[Pulmonary CT angiography in the first wave of the COVID-19 pandemic: comparison between patients with and without infection and with a pre-pandemic series]. / Angio-TC pulmonar durante la pandemia de COVID-19: comparación en pacientes con y sin la infección y con una serie prepandémica.

Background and aims: To analyze the diagnostic performance of pulmonary CT angiography and to compare different D-dimer cutoffs for the diagnosis of acute pulmonary embolism in patients with and without SARS-CoV-2 infections. Materials and methods: We retrospectively analyzed all consecutive pulmonary CT angiography studies done for suspected pulmonary embolism in a tertiary hospital during two time periods: the first December 2020 through February 2021 and the second December 2017 through February 2018. D-dimer levels were obtained less than 24 hours before the pulmonary CT angiography studies. We analyzed the sensitivity, specificity, positive and negative predictive values, area under the receiver operating curve (AUC), and pattern of pulmonary embolism for six different values of D-dimer and the extent of the embolism. During the pandemic period, we also analyzed whether the patients had COVID-19. Results: After excluding 29 poor-quality studies, 492 studies were analyzed; 352 of these were done during the pandemic, 180 in patients with COVID-19 and 172 in patients without COVID-19. The absolute frequency of pulmonary embolism diagnosed was higher during the pandemic period (34 cases during the prior period and 85 during the pandemic; 47 of these patients had COVID-19). No significant differences were found in comparing the AUCs for the D-dimer values. The optimum values calculated for the receiver operating characteristic curves differed between patients with COVID-19 (2200 mcg/L), without COVID-19 (4800 mcg/L), and diagnosed in the prepandemic period (3200 mcg/L). Peripheral distribution of the emboli was more common in patients with COVID-19 (72%) than in those without COVID-19 and than in those diagnosed before the pandemic [OR 6.6, 95% CI:1.5?24.6, p< 0.05 when compared to central distribution]. Conclusions: The number of CT angiography studies and the number of pulmonary embolisms diagnosed during the pandemic increased due to SARS-CoV-2 infection. The optimal D-dimer cutoffs and the distribution of the pulmonary embolisms differed between the groups of patients with and without COVID-19.

[Extrathoracic manifestations of COVID-19 in adults and presentation of the disease in children]. / Manifestaciones extratorácicas de la COVID-19 en adultos y presentación de la enfermedad en niños.

In March 2020, the World Health Organization declared a global pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); epidemic conditions continue in nearly all countries today. Although the symptoms and imaging manifestations of COVID-19 predominantly involve the respiratory system, it is fundamental to know the manifestations of the disease and its possible complications in other organs to help in diagnosis and orient the prognosis. To improve the diagnostic process without increasing the risk of contagion unnecessarily, it is crucial to know when extrathoracic imaging tests are indicated and which tests are best in each situation. This paper aims to provide answers to these questions. To this end, we describe and illustrate the extrathoracic imaging manifestations of COVID-19 in adults as well as the entire spectrum of imaging findings in children.

Distribution of IFITM3 polymorphism (dbSNP: rs12252) in mestizo populations in four states of Mexico.

Interferon-inducible transmembrane protein 3 (IFITM3) participates in the defense against viral infections. This study identified and compared the frequency of the IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western Mexican allelic frequencies (frequency of the "C" allele = 0.18) differ from some American, East Asian and European populations.

Scalp hypothermia as a preventative measure for chemotherapy-induced alopecia: a review of controlled clinical trials.

