Peripheral Distribution Research Articles

Microvascular inflammation in the absence of human leukocyte antigen-donor-specific antibody and C4d: An orphan category in Banff classification with cytotoxic T and natural killer cell infiltration

Isolated microvascular inflammation (iMVI) without HLA donor-specific antibodies or C4d deposition in peritubular capillaries remains an enigmatic phenotype that cannot be categorized as antibody-mediated rejection (ABMR) in recent Banff classifications. We included 221 kidney transplant recipients with biopsies with ABMR (n = 73), iMVI (n = 32), and normal (n = 116) diagnoses. We compared peripheral blood leukocyte distribution by flow cytometry and inflammatory infiltrates in kidney transplant biopsies among groups. Flow cytometry showed fewer lymphocytes and total, CD4+, and CD8+ peripheral T cells in iMVI compared with ABMR and normal cases. ABMR and iMVI had fewer total natural Killer (NK) cells but more NKG2A+ NK cells. Immunohistochemistry indicated that ABMR and iMVI had greater CD3+ and CD68+ glomerular infiltration than normal biopsies, whereas CD8+ and TIA1+ cells showed only increased iMVI, suggesting they are cytotoxic T cells. Peritubular capillaries displayed more CD3+, CD56+, TIA1+, and CD68+ cells in both ABMR and iMVI. In contrast, iMVI had less plasma cell infiltration in peritubular capillaries and interstitial aggregates than ABMR. iMVI displayed decreased circulating T and NK cells mirrored by T cell and NK cell infiltration in the renal allograft, similar to ABMR. However, the lesser plasma cell infiltration in iMVI may suggest an antibody-independent underlying stimulus.

Chest CT features of coronavirus disease 2019 (COVID-19) in pediatric patients and its correlation with the clinical condition

BackgroundAll pediatric health organizations are concerned about the impact of coronavirus disease on children, especially on those with other comorbidities; fortunately, pediatric cases appear to be less severe than in adults (De Luca et al. in Pediatr Respir Rev 5:9–14, 2020). The purpose of this study is to characterize chest CT findings of children with and without comorbidities who had confirmed coronavirus disease (COVID-19) and to investigate the relation between chest CT findings and the clinical severity of COVID-19 pneumonia and their laboratory findings.ResultsThe study was conducted on 36 patients, 72.2% of whom had associated comorbidities. Twenty-three patients (63.88%) had abnormal CT findings. Consolidative patches were the most common radiological sign (55.6%) followed by ground glass opacities (50%). The lesions were bilateral (58.3%), having predominantly peripheral distribution (38.9%) with predominant left lower lobe affection (25%). Cases with clinically severe chest conditions had significantly more prevalent consolidative patches (p = 0.026) which show a higher CT density (p = 0.01) and a significantly higher CT severity score (SS) compared to other groups (p = 0.029). The cutoff of severity score 4/20 had 100% sensitivity and 78.12% specificity in the diagnosis of severe cases. There were no statistically significant differences between patients with or without comorbidities regarding CT-SS or any radiological signs.ConclusionsConsolidation was the most common radiological finding in children with COVID-19 and was more prevalent and denser in severe cases. The CT-SS may be used as a complementary tool for the evaluation of the severity of the chest condition. Chest CT-SS more than 4 can be used as an indicator of severe cases, yet no significant difference in CT-SS between patients with associated comorbidities or not.

Dermoscopic Features and Their Diagnostic Values Among Common Inflammatory and Infectious Dermatoses: A Cross-Sectional Study

Dermoscopy is a non-invasive tool widely used to improve the diagnostic accuracy of general dermatological conditions. To determine the dermoscopic features and their diagnostic value in distinguishing common inflammatory and infectious dermatoses. A cross-sectional study was conducted on patients clinically diagnosed with common inflammatory or infectious skin diseases. Baseline characteristics and clinical and dermoscopic findings were recorded. Dermoscopic variables were analyzed using a correlation matrix. A skin biopsy was performed for each patient for a definitive diagnosis. Of 102 patients, 43 with dermatitis, 30 with psoriasis, 14 with lichen planus (LP), 5 with pityriasis rosea (PR), and 10 with others were included. Dull red background, patchy vessels, and scales showed significant positive correlations with dermatitis (r = 0.401, 0.488, and 0.327, respectively; p < 0.01), whereas bright red background, glomerular vessels, regular vascular distribution, and diffuse scales revealed significant positive correlations with psoriasis (r = 0.412, 0.266, 0.798, and 0.401, respectively; p < 0.01). For LP, whitish reticulate structures, purplish background, and dotted vessels mixed with linear vessels in the peripheral distribution were significantly positively correlated (r = 0.831, 0.771, 0.224, and 0.558, respectively; p < 0.05). Yellowish background and peripheral scales were predictive of PR diagnosis (r = 0.254 and 0.583, respectively; p < 0.01). Dermoscopy can be used as an adjunctive tool to differentiate conditions among common inflammatory and infectious dermatoses in order to minimize unnecessary invasive diagnostic procedures.

