Intraocular leucocyte subpopulations analysis by multiparametric flow cytometry in human uveitis

PurposeThe aim of this study was to describe the cellular infiltrate in aqueous and vitreous samples of patients with uveitis analysed by multiparametric flow cytometry.MethodsThis is a retrospective analysis of aqueous and vitreous samples analysed by flow cytometry for diagnostic purposes, in cases of masquerade syndromes and infectious and non-infectious uveitis. Data collected included demographics, anatomical classification of uveitis, phenotypic diagnosis, anterior chamber cells grading, vitreous haze and time of follow-up since presentation to sample obtained.ResultsThirty-one samples (17 aqueous and 14 vitreous fluids) from 31 patients, 18 men, were analysed. The mean age at the time of sample collection was 60.23±17.03 years. The most frequent anatomical classification was panuveitis (14 of 31). T cells accounted for the main cellular component in the majority of the samples (10 of 13 aqueous samples; 7 of 14 in vitreous samples). CD4:CD8 ratios ranged from 0.21 to 16.3 in the case of aqueous samples and from 0.5 to 9.7 in the case of vitreous samples.DiscussionFlow cytometry analysis of aqueous and vitreous samples from patients with uveitis could provide insight into the pathogenesis of human uveitis and help develop accurate animal models which better mimic human disease.

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Secondary intra-arterial chemotherapy and/or intravitreal chemotherapy as salvage treatment for retinoblastoma

European Journal of Ophthalmology ◽

10.1177/1120672120957587 ◽

2020 ◽

pp. 112067212095758

Author(s):

Ibadulla Mirzayev ◽

Ahmet Kaan Gündüz ◽

Kıvılcım Yavuz ◽

Mehmet Zahid Şekkeli ◽

Funda Seher Özalp Ateş ◽

...

Keyword(s):

Survival Rates ◽

Primary Treatment ◽

Salvage Treatment ◽

External Radiotherapy ◽

Intravitreal Chemotherapy ◽

The Mean ◽

Group B ◽

Group D

Purpose: To evaluate the results of secondary intra-arterial chemotherapy (IAC) and/or intravitreal chemotherapy (IVC) as a salvage treatment for retinoblastoma (RB). Materials and Methods: The medical records of 31 (20 male, 11 female) cases (with 38 eyes) who underwent secondary IAC and/or IVC between February 2010 and June 2019 were retrospectively reviewed. Results: Thirteen (41.9%) cases had unilateral and 18 (58.1%) had bilateral RB. According to the International Classification of RB, 6 (15.8%) eyes had group B, 9 (23.7%) eyes had group C, 16 (42.1%) eyes had group D, and 7 (18.4%) eyes had group E RB at diagnosis. All patients underwent six-cycle intravenous chemotherapy as primary treatment and 8 eyes received external radiotherapy before IAC/IVC. Secondary IAC was performed in 21 (55.3%) eyes, IVC in 10 (26.3%) eyes, and IAC + IVC in 7 (18.4%) eyes. External radiotherapy was applied in 2 (5.3%) eyes after IAC/IVC, one of which was later enucleated. In total, 17 (44.7%) eyes undergoing secondary IAC/IVC treatments were enucleated. Metastasis and death were not observed in any case during the mean follow-up period of 59.3 (median 61, range: 10–98) months. Discussion: Although 60.5% of the eyes undergoing IAC/IVC consisted of groups D and E RB, globe salvage and survival rates were 55.3% and 100.0%, respectively. External radiotherapy was required in 5.3% of the eyes after IAC/IVC. In conclusion, IAC and IVC are safe and effective treatment methods in eyes with RB unresponsive to other eye-preserving treatments and those demonstrating recurrence.

