Patient preference for deferasirox film-coated versus dispersible tablet formulation: a sequential-design phase 2 study in patients with thalassemia.

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.

The development of an international childhood cancer hospital register database in 13 African countries. A project of the French African Pediatric Oncology Group (GFAOP).

BACKGROUND AND AIM: The establishment of an international hospital-based register (HBR) for the French African Pediatric Oncology Group (GFAOP) was a necessary step in the group's clinical research program. With help from the Sanofi Espoir Foundation's "My Child Matters" program, the GFAOP resolved to develop an international HBR network to collect quality data on children attending the Pediatric Oncology Units (POUs). METHODS: All children entering POUs from January 2016 to December 2018 were registered using an online questionnaire. Data collection included information on diagnosis, disease stage, demographics, socioeconomic status, and outcome. An intensive training program was developed to improve both data quality and quantity. RESULTS: Among the 3348 children registered, 3230 had a suspected cancer, 681 were not confirmed. A diagnosis was confirmed on radiological, clinical, or histological examination for 2549 children including Burkitt lymphoma (516: 20%)-the most frequent diagnosis, Wilms' tumor (459: 18%), retinoblastoma (357: 14%), and acute lymphoblastic leukemia (345: 13%). Of these, 2187 children were treated. Early deaths, abandonment, economic difficulties, and lack of equipment were some of the reasons offered to explain the numbers of undiagnosed and untreated children. Vital status is known for 1994 children: 1187 died and 807 were alive, 551 of these with a follow-up > 12 months. CONCLUSION: This work has provided reliable data on children attending the POUs, especially clarifying reasons and occasions for care rupture. The data will help to identify material, human resources, and staff training needs, to evaluate progress, and to encourage consideration of pediatric cancer in national cancer plans.

Global Neuroblastoma Network: An international multidisciplinary neuroblastoma tumor board for resource-limited countries.

BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.

Association of TP53 gene polymorphisms with the risk of acute lymphoblastic leukemia in Moroccan children.

BACKGROUND: TP53 gene plays a pivotal role in maintaining genetic stability and prevention of malignancies. Alterations of this gene are implicated in more than half of human cancers. To the best of our knowledge, this study is the first to explore TP53 polymorphisms in Moroccan childhood acute lymphoblastic leukemia (ALL). METHODS AND RESULTS: DNA samples of 45 ALL children were obtained from peripheral blood. A total of 333 healthy Moroccans were used as controls. Polymerase chain reaction and Sanger sequencing were performed to analyze TP53 hotspot exons in cases. We identified a significant protective effect of the TP53-Arg variant at rs1042522 [OR 0.4593 (0.249-0.8472), p = 0.0127] and the Pro/Arg genotype [OR 0.0350 (0.0047-0.2583), p = 0.0010]. Additionally, we found a novel association between the C-allele of Arg213Arg 1800372 [OR 2.7736 (1.3821-5.5664), p = 0.0041] and the risk of childhood ALL. Importantly, TC/CC genotypes of this polymorphism were revealed to enhance the risk of ALL among females [OR 9.0 (3.1555-25.6693), p < 0.0001]. Arg213Arg was also noticed to be associated with the hemoglobin count of patients at diagnosis by linear regression (p = 0.0318). The analysis of penetrance showed a significant association of the CG/GG genotypes at rs1042522 and TC/CC genotypes at rs1800372 to childhood ALL via dominant model [OR 0.2090 (0.09074-0.4814), p = 0.0002 and OR 3.4205 (1.6084-7.2742), p = 0.0014 for rs1042522 and rs1800372 respectively]. No association was found between TP53 polymorphisms and patients survival. CONCLUSION: Altogether, our findings indicated that TP53 polymorphisms are significantly involved in the genetic susceptibility to childhood ALL in Morocco.

Prevalence and burden of dengue infection in Europe: A systematic review and meta-analysis.

