Non-treated Patients Research Articles

Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib

Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib

Sequential Study By RNA-Seq Shows a Reduction in Inflammation and a Cell Cycle Activation in T-Lymphocytes from Myelodysplastic Syndrome with Del(5q) after Lenalidomide Treatment in Patients Included in the “Sintra-REV” Clinical Trial

Introduction: Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. The clinical efficacy of lenalidomide in MDS patients has been extensively reviewed and although the mechanisms of action in del(5q) clone have been previously described, in vivo sequential studies of modulatory effect on T lymphocytes are lacking. Our study was conducted in patients included in the Sintra-REV Clinical Trial: Lenalidomide (Revlimid) phase III, multicenter, randomized, double-blind study versus placebo in patients with low-risk MDS (low and intermediate IPSS-1) with del(5q), with anemia (HB≤12gr/dl) and without transfusion needs. Aim: The aim of this study was to explore the effect of lenalidomide in T-lymphocytes in MDS patients with del(5q) and without transfusion dependence. Materials and Methods: Sequential study was carried out in 26 samples from 13 paired MDS patients with del (5q). Seven out 13 were treated with lenalidomide and achieved a major erythroid and cytogenetic response. Peripheral blood (PB) samples were collected before and one month after treatment in treated-patients and at the same time points for non-treated patients. CD3+ cells were collected from PB samples and total RNA was isolated. SureSelect Strand Specific RNA library (Agilent Technologies) was applied to study changes in RNA levels. Raw reads were aligned against the Human genome GRCh37 using the STAR aligner. Counts were assigned to Ensembl gene IDs through HTseq using its UNION version. Differential gene expression was determined with DESeq2, considering as statistically significant those genes with FDR < 0.05. Pathway over-representation analysis (ORA) was conducted in the Webgestalt suite. Results: 332 genes were differentially expressed in CD3+ lymphocytes one month after lenalidomide treatment in our cohort of patients; 199 of them were over-expressed after the administration of this drug (Fig 1a). Of note, none of them were observed in non-treated patients after one month. The ORA revealed significant differences in the gene expression profile of sixteen cytokines and enrichment of genes of the cell cycle pathway (35 genes). The most relevant up-regulated cytokines were: IL10, TNFSF10, IFNGand IL6. These data explain lenalidomide-induced activation of an antileukemic immune response and secretion of anti-inflammatory cytokines. Although lenalidomide has been reported to reduce the expression of IL6 secreted by myeloid cell derived from MDS clon, we have observed upregulation of this gene in T-lymphocytes. Moreover, our study showed a downregulation of MBP6 that may help to correct the anemia and also attenuate inflammation signaling in MDS patients with del(5q) (Fig 1b). In addition, the most represented up-regulated genes related to cell cycle pathway were: cyclines (CCNB1, CCNB2, CDK1), centromere genes (CENPE, CENPM, CENPU), kinesin family members (KIF18A, KIF23, KIF2C), BUB1 mitotic checkpoint genes (BUB1, BUB1B), and genes involved in cell division (CDC6, CDC7,CDC25A). It has been described that lenalidomide inhibits CDC25A selectively in the del(5q) clone resulting in G2/M arrest and apoptosis. By contrast, our study showed that this gene was upregulated in T-lymphocytes promoting cell cycle and proliferation of these cells (Fig 1b). Conclusions: The immunomodulatory properties of lenalidomide can be summarized in two: a) regulation of antileukemic and anti-inflammatory cytokines production, b) activation of cell cycle and proliferation in T cells. To our knowledge, this is the first report describing RNA expression profiles in PB CD3+ lymphocytes collected from lenalidomide-treated del(5q) patients, contributing to overall understanding of lenalidomide action. Disclosures Sanz: Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; LaHoffman Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Ltd.: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Diez-Campelo:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: Lenalidomide was administered in anemic but not transfusion-dependence patients with low-risk MDS and del(5q)

COVID-19 Impact on Lymphoma Patients' Clinical Outcomes - an Observational Cohort Study

