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Objectives: To validate novel dedicated 3D-QCA based on the software to calculate post PCI vessel-FFR (vFFR) in a consecutive series of patients, to assess the diagnostic accuracy, and to assess inter-observer variability. Background: Low post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) predicts future adverse cardiac events. However, FFR assessment requires the insertion of a pressure wire in combination with the use of a hyperemic agent. Methods: FAST POST study is an observational, retrospective, single-center cohort study. One hundred patients presenting with stable angina or non ST-elevation myocardial infarction, who underwent post PCI FFR assessment using a dedicated microcatheter were included. Two orthogonal angiographic projections were acquired to create a 3D reconstruction of the coronary artery using the CAAS workstation 8.0. vFFR was subsequently calculated using the aortic root pressure. Results: Mean age was 65±12 years and 70% were male. Mean microcatheter based FFR and vFFR were 0.91±0.07 and 0.91±0.06, respectively. A good linear correlation was found between FFR and vFFR (r = 0.88; p

Background Characteristics of primary APS (PAPS) in the youth population have never been studied. In contrast with children, pregnancy is genuinely relevant in the youth age, and understanding clinical characteristics of PAPS patients within this specific age stratum may also provide insights regarding the well-known risk of poor obstetric outcomes during the adolescence. Objective To evaluate clinical and laboratory characteristics of patients with youth-onset PAPS (15–24 years) and compare them with adult-onset PAPS (over 24 years old). Methods This was a cross-sectional study derived from two rheumatology outpatient clinics. Patients who fulfilled Sidney criteria and who were 15 years of age or older at disease onset were included. Secondary APS patients were excluded. We subdivided patients into two groups: youth- (15–24 years) and adult-onset (over 24 years) and compared them regarding demographic characteristics, criteria and non-criteria manifestations, cardiovascular risk factors, and aPL status. For the pregnancy outcomes analysis, ever-pregnant patients were divided in three groups: youth-onset, early adult-onset (25–34 years), and late adult-onset (35–49 years). Results A total of 250 consecutive PAPS patients were included. Groups had a comparable female and Caucasian distribution. We found a similar disease duration (14.0±7.9 vs 17.0±10.1 years, p = 0.079) and similar rates of thrombotic arterial (34.2% vs. 42.0%, p = 0.250) and venous events (69.7% vs. 69.5%, p = 0.975) between them. Skin ulcers were more frequent in the youth-onset group (17.1% vs. 4.0%, p = 0.001), whereas nephropathy was less common (1.3% vs. 8.0%, p = 0.039). No differences were observed for the other criteria and non-criteria manifestations. The adult-onset group presented more frequently with hypertension ( p = 0.002), hyperlipidemia ( p = 0.008), and smoking ( p = 0.003). The youth-onset group presented a higher frequency of obstetric events as the first manifestation of PAPS (30.3% vs. 21.7%, p = 0.005), with worse pregnancy outcomes, namely, fetal death (58.5% vs. 46.4% vs. 24.1%, p = 0.012) and premature delivery (35.8% vs. 19.0% vs. 10.3%, p = 0.016). Of note, all groups had a comparable number of pregnancies (2.81±2.52 vs 2.74±2.07, p = 0.899). Conclusion This study provides novel evidence that youth-onset PAPS presents a higher frequency of obstetric complications as its first manifestation, with an increased risk of fetal death and preterm delivery. Early recognition of this condition by obstetricians is essential to improve prognosis.

Background Pneumonia is the main manifestation of coronavirus disease 2019 (COVID-19) infection. Chest computed tomography is recommended for the initial evaluation of the disease; this technique can also be helpful to monitor the disease progression and evaluate the therapeutic efficacy. Aim To review the currently available literature regarding the radiological follow-up of COVID-19-related lung alterations using the computed tomography scan, to describe the evidence about the dynamic evolution of COVID-19 pneumonia and verify the potential usefulness of the radiological follow-up. Methods We used pertinent keywords on PubMed to select relevant studies; the articles we considered were published until October 30, 2020. Through this selection, 69 studies were identified, and 16 were finally included in the review. Results Summarizing the included works' findings, we identified well-defined stages in the short follow-up time frame. A radiographic deterioration reaching a peak roughly within the first 2 wk; after the peak, an absorption process and repairing signs are observed. At later radiological follow-up, with the limitation of little evidence available, the lesions usually did not recover completely. Conclusion Following computed tomography scan evolution over time could help physicians better understand the clinical impact of COVID-19 pneumonia and manage the possible sequelae; a longer follow-up is advisable to verify the complete resolution or the presence of long-term damage.

Background Systemic lupus erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS) overlap clinical and immunological features. Therefore, misclassification of PAPS patients as SLE is a concern. The ACR/EULAR 2019 SLE classification has never been studied in PAPS. Objective To verify if the ACR/EULAR 2019 SLE classification can correctly classify a PAPS patient as not having SLE and compare its performance with the SLICC 2012 SLE classification. Methods: One-hundred thrombotic PAPS patients who fulfilled the Sidney criteria were consecutively screened and those who attended the inclusion criteria were submitted to ACR/EULAR 2019 and SLICC 2012 classifications. Results Sixty-seven PAPS patients were included in this study. The majority was female (89.6%) with median age at study inclusion of 45 years (35–53) and median PAPS disease duration of 13 years (8–19). PAPS correct classification was observed more often with ACR/EULAR 2019 than SLICC 2021 criteria (94.0% vs. 64.2%; p Conclusion ACR/EULAR 2019 had high accuracy for distinguishing PAPS from SLE, whereas the SLICC 2012 incorrectly classified more than one third of the PAPS patients as having SLE.

Background and Purpose The pathogenesis of amyotrophic lateral sclerosis (ALS) is not fully clarified, although excessive glutamate (Glu) transmission and the downstream cytotoxic cascades are major mechanisms for motor neuron death. Two metabotropic glutamate receptors (mGlu1 and mGlu5) are overexpressed in ALS and regulate cellular disease processes. Expression and function of mGlu5 receptors are altered at early symptomatic stages in the SOD1G93A mouse model of ALS and knockdown of mGlu5 receptors in SOD1G93A mice improved disease progression. Experimental Approach We treated male and female SOD1G93A mice with 2‐chloro‐4‐((2,5‐dimethyl‐1‐(4‐(trifluoromethoxy)phenyl)‐1H‐imidazol‐4‐yl)ethynyl)pyridine (CTEP), an orally available mGlu5 receptor negative allosteric modulator (NAM), using doses of 2 mg·kg−1 per 48 h or 4 mg·kg−1 per 24 h from Day 90, an early symptomatic disease stage. Disease progression was studied by behavioural and histological approaches. Key Results CTEP dose‐dependently ameliorated clinical features in SOD1G93A mice. The lower dose increased survival and improved motor skills in female mice, with barely positive effects in male mice. Higher doses significantly ameliorated disease symptoms and survival in both males and females, females being more responsive. CTEP also reduced motor neuron death, astrocyte and microglia activation, and abnormal glutamate release in the spinal cord, with equal effects in male and female mice. No differences were also observed in CTEP access to the brain. Conclusion and Implications Our results suggest that mGlu5 receptors are promising targets for the treatment of ALS and highlight mGlu5 receptor NAMs as effective pharmacological tools with translational potential.

