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1.
Retina ; 44(7): 1134-1141, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38437825

ABSTRACT

PURPOSE: Long-term study to evaluate the clinical and surgical outcomes of scleral buckle (SB) surgery for primary rhegmatogenous retinal detachment (RRD) at a large tertiary eye center. METHODS: Noncomparative, retrospective case series of 589 eyes of 569 patients with primary RRD who underwent SB surgery between 2004 and 2022 with a median follow-up of 6 months. The main outcome measures were best-corrected visual acuity, surgical outcomes, complications, and classification of RRD. RESULTS: At baseline, 447/589 (76.1%) round hole RRD, and 133/589 (22.7%) retinal dialysis RRD. Overall primary SB success rate was 83.7% for all retinal detachment subtypes, with round hole retinal detachment 84.8% and dialysis RRD 81.2%. Overall, the baseline best-corrected visual acuity was 0.42 logarithm of the minimum angle of resolution (logMAR) and the final best-corrected visual acuity was 0.26 logMAR ( P < 0.0001). In macula-off RRD, the best-corrected visual acuity significantly improved from 0.79 to 0.48 logMAR ( P < 0.0001). In patients with macula-on RRD, it improved from 0.19 to 0.12 logMAR ( P = 0.014). Binary logistic regression showed registrar surgeon grade (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.55), and partial or complete posterior vitreous detachment (OR 0.21, 95% CI 0.10-0.49) was associated with reduced odds of primary success. Higher surgical failure was associated with low pre-fellowship SB surgeon experience ( P = 0.024). CONCLUSION: Favorable visual and functional outcomes have been reported in a large series of SB for primary retinal detachment, mainly for patients with round hole RRD and retinal dialysis RRD.


Subject(s)
Retinal Detachment , Scleral Buckling , Visual Acuity , Humans , Scleral Buckling/methods , Retinal Detachment/surgery , Retinal Detachment/physiopathology , Retinal Detachment/diagnosis , Retrospective Studies , Visual Acuity/physiology , Female , Male , Middle Aged , Follow-Up Studies , Adult , Aged , Treatment Outcome , Young Adult , Postoperative Complications
2.
Eye (Lond) ; 38(9): 1642-1646, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38388833

ABSTRACT

BACKGROUND/OBJECTIVE: To evaluate the outcomes of trans-scleral sutured posterior chamber black diaphragm intraocular lens (BDIOL) (Morcher®) implantations over 11 years. SUBJECTS/METHODS: Retrospective case-series of patients, who underwent BDIOL implantation, identified from electronic patient records system from 2006 to 2016, Moorfields Eye Hospital. Demographics, pre/post-operative, final best-corrected visual acuity (BCVA), diagnosis, symptomatic improvement, intraoperative and postoperative complications immediate or late were collected and analysed to relate outcomes to surgical indication. RESULTS: Forty eyes of 38 patients (F:M 1:2.8) underwent BDIOL implantation with a mean surgical age of 46.6 years and follow-up of 44.5 months (range of 8-132 months). Indications included 23(57%) ocular trauma, 7(17%) congenital aniridia, 7(17%) iatrogenic lens and/or iris loss, and 3(7%) infectious keratitis. Mean preoperative BCVA was 1.64 logMAR and mean final postoperative BCVA was 0.94 logMAR with an average improvement in BCVA of 0.23 logMAR, equivalent to 1.5 lines of Snellen visual acuity. Visual results varied according to indications. Infectious cause patients had the greatest vision improvement (-0.7 logMAR), followed by trauma (-0.3 logMAR), and 25% of these achieved vision of 0.3 logMAR (6/12 in Snellen acuity) or better. Conversely, the aniridia group had the least improvement (worsened vision of 0.01 logMAR), 17 patients (42%) reported subjective improvement. CONCLUSION: BDIOLs achieve reasonably good visual outcomes in eyes with complex vision threatening pathology. No significant intra-operative complications are documented and most post-operative complications are related to the pre-existing pathology. Post - trauma and iatrogenic aniridia have better outcomes compared to congenital aniridia.


