Tixagevimab/cilgavimab (AZD7442/Evusheld) prevent from COVID19 in patients with hematologic malignancies under active chemotherapy.

Despite the efficacy of COVID-19 vaccines, patients with hematologic malignancy may still be fatal from COVID19. Therefore, we prospectively performed the analysis of administration of tixagevimab/cilgavimab in the real-world. In August 2022, 94 patients under active chemotherapy for lymphoma, multiple myeloma, or acute leukemia received a single dose AZD7442/Evusheld (two consecutive intramuscular injections of tixagevimab and cilgavimab, 300 mg each). Quantitative measurement of anti-SARS-CoV-2 spike protein (anti-S) and viral nucleocapsid (anti-N) titers were conducted before administration of tixagevimab/cilgavimab and at 1, 3, and 6 months after administration. Twenty-five patients (26.6%) had previously confirmed COVID-19 infection. Fifty-eight patients (61.7%) had previously received COVID-19 vaccinations, with a median of two doses (range, 1-5). The median anti-S Ab level increased from baseline (997.05 AU/mL) to 1 month (20,967.25 AU/mL), then decreased at 3 months (13,145.0 AU/mL), and 6 months (7123.0 AU/mL) (p < 0.001). There was no significant safety issue with tixagevimab/cilgavimab. With a median follow-up time of 6 months, thirteen patients (13.8%) had documented SARS-Cov-2 infection. A 20.2% rate of anti-N positivity was observed six months after the administration of tixagevimab/cilgavimab. The results of this study support the potential role of tixagevimab/cilgavimab for the prevention of symptomatic and severe COVID-19.Trial registration: KCT0007617; August 16, 2022.

Ischemia-modified albumin: a novel blood marker of endoscopic mucosal healing in inflammatory bowel disease.

BACKGROUND/AIMS: The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity. METHODS: A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn's disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings. RESULTS: Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed. CONCLUSIONS: IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.

T-large granular lymphocytic leukemia.

T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway. Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

Performance Validation of Three Scoring Systems for the Prediction of Thrombotic Microangiopathy Due to Severe ADAMTS13 Deficiency and the Response to Therapeutic Plasma Exchange: First Study in Korea.

Background: The BENTLEY score (B-S), French thrombotic microangiopathy (TMA) Reference Center score (FTMA-S), and PLASMIC score (PLASMIC-S) have been developed for TMA diagnostic prediction. We retrospectively validated their predictive performances in patients with severe (<10%) disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in terms of the risk of TMA and response to therapeutic plasma exchange (TPE). Methods: The predictive performances of the three scoring systems were compared in 145 patients with suspected TMA who underwent ADAMTS13 activity tests between January 2014 and September 2022. The response to TPE and mortality in TMA-positive patients were compared after risk stratification, using the Mann-Whitney U and Fisher's exact tests. Results: The PLASMIC-S, FTMA-S, and B-S showed area under the curve values of 0.820, 0.636, and 0.513, respectively, for predicting TMA positivity in high-risk patients. The PLASMIC-S showed higher sensitivity (81.8%), negative predictive value (91.2%), positive predictive value (PPV; 66.7%), and accuracy (82.1%) than the FTMA-S (72.7%, 82.1%, 41.0%, and 60.0%, respectively) and B-S (4.6%, 70.2%, 50.0%, and 69.7%, respectively). The PLASMIC-S also showed higher specificity than the FTMA-S (82.2% vs. 54.5%). The modified PLASMIC-S, including lactate dehydrogenase/upper limit of normal ratios, increased the specificity, PPV, and accuracy to 97.0%, 92.3%, and 92.4%, respectively. In TMA-positive patients, high risk assessed by the PLASMIC-S predicted higher platelet recovery rates and less TPE sessions required for recovery than for those assessed at low-to-intermediate risk. Conclusions: PLASMIC-S is the preferred scoring system for detecting patients with TMA positivity and for prognosis before confirmation of ADAMTS13 activity.

Research use only and cell population data items obtained from the Beckman Coulter DxH800 automated hematology analyzer are useful in discriminating MDS patients from those with cytopenia without MDS.