Fibrocalculous pancreatic diabetes

Chronic Pancreatitis and the type of diabetes associated with it have been named as “Fibrocalcific Pancreatic Diabetes” (FCPD). Initially categorized by WHO in 1985 as a subtype of Malnutrition Related Diabetes Mellitus (MRDM), FCPD has subsequently been included as a disease of the exocrine pancreas under other specific forms of diabetes. Despite many years since its first description, the etiopathogenesis of FCPD remains obscure. While insulin secretion defects are definitely the crux of the problem, there is growing body of evidence to suggest that insulin resistance may play a key role in glucose metabolism in these individuals. Moreover, the role of free fatty acids, counter-regulatory hormones like glucagon and impact of hepatic and peripheral lipid distribution on the dynamics of insulin secretion remains to be explored. Other factors related to alterations in energy expenditure may compound the pathogenetic picture. In fact, not all people with Fibro calculous Pancreatitis will develop diabetes and a search for the exact triggers for hyperglycemia might provide the clue to this enigmatic disease pathophysiology.

Chest CT Scan In Patients With Contusion and COVID 19 A Comparative Study With Pure Lung Contusion

Resource allocation for traumatic patients who are positive/negative for COVID-19 challenges the diagnosis. This study aims to compare the chest CT of COVID-19 associated with lung contusion versus those with lung contusion only. CT-scans of 9 RT-PCR positive patients with lung contusion due to MVA (CC group) and 16 patients with lung contusions from pre-COVID-19 (CO group) were revaluated. The distribution and characteristics of presenting CT-scan findings; including presence, shape, distribution of GGO, consolidations, subpleural sparing, crazy-paving and Atoll sign. Presence of effusions and cavities were compared. Time course of the opacities was compared. Bilateral distribution of opacities was noted in 100% of CC and 87.5% of CO group. There was no significant difference between GGO or consolidation shapes (P=0.44 and P=0.66). Both GGO and consolidations were more diffusely distributed in CC, a predominantly peripheral distribution was more commonly seen in the CO group (P=0.03 and P=0.01). Subpleural sparing was noted in 93.8% of CO as compared to 44% of CC group (p=0.04). Time to resolution was significantly longer in CC (15±6days) comparing to CO patients (P=0.02). 'Typical' chest CT findings including bilateral peripheral GGO and consolidations, crazypaving, Atoll signs and also less typical findings e.g. subpleural sparing is seen in lung contusion and COVID-19 pneumonitis. Lesion Time course might be a better radiologic discriminator between the two entities.

Effect of Different Calcium Salts on Calcium Carbonates Formation Induced by Halophilic Bacillus oceanisediminis CB1

Biomineralization through the biomimetic CO2 sequestration process has been gaining attraction in recent years due to the formation of carbonates widely used as raw material in various industrial processes. The deposition and dissolution of calcium carbonate can be affected by physiochemical factors, such as the type of calcium salt. However, most studies have focused on calcium chloride (CaCl2). In the present study, A potent bacterial carbonic anhydrase (CA) producer, Bacillus oceanisediminis CB1, was screened on CA activity from mangrove plant Avicennia marina, collected from Ghogha, Bhavnagar, India (21.68°N 72.28°E). We premeditated deposition experiments to determine the effects of different calcium salts on calcium carbonate deposition in Bacillus oceanisediminis CB1 colonies. The results demonstrated the calcite formation observed in calcium salt-supplemented nutrient agar, calcium chloride, and calcium acetate. Merely uniform distribution and peripheral distribution of calcite particles found in calcium acetate and calcium chloride supplemented into nutrient agar, respectively. Calcite formation was confirmed by staining with Alizarin Red S dye followed by SEM-EDX. This study will provide a vital reference for designing and applying microbial-induced carbonate precipitation using different calcium salts.

PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis.

Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4+PD1+ cells were higher in sarcoidosis and GPA than in HC (p = 0.0250 and p = 0.0253, respectively). CD56+CTLA4+ were higher in sarcoidosis than GPA, MPA and HC (p = 0.0085, p = 0.0042 and p = 0.0004, respectively). CTLA4+NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1+CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures.

Chest X-Rays Findings and Correlation to Clinical Severity in COVID-19 Patients

Background: The manifestations of COVID-19 infection show a wide range of respiratory symptoms. Chest X-ray (CXR) is helpful for assessment, treatment, and monitoring hospitalization. Objective: To describe and distinguish CXR findings of patients confirming COVID-19 with correlation to clinical severity. Material and Methods: Between March and May 2020 all patients at Pattani provincial and field hospitals in Pattani Province with positive RTPCR results for COVID-19 were retrospectively reviewed. Patients’ demographics and clinical characteristics were evaluated and clustered in two groups based on clinical severity. Baseline CXRs were reviewed and correlated with clinical severity. Results: Forty-eight patients, including 31 males (64.6%) males and 17 females (35.4%), were admitted with confirmed COVID-19. Their age ranged from 3 to 91 years (48.7±18.4 years). Fifteen (31.3%) of the cases had comorbidities. Forty-eight baseline CXRs were obtained, in which 25.0% (12) of CXRs showed abnormalities. The most common pattern and distribution on CXRs was patchy and/or confluent ground-glass opacities and peripheral subpleural distribution in 10/12 (83.3%). The non-severe group showed predominance in the lower lung zone in 4/5 (80%), while in the severe group, they showed multiple zones of lung involvement in 6/7 (85.7%). Bilateral lung involvement in 5/7 (71.4%) was most frequent in the severe group (p&lt;0.001). Conclusion: The most frequent abnormal pattern on CXRs in COVID-19 were patchy and/or confluent ground-glass opacities with peripheral subpleural distribution. The severe group showed bilateral and multiple lung zones involvement. The CXR findings of lung consolidation, perihilar distribution, bilateral, and multiple lower lung zone opacities, in conjunction with other zones of lung involvement suggested a higher risk of a patient developing severe manifestations of COVID-19. Keywords: Chest X-ray; Coronavirus; COVID-19; SARS-CoV-2; Severity

RDW-to-ALB Ratio Is an Independent Predictor for 30-Day All-Cause Mortality in Patients with Acute Ischemic Stroke: A Retrospective Analysis from the MIMIC-IV Database.

Previous studies have shown that the peripheral red blood cell distribution width (RDW) and human serum albumin (ALB) were both predictors of the risk and mortality of cerebrovascular diseases, and the ratio of RDW to ALB (RAR) was a combined new index that can predict the prognosis of the cardiovascular and respiration systemic diseases, but its role in cerebrovascular diseases had not been effectively evaluated. This study is aimed at exploring whether RAR can effectively predict the 30-day all-cause mortality of acute ischemic stroke (AIS) patients. This retrospective cohort study was conducted on AIS patients (age > 18 years) in the intensive care database MIMIC-IV. The RAR was measured based on the red blood cell distribution width and albumin. The main result was 30-day all-cause mortality, and the secondary results were ICU mortality and hospital mortality. Obtain the odds ratio (OR) estimate from the logistic regression model of log-transformed RAR values and mortality. We had used another database for external validation. A total of 1412 patients were enrolled, with an average age of 68.8 ± 15.9, including 708 (50.1%) males. When log-transformed RAR values were used as a continuous variable, as the values increases, the risk of death increases (30-day all-cause mortality OR = 4.02 (2.21, 7.32) P < 0.0001, ICU mortality OR = 3.81 (1.92, 7.54) P = 0.0001, and hospital mortality OR = 3.31 (1.83, 6.00) P < 0.0001), when the values were used as three-category variables and as a trend variable was also positively correlated with each mortality rate. Especially as the categorical variables, a dose-response relationship was clearly observed, that was, as the category of RAR increased (Q1 to Q3), the HR value of the risk of death gradually steadily increased. Such a relationship can also be observed in the external validation database. In the subgroup analysis, we observed an increased risk of death in the patient with hyperlipidemia and low HAS-BLED scores; however, no significant interaction was found in other subgroup analyses (including the diagnostic sequence of AIS). RAR was a predictor of mortality in AIS patients. However, more in-depth research is needed to further analyze and confirm the role of RAR in AIS patients.

