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The dramatic rise in online shopping means that the last mile delivery (LMD) task is becoming extremely important. However, last mile delivery faces many economic, social, and environmental challenges. A fast-growing innovative solution is Crowd Logistics Delivery (CLD). This study investigates how CLD is meeting these challenges in a rapidly emerging economy (Saudi Arabia). It uses semi-structured interviews to analyse CLD from the perspectives of multiple stakeholders, focusing on its implementation, benefits to different stakeholders, and its limitations. While the findings of this study broadly support the work of other studies in this area, it provides several new insights. It observed three different business models being used for CLD: B2B, B2C, and C2C. It identified the internal success factors of each business model, including registration, assigning orders, compensation, and the payment model. It revealed the motivations for stakeholders to use CLD as a last mile delivery solution, such as LMD-related benefits and the social impact on society. In addition, the study highlighted the four main challenges these CLD implementations face that impede their success: legislation, availability of supply/drivers, trust, and culture. These results add to the rapidly expanding field of CLD.

I flussi dei dati amministrativi sanitari regionali possono costituire una fonte preziosa per intercettare patologie di interesse. In particolare, dalle Schede di Dimissione Ospedaliera (SDO) si potrebbero intercettare i pazienti con Malattia Renale Cronica (MRC) mediante l’uso della sottocategoria (codice a 4 cifre) del codice 585 della classificazione ICD9-CM. Con il presente studio abbiamo fornito una valutazione sulla qualità della codifica della MRC nelle SDO della regione Emilia-Romagna, usando come gold standard il database del progetto PIRP, che raccoglie dati di circa 30.000 pazienti con diagnosi accertata di MRC in fase conservativa e in cui la definizione dello stadio di malattia è basata sui valori degli esami di laboratorio. Sono stati selezionati tutti i ricoveri ospedalieri dei pazienti in MRC partecipanti al progetto PIRP effettuati nel periodo 1.1.2009-31.12.2017. La valutazione di qualità delle SDO si è basata su di una classificazione delle schede in quattro categorie esaustive in base al match con esami PIRP eseguiti entro 15 gg. (±) dal ricovero: a) MRC assente: le SDO in cui non era stato riportato in nessuna posizione della diagnosi un codice ICD9-CM di malattia renale cronica 585.x (Malattia renale cronica) o 586 (Insufficienza renale, non specificata); b) MRC non specificata: quando la MRC era stata riportata con i codici 585.9 (Malattia renale cronica, non specificata) oppure 586; c) MRC errata: le SDO in cui la quarta cifra del codice ICD9-CM etichettava uno stadio di MRC diverso da quello dell’esame PIRP e d) MRC corretta: quelle in cui i due stadi corrispondevano. Nelle 4.168 SDO selezionate, 1.848 (44.3%) non includevano alcun codice di MRC; le SDO con MRC non specificata erano 446 (10.7%); con MRC errata erano 833 (20.0%) e con MRC corretta erano 1.041 (25.0%). Il trend temporale delle MRC corrette appare in decremento dopo un iniziale miglioramento (22.3% nel 2017), mentre al contrario è cresciuta dal 32.9% del 2009 al 56.6% del 2017 la quota di MRC assenti. Tra le discipline di dimissione, Nefrologia aveva la più alta percentuale di MRC corrette (69.1%), e solamente Geriatria superava il 20% tra le altre discipline con almeno 50 schede di dimissione. La bassa qualità della codifica SDO per la MRC tra i ricoveri eseguiti in reparti diversi dalla Nefrologia preclude sostanzialmente la possibilità di utilizzare le SDO come fonte per identificare pazienti con MRC non noti ai nefrologi. Inoltre, la MRC non compare nella lettera di dimissione dal ricovero se non viene inclusa nelle SDO, e così il medico di famiglia perde un’informazione che con ogni probabilità lo avrebbe motivato ad inviare il paziente presso gli specialisti nefrologi. Occorre pertanto intensificare la formazione degli addetti alla compilazione delle SDO, sensibilizzandoli all’utilizzo della quarta cifra, nonché “rivisitare” il significato delle SDO, che hanno molte potenzialità per la ricerca epidemiologica. La qualità della codifica SDO potrebbe inoltre migliorare sensibilmente se l’input del valore della creatinina venisse reso obbligatorio per tutte le discipline. Administrative databases contain precious information that can support the identification of specific pathologies. Specifically, chronic kidney disease (CKD) patients could be identified using hospital discharge records (HDR); these should contain information on the CKD stage using subcategories of the ICD9-CM classification's 585 code (subcategories can be expressed just by adding a fourth digit to this code). To verify the accuracy of HDR data regarding the coding of CKD collected in the Italian region Emilia-Romagna, we analyzed the HDR records of patients enrolled in the PIRP project, which could easily be matched with eGFR data obtained through laboratory examinations. The PIRP database was used as the gold standard because it contains data on CKD patients followed up since 2004 in thirteen regional nephrology units and includes data obtained from reliable and homogeneous laboratory measurement. All HDR of PIRP patients enrolled between 2009 and 2017 were retrieved and matched with available laboratory data on eGFR, collected within 15 days before or after discharge. We analyzed 4.168 HDR, which were classified as: a) unreported CKD (n=1.848, 44.3%); b) unspecified CKD, when code 585.9 (CKD, not specified) or 586 was used (n=446, 10.7%); c) wrong CKD (n=833, 20.0%); d) correct CKD (n=1041, 25.0%). We noticed the proportion of unreported CKD growing from 32.9% in 2009 to 56.6% in 2017, and the correspondent proportion of correct CKDs decreasing from 25.4% to 22.3%. Across disciplines, Nephrology showed the highest concordance (69.1%) between the CKD stage specified in the HDRs and the stage reported in the matched laboratory exam, while none of the other disciplines, except for Geriatrics, reached 20% concordance. When the CKD stage was incorrectly coded, it was generally underestimated; among HDRs with unreported or unspecified CKD at least half of the discharges were matched with lab exams reporting CKD in stage 4 or 5. We found that the quality of CKD stage coding in the HDR record database was very poor, and insufficient to identify CKD patients unknown to nephrologists. Moreover, the growing proportion of unreported CKD could have an adverse effect on patients' timely referral to a nephrologist, since general practitioners might remain unaware of their patients' illness. Actions aimed at improving the training of the operators in charge of HDRs compilation and, most of all, at allowing the exploitation of the informative potential of HDRs for epidemiological research are thus needed.

