The Potential Immunonutritional Role of Parmigiano Reggiano Cheese in Children with Food Allergy

Parmigiano Reggiano (PR) is a ripened cheese with high nutritional value. Throughout ripening the bacteria contained in PR promote an extensive hydrolysis of cow’s milk proteins resulting in peptides that exhibit positive immunoregulatory activities. Additional modulatory activities on immune system are induced by butyrate, a short chain fatty acid widely expressed in PR. These findings suggest a possible immunonutritional role for PR able to stimulate oral tolerance in children with food allergy (FA)

Step-Up Approach for Sodium Butyrate Treatment in Children With Congenital Chloride Diarrhea

Objectives: Oral salt substitutive therapy is pivotal for the survival of patients with congenital chloride diarrhea (CLD), however this therapy is unable to influence the symptoms severity. Butyrate has been proposed to limit diarrhea severity in CLD. Unfortunately, the optimal dose schedule is still largely undefined. In addition, butyrate seems not to be well-tolerated by all patients, with some subjects reporting diarrhea worsening. We investigated the efficacy of a step-up therapeutic approach with sodium butyrate in patients who experienced a diarrhea worsening or an absent improvement after the direct administration of 100 mg/kg/day of sodium butyrate. Methods: The efficacy of a step-up therapeutic approach starting from 50 mg/Kg/day with a subsequent 25 mg/kg/day weekly increase up to 100 mg/kg/day of oral sodium butyrate was investigated in previously three unresponsive CLD children. Results: The step-up therapeutic approach resulted effective in limiting diarrhea severity in all our three previously unresponsive CLD patients. Conclusions: Our results suggest the efficacy of the step-up therapeutic approach in CLD children

New Insights and Perspectives in Congenital Diarrheal Disorders

Purpose of Review We highlight new entities of congenital diarrheal disorders (CDDs) and progresses in understanding of functionally related genes, opening new diagnostic and therapeutic perspectives. Recent Findings The more significant advances have been made in field of pathogenesis, encouraging a better under- standing not only of these rare diseases but also of more com- mon pathogenetic mechanisms. Summary CDDs represent an evolving group of rare chronic enteropathies with a typical onset early in the life. Usually, severe chronic diarrhea is the main clinical manifestation, but in other cases, diarrhea is only a component of a more complex systemic disease. The number of conditions has gradually increased, and many new genes have been indentified and functionally related to CDDs, opening new diagnostic and therapeutic perspectives. Advances in molecu- lar analysis procedures havemodified the diagnostic approach in CDDs, leading to a reduction in invasive and expensive procedures. Keywords Chronic diarrhe

CHRONIC RHINOSINUSITIS IN CYSTIC FIBROSIS PATIENTS: SMELL EVALUATION

Cystic Fibrosis (CF) involves the upper airways with chronic rhinosinusitis (CRS) causing nasal congestion, rhinorrhea, mouth breathing, facial pain, and olfactory dysfunction. Twelve to 71% of CF patients report smelling alterations impacting nutrition and quality of life. The aim was to study olfaction performance in CF patients with CRS that worsens quality of life. One hundred and twenty-one subjects were enrolled in this study. Seventy-one had CF and underwent ear, nose, and throat evaluation with nasal endoscopy, SNOT-22, VAS and “Sniffin’ Sticks”. Fifty subjects were age-matched with healthy controls. All 71 CF patients were affected by CRS; 59/71 (83.1%) had CRS without nasal polyps and 12/71 (16.9%) had CRS with early nasal polyps. None of the 50 controls had CRS. Total SNOTT-22 mean values in the 71 CF patients was 38.10 ± 21.08 pts. If considering only the 59 CF patients without nasal polyps the SNOTT-22 mean value was 36.76 ± 21.52 pts. Moreover, based on the VAS scores, the degree of nasal symptoms was classified as mild for facial pain, smell alteration, nasal discharge, and sneezing and resulted in moderate symptoms for nasal blockage and headache. Among the CF patients, 55/71 (76.5%) declared normosmia while the smelling ability assessed by “Sniffin’ Sticks” showed that only 4/71 (5.63%) were normosmic, 58 (81.69%) were hyposmic, and 9 (12.68%) were anosmic. In the controls 41(82%) were normosmic, 9 (18%) were hyposmic, and none were reported anosmia (p < 0.001). The study confirms that most CF patients have a relevant olfactory impairment, although only a low percentage declare it. A careful evaluation with simple and rapid tests helps to select the patients that may benefit from specific therapies

Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved. For permissions, please email: [email protected]: Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice. Methods: We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD. Results: In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn's disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5-23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment. Conclusions: A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.Peer reviewe

Novel insights in the clinical management of hyperimmune patients before and after transplantation

Despite improvements in anti-Human Leucocyte Antigens antibody detection, identification, and characterization offer a better in peri-operative management techniques, antibodies remain a serious cause of morbidity and mortality for patients both before and after organ transplantation. Hyperimmune patients are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. They could benefit from desensitization protocols in both pre- and post-transplantation period. Clinical studies are underway to highlight which best desensitization strategies could be assure the best outcome in both heart and kidney transplantation. Although most clinical evidence about desensitization strategies by using anti-CD20 monoclonal antibodies, proteasome inhibitors, anti-CD38 monoclonal antibodies, interleukin-6 blockade, cysteine protease and complement inhibitors, comes from kidney transplantation studies, many of the debated novel concepts can be easily applied to desensitization also in heart transplantation.Here, we discuss the candidates and recipients’ management by using most common standard of care and novel therapeutics, desensitization endpoints, and strategies for future studies

