Ocular injuries associated with motor vehicle accidents: long term effects on quality of life.

PURPOSE: To describe the prevalence and outcome of motor vehicle accidents-associated ocular injuries. METHODS: A survey of patients who presented to the emergency room at a level 1 trauma center with motor vehicle accidents-associated ocular injuries. A patient questionnaire and review of clinical notes were conducted for all patients. RESULTS: Of 274 motor vehicle accident victims with ocular injuries who presented to the emergency room, 40 (15%) responded to the survey. Over half of them were driving a vehicle, and most reported wearing a seat belt or a helmet. Most ocular injuries were mild. The most common injuries were bone fractures, subconjunctival hemorrhage, eyelid involvement and corneal injury. Most respondents had no change in vision and perceived their ocular involvement as a minor part of their injury. Most respondents returned to work and to driving within a year. CONCLUSION: Our study sheds light on the details and extent of ocular involvement and the visual ability to perform daily activities following motor vehicle accidents.

Neuromyelitis Optica Spectrum Disorder: Disease Course and Long-Term Visual Outcome.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that classically manifests as attacks of optic neuritis (ON) and transverse myelitis (TM). The prevalence, course, and severity of NMOSD vary considerably. Few studies report the neuro-ophthalmologic disease course and visual outcome. OBJECTIVE: We sought to describe the course and long-term visual outcome in a cohort of NMOSD patients treated in a single tertiary referral center. METHODS: The database was searched for all patients with NMOSD who were treated in our center from 2005 to 2014. Data collected included detailed visual outcome, grade of final visual disability, neuroimaging, and results of optical coherence tomography. Details on relapses, acute episodes, and maintenance therapies were recorded. RESULTS: Of the 12 patients with NMOSD who were followed for a mean duration of 9.06 years, 10 (83%) were women. Mean age at presentation was 33.90 ± 16.94 years. Patients with acute attacks were treated with high-dose intravenous methylprednisolone and offered immunosuppressive maintenance. ON occurred in 18 eyes of 12 patients, with a cumulative total of 37 ON episodes. At the end of the follow-up period, no patient had become legally blind and only 1 patient had lost her driver's license. Pain associated with acute ON was common (83%), whereas optic disc edema was a rare finding in our patient cohort (6%). CONCLUSIONS: In this retrospective series of 12 patients with NMOSD, followed for a mean of 9.06 years, acute-phase treatment was given within 8 days of relapse, followed by maintenance therapy. Functional visual outcome, as measured by the World Health Organization/International Classification of Diseases, Tenth Revision visual disability scale was better than reported in previous studies and driver's license was preserved in 11 of 12 patients. Pain accompanied 83% of ON attacks and may not aid differentiating multiple sclerosis from NMOSD-related ON.

Factor XIII Assays and associated problems for laboratory diagnosis of factor XIII deficiency: an analysis of International Proficiency testing results.

We analyzed results from the External quality Control of diagnostic Assays and Tests program to assess current clinical laboratory practice and performance of different methods for factor XIII (FXIII) testing internationally. FXIII proficiency testing data from all eight surveys conducted in 2010 and 2011 were analyzed (1,283 results), comparing the three available methods for detecting FXIII deficiency, thus including clot-solubility qualitative activity, quantitative activity, and antigen. Clot-solubility qualitative assays detected a deficiency in only 16% (11/69) of samples with less than 2% FXIII. Assays using added thrombin detected more deficiencies (33%) than did assays without added thrombin (11%). The most commonly used quantitative activity method tended to produce higher results for low FXIII samples than other quantitative activity methods. Antigen results generally showed good accuracy compared with expected levels. The mean interlaboratory coefficients of variation showed wide variability, especially for samples with less than 10% FXIII activity. Laboratory self-classification of results (as normal vs. abnormal) was good, and was slightly better for specimens with ≤ 25% FXIII than for specimens with 26 to 70% or those with >70% FXIII. We conclude that quantitative activity assays perform better for detecting FXIII deficiency than clot solubility assays, although some quantitative activity assays overestimate low FXIII levels.

Visual acuity outcome in patients with subretinal hemorrhage - office procedure vs. surgical treatment.