Subject(s)
Aniridia , Lens Implantation, Intraocular , Lenses, Intraocular , Sclera , Suture Techniques , Visual Acuity , Humans , Middle Aged , Female , Retrospective Studies , Male , Visual Acuity/physiology , Lens Implantation, Intraocular/methods , Sclera/surgery , Aged , Aniridia/surgery , Adult , Adolescent , Young Adult , Postoperative Complications , Follow-Up Studies , Child , Eye Injuries/surgery , Aged, 80 and over , Treatment Outcome , Intraoperative Complications , Prosthesis Design
3.
Pediatr Blood Cancer ; 71(2): e30728, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38069808

ABSTRACT

Hydroxyurea is highly effective in sickle cell disease, but it is still underutilized. Reports of hydroxyurea utilization largely use Medicaid data, and socioeconomics is often cited as a barrier. To address whether patient demographics influenced the high hydroxyurea usage rate recently reported for the pediatric sickle cell program of Northern Virginia, analysis of data from 2011 to 2021 revealed no statistical difference in hydroxyurea usage rate between Medicaid and non-Medicaid, African American and African, or age less than 13 and age greater than or equal to 13 years cohorts, demonstrating that hydroxyurea can be successfully implemented across demographic groups.


Subject(s)
Anemia, Sickle Cell , Hydroxyurea , United States/epidemiology , Humans , Child , Hydroxyurea/therapeutic use , Hospitalization , Anemia, Sickle Cell/drug therapy , Medicaid , Demography , Antisickling Agents/therapeutic use
5.
Pediatr Blood Cancer ; 70(8): e30423, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37247190

ABSTRACT

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.


Subject(s)
Anemia, Sickle Cell , Exercise Test , Adolescent , Humans , Anemia, Sickle Cell/drug therapy , Exercise Test/methods , Hemoglobins , Oxygen , Oxygen Consumption , Pilot Projects
6.
Eur J Haematol ; 109(5): 465-473, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35811388

ABSTRACT

Hydroxyurea (HU) has proven benefit in sickle cell anemia (SCA), but HU is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia prescribes HU regardless of symptoms to all SCA patients age ≥ 9 months and prospectively tracks outcomes. HU is dosed to maximum tolerated dosing (MTD), targeting 30% Hgb F. Longitudinal data from 2009 to 2019 encompassing 1222 HU-eligible and 950 HU-exposure patient-years were analyzed in 2-year intervals for hemoglobin (Hgb), fetal hemoglobin (Hgb F), hospitalizations, transfusions, and treat-and-release ED visits. Comparing HU-eligible patients in the interval prior to HU implementation (2009-2011) to the last interval analyzed after HU implementation (2017-2019), HU usage increased from 33% to 93%, average Hgb increased from 8.3 ± 0.98 to 9.8 ± 1.3 g/dl (p < .0001), average Hgb F rose from 13 ± 8.7% to 26 ± 9.9% (p < .0001), hospitalizations decreased from 0.71 (95% CI 0.54-0.91) to 0.2 (95% CI 0.13-0.28) admissions/person-year, sporadic transfusions decreased from 0.4 (95% CI 0.27-0.55) to 0.05 (95% CI 0.02-0.12) transfusions/person-year. Treat-and-release ED visit rates remained unchanged, varying between 0.49 (95% CI 0.36-0.64) and 0.64 (95% CI 0.48-0.83) visits/person-year. By the last interval, 72% of patients had Hgb ≥ 9 g/dl, 42% had Hgb F ≥ 30%, 79% experienced no hospitalizations, and 94% received no transfusions. Uniform HU prescription for SCA patients with close monitoring to achieve high Hgb F resulted in significant improvements in laboratory and clinical outcomes within 2 years, which continued to improve over the next 6 years. Rigorous HU implementation in a pediatric sickle cell population is feasible, effective, and sustainable.


