To evaluate the utility of the revised coma remission scale (CRS-r), together with other clinical variables, in predicting emergence from disorders of consciousness (DoC) during intensive ...rehabilitation care.
Data were retrospectively extracted from the medical records of patients enrolled in a specialized intensive rehabilitation unit. 123 patients in a vegetative state (VS) and 57 in a minimally conscious state (MCS) were included and followed for a period of 8 weeks. Demographical and clinical factors were used as outcome measures. Univariate and multivariate Cox regression models were employed for examining potential predictors for clinical outcome along the time.
VS and MCS groups were matched for demographical and clinical variables (i.e., age, aetiology, tracheostomy and route of feeding). Within 2 months after admission in intensive neurorehabilitation unit, 3.9% were dead, 35.5% had a full recovery of consciousness and 66.7% remained in VS or MCS. Multivariate analysis demonstrated that the best predictor of functional improvement was the CRS-r scores. In particular, patients with values greater than 12 at admission were those with a favourable likelihood of emergence from DoC.
Our study highlights the role of the CRS-r scores for predicting a short-term favorable outcome.
Support vector machines (SVMs) are well-known machine learning algorithms for classification and regression applications. In the healthcare domain, they have been used for a variety of tasks ...including diagnosis, prognosis, and prediction of disease outcomes. This review is an extensive survey on the current state-of-the-art of SVMs developed and applied in the medical field over the years. Many variants of SVM-based approaches have been developed to enhance their generalisation capabilities. We illustrate the most interesting SVM-based models that have been developed and applied in healthcare to improve performance metrics on benchmark datasets, including hybrid classification methods that combine, for instance, optimization algorithms with SVMs. We even report interesting results found in medical applications related to real-world data. Several issues around SVMs, such as selection of hyperparameters and learning from data of questionable quality, are discussed as well. The several variants developed and introduced over the years could be useful in designing new methods to improve performance in critical fields such as healthcare, where accuracy, specificity, and other metrics are crucial. Finally, current research trends and future directions are underlined.
Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress ...and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.
Nod-like receptor protein 3 (NLRP3) is a multi-protein complex belonging to the innate immune system, whose activation by danger stimuli promotes inflammatory cell death. Evidence supports the ...crucial role of NLRP3 inflammasome activation in the transition of acute kidney injury to Chronic Kidney Disease (CKD), by promoting both inflammation and fibrotic processes. Variants of NLRP3 pathway-related genes, such as NLRP3 itself and CARD8, have been associated with susceptibility to different autoimmune and inflammatory diseases. In this study, we investigated for the first time the association of functional variants of NLRP3 pathway-related genes (
,
), with a susceptibility to CKD. A cohort of kidney transplant recipients, dialysis and CKD stage 3-5 patients (303 cases) and a cohort of elderly controls (85 subjects) were genotyped for the variants of interest and compared by using logistic regression analyses. Our analysis showed a significantly higher G allele frequency of the NLRP3 variant (67.3%) and T allele of the CARD8 variant (70.8%) among cases, compared with the control sample (35.9 and 31.2%, respectively). Logistic regressions showed significant associations (
< 0.001) between NLRP3 and CARD8 variants and cases. Our results suggest that the
and
variants could be associated with a susceptibility to CKD.
Cancer has been described as a risk factor for greater susceptibility to SARS-CoV-2 infection and severe COVID-19, mainly for patients with metastatic disease. Conversely, to that reported for most ...solid and hematological malignancies, the few available clinical studies reported that the infection did not increase the risk of death in renal cancer patients. The expression on proximal tubular renal cells of the key players in cellular viral uptake, ACE2, TMPRSS2, and NRP1, seems to be the mechanism for the direct kidney injury seen in patients with COVID-19. Interestingly, data from The Cancer Genome Atlas and experimental analyses on various renal cancer cell lines demonstrated that the above-reported receptors/cofactors are maintained by renal cancer cells. However, whether SARS-CoV-2 infection directly kills renal cancer cells or generates enhanced immunogenicity is a question worth investigating. In addition, some researchers have further addressed the topic by studying the expression and prognostic significance of gene signatures related to SARS-CoV-2 infection in renal cancer patients. The emerging data highlights the importance of better understanding the existence of a link between renal cancer and COVID-19 since it could lead to the identification of new prognostic factors and the development of new therapeutic targets in the management of renal cancer patients.
