Erdheim-Chester disease : from palliative care to targeted treatment

Erdheim-Chester disease (ECD) is a life-threatening multi-systemic non-Langerhans histiocytosis with cardiovascular complications as the leading cause of death. ECD affects the kidneys in up to 30% of cases, with fibrotic tissue deposition in the perirenal fat and renal hilum. Diagnosis is usually based on histological analysis of the pathologic tissue, which typically shows xanthogranulomatous infiltrates of foamy CD68+/CD1a-histiocytes surrounded by fibrosis. A consistent percentage of patients affected by ECD develop renal failure and hypertension as a consequence of renal artery stenosis and hydronephrosis. These conditions have been generally treated with the placement of stents and nephrostomies that frequently led to disappointing outcomes. Before the introduction of interferon-alpha (IFN\u3b1) treatment, the mortality rate was as high as 57% in the long term. Recent studies have granted new insights into the pathogenesis of ECD, which seems to bear a dual component of clonal and inflammatory disease. These advances led to use specific therapies targeting either the oncogenes (BRAFV600E) or the effectors of the immune response implicated in ECD (IL-1, TNF\u3b1). Drugs such as anakinra (recombinant human IL-1 receptor antagonist), infliximab (monoclonal antibody against TNF\u3b1) and vemurafenib (inhibitor of mutant BRAF) showed promising results in small single-centre series. Although larger trials will be needed to address the impact of these drugs on ECD prognosis and to select the most effective treatment, targeted therapies hold the premises to drastically change the outcome of this condition. \ua9 2014 The Author

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity

Should we really STOP treating patients with IgA nephropathy with steroids?

IgA nephropathy (IgAN) is the most common primary glomerulonephritis all over the world. Once considered as a benign disease, today the scientific community is aware that a significant percentage of patients eventually progress to end-stage kidney disease (ESKD). The rate of progression is often very slow. Since 1980s, several therapeutic attempts have been made with steroids. Despite different molecules, doses, and lengths of treatment, the majority of uncontrolled and controlled studies found benefits in terms of proteinuria reduction and reduction of the risk of ESKD. This was obtained with reasonable safety and tolerability, especially when steroids are given at relatively low dose and for a period not exceeding 6 months. Recently, two randomized controlled trials have questioned the efficacy and safety of steroid therapy in IgAN. However, these trials have many drawbacks that are to be considered when interpreting the findings

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

<p>Abstract</p> <p>Background</p> <p>Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.</p> <p>Methods</p> <p>A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFR_e), histopathology, type and duration of treatment, and clinical status at final evaluation.</p> <p>Results</p> <p>13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFR_e. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFR_ewas 127 ± 57 mL/min/m². Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.</p> <p>Conclusion</p> <p>IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.</p

New Insight on the Bioactivity of Solanum aethiopicum Linn. Growing in Basilicata Region (Italy): Phytochemical Characterization, Liposomal Incorporation, and Antioxidant Effects

Food extract’s biological effect and its improvement using nanotechnologies is one of the challenges of the last and the future decades; for this reason, the antioxidant effect of scarlet eggplant extract liposomal incorporation was investigated. Scarlet eggplant (Solanum aethiopicum L.) is a member of the Solanaceae family, and it is one of the most consumed vegetables in tropical Africa and south of Italy. This study investigated the antioxidant activity and the phytochemical composition of S. aethiopicum grown in the Basilicata Region for the first time. The whole fruit, peel, and pulp were subjected to ethanolic exhaustive maceration extraction, and all extracts were investigated. The HPLC-DAD analysis revealed the presence of ten phenolic compounds, including hydroxycinnamic acids, flavanones, flavanols, and four carotenoids (one xanthophyll and three carotenes). The peel extract was the most promising, active, and the richest in specialized metabolites; hence, it was tested on HepG2 cell lines and incorporated into liposomes. The nanoincorporation enhanced the peel extract’s antioxidant activity, resulting in a reduction of the concentration used. Furthermore, the extract improved the expression of endogenous antioxidants, such as ABCG2, CAT, and NQO1, presumably through the Nrf2 pathway

A Proposed Classification of the Immunological Diseases

The formal recognition and genetic understanding of the autoinflammatory diseases has defined mechanisms of self-directed inflammation that are independent of adaptive immunity