Oral microbiota in obstructive sleep apnea patients: a systematic review.

PURPOSE: Evidence suggests that patients with obstructive sleep apnea (OSA) are at increased risk of suffering from periodontitis, a chronic inflammatory disease of the tooth-supporting tissues associated with a dysbiotic oral microbiota. This systematic review aims to explore the current literature about the composition of the oral microbiota in patients with OSA compared to those without OSA. METHODS: Medline, Embase, and Cochrane Library were searched in May 2022 to identify original articles investigating the oral microbiota composition and/or oral microbiome (any microbiological technique) of patients with OSA (adults or children) vs. controls. Case report, reviews, and animal studies were excluded. RESULTS: Of over 279 articles initially identified, 8 were selected, of which 3 dealt with pediatric patients. Overall, 344 patients with OSA and 131 controls were included. Five studies used salivary samples, 2 oral mucosal swabs, and 1 subgingival plaque sample. With different methods to characterize oral microbiota, 6/8 studies observed significant differences between patients with OSA patients and controls in the composition and relative abundance of several bacteria species/genera linked to periodontitis. CONCLUSION: Within the limitations of the available literature, the present systematic review indicates that OSA and related conditions (e.g., mouth breathing) are associated with different oral microbiota compositions, which may underlie the association between OSA and periodontitis.

KRAS: A Druggable Target in Colon Cancer Patients.

Mutations in KRAS are among the most frequent aberrations in cancer, including colon cancer. KRAS direct targeting is daunting due to KRAS protein resistance to small molecule inhibition. Moreover, its elevated affinity to cellular guanosine triphosphate (GTP) has made the design of specific drugs challenging. Indeed, KRAS was considered 'undruggable'. KRASG12C is the most commonly mutated variant of KRAS in non-small cell lung cancer. Currently, the achievements obtained with covalent inhibitors of this variant have given the possibility to assess the best therapeutic approach to KRAS-driven tumors. Mutation-related biochemical assets and the tissue of origin are expected to influence responses to treatment. Further attempts to obtain mutant-specific KRAS (KRASG12C) switch-II covalent inhibitors are ongoing and the results are promising. Drugs targeted to block KRAS effector pathways could be combined with direct KRAS inhibitors, immunotherapy or T cell-targeting approaches in KRAS-mutant tumors. The development of valuable combination regimens will be essential against potential mechanisms of resistance that may arise during treatment.

Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes.

The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.

Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers.

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed E⇔M states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

Prognostic and Predictive Cross-Roads of Microsatellite Instability and Immune Response to Colon Cancer.

Understanding molecular features of colon cancer has shed light on its pathogenesis and progression. Over time, some of these features acquired clinical dignity and were incorporated in decision making. Namely, microsatellite instability (MSI) due to mismatch repair of defects, which primarily was adopted for the diagnosis of Lynch syndrome, became recognized as the biomarker of a different disease type, showing a less aggressive behavior. MSI tumors harbor high amounts of tumor infiltrating lymphocytes (TILs) due to their peculiar load in neoantigens. However, microsatellite stable colon cancer may also show high amounts of TILs, and this feature is as well associated with better outcomes. High TIL loads are in general associated with a favorable prognosis, especially in stage II colon cancer, and therein identifies a patient subset with the lowest probability of relapse. With respect to post-surgical adjuvant treatment, particularly in stage III, TILs predictive ability seems to weaken along with the progression of the disease, being less evident in high risk patients. Moving from cohort studies to the analysis of a series from clinical trials contributed to increase the robustness of TILs as a biomarker. The employment of high TIL densities as an indicator of good prognosis in early-stage colon cancers is strongly advisable, while in late-stage colon cancers the employment as an indicator of good responsiveness to post-surgical therapy requires refinement. It remains to be clarified whether TILs could help in identifying those patients with node-positive cancers to whom adjuvant treatment could be spared, at least in low-risk groups as defined by the TNM staging system.

Eosinophilic esophagitis in children: doubts and future perspectives.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies. MAIN BODY: Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells. CONCLUSIONS: Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

Role of the intestinal microbiome in colorectal cancer surgery outcomes.

