Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Preoperative chemoradiotherapy affects postoperative outcomes and functional results in patients treated with transanal endoscopic microsurgery for rectal neoplasms.

BACKGROUND: The aim of this study was to quantify the incidence of short-term postoperative complications and functional disorders at 1 year from transanal endoscopic microsurgery (TEM) for rectal neoplasms, to compare patients treated with TEM alone and with TEM after preoperative chemoradiotherapy (CRT) and to analyse factors influencing postoperative morbidity and functional outcomes. METHODS: A retrospective study was conducted on all patients treated with TEM for rectal neoplasms at our institution in January 2000-December 2017. Data from a prospectively maintained database were retrospectively analysed. Patients were divided into two groups: adenoma or early rectal cancer (no CRT group) and locally advanced extraperitoneal rectal cancer with major or complete clinical response after preoperative CRT (CRT group). Short-term postoperative mortality and morbidity and the functional results at 1 year were recorded. The two groups were compared, and a statistical analysis of factors influencing postoperative morbidity and functional outcomes was performed. Functional outcome was also evaluated with the low anterior resection syndrome (LARS) score (0-20 no LARS, 21-29 minor LARS and 30-42 major LARS). RESULTS: One hundred and thirteen patients (71 males, 42 females, median age 64 years [range 41-80 years]) were included in the study (46 in the CRT group). The overall postoperative complication rate was 23.0%, lower in the noCRT group (p < 0.001), but only 2.7% were grade ≥ 3. The most frequent complication was suture dehiscence (17.6%), which occurred less frequently in the noCRT group (p < 0.001). At 1 year from TEM, the most frequent symptoms was urgency (11.9%, without significant differences between the CRT group and the noCRT group); the noCRT group experienced a lower rate of soiling than the CRT group (0% vs. 7.7%; p: 0.027). The incidence of LARS was evaluated in 47 patients from May 2012 on and was 21.3% occurring less frequently in the noCRT group (10% vs. 41.2%; p: 0.012). Only 6.4% of the patients evaluated experienced major LARS. In multivariate analysis, preoperative CRT significantly worsened postoperative morbidity and functional outcomes. CONCLUSIONS: TEM is a safe procedure associated with only low risk of severe postoperative complications and major LARS. Preoperative CRT seems to increase the rate of postoperative morbidity after TEM and led to worse functional outcomes at 1 year after surgery.

Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): ulcerative colitis.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position Statement of Italian colorectal surgeons to address the surgical aspects of ulcerative colitis management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of ulcerative colitis. The committee was able to identify some points of major disagreement and suggested strategies to improve the quality of available data and acceptance of guidelines.

Correction to: Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): ulcerative colitis.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication.

Correction to: Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication. The complete correct affiliation should read as follows.

Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position Statement of Italian colorectal surgeons to address the surgical aspects of inflammatory bowel disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the general principles of surgical treatment of inflammatory bowel disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study.

BACKGROUND: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. METHODS: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. RESULTS: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25-10.16 and OR 6.43 95% CI 3.33-12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33-14.74 and OR 3.14 95% CI 1.68-5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78-7.62 and OR 2.09 95% CI 1.10-3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. CONCLUSIONS: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy.

Viral reactivations and associated outcomes in the context of immune reconstitution after pediatric hematopoietic cell transplantation.

BACKGROUND: Viral reactivations (VRs) after hematopoietic cell transplantation (HCT) contribute to significant morbidity and mortality. Timely immune reconstitution (IR) is suggested to prevent VR. OBJECTIVES: We studied the relation between IR (as a continuous predictor over time) and VR (as a time-varying predictor) and the relation between VR and other clinical outcomes. METHODS: In this retrospective analysis all patients receiving a first HCT between January 2004 and September 2014 were included. IR (CD3/CD4/CD8 T, natural killer, and B cells) was measured biweekly until 12 weeks and monthly thereafter. Main outcomes of interest were VR of adenovirus, EBV, human herpesvirus 6 (HHV6), cytomegalovirus (CMV), and BK virus screened weekly. Clinical outcomes included overall survival (OS), event-free-survival, nonrelapse mortality (NRM), and graft-versus-host disease. Cox proportional hazard and Fine and Gray competing risk models were used. RESULTS: Two hundred seventy-three patients (age, 0.1-22.7 years; median follow-up, 58 months) were included. Delayed CD4 reconstitution predicted reactivation of adenovirus (hazard ratio [HR], 0.995; P = .022), EBV (HR, 0.994; P = .029), and HHV6 (HR, 0.991; P = .012) but not CMV (P = .31) and BK virus (P = .27). Duration of adenovirus reactivation was shorter with timely CD4 reconstitution, which was defined as 50 × 106 cells/L or greater within 100 days. Adenovirus reactivation predicted lower OS (HR, 2.17; P = .0039) and higher NRM (HR, 2.96; P = .0008). Concomitant CD4 reconstitution abolished this negative effect of adenovirus reactivation (OS, P = .67; NRM, P = .64). EBV and HHV6 reactivations were predictors for the occurrence of graft-versus-host disease, whereas CMV and BK virus reactivation did not predict clinical outcomes. CONCLUSION: These results stress the importance of timely CD4 reconstitution. Strategies to improve CD4 reconstitution can improve HCT outcomes, including survival, and reduce the need for toxic antiviral therapies.