Imported dengue cases are thought to be important source for transmission of autochthonous dengue in Europe. We aimed to investigate the prevalence of dengue in Europe, its severity, and factors associated with it. Out of 5287 reports resulting from the search of nine electronic search engines, we included 174 reports. Meta-analysis was performed by pooling the event rate and 95% confidence interval (CI). Subgroup meta-analyses were performed to test the effect of the covariates. Among 20 284 reported cases, 130 autochthonous dengue cases were reported in eight countries with the highest number of cases reported in Israel (n = 41). The highest number of imported dengue cases was in Germany (n = 6638) then France (n = 6610). Most cases were imported from Southeast Asia (n = 2533) especially Thailand. Dengue infection cases increased with time, with 4157 cases reported in 2010. Second dengue infection and dengue serotype 2 were positively associated with dengue severity. The proportion of autochthonous dengue infection increased with time to reach 14.8% (95% CI, 7.6-26.9) in 2015. The pooled proportion of severe dengue was 6.18% (95% CI, 2.7-13.3). The United Kingdom and France had the highest rate of severe dengue (25%; 95% CI, 6.3-62.3, and 21.4%; 95% CI, 24.5-18.7, respectively). This change may be due to the surveillance efforts instead of true biological phenomenon; thus, the lack of surveillance is an obvious limitation. In conclusion, imported and autochthonous dengue has been increasing in Europe. Severe dengue began to increase recently in Europe. European health authorities should pay more attention for the diagnosis and control of dengue infection among returning travelers, especially the travelers with fever of unknown origin.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Metro-SMHOP 01: Metronomics combination with cyclophosphamide-etoposide and valproic acid for refractory and relapsing pediatric malignancies.

BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.

Risk of perioperative bleeding complications in rhegmatogenous retinal detachment surgery: a retrospective single-center study.

PURPOSE: The goal of this study was to analyze the incidence of perioperative bleeding complications in rhegmatogenous retinal detachment. The handling of perioperative anticoagulation during vitreoretinal surgery remains controversial, since the risk of bleeding complications by its continuation has to be balanced against the risk of progression of retinal detachment and the risk of thromboembolic events when anticoagulation is interrupted. Nevertheless, only few studies have investigated the risk of perioperative bleeding complications in an emergency such as retinal detachment surgery. METHODS: We therefore examined the rate of all perioperative hemorrhages and separately the rate of only severe bleedings during vitrectomy, scleral buckling with or without drainage of subretinal fluid (SRD), or combined procedures due to retinal detachment in patients undergoing different types of perioperative anticoagulation including acetylsalicylic acetate (ASA), clopidogrel, heparin, low molecular weight heparin, and phenprocoumon. RESULTS: This retrospective single-center study included 893 patients with primary rhegmatogenous retinal detachment, n = 192 on anticoagulation and n = 701 serving as control without anticoagulation. Our analysis revealed no significantly increased rate of perioperative hemorrhages under anticoagulation with ASA 100 mg (all, 11.4%; severe, 5.0%) or phenprocoumon (all, 11.6%; severe, 2.3%) compared with controls (all, 13.0%; severe, 5.4%). However, frequencies of bleeding complications varied markedly regarding the type of surgical procedure: Scleral buckling plus SRD showed the highest rates of hemorrhages (all, 18.9%; severe, 9.1%) with significant difference (P < 0.001) compared with scleral buckling without SRD (all, 3.8%; severe, 0.6%) and vitrectomy (all, 9.2%; severe, 1.5%), respectively. Furthermore, subretinal bleeding was the most common type of perioperative hemorrhage. CONCLUSIONS: The data suggest not to stop ASA therapy prior to vitreoretinal surgery. Furthermore, we found no evidence of an increased risk for perioperative bleedings in patients under anticoagulation with vitamin-k antagonists with an INR within the sub-therapeutic range. SRD during scleral buckling procedure should be avoided as possible and regardless of any type of anticoagulation.

Informational Support in Pediatric Oncology: Review of the Challenges Among Arab Families.

Childhood cancer and its invasive treatment is a distressing life experience for the child and his family. Providing informational support is an essential part of community care, and defining parent's burden is an important part of this goal. However, providing such information can be particularly challenging in Arab countries where beliefs, traditions, religion, and socioeconomic factors influence parents' needs and their priorities of needs. This article presents a review of these specificities among Arab families. Implications of health-care providers are also discussed.