Subject(s)
Anemia, Sickle Cell , Hydroxyurea , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/epidemiology , Antisickling Agents/therapeutic use , Blood Transfusion , Child , Erythrocytes, Abnormal , Fetal Hemoglobin , Humans , Hydroxyurea/therapeutic use , Infant
8.
Eye (Lond) ; 36(7): 1468-1475, 2022 07.
Article in English | MEDLINE | ID: mdl-34234292

ABSTRACT

OBJECTIVE OR PURPOSE: To develop and test a patient-reported outcome measure for assessing health-related quality of life (HRQOL) in surgically amenable epiphora. DESIGN: Questionnaire development and validation study. PARTICIPANTS: 201 patients with a cause of epiphora amenable to surgical intervention, recruited across three independent centres. METHODS, INTERVENTION OR TESTING: The watery eye quality of life (WEQOL) questionnaire was developed and refined according to defined psychometric standards. Both surgical and non-surgical participants completed WEQOL at baseline and follow-up (>3 months), along with the Lacrimal Symptom Questionnaire (Lac-Q), RAND Short Form Health Survey (SF-36) and Glasgow Benefit Inventory (GBI). Convergent validity of WEQOL was evaluated according to correlation (R > 0.40) with each of these additional tests. Responsiveness of WEQOL to intervention was evaluated according to patient-reported success. Test-retest reliability was assessed by the Bland-Altman method and intraclass correlation (ICC) in a subset of 64 participants at baseline. MAIN OUTCOME MEASURES: WEQOL construct validity, responsiveness and test-retest reliability. RESULTS: WEQOL was moderately correlated (R > 0.4) with the Lac-Q and several subscales of the SF-36 (physical role limitation, social, emotional role limitation and emotional well-being). A stronger correlation was found between the change in WEQOL at follow-up and GBI (R = 0.61). An appropriate graded response was found with a significant change in WEQOL score being observed in patients reporting successful (-28%, p < 0.0001) and partially successful surgery (-6%, p = 0.04), but not in those reporting unsuccessful surgery (+2%, p = 0.9). High test-retest reliability was observed (ICC = 0.93). CONCLUSIONS: The WEQOL questionnaire has been developed systematically according to modern psychometric standards and has been designed to evaluate the quality of life in patients with epiphora that is of a surgically amenable cause. In this study, it has demonstrated appropriate test-retest reliability, responsiveness and construct validity.


Subject(s)
Lacrimal Apparatus Diseases , Quality of Life , Humans , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/surgery , Patient Reported Outcome Measures , Reproducibility of Results , Surveys and Questionnaires
9.
Cardiovasc Eng Technol ; 13(1): 104-119, 2022 02.
Article in English | MEDLINE | ID: mdl-34286479

ABSTRACT

PURPOSE: Pediatric and adult patients with sickle cell anemia (SCA) are at increased risk of stroke and cerebrovascular accident. In the general adult population, there is a relationship between arterial hemodynamics and pathology; however, this relationship in SCA patients remains to be elucidated. The aim of this work was to characterize circle of Willis hemodynamics in patients with SCA and quantify the impact of viscosity choice on pathophysiologically-relevant hemodynamics measures. METHODS: Based on measured vascular geometries, time-varying flow rates, and blood parameters, detailed patient-specific simulations of the circle of Willis were conducted for SCA patients (n = 6). Simulations quantified the impact of patient-specific and standard blood viscosities on wall shear stress (WSS). RESULTS: These results demonstrated that use of a standard blood viscosity introduces large errors into the estimation of pathophysiologically-relevant hemodynamic parameters. Standard viscosity models overpredicted peak WSS by 55% and 49% for steady and pulsatile flow, respectively. Moreover, these results demonstrated non-uniform, spatial patterns of positive and negative WSS errors related to viscosity, and standard viscosity simulations overpredicted the time-averaged WSS by 32% (standard deviation = 7.1%). Finally, differences in shear rate demonstrated that the viscosity choice alters the simulated near-wall flow field, impacting hemodynamics measures. CONCLUSIONS: This work presents simulations of circle of Willis arterial flow in SCA patients and demonstrates the importance and feasibility of using a patient-specific viscosity in these simulations. Accurately characterizing cerebrovascular hemodynamics in SCA populations has potential for elucidating the pathophysiology of large-vessel occlusion, aneurysms, and tissue damage in these patients.


