Development of an Algorithm To Differentiate Uterine Sarcoma From Fibroid Using MRI and LDH Levels

This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined using a test set of 61 cases, including 14 cases of uterine sarcoma, by four evaluators with different imaging experience and abilities. From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroid, we found that all sarcomas were included in the group with high T2WI and either high T1WI, unclear margin, or high LDH value. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings in T2WI, T1WI, margin, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators, and the sensitivity of sarcoma detection ranged from 71–93%. We established an algorithm that is not uterine sarcoma if tumors in the myometrium with low T2WI and DWI.

ASYMPTOMATIC SARS-CoV-2 INFECTION IN CHILDREN

The aim was to determine hematological and biochemical changes in children who are carriers of SARS-CoV-2. Unlike H1N1 influenza-like illness the predictive factors of SARS-CoV-2 in asymptomatic children (carriers of SARS-CoV-2) are distinctive ratio between lymphocytes and monocytes more than 2, with occasional eosinophila, and a dicrease in erythrocyte indices (MCH and MCV), and a rapid and strong increase in serum LDH value. The predictive factors are, presumably, useful for fast and cheap triage of children “from contact” until a PCR test result for SARS-CoV-2 arrives.

Incomplete Complement Inhibition in Patients with PNH on Eculizumab - 5 Year Experience from the National PNH Service Leeds

Background Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired disorder characterised by intravascular hemolysis and thrombosis. Patients with symptomatic PNH are commenced on the complement inhibitor eculizumab (600mg weekly for 5 weeks then 900mg 2 weekly). This monoclonal antibody targets C5 in the complement cascade, halting terminal complement activation thus inhibiting intravascular hemolysis. In some patients intravascular hemolysis is not adequately controlled on the standard regimen. Patient symptoms, transfusion requirements and raised Lactate dehydrogenase (LDH) levels are indicators for suboptimal control of PNH and review of eculizumab dosing. The 50% hemolytic complement (CH50) test is a functional assay assessing capability of serum complement components of the classical pathway to lyse sheep red blood cells pre-coated with rabbit anti-sheep red blood cell antibody. Patients with complement inhibited PNH should demonstrate absent lysis. As the test is expensive and difficult to organise, we tested if incomplete complete blockade as determined by CH50 activity would be better to confirm under-dosing than LDH value. Methods The Leeds (UK) PNH National Service reviewed patients who underwent CH50 assay between January 2015 and March 2020. All patients were on eculizumab with clinical concerns regarding suboptimal control of PNH. Patients receive eculizumab infusions intravenously every 14 days and routine follow up from the PNH Service. Serum samples were obtained 24 hours prior to infusions for CH50 assay; LDH values were routinely collected. Complete complement blockade was defined by <10% CH50 activity; intravascular hemolysis was indicated by LDH value >1.5x upper limit of normal (ULN). Confidence intervals were set at 95% and significance set at p<0.05. Results In the study period, 327 tests (median 2, range 1 - 8) were carried out in 146 patients (median age 54 years, range 16 - 89; 74 female). 81% (265) were successful; 19% (62) were unsuccessful due to processing errors. Of the successful tests, 74% (197 in 127 patients) indicated complete complement blockade and 26% (68 in 38 patients) indicated incomplete blockade. Of the patients with incomplete blockade, 68% (26) demonstrated complete blockade on repeat testing and 32% (12) had their eculizumab dose increased. Clinical symptoms of under-dosing in the 12 patients requiring a dose increase included increased transfusion requirements and/or breakthrough hemolysis (7), pregnancy (2; both returned to 900mg post pregnancy) and significant lethargy (3). Of the patients requiring a dose increase, 3 were on 1200mg before 2015; their dose was increased to 1500mg. Repeat testing was carried out in 10/12 patients after dose increase; 8 indicated complete blockade; 2 patients were incompletely blocked at 1200mg and received a further dose increase to 1500mg. Further testing indicated complete blockade in 1 patient; 1 required a 3rd dose increase to 1800mg due to incomplete blockade and ongoing transfusion requirement. Corresponding LDH values were analysed; median LDH for the complete blockade group was 1.16xULN (range 0.54 - 2.16) and 1.28xULN (range 0.76 - 2.38) for the incomplete blockade group. LDH values were not significantly higher in the incomplete blockade group compared to the complete blockade group, p=0.08. There was no significant difference in LDH values pre- and post-dose increase, p=0.38 (Figure 1); median pre-dose increase LDH 1.14xULN; median post-dose increase LDH 1.13xULN. Correlation coefficient shows that CH50 activity was positively correlated with LDH value, r(123)=0.18, p=0.04. Conclusion We report the effective utilisation of CH50 analysis where there is clinical concern of suboptimal control of PNH. All patients demonstrating hemolytic activity on CH50 assays indicated subsequent complement blockade following increase of eculizumab dose. Increasing eculizumab is costly requiring robust evidence of suboptimal complement inhibition; a positive correlation between CH50 activity and LDH values was shown however this is not sufficient to guide clinical decisions. LDH values of the incomplete blockade group were not significantly higher than those with complete blockade, suggesting the use of LDH values as an assessment of complement inhibition in patients with ongoing symptoms or transfusion requirements is not sufficient to guide eculizumab dose increases. Disclosures Munir: Alexion: Honoraria; F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Pike:Apellis: Research Funding. Arnold:Alexion Pharmaceuticals: Honoraria. Hillmen:AstraZeneca: Consultancy, Speakers Bureau; Alexion: Consultancy, Research Funding, Speakers Bureau; Acerta: Other: Financial or material support; Roche: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; Pharmacyclics: Other: Financial or material support, Research Funding; Janssen: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; Apellis: Consultancy, Research Funding, Speakers Bureau; Gilead: Other: Financial or material support, Research Funding. Griffin:Alexion Pharmaceuticals: Honoraria, Other: Conference Support; Biocryst: Membership on an entity's Board of Directors or advisory committees.

