Minimal Clinically Important Difference and Patient Acceptable Symptom State in Patients With Knee Osteoarthritis Treated With PRP Injection

Background: Although several injection-based treatments have been proposed to address knee osteoarthritis (OA), it is often difficult to understand the clinical relevance of the obtained results. The psychometric measures of minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were developed to better interpret study findings. Purpose: To establish the MCID and the PASS for the International Knee Documentation Committee (IKDC) Subjective score and the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients treated with intra-articular platelet-rich plasma (PRP) injections for knee OA. Study Design: Case series; Level of evidence, 4. Methods: This study included 215 patients with knee OA (68% men, 32% women; age, 53.2 ± 11.3 years; body mass index, 26.8 ± 4.3 kg/m2) who underwent intra-articular PRP injections. Patients were assessed through the IKDC Subjective score and KOOS subscales, and the MCID and the PASS for both measures were independently calculated at 6 and 12 months post-injection. The MCID was calculated using the value equal to half of the standard deviation of the overall cohort improvement. The PASS was assessed using a 2-point scale (satisfied or not satisfied), with threshold values being detected through a receiver operating characteristic curve analysis and the Youden index to maximize the sensitivity and the specificity of the threshold values. Results: All scores improved significantly from baseline to 6 months and baseline to 12 months (P <.001 for all scores). All scores were stable from 6 to 12 months except for the KOOS Quality of Life subscale, which improved further (P =.033). For the IKDC, the MCID values were 8.6 and 8.5 points and the PASS scores were 59.7 and 62.1 at 6 and 12 months, respectively. Overall, the MCID and the PASS for all KOOS subscales remained constant at the 2 follow-up points. The percentage of patients who achieved the MCID and the PASS was higher than 85% at both 6 and 12 months post-injection. Conclusion: This study provided the MCID and PASS thresholds for the IKDC and KOOS scores in patients with knee OA treated with PRP injections. These psychometric measures may allow a better interpretation of the clinical relevance of injection-based treatment outcomes for knee OA

Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.info:eu-repo/semantics/publishedVersio

Overexpression of the Cytokine BAFF and Autoimmunity Risk

$\textbf{BACKGROUND}$: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. $\textbf{METHODS}$: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. $\textbf{RESULTS}$: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. $\textbf{CONCLUSIONS}$: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).Supported by grants (2011/R/13 and 2015/R/09, to Dr. Cucca) from the Italian Foundation for Multiple Sclerosis; contracts (N01-AG-1-2109 and HHSN271201100005C, to Dr. Cucca) from the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH); a grant (FaReBio2011 “Farmaci e Reti Biotecnologiche di Qualità,” to Dr. Cucca) from the Italian Ministry of Economy and Finance; a grant (633964, to Dr. Cucca) from the Horizon 2020 Research and Innovation Program of the European Union; a grant (U1301.2015/AI.1157.BE Prat. 2015-1651, to Dr. Cucca) from Fondazione di Sardegna; grants (“Centro per la ricerca di nuovi farmaci per malattie rare, trascurate e della povertà” and “Progetto collezione di composti chimici ed attività di screening,” to Dr. Cucca) from Ministero dell’Istruzione, dell’Università e della Ricerca; grants (HG005581, HG005552, HG006513, and HG007022, to Dr. Abecasis) from the National Human Genome Research Institute; a grant (9-2011-253, to Dr. Todd) from JDRF; a grant (091157, to Dr. Todd) from the Wellcome Trust; a grant (to Dr. Todd) from the National Institute for Health Research (NIHR); and the NIHR Cambridge Biomedical Research Centre. Dr. Idda was a recipient of a Master and Back fellowship from the Autonomous Region of Sardinia

Control of fermentation duration and pH to orient biochemicals and biofuels production from cheese whey

Batch dark fermentation tests were performed on sheep cheese whey, without inoculum addition at different operating pHs, relating the type and production yields of the observed gaseous and liquid by-products to the evolution of fermentation. Cheese whey fermentation evolved over time in two steps, involving an initial conversion of carbohydrates to lactic acid, followed by the degradation of this to soluble and gaseous products including short-chain fatty acids (mainly acetic, butyric and propionic acids) and hydrogen. The operating pH affected the production kinetics and yields, as well as the fermentation pathways. By varying the duration of the fermentation process, different cheese whey exploitation strategies may be applied and oriented to the main production of lactic acid or hydrogen or other organic acids

Dark fermentation of sheep cheese whey: biochemicals and biofuels production as a function of fermentation time and pH

Cheese whey (CW) is the main by-product of the cheese making process and is composed mainly by lactose, proteins, lipids and mineral salts. The environmental impacts and other potential negative effects linked to the traditional management strategies of CW are no longer considered sustainable, therefore alternatives need to be explored. Dark fermentation (DF) may be a promising approach for CW valorization. Though the issue has been already addressed by several studies with particular emphasis on biohydrogen production, less attention has been paid to the possibility of recovering also other valuable products. Optimizing the effects of operating pH and fermentation time is a strategy worth to be studied in order to obtain specific biochemicals and/or biofuels from CW. In this framework, batch DF tests were performed under mesophilic conditions on sheep CW, without inoculum addition, adopting different operating pHs, and relating type and production yields of the observed gaseous and liquid byproducts to the duration of the process. CW fermentation evolved over time according to two steps; the first phase was characterised by lactose conversion to lactic acid, whilst during the second one lactic acid was degraded to soluble and gaseous products such as short chain fatty acids (mainly acetate, butyrate and propionate) and hydrogen. The adopted operating pHs affected the production kinetics and yields, as well as metabolic pathways. In particular, setting the operating pH to 6 proved to be optimal in terms of both lactic acid or hydrogen production yields

A cascade biorefinery for grape marc: Recovery of materials and energy through thermochemical and biochemical processes

The agro-industrial sector makes a high contribution to greenhouse gas emissions; therefore, proper waste management is crucial to reduce the carbon footprint of the food chain. Hydrothermal carbonization (HTC) is a promising and flexible thermochemical process for converting organic materials into energy and added-value products that can be used indifferent applications. In this work, grape marc residues before and after an extraction process for recovering polyphenols were hydrothermally treated at 220 degrees C for 1 h. The resulting hydrochar and process water were investigated to test an innovative cascade approach aimed at a multiple product and energy recovery based on the integration of HTC with anaerobic digestion. The results show that this biorefinery approach applied to grape marc could allow to diversify and integrate its potential valorisation options. The produced hydrochars possess an increased fixed carbon content compared to the feedstock (up to +70%) and, therefore, can be used in soil, immobilizing carbon in a stable form and partially replacing peat in growing media (up to 5 % in case of hydrochar from grape marc after extraction), saving the consumption of this natural substrate. In addition, energy can be recovered from both hydrochar by combustion and from process water through anaerobic digestion to produce biogas. Hydrochars show good properties as solid fuel similar to lignite, with an energy content of around 27 MJ kg(-1) ( +30 % compared to the feedstock). The anaerobic digestion of the process water allowed obtaining up to 137 mL of biomethane per gram of fed COD. Finally, while HTC process waters are suitable for biological treatment, attention must be paid to the presence of inhibiting compounds that induce acute toxic effects in aerobic conditions. The proposed approach is consistent with the principles of circular economy and could increase the overall sustainability and resilience of the agro-industrial sector