Gut dysbiosis refers to an imbalance in gut microbiota composition and function.
extract has been shown to modulate gut microbiota by improving SCFA production in vivo and gastrointestinal discomfort ...(GD) in humans. The aim of this study was to demonstrate the efficacy of Odilia
on gastrointestinal health by changing the microbial diversity of species involved in inflammation, immunity, oxidation, and the brain-gut-muscle axis. A randomized, double-blind clinical trial was conducted in 80 adults with gut dysbiosis. The intervention consisted of a 300 mg daily intake of Odilia
(n = 40) or maltodextrin as a placebo (n = 40), administered for 8 weeks. Intervention effect was evaluated using 16S metagenomics and GIQLI/GSAS scores at baseline, at 4 and 8 weeks. Eight weeks of Odilia
supplementation positively modulates gut microbiota composition with a significant reduction in the
to
ratio (
= 0.0012). Relative abundances of beneficial bacteria (
and
) were significantly increased (
< 0.001), in contrast to a significant reduction in pro-inflammatory bacteria (
< 0.001). Accordingly, GIQLI and GSAS scores revealed successful improvement in GD. Odilia
may represent an effective and well-tolerated treatment in subjects with gut dysbiosis.
In this study, we sought to assess the predictors of outcome in patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI) during neurorehabilitation stay. 96 patients ...with DOC (vegetative state, minimally conscious state, or emergence from minimally conscious state) were enrolled (69 males; mean age 43.6 ± 20.8 years) and the improvement of the degree of disability, as assessed by the Disability Rating Scale, was considered the main outcome measure. To define the best predictor, a series of demographical and clinical factors were modeled using a twofold approach: a) logistic regression to evaluate a possible causal effect among variables and b) machine learning algorithms (ML), to define the best predictive model. Univariate analysis demonstrated that disability in DOC patients statistically decreased at the discharge with respect to admission. The genitourinary was the most frequent medical complication (MC) emerging during the neurorehabilitation period. The logistic model revealed that the total amount of MCs is a risk factor for lack of functional improvement. ML discloses that the most important prognostic factors are the respiratory and hepatic complications together with the presence of the upper gastrointestinal comorbidities. Our study provides new evidence on the most adverse short-term factors predicting a functional recovery in DOC patients after severe TBI. The occurrence of medical complications during neurorehabilitation stay should be considered for avoiding poor outcomes.
Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to ...globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway’s activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1β, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband’s PBMC exhibited higher expression of TGFβ 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant’s contribution to cellular and tissue damage.
Partial nephrectomy (PN) is the primary surgical method for renal tumor treatment, typically involving clamping the renal artery during tumor removal, leading to warm ischemia and potential renal ...function impairment. Off-clamp approaches have been explored to mitigate organ damage, yet few results have emerged about the possible effects on hemoglobin loss. Most evidence comes from retrospective studies using propensity score matching, known to be sensitive to PS model misspecification. The energy balancing weights (EBW) method offers an alternative method to address bias by focusing on balancing all the characteristics of covariate distribution. We aimed to compare on- vs. off-clamp techniques in PN using EB-weighted retrospective patient data. Out of 333 consecutive PNs (275/58 on/off-clamp ratio), the EBW method achieved balanced variables, notably tumor anatomy and staging. No significant differences were observed in the operative endpoints between on- and off-clamp techniques, although off-clamp PNs showed slight reductions in hemoglobin loss and renal function decline, albeit with slightly higher perioperative blood loss. Our findings support previous evidence, indicating comparable surgical outcomes between standard and off-clamp procedures, with the EBW method proving effective in balancing baseline variables in observational studies comparing interventions.
Patients with kidney transplantation often have a worse quality of life than the general population. One of the reasons for this, in male patients, is the high prevalence of erectile dysfunction. ...This is mainly due to the presence of comorbidities, surgery for kidney transplantation, adverse drug effects, psychological changes related to chronic disease, as well as hyperprolactinemia and hypogonadism. Whenever these endocrine dysfunctions occur after kidney transplantation, they must be corrected with appropriate treatment, i.e., testosterone replacement therapy. Administration of the phosphodiesterase-5 inhibitor (PDE5i) sildenafil at the recommended posology does not significantly alter the pharmacokinetics of the calcineurin inhibitors cyclosporin A or tacrolimus and does not impair kidney allograft function. Tacrolimus increases the peak concentration and prolongs the half-life of PDE5i in kidney transplant patients and, therefore, daily administration cannot be recommended due to the significant drop in blood pressure. Intracavernous injection or topical application of alprostadil can be a second-line option for the treatment of erectile dysfunction after kidney transplantation, which does not alter cyclosporine concentrations and does not deteriorate kidney function. Finally, penile prostheses can be successfully implanted following pelvic organ transplantation after eliminating the risk of infection associated with surgery.
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