The value of bendamustine dose and cycles, sIL-2R, and LDH in follicular lymphoma patients treated with bendamustine plus rituximab.

e20055 Background: Bendamustine plus rituximab therapy (BR) is one of the mainstays of therapy for follicular lymphoma (FL) patients (pts). Adverse events such as lymphopenia, neutropenia, and skin lesions sometimes prevent the completion of six cycles of BR. Till date, the bendamustine dose, treatment cycle of BR, and prognostic markers of FL response to BR have not been analyzed sufficiently. Methods: We retrospectively evaluated 56 FL pts treated with BR from January 2011toJanuary 2019 at our hospital; 19 pts and 37 pts received BR as first-line therapy and salvage therapy, respectively. Results: There was no statistical difference in the response rate, OS, and PFS between the first-line group and the salvage group. The table summarizes the survival analyses. Comparing the OS and PFS according to FL grades 1, 2, and 3 in all pts, there were significant differences in both OS (P = 0.0028) and PFS (P = 0.0058). Patients were divided into two groups based on a cutoff sIL-2R value of 682 U/mL; survival benefits were observed in the sIL-2R-low group in OS (P = 0.0226) and PFS (P = 0.0265). Similarly, on dividing the pts into two groups based on a cutoff LDH value of 225 U/L, survival benefits were observed in the LDH-low group in OS (P = 0.0375) and PFS (P = 0.0453). The LDH value was significantly high in pts with progression of disease within 24 months (POD24) compared to pts without POD24 (P = 0.0134). However, there was no statistical relationship between sIL-2R and POD24.The rate of treatment cycles ≧4 was 69%, and the mean number of treatment cycles was 4.3. Survival benefits were observed in pts who were treated for more than 3 cycles in OS (P = 0.0094) and PFS (P = 0.0103). The mean bendamustine dose was 78.5 mg/m2. Conclusions: Approximately 30% pts could not receive more than 3 cycles of BR, probably because of adverse events and preexisting bone marrow suppression with previous chemotherapy, suggesting that 90 mg/m2of bendamustine in BR may be excessive, especially in pts requiring salvage therapy. Our data suggest that 75−80 mg/m2of bendamustine may be appropriate. Our survival data also suggest that new treatment strategies may be needed for FL pts with high levels of sIL-2 ( >682 U/mL) and LDH ( >225 U/L) and grade 3 disease. [Table: see text]

UJI DAYA HAMBAT SEDIAAN SABUN CAIR EKSTRAK DAUN PALA (Myristica fragrans houtt) TERHADAP Propionibacterium acnes dan Staphylococcus aureus