Risk of progression in macula-on rhegmatogenous retinal detachment.

PURPOSE: To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. METHODS: Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. RESULTS: A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. CONCLUSIONS: For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

SIOP-PODC adapted risk stratification and treatment guidelines: Recommendations for neuroblastoma in low- and middle-income settings.

Neuroblastoma is the most common extracranial solid tumor in childhood in high-income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. However, in low- and middle- income countries (LMIC), suboptimal diagnosis, risk stratification, and treatment may occur due to limited resources and unavailable infrastructure. The clinical practice guidelines outlined in this manuscript are based on current published evidence and expert opinions. Standard risk stratification and treatment explicitly adapted to graduated resource settings can improve outcomes for children with neuroblastoma by reducing preventable toxic death and relapse.

Childhood acute lymphoblastic leukemia in the Middle East and neighboring countries: a prospective multi-institutional international collaborative study (CALLME1) by the Middle East Childhood Cancer Alliance (MECCA).

BACKGROUND: Little is known about childhood ALL in the Middle East. This study was undertaken by MECCA as initial efforts in collaborative data collection to provide clinical and demographic information on children with ALL in the Middle East. PROCEDURE: Clinical and laboratory data for patients with ALL between January 2008 and April 2012 were prospectively collected from institutions in 14 Middle East countries and entered into a custom-built-database during induction phase. All laboratory studies including cytogenetics were done at local institutions. RESULTS: The 1,171 voluntarily enrolled patients had a mean age of 6.1 ± 3.9 years and 59.2% were boys. T-ALL represented 14.8% and 84.2% had B-precursor ALL. At diagnosis, 5.6% had CNS disease. The distribution of common genetic abnormalities reflected a similar percentage of hyperdiploidy (25.6%), but a lower percentage of ETV6-RUNX1 translocation (14.7%) compared to large series reported from Western populations. By clinical criteria, 47.1% were low/standard risk, 16.9% were intermediate risk, and 36% were high risk. Most patients received all their care at the same unit (96.9%). Patients had excellent induction response to chemotherapy with an overall complete remission rate of 96%. Induction toxicities were acceptable. CONCLUSIONS: This first collaborative study has established a process for prospective data collection and future multinational collaborative research in the Middle East. Despite the limitations of an incomplete population-based study, it provides the first comprehensive baseline data on clinical characteristics, laboratory evaluation, induction outcome, and toxicity. Further work is planned to uncover possible biologic differences of ALL in the region and to improve diagnosis and management.

Cytogenetic abnormalities and TP53 and RAS gene profiles of childhood acute lymphoblastic leukemia in Morocco.

BACKGROUND: Recurrent genetic abnormalities affecting pivotal signaling pathways are the hallmark of childhood acute lymphoblastic leukemia (ALL). The identification of these aberrations remains clinically important. Therefore, we sought to determine the cytogenetic profile and the mutational status of TP53 and RAS genes among Moroccan childhood cases of ALL. METHODS: In total, 35 patients with childhood ALL were enrolled in the study. The diagnosis and treatment were established in the Pediatric Hematology and Oncology Center at the Children's Hospital of Rabat. Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Blood samples were screened for TP53 and RAS mutations using Sanger sequencing. RESULTS: Of the 35 cases, 30 were B-lineage ALL (85.7 %). Moreover, a male predominance was observed. Cytogenetic analysis revealed chromosomal anomalies in 27 cases (77.1 %). The most frequent aberrations were high hyperdiploidy and BCR/ABL rearrangement. Interestingly, we found the rare t(15;16) and the t(8;14), which are uncommon translocations in pediatric B-ALL. The mutational analysis revealed Pro72Arg (rs1042522:C > G) and Arg213Arg (rs1800372:A > G) in TP53. In correlation with cytogenetic data, rs1042522:C > G showed a significant association with the occurrence of chromosomal translocations (p = 0.04). However, no variant was detected in NRAS and KRAS genes. CONCLUSION: Our findings emphasize the significance of detecting chromosomal abnormalities as relevant prognostic markers. We also suggest a low occurrence of genetic variants among Moroccan children with ALL.