Chemotherapy-induced alopecia (CIA) is a temporary, yet psychologically devastating form of hair loss that affects 65% of patients receiving cancer chemotherapy. In the 1970s, scalp hypothermia was introduced as a preventative measure against the development of CIA. Numerous studies provide evidence for the effectiveness of scalp cooling to prevent CIA, although results varied because of differences in chemotherapy regimen, cooling technique, mode of administration and patient factors. However, many of the existing studies are uncontrolled or consist of small sample sizes, and data from randomized, randomized studies are limited. To date, no clear guidelines have been established for optimum scalp cooling use as a treatment modality and its efficacy remain unknown. Nonetheless, scalp cooling remains the most widely utilized method for the prevention of CIA, and in December 2015, the United States Food and Drug Administration (FDA) cleared the DigniCap® Scalp Cooling System (Dignitana AB, Sweden) for marketing and the Orbis from Paxman® Coolers Ltd. received clearance in 2017. This literature review is one of the first to provide up-to-date review and side-by-side comparisons of controlled and randomized clinical trials (CCTs and RCTs) evaluating scalp hypothermia for the prevention of CIA. Our analyses of CCTs and RCTs to date show that scalp hypothermia is effective in reducing the occurrence rate of CIA, by 2.7-fold in the CCTs and 3.9-fold in the RCTs. These results suggest that scalp hypothermia represents an effective preventative measure for CIA, and provide guidance for management of anticipated alopecia following chemotherapy and for future investigations.

Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss.

Idiopathic recurrent pregnancy loss (IRPL) is defined by three or more consecutive miscarriages occurring before the twentieth week of gestation as a result of unidentified etiological factors. The results of previous studies have indicated that prothrombotic factors play a pathogenic role in early and late pregnancy. This study aimed to identify inherited prothrombotic and hypofibrinolytic risk factors in Mexican-Mestizo patients with IRPL. Fifty-six women with IRPL and 50 control women with at least two full-term pregnancies and no history of RPL were included in this case-control study. Four prothrombotic (F5 G1691A, F2 G20210A, MTHFR C677T-A1298C) and one hypofibrinolytic (PAI1 4G/5G) restricted fragment length polymorphisms were subjected to molecular analysis. In the case of hypofibrinolytic ACE Ins/Del (I/D), identification was performed by direct PCR. The independent risk correlated with the presence of polymorphisms in IRPL patients was estimated using odds ratio (OR) with a 95% confidence interval (CI). MTHFR 677TT was the most frequent prothrombotic factor in the IRPL group (23%), followed by the compound-heterozygous C677T-A1298C (16%) and heterozygous F2 20210GA (3.6%). The heterozygous ACE I/D (62%) was the main hypofibrinolytic risk factor of IRPL, followed by the homozygote PAI1 4G/4G (18%). The ACE I/D polymorphism was the only significantly different factor among the cases and controls. The dominant genetic model D/D+I/D vs I/I showed an OR (95%CI) of 2.89 (1.22-6.89) and P = 0.019 in Mexican-Mestizo women. The results of this study support an association between the ACE I/D polymorphism and IRPL risk in a Mexican population.

Computed tomography protocols used in staging bronchopulmonary carcinoma: results of a national survey. / Protocolos de tomografía computarizada empleados en la estadificación del carcinoma broncopulmonar: resultados de una encuesta a nivel nacional.

OBJECTIVES: To know the protocols used for staging bronchopulmonary carcinoma by computed tomography in Spain. MATERIAL AND METHODS: Radiologists in 129 hospitals were sent email questionnaires about the organization of their department, scanner type and manufacturer, study extension, techniques employed, and protocol for administering contrast material. RESULTS: A total of 109 hospitals responded with data from 91 teams. Most hospitals were affiliated with a university, and most departments were organized by organ-systems. Scanners were from four manufacturers, and 68% had either 16 or 64 detectors. In 61% of the hospitals, the dose of contrast agent is modified only in patients with extreme body weights, and in 22% the dose is not individualized. Most hospitals do contrast-enhanced studies of the chest and upper abdomen, 42.4% through a single thoracoabdominal acquisition and 55.9% through independent chest and abdominal acquisitions; there was a significant association between these approaches and the scanner manufacturer's protocols and whether the hospital was affiliated with a university. The most commonly used technical parameters were 120kV with dose modulation and variable milliamperage. CONCLUSION: There is very little variability among hospitals in the type of scanner used, the study extension, and the technical parameters used to stage bronchopulmonary carcinoma. Most centers individualize the dose of contrast agent only in extreme weights. There is a broad division between using one or two acquisitions to image the thorax and abdomen, and the number of acquisitions is related to the scanner manufacturer and whether the hospital is affiliated with a university.

A Methodological Approach for Spatiotemporally Analyzing Water-Polluting Effluents in Agricultural Landscapes Using Partial Triadic Analysis.

