Background. Percutaneous ultrasound (US)-guided renal biopsy is the gold standard in the evaluation of renal diseases, but some patients, such as the obese, may not be eligible for this procedure. ...Aim of this study was to determine the feasibility, efficacy and safety of US-guided percutaneous renal biopsy in supine antero-lateral position (SALP) in high-risk patients (BMI > 30 and/or respiratory difficulty), as well as to compare the overall outcome of SALP with that of traditional prone position (PP) in low-risk patients (BMI ≤ 30/no respiratory difficulty). Methods. One hundred and ten consecutive patients scheduled for native kidney biopsy were recruited. Ninety low-risk patients were randomized following a permuted block randomization list to receive either US-guided renal biopsy in PP (Group 1) or SALP (Group 2), whereas 20 high-risk patients received US-guided renal biopsy in SALP (Group 3) and were our observational cohort study. Comfort compliance and breathing difficulty in each group were evaluated by the Visual Analogue Scale (VAS). Bleeding complications were evaluated through US renal scanning. Results. Mean operating time was 7 min. Comfort compliance and breathing difficulty were significantly better for SALP in both low- and high-risk patients; there were no significant differences in pain after biopsy among the three groups. Bleeding complications were slightly higher in Group 1. Diagnostic yield was similar in all groups. Conclusions. SALP is reliable, minimally invasive, easy, highly successful, timesaving and almost free from severe side-effects. A better VAS score for breathing difficulty and comfort compliance characterizes this procedure, making it particularly suitable for obese patients.
•A lower (higher) brain integration was found in the MCS- group in the α (δ) band.•Elastic-Net trained on imaginary coherency was the most accurate predictive model.•Cross-validated analysis led to a ...specificity/sensitivity of 74%/85% in detecting MCS+.
Objective: Within the continuum of consciousness, patients in a Minimally Conscious State (MCS) may exhibit high-level behavioral responses (MCS+) or may not (MCS−). The evaluation of residual consciousness and related classification is crucial to propose tailored rehabilitation and pharmacological treatments, considering the inherent differences among groups in diagnosis and prognosis. Currently, differential diagnosis relies on behavioral assessments posing a relevant risk of misdiagnosis. In this context, EEG offers a non-invasive approach to model the brain as a complex network. The search for discriminating features could reveal whether behavioral responses in post-comatose patients have a defined physiological background. Additionally, it is essential to determine whether the standard behavioral assessment for quantifying responsiveness holds physiological significance. Methods: In this prospective observational study, we investigated whether low-density EEG-based graph metrics could discriminate MCS+/− patients by enrolling 57 MCS patients (MCS−: 30; males: 28). At admission to intensive rehabilitation, 30 min resting-state closed-eyes EEG recordings were performed together with consciousness diagnosis following international guidelines. After EEG preprocessing, graphs’ metrics were estimated using different connectivity measures, at multiple connection densities and frequency bands (α,θ,δ). Metrics were also provided to cross-validated Machine Learning (ML) models with outcome MCS+/−. Results: A lower level of brain activity integration was found in the MCS− group in the α band. Instead, in the δ band MCS− group presented an higher level of clustering (weighted clustering coefficient) respect to MCS+. The best-performing solution in discriminating MCS+/− through the use of ML was an Elastic-Net regularized logistic regression with a cross-validation accuracy of 79% (sensitivity and specificity of 74% and 85% respectively). Conclusion: Despite tackling the MCS+/− differential diagnosis is highly challenging, a daily-routine low-density EEG might allow to differentiate across these differently responsive brain networks. Significance: Graph-theoretical features are shown to discriminate between these two neurophysiologically similar conditions, and may thus support the clinical diagnosis.
Introduction and objective: Computer Aided Diagnosis (CAD) systems based on Medical Imaging could support physicians in several fields and recently are also applied in histopathology. The aim of this ...work is to discuss in detail the design and testing of a CAD system for segmentation and discrimination of blood vessels versus tubules from biopsies in the kidney tissue through the elaboration of histological images.