Bacteria that cause acne include Staphylococcus aureus and Propionibacterium acnes. Nutmeg leaves are plants that contain antibacterial substances that can inhibit bacterial growth. The purpose of this study is to make soap preparations from nutmeg leaf extracts and find out the formula that is most effective in inhibiting the growth of P.acnes and Staphylococcus aureus bacteria. Nutmeg leaves were extracted using maceration method with 96% ethanol solvent. Liquid soap preparations are made in 4 formulas. Antibacterial activity test was carried out by the dilution method for MIC and disk diffusion methods to determine LDH liquid soap preparations. Based on the test of the antibacterial activity of 96% ethanol extract, nutmeg leaves have the ability to inhibit the growth of Staphylococcus aureus with a MIC value at a concentration of 0.5% and negative on Propionibacterium acnes. Liquid soap preparations in F1 (extract 2%) have LDH values of 9.87 ± 0.41 mm; F2 (extract 4%) has an LDH value of 10.50 ± 0.35 mm; F3 (extract 8%) has an LDH value of 10.70 ± 0.25 mm; F4 (extract 10%) has an LDH value of 11.87 ± 0.25 mm. The highest LDH value is F4 with a concentration of 10% extract, LDH F4 is a formula that has the most antibacterial activity approaching LDH positive control JF Sulfur which has an LDH value of 13.25 ± 0.25 mm

Natural History of Paroxysmal Nocturnal Hemoglobinuria Clones In Patients Presenting as Aplastic Anemia

Abstract 4428 Introduction: Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are closely related bone marrow failure disorders. Most AA results from an autoimmune attack directed against hematopoietic stem/progenitor cells. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a PIG-A mutation. The PIG-A gene mutation leads to glycosylphosphatidylinositol-anchor protein (GPI-AP) biosynthesis deficiency and subsequent hemolysis secondary to the absence of complement regulatory proteins (CD55 and CD59). Both PNH and AA can be cured by allogeneic bone marrow transplantation (alloBMT), but only a minority of patients is offered this approach due to the potential morbidity and mortality. AA can be treated with immunosuppressive therapy (IST) and PNH can be controlled by eculizumab. It has been estimated that more than 50% of AA patients harbor small, but expandable PNH populations at diagnosis. The natural history of PNH clones in AA patients following non-transplant therapy is not well studied. The purpose of this study is to determine the fate and clinical relevance of these PNH clones in patients with AA who did not receive an alloBMT. Patients and Method: Twenty-seven patients with AA and a detectable PNH clone were monitored for a median of 5.3 years (range,1.5 to 11.5 years). The PNH granulocyte clone sizes were measured using flow cytometry and analyzed via CellQuest software. PE-conjugated anti-CD15 and fluoresceinated aerolysin variant (FLAER) staining were used to define granulocytes and GPI-AP deficient cells respectively. Serum lactate dehydrogenase (LDH) value was used as a surrogate for monitoring hemolysis and 1.5× the upper limit of normal LDH value (330mg/dL) as a cut-off point to define clinically apparent hemolysis. A PNH size change <2.5% was considered as stable. Patients were treated with IST, HiCy, or both. Result: We found a linear relationship between PNH granulocyte clone size and LDH values (Pearson correlation coefficient=0.73; P<0.0001). A PNH clone size above 23% was the threshold to identify hemolysis as measured by LDH (ROC analysis with AUC=0.88). Higher LDH values over the period of follow-up were associated with larger PNH granulocyte clone size at diagnosis (P=0.03). Patients with small (≤15%) initial PNH granulocytes had lower LDH levels at 5 years after diagnosis (mean±SD: 236.9±109.9 vs 423.1±248.8; P=0.02), and were less likely to develop hemolysis (13.3% vs 55.6%, P=0.06) comparing to those with larger (>15%) initial PNH granulocytes. Of 9 patients who initially were treated with traditional IST (ATG, CsA, and prednisone), 7 did not respond to treatment and eventually received high-dose cyclophosphamide (HiCy) salvage therapy, 2 achieved a remission and did not require further treatment though one demonstrated PNH clone size expansion to 50% after 37 months. After HiCy salvage, all 7 patients became transfusion independent and 4 of them had no further PNH clone expansion. PNH clone expansion was observed in 7 of 9 patients at a median time of 3 (range: 2 to 87) months after treatment. Of 15 patients who received HiCy as initial therapy, 14 achieved remissions. Later expansion of PNH size was observed in 7 patients, of which 5 eventually required intermittent blood transfusion but only 1 developed symptomatic hemolysis necessitating eculizumab therapy. The median time to PNH granulocyte clone expansion after HiCy was 52 (range: 18 to 106) months. In 5 patients who received HiCy and then relapsed, their PNH clone size only increased (1±0.7)% in (71±31) months observation during post treatment remission; however, their PNH clone size increase accelerated to (38±14)% in (34±21) months after AA relapse (P=0.04). Two nSAA patients with an initial PNH clone size ≤15% spontaneously recovered hematopoiesis at 84 and 56 months respectively, neither had PNH clone size expansion. In this study, 25.9% patients kept a stable PNH size, 48.1% patients increased the size, and 26% patients decreased the size. The group with small initial PNH clone sizes (≤15%) was the most stable over time. Conclusion: The risk of developing clinically significant PNH over 10 years appears to be low in AA patients with PNH clones, especially for those with small initial PNH granulocyte clones (≤15%) and for those who maintain remission following therapy. Disclosures: No relevant conflicts of interest to declare.