COVID-19 Impact on Lymphoma Patients' Clinical Outcomes - an Observational Cohort Study

Ruxolitinib Treatment Is Associated with Increased Incidence of Infections and Higher Risk of HSV/Vzv Recurrence in Patients with Myeloproliferative Neoplasm (MPN) Related Myelofibrosis (MF)

Introduction: Ruxolitinib (RUX) is a JAK 1/2 inhibitor approved for the treatment of intermediate and high-risk primary or secondary MF. In addition to the intrinsic immune system modulation in MF patients, JAK inhibition exerts an immunosuppressive effect that may increase the risk of infections (Heine A et al., Blood, 2013). We aimed to investigate the association between treatment with RUX and infectious complications in a large monocentric cohort of MF patients. Methods: We performed a retrospective study including all patients diagnosed with primary, post-polycythemia vera or post-essential thrombocythemia MF in our MPN clinic between January 2011 and April 2020. Patients were considered RUX treated when exposed to treatment for at least two consecutive months. Clinical and biological characteristics at time of MF diagnosis and follow-up were collected from medical charts and electronic medical records. We used logistic regression models to identify specific infection subtypes associated with RUX treatment. Univariate and multivariate analysis assessing the impact of categorical and continuous variables on infectious events cumulative incidence were performed using Cox models. Results: 213 MF patients were included in the study. 114 (51.1%) patients were treated with RUX while 99 didn't receive RUX. Overall 102 patients exhibited a total of 231 infectious episodes. To search for factors associated with occurrence of infectious events, we evaluated the characteristics of MF, potential clinical and biological immune suppression factors (immunosuppressive treatment, prior non-MPN cancer, diabetes, hepatic/renal failure, neutropenia, lymphopenia, hypo-gammaglobulinemia, complement deficiency, prior history of infection), use of infection prophylaxis and RUX treatment using Cox models. In this cohort of MF patients, we found that RUX treatment (HR 5.91, 95%CI[3.48; 10.04], p<0.001) and a performance status > 2 (HR 4.91, 95%CI[2.62; 9.21], p<0.001) were independently associated with infectious complications (Figure A). Infections rates were 74.0% in RUX treated patients versus 28.3% in non-RUX patients. 41 (22.2%) and 16 (34.0%) infections were of grade 3-4, 61 (33.1%) and 19 (40.4%) required hospitalization, while 8 (4.3%) and 2 (4.2%) resulted in patients' death, in RUX treated and RUX naïve patients, respectively (all non-significantly different). Bacterial infections represented 48.0%, viral infections 16.0% and fungal infections 4.8% of the total infectious events. The most frequently infected sites were lungs/respiratory tract (28.1%) and skin/soft tissue (24.2%). RUX treatment was significantly associated with recurrence of HSV-1/2 or VZV (OR 7.57, 95%CI[1.01-57.30], p=0.050), and skin/soft tissue infections including the above herpetic recurrences (OR 3.33, 95%CI[1.13-9.78], p=0.029). 17 (14.9%) patients presented with HSV/VZV recurrence in the RUX treated group compared to 1 (1.0%) in non-treated patients (Figure B). We then thought to evaluate the impact of potential infections risk factors in RUX treated patients at time of treatment initiation in order to inform clinicians' therapeutic decision and follow-up guidance. For this analysis, we evaluated the characteristics of MF, potential clinical and biological immune suppression factors, treatment lines prior to RUX, dose and cumulative exposition to RUX. No clinical or biological factor was significantly associated with the overall risk of infectious events. However, hypo-gammaglobulinemia at time of RUX initiation was independently associated with HSV and/or VZV recurrence (HR 4.57, 95%CI[1.29-16.16], p=0.018). The higher rate of infections in RUX treated patients was associated with a not statistically significant trend towards shorter OS (HR 1.97, 95%CI[0.98; 3.94], p=0.055). Conclusion: This retrospective study shows an association between the occurrence of infectious complications and Ruxolitinib treatment in MF patients, and in particular, a higher incidence of HSV/VZV recurrence and skin/soft tissue infection. Patients with hypo-gammaglobulinemia at time of RUX initiation were at higher risk of HSV/VZV recurrence, suggesting that protein electrophoresis should be performed prior to treatment initiation and primary antiviral prophylaxis proposed to patients with hypo-gammaglobulinemia. Disclosures Rea: BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kiladjian:AbbVie: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Benajiba:Gilead Foundation: Research Funding.