PURPOSE: To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) and gas vs. pars plana vitrectomy (PPV) surgery as first-line treatment for subretinal hemorrhage. METHODS: Retrospective study of 107 adults treated for subretinal hemorrhage at a tertiary hospital during 2008-2019; 51 received injection of tPA and gas and 56 underwent PPV. RESULTS: No between-group differences were found in age and sex, medical history, use of anticoagulants or antiplatelets, history of ocular surgeries, and previous use of intravitreal anti-VEGF. Overall follow-up time was longer in the PPV group (median 4.9 vs 3.28 years, p = 0.005). The hemorrhage was displaced in a similar percentage of patients in the tPA-and-gas group (n = 40, 78.4%) and the PPV group (n = 45, 80.4%) (p = 0.816). Approximately 80% of patients in the tPA-and-gas group were able to forgo PPV surgery. Visual acuity (in LogMAR) was similar in the two groups prior to the diagnosis of subretinal hemorrhage but better in the tPA-and-gas group at the end of follow-up (p < 0.001). CONCLUSION: Injection of gas and tPA can be done immediately following diagnosis of subretinal hemorrhage as an office procedure. Visual acuity outcome is good, with a high rate of blood displacement. About 20% of patients might require additional PPV as secondary intervention.

Dynamics of Peripheral Blood T-lymphocytes Have Predictive Values for the Clinical Outcome of COVID-19 Patients in Intensive Care Unit.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients with severe disease had a high mortality rate. It's imperative to identify risk factors associated with disease progression and prognosis. Immune responses played an important role in the host's defense against the virus. We studied the dynamics of peripheral blood lymphocytes (PBLs) in relation to the clinical outcome in COVID-19 patients in intensive care unit (ICU). DESIGN: This cohort included 342 COVID-19 patients who were admitted to ICU between February 1 and May 30, 2020, with 178 having follow-up PBL analysis. The patients were divided into a group that survived and an expired group. PBL analysis was performed by flow cytometry. RESULTS: At time of initial flow analysis, there were no statistically significant differences in lymphocyte, T-cell and subsets, B-cell or natural killer (NK) cell counts between the 2 groups. However, during the ICU course, the surviving group demonstrated a full recovery of CD3+ T-cells, CD4+ T-cells, and CD8+ T-cells, with no significant change in B-cells, and a slight upward trend in NK-cells. In contrast, the expired group showed no recovery in T-cells (and subsets) and no significant changes in B-cells and NK-cells. We identified the earliest time points and cut-off values for T-cell subsets that predict clinical outcomes. CONCLUSION: The results of this study suggest that evaluation of PBL in COVID-19 patients could be valuable in the study of the immune responses to the disease and the prognostication of outcome.

CSF3R T618I mutant myelodysplastic/myeloproliferative neoplasm in the elderly: An age-related disease with unfavorable prognosis.

We reported two MDS/MPN-U and one CMML patients with CSF3R T618I mutation. There were two males and one female, with a median age of 84 years. Three patients presented with leukocytosis and anemia, two with thrombocytopenia, and one with monocytosis. In all the patients, bone marrow showed hypercellularity with myeloid or erythroid predominant trilineage hematopoiesis and dysplasia. Two cases carried -7/-7q abnormalities. In addition to CSF3R T618/I mutation, each case carried 3-5 additional somatic mutations. The median survival was only 2 months. These rare patients were characterized by old age, high mutation rates, clonal hematopoiesis-associated mutations, clonal evolution, and unfavorable prognosis.

Vitamin D status in Israeli pediatric type 1 diabetes patients: the AWeSoMe Study Group experience and literature review.

Background The prevalence of both vitamin D (VitD) deficiency and type 1 diabetes mellitus (T1DM) has increased worldwide over the last few decades. The objectives of this study were: (1) to evaluate the prevalence of VitD deficiency and insufficiency among Israeli youth with T1DM and (2) to assess the association between VitD status, seasonality and T1D glycemic control characteristics. Methods This was a multi-centered, cross-sectional study. VitD levels were routinely tested during the years 2008-2011 in T1DM patients aged up to 21 years. Medical records were reviewed for demographic, clinical and laboratory characteristics. Results The study population consisted of 199 participants (53% males), mean age 12.24±4.11 years, mean T1DM duration 3.77±3.43 years. VitD levels were within the normal range in 19.6%, insufficient (15-29 ng/mL, 37-72 nmol/L) in 62.3% and deficient (<15 ng/mL, <37 nmol/L) in 18.1%. Mean VitD level was higher during the summer than during spring, autumn and winter (28.65 ng/mL, 23.16 ng/mL, 21.65 ng/mL, 17.55 ng/mL, respectively, p<0.001). Mean VitD level was higher among secular patients compared to the religious (whole-year heavily dressed) population (23.57 ng/mL, 15.54 ng/mL, respectively, p<0.001). VitD level was negatively associated with body mass index calculation of standard deviation scores (BMI-SDS), high-density lipoprotein (HDL) and age at diagnosis (r=-0.171, p=0.016; r=-0.149, p=0.043; r=-0.150, p=0.037, respectively). No association was demonstrated with disease duration and glycemic control indices and metabolic parameters. Conclusions VitD insufficiency is largely prevalent among Israeli youth with T1DM, as is in Israeli youth in general. The VitD level is associated with seasonality, clothing habits and BMI.