Room Temperature Formability of Mg Alloys

Room temperature formability of twin-roll cast Mg alloys has been investigated and correlated with their work hardening behavior. Tensile properties of these alloys were measured and their work hardening behaviour was analysed by using constitutive equations. Room temperature formability of the alloys was evaluated by the limiting dome height (LDH) value, obtained by the Erichsen cupping test. It shows that there is a linear relationship between LDH value and the inverse of yield ratio, which is a function of work hardening exponents. An increase in grain size increases work hardening exponent and concurrently increases LDH.

Primary Colonic Lymphoma

Surgical resection of primary colonic lymphoma can be an important therapeutic tool. We performed a nonrandomized retrospective descriptive study at the University hospital tertiary care center. From January 1990 to June 2002, a total of 15 patients with primary colonic lymphoma were identified from the tumor registry at University of Alabama at Birmingham and retrospectively reviewed under Institutional Review Board approved protocol. Demographic data, clinical features, treatment method (surgery and/or chemotherapy), recurrence rate, and survival were analyzed. The results are presented as mean ± standard deviation or median and range. Differences in survival were evaluated by the log-rank test and the interval of disease-free survival was calculated using the Kaplan-Meier method. A P value of <0.05 was considered statistically significant. Main outcome measures included surgical results, morbidity, mortality, and recurrence rate. Mean age was 51.5 years (standard deviation 16.4), 33 per cent were male and 67 per cent were female. Presenting symptoms were diarrhea (53.5%), lower gastrointestinal bleeding (13.3%), and nausea and vomiting (46.7%) secondary to low-grade obstruction. Concomitant colorectal disease was present in one patient with ulcerative colitis. Preoperative diagnosis of lymphoma was made in 13 patients (87%) with colonoscopy and biopsy. CT scan was performed in all patients; and none had radiographic evidence of systemic extension. Only one patient had a history of lymphoproliferative disease and exposure to radiation. The most common disease location was the cecum (60%), followed by the right colon (27%), and the sigmoid colon (13%). The mean lactic dehydrogenase (LDH) value was 214.9 u/L (range 129–309). Thirty-three per cent of the patients had an LDH value that was above the upper normal limit. LDH returned to normal after treatment in all patients. Operations performed consisted of right hemicolectomy (13), total proctocolectomy with ileal J J-pouch (1), and sigmoid colectomy (1). Eighty-seven per cent had negative margins at the time of operation. Twelve patients received postoperative chemotherapy (80%). According to the clinical classification of primary non-Hodgkin lymphoma (NHL) of the gastrointestinal tract (Lugano, 1993) all patients corresponded to stage IE. Mean hospital stay was 6.4 days (range 3–26). There was no surgical mortality and the morbidity rate was 20 per cent (3 patients). One patient had a systemic recurrence (7%) approximately 4 months after surgical resection. Mean follow-up was 31 months (median 2–73). Surgical resection of localized, primary colonic lymphoma provides excellent local disease control and should be considered a primary treatment option. The role of chemotherapy remains controversial depending on the grade, stage, and extension of residual disease.