial tortoises with oxyurids were used to: (i) compare the 1-month storage efficacy of eggs from different conservation protocols (faeces without preserver at -20 °C, faeces with DESS solution at room temperature, faeces with DESS solution at -20 °C and faeces with ethanol 70% at room temperature); (ii) address morphological nematode identification after 2 years of storage with DESS. We also corroborated that nematode DNA remained viable after 2 years. Overall, our results showed that DESS solution at room temperature is an advisable alternative to conserve both parasite eggs and adult nematodes for morphological identification and genetic purposes. It also offers the advantages of being low-cost, safe and suitable for fieldwork conditions and shipments without refrigeration for nematode preservation.

Eudragit® L100/chitosan composite thin bilayer films for intravaginal pH-responsive release of Tenofovir.

The high rate of HIV new infections and AIDS-related deaths each year make prevention tools still necessary today. Different dosage forms - including films - for vaginal administration of antiretroviral drugs have been developed for this purpose. Six batches of Tenofovir-loaded films were formulated based on Eudragit® L100 (EL100) and chitosan, containing triethyl citrate and glycerol. In all the cases films structured in two layers - the upper layer mainly attributed to EL100 and the lower layer to chitosan - were revealed by SEM. A higher content in EL100 and plasticizers improves the mechanical properties and control over drug release in the vaginal medium without affecting mucoadhesion. The EL100-based layer acts as a structuring agent that controls Tenofovir release for days in the vaginal medium while it occurs in a few hours in the presence of seminal fluid. Bilayer films with the highest tested content of EL100 and plasticizers would be the most suitable as vaginal microbicides as they are easier to administer due to their excellent mechanical properties and they offer more comfortable posology and enhanced protection against HIV during intercourse due to their pH-responsive release of Tenofovir.

Lymecycline vs. clindamycin plus rifampicin in hidradenitis suppurativa treatment: clinical and ultrasonography evaluation.

BACKGROUND: Antibiotic therapy remains the first-line treatment for hidradenitis suppurativa (HS). However, literature data on its comparative clinical efficacy and safety are limited. AIM: To investigate the efficacy of tetracycline (lymecycline 300 mg daily) vs. the combination therapy clindamycin and rifampicin (600 mg plus 600 mg daily) by evaluating and comparing the clinical response at the end of antibiotic treatment (10 weeks). METHODS: The study retrospectively analysed 52 patients divided in two groups of 26 patients: Group A received lymecycline and Group B received clindamycin plus rifampicin for 10 weeks. Subjects had mild, moderate and severe HS. The clinical and ultrasonography extent of disease was measured by the Hurley Score, Sonographic Score of Hidradenitis Suppurativa, International Hidradenitis Suppurativa Severity Score System (IHS4), pain visual analogue scale (pain VAS) and Dermatology Life Quality Index (DLQI). The primary outcome was the clinical response at the end of the antibiotic treatment period, according to the Hidradenitis Suppurativa Clinical Response measure. RESULTS: Both groups showed a significant improvement in IHS4, pain VAS and DLQI from baseline, but this was more marked in Group A. Reductions in nodule counts were similar between the two groups, whereas the number of abscesses and draining tunnels decreased more in Group B. Disease-free survival was similar between the two groups. CONCLUSION: Lymecycline monotherapy and clindamycin plus rifampicin combination are both effective treatments for patients with moderate-severe HS. Nodular-type HS seems to respond better to lymecycline, whereas the abscess/tunnel type seems to respond better to clindamycin plus rifampicin.

Clinical response rate and flares of hidradenitis suppurativa in the treatment with adalimumab.

BACKGROUND: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, skin disease. adalimumab is the sole approved drug for the treatment of HS, but it only partially controls the symptoms. AIM: To evaluate the incidence of flares during 108 weeks of therapy and the clinical response to adalimumab. METHODS: In total, 20 patients with moderate-severe HS treated with adalimumab were included to evaluate the number of flares, mean time interval between flares, lesion count number of patients who reached the Hidradenitis Suppurativa Clinical Response (HiSCR) of ≥ 50% reduction in inflammatory lesion count, and the International Hidradenitis Suppurativa Severity Score System (IHS4), pain visual analogue scale (VAS) and Dermatology Life Quality Index (DLQI). RESULTS: In total, 90% of patients reported at least 1 flare, and in total 48 flares were counted for the whole group; mean time between flares was 26.9 ± 16.4 weeks. Duration between flares was 30.5 ± 16.3 and 12.5 ± 5.7, respectively, in responders and nonresponders. A progressive decline in flares was observed with treatment, while a gradual increase in the number of patients achieving HiSCR was attained during the observational period. Lesion count, IHS4, pain VAS and DLQI decreased throughout the study. In detail, adalimumab showed a higher efficacy on nodules and abscesses than on draining tunnels. The study was limited by its retrospective nature and small number of patients. CONCLUSION: Adalimumab is an effective and safe treatment for patients with HS despite the high number of flares.

Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment.

PURPOSE: Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3-60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12-70]); and 50 (15%) patients underwent surgery. RESULTS: Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31-88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025). CONCLUSIONS: HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.

Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

Quantification of hyaluronan in human fasciae: variations with function and anatomical site.

Recently, alterations in fascial gliding-like movement have been invoked as critical in the etiology of myofascial pain. Various methods have been attempted for the relief of this major and debilitating clinical problem. Paramount have been attempts to restore correct gliding between fascial layers and the movement over bone, joint, and muscular structures. One of the key elements that underlies such fascial movement is hyaluronan. However, until now, the precise content of hyaluronan within fasciae has been unknown. This study quantifies for the first time the hyaluronan content of human fascial samples obtained from a variety of anatomic sites. Here, we demonstrate that the average amount varies according to anatomic site, and according to the different kinds of sliding properties of the particular fascia. For example, the fascia lata has 35 µg of hyaluronan per gram of tissue, similar to that of the rectus sheath (29 µg g-1 ). However, the types of fascia adherent to muscle contain far less hyaluronan: 6 µg g-1 in the fascia overlying the trapezius and deltoid muscles. In the fascia that surrounds joints, the hyaluronan increases to 90 µg g-1 , such as in the retinacula of the ankle, where greater degrees of movement occur. Surprisingly, no significant differences were detected at any site as a function of age or sex (P-value > 0.05, t-test) with the sole exception of the plantar fascia. This work can provide a better understanding of the role of hyaluronan in fascia. It will facilitate a better comprehension of the modulation of the hyaluronan-rich layer that occurs in relation to the various conditions that affect fascia, and the diverse factors that underlie the attendant pathologies.

Power Doppler ultrasound assessment of vascularization in hidradenitis suppurativa lesions.

BACKGROUND: Ultrasound (US) and Power Doppler (PD) US are useful tools to study and monitor the patients with hidradenitis suppurativa (HS). OBJECTIVE: Describe the PD signal of HS nodules, abscesses and fistulas. METHODS: A retrospective analysis of PD in mild, moderate and severe HS patients, collecting all demographic and clinical data. The lesions were classified according to their US morphology, describing the vascular degree - high, moderate and minimal - and distribution - peripheral, internal and mixed. Statistical analysis was performed using odds ratio and bivariate regression. RESULTS: A total of 241 lesions, 62 nodules, 64 abscesses, 99 simple fistulas and 16 complex fistulas, from 61 patients with HS, were included. Vascular distribution was defined peripheral in 143/241, mixed in 55/241 and internal in 0/241 lesions, regardless the clinical type. Qualitative Doppler showed high vascularization in 44/241 lesions, moderate in 79/241 and minimal in 75/241, despite the clinical type. All lesions showed resistive index <0.7. Age, disease's duration, size of the lesions, high Sartorius score and high BMI showed positive statistical correlation with both PD signal and mixed vascular distribution. No statistical significance was evidenced for vascular degree measurements. LIMITATIONS: US cannot detect lesions <0.1 mm. CONCLUSION: Vascular distribution of HS lesions can be evaluated by PD with additional relevant information for earlier and better disease management.

Influence of shear stress and size on viability of endothelial cells exposed to gold nanoparticles.

Screening nanoparticle toxicity directly on cell culture can be a fast and cheap technique. Nevertheless, to obtain results in accordance with those observed in live animals, the conditions in which cells are cultivated should resemble the one encountered in live systems. Microfluidic devices offer the possibility to satisfy this requirement, in particular with endothelial cell lines, because they are capable to reproduce the flowing media and shear stress experienced by these cell lines in vivo. In this work, we exploit a microfluidic device to observe how human umbilical vein endothelial cells (HUVEC) viability changes when subject to a continuous flow of culture medium, in which spherical citrate-stabilized gold nanoparticles of different sizes and at varying doses are investigated. For comparison, the same experiments are also run in multiwells where the cells do not experience the shear stress induced by the flowing medium. We discuss the results considering the influence of mode of exposure and nanoparticle size (24 and 13 nm). We observed that gold nanoparticles show a lower toxicity under flow conditions with respect to static and the HUVEC viability decreases as the nanoparticle surface area per unit volume increases, regardless of size.

Drug kinetics release from Eudragit - Tenofovir@SiOC tablets.

A novel drug release system has been obtained in form of tablets from Eudragit® RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative purposes. The porous silicon oxycarbide presents a bimodal mesopore size distribution that is maintained after functionalization with amino groups. We have studied the adsorption kinetics and adsorption equilibrium when the materials are loaded with tenofovir and, in all cases, pseudo-second order kinetics and Langmuir isotherm have been revealed as the most representative models describing the kinetic and thermodynamic parameters. Besides, the tenofovir adsorption on these materials turns out to be a favorable process. In vitro release of tenofovir has been studied in simulated vaginal medium by applying different release models. Continuous tenofovir release for >20days has been obtained for the SiOC material functionalized with amine groups. We concluded that the drug release occurs in two steps that involve a drug diffusion step through the material pores and diffusion through the swollen polymer. The interactions between the tenofovir drug and de amine groups of the functionalized silicon oxycarbide also play an important role in the release process.