Investigating animal models of optic neuropathy: An accurate method for optic nerve and chiasm dissection in mice.

BACKGROUND: Numerous disorders affecting the optic nerve require histological examination of whole length optic nerves and chiasm. Most methods employed to study the histopathology of the optic nerves in animal models of human diseases involve resection of a short retrobulbar section after eye globe exenteration, commonly obtained in mice. This approach might affect the morphology of the optic nerve, thus limiting accurate identification of pathological changes in the tissue. Some histological studies were performed on longer or more posterior parts of the anterior visual pathway included the chiasm. However, an accurate replicable protocol for such whole length (eye globe to chiasm) dissection is currently unavailable in published literature. NEW METHOD: Here we describe a protocol for dissecting the whole length of the optic nerves and chiasm through a craniotomy incision. RESULTS: We describe in detail the stages necessary for exposing the optic nerves, the chiasm and the optic tracts, and for detaching them with minimal traction. COMPARISON WITH EXISTING METHOD: The existing replicable method provide only a sample of the retrobulbar optic nerve and the sample might be affected by traction. Our protocol provides a whole length specimen of the optic nerve and chiasm without concern of traction artifacts. CONCLUSIONS: We present a simple and straightforward approach to isolate the complete anterior visual pathway in the mouse for histopathological evaluation.

Primary Low-Grade B-Cell Lymphoma of Skull With Translocation Between Immunoglobulin and Interferon Regulatory Factor 4 Genes.

Low-grade B-cell lymphoma with immunoglobulin (IG) and interferon regulatory factor 4 (IRF4) gene rearrangement is extremely rare, with only 4 cases being previously reported. In this article, we report one additional case that arises from the skull and review the literature. The patient was a 69-year-old man who presented with recurrent and disabling vertigo and was found to have a 5.0 × 1.7 cm lesion within the left posterior parietal bone. Histological examination revealed a bone lesion with diffuse lymphoid infiltrate comprising of mostly small lymphocytes with scant cytoplasm, slightly irregular nuclei and inconspicuous nucleoli, and scattered larger cells resembling prolymphocytes and paraimmunoblasts. Immunohistochemical studies showed that the neoplastic cells were positive for CD20, CD79a, PAX5, CD23, CD43, BCL-2, BCL-6, MUM-1, LEF-1, and IgM and negative for CD5, CD10, cyclinD1, SOX11, and IgD. Flow cytometric analysis identified CD5 negative and CD10 negative monoclonal B cells with lambda light chain restriction. Fluorescence in situ hybridization analysis revealed del(13q) abnormality, but was negative for IGH/BCL2, IGH/CCND1, and BIRC3/MALT1 translocations. Next-generation sequencing identified IGK-IRF4 rearrangement and BRD4 E1113 del abnormalities. Given a low clinical stage (IE) of the disease, the patient did not receive additional treatments and was free of disease at 1 year after the diagnosis.

Classical Hodgkin Lymphoma With Aberrant CD8 Expression: A Clinicopathologic Study of Five Cases.

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (CHL) are of B-cell origin. In a small number of CHL cases, the tumor cells can express T-cell antigens. CD8 expression in this setting is extremely rare. We identified 5 cases of CHL with aberrant CD8 expression from our database. The patients included 3 men and 2 women with a median age of 33 years (range = 20-59 years). All the patients initially presented with lymphadenopathy and variable number of RS cells. Two cases were classified as mixed cellularity type that showed prominent vascular proliferation mimicking peripheral T-cell lymphoma. Two cases represented nodular sclerosis type. The tumor cells in all cases were positive for CD8 and negative for CD2, CD3, CD4, and CD7 and carried germline T-cell receptor genes. Molecular studies revealed T-cell receptor genes to be in germline configuration in 4 cases with available information. Given the morphologic overlap with peripheral T-cell lymphoma and the rarity of this type of CHL, identifying more cases will help our better understanding of this entity.

Transient myeloproliferative disorder in neonates with and without Down syndrome: a tale of 2 syndromes.

Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better.

Aggressive natural killer cell leukemia mimicking interstitial lung diseases with the activation of the mitogen-activated protein kinase pathway.