The effect of silicone gel versus contractubex gel on the upper-extremity postsurgical scars: A randomized, double-blinded, controlled trial.

Background: Wound healing is a process that has three overlapping inflammatory, proliferative, and reconstruction phases. Silicone gel and Contractubex (onion extract gel) are two main topical agents used for the prevention and treatment of hypertrophic scars. This clinical trial study aimed to evaluate the efficacy and safety of onion extract and silicone gel on hypertrophic scars of the upper extremity and compare it to non-treated patients. Methods: This randomized, double-blind, parallel, clinical trial was done on 120 male patients who had undergone upper extremity sharp injury repair. Patients were assigned to three groups, i.e., Silicone gel (Kelo-cortTM; WA, USA) (group 1; 40 patients), Onion extract (ContractubexTM, Merz Pharma, Frankfurt, Germany) gel (group 2; 40 patients), and No Intervention (group 3; 40 patients), using drawing sealed envelopes and a computer-based table of randomization. Data were recorded using the Vancouver scale in each visit by two surgeons who were blinded to the study groups. IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY: IBM Corp). Data were compared using the ANOVA test. A P-value of less than 0.05 was considered statistically significant. Results: Vascularity (p=0.200), pliability (p=0.058), pigmentation (p=0.701), and height (p=0.438) as subjective scar parameters were approximately similar in post-upper extremity sharp injury wound hypertrophic scar among the three groups. Conclusion: Vascularity, pliability, pigmentation and height, as subjective scar parameters, were not statistically different in post-upper extremity sharp injury wound hypertrophic scar among the groups. Even though onion extract gel and Silicone gel show preventive effects in the literature, especially in burns wounds, further studies are recommended to be conducted to prove the topical effects of above-mentioned gels in patients.

Brain Structural Changes in Focal Dystonia-What About Task Specificity? A Multimodal MRI Study.

The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.

Features of Serum Fatty Acids at Acute Ischemic Stroke Onset in Statin-Treated Patients with Hypercholesterolemia.

In addition to diet therapy, statins are used to prevent cardiovascular disease in patients with hypercholesterolemia (HC). However, acute ischemic stroke (AIS) still occurs in statin-treated patients. How strictly statin-treated patients follow diet therapy before they experience AIS and whether they increase seafood consumption remains unknown. We investigated the serum concentrations and proportions (weight percentages: wt %) of fatty acids (FAs) at AIS onset in statin-treated patients (statin group), compared to those in non-treated patients with HC (6.465 mmol/L or higher) as controls (non-treated group). We included patients with AIS admitted between 2016 and 2019 within 24 h of AIS onset who underwent analysis of serum FAs. During the study period, 188 patients met the inclusion criteria: 133 in the statin group and 55 in the non-treated group. Interestingly, serum FA concentrations in the statin group were lower than those in the non-treated group. However, serum FA wt % in the statin group was almost identical to that in the non-treated group. In conclusion, statin-treated AIS patients had low FA concentrations and identical FA wt %, compared to non-treated AIS patients with HC.

Hepatitis C Virus Infection and Treatment as Independent Prognostic Factors in Diffuse Large B-Cell Lymphoma Egyptian Patients.