Computed Tomography Thorax Patterns in the Patients of Chronic Kidney Disease with Microbiologically Confirmed Coronavirus Disease-2019: An Experience from a Tertiary Care Hospital

Introduction: A retrospective study aimed at analyzing the patterns in the CT scans of patients of CKD infected with COVID-19 in the period of two months. We reviewed the CT scans for the pattern of Lung involvement, number of lobe involved, distribution of the lesions and characteristic appearances, along with other coexisting features. Methodology: After consent, we studied the parameters of interest among the patients admitted in the dedicated COVID-19 hospital in Bengaluru, Karnataka, who were admitted during the months of October and November 2020. Each CT scan was reported by in-house radiologist and results were analyzed. Results: We found that of the 92 CKD patients, 51 had got a CT thorax done, out of which 45 had lung parenchymal involvement of COVID-19; of which 44 were bilateral. 26 of the patients had only peripheral lesions and 19 had both central and peripheral distribution. The most common finding was GGOs occurring in 43 of them while 30 of them had GGOs with consolidation. This study shows that the CT patterns in patients of CKD with COVID-19 involves mainly peripheral distribution of lesions with majority involving &gt;2 lobes, with GGOs being most common finding; similar to those without CKD, but the incidence of pleural effusions and mediastinal lymphadenopathy is slightly higher, possibly because of coexistent comorbidities contributing to the same. Conclusion: We conclude that though some patients with CKD and COVID-19 can have a normal lung, the involvement of lungs is more severe and extensive in distribution, implying a more severe involvement of the lung. Hence, further Studies are required on larger population to ascertain the findings and further resources should be allocated for the benefit of this significantly vulnerable patients in this era.

Severe COVID-19 in 2 Kidney Transplant Patients in Gabon.

BACKGROUND Kidney failure is a public health problem that may require transplantation for patient survival and for those at risk of developing infectious diseases such as COVID-19 due to severe immunosuppression. We report the case of 2 kidney transplant patients who contracted COVID-19. CASE REPORT Patient 1: A 60-year-old Gabonese man presented with 8 days of wet cough, fever, and myalgias associated secondarily with dyspnea, without anosmia or ageusia. His medical history included renal transplant for malignant nephro-angiosclerosis and high blood pressure. The oxygen saturation level subsequently fell to 89-90%. The diagnosis of acute hypoxic respiratory failure secondary to COVID-19 pneumonia with heart and acute renal failure on renal transplant was made based on clinical symptoms, lung imaging results, and a positive SARS-CoV-2 nasal swab PCR test. Patient 2: A 79-year-old Gabonese man presented with 10 days of dry cough associated with intermittent fevers not quantified, anorexia, and fatigue. The patient's medical history was high blood pressure, diabetes mellitus, and renal transplantation. Oxygen saturation level decreased to 85-89% in ambient air. Clinical signs and chest CT scan showed 70% lung lesions with large areas of ground-glass opacity with essentially peripheral distribution of both lungs associated with crazy paving, condensation, bronchiectasis, and arterial dilatation, suggesting severe COVID-19. CONCLUSIONS Those 2 presentations highlight the fact that a severe clinical form of COVID-19 associated with acute renal failure and kidney transplant can be fatal. Kidney transplantation is a risk factor for poor prognosis in patients with severe COVID-19 and greatly worsens the mortality rate of immunocompromised patients.

Radiograph Feature in COVID-19 Patients With Diabetes Mellitus At Dr. Soetomo Hospital Surabaya