Subject(s)
Anemia, Sickle Cell , Models, Cardiovascular , Adult , Anemia, Sickle Cell/diagnosis , Child , Hemodynamics/physiology , Humans , Shear Strength , Stress, Mechanical , Viscosity
10.
Br J Haematol ; 196(1): 193-203, 2022 01.
Article in English | MEDLINE | ID: mdl-34786695

ABSTRACT

Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence-based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU-eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU-eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP-HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6-month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care.


Subject(s)
Anemia, Sickle Cell/epidemiology , Community Health Workers , Medication Adherence , Adult , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/therapy , Erythrocyte Indices , Female , Humans , Hydroxyurea/administration & dosage , Hydroxyurea/adverse effects , Hydroxyurea/therapeutic use , Intention to Treat Analysis , Male , Middle Aged , Patient Care , Quality Improvement , Quality of Life , Treatment Outcome , Young Adult
11.
Front Surg ; 8: 693607, 2021.
Article in English | MEDLINE | ID: mdl-34386516

ABSTRACT

Purpose: The decision for open reduction and internal fixation (ORIF) of orbital fractures is usually based on clinical severity and soft tissue and bony findings. This study aimed to identify prognostic factors for a successful surgical outcome. Materials and Methods: We included all orbital fractures treated by ORIF referred to the Ophthalmology clinic for assessment over a 12-year period. A successful outcome was defined as (i) a single operation, (ii) improved diplopia and globe position at 6 months, (iii) no surgical complications, and (iv) patient satisfaction. Data was collected on presenting symptoms, orthoptic measurements, time interval from injury to surgery, fracture geometry and involvement of internal, and external bony landmarks. Univariate and multivariate regression was used to identify predictive factors for success. Results: There were 143 cases with median age 35.4 years and 81.8% (117/143) male. 51% (73/143) were complex fractures involving multiple orbital walls. 63.6% (91/143) achieved significant improvement in both enophthalmos and diplopia at 6 months. 15.3% (22/143) had significant preoperative soft tissue or neurogenic injury. 11.8% (17/143) required orbital plate repositioning or removal. 1.4% (2/143) developed orbital haematoma and 4.2% (6/143) had cicatricial entropion. Pre-operative nerve or muscle damage (OR 0.05, p = 0.01) and infraorbital fissure fracture (OR 0.38, p = 0.04) were associated with poor outcomes, whereas an intact posterior ledge was associated with successful outcomes (OR 3.03, p = 0.02). Conclusion: Careful ocular motility evaluation to ascertain neurogenic injury and muscle compartment syndrome, and radiological analysis of the integrity of the posterior ledge and the inferior orbital fissure can facilitate management and expectations of ORIF surgery.

13.
Orphanet J Rare Dis ; 16(1): 128, 2021 03 12.
Article in English | MEDLINE | ID: mdl-33712029

ABSTRACT

PURPOSE: To present the detailed retinal phenotype of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy (LCA/EOSRD) caused by sequence variants in four genes, either not (n = 1) or very rarely (n = 3) previously associated with the disease. METHODS: Retrospective case series of LCA/EOSRD from four pedigrees. Chart review of clinical notes, multimodal retinal imaging, electrophysiology, and molecular genetic testing at a single tertiary referral center (Moorfields Eye Hospital, London, UK). RESULTS: The mean age of presentation was 3 months of age, with disease onset in the first year of life in all cases. Molecular genetic testing revealed the following disease-causing variants: PRPF8 (heterozygous c.5804G > A), PRPH2 (homozygous c.620_627delinsTA, novel variant), RP1 (homozygous c.4147_4151delGGATT, novel variant) and RPGR (heterozygous c.1894_1897delGACA). PRPF8, PRPH2, and RP1 variants have very rarely been reported, either as unique cases or case reports, with limited clinical data presented. RPGR variants have not previously been associated with LCA/EOSRD. Clinical history and detailed retinal imaging are presented. CONCLUSIONS: The reported cases extend the phenotypic spectrum of PRPF8-, PRPH2-, RP1-, and RPGR-associated disease, and the genotypic spectrum of LCA/EOSRD. The study highlights the importance of retinal and functional phenotyping, and the importance of specific genetic diagnosis to potential future therapy.


