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  • 1
    In: Blood Purification, S. Karger AG, Vol. 49, No. 3 ( 2020), p. 372-378
    Abstract: Coupled plasma filtration adsorption (CPFA) is an extracorporeal supportive therapy based on nonspecific adsorption of pro- and anti-inflammatory mediators combined with continuous renal replacement therapy. The main field of CPFA application is septic shock, and there are limited data about its efficacy in the treatment of other acute conditions characterized by a dysregulation in immune homeostasis. Capillary leak syndrome (CLS) defines a life-threatening condition sustained by hypercytokinemia and characterized by abrupt onset of increased capillary permeability leading to severe generalized edema and hypovolemic shock refractory to fluid administration. Therapy for CLS is not specific and, at present time, it consists in the use of steroids or intravenous immunoglobulins. We present the case of a 34-year-old woman who developed CLS superimposed to acute generalized exanthematous pustulosis after initiating therapy with hydroxychloroquine for undifferentiated connective tissue disease. CLS did not respond to steroids and intravenous immunoglobulins, while it was successfully treated with CPFA. This observation supports the possible role of CPFA in restoring a proper immunologic homeostasis not only in sepsis but also in other devastating conditions sustained by hypercytokinemia.
    Type of Medium: Online Resource
    ISSN: 0253-5068 , 1421-9735
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 1482025-0
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  • 2
    In: Cytogenetic and Genome Research, S. Karger AG, Vol. 147, No. 1 ( 2015), p. 10-16
    Abstract: Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to 〉 11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations.
    Type of Medium: Online Resource
    ISSN: 1424-8581 , 1424-859X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 2061918-2
    SSG: 12
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  • 3
    In: Blood Purification, S. Karger AG, Vol. 23, No. 1 ( 2005), p. 91-98
    Abstract: 〈 i 〉 Aim: 〈 /i 〉 The aim of the study was to evaluate biocompatibility of anew polystyrene-type adsorbent (BetaSorb 〈 sup 〉 TM 〈 /sup 〉 ) designed for hemoperfusion, using second-level biomolecular analyses. The device has recently been developed to enhance β 〈 sub 〉 2 〈 /sub 〉 -microglobulin removal during hemodialysis. Molecular structure and chemical modifications of the surface beads of this cartridge should prevent exposure of dense hydrophobic surface sites to proteins, and avoid the major drawbacks of previous polystyrene-type adsorbent materials. 〈 i 〉 Methods: 〈 /i 〉 Whole blood of healthy donors was incubated in sterile minicolumns packed with BetaSorb Cuprophan, Hemophan, polysulfone and  cellulose acetate. In parallel experiments, whole blood was recirculated for 180 min in a sham dialysis circuit equipped with the study sorbent or Hemophan or polysulfone. Biocompatibility was assessed by means of new biomolecular approaches focused on nuclear factor ĸB (NF-ĸB) activation (assessed by electrophoretic mobility shift assay), TNF-α and IL-1β gene expression (evaluated by real-time PCR), TNF-α and IL-1β production (measured by Western blot assay and ELISA), nitric oxide (NO) generation (detected by electron paramagnetic resonance), free oxygen radical production (by chemiluminescence in a biological assay) and the generation of the complement breakdown product C3d. 〈 i 〉 Results: 〈 /i 〉 In coincubation experiments, 5-min contact with any dialysis device, but BetaSorb, was enough to induce activation of NF-ĸB. The amount of TNF-α precursor form was found to increase after 5 min of exposure to each tested polymer, but no traces of mature forms of TNF-α or IL-1β were detected in in vitro experimental conditions using healthy blood. NO and free oxygen radical generation were significantly lower in blood samples exposed to BetaSorb than in control dialysis devices. C3d levels were found to be increased with Hemophan, unaffected by polysulfone, and remarkably decreased with the BetaSorb device. In the sham hemodialysis experiments, NF-ĸB activation and C3d and NO profiles were similar to direct incubation experiments. Compared to basal levels, quantitation of TNF-α and IL-1β mRNA revealed a 15- and 9-fold increase, respectively, in samples exposed to Hemophan for 180 min. 〈 i 〉 Conclusions: 〈 /i 〉 The new BetaSorb device not only appears to be highly biocompatible, but shares properties that make it probably able to interfere with the activation of the inflammatory state.
    Type of Medium: Online Resource
    ISSN: 0253-5068 , 1421-9735
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2005
    detail.hit.zdb_id: 1482025-0
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  • 4
    In: Cytogenetic and Genome Research, S. Karger AG, Vol. 146, No. 1 ( 2015), p. 39-43
    Abstract: Interstitial 1p deletions are rare events. Very few cases of 1p31.1p31.3 deletions characterized by variable phenotypes have been reported. No clear genotype-phenotype correlation has been determined yet. We present a child with a de novo interstitial 1p31.1p31.3 deletion, identified by array CGH, associated with intellectual disability and severe language impairment. The deleted region contains 20 OMIM genes, but we focused on 〈 i 〉 GADD45A 〈 /i 〉 (MIM 126335; growth arrest- and DNA damage-inducible gene), 〈 i 〉 LRRC7 〈 /i 〉 (MIM 614453; leucine-rich repeat-containing protein 7), and 〈 i 〉 NEGR1 〈 /i 〉 (MIM 613173; neuronal growth regulator 1). We discuss whether these genes play a role in determining the phenotype of our patient in order to investigate the possibility of a genotype-phenotype correlation.