Rectal sparing approach after preoperative radio- and/or chemotherapy (RESARCH) in patients with rectal cancer: a multicentre observational study.

BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. CONCLUSION: This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).

T1 colon cancer in the era of screening: risk factors and treatment.

BACKGROUND: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit. METHODS: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases. RESULTS: Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN. CONCLUSIONS: Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.

Practice parameters for early colon cancer management: Italian Society of Colorectal Surgery (Società Italiana di Chirurgia Colo-Rettale; SICCR) guidelines.

Early colon cancer (ECC) has been defined as a carcinoma with invasion limited to the submucosa regardless of lymph node status and according to the Royal College of Pathologists as TNM stage T1 NX M0. As the potential risk of lymph node metastasis ranges from 6 to 17% and the preoperative assessment of lymph node metastasis is not reliable, the management of ECC is still controversial, varying from endoscopic to radical resection. A meeting on recent advances on the management of colorectal polyps endorsed by the Italian Society of Colorectal Surgery (SICCR) took place in April 2014, in Genoa (Italy). Based on this material the SICCR decided to issue guidelines updating the evidence and to write a position statement paper in order to define the diagnostic and therapeutic strategy for ECC treatment in context of the Italian healthcare system.

Practice parameters for early rectal cancer management: Italian Society of Colorectal Surgery (Società Italiana di Chirurgia Colo-Rettale; SICCR) guidelines.

The introduction of new technologies for diagnosis and screening programs led to an increasing rate of early detection of colorectal cancer. This, associated with the evolution of endoscopic techniques of local excision, led to the assessment of new strategies to reduce morbidity related to treatment, especially for early rectal cancer (ERC). Nevertheless, the definition of ERC and its staging and treatment algorithm are still under debate. The Italian Society of Colorectal Surgery developed practice guidelines to provide recommendations on the diagnosis, staging and treatment of ERC. A systematic review on the topic was performed by a multidisciplinary group of experts selected based on their clinical and scientific expertise in endoscopy, endoscopic ultrasound, magnetic resonance and surgery, with the aid of an external international audit.

Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer.

BACKGROUND: The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery. METHODS: Data for patients who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from June 1992 to June 2009 were reviewed. The primary outcomes measured were the number of lymph nodes retrieved, their status, and patient survival. RESULTS: In total, 345 patients underwent neoadjuvant chemoradiotherapy followed by surgery, and 95 patients had surgery alone. Neoadjuvant chemoradiotherapy decreased both the median (range) number of lymph nodes retrieved (7 (1-33) versus 12.5 (0-44) respectively; P < 0.001) and the number of positive lymph nodes (0 (0-11) versus 0 (0-16); P = 0.001). After neoadjuvant chemoradiotherapy, the number of retrieved lymph nodes was inversely correlated with tumour regression, and with the interval between treatment and surgery. The 5-year overall and disease-free survival rates were 86.5 and 79.1 per cent respectively. After neoadjuvant therapy, lymph node status was found to be an independent predictor of survival, whereas the number of retrieved lymph nodes did not represent a prognostic factor for either overall or disease-free survival. CONCLUSION: Low lymph node count after neoadjuvant chemoradiotherapy for rectal cancer does not signify an inadequate resection or understaging, but represents an increased sensitivity to the treatment.

Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer: short-term morbidity and functional outcome.