We investigated the performance of research use only/cell population data (RUO/CPD) items obtained from the Beckman Coulter DxH800 automated hematologic analyzer in discriminating MDS patients from cytopenic patients without MDS.Total of 14 routine CBC, 18 research use only (RUO) items, and 70 CPD items were obtained retrospectively at diagnosis. The results were then compared between 94 MDS patients and 100 cytopenic patients without MDS. In items with statistically significant differences, receiver operating characteristic (ROC) analysis was performed and the results were compared.Four CBC/RUO items [red cell distribution width-standard deviation (RDW-SD), immature reticulocyte fraction (IRF), mean sphered cell volume (MSCV), high light scatter reticulocytes (HLR)], and two CPD items [mean volume of neutrophils (NE-V-Mean) and mean volume of early granulated cells (EGC-V-Mean)] showed area-under the curve (AUC) scores > 0.750. Notably, four RUO/CPD items (MSCV > 81.4/HLR > 0.15%/NE-V-Mean > 145/EGC-V-Mean > 156) showed high sensitivity (91.9%/93.6%/88.1%/90.2%, respectively) in discriminating MDS patients from cytopenic patients without MDS. With these six items, scores ≥ 4 (defined as ≥ 4 items exceeding cutoff values out of six items) showed AUC scores/sensitivity/specificity/accuracy (0.891/87.3%/79.0%/83.0%, respectively).Six CBC/RUO/CPD items showed satisfactory AUC scores of > 0.750, and four RUO/CPD items showed high sensitivity in discriminating MDS patients from cytopenic patients without MDS. Scoring system with six items showed high sensitivity, specificity, and accuracy with decision criteria of ≥ 4 scores. Therefore, DxH800 RUO/CPD items would be useful in discriminating MDS patients from cytopenic patients without MDS.

A robust scheme for unidirectional emission from a hybrid whispering gallery cavity system based on transformation optics.

Using the transformation cavity, a gradient index cavity designed by transformation optics, we propose a hybrid resonator system to extract unidirectional narrow-beam emission from high-Q whispering gallery modes by embedding a transformation cavity inside a deformed uniform index cavity that exhibits unidirectional narrow-beam emission. For effective mode coupling between the transformation cavity and enclosing cavity, the embedded transformation cavity is designed to have bidirectional evanescent emission, which enables most of the emission from the transformation cavity to be laterally incident on the rim of the enclosing deformed cavity. Consequently, ultrahigh-Q resonances of this system can provide a sharp free-space light output, which is difficult to achieve by embedding a homogeneous disk cavity instead of the transformation cavity.

Birefringent whispering gallery cavities designed by linear transformation optics.

It was reported that whispering gallery cavities designed by conformal transformation optics can support high-Q resonant modes with emission directionality. Intrinsically, these cavities have gradient index profiles implementing conformal mappings in physical space. In this paper, using the linear coordinate transformation, we propose another design scheme of whispering gallery cavities with (piecewise-) homogeneous, anisotropic index profile. We numerically show that so-designed cavities are also able to support high-Q whispering gallery modes with directional far-field emission patterns. We verify such characteristics by using a phase space representation (called the Poincaré Husimi function) of the intracavity wave function.

Universal light-guiding geometry for on-chip resonators having extremely high Q-factor.

By providing an effective way to leverage nonlinear phenomena in integrated devices, high-Q optical resonators have led to recent advances in on-chip photonics. However, developing fabrication processes to shape any new material into a resonator with extremely smooth surfaces on a chip has been an exceptionally challenging task. Here, we describe a universal method to implement ultra-high-Q resonators with any new material having desirable properties that can be deposited by physical vapor deposition. Using this method light-guiding cores with surface roughness on the molecular-scale are created automatically on pre-patterned substrates. Its efficacy has been verified using As2S3, a chalcogenide glass that has high-nonlinearity. The Q-factor of the As2S3 resonator so-developed approached the propagation loss record achieved in chalcogenide fibers which were limited by material losses. Owing to the boosted Q-factor, lasing by stimulated Brillouin scattering has been demonstrated with 100 times lower threshold power than the previous record.

Distinct Clinical Features of Plasma Cell Myeloma Patients Exhibiting Dysmorphic Plasma Cells: Association with More Plasma Cells at Diagnosis.