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A long-term prospective observational study in 31 patients with hemicrania continua

Cephalalgia Reports ◽

10.1177/2515816318824694 ◽

2019 ◽

Vol 2 ◽

pp. 251581631882469 ◽

Cited By ~ 1

Author(s):

Sanjay Prakash ◽

Chaturbhuj Rathore ◽

Kaushik Rana ◽

Hemant Joshi ◽

Jay Patel ◽

...

Keyword(s):

Hemicrania Continua ◽

Background Pain ◽

Headache Diary ◽

The Mean ◽

Drug Leads ◽

Observation Period ◽

Structured Questionnaire

Introduction: Till date, there is no prospective study in patients with hemicrania continua (HC). Methods: Patients fulfilling the international classification of headache disorders criteria for HC were evaluated prospectively. All patients were subjected to a detailed clinical interview, based on a structured questionnaire. Before starting indomethacin, all patients were instructed to fill a headache diary for at least 5 days. Gradual tapering of indomethacin was done at regular intervals. Results: We enrolled 41 patients over 4.5 years, 31 of whom met the criteria after confirming the indomethacin response. The mean age was 41 years, and 55% were female. The mean duration of headache was 43.6 months. All patients had continuous strictly unilateral pain with episodic exacerbations. At least one cranial autonomic feature was noted in 81% of patients. Twenty-five patients (81%) felt a sense of restlessness during exacerbations. The mean follow-up was 2.5 years. Three-fourths of patients noted a reduction in indomethacin dose after an average 2.5 of years follow-up. The mean reduction of the dose in the follow-up was statistically significant (172 mg vs. 110 mg, p < 0.001). All patients missed the drug for various reasons over the observation period. The headache reappeared within 48 h in 97% of patients. Conclusion: Misdiagnosis of HC is still very common. Patients may not volunteer about the background pain and will focus only on the exacerbations. HC rarely remits, but indomethacin requirements may decrease over time. Skipping of the effective drug leads to the immediate reappearance of pain.

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Detection of Circulating Antigen-Specific CD8+ Lymphocytes against Leukemia Associated Antigens WT1, PR1 and Survivin Using HLA 0201 Pentamers After Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.5115.5115 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5115-5115

Author(s):

Juana Serrano-Lopez ◽

Joaquin Sanchez Garcia ◽

Josefina Serrano ◽

Carmen Martin ◽

Rafael Rojas ◽

...

Keyword(s):

Flow Cytometry ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Peripheral Blood ◽