Objectives : COVID-19 disease causes considerable morbidity and mortality. Older age and the presence of diabetes mellitus, hypertension and obesity significantly increase the risk of hospitalization and death in COVID-19 patients. COVID-19 patients with other comorbidities such as diabetes are at higher risk of developing severe pneumonia. Several studies have shown a higher susceptibility to several infectious diseases in people with diabetes, possibly due to an unregulated immune system. Plasma glucose levels and diabetes are independent predictors of mortality and morbidity in patients with SARS. Chest X-ray imaging plays an important role in both assessment of disease extent and follow-up, by knowing the pattern of chest radiography in patients with COVID-19 with Diabetes Mellitus, a radiologist can assist clinicians in predicting the progression of chest radiography in relation to blood glucose levels in patients. Method : A descriptive study with a retrospective design was conducted on 134 patients with confirmed COVID-19 and diabetes mellitus who were admitted to Dr. Soetomo General Academic Hospital in 2020. Data on chest radiography and random blood glucose levels were obtained during the first 24 hours of treatment. We evaluated the lung disease based on features, distribution and location. Result : The gender of COVID-19 patients who had the most Diabetes Mellitus was male (55.2%) with the highest age group being more than 50 years (70.8%) with the highest random glucose levels > 200 mg/dl (64.9%). The most radiographic features in COVID-19 patients with Diabetes Mellitus were consolidation/alveolar infiltrate both in patients with glucose level > 200 mg/dl (64.9%) or < 200 mg/dl (35.1%), with the most peripheral distribution (97,8%) and the most locations being a combination of the upper-middle-lower zone at right lung (81,3%) and left lung (70,9%) Conclusion: Radiograph feature of COVID-19 patients with Diabetes Mellitus both in patients with glucose level > 200 mg/dl and < 200 mg/dl were mostly consolidation/alveolar infiltrate, with the most peripheral distribution and the most locations being a combination of the upper-middle-lower zone.

Rab32/38-Dependent and -Independent Transport of Tyrosinase to Melanosomes in B16-F1 Melanoma Cells.

B16-F1 melanoma cells have often been used as a model to investigate melanogenesis, but the evidence that melanosome biogenesis and transport occur by the same mechanisms in normal melanocytes and B16-F1 cells is insufficient. In this study, we established knockout B16-F1 cells for each of several key factors in melanogenesis, i.e., tyrosinase (Tyr), Hps4, Rab27A, and Rab32·Rab38 (Rab32/38), and then compared their phenotypes with the phenotypes of corresponding mutant mouse melanocyte cell lines, i.e., melan-c, melan-le, melan-ash, and Rab32-deficient melan-cht cells, respectively. The results showed that Tyr and Rab27A are also indispensable for melanin synthesis and peripheral melanosome distribution, respectively, in B16-F1 cells, but that Hps4 or its downstream targets Rab32/38 are not essential for Tyr transport in B16-F1 cells, suggesting the existence of a Rab32/38-independent Tyr transport mechanism in B16-F1 cells. We then performed comprehensive knockdown screening of Rab small GTPases and identified Rab10 and Rab24, previously uncharacterized Rabs in melanocytes, as being involved in Tyr transport under Rab32/38-null conditions. Our findings indicate a difference between the Tyr transport mechanism in melanocytes and B16-F1 cells in terms of Rab32/38-dependency and a limitation in regard to using melanoma cells as a model for melanocytes, especially when investigating the mechanism of endosomal Tyr transport.

A SINGLE-CENTRE RETROSPECTIVE AND OBSERVATIONAL INVESTIGATION ON THE MANIFESTATIONS OF COVID-19 ON CHEST HRCT IN THEPOPULATION OF ANDHRA PRADESH, INDIA

Background: The clinical symptoms of COVID-19 in conjunction with chest high resolution computed tomography (HRCT) can give quick screening and determine the disease's severity. HRCT plays an important role in the evaluation and clinical management of COVID-19, which would benet from a more comprehensive overview of its clinical diagnosis and therapy. To dene the spectrum of HRCT results in Objective: COVID 19 individuals with symptoms and to connect HRCT ndings with clinical symptoms of the disease. A retrospective r Methods: esearch of 1513 COVID patients recently diagnosed with COVID-19 and positive RT-PCR test ndings; both sexes were included from the middle of March to the end of May 2021. The patients were separated into three age groups and their HRCT CT severity scores (CTSS) were evaluated. Different age groups' clinical symptoms were connected with the derived CTSS. Results: The average age of the patients was 50.14 percent, with 34% falling between the ages of 35 and 54. The majority of them had fever, cough, dyspnea, myalgia, and headache, but other symptoms like sore throat, diarrhoea, nausea, anosmia, and chest discomfort were less common. In the current study, clinical characteristics had the strongest relationship with moderate CTSS. HRCT ndings include ground-glass opacity (GGO), consolidation, bronchovascular thickening, crazy paving look, subpleural bands/brosis, and bronchiectasis. In moderate and severe patient groups, the CTSS link with lung lobe distribution and gender was highly signicant. Bilateral lung distribution changes (83.6%) were more common in group 2 than central and peripheral distribution changes (70.5%), with lower lobe involvement in both genders. Conclusion: HRCT helps identify COVID-19's pulmonary symptoms in diagnosis and treatment. Imaging patterns depending on infection duration help understand pathophysiology and predict illness development and effects. This study may link clinical symptoms to CTSS and COVID-19 pulmonary changes. It could mean understanding the following wave's features and management. HRCT chest detects early parenchymal abnormalities, measures disease severity in all symptomatic patients, and diagnoses COVID infection regardless of RT-PCR status.