La Enfermedad de Chagas (ECh), ocasionada por el parásito flagelado Trypanosoma cruzi (T. cruzi), es una de las parasitosis de mayor impacto en la Salud Pública de Latinoamérica. Si bien actualmente existen medidas de prevención como el tamizaje en bancos de sangre, el control a las embarazadas y el control vectorial, aún se requiere de estrategias más eficaces para evitar nuevos casos. Una de estas posibles estrategias es el desarrollo de una vacuna profiláctica contra T. cruzi. Desde el descubrimiento de la enfermedad en 1909, se han evaluado diferentes vacunas experimentales, pero aún no se ha logrado el desarrollo clínico de una formulación efectiva contra el parásito. En este artículo realizamos una revisión bibliográfica acerca de las distintas estrategias de vacunación que se evaluaron hasta la actualidad y, particularmente, el uso de la enzima Transialidasa (TS) como antígeno vacunal. También abordamos distintos aspectos de la superfamilia de la TS, como la clasificación de las distintas proteínas, sus características funcionales y su rol en la infección por T. cruzi. A lo largo de 100 años se han abordado y perfeccionado una gran diversidad de estrategias vacunales contra T. cruzi, lo cual permite augurar el salto desde el campo pre—clínico al desarrollo clínico de una vacuna efectiva en un futuro cercano.

We reviewed frequency, microbiological pattern, predictors, and outcomes of early infections following transcatheter aortic valve replacement (TAVR).Five hundred thirty-nine patients who underwent successful TAVR at a single, high-volume center between January 2014 and December 2019 were enrolled. We defined early infections as occurring within 30-day from TAVR.Mean age was 83.5 ± 5.4 years; 230 (42.7%) patients were men. Median follow-up was 12.0 (5.7-18.3) months; 30-day and 1-year death rates were 8/539 (1.5%) and 30/539 (5.6%), respectively. Early infections occurred in 61/539 (11.3%) patients, of whom 2 had infections in two sites. Of the 63 infections, 10 were bloodstream infections (BSI), 5 urinary tract, 27 pulmonary (2 with sepsis), 6 access site infections, 1 enterocolitis, and 14 were clinically diagnosed (no specific site). We observed 31/63 (49.2%) microbiologically-documented infections: Gram+ bacteria were isolated in 12/31 (38.7%), Gram- in 17/31 (54.3%), both Gram+ and Gram- in 2/31 (6.5%); in thirty-two infections no specific pathogen could be isolated (clinically-documented infections). Early infections were more prevalent in patients who died within 30-day (8.2% vs. 0.6%, p0.001) or 1-year (14.8% vs. 4.4%, p0.001) from TAVR. At multivariable analysis, early infections were independently associated with 30-day (HR: 8.82, 95% CI: 1.11-19.83, p = 0.035) and 1-year mortality (HR: 2.10, 95%CI: 1.28-6.21, p = 0.041). The predictive value for 1-year mortality was maintained even restricting the analysis to documented infections only, or to more severe infections (BSI and pneumonia only) (all p0.05).Early infections occur in 1/10th of TAVR and are associated with increased short- and long-term mortality. Whereas a causal relationship between early infections and the risk of death cannot be unequivocally proven, careful surveillance of infected patients may improve TAVR results.

Peri-procedural myocardial injury (PPMI) is a common complication after transcatheter valve replacement (TAVR), often remaining clinically silent. The role of valve type on PPMI and the association between PPMI and mortality are still unclear. We sought to evaluate predictors and outcome of PPMI after TAVR, and the impact of self-expandable valve (SEV) vs. balloon-expandable valve (BEV) deployment on PPMI. Consecutive patients who underwent successful TAVR in a single-center from January 2014 to December 2019 were included. PPMI was defined according to a modified Valve Academic Research Consortium (VARC)-2 definition as a post-procedure elevation of troponin (with a peak value ≥ 15-times the upper-reference limit) p p = 0.011), and baseline ejection fraction (OR 1.05, 95% CI 1.02–1.07, p p = 0.488) or 1-year (p = 0.139) all-cause mortality were found. Independent predictors of 30-day mortality were increasing EUROSCORE II (HR 1.16 per score point, 95% CI 1.08–1.19, p p = 0.019), whereas EUROSCORE II (HR 1.08, 95% CI 1.04–1.13, p = 0.031) and acute kidney injury (HR 2.59, 95% CI 1.20–5.35, p = 0.020) were related to 1-year mortality. PPMI is frequent after TAVR, but it does not affect 30-day or 1-year all-cause mortality. SEV implantation is associated with an increased frequency of PPMI.

In chronic obstructive pulmonary disease (COPD) patients, bacterial and viral infections play a relevant role in worsening lung function and, therefore, favour disease progression. The inflammatory response to lung infections may become a specific indication of the bacterial and viral infections. We here review data on the bacterial–viral infections and related airways and lung parenchyma inflammation in stable and exacerbated COPD, focussing our attention on the prevalent molecular pathways in these different clinical conditions. The roles of macrophages, autophagy and NETosis are also briefly discussed in the context of lung infections in COPD. Controlling their combined response may restore a balanced lung homeostasis, reducing the risk of lung function decline.KEY MESSAGEBacteria and viruses can influence the responses of the innate and adaptive immune system in the lung of chronic obstructive pulmonary disease (COPD) patients.The relationship between viruses and bacterial colonization, and the consequences of the imbalance of these components can modulate the inflammatory state of the COPD lung.The complex actions involving immune trigger cells, which activate innate and cell-mediated inflammatory responses, could be responsible for the clinical consequences of irreversible airflow limitation, lung remodelling and emphysema in COPD patients.

Purpose Chest imaging modalities play a key role for the management of patient with coronavirus disease (COVID-19). Unfortunately, there is no consensus on the optimal chest imaging approach in the evaluation of patients with COVID-19 pneumonia, and radiology departments tend to use different approaches. Thus, the main objective of this survey was to assess how chest imaging modalities have been used during the different phases of the first COVID-19 wave in Italy, and which diagnostic technique and reporting system would have been preferred based on the experience gained during the pandemic. Material and Methods The questionnaire of the survey consisted of 26 questions. The link to participate in the survey was sent to all members of the Italian Society of Medical and Interventional Radiology (SIRM). Results The survey gathered responses from 716 SIRM members. The most notable result was that the most used and preferred chest imaging modality to assess/exclude/monitor COVID-19 pneumonia during the different phases of the first COVID-19 wave was computed tomography (51.8% to 77.1% of participants). Additionally, while the narrative report was the most used reporting system (55.6% of respondents), one-third of participants would have preferred to utilize structured reporting systems. Conclusion This survey shows that the participants’ responses did not properly align with the imaging guidelines for managing COVID-19 that have been made by several scientific, including SIRM. Therefore, there is a need for continuing education to keep radiologists up to date and aware of the advantages and limitations of the chest imaging modalities and reporting systems.