Median Percentage ◽

Blood Samples ◽

Hematological Disorders ◽

Multiparametric Flow Cytometry ◽

Leukemia Antigen

Abstract Abstract 5115 INTRODUCTION Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment option for patients with hematological disorders. Alloreactive donor-derived T lymphocytes exert a beneficial graft-versus-leukemia (GVL) effect through the recognition of leukemia-restricted (or preferentially expressed) antigens as Wilms tumor protein (WT1), survivin (SURV) or proteinase (PR1). Currently research in transplant immunology focuses in enhancing GVL while preventing the deleterious graft-versus-host disease (GVHD) that could be achieved by manipulating donor-derived antigen-specific T-populations. In this study we tested the presence of peripheral blood leukemia-associated antigen-specific CD8+ T-lymphocytes during post allo-SCT follow-up. PATIENTS AND METHODS Forty-three consecutive HLA*0201 patients (homo or heterozygotous) undergoing conventional myeloablative (n=24) or non-myeloablative (n=19) allo-SCT as treatment of hematological disorders were included. Allogeneic donor was an HLA-identical sibling in 26 cases (60.5%) and unrelated in 17 cases (39.5%). Hematopoietic stem cell source included mobilized peripheral blood (n=20), bone marrow (n=18) and umbilical cord blood (n=5). As GVHD prophylaxis regimens Cyclosporine plus Methotrexate (n=20) or Cyclosporine plus Mofetil micofenolate (n=23) were employed. In addition, 22 patients received rabbit antithymocyte globulin at 6-8mg/kg. At last follow-up four patients had relapsed 9-14 months after allo-SCT. We sought for leukemia-antigen specific CD8 lymphocytes in peripheral blood samples drawn within a median of 7 months (range 2-38) when lymphocyte recovery had occurred and complete donor chimerism was achieved. We used four color multiparametric flow cytometry in a FACSCanto II acquiring at least 5 ×105 viable (Propidium Iodide low) lymphoid gated events, stained with MnAbs: CD8-FITC and CD3PE/APC MnAb. To identify leukemia-antigen specific CD8 lymphocytes we used class I HLA pentamers 0201 APC or PE conjugated (Proimmune, London, UK) against the following nonapeptides: Proteinase 1: VLQELNVTV (169-177) WT1: RMFPNAPYL (126-134) and SURV: ELTLGEFLKL (95-104). As positive staining control we used CMV pp65: NLVPMVATV (495-503) and as negative controls we used irrelevant nonapeptide and peripheral blood samples from patients lacking HLA* 0201 genotype. RESULTS Detection of donor-derived CD8+ lymphocytes against CMV pp65 occurred in 61% of recruited patients with a median percentage of 0.1% (range 0.03-13 over CD3+CD8+ events). Likewise, it was possible to detect CD8+ lymphocytes specific for PR1, WT1 and SURV in 65.2%, 47.8% y 39.1% of recruited patients respectively. Median percentage of PR1 and WT1 leukemia-antigen specific lymphocytes was 0.1% (range 0.04-1% over CD3+CD8+ events) and for WT1 0.1% (range: 0.01-0.2%). Detection of leukemia-antigen specific CD8+ lymphocytes was not significantly associated with clinical variables such as conditioning regimen (conventional or non-myeloablative), Disease status at transplant, donor type (sibling or unrelated), ATG use or HLA-disparity degree. The presence of WT1 specific CD8+ lymphocytes was significantly more frequent in patients undergoing allo-SCT for lymphoid hematological malignancy (p=0.04). By contrast, the presence of circulating anti-PR1 specific CD8+ lymphocytes was not more frequently found in patients undergoing allo-SCT for myeloid malignancies. Of note, none of the four patients who eventually relapsed harbored circulating leukemia-specific CD8+ lymphocytes. CONCLUSIONS Multiparametric flow cytometry is a useful tool to detect and quantify rare donor-derived CD8+ lymphocytes specific for leukemia-associated antigens as PR1, WT1 or SURV. The presence of these populations in peripheral blood is not associated to conventional clinical variables and in our series anti-WT1 CD8+ lymphocytes were more frequently detected in patients receiving allo-SCT for lymphoid malingnacies. By contrast, larger series are needed to assess if the lack of these leukemia-associated antigen-specific CD8 lymphocytes in peripheral blood could identify patients in a higher risk of relapse. Financial support This study was supported by a grant of Conserjeria de Salud, Junta de Andalucia 2006/0355. J. Serrano López is a post-doc fellow from Fundación Española de Hematología y Hemoterapia Disclosures No relevant conflicts of interest to declare.

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Prevalence of Low Count (LC) Monoclonal B Cell Lymphocytosis (MBL) and Serious Infections in a Population-Based Cohort of U.S. Adults Participating in a Large Bio-Repository

Blood ◽

10.1182/blood.v130.suppl_1.831.831 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 831-831

Author(s):

Tait D. Shanafelt ◽

Neil E. Kay ◽

Curtis A. Hanson ◽

Sameer A. Parikh ◽

Sara J Achenbach ◽

...