BACKGROUND: Transanal endoscopic microsurgery (TEM) after radiochemotherapy (RCT) has been reported in selected cases of locally advanced rectal cancer as an alternative to traditional radical resection with total mesorectal excision with a curative intent or as diagnostic tool to confirm a pathological complete response of the primary tumor. No study has evaluated functional outcome after TEM in preoperatively irradiated patients. METHODS: This study was designed to evaluate short-term morbidity (according to Clavien's classifications) and establish (by a questionnaire) continence and evacuative function after RCT and TEM, at 1 year from surgery, analyzing the impact of RCT on postoperative outcomes. Patients with locally advanced rectal cancer treated by RCT and TEM (group 1) or with early T1 or adenomas treated only by TEM (group 2) entered this cohort comparative study. RESULTS: Twenty-two patients entered the study as group 1 and 25 as group 2. No postoperative mortality occurred. The morbidity rate was 36.4 % in group 1 vs. 16 % in group 2 (p = 0.114). The rate of suture dehiscence was 22.7 % in group 1 vs. 4 % in group 2 (p = 0.068). No grade III complications, reoperation, or hospital readmission within 30 days was recorded in either group. One year after surgery, continence and evacuative scores in group 1 were 1.05 ± 1.25 and 24.72 ± 2.79, respectively, which were similar to group 2 (p = 0.081 and 0.288, respectively). CONCLUSIONS: TEM after RCT in selected rectal cancer patients has an acceptable morbidity and functional results at 1 year from surgery. Preoperative irradiation could increase postoperative short-term morbidity, but it does not seem to influence evacuative or sphincter function after 1 year from surgery.

LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals.

AIM: Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients. PATIENTS AND METHODS: We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated with the viral envelope protein gp120 or lipopolysaccharide (LPS). RESULTS: The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. In multivariate analysis, the association was still significant only for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant. CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.

Advance in diagnosis and treatment of small bowel tumors: a single-center report.

BACKGROUND: The past decade has seen significant advances in the evaluation of the small bowel, long considered as the "black box" in gastroenterology. The development of several endoscopic techniques, including capsule endoscopy (CE) and double (DBE)- and single (SBE)-balloon enteroscopy, has improved the evaluation of this part of the gut and led to reach a more precise preoperative diagnosis of small-bowel tumors. These rare tumors were previously diagnosed only after laparotomy, although laparoscopic advanced surgery can be used for minimally invasive therapeutic approach in these patients. This study was designed to evaluate the diagnostic and therapeutic impact of endoscopic procedures on small-bowel tumors. METHODS: During October 2010, 148 SBE procedures were performed; in 14 patients (7 males and 7 females, mean age 58.8 years; range 37-82 years) who suffered from obscure gastrointestinal bleeding, with previous negative upper and lower GI endoscopy, a diagnosis of small-bowel tumor was suspected according to CT scan (7 cases) and/or CE (11 patients). Then, an enteroscopy was performed. RESULTS: Multiple biopsies were taken in 9 cases; endoscopic tattoos were performed in 11 cases. After endoscopic procedures, histological examination showed melanoma in one case, adenocarcinoma in seven, and adenoma in one case. In 11 of 14 patients, a laparoscopic partial resection of small bowel involved was possible due to endoscopic tattoos. In one patient, the involvement of colic segment precluded a laparoscopic resection. In two patients, the laparoscopic resection was not possible for technical problems. Histological findings on resected specimens were indicative for melanoma in one case, gastrointestinal stromal tumor (GIST) in four cases, gastrointestinal autonomic nerve tumor (GANT) in one case, adenoma in one, and adenocarcinoma in seven cases. CONCLUSIONS: New development of different endoscopic approaches to the small bowel has led to reach an earlier diagnosis of small-bowel tumors and a preoperative diagnosis with consequent minimally invasive surgical approach.

Improved clinical outcomes in patients with juvenile idiopathic arthritis associated uveitis in the last decade.

PURPOSE: The purpose of the study was to analyse the development of ocular complications and visual prognosis in juvenile idiopathic arthritis associated uveitis (JIA-uveitis) compared to the previous decade in the light of new treatment guidelines. METHODS: In this retrospective cohort, 143 patients with JIA-uveitis were stratified into two cohorts based on the year of diagnosis of uveitis, <2010 (n = 61) and ≥2010 (n = 82). Development of ocular complications and visual outcomes were analysed by univariate and multivariate methods. Treatment with systemic corticosteroids and immunomodifying medication (IMT) were documented. RESULTS: In total, 109 and 133 affected eyes, respectively, for cohort 1 (<2010) and cohort 2 (≥2010) were included for analysis. In the multivariate analysis with correction for paired eyes, patients in cohort 1 were at higher risk for cataract surgery (p = 0.03) and secondary glaucoma (p = 5.15 × 10-3 ). Also, the number of eyes that were legally blind and visually impaired at 5 years of follow-up was significantly higher in cohort 1 (7% versus 2% and 8% versus 0%, p = 0.01 respectively). The number of patients that started IMT was significantly higher in cohort 2 (57% versus 98%, p = 2.17 × 10-6 ). In cohort 2, both methotrexate and anti-TNF-α therapy were prescribed earlier in the disease course (1.41 versus 0.05 years, p = 8.31 × 10-6 and 6.07 versus 1.84 years, p = 5.14 × 10-5 respectively). CONCLUSIONS: The prognosis of JIA-uveitis has improved during the last decade. There is a reduction in the number of cataract surgeries and secondary glaucoma and fewer patients lose their vision parallel with earlier access to tertiary care and earlier introduction of IMT.