Context The syndrome CAH-X is due to a contiguous gene deletion of CYP21A2 and TNXB resulting in TNXA/TNXB chimeras. Objective To analyze TNXB gene status and to clinically evaluate the Ehlers–Danlos syndrome phenotype in a large cohort of Argentine congenital adrenal hyperplasia (CAH) patients to assess the prevalence of this condition in our population. Methods TNXB gene analysis was performed in 66 nonrelated CAH patients that were carriers of the CYP21A2 gene deletion. A molecular strategy based on multiplex ligation–dependent probe amplification and Sanger sequencing analysis was developed allowing for the detection of different, previously described TNXA/TNXB chimeras, named CH1, CH2, and CH3. The main outcome measures were TNXB status of CAH patients that were carriers of the CYP21A2 deletion in the homozygous or heterozygous state. Results TNXA/TNXB CH1 was found in 41%, CH2 in 29%, and CH3 in 1% of nonrelated alleles carrying the CYP21A2 deletion. Thus, overall 71% of alleles were found to carry a contiguous gene deletion. Sixty-seven percent of patients analyzed had a monoallelic form and 6% a biallelic form. All patients with the biallelic form had severe skin hyperextensibility and generalized joint hypermobility. Conclusion Based on the high frequency of TNXB alterations found in CYP21A2 deletion carrier alleles, we recommend evaluating TNXB status in these patients, and assessing connective tissue dysplasia, including cardiologic alterations in positive cases. The number of patients undergoing cardiological evaluation should be expanded to determine the incidence of structural and functional abnormalities in this cohort.

Parkinson's disease is the second most common neurodegenerative disorder in the world. Assumed that gait dysfunctions represent a major motor symptom for the pathology, gait analysis can provide clinicians quantitative information about the rehabilitation outcome of patients. In this scenario, wearable inertial systems for gait analysis can be a valid tool to assess the functional recovery of patients in an automatic and quantitative way, helping clinicians in decision making. Aim of the study is to evaluate the impact of the short-term rehabilitation on gait and balance of patients with Parkinson's disease. A cohort of 12 patients with Idiopathic Parkinson's disease performed a gait analysis session instrumented by a wearable inertial system for gait analysis: Opal System, by APDM Inc., with spatial and temporal parameters being analyzed through a statistic and machine learning approach. Six out of fourteen motion parameters exhibited a statistically significant difference between the measurements at admission and at discharge of the patients, while the machine learning analysis confirmed the separability of the two phases in terms of Accuracy and Area under the Receiving Operating Characteristic Curve. The rehabilitation treatment especially improved the motion parameters related to the gait. The study shows the positive impact on the gait of a short-term rehabilitation in patients with Parkinson's disease and the feasibility of the wearable inertial devices, that are increasingly spreading in clinical practice, to quantitatively assess the gait improvement.

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients. RESUMO OBJETIVO: Avaliar a concentração da peptidilarginina deiminase 4 (PAD4) e os polimorfismos de PADI4, como preditores de desenvolvimento de lesão renal aguda, necessidade de terapia renal substitutiva (TRS) e mortalidade em pacientes com choque séptico. MÉTODOS: Foram incluídos indivíduos com idade ≥18 anos, com diagnóstico de choque séptico na admissão na Unidade de Terapia Intensiva (UTI). Amostras de sangue foram coletadas nas primeiras 24 horas após a admissão do paciente para determinar a concentração sérica de PAD4 e seus polimorfismos PADI4 (rs11203367) e (rs874881). Os pacientes foram acompanhados durante a internação na UTI e tiveram avaliados desenvolvimento da lesão renal aguda séptica (Sepsis-induced acute kidney injury - Saki), necessidade TRS e mortalidade. RESULTADOS: Foram avaliados 99 pacientes; 51,5% desenvolveram Saki e, desses, 21,5% necessitaram de TRS e 80% morreram na UTI. Não houve diferença entre a concentração de PAD4 (p=0,116) e seus polimorfismos rs11203367 (p=0,910) e rs874881 (p=0,769) entre os pacientes. No entanto, o PAD4 apresentou correlação positiva com a concentração plasmática de ureia (r=0,269; p=0,007) e creatinina (r=0,284; p=0,004). A concentração de PAD4 e os polimorfismos da PADI4 também não foram associados à TRS e à mortalidade em pacientes com Saki. CONCLUSÕES: A concentração de PAD4 e seus polimorfismos não foram associados ao desenvolvimento de Saki, à necessidade de TRS ou à mortalidade em pacientes com choque séptico. No entanto, as concentrações de PAD4 foram associadas às concentrações de creatinina e ureia nesses pacientes.

Light-chain deposition disease (LCDD) is a rare paraproteinaemia characterized by the deposition of monoclonal immunoglobulins with a non-fibrillar structure and hence Congo red negative deposits. Kidney disease is the more frequent manifestation, but other organs may also be involved. A 70-year-old man with hypertension and mild chronic renal failure showed a hepatomegaly without splenomegaly. His renal and liver test rapidly got worse. A serum electrophoresis and immunofixation isolated monoclonal kappa light-chain gammopathy, with serum free kappa light chain excess. The bone marrow biopsy showed the presence of interstitial infiltration of plasma cells like multiple myeloma type at initial phase. Periumbilical fat biopsy was negative. Echocardiography demonstrated an infiltrative cardiac disease. The biopsies of the duodenum small intestine mucosa showed flaps with eosinophil material (Masson’s staining) with atrophic crypts and chronic inflammation at chorion level. Amyloid substance was negative. There was a strong positivity for light chains kappa compatible with LCDD. A liver biopsy confirmed this finding. Therapy with dexamethasone and bortezomib improved clinical state and hepatic and renal laboratory tests. Chemotherapy based on novel anti-myeloma agents should be rapidly considered in LCDD patients with severe organ involvement.

Incidences of repetitive mild TBI (r-mTBI), like those sustained by contact sports athletes and military personnel, are thought to be a risk factor for development of neurodegenerative disorders. Those suffering from chronic TBI-related illness demonstrate deficits in cerebrovascular reactivity (CVR), the ability of the cerebral vasculature to respond to a vasoactive stimulus. CVR is thus an important measure of traumatic cerebral vascular injury (TCVI), and a possible in vivo endophenotype of TBI-related neuropathogenesis. We combined laser speckle imaging of CVR in response to hypercapnic challenge with neurobehavioral assessment of learning and memory, to investigate if decreased cerebrovascular responsiveness underlies impaired cognitive function in our mouse model of chronic r-mTBI. We demonstrate a profile of blunted hypercapnia-evoked CVR in the cortices of r-mTBI mice like that of human TBI, alongside sustained memory and learning impairment, without biochemical or immunohistopathological signs of cerebral vessel laminar or endothelium constituent loss. Transient decreased expression of alpha smooth muscle actin and platelet-derived growth factor receptor β, indicative of TCVI, is obvious only at the time of the most pronounced CVR deficit. These findings implicate CVR as a valid preclinical measure of TCVI, perhaps useful for developing therapies targeting TCVI after recurrent mild head trauma.