Subject(s)
Eye Proteins , Retinal Dystrophies , Eye Proteins/genetics , Humans , Infant , Microtubule-Associated Proteins , Mutation/genetics , Pedigree , Phenotype , RNA-Binding Proteins , Retinal Dystrophies/genetics , Retrospective Studies
14.
Am J Ophthalmol ; 219: 271-283, 2020 11.
Article in English | MEDLINE | ID: mdl-32479808

ABSTRACT

PURPOSE: To provide data on visual acuity (VA) outcomes and prognostic factors of microincision (23-gauge) vitrectomy surgery (MIVS) for retained lens fragments after complicated cataract surgery. DESIGN: Retrospective, interventional case series from 2012 to 2017. METHODS: Precataract surgery and intraoperative (vitrectomy) parameters, postvitrectomy complications, and best-corrected visual acuities (BCVAs) were identified. Vitrectomy was performed as early as corneal clarity permitted. Univariate and multivariate logistic regression were used to characterize factors associated with achieving VA better than 20/40, or worse than 20/200 at 6 months. RESULTS: This study included 291 consecutive eyes (291 patients). LogMAR BCVA improved from 0.73 ± 0.70 before cataract surgery to 0.46 ± 0.63 (P < .001) after vitrectomy. The previtrectomy VA was 1.43 ± 0.79. At 6 months, 183 (62.9%) and 45 patients (15.5%) achieved BCVAs better than 20/40 and worse than 20/200, respectively. Most frequent complications were de novo ocular hypertension (29 eyes, 10%) and transient cystoid macular edema (25 eyes, 8.6%). Postvitrectomy retinal detachment occurred in 9 eyes (3.1%). Final VA of 20/40 or better was independently associated only with better precataract surgery VA, age <75 years, absence of preexisting diabetic macular edema (DME) or postvitrectomy persistent cystoid macular edema (P < .05). Only poorer precataract surgery VA, delaying vitrectomy to later than 2 weeks, and final aphakic status were independently predictive of 20/200 or worse VA (P < .05). CONCLUSION: Contemporary VA outcomes of 23-gauge vitrectomy for retained lens fragments are comparable with that of prior predominantly non-MIVS cohorts, but fall short of benchmarks for uncomplicated cataract surgery. IOL type or timing of placement do not impact final VA.


Subject(s)
Lens Subluxation/surgery , Phacoemulsification/adverse effects , Vision Disorders/surgery , Visual Acuity/physiology , Vitrectomy , Aged , Aged, 80 and over , Female , Humans , Intraocular Pressure , Lens Subluxation/etiology , Lens Subluxation/physiopathology , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Vision Disorders/etiology , Vision Disorders/physiopathology
15.
Eye (Lond) ; 34(7): 1170-1171, 2020 07.
Article in English | MEDLINE | ID: mdl-32398836
16.
Pediatr Hematol Oncol ; 37(6): 475-488, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32427521

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions. We conducted a pilot study to test whether differences can be detected between stool microbiota of pediatric ALL survivors and their siblings. Stool samples were collected from 38 individuals under age 19 who were at least 1 year after completion of therapy for ALL. Stool samples collected from 16 healthy siblings served as controls. 16S ribosomal RNA gene sequencing was performed on the stool samples. Comparing microbiota of survivors to sibling controls, no statistically significant differences were found in alpha or beta diversity. However, among the top 10 operational taxonomic units (OTUs) from component 1 in sparse partial least squares discriminant analysis (sPLS-DA) with different relative abundance in survivors versus siblings, OTUs mapping to the genus Faecalibacterium were depleted in survivors. Differences in gut microbial composition were found between pediatric survivors of childhood ALL and their siblings. Specifically, the protective Faecalibacterium is depleted in survivors, which is reminiscent of gut microbiota alteration found in adult survivors of childhood ALL and reported in obesity, suggesting that microbiota alterations in pediatric ALL survivors start in childhood and may play a role in predisposition to chronic illness in later years of survivorship.