OBJECTIVES: Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery. METHODS: A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were selected. Patients with any stage of colorectal cancer were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles. RESULTS: Overall, 8 studies (7 cohort studies and 1 case-control) published between 2014 and 2018 were included. Only one study focused on short-term surgical outcomes, showing that anastomotic leakage is associated with low microbial diversity and abundance of Lachnospiraceae and Bacteroidaceae families in the non-cancerous resection lines of the stapled anastomoses of colorectal cancer patients. The other 7 studies focused on long-term oncological outcomes, including survival and cancer recurrence. The majority of the studies (5/8) found that a higher level of Fusobacterium nucleatum adherent to the tumor tissue is associated with worse oncological outcomes, in particular, increased cancer-specific mortality, decreased median and overall survival, disease-free and cancer-specific survival rates. Also a high abundance of Bacteroides fragilis was found to be linked to worse outcomes, whereas the relative abundance of the Prevotella-co-abundance group (CAG), the Bacteroides CAG, and the pathogen CAG as well as Faecalibacterium prausnitzii appeared to be associated with better survival. CONCLUSIONS: Based on the limited available evidence, microbiome composition may be associated with colorectal cancer surgery outcomes. Further studies are needed to elucidate the role of the intestinal microbiome as a prognostic factor in colorectal cancer surgery and its possible clinical implications.

Transverse flap duodenoplasty (TFD): a new technique in autologous bowel reconstructive surgery.

BACKGROUND: Bowel dilatation is a common adaptive mechanism after intestinal resection. The symptomatic dilated dysmotile duodenum is difficult to manage, since conventional bowel tailoring and lengthening techniques are potentially hazardous because of the anatomy of the duodenal blood supply, the proximity to the pancreas, and the risk of injury to the common bile duct. METHODS: A 2-month-old child with short bowel and a symptomatic massively dilated duodenum was treated with a Transverse Flap Duodenoplasty (TFD). The duodenum was opened longitudinally along its antimesenteric border preserving an intact strip of tissue overlying the pancreatic head. Three full thickness vascularized pedicle flaps were cut on both the anterior and posterior walls and were spirally rotated and sutured to create a uniform propulsive duodenum without diverticulae. RESULTS: Healing was complicated by a soft anastomotic duodeno-ileal stenosis that resolved after three elective balloon dilatations. Oral feeding established rapidly. The child is growing, does not vomit, and passes 1-2 semiformed motions daily. CONCLUSIONS: TFD is a safe and versatile technique that preserves all duodenal absorptive mucosa and that removes any risk to the pancreas, bile duct, and ampulla of Vater. Our experience, although limited, has been encouraging and leads us to suggest TFD for the management of the difficult symptomatic dysmotile dilated duodenum.

The role of endoscopic ultrasound in children with Pancreatobiliary and gastrointestinal disorders: a single center series and review of the literature.

BACKGROUND: The role of endoscopic ultrasound (EUS) in the management of pancreatobiliary and digestive diseases is well established in adults, but it remains limited in children. The aim of this study was to evaluate the feasibility, safety, and clinical impact of EUS use in children. METHODS: This is a retrospective analysis of a prospectively acquired database of consecutive pediatric (< 18 years) patients presenting an indication for EUS for pancreatobiliary and gastrointestinal disorders. RESULTS: Between January 2010 and January 2016, 47 procedures were performed in 40 children (mean age of 15.1 ± 4.7 years; range 3-18). The majority of EUS (n = 32; 68.1%) were performed for pancreatobiliary and upper gastrointestinal pathologies, including suspected common bile duct stones (CBDs), acute biliary pancreatitis, recurrent/chronic pancreatitis, cystic pancreatic mass, recurrent hypoglycemia, duodenal polyp, gastric submucosal lesion, and perigastric abscess. In only 2 out of 18 children with suspected CBDs or acute biliary pancreatitis, EUS confirmed CBDs. EUS-guided fine needle aspiration was performed in 3 (6.4%) patients. Fifteen (31.9%) procedures were performed for lower gastrointestinal tract disorders, including suspected anal Crohn's disease, fecal incontinence, and encopresis. Overall, EUS had a significant impact on the subsequent clinical management in 87.2% of patients. CONCLUSION: The present findings were consistent with results observed in the current relevant literature and support EUS as a safe and feasible diagnostic and therapeutic tool, which yields a significant clinical impact in children with pancreatobiliary and gastrointestinal disorders.