Healthcare workers (HCWs) have an increased risk to be exposed to infectious diseases compared to the general population. For this reason, according to the National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles, mumps, rubella, varicella and Hepatitis B. Earlier studies have already shown that a large percentage of Italian operators lacked immune protection for one or more of those pathogens. The aim of this study was to evaluate the immunization status for vaccine-preventable diseases of HCWs in a large Italian teaching hospital. We retrospectively evaluated clinical records and serological data of HCWs who followed the occupational health surveillance program between January 1 and December 31 2019. We reviewed the clinical records of 1,017 HCWs: 393 males and 624 females with a median age of 35.69 y (range: 19–67). Protective IgG antibody values were documented in the 88.0%, 75.7%, 90.3%, 87.4% and 85.7% of the HCWs screened, respectively, against measles, mumps, rubella, varicella and Hepatitis B. Age was significantly related to serological protection against measles, mumps and varicella but was not significantly related to protective IgG levels for rubella and HBV. Female gender was significantly related to a higher protection rate against Hepatitis B (87.8 vs 82.4%; p

Background The Barthel Index dyspnea (BId) is responsive to physiological changes and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established yet. Aim To identify the MCID of BId in patients with COPD stratified according to the presence of chronic respiratory failure (CRF) or not. Materials and Methods Using the Medical Research Council (MRC) score as an anchor, receiver operating characteristic curves and quantile regression were retrospectively evaluated before and after pulmonary rehabilitation in 2327 patients with COPD (1151 of them with CRF). Results The median post-rehabilitation changes in BId for all patients were -10 (interquartile range = -17 to -3, p

Hereditary Spastic Paraplegia (HSP) is a rare inherited neurological disorder, whose predominant feature is a spastic gait. Gait analysis represents an objective tool to quantify the impairment of gait pattern in patients with HSP, thus supporting diagnosis and monitoring of disease progression. This study contributes to the characterization of HSP pathological gait, providing the assessment of test-retest repeatability of 122 parameters regarding postural sway, anticipatory postural adjustment in step initiation, gait and turn tasks. Data are collected on a cohort of thirty-five HSP patients, performing three consecutive repetitions of the Instrumented Stand and Walk (iSAW) test provided by Mobility Lab gait analysis system by APDM. Intraclass Correlation Coefficient (ICC) is used to assess repeatability. Repeatability Limit (RL) has also been evaluated and compared to the absolute value of difference (DoM) of HSP patients' measurements mean and normative mean of the same variable, in order to understand which variable can better characterize HSP gait with respect to normal gait. Results show that gait and turn measurements are more repeatable than sway and anticipatory postural adjustments variables. Furthermore, this study confirms previous findings in this field, identifying, among other gait parameters, cadence, gait velocity, stride length and RoM of the shanks as the main distinctive parameters of the pathology. Conversely, the RoM of the knees presents excellent repeatability, but low difference between healthy and pathological subjects.

PURPOSE: The management of diabetes comprises diet, pharmacological therapy, lifestyle counseling, patient education, and physical exercising, to achieve change in health behavior and control of the disease. However, a large proportion of diabetes patients does not adhere to treatment recommendations, mainly in the lifestyle aspect, which remains sedentary. Considering that self-efficacy is an essential determinant of health behaviors such as exercise practicing, the objective of the study was to investigate the psychometric properties of the Brazilian Portuguese version of Bandura’s Exercise Self-Efficacy Scale (BESES) to be used in diabetes patients. METHODS: The BESES was initially completed by thirty diabetes patients to confirm the feasibility of the answers be provided by themselves. The psychometric properties (i.e., internal consistency, test-retest reproducibility, convergent validity, and ceiling and floor effects) were tested in other two-hundred diabetes patients (≥18 years old). RESULTS: The BESES achieved significant internal consistency (Cronbach’s alpha coefficient = 0.92), substantial test-retest reproducibility (intraclass correlation coefficient = 0.83). The convergent validity was confirmed by negative correlations between BESES total scores and barriers to exercise total scores (ρ = −0.333; P = 0.018) and rate of perception exercise corrected by distance covered in the incremental shuttle walking test (ρ = −0.426; P = 0.002). Ceiling and floor effects were not found. In addition, physically active patients had BESES total scores higher compared to sedentary (56.8 ± 21.4 vs. 47.9 ± 20.0; P = 0.003). CONCLUSION: The Brazilian Portuguese version of the BESES showed adequate psychometric properties and proved to be valid for assessing the exercise self-efficacy in diabetes patients in Brazil. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40200-020-00581-6) contains supplementary material, which is available to authorized users.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for coronavirus disease 2019 (COVID-19). Respiratory and gastrointestinal manifestations of SARS-CoV-2 are well described, less defined is the clinical neurological spectrum of COVID-19. We reported a case of COVID-19 patient with acute monophasic Guillain-Barré syndrome (GBS), and a literature review on the SARS-CoV-2 and GBS etiological correlation. Case Description A 68 years-old man presented to the emergency department with symptoms of acute progressive symmetric ascending flaccid tetraparesis. Oropharyngeal swab for SARS-CoV-2 tested positive. Neurological examination showed bifacial nerve palsy and distal muscular weakness of lower limbs. The cerebrospinal fluid assessment showed an albuminocytologic dissociation. Electrophysiological studies showed delayed distal latencies and absent F waves in early course. A diagnosis of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) subtype of GBS was then made. Conclusions Neurological manifestations of COVID-19 are still under study. The case we described of GBS in COVID-19 patient adds to those already reported in the literature, in support of SARS-CoV-2 triggers GBS. COVID-19 associated neurological clinic should probably be seen not as a corollary of classic respiratory and gastrointestinal symptoms, but as SARS-CoV-2-related standalone clinical entities. To date, it is essential for all Specialists, clinicians and surgeons, to direct attention towards the study of this virus, to better clarify the spectrum of its neurological manifestations.

The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.

The optimal revascularization strategy for residual coronary stenosis following primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) remains controversial. This is a retrospective single-centre study including patients with STEMI and MVD. Based on the revascularization strategy, 3 groups were identified: (1) culprit only (CO), (2) ad hoc multivessel revascularization (MVR), and (3) staged MVR. Clinical outcomes were compared in terms of major adverse cardiac events (MACE), a composite of cardiac death, any myocardial infarction, and any unplanned revascularization at a long-term follow-up. A total of 958 patients were evaluated, 489 in the CO, 254 in the ad hoc, and 215 in the staged group. In the staged group, 65.6% of the patients received planned percutaneous coronary intervention, 9.7% coronary artery bypass grafting, 8.4% no further intervention after lesion reassessment, and in 16.3% an event occurred before the planned procedure. At 1,095 days, MACE was 36.1%, 16.7%, and 31% for CO, ad hoc, and staged groups, respectively. A MVR strategy was associated with lower rate of all-cause death compared with CO (HR 0.50; 95%CI [0.31 to 0.80]; p = 0.004). Complete revascularization reduced the rate of MACE (HR 0.30 [0.21 to 0.43] p < 0.001) compared with incomplete revascularization. Ad hoc MVR had lower rate of MACE compared with staged MVR (HR 0.61 [0.39 to 0.96] p = 0.032) mainly driven by less unplanned revascularizations. In conclusion, in patients with STEMI and MVD, complete revascularization reduced the risk of MACE. Ad hoc MVR appeared a reasonable strategy with lower contrast and stent usage and costs.