Circulating microRNA profiles in Wilms tumour (WT): A systematic review and meta-analysis of diagnostic test accuracy.

Background: Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods: Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results: Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions: Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number: CRD42022301597.

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

B/T mixed phenotype acute leukemia with high hyperdiploidy and lineage switch to B-cell acute leukemia.

Acute leukemias are often of myeloid or lymphoid origin. However, some acute leukemias revealed an undefined differentiation into a single lineage. Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis were blasts can share B/T/myeloid phenotype. Here, we report a rare case of a 17-year-old Moroccan female diagnosed with B/T mixed phenotype acute leukemia and a high hyperdiploid karyotype who relapsed after one year of complete remission with a lineage switch to B-cell acute lymphoblastic leukemia. This case report corroborates the disclosed findings about the high occurence of abnormal karyotypes and poor prognosis of MPAL.

Abnormal High-sensitivity C-reactive Protein is Associated with an Increased Risk of Cardiovascular Disease and Renal Dysfunction among Patients Diagnosed with Type 2 Diabetes Mellitus in Palestine.

OBJECTIVE: In this study, we aimed to evaluate the prevalence of high sensitivity C-reactive protein (hsCRP) as an inflammatory mediator and its association with renal function and other biochemical markers in patients with type 2 diabetes mellitus. METHODS: We carried out a cross-sectional study at private healthcare center. We included 453 patients (48.6% males and 51.4% females) with type 2 diabetes mellitus. We obtained socio- demographic, clinical, and laboratory data from patient medical records. We carried out statistical analysis to ascertain associations between parameters. RESULTS: The overall risk of cardiovascular disease (hsCRP > 1 mg/L) among the study participants was 27.2%. Age, gender, body mass index, fasting blood glucose and serum creatinine were significantly associated with risk of cardiovascular disease (hsCRP > 1 mg/L) whereas estimated glomerular filtration rate, vitamin B12, calcium, sodium and metformin users were negatively associated with the hsCRP. CONCLUSIONS: We found a significant positive association of elevated level of C-reactive protein with type 2 diabetes mellitus. Moreover, additional to increased cardiovascular disease risk, hsCRP also seems to be a major inflammatory risk marker indicating renal function loss.

Influence of the Size of the Foveal Avascular Zone on Functional and Morphological Parameters in Patients with Early-Stage Diabetic Retinopathy.

Purpose: To correlate functional and morphological parameters with foveal avascular zone's (FAZ) size in diabetic patients with mild to moderate stage nonproliferative diabetic retinopathy. Methods: Monocentric and prospective study of a consecutive case series of diabetic patients. Medical history, best corrected visual acuity (BCVA), best corrected high/low contrast visual acuity (BChcVA/BClcVA), mean sensitivity (MS) and mean defect (MD) in central visual field testing, and FAZ size in fluorescein-angiography (FAG) were recorded. Macular thickness (central point thickness CPT, central subfield thickness CST) and volume measurements (central subfield volume CSV, total macular volume) were taken from SD-OCT (6x6mm ETDRS-grid). Groups were categorised as presenting FAZ sizes smaller (G1) or larger (G2) than 0.35mm2. Smallest (Q1) and largest quartiles (Q3) were also compared. Results: Thirty-six of 40 patients were included. MS differed significantly between G1 (n = 6) and G2 (n = 30), and BChcVA/BClcVA as well as TMV correlated significantly with FAZ size in correlation analysis. Mean HbA1c tended to be lower in G1 than G2. Patients in G1 were slightly older than in G2. Treatment period with insulin was shorter in G1/Q1 than in G2/Q3. CPT and TMV were lower in G1/Q1 than in G2/Q3. Our analysis of the FAZ in terms of patient age, HbA1c, disease duration and insulin therapy duration revealed no significance. That lack of significance also applies to BCVA, MS, MD, CPT, CST and CSV. Conclusion: As significantly associated, contrast sensitivity, central visual field parameters and potentially retinal thickness or volume seem to be suitable to detect early macular ischaemia. However, we failed to establish any correlation between FAZ and BCVA.

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. METHODS AND FINDINGS: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. CONCLUSION: In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04425382.

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin ß2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.