Clofarabine-fludarabine-busulfan in HCT for pediatric leukemia: an effective, low toxicity, TBI-free conditioning regimen.

We prospectively studied clofarabine-fludarabine-busulfan (CloFluBu)-conditioning in allogeneic hematopoietic cell therapy (HCT) for lymphoid and myeloid malignancies and hypothesized that CloFluBu provides a less toxic alternative to conventional conditioning regimens, with adequate antileukemic activity. All patients receiving their first HCT, from 2011-2019, were included and received CloFluBu. The primary endpoint was event-free survival (EFS). Secondary endpoints were overall survival (OS), graft-versus-host disease (GvHD)-relapse-free survival (GRFS), treatment-related mortality (TRM), cumulative incidence of relapse (CIR), acute and chronic GvHD (aGvHD and cGvHD), and veno-occlusive disease (VOD). Cox proportional hazard and Fine and Gray competing-risk models were used for data analysis. One hundred fifty-five children were included: 60 acute lymphoid leukemia (ALL), 69 acute myeloid leukemia (AML), and 26 other malignancies (mostly MDS-EB). The median age was 9.7 (0.5 to 18.6) years. Estimated 2-year EFS was 72.0% ± 6.0 in ALL patients, and 62.4% ± 6.0 in AML patients. TRM in the whole cohort was 11.0% ± 2.6, incidence of aGvHD 3 to 4 at 6 months was 12.3% ± 2.7, extensive cGvHD at 2 years was 6.4% ± 2.1. Minimal residual disease-positivity prior to HCT was associated with higher CIR, both in ALL and AML. CloFluBu showed limited toxicity and encouraging EFS. CloFluBu is a potentially less toxic alternative to conventional conditioning regimens. Randomized prospective studies are needed.

The diagnostic accuracy and prognostic value of OCT for the evaluation of the visual function in children with a brain tumour: A systematic review.

PURPOSE: To systematically review the evidence on the diagnostic accuracy and prognostic value of retinal optical coherence tomography (OCT) to detect visual acuity (VA) or visual field (VF) loss in children with a brain tumour. METHODS: PubMed, Embase and Cochrane Library databases were searched from inception to February 2021. We included studies evaluating retinal OCT and standard visual function parameters (VA and or VF) in children with a brain tumour. Two authors independently extracted data from each included study. They also assessed the methodological quality of the studies using the QUADAS-2 or QUIPS tool. The diagnostic accuracy of OCT was evaluated with receiver operating characteristic analysis, sensitivity, specificity, positive predictive value and negative predictive value. The prognostic value of OCT was evaluated with predictive measures (odds ratio). RESULTS: We included five diagnostic studies, with a total of 186 patients, all diagnosed with optic pathway glioma. No prognostic studies were eligible for inclusion. Included studies evaluated either retinal nerve fiber layer (RNFL) thickness or ganglion cell layer-inner plexiform layer (GCL-IPL) thickness. There was considerable heterogeneity between OCT devices, OCT protocols, visual function parameters and threshold values. Sensitivity and specificity for RNFL thickness measurement ranged from 60.0% to 100.0% and 76.6% to 100%, respectively. For GCL-IPL thickness measurement, area under the curve ranged from 0.91 to 0.98 for different diameters. CONCLUSION: The literature regarding the diagnostic accuracy and prognostic value of OCT parameters in children with a brain tumour is scarce. Due to heterogeneity and a considerable risk of bias of included studies, we cannot draw solid conclusions regarding the accuracy of retinal OCT. Future research should investigate the potential of OCT as diagnostic and prognostic tool for the evaluation of the visual function and detection of visual impairment in children with any type of brain tumour.

Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma.

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.