STUDY OBJECTIVES: There are few studies evaluating (1) exercise capacity as assessed by the 6-minute walking distance (6MWD) test in large populations with obstructive sleep apnea (OSA); and (2) correlations with patients’ comorbidities. METHODS: This study presents a cluster analysis performed on the data of 1,228 patients. Severity of exercise limitation was defined on the basis of 6MWD. RESULTS: Sixty-one percent showed exercise limitation (29.2% and 31.9% mild and severe exercise limitation, respectively). About 60% and 40% of patients were included in cluster 1 (CL1) and 2 (CL2), respectively. CL1 included younger patients with high prevalence of apneas, desaturations, and hypertension with better exercise tolerance. CL2 included older patients, all with chronic obstructive pulmonary disease (COPD), high prevalence of chronic respiratory failure (CRF), fewer apneas but severe mean desaturation, daytime hypoxemia, more severe exercise limitation, and exercise-induced desaturations. Only CRF and COPD significantly (P < .001) correlated with 6MWD < 85% of predicted value. 6MWD correlated positively with apnea-hypopnea index, oxygen desaturation index, nocturnal pulse oxygen saturation (SpO(2)), resting arterial oxygen tension, mean SpO(2) on exercise, and negatively with age, body mass index, time spent during night with SpO(2) < 90%, mean nocturnal desaturation, arterial carbon dioxide tension, and number of comorbidities. Patients without severe comorbidities had higher exercise capacity than those with severe comorbidities, (P < .001). Exercise limitation was significantly worse in OSA severity class I when compared to other classes (P < .001). CONCLUSIONS: A large number of patients with OSA experience exercise limitation. Older age, comorbidities such as COPD and CRF, OSA severity class I, severe mean nocturnal desaturation, and daytime hypoxemia are associated with worse exercise tolerance. CITATION: Vitacca M, Paneroni M, Braghiroli A, et al. Exercise capacity and comorbidities in patients with obstructive sleep apnea. J Clin Sleep Med. 2020;16(4):531–538.

Aims: To evaluate the nutritional status, resting energy expenditure, caloric and protein intake, and evolution of biochemical parameters in three stages of chronic kidney disease: pre-dialytic, at the beginning of the dialysis treatment, and 30 days after starting treatment. Methods: The chi-square and Student’s t tests were used to compare the variables, and analysis of repeated measurements was used to compare the data obtained in the three moments evaluated. The results were discussed at the 5% level of significance. Results: We evaluated 35 patients, 60% female and 60% with diabetes mellitus. There was a decrease in midarm circumference and serum albumin. Inflammatory state and caloric and protein intake increased. There was no significant difference in resting energy expenditure in the three moments. The serum urea and serum albumin, handgrip strength, and protein consumption after 30 days from the start of dialysis were greater in the peritoneal dialysis patients, when compared to the hemodialysis population. Conclusion: there was a decrease in midarm circumference and serum albumin and an increase in protein intake after dialysis. The peritoneal dialysis patients had higher muscle strength, even with lower protein intake. Resting energy expenditure was not different between dialysis methods and the moments evaluated. Resumo Objetivos: Avaliar o estado nutricional, o gasto energético em repouso, o gasto calórico e proteico e a evolução dos parâmetros bioquímicos em três estágios da doença renal crônica: pré-dialítico, no início do tratamento dialítico e 30 dias após o início do tratamento. Métodos: O teste do qui-quadrado e o teste t de Student foram utilizados para comparar as variáveis, e a análise das medidas repetidas foi utilizada para comparar os dados obtidos nos três momentos avaliados. Os resultados foram discutidos ao nível de significância de 5%. Resultados: Foram avaliados 35 pacientes, 60% mulheres e 60% com diabetes mellitus. Houve uma diminuição na circunferência do terço médio do braço (CMB) e na albumina sérica. O estado inflamatório e a ingestão calórica e protéica aumentaram. Não houve diferença significativa no gasto energético em repouso nos três momentos. A ureia sérica e a albumina sérica, a força de preensão manual e o consumo de proteínas após 30 dias do início da diálise foram maiores nos pacientes em diálise peritoneal, quando comparados com a população em hemodiálise. Conclusão: houve diminuição da circunferência do terço médio do braço e na albumina sérica, e aumento da ingestão protéica após a diálise. Os pacientes em diálise peritoneal apresentaram maior força muscular, mesmo com menor consumo proteico. O gasto energético em repouso não foi diferente entre os métodos de diálise e os momentos avaliados.

Welder Zamoner,1 Isabella Gonçalves Pierri,1 Karina Zanchetta Cardoso Eid,1 Lais Maria Bellaver de Almeida,1 Adriano dos Santos,2 André Luís Balbi,1 Daniela Ponce1 1Botucatu School of Medicine, São Paulo State University - UNESP, Botucatu, São Paulo, Brazil; 2Clinics Hospital Pharmacy, Botucatu School of Medicine, Botucatu, São Paulo 18618-970, BrazilCorrespondence: Welder Zamoner Tel +55 14 9821 72334Email welder.zamoner@unesp.brIntroduction and Aim: There have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes.Methodology: This was a cohort-unicentric study that evaluated septic patients aged > 18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development < 48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women.Results: We evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of > 21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62– 0.98, p=0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes.Conclusion: Serum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin > 21.5 mg/L was the only variable associated with death in the Cox model.Keywords: sepsis, acute kidney injury, vancomycin, nephrotoxicity

Aims The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). Methods and results Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset Conclusions The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.