Egypt is one of the highest hepatitis C virus (HCV) endemic areas. Chronic HCV infection has extra-hepatic manifestations, including non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is commonly associated with HCV infection. The prognostic value of HCV infection and HCV treatment in patients with DLBCL remains unclear until now. The aim of our study is to evaluate the impact of HCV infection and HCV treatment as independent prognostic factors on the event-free survival (EFS) and overall survival (OS) in Egyptian patients with HCV associated DLBCL. This study included 353 patients with DLBCL, collected retrospectively. While 34 patients with HCV who received HCV antiviral therapy were collected prospectively. Patient's characteristics were collected from the patient records at the time of diagnosis. The status of the patients about HCV infection and HCV treatment were also recorded. Disease progression, relapse, retreatment or deaths were also verified through medical records. EFS and OS were calculated. EFS and OS significantly decrease in HCV infected and HCV non-treated patients when compared with HCV non-infected and HCV treated patients, respectively. HCV infection but not HCV treatment was independently associated with EFS and OS using univariate and multivariate analysis. Hepatitis C virus infection is an independent prognostic factor for EFS and OS in diffuse large B-cell lymphoma. HCV treatment is associated with higher EFS and OS but can not be considered as an independent prognostic factor.

A cross-sectional retrospective study of normal changes in the pharyngeal airway volume in white children with 3 different skeletal patterns from age 9 to 15 years: Part 1

This study investigated correlations between airway size and age, sex, and skeletal patterns; identified airway change trends; and measured volumetric norms in children via cone-beam computed tomography. Four hundred twenty nontreated white patients were stratified by age, sex, and anteroposterior skeletal pattern. The nasopharyngeal airway (NPA), oropharyngeal airway (OPA), and total pharyngeal airway (TPA) volumes were delineated on 3-dimensional digital cephalograms. SPSS (SPSS, Chicago, Ill) was used to run an analysis of variance and post-hoc analyses. The Class III group had significantly larger OPA volumes than Class I and II groups. Male subjects had considerably larger NPA volumes than female subjects. Age was significantly associated with all 3 airway volumes (P<0.05). The young cohort (ages, 9-10years) had a mean TPA of 11,435.34±484.45mm3, the middle cohort (ages, 11-13years) had a mean TPA of 14,152.07±395.46mm3, and the older cohort (ages, 14-15years) had a mean TPA of 18,057.99±484.25mm3. An effect of skeletal classification on OPA and a sex effect on NPA were observed. The annual change in the mean of TPA volume decreased in subjects aged 10-12years, then rebounded until 14years. TPA change peaked in female subjects 1year before male subjects.

Implant failures before and after peri‐implantitis surgery: A retrospective study on 207 consecutively treated patients

This study aimed to report implant failures before and after peri-implantitis surgery (P-IS) and to compare the pattern of implant failures with in untreated at-risk patients during the same period. A total of 5628 untreated at-risk patients (7240 jaws) and 207 consecutively patients treated with P-IS (212 jaws) were included in two groups. Implants were placed and followed-up between 1986 and 2018. Cumulative survival rates (CSR) for patients treated with P-IS after 2003 were calculated before and after P-IS and compared with those for nontreated patients. The overall 15-year CSR was 91.2% (CI 95%; 90.5%-91.9%) and 68.5%, (CI 95%, 62.1%-75.5%) for untreated patients at risk and P-IS patients, respectively (P < .05). The 10-year CSR (baseline 1 year after implant surgery) was 97.2% (CI 95%, 95.2%-100%) for treated patients before P-IS which was comparable with that for untreated patients: 95.4% (CI 95%, 94.8%-97.7%). The corresponding 10-year CSR for P-IS patients after surgery was significantly lower (71.6%: CI 95%, 63.1%-81.3% (P < .05)). CSR for patients/jaws without implant failures was comparable between untreated and treated P-IS patients before, but lower for P-IS patients after P-IS (P < .05). A negative effect of P-IS on implant survival after treatment cannot be disregarded.

Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index

Psoriasis is an immune-mediated skin disorder. Imbalance of gut microbial populations has been implicated in many diseases. We aimed to investigate whether there were differences in gut microbiota in psoriasis patients vs non-psoriasis controls and between psoriasis severity groups. 55 psoriasis patients and 27 controls were included. V3–V4 regions of the 16S rRNA gene of fecal samples were analyzed using Illumina MiSeq. Bioinformatic analysis was performed. We found changes in gut microbiome composition depending on their psoriasis status as determined by weighted unifrac (p < 0.05), in particular an increase in Firmicutes and depletion of Bacteroidetes in psoriasis patients. Additionally, the Faecalibacterium and Blautia genus were higher in psoriasis patients while Bacteroides and Paraprevotella in non-psoriasis controls (p < 0.05, LDA score > 2). Moderate-to-severe psoriasis patients had lower biodiversity than mild psoriatic patients (p = 0.049). No differences for beta-diversity were found. We developed a Psoriasis-Microbiota Index (PMI), which discriminated among psoriasis patients and controls with sensitivity: 0.78 and specificity: 0.79. Furthermore, we performed a meta-analysis with published data to validate this index. We demonstrated gut dysbiosis in psoriasis patients, suggesting a role in psoriasis pathophysiology. Furthermore, we developed a PMI with the potential to discriminate between psoriasis patients and controls across different populations, which could be used as a biomarker in the clinical practice.

Human gut-derived commensal suppresses generation of T-cell response to gliadin in humanized mice by modulating gut microbiota

The human intestinal tract is colonized by a large number of diverse microorganisms that play various important physiologic functions. In inflammatory gut diseases including celiac disease (CeD), a dysbiotic state of microbiome has been observed. Interestingly, this perturbed microbiome is normalized towards eubiosis in patients showing recovery after treatment. The treatment has been observed to increase the abundance of beneficial microbes in comparison to non-treated patients. In this study, we investigated the effect of Prevotella histicola or Prevotella melaninogenica, isolated from the duodenum of a treated CeD patient, on the induction and maintenance of oral tolerance to gliadin, a CeD associated subgroup of gluten proteins, in NOD.DQ8.ABo transgenic mice. Conventionally raised mice on a gluten free diet were orally gavaged with bacteria before and after injection with pepsin trypsin digested gliadin (PTD-gliadin). P. histicola suppressed the cellular response to gliadin, whereas P. melaninogenica failed to suppress an immune response against gliadin. Interestingly, tolerance to gliadin in NOD.DQ8.ABo mice may be associated with gut microbiota as mice gavaged with P melaninogenica harbored a different microbial diversity as compared to P. histicola treated mice. This study provides experimental evidence that gut microbes like P. histicola from treated patients can suppress the immune response against gliadin epitopes.

Decreased overall mortality rate with Chinese herbal medicine usage in patients with decompensated liver cirrhosis in Taiwan

BackgroundLiver cirrhosis is one of the main causes of the morbidity and mortality in liver diseases. Chinese herbal medicine (CHM) has long been used for the clinical treatment of liver diseases. This study was designed to explore the usage frequency and prescription patterns of CHM for patients with decompensated liver cirrhosis and to evaluate the long-term effects of CHM on overall mortality.MethodsTwo thousand four hundred sixty-seven patients with decompensated liver cirrhosis (ICD-9-CM code: 571.2, 571.5, and 571.6) diagnosed between 2000 and 2009 in Taiwan were identified from the registry for catastrophic illness patients. Of these, 149 CHM users and 298 CHM non-users were matched for age, gender, and Charlson comorbidity index score. The chi-squared test, paired Student’s t-test, Cox proportional hazard model, and Kaplan–Meier method were applied for various comparisons between these groups of patients.ResultsCHM-treated patients showed a lower overall mortality risk compared with non-treated patients (Multivariable: p < 0.0001; HR: 0.54, 95% CI: 0.42–0.69). The cumulative incidence of overall mortality was lower in the CHM-treated group (stratified log-rank test, p = 0.0002). The strongest CHM co-prescription pattern- Yin-Chen-Hao-Tang (YCHT) → Long-Dan-Xie-Gan-Tang (LDXGT) had the highest support, followed by Zhi-Zi (ZZ) → Yin-Chen-Wu-Ling-San (YCWLS) and Bai-Hua-She-She-Cao (BHSSC) → Da-Huang (DaH).ConclusionCHM, as adjunct therapy, might decrease the risk of overall mortality in patients with decompensated liver cirrhosis. CHM co-prescription patterns and network analysis showed that comprehensive herbal medicines have a protective role against liver fibrosis. Further studies are required to enhance the knowledge of safety and efficacy of CHM in patients with decompensated liver cirrhosis.