Keyword(s):

Flow Cytometry ◽

B Cell ◽

Mayo Clinic ◽

Research Funding ◽

Olmsted County ◽

Sample Collection ◽

Serious Infection ◽

Clinical Records ◽

The Relationship

Abstract Background: There is little prospective, longitudinal data on the health outcomes of low count MBL in the U.S. adult population. We screened for MBL in asymptomatic adults with normal blood counts using highly sensitive flow-cytometry in a clinic-based cohort of participants from the Mayo Clinic Biobank and explored the relationship between MBL and risk of hospitalization with infection. Methods: The Mayo Clinic Biobank is a large scale biorepository of 50,000 adults (age>18) seen in primary care-based clinics. All consented participants completed a health history questionnaire and provided blood samples. For the present study, we focused on the study participants from Olmsted County, Minnesota, 40 years of age or older who had stored PBMC. We used these PBMC to screen for MBL using an 8 color (CD38, CD45, Kappa, Lambda, CD19, CD23, CD5 and CD20) flow cytometry assay validated to consistently detect clonal B-cell events to the 0.005% level (1/20,000 events). The sensitivity of this approach of collecting 500,000 events from isolated PBMC is 2-3-fold higher than collecting 500,000 events from whole blood due to the increased concentration of lymphocytes in these samples. Infections associated with hospitalization were considered serious or life-threatening infections. Every hospitalization at both Mayo Clinic and Olmsted Medical Center hospitals in Olmsted County, MN following the sample collection was reviewed to document hospitalization with infection. Data on hospitalization with infection was abstracted from clinical records using our previously published approach (Moriera, Leukemia 27:136). This approach allows medical record validation and review of detailed clinical and treatment information related to infection. For this analysis, follow-up began at date of sample collection and ended at the earliest of death, migration from Olmsted County, or 12/31/2016. The individual abstracting information on hospitalization for infection was blinded to the results of MBL screening. Chi-square tests were used to assess associations between MBL status and demographic characteristics. Cox regression models were used to determine association with risk of hospitalization with infection accounting for the competing risk of death using Fine Gray models. Results : We screened for MBL in 1045 Olmsted County residents age 40 and older. Of these, 984 (94%) had interpretable results. 119 of these 984 (12%) had a clonal B-cell population detected including 106 (11%) with CLL phenotype (CD5, CD19, CD20 [dim], CD23, kappa or lambda light chain restriction [dim]).This analysis focused on the 106 individuals with CLL-like MBL clones (mean age 69 years, 55% male) and the 865 individuals with normal immunophenotype (mean age 61 years, 40% male). The presence of CLL phenotype MBL was strongly associated with age. MBL was detected in 3% of patients age 40-49 years, 7% of those 50-59, 10% of those 60-69, 20% of those 70-79, and 27% of those age 80+ (p<0.001). MBL was also more common among men (women 8%; men 14%; p=0.003). After a median follow-up of 7 years from biobank enrollment, 76 of the 971 participants were hospitalized with infection in Olmsted County at least once. The estimated cumulative incidence of infections at 7 years was 19% for LC MBL and 9% for those without MBL (Figure). The most frequent site of infections for which these individuals were first hospitalized were pneumonia (14 individuals; 18%), cellulitis (20 individuals; 26%), urinary tract infection (21 individuals; 26%), and blood stream infection (6 individuals; 8%). An association between LC MBL and hospitalization with infection was observed with the unadjusted HR for hospitalization with infection among the 106 Olmsted County residents with LC MBL relative to the 865 Olmsted County residents with normal immunophenotype is 2.41 (95%CI: 1.39-4.19; p=0.002). After adjusting for age and sex, the HR is 1.65 (95% CI: 0.95-2.88; p=0.08). Conclusions: We report one of the first studies to systematically explore the relationship between LC MBL and the risk of serious infection. It appears that individuals with LC MBL may be at increased risk for serious infection. If this observation is confirmed, it would suggest that 5-10% of adults over age 40 (6-12 million U.S. adults) have a largely unstudied condition with potentially serious health implications. Figure 1 Figure 1. Disclosures Shanafelt: Hospira: Research Funding; AbbVie: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Jannsen: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Research Funding. Kay: Gilead: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Tolero Corporation: Research Funding. Parikh: Pharmacyclics: Research Funding; AstraZeneca: Honoraria; Pharmacyclics: Honoraria.