Background The burden of cardiovascular (CV) complications in patients hospitalised for community-acquired pneumonia (CAP) is still uncertain. Available studies used different designs and different criteria to define CV complications. We assessed the cumulative incidence of acute of CV complications during hospitalisation for CAP in Internal Medicine Units (IMUs). Methods This was a prospective study carried out in 26 IMUs, enrolling patients consecutively hospitalised for CAP. Defined CV complications were: newly diagnosed heart failure, acute coronary syndrome, new onset of supraventricular or ventricular arrhythmias, new onset hemorrhagic or ischemic stroke or transient ischemic attack. Outcome measures were: in-hospital and 30-day mortality, length of hospital stay and rate of 30-day re-hospitalisation. Results A total of 1266 patients were enrolled, of these 23.8% experienced at least a CV event, the majority (15.5%) represented by newly diagnosed decompensated heart failure, and 75% occurring within 3 days. Female gender, a history of CV disease, and more severe pneumonia were predictors of CV events. In-hospital (12.2% vs 4.7%, p p = 0.0001) mortality was higher in patients with CV events, as well as the re-hospitalisation rate (13.3% vs 9.3%, p = 0.002), and mean hospital stay was 11.4 ± 6.9 vs 9.5 ± 5.6 days (p p = 0.009). Conclusion Cardiovascular events are frequent in CAP, and their occurrence adversely affects outcome. A strict monitoring might be useful to intercept in-hospital CV complications for those patients with higher risk profile. Trial registration NCT03798457 Registered 10 January 2019 - Retrospectively registered

The presence of melanin pigment and melanocytic markers expression have been rarely reported in salivary gland tumors. Herein, two cases of carcinoma arising in pleomorphic adenoma of the parotid gland and showing diffuse expression of myoepithelial and melanocytic markers are described. The clinical-pathological clues useful in the differential diagnosis with melanoma are discussed. In addition, a review of the pertinent literature is also proposed, discussing the pathologic mechanisms potentially involved in this phenomenon. Supplementary Information The online version of this article (10.1007/s12105-021-01299-4) contains supplementary material, which is available to authorized users.

We report a case of 3 autopsy proven incidental cardiac aspergillomas, a rare and yet deadly manifestation caused by Aspergillus. A 48-year-old Caucasian woman affected by a large B-cell lymphoma was referred to our institute for a whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography restaging examination, which demonstrated 3 intracardiac masses. The patient was hospitalized, and both a transthoracic echocardiogram and a cardiac magnetic resonance imaging examination were performed. None of the imaging modalities provided a definitive diagnosis. A positive serum galactomannan assay allowed for the initiation of antifungal therapy, but, nevertheless, the patient died a few days later. This case highlights the need to consider cardiac aspergilloma in the differential diagnosis of cardiac masses, especially in immunocompromised patients. Though noninvasive imaging modalities and cardiac magnetic resonance imaging, in particular, help determine the nature of a cardiac lesion, cardiac aspergilloma shows no distinctive radiological features. A high degree of clinical suspicion is therefore key to achieving a timely diagnosis. Histopathological examination with microbiological confirmation remains the diagnostic gold standard. Keywords: Aspergilloma, Cardiac masses, Immunocompromised host

Background Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. Methods We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). Results We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p p p p Conclusions Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.

Background Renal impairment takes a relevant role in worsening clinical outcomes and increasing mortality risk in patients with heart failure (HF). In this context, the interplay between venous congestion and systemic perfusion in the pathogenesis of cardiorenal syndrome is currently a matter of extensive debate1. Purpose To investigate the relationship between renal function and hemodynamic variables, as the cardiac index and right atrial pressure, in a broad spectrum of HF patients undergoing right heart catheterization, as part of their pulmonary hypertension (PH) diagnostic work-up. Patients and methods From 1st September 2005 until 31st October 2019, hemodynamic data from 286 consecutive patients were collected, of whom 267 had available plasmatic creatinine values. The estimated glomerular filtration rate (eGFR) was calculated by using the Chronic Kidney Disease Epidemiology Collaboration formula. The overall study population was stratified in no PH group, pre-capillary PH group and post-capillary PH group, on the basis of the available hemodynamic values of mean pulmonary arterial pressure and pulmonary artery wedge pressure. Results Of the overall population, 46.1% of them were male, the mean age at the right heart catheterization was 65.5±13.7 years, and the mean eGFR value was 70.0±0.2 mL/min/1.73 m2. On the basis of hemodynamic parameters, 71 patients constituted the no PH group, 107 the pre-capillary PH group, and 63 the post-capillary PH group. Post-capillary PH patients were significantly older than both no PH and pre-capillary PH subjects (69.4±11.7 years; 61.2±16.7 years and 65.7±12.9 years respectively, p=0.003). eGFR was significantly lower in the post-capillary PH group, compared to both no PH group (63.1±22.8 mL/min/1.73 m2 vs. 73.0±23.9 mL/min/1.73 m2, p=0.029) and pre-capillary PH group (63.1±22.8 mL/min/1.73 m2 vs. 71.6±26.6 mL/min/1.73 m2, p=0.041). In post-capillary PH group, multivariate logistic regression analysis showed a significant correlation between eGFR Conclusions A significant association between renal impairment and both low systemic perfusion and venous congestion, was found in patients with post-capillary PH, rather than in other hemodynamic subsets. Further investigations are needed to disentangle the impact of the both sides of circulation on renal function, in different hemodynamic phenotypes. Funding Acknowledgement Type of funding sources: None.

Background The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from timesensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. Methods We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. Results Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. Conclusions Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

Stroke is a leading cause of death and disability worldwide, with limited treatments being available. However, advances in optic methods in neuroscience are providing new insights into the damaged brain and potential avenues for recovery. Direct brain stimulation has revealed close associations between mental states and neuroprotective processes in health and disease, and activity-dependent calcium indicators are being used to decode brain dynamics to understand the mechanisms underlying these associations. Evoked neural oscillations have recently shown the ability to restore and maintain intrinsic homeostatic processes in the brain and could be rapidly deployed during emergency care or shortly after admission into the clinic, making them a promising, non-invasive therapeutic option. We present an overview of the most relevant descriptions of brain injury after stroke, with a focus on disruptions to neural oscillations. We discuss the optical technologies that are currently used and lay out a roadmap for future studies needed to inform the next generation of strategies to promote functional recovery after stroke.

Bilateral thalamic infarctions are uncommon and often lead to more severe and long-lasting symptoms than unilateral thalamic infarctions. This article describes a patient with bilateral thalamic infarction caused by occlusion in the artery of Percheron, an anatomic variant thought to be present in 4% to 12% of the population.

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (> 1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.

Chronic obstructive pulmonary disease (COPD) is due to structural changes and narrowing of small airways and parenchymal destruction (loss of the alveolar attachment as a result of pulmonary emphysema), which all lead to airflow limitation. Extracorporeal shock waves (ESW) increase cell proliferation and differentiation of connective tissue fibroblasts. To date no studies are available on ESW treatment of human bronchial fibroblasts and epithelial cells from COPD and control subjects. We obtained primary bronchial fibroblasts from bronchial biopsies of 3 patients with mild/moderate COPD and 3 control smokers with normal lung function. 16HBE cells were also studied. Cells were treated with a piezoelectric shock wave generator at low energy (0.3 mJ/mm2, 500 pulses). After treatment, viability was evaluated and cells were recultured and followed up for 4, 24, 48, and 72 h. Cell growth (WST-1 test) was assessed, and proliferation markers were analyzed by qRT-PCR in cell lysates and by ELISA tests in cell supernatants and cell lysates. After ESW treatment, we observed a significant increase of cell proliferation in all cell types. C-Kit (CD117) mRNA was significantly increased in 16HBE cells at 4 h. Protein levels were significantly increased for c-Kit (CD117) at 4 h in 16HBE (p p = 0.037); for PCNA at 4 h in 16HBE (p = 0.046); for Thy1 (CD90) at 24 and 72 h in CS-fibroblasts (p = 0.031 and p = 0.041); for TGFβ1 at 72 h in CS-fibroblasts (p = 0.038); for procollagen-1 at 4 h in COPD-fibroblasts (p = 0.020); and for NF-κB-p65 at 4 and 24 h in 16HBE (p = 0.015 and p = 0.0002). In the peripheral lung tissue of a representative COPD patient, alveolar type II epithelial cells (TTF‐1+) coexpressing c-Kit (CD117) and PCNA were occasionally observed. These data show an increase of cell proliferation induced by a low dosage of extracorporeal shock waves in 16HBE cells and primary bronchial fibroblasts of COPD and control smoking subjects.