Treatment of borderline infiltrates with minimal inflammation in kidney transplant recipients has no effect on allograft or patient outcomes

In 2005, the Banff committee expanded the "borderline changes" category to include lesions with minimal (<10%) inflammation: "i0" borderline infiltrates. Clinical significance and optimal treatment of i0 borderline infiltrates are not known. Data suggest that i0 borderline infiltrates may have a more favorable prognosis than borderline infiltrates with higher grades of interstitial inflammation. In this single-center, retrospective, observational study, we assessed 90 renal transplant recipients with i0 borderline infiltrates on biopsies indicated for graft dysfunction. We studied the impact of treatment with corticosteroids on allograft function, allograft survival, and patient survival. We found no differences between treated and untreated groups with respect to eGFR at 4weeks and 6months after biopsy. Follow-up biopsies, available in 67% of patients, were negative for rejection in almost half of all cases, regardless of treatment status. The frequencies of persistent borderline infiltrates (38%) and higher-grade T cell-mediated rejection (1A or greater, 14%) on follow-up biopsies were similar between the two groups. There were no differences in rejection-free allograft survival, death-censored graft failure, or patient mortality among treated vs non-treated i0 borderline patients. Our findings suggest that the natural history of i0 borderline infiltrates, in relatively low immunologic risk patients, is not affected by corticosteroid treatment.

Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized.We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions.Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated.The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization.Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles.Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

Costochondral graft in growing patients with hemifacial microsomia case series: Long-term results compared with non-treated patients.

The aim of this study was to evaluate the long-term effectiveness of costochondral graft in hemifacial microsomia (HFM) type III patients. A sample of 10 patients affected by HFM type III treated during growth in the same Centre with costochondral graft (CCG patients group) is compared with a control group (CG) sample of 10 non-treated patients affected by the same malformation in order to understand whether surgery during growth provides advantages in terms of bony and facial symmetry after an 8-year follow-up. The growth of the CCG was assessed on panoramic X-rays. To assess facial symmetry, a photometric evaluation on the frontal view was carried out. In CCG patients group the graft grown in mean less than the healthy ramus, a good facial symmetry was achieved after surgery, but was lost in the majority of the cases at the most recent control. In CG, occlusal canting slightly increased and facial asymmetry was relatively stable during the years. In patients with a congenital deformity, restoring the height of the ramus leads to an immediate restitution of facial symmetry, but in the long term, there is a return to the asymmetrical pattern. In CG, the asymmetry is stable during years with no increase of the facial deformity.

Molluscum contagiosum in pediatric patients: to treat or not to treat? Could a personalized imiquimod regimen be the answer to the dilemma?

