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.

Endotyping of Cholesteatoma: Which Molecular Biomarkers? A Systematic Review.

BACKGROUND: So far, no medical treatment is available for cholesteatoma (C) and the only effective therapy is complete surgical removal, but recurrence is common even after surgical treatment. While C is classically divided into two clinical phenotypes, congenital and acquired, only a few studies have focused on its potential biomarkers. This study aims to revise the literature to identify which biomarkers can define the endotype of C. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process to identify published experimental articles about molecular biomarkers in C. RESULTS: KGF and its receptor, MMP-9, KRT-1, KRT-10, and MIF might be considered biomarkers of recurrence, whereas Ki-67, TLR-4, RANKL, IL17, MMP-2, MMP-9, IL6, TNF-α, should be considered more specifically as biomarkers of bony erosion. CONCLUSIONS: These results are interesting especially from a prognostic point of view, nevertheless more studies are needed to search new biomarkers of C that could completely change not only the therapeutic standards of the disease, but also the clinical history of C itself in the era of precision medicine.

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' 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.

Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea.

BACKGROUND: 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.

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.