Background Globally, the incidence of diabetes is increasing and strategies to reach a comprehensive approach of care are needed, including education in self-management. This is particularly true in low and middle-income countries where the number of people living with diabetes is higher than in the high-income ones. This article describes the development of a structured patient education program for Brazilians living with diabetes or prediabetes. Methods These steps were undertaken: 1) a 4-phase needs assessment (literature search of local diabetes guidelines, environmental scan, evaluation of information needs of patients identified by diabetes experts, and patient focus groups); and, 2) the translation and cultural adaptation of the patient guide (preparation, translation, back-translation, back-translation review, harmonization, and proofreading). Results Four of the seven guidelines identified include educational aspects of diabetes management. No structured education program was reported from the environmental scan. Regarding the information needs, 15 diabetes experts identified their patients’ needs, who referred that they have high information needs for topics related to their health condition. Finally, results from six patient focus groups were clustered into six themes (self-management, physical activity, eating habits, diabetes medication, psychosocial being, and sleep), all embedded into the new education program. Constructive theory, adult learning principles, and the Health Action Process Approach model were used in program development and will be used in delivery. The developed program consists of 18 educational sessions strategically mapped and sequenced to support the program learning outcomes and a patient guide with 17 chapters organized into five sections, matched with weekly lectures. Conclusions This program is a sequential and theoretical strategic intervention that can reach programs in Brazil to support diabetes and prediabetes patient education.

Background: Chronic obstructive pulmonary disease (COPD) is a complex, progressive respiratory condition characterized by heterogeneous clinical presentations (phenotypes). The aim of this study was to assess the prevalence of the main COPD phenotypes and match each phenotype to the most fitting clinical and lung function profile.Methods: The CLIMA (Clinical Phenotypes in Actual Clinical Practice) study was an observational, cross-sectional investigation involving twenty-four sites evenly distributed throughout Italy. Patients were tentatively grouped based on their history and claimed prevailing symptoms at recruitment: chronic cough (CB, suggesting chronic bronchitis); dyspnoea (possible emphysema components, E); recurrent wheezing (presuming asthma components, A). Variables collected were: anagraphics; smoking habit; history of asthma; claim of >1 exacerbations in the previous year; blood eosinophil count; total blood IgE and alpha1 anti-trypsin (α1-AT) levels; complete lung function, and the chest X-ray report. mMRC, CAT, BCS, EQ5d-5L were also used. The association between variables and phenotypes were checked by Chi-square test and multinomial logistic regression.Results: The CB phenotype was prevalent (48.3%), followed by the E and the A phenotypes (38.8% and 12.8%, respectively). When dyspnea was the prevailing symptom, the probability of belonging to the COPD-E phenotype was 3.40 times higher. Recurrent wheezing was mostly related to the COPD-A phenotype. Lung function proved more preserved in the COPD-CB phenotype. Smoke; n. exacerbations/year; VR, and BODE index were positively correlated with the COPD-E phenotype, while SpO2, FEV1/FVC, FEV1/VC, and FEV1 reversibility were negatively correlated. Lower DLco values were highly probative for the COPD-E phenotype (p

Primary or secondary bone tumors can manifest in different ways, from simple bone pain to possible pathological fractures. Hypervascularized tumors are of greatest concern, with increased incidence of complications. Preoperative embolization of the bone tumor is an effective measure for reducing blood loss during open surgery to excise the tumor. With appropriate experience, the risks of the procedure are minimal and final outcomes are highly satisfactory. The purpose of this paper is to describe the case of a 43-year-old male patient with a metastatic renal cell tumor in the left proximal femur (seen on lower limb computed tomography) who underwent selective preoperative embolization. The procedure resulted in a remarkable absence of bleeding and successful response to subsequent onco-orthopedic surgery.

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe thyroidal ER stress and thyroid cell death. Nevertheless, thyroxine was synthesized, and brief treatment of TGrdw/rdw rats with antithyroid drug was lethal to the animals. When untreated, remarkably, thyroxine was synthesized on the mutant thyroglobulin protein, delivered via dead thyrocytes that decompose within the follicle lumen, where they were iodinated and cannibalized by surrounding live thyrocytes. As the animals continued to grow goiters, circulating thyroxine increased. However, when TGrdw/rdw rats age, they cannot sustain goiter growth that provided the dying cells needed for ongoing thyroxine synthesis, resulting in profound hypothyroidism. These results establish a disease mechanism wherein dead thyrocytes support organismal survival. Fil: Zhang, Xiaohan. University of Michigan; Estados Unidos Fil: Kellogg, Aaron P.. University of Michigan; Estados Unidos Fil: Citterio, Cintia Eliana. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Zhang, Hao. University of Michigan; Estados Unidos Fil: Larkin, Dennis. University of Michigan; Estados Unidos Fil: Morishita, Yoshiaki. University of Michigan; Estados Unidos Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina Fil: Arvan, Peter. University of Michigan; Estados Unidos

Made available in DSpace on 2022-04-29T08:35:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-23 This study aimed to explore the role of peritoneal dialysis (PD) in acute-on-chronic liver disease (ACLD) in relation to metabolic and fluid control and outcome. Fifty-three patients were treated by PD (prescribed Kt/V = 0.40/session), with a flexible catheter, tidal modality, using a cycler and lactate as a buffer. The mean age was 64.8 ± 13.4 years, model of end stage liver disease (MELD) was 31 ± 6, 58.5% were in the intensive care unit, 58.5% needed intravenous inotropic agents including terlipressin, 69.5% were on mechanical ventilation, alcoholic liver disease was the main cause of cirrhosis and the main dialysis indications were uremia and hypervolemia. Blood urea and creatinine levels stabilized after four sessions at around 50 and 2.5 mg/dL, respectively. Negative fluid balance (FB) and ultrafiltration (UF) increased progressively and stabilized around 3.0 L and −2.7 L/day, respectively. Weekly-delivered Kt/V was 2.7 ± 0.37, and 71.7% of patients died. Five factors met the criteria for inclusion in the multivariable analysis. Logistic regression identified as risk factors associated with Acute Kidney Injury (AKI) in ACLD patients: MELD (OR = 1.14, CI 95% = 1.09–2.16, p = 0.001), nephrotoxic AKI (OR = 0.79, CI 95% = 0.61–0.93, p = 0.02), mechanical ventilation (OR = 1.49, CI 95% = 1.14–2.97, p < 0.001), and positive fluid balance (FB) after two PD sessions (OR = 1.08, CI 95% = 1.03–1.91, p = 0.007). These factors were significantly associated with death. In conclusion, our study suggests that careful prescription may contribute to providing adequate treatment for most Acute-on-Chronic Liver Failure (ACLF) patients without contraindications for PD use, allowing adequate metabolic and fluid control, with no increase in the number of infectious or mechanical complications. MELD, mechanical complications and FB were factors associated with mortality, while nephrotoxic AKI was a protective factor. Further studies are needed to better investigate the role of PD in ACLF patients with AKI. Department of Internal Medicine Botucatu Medical School – University of São Paulo State – UNESP Botucatu Medical School – University of São Paulo State – UNESP Department of Internal Medicine Botucatu Medical School – University of São Paulo State – UNESP Botucatu Medical School – University of São Paulo State – UNESP

