Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis.

The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8+ T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4+ T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8+ T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies.

Sustainable Gas Storage: CO2 Activation of Edge-Functionalized Graphitic Nanoplatelets.

Graphitic nanoplatelets (GnPs), edge-selectively carboxylated graphitic nanoplatelets (ECGnPs), are functionalized with a carboxylic acid at the edge increasing their surface area, and are highly dispersible in various solvents. However, there is a limit in that the basal plane remains intact because it is functionalized only in the part where the radical is generated at the edge. Here, we activate ECGnPs to have porous structures by flowing CO2 at 900 °C. Etching of the ECGnPs structure was performed through the Boudouard reaction, and the surface area increased from 579 m2 g-1 to a maximum of 2462 m2 g-1. In addition, the pore structure was investigated with various adsorption gases (CH4, Ar, CO2, H2, and N2) according to the reaction time. This study provides the overall green chemistry in that it utilizes CO2 from manufacturing to activation compared to the process of activating with conventional chemical treatment.

Advancing mass spectrometry-based chemical imaging: A noncontact continuous flow surface probe in mass spectrometry for enhanced signal detection and spatial resolution.

A new method has been developed for mass spectrometric imaging of small molecules and proteins on tissue or in thinly sliced materials. A laser desorption Venturi electrospray ionization-mass spectrometer was developed for molecular imaging. This method combines laser desorption (LD) and electrospray ionization (ESI) systems before a mass spectrometer (MS). To carry out laser desorption, samples are excited with a laser from the back side of a glass substrate. The desorbed molecules or particles are then captured by a solvent flow. In the ESI system, these desorbed particles and molecules are ionized. The spray part of the solvent system consists of two capillaries: one delivers solvent to the sample plate sides to capture desorbed molecules and particles, and the other carries the solution to the mass spectrometry side using the Venturi effect. A 2D stage facilitates sampling. The system is designed to minimize the sample size after desorption using a 355 nm diode laser, and it is optimized for molecules of various sizes, including organic molecules, amino acids, and proteins. Despite challenging atmospheric conditions for protein desorption, this specialized design enables the collection of protein spectra. The amino acids and other small molecules showed high sensitivity in the MSI measurements. This innovative MS imaging system can be directly applied to real tissue systems and other plant samples to visualize the molecular level distributions.

Metabolomic changes in culture media with varying passage numbers of pig muscle stem cell culture for cultured meat production.

Selecting the primary cells in an optimal state for cultured meat production is a crucial challenge in commercializing cultured meat. We investigated the metabolomic changes in culture media according to passage numbers for indirectly assessing the state of primary cells. Pig skeletal muscle stem cells (PSCs) harvested from the biceps femoris muscles of 7-d-old crossbred pigs (Landrace × Yorkshire × Duroc, LYD) were used for cell characterization. Fresh media (FM) and spent media (SM) of PSCs during passages 1 to 3 in vitro culture were prepared for metabolomics analysis. SM was collected on the third day of proliferation for each passage of PSCs. Cell characterization analysis revealed that the proliferation rate was highest at passage 2; however, a significant loss of expression of myogenic marker genes was observed at passage 3. Based on metabolomic profiles of culture media, FM and SM groups (SM1, SM2, and SM3) were clearly separated by partial least squares-discriminant analysis. A total of seven differentially abundant metabolites (DAMs) were identified from FM and SM for each passage, based on the following criteria: P < 0.05, fold change > 1.5 or < 0.66, and a variable importance in projection score > 1.5. All seven DAMs and their interconnected metabolites might be primarily used as substrates for energy production and most of them were relatively abundant in SM3. Among the seven DAMs, the three potential biomarkers (γ-glutamyl-L-leucine, cytosine, and ketoleucine), which showed significant changes exclusively in SM3, each had an area under the curve value of 1. Therefore, monitoring the levels of these key metabolites in culture media could serve as a quality control measure for cultured meat production by enabling the indirect detection of suboptimal PSCs based on their proliferation ability.

Corrigendum to "Advancing mass spectrometry-based chemical imaging: A noncontact continuous flow surface probe in mass spectrometry for enhanced signal detection and spatial resolution" [Talanta 273 (2024) 125858].