Subject(s)
Cancer Survivors , Faecalibacterium , Feces/microbiology , Gastrointestinal Microbiome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology , Siblings , Adolescent , Child , Child, Preschool , Faecalibacterium/classification , Faecalibacterium/growth & development , Female , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
17.
Pediatr Blood Cancer ; 66(9): e27816, 2019 09.
Article in English | MEDLINE | ID: mdl-31157521

ABSTRACT

BACKGROUND: Hydroxyurea (HU) increases fetal hemoglobin (HgbF) and ameliorates sickle cell disease (SCD) symptoms. Studies have demonstrated the safety and efficacy of HU in infants and children. Initiation of HU in infancy for children with SCD needs to be implemented in community practice. PROCEDURE: Starting in 2011, the Pediatric Sickle Cell Program of Northern Virginia initiated HU in infants with SCD. A prospective longitudinal database tracked the clinical course and outcomes. RESULTS: Twenty-four children with HgbSS who started HU by age 1 were continuously followed for a total of 95 person-years. Age at the time of analysis ranged from 2 to 7 years. Average hemoglobin at 6-month intervals ranged from 9.5 + 1.9 to 10.7 + 0.8 g/dL, and average HgbF ranged from 27.8 + 5.0% to 34.1 + 6.6%. Twenty-seven hospitalizations occurred (0.28/person-year), all before age 3, including 19 (70%) for fever or infection, five (19%) for splenic sequestration, and one (4%) for pain in an infant prior to starting HU. The treat-and-release emergency department visits totaled 68 (0.72/person-year), including 62 visits (91%) for fever, infection, or viral illness, and two visits (3%) for pain/dactylitis in infants before HU initiation. Splenic sequestration accounted for all five transfusions. No pain episodes requiring medical attention were documented after HU initiation. No complicated acute chest syndrome, no abnormal or conditional transcranial Doppler ultrasound, and no overt strokes occurred. CONCLUSION: Implementation of HU in infancy for patients with SCD in community practice is feasible and is highly effective in preventing disease complications.


Subject(s)
Anemia, Sickle Cell , Blood Transfusion , Hospitalization , Hydroxyurea/administration & dosage , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/therapy , Child , Child, Preschool , Female , Fetal Hemoglobin/metabolism , Fever/blood , Fever/prevention & control , Follow-Up Studies , Hemoglobin, Sickle/metabolism , Humans , Infant , Longitudinal Studies , Male , Prospective Studies , Virus Diseases/blood , Virus Diseases/prevention & control
18.
BMC Cancer ; 19(1): 357, 2019 Apr 16.
Article in English | MEDLINE | ID: mdl-30991985

ABSTRACT

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy. The aim of this study is to use sequencing of blood cells to identify germline haplotypes strongly associated with drug resistance in osteosarcoma patients. METHODS: We used sequencing data from two patient datasets, from Inova Hospital and the NCI TARGET. We explored the effect of mutation hotspots, in the form of haplotypes, associated with relapse outcome. We then mapped the single nucleotide polymorphisms (SNPs) in these haplotypes to genes and pathways. We also performed a targeted analysis of mutations in Drug Metabolizing Enzymes and Transporter (DMET) genes associated with tumor necrosis and survival. RESULTS: We found intronic and intergenic hotspot regions from 26 genes common to both the TARGET and INOVA datasets significantly associated with relapse outcome. Among significant results were mutations in genes belonging to AKR enzyme family, cell-cell adhesion biological process and the PI3K pathways; as well as variants in SLC22 family associated with both tumor necrosis and overall survival. The SNPs from our results were confirmed using Sanger sequencing. Our results included known as well as novel SNPs and haplotypes in genes associated with drug resistance. CONCLUSION: We show that combining next generation sequencing data from multiple datasets and defined clinical data can better identify relevant pathway associations and clinically actionable variants, as well as provide insights into drug response mechanisms.