Dysmorphic plasma cells are occasionally found in bone marrow (BM) aspirates of plasma cell myeloma (PCM) patients. We retrospectively analyzed the incidences of significant dysmorphic plasma cells (SDPC) presentations and their associations with clinical features in PCM patients. Total 91 PCM patients diagnosed from January 2013 to December 2017 at author's institution were enrolled. SDPC presentation was determined as ≥ 5% (SDPC5) or ≥ 10% (SDPC10) among total PC and clinical features of PCM patients were compared with respect to SDPC presentation status. Incidence of SDPC5/SDPC10 presentation was 39.6%/18.7%. Patients with SDPC5/SDPC10 showed significantly more BM PC (P = 0.004/0.020) and higher incidences of CKS1B gains (P = 0.022/0.001) and RB1 loss (P = 0.032 for SDPC10 only) at diagnosis than those without SDPC5/SDPC10. Patients with SDPC5/SDPC10 also showed significantly greater absolute BM PC (P = 0.007/0.034 and 0.047/0.049 for 1st and 2nd follow-up, respectively) and serum M-protein (P = 0.041/0.044 and 0.039/0.049 for 1st and 2nd follow-up, respectively) reductions after chemotherapy than those without SDPC5/SDPC10. SDPC5/SDPC10 presentation was confirmed as an independent predictor of BM PC ≥ 37.7% [hazard ratio (HR) 4.649/2.613, P = 0.005/0.039]. Our present study demonstrated that SDPC presentation would be an independent predictor of more BM PC at diagnosis in PCM patients. Associations between SDPC presentation and higher incidence of CKS1B gains and RB1 loss, greater PC/serum monoclonal protein reductions after chemotherapy were also identified. Association between SDPC presentation and favorable treatment response should be evaluated in more comprehensive study.

Performance Evaluation of Automated Immunohematology Analyzer IH-500 for Blood Bank Testing.

The automated immunohematology analyzer IH-500 (Bio-rad, Cressier FR, Switzerland) was developed recently for blood bank tests and this study evaluated performance of IH-500. 200 blood samples for ABO/Rh typing were collected. ABO/Rh typing results measured by IH-500 was compared with conventional manual methods. Antibody screening tests were performed with 100 samples using both IH-500 and the Ortho BioVue System, and results were compared. Antibody identification tests were conducted on 5 samples using both IH-500 and the Ortho BioVue System and results were compared. Crossmatching was performed with both IH-500 and conventional manual tube method using 4 patient serum samples and 10 blood cell donors, and 40 results were compared. Isoagglutinin titer of anti-A and anti-B was determined in 10 samples using both IH-500 and the automated analyzer Ortho AutoVue Innova and concordance rates were obtained. The concordance rates of ABO/Rh typing, antibody screening test, antibody identification test, and crossmatching between comparative manual methods and the IH-500 were all 100%. In the evaluation of isoagglutinin titer, 8 (80.0%) results out of 10 samples (80%) showed results within ± 1 titer between the IH-500 and the AutoVue Innova, which indicates the concordance rates of 80.0%. IH-500 reported results with two titers lower than Ortho AutoVue Innova in two samples. The IH-500 demonstrated good concordance rates and provided reliable results compared to comparative manual methods in the blood bank testing. IH-500 would be useful as a possible replacement for conventionally performed manual methods in blood bank testing.

Clinical Utility of 18F-Florbetaben PET for Detecting Amyloidosis Associated With Multiple Myeloma: A Prospective Case-Control Study.