Multivariate techniques for two-dimensional data matrices are normally used in water quality studies. However, if the temporal dimension is included in the analysis, other statistical techniques are recommended. In this study, partial triadic analysis was used to investigate the spatial and temporal variability in water quality variables sampled in a northeastern Spain river basin. The results highlight the spatiality of the physical and chemical properties of water at different sites along a river over 1 yr. Partial triadic analysis allowed us to clearly identify the presence of a stable spatial structure that was common to all sampling dates across the entire catchment. Variables such as electrical conductivity and Na and Cl ions were associated with agricultural sources, whereas total dissolved nitrogen, NH-N concentrations, and NO-N concentrations were linked to polluted urban sites; differences were observed between irrigated and nonirrigated periods. The concentration of NO-N was associated with both agricultural and urban land uses. Variables associated with urban and agricultural pollution sources were highly influenced by the seasonality of different activities conducted in the study area. In analyzing the impact of land use and fertilization management on water runoff and effluents, powerful statistical tools that can properly identify the causes of pollution in watersheds are important. Partial triadic analysis can efficiently summarize site-specific water chemistry patterns in an applied setting for land- and water-monitoring schemes at the landscape level. The method is recommended for land-use decision-making processes to reduce harmful environmental effects and promote sustainable watershed management.

[Analysis of notifications of drug-induced skin ulcers in Spain]. / Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España.

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. AIM: To study the role of drugs in the aetiology of skin ulcers. MATERIAL AND METHOD: A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. RESULTS: A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. DISCUSSION: Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.

Prevalence and prognostic meaning of interstitial lung abnormalities in remote CT scans of patients with interstitial lung disease treated with antifibrotic therapy.

OBJECTIVES: To describe the prevalence and characteristics of interstitial lung abnormalities (ILA) in CT scans performed prior to the initiation of antifibrotics in a series of patients with interstitial lung disease (ILD), and to identify characteristics apparent on early CT scans that could help to predict outcomes. METHODS: We conducted a retrospective observational study. The original cohort consisted of 101 patients diagnosed with ILD and treated with antifibrotics in a tertiary hospital. Patients were included if they had a thoracic CT scan performed at least one year before initiation of therapy. They were classified radiologically in three groups: without ILA, with radiological ILA and extensive abnormalities. ILA were classified as subpleural fibrotic, subpleural non-fibrotic and non-subpleural. The initial scan and the latest CT scan performed before treatment were read for assessing progression. The relationship between CT findings of fibrosis and the radiological progression rate and mortality were analyzed. RESULTS: We included 50 patients. Only 1 (2%) had a normal CT scan, 25 (50%) had extensive alterations and 24 (48%) had radiological criteria for ILA, a median of 98.2 months before initiation of antifibrotics, of them 18 (75%) had a subpleural fibrotic pattern. Significant bronchiectasis and obvious honeycombing in the lower zones were associated with shorter survival (p = 0.04). Obvious honeycombing in the lower zones was also significantly (p < 0.05) associated with a faster progression rate. CONCLUSIONS: Fibrotic ILAs are frequent in remote scans of patients with clinically relevant ILD, long before they require antifibrotics. Findings of traction bronchiectasis and honeycombing in the earliest scans, even in asymptomatic patients, are related to mortality and progression later on.

Pulmonary CT angiography in the first wave of the COVID-19 pandemic: Comparison between patients with and without infection and with a pre-pandemic series.