    Type of Medium: Online Resource
    ISSN: 1424-8581 , 1424-859X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 2061918-2
    SSG: 12
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  • 5
    In: Cytogenetic and Genome Research, S. Karger AG, Vol. 162, No. 3 ( 2022), p. 132-139
    Abstract: Interstitial 2q24.2q24.3 microdeletions are rare cytogenetic aberrations associated with heterogeneous clinical features depending on the size of the deletion. Here, we describe 2 patients with overlapping de novo 2q24.2q24.3 deletions, characterized by array-CGH. This is the smallest 2q24.2q24.3 region of overlap described in the literature encompassing only 9 genes ( 〈 i 〉 SLC4A10 〈 /i 〉 , 〈 i 〉 DPP4 〈 /i 〉 , 〈 i 〉 GCG 〈 /i 〉 , 〈 i 〉 FAP 〈 /i 〉 , 〈 i 〉 IFIH1 〈 /i 〉 , 〈 i 〉 GCA 〈 /i 〉 , 〈 i 〉 KCNH7 〈 /i 〉 , 〈 i 〉 FIGN 〈 /i 〉 , 〈 i 〉 GRB14 〈 /i 〉 ). We focused our attention on 〈 i 〉 SLC4A10, DPP4, 〈 /i 〉 and 〈 i 〉 KCNH7, 〈 /i 〉 genes associated with neurological features. Our patients presented similar features: intellectual disability, developmental and language delay, hypotonia, joint laxity, and dysmorphic features. Only patient 2 showed profound deafness and also carried a heterozygous mutation of the 〈 i 〉 GJB2 〈 /i 〉 gene responsible for autosomal recessive deafness 1A (DFNB1A: OMIM 220290). Could the disruption of a gene present in the 2q24.2q24.3 deleted region be responsible for her profound hearing loss?
    Type of Medium: Online Resource
    ISSN: 1424-8581 , 1424-859X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2061918-2
    SSG: 12
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  • 6
    In: Audiology and Neurotology, S. Karger AG, Vol. 27, No. 1 ( 2022), p. 64-74
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Sudden sensorineural hearing loss (SSHL) is a relatively frequent disease, but a sensitive marker or a reliable test to identify the underlying cause is still unavailable. Neuroradiology appears to offer the most promising tools, especially magnetic resonance imaging (MRI). In a recent study from our group, we explored the ability of MRI to detect subtle changes in the inner ear compartments by means of a 3D-fluid-attenuated inversion recovery sequence, aiming at identifying 3 distinct MRI patterns (haemorrhagic, inflammatory, brain-labyrinth barrier breakdown). In the present study, we contrasted the MRI patterns at onset with relevant prognostic factors, with the audiological features of each patient’s SSHL and with treatment outcomes. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In this retrospective study, we enrolled 50 adult subjects (54.61 ± 18.26 years) with SSHL. They underwent an MRI within 72 h from admission, and 5 audiological evaluations: at admission, on the 5th day after the start of medical therapy, at the end of the first cycle of hyperbaric oxygen therapy, then 1 and 6 months later. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Abnormalities of the MRI signal and/or post-contrast enhancement asymmetry of the cochlea (“pattern+ MRI”) correlated with worse audiological outcomes at 1 month, but the different MRI patterns were not correlated with any specific prognostic model, despite rigid protocol settings. However, a significant difference was found for low-tone SSHL, which were always “pattern 〈 i 〉 ” 〈 /i 〉 negative at MRI ( 〈 i 〉 p 〈 /i 〉 = 0.01), and for profound SSHL which demonstrated a pattern+ MRI in 80% ( 〈 i 〉 p 〈 /i 〉 = 0.04). At the onset of SSHL, a pattern+ MRI was found in 29/50 cases (58.0%) and was related with lesser degree of recovery of pure-tone average at 1 month and lesser chance to retain the hearing threshold benefit in the long term. Given the limited numbers of patients enrolled so far, the relative impact of comorbidities on each MRI pattern remains uncertain. At 6 months, we observed a trend of greater and more stable recovery ( 〈 i 〉 p 〈 /i 〉 = 0.023) and less frequent recurrence of SSHL in patients with a normal MRI. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The 3 observed MRI patterns did not correlate consistently with specific audio-vestibular features or any peculiar aspect of the patient’s clinical history. Larger series of patients with SSHL are needed, possibly from multicentric studies.