Olfaction Recovery following Dupilumab Is Independent of Nasal Polyp Reduction in CRSwNP

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic type 2 inflammatory disease characterized by olfactory impairment (OI) as one of the most troublesome symptoms. Currently, biologics represent a new option in the treatment of uncontrolled type 2 CRSwNP. This is a retrospective real-life observational study involving adult patients affected by severe uncontrolled CRSwNP. At baseline, and 3 and 6 months after Dupilumab add on to intranasal steroids (INS), patients underwent the 22-item Sinonasal Outcome Test (SNOT-22), nasal endoscopy, Visual Analogue Scale (VAS) scale for OI, and Sniffin Sticks-16 items identification test (SS-I). We observed improvement in all clinical outcomes with a significant correlation between VAS-SS-I/SNOT22, whereas we did not find a correlation between Nasal Polyp Score (NPS) and SS-I or VAS. Interestingly, patients reported a higher degree of improvement of OI on the VAS than on the SS-I. These data demonstrate that the patients were not aware about the degree of their OI and the perception of general improvement in their health-related quality of life (HRQoL) may have influenced the VAS score. Moreover, we observed a lack of correlation between NPS and SS-I or VAS, suggesting that OI did not depend on the polyps&rsquo; volume and may be due mainly to the resolution of inflammation. So, the physiopathological mechanisms underlying OI in CRSwNP and its recovery after Dupilumab might be unrelated to the volume of the polyps and might depend mainly on the anti-inflammatory effects. Future studies including biomarkers may be useful to clarify this aspect

Olfaction Recovery following Dupilumab Is Independent of Nasal Polyp Reduction in CRSwNP

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic type 2 inflammatory disease characterized by olfactory impairment (0I) as one of the most troublesome symptoms. Currently, biologics represent a new option in the treatment of uncontrolled type 2 CRSwNP. This is a retrospective real-life observational study involving adult patients affected by severe uncontrolled CRSwNP. At baseline, and 3 and 6 months after Dupilumab add on to intranasal steroids (INS), patients underwent the 22-item Sinonasal Outcome Test (SNOT-22), nasal endoscopy, Visual Analogue Scale (VAS) scale for OI, and Sniffin Sticks-16 items identification test (55-I). We observed improvement in all clinical outcomes with a significant correlation between VAS-SS-I/SNOT22, whereas we did not find a correlation between Nasal Polyp Score (NPS) and SS-I or VAS. Interestingly, patients reported a higher degree of improvement of CH on the VAS than on the SS-I. These data demonstrate that the patients were not aware about the degree of their CH and the perception of general improvement in their health-related quality of life (HRQoL) may have influenced the VAS score. Moreover, we observed a lack of correlation between NPS and SS-I or VAS, suggesting that OI did not depend on the polyps' volume and may be due mainly to the resolution of inflammation. So, the physiopathological mechanisms underlying OI in CRSwNP and its recovery after Dupilumab might be unrelated to the volume of the polyps and might depend mainly on the anti-inflammatory effects. Future studies including biomarkers may be useful to clarify this aspect

Clinical Markers of Need for Surgery in Orbital Complication of Acute Rhinosinusitis in Children: Overview and Systematic Review

Background: Although they can occur at all ages, orbital (OC) and periorbital cellulitis (POC) prevail in the pediatric population. Acute rhinosinusitis (ARS) is the most frequent predisposing factor of OC. Recent literature has suggested a medical management approach for OC and POC, with surgery reserved only for more severe cases. However, there is still a lack of consensus on the clinical markers of a need for surgery. The aim of this systematic review was to identify clinical markers of a need for surgery in children with OC. Our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1289 articles finally screened. This resulted in 31 full texts that were included in a qualitative analysis. The results of this review suggest that in children aged over 9 years, large subperiosteal orbital abscesses (SPOAs), impaired vision, ophthalmoplegia, proptosis, elevated C-reactive protein (CRP) and absolute neutrophil counts (ANC), hemodynamic compromise, no clinical improvement after 48/72 h of antibiotic therapy, and a Chandler III score or higher are clinical markers of the need for surgery. However, most of the studies are observational and retrospective, and further studies are needed to identify reliable and repeatable clinical markers of the need for surgery

Clinical Markers of Need for Surgery in Orbital Complication of Acute Rhinosinusitis in Children: Overview and Systematic Review

Background: Although they can occur at all ages, orbital (OC) and periorbital cellulitis (POC) prevail in the pediatric population. Acute rhinosinusitis (ARS) is the most frequent predisposing factor of OC. Recent literature has suggested a medical management approach for OC and POC, with surgery reserved only for more severe cases. However, there is still a lack of consensus on the clinical markers of a need for surgery. The aim of this systematic review was to identify clinical markers of a need for surgery in children with OC. Our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1289 articles finally screened. This resulted in 31 full texts that were included in a qualitative analysis. The results of this review suggest that in children aged over 9 years, large subperiosteal orbital abscesses (SPOAs), impaired vision, ophthalmoplegia, proptosis, elevated C-reactive protein (CRP) and absolute neutrophil counts (ANC), hemodynamic compromise, no clinical improvement after 48/72 h of antibiotic therapy, and a Chandler III score or higher are clinical markers of the need for surgery. However, most of the studies are observational and retrospective, and further studies are needed to identify reliable and repeatable clinical markers of the need for surgery