In the statement "This innovative MS imaging system can be directly applied to real tissue systems and other plant samples to visualize the molecular level distributions." "innovative" should be read as "important".

High-performance peptide and disulfide mapping by direct injection of intact proteins using on-line coupled UV-liquid chromatography microdroplet mass spectrometry (UVLC-MMS).

Microdroplet mass spectrometry (MMS), achieving ultra-fast enzyme digestion in the ionization source, holds great promises for innovating protein analysis. Here, in-depth protein characterization is demonstrated by direct injection of intact protein mixtures via on-line coupling MMS with capillary C4 liquid chromatography (LC) containing UV windows (UVLC-MMS) through an enzyme introduction tee. We showed complete sets of peptides of individual proteins (hemoglobin, bovine serum albumin, and ribonuclease A) in a mixture could be obtained in one injection. Such full (100%) sequence coverage, however, could not be achieved by conventional nanoLC-MS method using bottom-up approach with single enzyme. Moreover, direct injection of a chaperone α-crystalline (α-Cry) complex yielded identification of post-translational modifications including novel sites and semi-quantitative characterization including 3:1 stoichiometry ratio of αA- and αB-Cry sub-units and ∼1.4 phosphorylation/subunit on S45 (novel site) and S122 (main site) of αA-Cry, ∼0.7 phosphorylation/subunit on S19 (main site) and S45 of αB-Cry, as well as 100% acetylation on both N-termini of each subunits by matching the mass and retention time of the intact and its digested peptides. Furthermore, trifluoroacetic acid was able to be used in the mobile phase with UVLC-MMS to improve the separation of differentially reduced intact species and detectability of the droplet-digested products. This allowed us to completely map four disulfide linkages of ribonuclease A based on collision-induced dissociation of disulfide clusters, some of which would otherwise not be detected, preventing scrambling or shuffling errors arising from lengthy bulk solution digestion by the bottom-up approach. Integration of UVLC and MMS greatly improves droplet digestion efficiency and MS detection, enabling highly efficient workflow for in-depth and accurate protein characterization.

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis and Bioevaluation.

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides (4 a-i, 7 a-g) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI-H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a-i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a-g in all biological assays. Compounds 7 e-f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 µM and 1.794±0.159 µM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

The effect of home-based cardiac rehabilitation on arterial stiffness and peak oxygen consumption in patients with myocardial infarction.

Objectives: This study aims to investigate the effectiveness of home-based cardiac rehabilitation (CR) on arterial stiffness in patients with acute myocardial infarction (AMI). Patients and methods: Between January 2015 and December 2017, a total of 135 patients (120 males, 15 females; mean age: 58.8±11.1 years) with AMI who were referred for CR were included. Home-based CR was prescribed based on a cardiopulmonary exercise test (CPET) for at least six months. All patients completed three consecutive CPETs and brachial-ankle pulse wave velocity (baPWV) measurements at one, four, and seven months after onset. Results: After six months of CR, there was an improvement in peak oxygen consumption (pVO2) (Month 1, 28.7±6.4 mL/kg/min; Month 4, 31.6±6.3 mL/kg/min; Month 7, 31.2±7.1 mL/kg/min, p<0.001) and a reduction in baPWV (Month 1, left, 1546.0±311.2 cm/sec, right 1545.5±301.5 cm/sec; Month 4, left, 1374.9±282.5 cm/sec, right 1371.6±287.5 cm/sec; Month 7, left, 1362.9±287.0 cm/sec, right 1365.5±281.1 cm/sec, p<0.001). Conclusion: In patients with AMI, arterial stiffness and aerobic capacity improved after six months of home-based CR, particularly in the early stages of rehabilitation. These results suggest that changes in baPWV are useful in determining the effectiveness of CR and pVO2 in the initial stages of CR.

Two Cases of Multiple Ossicular Chain Disruption After Penetrating Injury and Tympanic Membrane Healing

Ossicular chain disruption is a typical consequence of temporal bone trauma. However, it can also occur as a result of direct trauma to the ossicular chain due to penetrating injuries. Hearing loss, dizziness, and facial nerve damage could also occur after penetrating middle ear injuries. Multiple ossicular chain disruption is a rare traumatic ossicular complication caused by direct penetrating lesions in the external auditory canal. We present two cases of multiple ossicular disruptions (dislocation of the incudostapedial and malleoincudal joints) after ear-pick injuries, both of which resulted in conductive hearing loss. The condition improved after delayed surgical intervention (ossiculoplasty).