Materials and methods: Materials consist in 10 Kidney Biopsy Slides (KBS) with Periodic Acid Schiff (PAS) staining. The Regions Of Interest (ROI) identified by expert are in total 221:71 vessels and 150 tubules. KBS preparation and digital acquisition have been conducted by expert technicians at the Department of Emergency and Organ Transplantation (DETO) of the University of Bari Aldo Moro (Italy). Each slice is a Red Green Blue (RGB) format image with a resolution of 0.50µm/pixel. Starting from KBS images, several techniques were tested for ROI's segmentation and classification. In particular, we formerly describe the innovative preliminary step to segment regions of interest, the procedure to extract significant features from them and finally discuss the supervised Artificial Neural Networks (ANNs) architecture based on error back propagation training algorithm. All the training sets were builts by using vessels and non vessels (tubules) ROI samples, whose dimensions were correlated to the vessels to be detected.
Results: The performance of the best ANN architecture, trained by using a training set of 35 vessels among the 71 available vessels in dataset, were evaluated in terms of False Positives (FPs) and False Negatives (FNs). On an initial reduced dataset, it reveals good performance and robustness in terms of FPs reduction.
Conclusion: Tests determined that the supervised ANN approach is consistent and reveals good performance, after a training phase based on vessels and non-vessels (tubules) samples. Moreover, our method could be improved by using a larger dataset diagnosed by expert nephropathologists.
•After receiving a COVID-19 booster, the antibody response increases in controls and rheumatoid arthritis (RA)-patients.•After the booster, interferon-γ release assay-specific response remains stable ...in RA.•After the booster, the spike-specific response is clusters of differentiation (CD)4-driven in health care workers and patients with RA.•In RA, the booster is associated with low spike-CD4 response and interleukin-2 impairment.
To characterize the kinetics of humoral and T-cell responses in rheumatoid arthritis (RA)-patients followed up to 4-6 weeks (T3) after the SARS-CoV-2 vaccine booster dose.
Health care workers (HCWs, n = 38) and patients with RA (n = 52) completing the messenger RNA vaccination schedule were enrolled at T3. In each cohort, 25 subjects were sampled after 5 weeks (T1) and 6 months (T2) from the first vaccine dose. The humoral response was assessed by measuring anti-receptor-binding domain (RBD) and neutralizing antibodies, the T-cell response by interferon-γ-release assay (IGRA), T cell cytokine production, and B cell phenotype at T3 by flow cytometry.
Patients with RA showed a significant reduction of antibody titers from T1 to T2 and a significant increase at T3. T-cell response by IGRA persisted over time in patients with RA, whereas it increased in HCWs. Most patients with RA scored positive for anti-RBD, neutralizing antibody and T-cell responses, although the magnitude was lower than HCWs. The spike-specific-cytokine response was mainly clusters of differentiation (CD)4+ T cells restricted in both cohorts and significantly lower with reduced interleukin-2 response and CD4-antigen-responding naïve T cells in patients with RA. Unswitched memory B cells were reduced in patients with RA compared with HCWs independently of vaccination.
COVID-19 vaccine booster strengthens the humoral immunity in patients with RA even with a reduced cytokine response.
The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks ...remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial ...fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30ml/min per 1.73m2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.
Compositional data with a tridimensional structure are not uncommon in social sciences. The CANDECOMP/PARAFAC model is one of the most adequate techniques for modeling these arrays without confusing ...modes variability. Estimating parameters in this setting can be particularly difficult because compositional data are multicollinear by definition and because, in general, for socio-economic data the exact number of latent variables is harder to determine. The most used fitting procedure in the literature is the PARAFAC-ALS algorithm which, however, is sensitive to both the difficulties presented, namely it is sensitive to multicollinearity and to the use of the wrong number of factors. In this work an integrated PARAFAC-ALS algorithm initialized with SWATLD steps is proposed as an effective solution to these deficiencies. This approach is tested on simulated multicollinear data in comparison with standard ALS and proves capable of performing better in terms of robustness against over-factoring and temporary degeneracies, it is faster at converging even in case of collinearity and it still provides a least-squares solution.