Management of duodenal-jejunal polyps in children with peutz-jeghers syndrome with single-balloon enteroscopy.

OBJECTIVES: Children with Peutz-Jeghers syndrome (PJS) have increased risk of polyp-related complications and emergency laparotomies. The aim of the present study was to assess the efficacy and the safety of endoscopic therapy of small bowel polyps using single-balloon enteroscopy (SBE) in children affected by PJS. METHODS: Between January 2010 and December 2011, prospectively consecutive PJS children with polyps >15 mm or polyps actively bleeding previously identified using video capsule endoscopy and magnetic resonance imaging underwent therapeutic SBE. The main outcome measurements were the feasibility, the technical performance, and the safety. RESULTS: A total of 10 children (6 boys; median age 13.7 years, range 5.6-15.6) underwent 23 SBE procedures. Four patients had a history of abdominal surgery. A total of 53 polyps were removed, and 23 of them were >15 mm. The majority of polyps were found in jejunum (85%). The mean insertion depths for antegrade and retrograde approach were 200 ± 80 and 100 ± 50 cm beyond the ileal valve, respectively. The mean procedure time was 75 ± 25 minutes. Mild abdominal pain was reported after 3 procedures. In 1 patient a postpolypectomy perforation occurred. CONCLUSIONS: In conclusion, SBE is an effective endoscopic tool for treating small bowel polyps in children with PJS, and well-timed polypectomy may optimize patients' care, preventing polyp-related complications and emergency laparotomy. Further larger multicenter studies are warranted to accurately determine the safety of therapeutic SBE in children.

NOD2 and Crohn's Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a multifactorial pathogenesis involving environmental and genetic factors. Since the late 20th century, the discovery of the first susceptibility gene (NOD2, previously referred to as CARD15) for CD has paved the way for further investigations into the correlations between clinical features and genetics, and its potential impact on clinical practice has fueled the research in the last 2 decades. Recent therapeutic advancements involving novel biologic drugs and small molecules have shifted inflammatory bowel disease management from a disease-centered to a patient-centric approach. To date, the role of NOD2 has not been fully understood yet. Recent data suggest that its clinical impact may be greater than currently recognized. This review overviews the most common NOD2 variants' role in real-life clinical practice. These genetic variants increase the risk of developing the disease and can aid in tailoring diagnosis and treatment. They are associated with the stricturing phenotype and ileal involvement and increase the risk of steroid refractoriness. In the meantime, limited and inconclusive evidence exists regarding their predictive role in response to azathioprine, biologic drugs, and small molecules. Eventually, their role in increasing the risk for surgery is evident, especially in those with the L1007fs variant. If further trials will support the initial evidence reported so far, NOD2 genetic variants will emerge as possible candidates for developing precision medicine in CD.

NOD2 is the most relevant susceptibility gene for Crohn's disease. It is associated with the tructuring disease phenotype, ileal involvement, and an increased risk for surgery. NOD2 genetic variants emerge as promising candidates for developing precision medicine in Crohn's disease.

Notch-Jagged1 signaling and response to bevacizumab therapy in advanced colorectal cancer: A glance to radiomics or back to physiopathology?

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate.