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels., Graphical abstract

Introduction Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. Methods We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non–immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). Results After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo–expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-α (TNF-α) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. Conclusion This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity., Graphical abstract

Individuals with kidney failure are at increased risk of cardiovascular events, as well as infections and malignancies, but the associated immunological abnormalities are unclear. We hypothesized that the uremic milieu triggers a chronic inflammatory state that, while accelerating atherosclerosis, promotes T cell exhaustion, impairing effective clearance of pathogens and tumor cells. Clinical and demographic data were collected from 78 patients with chronic kidney disease (CKD) (n = 42) or end-stage kidney disease (ESKD) (n = 36) and from 18 healthy controls (HC). Serum cytokines were analyzed by Luminex. Immunophenotype of T cells was performed by flow cytometry on peripheral blood mononuclear cells. ESKD patients had significantly higher serum levels of IFN-γ, TNF-α, sCD40L, GM-CSF, IL-4, IL-8, MCP-1, and MIP-1β than CKD and HC. After mitogen stimulation, both CD4+ and CD8+ T cells in ESKD group demonstrated a pro-inflammatory phenotype with increased IFN-γ and TNF-α, whereas both CKD and ESKD patients had higher IL-2 levels. CKD and ESKD were associated with increased frequency of exhausted CD4+ T cells (CD4+KLRG1+PD1+CD57−) and CD8+ T cells (CD8+KLRG1+PD1+CD57−), as well as anergic CD4+ T cells (CD4+KLRG1−PD1+CD57−) and CD8+ T cells (CD8+KLRG1−PD1+CD57−). Although total percentage of follicular helper T cell (TFH) was similar amongst groups, ESKD had reduced frequency of TFH1 (CCR6−CXCR3+CXCR5+PD1+CD4+CD8−), but increased TFH2 (CCR6−CXCR3−CXCR5+PD1+CD4+CD8−), and plasmablasts (CD3−CD56−CD19+CD27highCD38highCD138−). In conclusion, kidney failure is associated with pro-inflammatory markers, exhausted T cell phenotype, and upregulated TFH2, especially in ESKD. These immunological changes may account, at least in part, for the increased cardiovascular risk in these patients and their susceptibility to infections and malignancies.

While glomerulosclerosis commonly progresses to kidney failure, its mechanisms are unclear. Using murine models and human samples, the authors show that progressive glomerulosclerosis results from loss of decay-accelerating factor (DAF/CD55) on podocytes, which in turn initiates complement C3aR signaling and downstream IL-1β/IL-1R1–mediated podocyte injury and loss., Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models of adriamycin (ADR)-induced focal and segmental glomerulosclerosis (FSGS) and streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage of DAF from podocyte surfaces, leading to complement activation. C3 deficiency or prevention of C3a receptor (C3aR) signaling abrogates disease despite DAF deficiency, confirming complement dependence. Mechanistic studies show that C3a/C3aR ligations on podocytes initiate an autocrine IL-1β/IL-1R1 signaling loop that reduces nephrin expression, causing actin cytoskeleton rearrangement. Uncoupling IL-1β/IL-1R1 signaling prevents disease, providing a causal link. Glomeruli of patients with FSGS lack DAF and stain positive for C3d, and urinary C3a positively correlates with the degree of proteinuria. Together, our data indicate that the development and progression of glomerulosclerosis involve loss of podocyte DAF, triggering local, complement-dependent, IL-1β–induced podocyte injury, potentially identifying new therapeutic targets., Graphical Abstract

Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support use of Prevnar vaccination in individuals with SLE.