Background Although molluscum contagiosum virus (MCV) infection is a common disease widespread among children and young adults, there is no shared opinion on treatment that can be divided into physical, chemical, medical (immunomodulating or anti-viral). According to some authors, MCV is best left to clear by itself. Objectives To assess the clearance of MCV lesions in a sample of pediatric patients. It compares outcomes in treated with Imiquimod cream, compared with non-treated patients. Methods The sample consits of 48 pediatric patients affected by MVC clinically diagnosed. It was divided into two groups: Group I, treated with Imiquimod 5% cream once/day until the onset of a visible inflammatory reaction. Once the reaction was illicited, application was suspended until the irritation resolved. If the lesion was still present, drug was administered again using the same regimen. The cycle was repeated until complete clinical resolution. Group II, control, comprises non-treated patients. Follow up visits were carried out 12, 16, 20, 48, and 52 weeks from the beginning of treatment. Results At week 20, all patients except one in the treated group were lesion free. Persistence of MCV lesions was documented in one patient only until week 48. In the control group all patients were still affected by MCV lesions during the follow-up period. Spontaneous clinical resolution of the infection was observed in only 2 patients at week 52. The results of the study show Imiquimod’s significant efficacy. Conclusions Our study is one of the few case-control studies in pediatric population carried out with such long-term follow-up. Efficacy of this personalized treatment, scarce recurrence, absence of cicatricial sequelae and lack of necessity for deep sedation, in the case of children with disseminated lesions, makes the use of Imiquimod the first line of treatment compared with other destructive treatments or with no-treatment at all.

Multimodal Imaging in the Management of Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy.

The diagnosis and treatment of choroidal neovascularization (CNV) in eyes with chronic central serous chorioretinopathy (CSCR) can be challenging. The purpose of this study was to classify eyes with suspected CNV using multimodal imaging. The effect of intravitreal anti-vascular endothelial growth factor (VEGF) was assessed and compared to controls. This retrospective study included chronic CSCR patients with suspected secondary CNV who received intravitreal bevacizumab. Eyes were divided into “definite CNV” and “no CNV” based on optical coherence tomography angiography (OCTA). Eyes that did not undergo OCTA imaging were considered as “presumed CNV”. One-year outcome in visual acuity (VA) and central foveal thickness (CFT) were investigated and compared to non-treated control patients to assess the response to anti-VEGF. Logistic regression analysis was used to explore predictive biomarkers of CNV detection and improvement after anti-VEGF. Ninety-two eyes with chronic CSCR from 88 participants were included in this study. Sixty-one eyes received bevacizumab and 31 eyes were non-treated control subjects. The presence of subretinal hyperreflective material (SHRM) and shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) with sub-RPE hyperreflectivity on OCT was associated with a significantly increased risk of detecting CNV on OCTA. Intravitreal anti-VEGF caused significant functional and anatomical improvement in patients with neovascular CSCR as compared to non-treated eyes. In contrast, VA and CFT changes were not significantly different between treated and non-treated CSCR with no evidence of CNV on OCTA. No clinical or anatomical biomarkers were found to be associated with response to treatment. In conclusion, OCTA should be used to confirm the presence CNV in suspected chronic CSCR patients. Intravitreal anti-VEGF treatment resulted in a significantly better one-year outcome in patients with definitive OCTA evidence of CNV.

Polymerase Chain Reaction [PCR] versus Slit Skin Smear in Diagnosis of Leprosy

Background: Leprosy is a chronic infectious disease where delay in diagnosis or treatment can lead to deformities and disabilities for the rest of the patient’s life. Definite diagnosis of leprosy has long been based on clinical picture, histopathology and/or the detection of acid-fast bacilli (AFB) from tissue smears or tissue sections stained by Ziehl-Neelsen. Aim of the work: We evaluatedin this study, the usefulness of PCR for detection of M.leprae in the serum, as less invasive technique, in comparison to skin slit smear for the diagnosis of leprosy. Patients and Methods:This study included 30 non-treated patients of leprosy (9 multibacillary, 21 paucibacillary) skin slit smears had been taken. In addition, serum samples had been collected for polymerase chain reaction [PCR] test. Results: Negative Slit Skin Smear for AFB had been obtained in 20 cases with a rate of positivity of 33%. Serum PCR was positive in 20 patients giving an overall rate of positivity of 67% which confirm the diagnosis in 11 out of 20 cases with slit skin smear [SSS] negative. Conclusion: PCR does show to be more sensitive than slit skin smear [SSS] indicating its future use for diagnostic purposes especially in early leprosy cases.

MO014BORDERLINE T-CELL REJECTION IN RENAL TRANSPLANTATION: ARE WE AWARE OF THE REAL IMPACT IN GRAFT SURVIVAL?