PURPOSE: The aims of this study were to evaluate the diagnostic performance of F-florbetaben PET/CT for detecting amyloid deposits in patients with multiple myeloma (MM) and to identify the optimal PET analysis method. METHODS: Fourteen patients with MM were prospectively enrolled (6 with amyloidosis, 8 control subjects). Dynamic imaging of the kidneys was performed for 20 minutes, and the retention ratio was obtained. At 90 minutes after injection, PET was performed. All images were assessed qualitatively and quantitatively, and the SUVmax, SUVmean, and SUVratio were obtained. Variables were compared between the amyloidosis group and the control group. Amyloid deposition was confirmed according to international consensus guidelines. RESULTS: Tracer uptake was abnormal in all patients with amyloidosis. The visual detection rate was excellent (100%) in the heart, stomach, and tongue but limited in the kidneys (50%) and poor (0%) in the esophagus, liver, and colon. F-florbetaben PET/CT identified 13 unexpected cases of abnormal uptake, confirming further amyloid deposition. Both spherical and manual volumes of interest showed similar diagnostic performance when evaluating amyloidosis in target organs. There was no significant difference in diagnostic performance between the SUVmax, SUVmean, and SUVratio. CONCLUSIONS: F-florbetaben PET/CT can accurately detect systemic amyloid deposits in patients with MM. F-florbetaben PET/CT was particularly useful in the heart, stomach, and tongue but of limited value in the esophagus, liver, and colon. F-florbetaben PET/CT can provide clinical information on organ involvement and could replace pathologic examination for diagnosis of amyloidosis in the future.

Comparison of High Sensitivity and Conventional Flow Cytometry for Diagnosing Overt Paroxysmal Nocturnal Hemoglobinuria and Detecting Minor Paroxysmal Nocturnal Hemoglobinuria Clones.

BACKGROUND: High sensitivity flow cytometry (HS-FCM) was recently developed for diagnosing paroxysmal nocturnal hemoglobinuria (PNH). We compared its performance with conventional flow cytometry (C-FCM) for diagnosing overt PNH and detecting minor (0.1-1%) PNH clones in aplastic anemia (AA)/low-grade myelodysplastic syndrome (MDS) patients. METHODS: C-FCM and HS-FCM were performed simultaneously on 41 samples from healthy controls and 23 peripheral blood samples from 15 AA/low-grade MDS and eight PNH patients, using a Navios flow cytometer (Beckman Coulter, Miami, FL, USA). Results were compared. RESULTS: No healthy control samples had PNH clone size >0.01%. For granulocytes, C-FCM detected a smaller PNH clone size than HS-FCM (mean difference: 0.7-1.7%). In AA/low-grade MDS patients, three samples showed >1% PNH clones with C-FCM but not with HS-FCM. Seven samples showed minor PNH clones by C-FCM, but HS-FCM showed negative results for all these samples. In PNH patients, C-FCM detected a smaller PNH clone size than HS-FCM (mean difference: 1.9-5.0%). For red blood cells, C-FCM detected a greater PNH clone size than HS-FCM (mean difference: 1.5%). In AA/low-grade MDS patients, C-FCM showed >1% PNH clones in six samples, but HS-FCM showed >1% PNH clones in none of the samples. C-FCM detected minor PNH clones in nine samples, but six of them were negative by HS-FCM. In PNH patients, C-FCM detected a greater PNH clone size than HS-FCM (mean difference: 2.5%). CONCLUSIONS: HS-FCM can sensitively detect minor PNH clones and reduce false-positive C-FCM minor PNH clone cases in AA/low-grade MDS patients.

A description of Mycobacterium chelonae subsp. gwanakae subsp. nov., a rapidly growing mycobacterium with a smooth colony phenotype due to glycopeptidolipids.

Three rapidly growing mycobacterial strains, MOTTH4W, MOTT36WT and MOTT68W, were isolated from the sputa of three independent Korean patients co-infected with Mycobacterium yongonense Type II strains. The 16S rRNA gene sequences of all three strains were unique, which were closest to that of Mycobacterium chelonae subsp. bovis KCTC 39630T (99.9 % similarity). Multilocus sequence typing analysis targeting 10 housekeeping genes including hsp65 and rpoB revealed the distinct phylogenetic location of these strains, which were clustered with M. chelonae subsp. chelonae ATCC 35752T and M. chelonae subsp. bovis KCTC 39630T. Phylogenetic analysis based on whole genome sequences revealed a 95.89 % average nucleotide identity (ANI) value with M. chelonae subsp. chelonae, slightly higher than the 95.0 % ANI criterion for determining a novel species. In addition, phenotypic characteristics such as a smooth colony morphology and growth inhibition at 37 °C, distinct MALDI-TOF MS profiles of extracted total lipids due to surface glycopeptidolipids, and distinct drug susceptibility profiles further supported the taxonomic characterization of these strains as representing a novel subspecies of Mycobacterium chelonae. Mycobacterium chelonae subsp. gwanakae subsp. nov. is proposed and the type strain is MOTT36WT (=KCTC 29127T=JCM 32454T).