Aggressive natural killer (NK) cell leukemia (ANKL) is a rare form of leukemia with an aggressive clinical course. It commonly involves the peripheral blood, bone marrow, liver, and spleen but rarely involves the lungs. We report a 36 year-old woman who presented with pulmonary lesions we suspected to be interstitial lung disease on an imaging study. A lung biopsy showed extensive lymphoid infiltrate growing along pre-existing alveolar septa without destroying the alveolar spaces. Further workup revealed hepatomegaly, borderline splenomegaly, and multiple lymphadenopathies. Her laboratory tests showed leukocytosis, anemia, thrombocytopenia, abnormal liver enzymes, and elevated lactate dehydrogenase. A bone marrow (BM) aspirate smear revealed many intermediate to large lymphocytes with dispersed chromatin, basophilic cytoplasm, and some azurophilic granules. A BM biopsy showed hypercellularity with interstitial lymphoid infiltrate in a background of trilineage hematopoiesis and histiocytosis with hemophagocytosis. Immunohistochemical studies performed on both the lung and BM biopsies showed the neoplastic cells to be positive for CD2, CD3, CD7, CD56, granzyme B, phosphor-MAPK (pMAPK), EBER (Epstein-Barr Virus-encoded small RNA) by in situ hybridization; they were negative for CD4, CD5, CD8, CD30, LMP1, and phospho-STAT3 (pSTAT3). A flow cytometry analysis of the BM aspirate identified a population of atypical lymphocytes with the NK cell phenotype. Molecular studies were negative for T-cell receptor gene rearrangements, and the neoplastic cells displayed a complex karyotype. The patient responded initially to chemotherapy but died of multiorgan failure two months after the diagnosis. We present a case of ANKL mimicking interstitial lung disease with the activation of MAPK pathway.

Composite Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia and Follicular Lymphoma: A Clinicopathological Study of Six Cases.

BACKGROUND: Composite small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and follicular lymphoma (FL) is extremely rare, and only 13 cases have been reported previously. METHODS: We identified 6 cases of composite SLL/CLL and FL in our database and studied their clinical, histologic, immunophenotypic, and cytogenetic features. A literature review of the existing cases was also conducted. RESULTS: The patients included 4 males and 2 females, with a median age of 72 years. Four patients presented with lymphadenopathy and 2 with extranodal diseases. Lymphocytosis was seen in 2 cases. Serum lactate dehydrogenase levels were within normal range in all but one case. There were 2 histologic patterns: SLL/CLL predominant pattern (type I) and FL predominant or mixed pattern (type II). The type I pattern was exclusively associated with in situ follicular neoplasia (ISFN). The SLL/CLL showed typical morphology and immunophenotype in all the cases. The FL component included low grade (n = 3), ISFN (n = 2), and primary cutaneous FL (n = 1). Four cases had staging bone marrow biopsies including 3 cases with involvement by SLL/CLL and 1 case with involvement by SLL/CLL and FL. Four patients received treatments, one was under clinical surveillance, and one had no available information. All patients were alive after a median follow-up of 22 months. CONCLUSIONS: This is the largest case serial of composite SLL/CLL and FL. The CL affects elderly individuals, presents with advanced clinical stage, and appears to have a relatively indolent clinical course.

Myelin oligodendrocyte glycoprotein-positive optic neuritis masquerading as pseudotumor cerebri at presentation.

Optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. Other clinical manifestations include acute demyelinating encephalomyelitis, transverse myelitis and neuromyelitis optica spectrum disorders. Uncommon presentations of MOG-positive disease have recently been reported. ON in MOG-positive disease commonly involves the anterior portion of both optic nerves, leading to bilateral disc swelling. During the early stages of ON, in the setting of bilateral disc swelling and pain, patients may initially be suspected as pseudotumor cerebri (PTC). In this study, we report five cases presenting early in the course of MOG-IgG-related ON, which were misdiagnosed as PTC in the emergency department. MOG-IgG-positive ON requires timely treatment to prevent RNFL and vision loss secondary to the high relapse rate associated with these antibodies. Our aim is to increase the awareness of the unique findings of MOG-IgG-positive ON, which may initially mimic PTC, thereby delaying treatment.

Retinal Nerve Fiber Layer May Be Better Preserved in MOG-IgG versus AQP4-IgG Optic Neuritis: A Cohort Study.