The knowledge of Langerhans Cell Histiocytosis (LCH) is based on pediatric studies. Adults with LCH are usually treated with pediatric protocols. In 2001, guidelines for adults with LCH (GIMEMA LCH ...2001) were proposed, in order to standardize the diagnostic and therapeutic approaches for this category of patients. The aims of this retrospective study are: a) to evaluate the role of a multidisciplinary assessment in adults with LCH, according to the GIMEMA LCH 2001 guidelines, and b) to analyze the results obtained with the GIMEMA LCH 2001 guidelines and those obtained with pediatric protocols.
Pts aged >18 years with a diagnosis of LCH (S-100+, CD1a+, CD207+) managed at our Institution since 1985 to 2018 were considered. As diagnostic and treatment approaches, two different strategies were used over time: the GIMEMA LCH 2001 guidelines and the pediatric protocols. The GIMEMA LCH 2001 guidelines included a multidisciplinary diagnostic work-up with complete odontostomatologic, pulmonary and endocrinologic assessments; treatment strategy consisted of: wait and see or local therapy in unifocal single system (SS), indomethacin in bone multifocal SS and vinblastine combined with low-dose prednisone (PDN) in multi-system (MS), PDN in pulmonary honey-combing disease (PHCD) and cladribine in central nervous system involvement. DAL-HX 83 and 90, LCH-I and LCH II were the pediatric protocols utilized over time. Response to treatment was defined as complete (CR) or intermediate (IR). Persistence of the symptoms and/or appearance of new lesions were defined no response (NR). Progression was considered the appearance of symptoms and/or new lesions after initial response.
One-hundred-thirty-one LCH pts (females 72, males 59) with a median age at diagnosis of 36 years (range 18 - 71) were considered. Median follow up was 43 months (range 12 - 330). One-hundred-seven patients were managed according to the GIMEMA LCH 2001 guidelines, 16 of them previously treated with a pediatric protocol. Pulmonary and/or oral involvements were identified in 31/107 (29%) and 12/107 (11%) patients, respectively, 5/16 (31%) and 3/16 (19%), respectively, of previously treated asymptomatic patients.
Ninety-one newly diagnosed patients (median age at diagnosis: 36 years) were treated according to the GIMEMA LCH 2001 guidelines and 40 (median age at diagnosis: 33 years) were managed with pediatric protocols. All patients treated with the GIMEMA LCH 2001 were evaluable for response. In particular, all patients with SS-LCH achieved a response (100%), that was complete in 20/26 (76.9%) unifocal-SS and in 10/14 (71.4%) multifocal-SS. All but one patient with MS-LCH reached a response that was complete in 22/45 (48.9%). Of 6 pts with PHCD, 5 had a IR and one a CR. No pt presented CNS involvement at initial diagnosis.
Thirty-nine of 40 pts managed with pediatric protocols were evaluable for response. All 13 pts with SS-LCH had a response that was complete in 6 (46.1%). Among 26 patients with MS-LCH, 3 of them with organ risk involvement achieved a response, that was complete in 1, while among 23 patients without organ risk, 12 (52.2%), 8 (34.8%) and 3 (13%) had a CR, IR and NR, respectively.
Overall, 12 patients were lost to follow-up. Disease progression was recorded in 47/95 pts (49.5%) after a median time of 19 months (range: 6-147 months). The progression-free survival at 43 months was significantly better for patients treated according to the GIMEMA LCH 2001 guidelines compared to those managed with pediatric protocols, 67% (IC95% 53.14 - 80.86%) vs 48% (IC95% 31.37 - 64.63%), respectively (p 0.005). Overall, 7 deaths were recorded, 5 in patients treated with the pediatric protocols. The overall survival at 43 months, was similar in patients managed with the GIMEMA LCH 2001 guidelines and in those treated with pediatric protocols (97.9%, CI 95%: 93.75% - 100% and 97.3%, (IC95% 91.96% - 100%). BRAF V600E mutation was found in 13/35 (37%) evaluable cases. No differences in response and outcome between BRAFV600E-mutated patients and those not-mutated were found.
Our experience in a large cohort of LCH adults shows that a multidisciplinary approach is useful in identifying organ involvement in adults, including those asymptomatic. This is critical for an adequate treatment. Moreover, guidelines specific for adults with LCH proved efficacy in improving the outcome in this category of patients.
No relevant conflicts of interest to declare.
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