Non-cystic fibrosis bronchiectasis represents a heterogenous spectrum of disorders characterised by an abnormal and permanent dilatation of the bronchial tree associated with respiratory symptoms. To date, diagnosis relies on computed tomography (CT) evidence of dilated airways. Nevertheless, definite radiological criteria and standardised CT protocols are still to be defined. Although largely used, current radiological scoring systems have shown substantial drawbacks, mostly failing to correlate morphological abnormalities with clinical and prognostic data. In limited cases, bronchiectasis morphology and distribution, along with associated CT features, enable radiologists to confidently suggest an underlying cause. Quantitative imaging analyses have shown a potential to overcome the limitations of the current radiological criteria, but their application is still limited to a research setting. In the present review, we discuss the role of imaging and its current limitations in non-cystic fibrosis bronchiectasis. The potential of automatic quantitative approaches and artificial intelligence in such a context will be also mentioned.

Background Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. Methods We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB4, MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. Results AATD-AT patients were younger but had similar spirometric and DLCO values compared to cigarette smoke-associated COPD, despite a lower burden of smoking history. Compared to cigarette smoke-associated COPD, AATD-noT and AATD-AT patients had lower sputum neutrophil levels (p=0.0446, p=0.0135), total bacterial load (16S) (p=0.0081, p=0.0223), M. catarrhalis (p=0.0115, p=0.0127) and S. pneumoniae (p=0.0013, p=0.0001). Sputum IL-27 was significantly elevated in CS and cigarette smoke-associated COPD. AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD (p=0.0297) and these positively correlated with FEV1% predicted values (r=0.578, p=0.0307). Conclusions Compared to cigarette smoke-associated COPD, AATD-AT (COPD) patients have a distinct airway inflammatory and microbiological profile. The decreased sputum bacterial load and IL-27 levels in AATD-AT patients suggests that augmentation therapy play a role in these changes.

CO2-reactivity and neurovascular coupling are sequentially lost within the first 24 h after subarachnoid hemorrhage (SAH). Whether and when these impairments recover is not known. Therefore, we investigated the reactivity of pial and intraparenchymal vessels by in vivo two-photon microscopy one month after experimental SAH. C57BL/6 mice were subjected to either sham surgery or SAH by filament perforation. One month later, cerebral blood flow following CO2-challenge and forepaw stimulation was assessed by laser Doppler fluxmetry. Diameters of pial and intraparenchymal arterioles were quantified by in vivo two-photon microscopy. One month after SAH, pial and parenchymal vessels dilated in response to CO2. Neurovascular coupling was almost completely absent after SAH: vessel diameter did not change upon forepaw stimulation compared to a 20% increase in sham-operated mice. The current results demonstrate that neurovascular function differentially recovers after SAH: while CO2-reactivity normalizes within one month after SAH, neurovascular coupling is still absent. These findings show an acute and persistent loss of neurovascular coupling after SAH that may serve as a link between early brain injury and delayed cerebral ischemia, two distinct pathophysiological phenomena after SAH that were so far believed not to be directly related.

Health Care Workers (HCWs) have an increased risk of contracting contagious disease, including mumps. In January 2017 the Italian National Vaccine Prevention Plan 2017–2019, recommended the administration of a dose of MMR vaccine (Measles-Mumps-Rubella) to the Health Care Workers (HCWs) that, working in a risky environment, did not carry out the complete vaccination cycle of MMR or that are seronegative for at least one of the three vaccine viruses. In October of the same year, the Advisory Committee on Immunization Practices (ACIP) recommended a third dose of a vaccine containing Mumps Virus for people previously vaccinated with 2 doses, belonging to a group or to a population at increased risk of acquire mumps in the event of an epidemic. We analyzed the clinical records and values of mumps-specific IgG antibodies of 3032 HCWs (mean age 32.80 ± 10.75 years), that underwent occupational health surveillance between January 1st 2017 and March 31th 2018. The HCWs were also screened for measles, rubella, mumps using serological methods. 13% (405) was seronegative for mumps, especially among HCWs between 18 and 36 years. We calculated the cost-effectiveness of two-doses and three-doses MMR vaccination. The cost of vaccination without screening was significantly more expensive (cost difference: 99 712 € and 184 996 €) both in case of two-dose and three-dose MMR vaccination respectively. Our study suggests that, in HCWs, the assessment of the mumps antibody titer before vaccination may be a useful complement to vaccination itself, because it is more accurate and cost-effective than direct immunization of unvaccinated subjects.

Studies on vancomycin pharmacokinetics in acute kidney injury (AKI) patients on high-volume peritoneal dialysis (HVPD) are lacking. We studied the pharmacokinetics of intravenous (IV) vancomycin in AKI patients treated by HVPD who received a prescribed single IV dose of vancomycin (15 - 20 mg/kg total body weight) to determine the extent of vancomycin removal and to establish vancomycin dosing guidelines for the empirical treatment of AKI patients receiving HVPD. The application of 18 mg/kg vancomycin every 48 - 72 hours in AKI patients undergoing HVPD was required to maintain therapeutic concentrations.

Considering the importance of the renin-angiotensin system (RAS) in diabetic nephropathy (DN) and the link between mast cells (MC) and the RAS, this study evaluated the effects of RAS blockade on the MC cell population in the kidneys from rats with experimental diabetes. Wistar rats were divided into six groups: control non-diabetic (C); sham (S); diabetic (D); and D treated with enalapril (EN), losartan (LO), or aliskiren (AL). Ninety days after diabetes induction, glomerular filtration rate (GFR) and urinary albumin excretion (UAE) were determined. Kidneys were collected for MC counting. RAS blockers minimized changes in morphometrical parameters (EN), cortical collagen (LO, AL), GFR (AL) and UAE (EN, LO). An increased number of MC was observed in the kidneys from D animals. Only AL treatment prevented this increase. MC may be involved in some aspects of DN pathogenesis and the possible protective effects of AL on the kidneys might involve MC modulation.