BACKGROUND: Optic neuritis (ON) in patients with anti-myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies has been associated with a better clinical outcome than anti-aquaporin 4 (AQP4)- IgG ON. Average retinal nerve fiber layer thickness (RNFL) correlates with visual outcome after ON. OBJECTIVES: The aim of this study was to examine whether anti-MOG-IgG ON is associated with better average RNFL compared to anti-AQP4-IgG ON, and whether this corresponds with a better visual outcome. METHODS: A retrospective study was done in a consecutive cohort of patients following anti-AQP4-IgG and anti-MOG-IgG ON. A generalized estimating equation (GEE) models analysis was used to compare average RNFL outcomes in ON eyes of patients with MOG-IgG to AQP4-IgG-positive patients, after adjusting for the number of ON events. The final mean visual field defect and visual acuity were compared between ON eyes of MOG-IgG and AQP4-IgG-positive patients. A correlation between average RNFL and visual function was performed in all study eyes. RESULTS: Sixteen patients were analyzed; ten AQP4-IgG-positive and six MOG-IgG-positive. The six patients with MOG-IgG had ten ON events with disc edema, five of which were bilateral. In the AQP4-IgG-positive ON events, 1/10 patients had disc edema. Final average RNFL was significantly better in eyes following MOG-IgG-ON (75.33µm), compared to 63.63µm in AQP4-IgG-ON, after adjusting for the number of ON attacks (GEE, p = 0.023). Mean visual field defects were significantly smaller (GEE, p = 0.046) among MOG-IgG positive ON eyes compared to AQP-IgG positive ON eyes, but last visual acuity did not differ between the groups (GEE, p = 0.153). Among all eyes, average RNFL positively correlated with mean visual field defect (GEE, p = 0.00015) and negatively correlated with final visual acuity (GEE, p = 0.00005). CONCLUSIONS: Following ON, RNFL is better preserved in eyes of patients with MOG-IgG antibodies compared to those with AQP4-IgG antibodies, correlating with better visual outcomes.

Serial cytogenetic alterations resulting in transformation of a low-grade follicular lymphoma to Burkitt lymphoma.

Follicular lymphoma (FL) is the most common indolent or low-grade non-Hodgkin lymphoma (NHL). Histologic transformation to high-grade lymphoma, generally to diffuse large B-cell lymphoma, occurs in 25-35% of cases. Although t(14;18), the cytogenetic hallmark of FL, has been found in approximately 85% of these cases, multiple secondary cytogenetic and molecular genetic changes underlie the transformation process. We report the case of a 58-year-old patient who presented with stage IVA, grade 2 FL that subsequently transformed to Burkitt lymphoma. Multiple chromosomal aberrations, including three novel translocations, were observed related to this transformation. Inversion (1)(p36.3q12) and t(3;14;18)(p23;q32;q21) occurred prior to transformation and may have contributed to the transformation process. A t(1;11)(q25;q13) was acquired simultaneously with t(8;22) and, in conjunction with other chromosomal abnormalities, coincided with an extremely aggressive clinical course. The frequent breakage of 1q observed in this case suggests that the region harbors important genomic signals for the transformation of FL.

Polyclonal plasma cell proliferation with marked hypergammaglobulinemia and multiple autoantibodies.

A 77-yr-old man presented with marked peripheral blood and bone marrow plasmacytosis, marked hypergammaglobulinemia, and multiple autoantibodies. Serum protein immunofixation and immunophenotyping of bone marrow plasma cells by flow cytometry and immunohistochemistry disclosed polyclonal proliferation of plasma cells at various stages of differentiation. The presence of multiple autoantibodies in the patient's serum suggests that an autoimmune disease underlies the polyclonal proliferation of plasma cells.

Mantle cell lymphoma with in situ or mantle zone growth pattern: a study of five cases and review of literature.

We present two rare cases of in situ mantle cell lymphoma ("in situ MCL") and three cases of MCL with mantle zone growth pattern (MCL-MZGP). The patients include four males and one female, with a median age of 66 years (range, 52 to 86 years). Two present with isolated lymphadenopathy and three with multiple lymphadenopathy. At presentation, the complete blood count (CBC) and serum lactate dehydrogenase (LDH) are normal in all cases. Histologic examination reveals an in situ pattern in two cases and a mantle zone growth pattern in three cases. The staging bone marrow biopsies show minimal involvement by lymphoma in one case and no morphologic evidence of lymphoma in four cases. All cases are positive for cyclin D1, including two with typical MCL phenotype and three with CD5-negativity. Four out of five cases express kappa light chain. FISH study for t(11;14) is performed in three cases, of which one is positive and two are inconclusive. For four patients with a median follow-up of 38 months, three are in clinical remission and one has persistent disease. In conclusion, the "in situ MCL" is associated with incidental finding, indolent clinical course and lower tumor burden. The predominant usage of kappa light chain and frequent CD5-negativity observed in our cases are unusual. We review the clinical and laboratory features of "in situ MCL" cases in the literature.