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Prognostic Value of Minimal Residual Disease before Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-119437 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5733-5733

Author(s):

Olga Pérez-López ◽

Teresa Caballero-Velázquez ◽

Enrique Colado ◽

Sara Alonso ◽

José González-Campos ◽

...

Keyword(s):

Flow Cytometry ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Value ◽

Residual Disease ◽

Hematopoietic Stem ◽

Multiparametric Flow Cytometry ◽

Minimal Residual ◽

Acute Myeloid

Abstract Introduction Several studies have shown that the minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has a prognostic value after induction and consolidation therapy. Nevertheless the relapse is the most important cause of treatment failure in these patients, although they achieved a negative MRD, and even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays, the value of the MRD before allogeneic BMT is still controversial. Method Multicentric study where we have studied correlative AML patients who went under an allo-HSCT in a situation of complete response, between 2012 and April'18. The MRD was analyzed by 8-coloured multiparametric flow cytometry, at least with 2 tubes per patient and 1,000,000 events per tube. We evaluated the prognostic value of the MRD before allo-HSCT. Results Between January'12 and April'18 we have gathered 90 allogeneic BMT in AML patients who were in CR, with a median age of 45 years old (17 - 66). The pre-HSCT situation was 1st complete remission (CR) in 75 patients and 2nd CR in 15. In 45 patients the conditioning regimen was myeoablative. In the group of patients (67) where we could know the risk group at diagnosis, the distribution was: low risk 18%, intermediate risk 59.7% and high risk 22.4%. The 46.7% of the donors were not related. In the last follow-up after allo-HSCT 24 patients have suffered a relapse (26.7%) and 41 (45.5%) have died (17 cases of mortality related to the transplant and 24 not related). In the global analysis the median follow-up of the overall survival (OS) was 37.5 months. Among the 90 patients, MRD was valuable in 86. Ten of 59 patients (16.9%) with negative MRD relapsed vs 12/27 (44.4%) with positive MRD, p= 0.016. If we consider only patients in 1st CR, 9/50 (18%) patients with negative MRD relapsed vs 10/22 (45.5%) with positive MRD, p= 0.02. This statistically significant difference does not exist if we consider only patients in 2nd CR. The median follow-up of OS and event free survival (EFS) was not reached in the negative MRD group and 571 days and 299 days in the positive MRD group. OS and EFS at 2 years after transplantation were 65% and 64% in the negative MRD group and 42% and 37% in the positive MRD group, p= 0.03 and p= 0.008 respectively (figure 1). Conclusions The detected MRD by 8-colour multiparametric flow cytometry previous an allo-HSCT in patients with AML in 1st CR is a prognostic factor in terms of relapse. Patients with a positive MRD before the allo-HSCT have a poorer OS and EFS than the patients with a negative MRD. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Insights Into The Natural History Of Paroxysmal Nocturnal Hemoglobinuria (PNH): Analysis Of The Presenting Clinical, Haematological and Flow Cytometric Features Of 705 Patients Leads To Improved Classification and Prediction Of Clinical Course

Blood ◽

10.1182/blood.v122.21.3718.3718 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3718-3718 ◽

Cited By ~ 1

Author(s):

Stephen John Richards ◽

Richard Kelly ◽

Anita Hill ◽

Anita Dickinson ◽

Fiona Cullen ◽

...