Applications of Bioinspired Platforms for Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation in vivo. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.

Additional Clinical Benefit of Agomelatine Treatment for Major Depressive Disorder in Naturalistic Treatment Setting

Objective@#This study tried to observe additional benefit of agomelatine (AGO) treatment for major depressive disorder (MDD) in routine practice. @*Methods@#Retrospective chart review (n = 63) was conducted for additional benefit of combination with or switching to AGO in MDD patients without full remission. The primary endpoint was the mean change of Clinical Global Impression-Clinical Benefit (CGI-CB) total scores from baseline to the endpoint. Additional secondary endpoints were also collected. @*Results@#The changes of CGI-CB (Z = −3.073, p = 0.002) and Montgomery-Åsberg Depression Rating Scale (Z = −3.483, p ＜ 0.001) total scores were significantly decreased from baseline to the endpoint, respectively. At the endpoint, the remission rate was 22.6% (n = 18) and 28.6% of patient had improvement in CGI-CB total scores at the endpoint.No significant adverse events were observed. @*Conclusion@#This study has shown additional benefit of AGO treatment as combination or switching agent for MDD patients without full remission in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity

Background/Aims@#To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. @*Methods@#This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. @*Results@#Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. @*Conclusions@#In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. @*Materials and Methods@#Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. @*Results@#Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). @*Conclusion@#Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Recent advances in diagnosis and therapy in systemic mastocytosis

Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the KIT gene, most frequently KIT D816V, are detected in 90% of patients with SM. Expression of CD30 and any KIT mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

A case of vocal cord dysfunction diagnosed in a 10-year-old girl with recurrent wheezing and dyspnea

Vocal cord dysfunction is one of the causes of dyspnea and is characterized by paradoxical closure of the vocal cords. The paradoxical movement of the vocal cords produces the limitation of airflow, resulting dyspnea, chest tightening, hoarseness, stridor, or wheezing. These findings are similar to those of other upper airway obstruction diseases or asthma; therefore, a high index of suspicion and clear differential diagnosis are required. Here, we discuss a case of vocal cord dysfunction aged 10 years that presented recurrent wheezing and dyspnea. The abnormal movement of the vocal cords was observed by fiberoptic laryngotracheobronchoscopy, which was correlated with stridor during respiration. Repeated episodic symptoms were controlled by the multidisciplinary team approach; however, surgical treatment was needed to stabilize the symptom.

Thrombocytopenia Experienced by Healthy Peripheral Blood Stem Cell Donors at a Tertiary Hospital in Korea / 대한수혈학회지

In healthy peripheral blood stem cell (PBSC) donors, rare cases of transient thrombocytopenia have been reported due to the administration of granulocyte colony-stimulating factor (G-CSF) or the apheresis itself. Meanwhile, differentiating pseudothrombocytopenia induced by anticoagulants is crucial, as it can result in false low platelet counts. This study aimed to investigate the causes of thrombocytopenia in healthy PBSC donors. We investigated PBSC donors who experienced thrombocytopenia during transplantation at St. Mary’s Hospital, Seoul. Three donors were identified and donor workup studies were within the normal limits. After G-CSF administration prior to transplantation, the donors experienced a significant reduction in platelet counts. Apheresis resulted in lower levels, yet platelet counts returned to normal levels approximately two weeks later. In donor 3, thrombocytopenia was seen during the donor workup and ethylenediaminetetraacetic acid (EDTA)-induced pseudothrombocytopenia was identified after the supplementation of amikacin. For donor 3, we investigated whether his recipient’s sample showed EDTA-induced pseudothrombocytopenia through a review of any platelet clumping in the apheresis product and the presence of immunoglobulin M (IgM) or IgG antiplatelet antibodies in the recipient’s peripheral blood. In conclusion, the risk of severe thrombocytopenia with G-CSF administration in PBSC donors should be considered and accurate differentiation of pseudothrombocytopenia is imperative.