BACKGROUND AND AIMS: To analyze the diagnostic performance of pulmonary CT angiography and to compare different D-dimer cutoffs for the diagnosis of acute pulmonary embolism in patients with and without SARS-CoV-2 infections. MATERIALS AND METHODS: We retrospectively analysed all consecutive pulmonary CT angiography studies done for suspected pulmonary embolism in a tertiary hospital during two time periods: the first December 2020 through February 2021 and the second December 2017 through February 2018. D-dimer levels were obtained less than 24 h before the pulmonary CT angiography studies. We analysed the sensitivity, specificity, positive and negative predictive values, area under the receiver operating curve (AUC), and pattern of pulmonary embolism for six different values of D-dimer and the extent of the embolism. During the pandemic period, we also analysed whether the patients had COVID-19. RESULTS: After excluding 29 poor-quality studies, 492 studies were analysed; 352 of these were done during the pandemic, 180 in patients with COVID-19 and 172 in patients without COVID-19. The absolute frequency of pulmonary embolism diagnosed was higher during the pandemic period (34 cases during the prior period and 85 during the pandemic; 47 of these patients had COVID-19). No significant differences were found in comparing the AUCs for the D-dimer values. The optimum values calculated for the receiver operating characteristic curves differed between patients with COVID-19 (2200 mcg/l), without COVID-19 (4800 mcg/l), and diagnosed in the prepandemic period (3200 mcg/l). Peripheral distribution of the emboli was more common in patients with COVID-19 (72%) than in those without COVID-19 and than in those diagnosed before the pandemic [OR 6.6, 95% CI: 1.5-24.6, p < 0.05 when compared to central distribution]. CONCLUSIONS: The number of CT angiography studies and the number of pulmonary embolisms diagnosed during the pandemic increased due to SARS-CoV-2 infection. The optimal d-dimer cutoffs and the distribution of the pulmonary embolisms differed between the groups of patients with and without COVID-19.

A novel rat model for chemotherapy-induced alopecia.

BACKGROUND: More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. AIM: To develop a clinically relevant adult rat model for CIA. METHODS: We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. RESULTS: Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. CONCLUSIONS: A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA.

Monolithic integration of a 10 µm cut-off wavelength InAs/GaSb type-II superlattice diode on GaAs platform.

At room temperature, a 10 µm cut-off wavelength coincides with an infrared spectral window and the peak emission of blackbody objects. We report a 10 µm cut-off wavelength InAs/GaSb T2SL p-i-n diode on a GaAs substrate with an intentional interfacial misfit (IMF) array between the GaSb buffer layer and GaAs substrate. Transmission electron microscopy and energy-dispersive X-ray spectroscopy revealed that the heterostructure on GaSb-on-GaAs is epitaxial, single-crystalline but with a reduced material homogeneity, extended lattice defects and atomic segregation/intermixing in comparison to that on the GaSb substrate. Strain-induced degradation of the material quality is observed by temperature-dependent current-voltage measurements. The T2SL with the IMF array appears as a potentially effective route to mitigate the impact of the lattice mismatch once its fabrication is fully optimized for these systems, but additional strain compensating measures can enable a low cost, scalable manufacturing of focal plane arrays (FPA) for thermal imaging cameras for spectroscopy, dynamic scene projection, thermometry, and remote gas sensing.

Organizing pneumonia.

Organizing pneumonia is a nonspecific pathologic pattern of response to lung damage. It can be idiopathic, or it can occur secondary to various medical processes, most commonly infections, connective tissue disease, and pharmacological toxicity. Although there is no strict definition of the pattern of organising pneumonia as in other idiopathic interstitial pneumonias, the characteristic pattern of this disease could be considered to include patchy consolidations and ground-glass opacities in the peribronchial and subpleural areas of both lungs. Moreover, studies of the course of the disease show that these lesions respond to treatment with corticoids, migrate with or without treatment, and tend to recur when treatment is decreased or withdrawn. Other manifestations of organising pneumonia include nodules of different sizes and shapes, solitary masses, nodules with the reverse halo sign, a perilobular pattern, and parenchymal bands.

Bioinspired gelatin/bioceramic composites loaded with bone morphogenetic protein-2 (BMP-2) promote osteoporotic bone repair.