Keyword(s):

Flow Cytometry ◽

Board Of Directors ◽

Blood Count ◽

Clinical Course ◽

Red Cell ◽

Advisory Committees ◽

Clone Size ◽

Pnh Clone

Abstract In past 22 years, we have identified using flow cytometry 705 patients with detectable PNH (GPI deficient) populations of granulocytes, monocytes and red cells in the peripheral blood in samples sent for diagnosis. We undertook an analysis of presenting clinical features, blood count data and PNH clone sizes in order to better understand the natural history and provide a more objective classification of disease. Based on serial flow cytometry measurements of PNH clone sizes, we also studied disease stability, frequency of recovery and progression with an aim to guiding future management of individual patients. Clinical classification of patients at presentation was as follows; aplastic anemia (58%), hemolytic anemia (36.1%); myelodysplasia (2.5%); thrombosis (2.4%); hemolysis & thrombosis (0.6%), myeloproliferative neoplasm (0.3%); Fanconi anemia (0.1%). Median age at presentation was 45 years (observed range 0.5 – 90 years) and the Male:Female ratio was 1.05. Descriptive statistical analysis of presenting blood count data revealed novel gender related features not previously described in PNH. At presentation, pancytopenia was found in 61% of male and 47% of female patients; a normal blood count was present in only 0.3% of males and 4% of females. A combined low red blood cell count (RBC) and white cell count (WBC) was the most frequent bicytopenia affecting 19% males and 22% females. Leucopenia as a sole abnormality did not occur in males and was present in<1% of females; Leucocytosis was present in<1% of cases. Platelet counts were low in 79% of patients and normal in 20.3%. Low absolute numbers of RBC (mean 3.002 x 1012/L; IQR 2.52-3.47) were present in 97.6% of males and 87.6% of females (mean 3.009 x 1012/L; IQR 2.60 - 3.42). Similar findings were obtained for hemoglobin (Hb) values: males (mean 100.5 g/L; IQR 85-115): females (mean: 100.7 g/L; IQR 88-116). Unexpectedly, there were no statistically significant differences between male and female values for Hb or RBC counts. In a more detailed comparison, significant differences between aplastic PNH patients (n = 394) and hemolytic PNH patients (n = 245) were identified. Aplastic patients had significantly lower WBC, neutrophil, monocyte and platelet counts, and MCV (all P<0.01), though lymphocyte count was higher than in the hemolytic cohort. No statistical differences could be demonstrated for Hb or RBC counts between disease types or between males and females, confirming earlier results. For PNH clone sizes at presentation, aplastic patients showed a median red cell PNH clone size of 0.34% (IQR 0.05 - 2.14) and a median granulocyte PNH clone size of 2.58% (IQR 0.42 - 12.48). In contrast, hemolytic patients had a median red cell PNH clone size of 32.35% (IQR 22.04 - 51.67) and a median granulocyte PNH clone size of 90.61% (IQR 77.07 - 97.41). Follow up flow cytometry studies of 154 aplastic and hemolytic patients over a minimum period of 18 months (mean follow up 81 months, range 20-216 months), provided important insights into biology of the disease. Firstly, aplastic patients with granulocyte PNH clones of<1% at presentation, did not evolve to hemolytic PNH. Any increase in PNH clone sizes and progression to hemolytic disease within the aplastic cohort was associated with granulocyte clones of >5% at presentation, though this occurred in only 10/154 (6.5%) cases. For patients presenting with hemolytic disease, PNH granulocyte clones continued to increase in size in 44% of cases most likely reflecting a combination of on going selection in favour of the PNH clone and prompt diagnosis. In the 38 patients that presented with >95% granulocyte PNH clones, 92% remained stable over time (mean follow up 80 months (many on Eculizumab therapy)) with only 8% showing a gradual fall in clone size. The study shows that pancytopenia is a consistent feature of hemolytic and aplastic PNH patients. The degree of anemia is the same in both major groups of patients, but appears to be less severe for females. Not only are PNH clone sizes larger in hemolytic patients, but they also show higher platelet and leucocyte counts compared to aplastic patients, most likely reflecting a more active bone marrow. The data support the model that bone marrow failure is the primary underlying pathology in >95% of PNH patients and that sub classification on the basis of degree of aplasia, hemolysis (with or without thrombosis) and PNH clone size at presentation can be a powerful predictor of clinical course. Disclosures: Richards: Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kelly:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Hill:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Hillmen:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

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Infliximab for the treatment of CNS sarcoidosis

Neurology ◽

10.1212/wnl.0000000000004644 ◽

2017 ◽

Vol 89 (20) ◽

pp. 2092-2100 ◽

Cited By ~ 56

Author(s):

Jeffrey M. Gelfand ◽

Michael J. Bradshaw ◽

Barney J. Stern ◽

David B. Clifford ◽

Yunxia Wang ◽

...