Investigation of a nosocomial outbreak of fungemia caused by Candida pelliculosa (Pichia anomala) in a Korean tertiary care center.

BACKGROUND: Candida pelliculosa is a rare pathogen of fungemia. There have been a few nosocomial outbreaks of C. pelliculosa fungemia in nurseries and pediatric intensive care units (ICU), hematologic units, and surgical ICU. We describe an epidemiologic outbreak investigation, including case findings of C. pelliculosa fungemia in South Korea. METHODS: This outbreak investigation conducted in a 940-bed, tertiary referral center, Ulsan, South Korea and included active microbial surveillance and a case-control study. RESULTS: A patient in the trauma intensive care unit (ICU) with multiple trauma developed C. pelliculosa fungemia, and 10 patients in the trauma ICU, medical ICU, and 2 general wards subsequently contracted C. pelliculosa fungemia during the next 24 days (November 16 and December 9, 2015). The 16s rRNA sequencing of 4 isolates showed that C. pelliculosa was verified with 99-100% similarity (GenBank accession number: KF317892.1), and these isolates were identical in the randomly amplified polymorphic DNA (RAPD) assay. A case-control study showed that medical staff and staying in the interventional radiology procedure room were risk factor for development of C. pelliculosa fungemia. After intervention including strict hand washing, disinfecting medical equipment, and contact precautions, there have been no new C. pelliculosa infections since December 10, 2015. CONCLUSIONS: This is the first report of a nosocomial outbreak involving 11 patients in 2 ICUs and 2 general wards caused by C. pelliculosa in South Korea. Infection control measures are important for decreasing transmission of C. pelliculosa in the hospital.

Description of Mycobacterium chelonae subsp. bovis subsp. nov., isolated from cattle (Bos taurus coreanae), emended description of Mycobacterium chelonae and creation of Mycobacterium chelonae subsp. chelonae subsp. nov.

Three rapidly growing mycobacterial strains, QIA-37T, QIA-40 and QIA-41, were isolated from the lymph nodes of three separate Korean native cattle, Hanwoo (Bos taurus coreanae). These strains were previously shown to be phylogenetically distinct but closely related to Mycobacterium chelonae ATCC 35752T by taxonomic approaches targeting three genes (16S rRNA, hsp6 and rpoB) and were further characterized using a polyphasic approach in this study. The 16S rRNA gene sequences of all three strains showed 99.7 % sequence similarity with that of the M. chelonae type strain. A multilocus sequence typing analysis targeting 10 housekeeping genes, including hsp65 and rpoB, revealed a phylogenetic cluster of these strains with M. chelonae. DNA-DNA hybridization values of 78.2 % between QIA-37T and M. chelonae indicated that it belongs to M. chelonae but is a novel subspecies distinct from M. chelonae. Phylogenetic analysis based on whole-genome sequences revealed a 95.44±0.06 % average nucleotide identity (ANI) value with M. chelonae, slightly higher than the 95.0 % ANI criterion for determining a novel species. In addition, distinct phenotypic characteristics such as positive growth at 37 °C, at which temperature M. chelonae does not grow, further support the taxonomic status of these strains as representatives of a novel subspecies of M. chelonae. Therefore, we propose an emended description of Mycobacterium chelonae, and descriptions of M. chelonae subsp. chelonae subsp. nov. and M. chelonae subsp. bovis subsp. nov. are presented; strains ATCC 35752T(=CCUG 47445T=CIP 104535T=DSM 43804T=JCM 6388T=NCTC 946T) and QIA-37T (=KCTC 39630T=JCM 30986T) are the type strains of the two novel subspecies.

Severe Fever with Thrombocytopenia Syndrome Presenting with Hemophagocytic Lymphohistiocytosis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the newly discovered SFTS Bunyavirus, and there have been no case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis (HLH) in the English literature. We report a case of SFTS presenting with HLH in a 73-year-old immunocompetent male farmer. Although the patient had poor prognostic factors for SFTS, such as old age and central nervous system symptoms, he recovered fully with supportive care.