    Type of Medium: Online Resource
    ISSN: 1420-3030 , 1421-9700
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1481979-X
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  • 7
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 43, No. 4 ( 2018), p. 1263-1272
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Multiple myeloma (MM) represents 10% of all haematologic malignancies. Renal involvement occurs in 50% of MM patients; of them, 12-20% have acute kidney injury (AKI), with 10% needing dialysis at presentation. While hemodialysis (HD) has no effect upon circulating and tissue levels of monoclonal proteins, novel apheretic techniques aim at removing the paraproteins responsible for glomerular/tubular deposition disease. High cut-off HD (HCO-HD) combined with chemotherapy affords a sustained reduction of serum free light chains (FLC) levels. One alternative technology is haemodiafiltration with ultrafiltrate regeneration by adsorption on resin (HFR–SUPRA), employing a “super high-flux” membrane (polyphenylene S-HF, with a nominal cut-off of 42 kD). Aim of our pilot study was to analyze the effectiveness of HFR-SUPRA in reducing the burden of FLC, while minimizing albumin loss and hastening recovery of renal function in 6 subjects with MM complicated by AKI. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Six HD-dependent patients with MM were treated with 5 consecutive sessions of HFR-SUPRA on a Bellco® monitor, while simultaneously initiating chemotherapy. Levels of albumin and FLC were assessed, calculating the rates of reduction. Renal outcome, HD withdrawal and clinical follow-up or death were recorded. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 All patients showed a significant reduction of FLC, whereas serum albumin concentration remained unchanged. In three, HD was withdrawn, switching to a chemotherapy alone regimen. The other patients remained HD-dependent and died shortly thereafter for cardiovascular complications. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our study suggests that HFR-SUPRA provides a rapid and effective reduction in serum FLC in patients with MM and AKI, while minimizing the loss of albumin. When started early in combination with chemotherapy, blood purification by HFR-SUPRA was followed by the recovery of renal function in half of the patients treated.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482922-8
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  • 8
    Online Resource
    Online Resource
    S. Karger AG ; 2009
    In:  Blood Purification Vol. 27, No. 4 ( 2009), p. 338-344
    In: Blood Purification, S. Karger AG, Vol. 27, No. 4 ( 2009), p. 338-344
    Abstract: Secondary hyperparathyroidism (SHPT) is a classical feature of chronic kidney disease (CKD). Commonly, hypocalcemia, hyperphosphatemia, and vitamin D deficiency are involved into the pathogenesis of SHPT. Parathyroid (PT) glands are characterized by a low turnover and rarely undergo mitoses. However, in the presence of low calcium, high phosphorus, vitamin D deficiency, and uremia, PT cells leave quiescence. In the last decade, both new molecular and cellular mechanisms have been investigated in the pathophysiology of SHPT, between them the emerging role of the PT vitamin D receptor and calcium-sensing receptor. Furthermore, recent studies indicate that the fibroblast growth factor-23 may play a central role in the regulation of phosphate-vitamin D metabolism in CKD. Certainly, in the next future, these new insights into the pathogenesis of SHPT will give the possibility to improve the treatment of this condition in the CKD population.
    Type of Medium: Online Resource
    ISSN: 0253-5068 , 1421-9735
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
    detail.hit.zdb_id: 1482025-0
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  • 9
    In: Cytogenetic and Genome Research, S. Karger AG, Vol. 156, No. 1 ( 2018), p. 14-21
    Abstract: 〈 i 〉 ULK4 〈 /i 〉 and 〈 i 〉 BRWD3 〈 /i 〉 deletions have been identified in patients with developmental/language delay and intellectual disability. Both genes play pivotal roles in brain development. In particular, 〈 i 〉 ULK4 〈 /i 〉 encodes serine/threonine kinases that are critical for the development and function of the nervous system, while 〈 i 〉 BRWD3 〈 /i 〉 plays a crucial role in ubiquitination, as part of the ubiquitin/proteasome system. We report on 2 brothers, aged 7.6 and 20 years, presenting with cognitive impairment, epilepsy, autistic features, hearing loss, and obesity. Array-CGH analysis demonstrated 2 rare CNVs in both siblings: a paternally inherited microdeletion of ∼145 kb at 3p22.1, disrupting the 〈 i 〉 ULK4 〈 /i 〉 gene, and a maternally inherited microduplication of ∼117 kb at Xq21.1 including only the 〈 i 〉 BRWD3 〈 /i 〉 gene. As already described for other recurrent syndromes with variable phenotype, these findings are challenging in genetic counseling because of an evident variable penetrance. We discuss the possible correlations between the clinical phenotype of our patients and the function of the genes involved in these microrearrangements.
    Type of Medium: Online Resource
    ISSN: 1424-8581 , 1424-859X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 2061918-2
    SSG: 12
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  • 10
    In: European Neurology, S. Karger AG, Vol. 23, No. 6 ( 1984), p. 459-465
    Type of Medium: Online Resource
    ISSN: 0014-3022 , 1421-9913
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1984
    detail.hit.zdb_id: 1482237-4
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