Keyword(s):

Neurologic Recovery ◽

Clinical Responses ◽

The Mean ◽

Treatment Responses ◽

Factor Α ◽

Lost To Follow Up ◽

Necrosis Factor ◽

Clinical Stability

Objective:To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α.Methods:Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.Results:Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.Conclusions:Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.Classification of evidence:This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

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Surgical Strategy and Facial Nerve Outcomes in Petrous Bone Cholesteatoma

Audiology and Neurotology ◽

10.1159/000448584 ◽

2016 ◽

Vol 21 (5) ◽

pp. 275-285 ◽

Cited By ~ 15

Author(s):

Sampath Chandra Prasad ◽

Gianluca Piras ◽

Enrico Piccirillo ◽

Abdelkader Taibah ◽

Alessandra Russo ◽

...

Keyword(s):

Facial Nerve ◽

Petrous Bone ◽

Common Type ◽

Active Management ◽

Nerve Grafting ◽

The Mean ◽

Transotic Approach ◽

Petrous Bone Cholesteatoma

Objective: To review the classification and management of petrous bone cholesteatomas (PBCs) at our center and the outcomes of facial nerve (FN) management in these lesions. Methods: This was a retrospective study. The setting was a quaternary referral center for skull base pathology in Italy. A total of 200 patients with 201 PBCs were included in the study. All patients diagnosed radiologically with PBCs were classified according to the Sanna classification. All patients were surgically treated and followed up with radiology. The main outcome measures - classification of PBCs, the surgical approach used, disease control, and FN outcomes - were analyzed. Results: Supralabyrinthine PBCs were the most common type with 92 cases (45.8%) followed by the massive PBCs with 72 cases (35.8%). Preservation of preoperative FN function was highest in the infralabyrinthine (72.2%) and infralabyrinthine-apical (73.3%) types. The transotic approach was used in 66 cases (32.8%) in this series. The modified transcochlear approach type A was applied in 55 cases (27.3%). Active management of the nerve (rerouting, anastomosis, or grafting) was required in 53 cases (26.4%). Postoperatively, of the 116 cases with FN House-Brackmann grade I and II, 107 cases (92.2%) retained the same grade or improved. Recurrence was seen in 7 cases (3.5%). The mean duration of follow-up was 6.3 years. Conclusions: Radical disease clearance must take precedence over hearing and FN preservation in PBCs. Active FN management, including rerouting, end-to-end anastomosis, and cable nerve grafting, routinely come to play in the surgical management of PBCs, and the postoperative FN results after such interventions can be satisfactory in most cases.

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Mineral cloud and hydrocarbon haze particles in the atmosphere of the hot Jupiter JWST target WASP-43b

Astronomy and Astrophysics ◽

10.1051/0004-6361/202037633 ◽

2020 ◽

Vol 641 ◽

pp. A178 ◽

Cited By ~ 1

Author(s):

Ch. Helling ◽

Y. Kawashima ◽

V. Graham ◽

D. Samra ◽

K. L. Chubb ◽

...