Abstract Background and Aims Histological findings that meet criteria for borderline changes “suspicious” for acute T cell mediated rejection (BR) as defined by the Banff Classification (2017) are frequently seen. However, its clinical significance, as well as the appropriate clinical management, are still controversial. Our goal was to compare clinical outcomes of kidney transplant recipients with biopsy proven BR versus acute T cell mediated rejection (aTCMR) and the influence of treating BR rejection in graft outcomes. Method A retrospective cohort study was performed in all kidney transplant recipients with biopsy proven BR and aTCMR between January 2012 and December 2018. Data related to donor and recipient demographics, treatment and subsequent evolution of serum creatinine, proteinuria and graft survival were collected. Mean time at follow up was 31.2 ± 29.1 months. Results We included 91 patients with biopsy proven T cell rejection of which 34 (37.4%) had a BR and 57 (62.6%) aTCMR: 39 (68.4%) IA, 9 (15.8%) IB, 7 (28.1%) IIA and 2 (3.5%) IIB. There was no difference between groups (BR vs aTCMR) regarding age (45,5 vs 48,1, p=0,38), sex (male 73% vs 60%, p=0,27) or race (Caucasian 100% vs 93%, p=0.114). For both groups, deceased donor was more frequent (82% vs 95%, p=0.074), and there was no difference in cytotoxic PRA (mean 4.5 ± 9.2 vs 3.7 ± 12.8, p=0.762) or number of compatibilities (mean 2.2 ± 1.2 vs 2.4 ± 1.3, p=0.539). At the time of rejection diagnosis, the mean time of transplant was similar between groups (32.9 ± 43.6 vs 42.3 ± 67.4 months, p=0.467), but estimated glomerular filtration rate (GFR) was significantly higher in patients with BR when compared to aTCMR (32.0 ± 22.5 vs 19.9 ± 13.1 ml/min/1.73m2, p=0.009). We found no significant difference in proteinuria at the time of biopsy between the 2 groups. Treatment with steroids was started in 20 (58.8%) patients with BR and all the patients with aTCMR were treated with steroids with or without thymoglobulin, depending on the Banff class. Fourteen (41.2%) patients with BR were followed closely with no acute interventions. At 1-year post biopsy, graft survival was 70%, and we found no significantly statistical difference between the two groups (79.4% vs 64.3%, p=0.129). In patients with preserved graft, there was no difference in GFR (41.9 ± 17.7 vs 37.7 ± 19.8, p=0.401) at 12 months post biopsy for both groups. When performing Kaplan-Meyer survival curves at follow-up, we also found no difference between BR and aTCMR (57.6 ± 7.1 vs 43.6 ± 5.5 months, p=0.157) (Figure 1). When analyzing the BR group (N=34) and comparing the patients that were treated (N=20) versus the patients with conservative approach (N=14), we found no difference in demographic features, sCr at biopsy (3.0 ± 1.1 vs 2.8 ± 2.1 mg/dl, p=0.696) and time post-transplant (28.1 ± 43.2 vs 39.7 ± 44.8 months, p=0.454). Graft survival at 1-year was 80% for treated patients and 79% for non-treated patients, p=0.919 and GFR for patients with preserved graft was not different between groups (43.9 ± 21.0 vs 39.7 ± 13.5 ml/min/1.73m2, p=0.572). When performing survival curves, we found that treated patients had almost the double time with functioning graft compared to non-treated patients (71.9 ± 8.5 vs 41.3 ± 6.2 months, p=0.104), although not statistically different probably due to the small sample size (figure 2). Conclusion Our study showed that despite having better GFR at time of biopsy, patients with BR (overall and treated) did not present better graft survival nor graft function at 1 year post biopsy or at follow up, compared with aTCMR. We also found a tendency to better graft survival in patients with BR treated with steroids compared with conservative approach. These results reinforce the importance of borderline rejection in graft outcomes and that the decision of whether to treat or not can influence long-term outcomes.