DDEL-01. ANIMAL STUDIES WITH A NEW CNS DRUG DELIVERY DEVICE TO EFFECTIVELY TREAT LEPTOMENINGEAL CARCINOMATOSIS PATIENTS

Abstract Background Appropriate drug distribution is needed for effective treatment of brain metastases and leptomeningeal carcinomatosis. Lack of proper drug bioavailability in the CNS contributes to the poor outcome in these patients. EnClear Therapies has developed a device delivering intrathecal therapeutics utilizing the active control of CSF flow through an external pump. Herein, we look at intrathecal drug delivery of methotrexate with EnClear’s system and its impact of drug concentration in sheep and non-human primates. METHODS The EnClear device utilizes two implantable catheters (intracranial in the ventricular system and lumbar thecal sac) and an extracorporeal pump that controls the speed and direction of CSF flow. Software monitors the output from sensor arrays for pressure, respiration, and heart rate. Gadolinium and MRI were used to determine the CSF flow characteristics. Administration of Methotrexate via the EnClear system was compared to current two standards of delivery, intracerebroventricular or lumbar intrathecal administration. Methotrexate levels were measured with Liquid Chromatography/Mass Spectrometry in CSF, blood, and multiple CNS and peripheral tissues. RESULTS There was a two-fold increase in methotrexate levels in multiple regions of the brain including deeper brain structures including the striatum using the EnClear's system, compared to traditional lumbar intrathecal and intracerebroventricular delivery. Higher peak levels of methotrexate were reached in the CSF with the use of EnClear’s system, with simultaneous reduction in the peripheral nerves and systemic tissues – a potential source of toxicity. Conclusions In large animal studies, the EnClear device has for the first time, demonstrated increased brain parenchymal drug levels via intrathecal delivery. In addition to the drug parenchyma, drug delivery with this novel device has shown improved distribution throughout CNS and leptomeninges as compared to traditional intrathecal drug delivery and decreased peripheral distribution.

The NADPH oxidase NOX4 and the transcription factor STAT6 as two key regulators of peripheral fat distribution in diet-induced obesity

The NADPH oxidase NOX4 and the transcription factor STAT6 as two key regulators of peripheral fat distribution in diet-induced obesity

Tomography and Prognostic Indices in the State of the Art of Evaluation in Hospitalized Patients with COVID-19 Pneumonia.

Evaluation in medical emergencies of COVID-19 patients represents a challenge to regulate preventive and timely management. There are key imaging and laboratory tools to classify the severity. The aim of the study was to evaluate the chest CT score performance and prognostic indices in COVID-19 patients to predict the progression to critical illness. This was a retrospective study between run between April and December 2020, in which 109 patients were included. Patients of any age and gender and who required hospitalization due to a confirmed COVID-19 diagnosis by RT-PCR and chest CT and laboratory were analyzed. In 75% of them, there was at least one comorbidity, and 30% developed critical illness, and the average mortality was 10%. In 49.5%, there was a CORADS-5 on admission, and in 50%, there was a peripheral distribution of the interstitial infiltrate in the left lower lobe. The risk factors were FiO2, CT score &gt; 18, and the NRL index. The combination of the high-risk Quick COVID-19 Severity Index (qCSI) plus CT score &gt; 18 indices was the best prediction index for the development of a critical condition. The combined use of indices in infected COVID-19 patients showed diagnostic accuracy and predicted severity. Imaging and the laboratory tests are key tools independent of the wave of recurrence.