Subject(s)
Blood Cells/metabolism , Bone Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Genomics , Germ-Line Mutation , Osteosarcoma/genetics , Alleles , Biomarkers, Tumor , Bone Neoplasms/mortality , Gene Frequency , Genomics/methods , Genotype , High-Throughput Nucleotide Sequencing , Humans , Kaplan-Meier Estimate , Osteosarcoma/mortality , Polymorphism, Single Nucleotide , Prognosis
19.
BMC Ophthalmol ; 18(Suppl 1): 222, 2018 Sep 14.
Article in English | MEDLINE | ID: mdl-30255798

ABSTRACT

BACKGROUND: The surgical management of patients with uncontrolled glaucoma and scleroderma is challenging, as the hostile ocular surface poses a challenge to surgery. A serious complication is tube erosion, with the risk of subsequent endophthalmitis. Here, we present a novel technique of harvesting autologous tissue to successfully manage recurrent tube extrusion. CASE PRESENTATION: MG is a 60-year-old Arabic lady diagnosed with scleroderma, that was previously managed with systemic corticosteroids. She has chronic open angle glaucoma, with a failed left eye trabeculectomy, which was then managed by a Baerveldt tube (BVT) insertion. Eight months after this primary surgery, she developed an anterior uveitis. This was further complicated by conjunctival erosion, tube exposure, leak around the sclerostomy site and hypotony. The erosion was likely secondary to her tight eyelids as a result of her scleroderma. She was taken back to theatre for tube revision, with single layer amniotic membrane transplant (AMT) over the exposed area, but the tube was eroding again after 2 months. She eventually underwent tube extraction, pars plana tube plate stabilisation, pars plana vitrectomy (PPV), pars plana tube insertion, phacoemulsification and intra-ocular lens insertion, jointly with the vitreo-retinal surgeons and with high dose prednisolone cover both pre- and post-operatively. We harvested the capsule which had grown over the end plate of the original tube. We sutured this over the new tube, specifically over a single layer of tutoplast prior to conjunctival closure. Almost a year on, the pars plana tube remains in place with no complications. CONCLUSIONS: This case highlights the role of a pars plana tube in cases of cicatricial disease, with the use autologous tissue instead of grafts wherever possible. In patients with systemic disease such as scleroderma, pre-operative immunosuppression helps to reduce the of erosion in difficult cases.


Subject(s)
Conjunctival Diseases/surgery , Glaucoma Drainage Implants/adverse effects , Glaucoma, Open-Angle/surgery , Intraocular Pressure , Ophthalmologic Surgical Procedures , Prosthesis Failure/etiology , Scleroderma, Systemic/complications , Conjunctival Diseases/etiology , Female , Humans , Lens Implantation, Intraocular , Middle Aged , Phacoemulsification , Recurrence , Uveitis, Anterior/etiology , Vitrectomy
20.
Front Neurol ; 9: 338, 2018.
Article in English | MEDLINE | ID: mdl-29867744

ABSTRACT

Glaucoma is one of the leading causes of irreversible blindness in the world. It is characterized by the progressive loss of retinal ganglion cells (RGCs), mainly through the process of apoptosis. Glaucoma patients often come to clinical attention when irreversible loss of visual function has been already established; therefore, early recognition of RGC apoptosis is inordinately important in disease prevention. The novel technology called Detection of Apoptosing Retinal Cells (DARC) allows real-time in vivo quantification of apoptosing cells through the use of a fluorescent biomarker and a confocal scanning ophthalmoscope. A recent Phase I clinical trial has evaluated the safety of DARC and its ability to detect retinal apoptosis in glaucoma patients and healthy volunteers. Results suggest that DARC may have potential in the early detection of glaucoma, which could help alleviate the medical, social, and economic burden associated with this blinding condition.

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