BACKGROUND: In the eradication of H. pylori infection, even today, the main international guidelines recommend the triple therapy as first-line regimen, although its effectiveness is clearly decreasing. As second-line treatment, the bismuth-containing quadruple therapy is the most used regimen, although several other therapies are studied. The Italian guidelines recommend, alternatively, sequential therapy or triple therapy as first-line treatment and levofloxacin-containing triple therapy as second-line regimen. We wanted to assess the overall eradication rate of Helicobacter pylori infection in two therapeutic rounds following the Italian guidelines in clinical practice. MATERIALS AND METHODS: We treated 231 consecutive Helicobacter pylori-positive patients by sequential therapy and we verified the eradication 8-10 weeks after treatment by stool antigen test. Patients positive for stool antigen test received levofloxacin-containing triple therapy, as second-line therapy, according to Italian Guidelines and they were again submitted to the fecal test 8-10 weeks after the end of treatment. RESULTS: In the first-line regimen, we obtained an eradication rate of 92.6%, in the second-line of 75.0% and as cumulative result we achieved a 97.8% of eradication, in per-protocol analysis. CONCLUSIONS: Sequential therapy as first-line and levofloxacin-containing triple therapy as second-line represent a good combination to eradicate Helicobacter pylori infection in only two rounds.

Helicobacter pylori infection in clinical practice: probiotics and a combination of probiotics + lactoferrin improve compliance, but not eradication, in sequential therapy.

BACKGROUND: Sequential therapy (ST) seems to offer higher success rates than triple therapy (TT) in the eradication of Helicobacter pylori (H. pylori) infection. However, from the standpoint of therapeutic compliance, there is no difference between the two treatments. Adjuvant treatment (especially with probiotics (PB) and lactoferrin (LF)) has often improved compliance and eradication rates in patients subjected to TT, while ST had never been used in association with adjuvants. METHODS: Over a period of 2 years, we randomized and divided 227 consecutive adult patients with H. pylori infection into three groups. The patients were given ST with the addition of adjuvants, as follows: group A (ST + placebo), group B (ST + LF + PB), and group C (ST + PB). Our goal was to assess therapeutic compliance, so we prepared a questionnaire to help determine the severity of the side effects. We also determined the eradication rates for the groups. RESULTS: Patients with ST + placebo had the worst compliance as compared with the other two groups in terms of the absence of symptoms (p < .001 between B and A; p = .001 between C and A) and the presence of intolerable symptoms (p = .016 between B and A; p = .046 between C and A). The differences between the values for the treated groups and those for the placebo group were statistically significant. On the other hand, there was no statistically significant difference in compliance between groups B and C. The eradication rate was similar for the three groups. CONCLUSIONS: Probiotics associated with ST provide optimum therapeutic compliance compared with the placebo and, despite the need to take a larger number of tablets, they should be taken into consideration as an adjuvant to therapy for H. pylori infection. The addition of LF to the PB did not bring about any further improvements in compliance. As compared with the placebo, the eradication rate of ST did not improve by adding LF + PB or by using PB alone.

Antimicrobial Challenge in Acute Care Surgery.

The burden of infections in acute care surgery (ACS) is huge. Surgical emergencies alone account for three million admissions per year in the United States (US) with estimated financial costs of USD 28 billion per year. Acute care facilities and ACS patients represent boost sanctuaries for the emergence, development and transmission of infections and multi-resistant organisms. According to the World Health Organization, healthcare-associated infections affected around 4 million cases in Europe and 1.7 million in the US alone in 2011 with 39,000 and 99,000 directly attributable deaths, respectively. In this scenario, antimicrobial resistance arose as a public-health emergency that worsens patients' morbidity and mortality and increases healthcare costs. The optimal patient care requires the application of comprehensive evidence-based policies and strategies aiming at minimizing the impact of healthcare associated infections and antimicrobial resistance, while optimizing the treatment of intra-abdominal infections. The present review provides a snapshot of two hot topics, such as antimicrobial resistance and systemic inflammatory response, and three milestones of infection management, such as source control, infection prevention, and control and antimicrobial stewardship.

Robotic multiquadrant colorectal procedures: A single-center experience and a systematic review of the literature.

Purpose: Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods: At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results: In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04-0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42-190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7-59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions: Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016.

Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine.

The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p < 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p < 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients.

Impact of COVID-19 pandemic on pediatric endoscopy: A multicenter study on behalf of the SIGENP Endoscopy Working Group.

BACKGROUND: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. METHODS: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. RESULTS: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. CONCLUSIONS: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.