Prognostic Value of Radiological and Laboratory Biomarkers for Assessing Risk of Adverse Outcome in Patients with COVID-19

Objective: to study associations between laboratory and radiological biomarkers of COVID-19, to develop prognostic model of deterioration and lethal outcome in a patient with COVID-19.Material and methods. The study included 162 patients with COVID-19 stratified according to the presence or absence of deterioration during hospitalization. We evaluated chest computed tomography (CT) data, assessed empirically and using a semi-quantitative scale, blood cell counts and parameters of biochemical blood test. The predictive model was built using gradient boosting and artificial neural network with sigmoid activation function.Results. Both CT signs (crazy-paving pattern, bronchial dilatation inside a lesion, peripheral distribution of symptoms, absence of a predominant distribution pattern, lesion grade and extent), and most of laboratory markers were associated with deterioration and its criteria. The CT severity index correlated positively with the levels of leukocytes, neutrophils, urea, aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase, glucose, C-reactive protein, and negatively with the concentrations of albumin, calcium and the number of lymphocytes. Based on the results of the selection and training of classifying models, the optimal method for stratifying patients with COVID-19 on the basis of deterioration during hospitalization, the need for transfer to the intensive care unit, mechanical ventilation, and adverse outcome was gradient boosting.Conclusion. The prognostic model obtained in our study, based on a combination of radiological and laboratory parameters, makes it possible to predict the nature of COVID-19 course with high reliability.

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment.

The aims of this study are (i) to develop a population pharmacokinetic/pharmacodynamic model of daptomycin in patients with normal and impaired renal function, and (ii) to establish the optimal dose recommendation of daptomycin in clinical practice. Several structural PK models including linear and non-linear binding kinetics were evaluated. Monte Carlo simulations were conducted with a fixed combination of creatinine clearance (30–90 mL/min/1.73 m2) and body weight (50–100 kg). The final dataset included 46 patients and 157 daptomycin observations. A two-compartment model with first-order peripheral distribution and elimination kinetics assuming non-linear protein-binding kinetics was selected. The bactericidal effect for Gram+ strains with MIC ≤ 0.5 mg/L could be achieved with 5–12 mg/kg daily daptomycin based on body weight and renal function. The administration of 10–17 mg/kg q48 h daptomycin allows to achieve bactericidal effect for Gram+ strains with MIC ≤ 1 mg/L. Four PK samples were selected as the optimal sampling strategy for an accurate AUC estimation. A quantitative framework has served to characterize the non-linear binding kinetics of daptomycin in patients with normal and impaired renal function. The impact of different dosing regimens on the efficacy and safety outcomes of daptomycin treatment based on the unbound exposure of daptomycin and individual patient characteristics has been evaluated.

Automated diagnosis of COVID-19 using radiological modalities and Artificial Intelligence functionalities: A retrospective study based on chest HRCT database

Background and Objective:The spread of coronavirus has been challenging for the healthcare system’s proper management and diagnosis during the rapid spread and control of the infection. Real-time reverse transcription-polymerase chain reaction (RT-PCR), though considered the standard testing measure, has low sensitivity and is time-consuming, which restricts the fast screening of individuals. Therefore, computer tomography (CT) is used to complement the traditional approaches and provide fast and effective screening over other diagnostic methods. This work aims to appraise the importance of chest CT findings of COVID-19 and post-COVID in the diagnosis and prognosis of infected patients and to explore the ways and means to integrate CT findings for the development of advanced Artificial Intelligence (AI) tool-based predictive diagnostic techniques. Methods:The retrospective study includes a 188 patient database with COVID-19 infection confirmed by RT-PCR testing, including post-COVID patients. Patients underwent chest high-resolution computer tomography (HRCT), where the images were evaluated for common COVID-19 findings and involvement of the lung and its lobes based on the coverage region. The radiological modalities analyzed in this study may help the researchers in generating a predictive model based on AI tools for further classification with a high degree of reliability. Results:Mild to moderate ground glass opacities (GGO) with or without consolidation, crazy paving patterns, and halo signs were common COVID-19 related findings. A CT score is assigned to every patient based on the severity of lung lobe involvement. Conclusion:Typical multifocal, bilateral, and peripheral distributions of GGO are the main characteristics related to COVID-19 pneumonia. Chest HRCT can be considered a standard method for timely and efficient assessment of disease progression and management severity. With its fusion with AI tools, chest HRCT can be used as a one-stop platform for radiological investigation and automated diagnosis system.