Keyword(s):

Cloud Formation ◽

Phase Curve ◽

Hot Jupiters ◽

Thermodynamic Conditions ◽

Pressure Scale ◽

The Mean ◽

Cloud Particles ◽

Mean Molecular Weight ◽

Insight Into

Context. Having a short orbital period and being tidally locked makes WASP-43b an ideal candidate for the James Webb Space Telescope (JWST) phase curve measurements. Phase curve observations of an entire orbit will enable the mapping of the atmospheric structure across the planet, with different wavelengths of observation allowing different atmospheric depths to be seen. Aims. We provide insight into the details of the clouds that may form on WASP-43b and their impact on the remaining gas phase, in order to prepare the forthcoming interpretation of the JWST and follow-up data. Methods. We follow a hierarchical modelling strategy. We utilise 3D GCM results as input for a kinetic, non-equilibrium model for mineral cloud particles and for a kinetic model to study a photochemically-driven hydrocarbon haze component. Results. Mineral condensation seeds form throughout the atmosphere of WASP-43b. This is in stark contrast to the ultra-hot Jupiters, such as WASP-18b and HAT-P-7b. The dayside is not cloud free but it is loaded with few yet large mineral cloud particles in addition to hydrocarbon haze particles of a comparable abundance. Photochemically driven hydrocarbon haze appears on the dayside, but it does not contribute to the cloud formation on the nightside. The geometrical cloud extension differs across the globe due to the changing thermodynamic conditions. Day and night differ by 6000 km in pressure scale height. As reported for other planets, the C/O is not constant throughout the atmosphere and varies between 0.74 and 0.3. The mean molecular weight is approximately constant in a H2-dominated WASP-43b atmosphere because of the moderate day/night-temperature differences compared to the super-hot Jupiters. Conclusions. WASP-43b is expected to be fully covered in clouds which are not homogeneously distributed throughout the atmosphere. The dayside and the terminator clouds are a combination of mineral particles of locally varying size and composition as well as of hydrocarbon hazes. The optical depth of hydrocarbon hazes is considerably lower than that of mineral cloud particles such that a wavelength-dependent radius measurement of WASP-43b would be determined by the mineral cloud particles but not by hazes.

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Endoscopic Surveillance for Metachronous Esophageal Squamous Cell Neoplasms among Head and Neck Cancer Patients

Cancers ◽

10.3390/cancers12123832 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3832

Author(s):

Yi-Hsun Chen ◽

Yao-Kuang Wang ◽

Yun-Shiuan Chuang ◽

Wen-Hung Hsu ◽

Chao-Hung Kuo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Second Primary ◽

Primary Neoplasm ◽

The Mean ◽

Squamous Cell Neoplasms

Esophageal squamous cell neoplasms (ESCNs) are the most common second primary neoplasm in patients with head and neck squamous cell carcinoma (HNSCC), and few studies have focused on metachronous ESCNs. We aimed to evaluate the incidence of and risk factors for metachronous ESCNs and to provide a reasonable endoscopic follow-up plan for HNSCC patients. We extended our prospective cohort since October 2008 by recruiting incident HNSCC patients. All enrolled patients were interviewed to collect information on substance use (smoking, alcohol, and betel nut) and esophagogastroduodenoscopy (EGD) with Lugol chromoendoscopy results for synchronous ESCNs soon after HNSCC diagnosis. Endoscopic screenings for metachronous ESCNs were performed 6 to 12 months after the previous examinations. A total of 1042 incident HNSCC patients were enrolled, but only 175 patients met all the criteria and were analyzed. A total of 20 patients had metachronous ESCNs (20/175, 11.4%). Only the initial Lugol-voiding lesion (LVL) classification significantly predicted the development of metachronous ESCNs. Patients with an LVL classification of C/D had a higher risk of developing metachronous ESCNs than those with an LVL classification of A/B (adjusted odds ratio: 5.03, 95% confidence interval: 1.52–16.67). The mean interval for developing metachronous ESCNs was 33 months, but the shortest interval for developing metachronous esophageal squamous cell carcinoma was 12 months. Lugol chromoendoscopy screening among incident HNSCC patients predicts the risk of developing metachronous ESCNs. A closer follow-up with an endoscopy every 6 months is recommended for those with LVL classifications of C and D.

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