There are currently several commercialized products approved by the Food and Drug Administration and the European Medicines Agency based on the use of recombinant human BMP-2 for the treatment of non-unions long fractures and spinal fusion. However, the adverse effects recorded with the use of BMPs suggest the need for drug delivery carriers that allow reducing the required doses and improve their cost-effectiveness. Herein, we have developed a new osteoconductive scaffold that reduces the required doses of BMP-2 for promoting bone regeneration in an osteoporotic defect model. The composite is, in brief, a gelatin-based 3D scaffold reinforced with either calcium sulfate or hydroxyapatite as an inorganic osteoconductive biomaterial. To this end, the organic/inorganic composite systems showed high hydration capacity and good in vitro degradability. The incorporation of 7.5% (m/v) ceramic compounds resulted in scaffolds with stiffer Young modulus (179 and 75 kPa for CaSO4_7 and HA_7, respectively) than bare gelatin hydrogels (48 kPa). Studies with human bone-marrow derived mesenchymal stem cells (hBM-MSCs) revealed that the 3D scaffolds promote cell adhesion and proliferation along with osteogenic differentiation capabilities. Specifically, downregulation of stemness (Nanog, Oct4) genes and upregulation of osteogenic markers (ALP, Col1a1, Fmod) by two fold were observed over 10 days under basal culture conditions. Promisingly, the sustained in vitro release of BMP-2 observed from the porous reinforced scaffolds allowed us to address the critical-sized osteoporotic mice calvarial defects with a relatively low growth factor doses (600 ng BMP-2/scaffold) compared to conventional doses at 2-15 micrograms. Overall, this study demonstrates the promising potential of osteoconductive gelatin/calcium bioceramics composites as osteogenic growth factors delivery carriers for bone-regeneration via ultra-low growth factor doses.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

tert-butyl hydroperoxide, an organic peroxide, causes temporary delay in hair growth in a neonatal rat model.

tert-butyl hydroperoxide (tBHP), an organic peroxide, has been shown to cause irreversible damage to keratinocytes in vitro with prolonged administration at high concentrations, and reversible damage with short-term administration at low concentrations. To investigate the effects of tBHP on keratinocytes in vivo, we analysed hair growth in tBHP-treated neonatal rats. Sprague-Dawley and Long-Evans rat pups were injected subcutaneously with tBHP or vehicle once daily for 6 days, and hair growth was monitored. The tBHP-treated rats had a significant delay in hair growth. However, this delay reversed within days, and the hair coats, including hair pigmentation, of tBHP-treated and sham-treated rats were indistinguishable 2 weeks later. Histological analysis and BrdU labelling of S phase cells confirmed the delay in hair-follicle growth and its reversal in tBHP-treated rats. Our results indicated that the changes incurred in hair follicles by short-term use of high-dose oxidants in vivo are temporary and reversible.

Comment on "Global distribution of earthworm diversity".

Phillips et al (Reports, 25 October 2019, p. 480) incorrectly conclude that tropical earthworm communities are less diverse and abundant than temperate communities. This result is an artifact generated by some low-quality datasets, lower sampling intensity in the tropics, different patterns in richness-area relationships, the occurrence of invasive species in managed soils, and a focus on local rather than regional richness.

When pneumonia is not COVID-19. / Cuando la neumonía no es COVID-19.

During the COVID-19 epidemic, the prevalence of the disease means that practically any lung opacity on an X-ray could represent pneumonia due to infection with SARS-CoV-2. Nevertheless, atypical radiologic findings add weight to negative microbiological or serological tests. Likewise, outside the epidemic wave and with the return of other respiratory diseases, radiologists can play an important role in decision making about diagnoses, treatment, or preventive measures (isolation), provided they know the key findings for entities that can simulate COVID-19 pneumonia. Unifocal opacities or opacities located in upper lung fields and predominant airway involvement, in addition to other key radiologic and clinical findings detailed in this paper, make it necessary to widen the spectrum of possible diagnoses.

Extrathoracic manifestations of COVID-19 in adults and presentation of the disease in children.

In March 2020, the World Health Organization declared a global pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); epidemic conditions continue in nearly all countries today. Although the symptoms and imaging manifestations of COVID-19 predominantly involve the respiratory system, it is fundamental to know the manifestations of the disease and its possible complications in other organs to help in diagnosis and orient the prognosis. To improve the diagnostic process without increasing the risk of contagion unnecessarily, it is crucial to know when extrathoracic imaging tests are indicated and which tests are best in each situation. This paper aims to provide answers to these questions. To this end, we describe and illustrate the extrathoracic imaging manifestations of COVID-19 in adults as well as the entire spectrum of imaging findings in children.