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Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus emerged in late 2019 leading to the COVID‐19 disease pandemic that triggered socioeconomic turmoil worldwide. A precise, prompt, and affordable diagnostic assay is essential for the detection of SARS‐CoV‐2 as well as its variants. Antibody against SARS‐CoV‐2 spike (S) protein was reported as a suitable strategy for therapy and diagnosis of COVID‐19. We, therefore, developed a quick and precise phase‐sensitive surface plasmon resonance (PS‐SPR) biosensor integrated with a novel generated anti‐S monoclonal antibody (S‐mAb). Our results indicated that the newly generated S‐mAb could detect the original SARS‐CoV‐2 strain along with its variants. In addition, a SARS‐CoV‐2 pseudovirus, which could be processed in BSL‐2 facility was generated for evaluation of sensitivity and specificity of the assays including PS‐SPR, homemade target‐captured ELISA, spike rapid antigen test (SRAT), and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Experimentally, PS‐SPR exerted high sensitivity to detect SARS‐CoV‐2 pseudovirus at 589 copies/ml, with 7‐fold and 70‐fold increase in sensitivity when compared with the two conventional immunoassays, including homemade target‐captured ELISA (4 × 103 copies/ml) and SRAT (4 × 104 copies/ml), using the identical antibody. Moreover, the PS‐SPR was applied in the measurement of mimic clinical samples containing the SARS‐CoV‐2 pseudovirus mixed with nasal mucosa. The detection limit of PS‐SPR is calculated to be 1725 copies/ml, which has higher accuracy than homemade target‐captured ELISA (4 × 104 copies/ml) and SRAT (4 × 105 copies/ml) and is comparable with qRT‐PCR (1250 copies/ml). Finally, the ability of PS‐SPR to detect SARS‐CoV‐2 in real clinical specimens was further demonstrated, and the assay time was less than 10 min. Taken together, our results indicate that this novel S‐mAb integrated into PS‐SPR biosensor demonstrates high sensitivity and is time‐saving in SARS‐CoV‐2 virus detection. This study suggests that incorporation of a high specific recognizer in SPR biosensor is an alternative strategy that could be applied in developing other emerging or re‐emerging pathogenic detection platforms.

Abstract Identification of alloantibodies and achieving a reduction in the rate of red blood cell (RBC) alloimmunization are important issues to prevent transfusion complications. The aim of this study was to identify the antigen and alloantibodies in our patients and to study the association of alloimmunization with previous transfusion. Transfusion records from the blood bank of Kaohsiung Medical University Hospital between 2015 and 2017 were retrospectively enrolled in the study. Antigen and antibody identification was performed using routine blood bank methods. In total, 56,422 transfusion records from 2015 to 2017 were included in the study. Among them, 1858 alloantibody episodes were found in the pre‐transfusion survey, and anti‐Mia, anti‐E, and cold antibodies were the most common alloantibodies, with a prevalence of 3.29% (1858/56,422). Among them, 130 episodes involved newly found alloantibodies with no alloantibodies found in the previous transfusion survey. Tracing back to these newly transfusion‐induced alloantibodies, the antibody was found with a mean of 10.8 ± 7.8 units of packed RBC transfusion, a mean of 66.3 ± 52.8 days, and with a mean of 4.3 ± 2.7 times of transfusion from the first transfusion therapy. An antibody survey revealed that Rh‐ee (62.1%) was the most common phenotype in these newly identified antibodies. In summary, this hospital‐based study revealed that RBC alloantibody rates were present at rates of 3.29%, with anti‐Mia, anti‐E, and cold antibodies being the most common alloantibodies. Among them, anti‐E was the most commonly developed alloantibody. Given that the Rh‐ee group is the most common phenotype in our population, the strategy of using Rh‐ee blood for Rh‐ee recipients is reasonable for transfusion safety.

Abstract Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase‐deficient. Pegylated arginine deiminase (ADI‐PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI‐PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor‐risk AML patients. We conducted a phase I, dose‐escalation study combining ADI‐PEG20 and low‐dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI‐PEG20 at 18 or 36 mg/m2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI‐PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty‐three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose‐limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI‐PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5‐not reached) months. In seven treatment‐naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI‐PEG20 and LDC combination was well‐tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI‐PEG20 Plus Low‐Dose Cytarabine in Older Patients With AML, NCT02875093).

The aim of this study was to investigate the role of 2-fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the initial staging and prediction of bone marrow involvement in patients with newly diagnosed lymphoma. A total of 185 patients with newly diagnosed lymphoma were enrolled. All patients received PET/CT and bone marrow biopsy as part of a staging work-up. At the initial staging, 17 patients (9.2%) with occult nodal or extranodal lesions were upstaged after a review of the PET/CT studies. PET/CT was found to be useful in the differentiation of aggressive lymphoma subtypes from the indolent subtype based on higher standardized uptake value (SUV) (16.67 vs. 7.98, p

Cisplatin-induced acute kidney injury (AKI) is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and the urinary albumin to creatinine ratio (ACR) to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30%) who developed AKI (the study group). Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75 mg/m2) versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty-four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p

The synchronous existence of two different tumors in the gastrointestinal tract is uncommon. We report the case of a 75-year-old man who had a concurrent gastrointestinal stromal tumor and adenocarcinoma at the gastroesophageal junction. The two tumors arose at the same site but had distinct morphologies. The etiology of synchronous tumors is still unclear and their coexistence causes problems for the surgeon, oncologist and pathologist in terms of their diagnosis, treatment, and follow-up. We report a rare case of synchronous tumors and a review of the literature.

Primary liver lymphoma is extremely rare. The diagnosis depends on the physician's suspicions and histological examination. We report the case of a man aged 38 years who suffered from abdominal discomfort and hypercalcemia. Sonography showed a huge, solid liver tumor, and magnetic resonance imaging showed the tumor had characteristics of hypointensity on T1-weighted and hyperintensity on T2-weighted imaging. Primary liver lymphoma was diagnosed by histological examination from biopsy. We report this rare type of liver tumor and review the clinical presentation and treatment of the disease.

Gastrointestinal stromal tumors (GIST) are rare soft tissue sarcomas arising primarily from mesenchymal tissue in the gastrointestinal tract and abdomen. Since there is no effective treatment in the advanced stages, the outcome is poor in such patients. Recently, imatinib mesylate, a selective tyrosine kinase inhibitor, has shown a promising effect in GIST. Hence, we report our experience on the management of advanced GIST with imatinib therapy. A total of 14 patients were enrolled in this study, including 10 males and four females (median age, 51 years). The results showed that the small intestine was the most frequent site of primary lesion, while the liver was the most frequently metastasized organ. Most of the patients experienced tolerable side effects with imatinib therapy, including edema of periorbital area and/or legs and abdominal pain. Only two mortalities were noted during follow-up. The patients clinically benefited from imatinib therapy, with one patient having a complete response, three having a partial response, and seven having stable disease. The results demonstrate promising effects of imatinib in advanced GIST.

Combined small-cell lung carcinoma (SCLC) is a rare tumor. We report a case of combined SCLC of the lung, including adenocarcinoma and spindle-shaped cell tumor, with an unusual initial presentation. The patient suffered from a right shoulder mass, subsequently undergoing biopsy. A lung nodule was noted later after complete examination. The diagnosis turned out to be combined cell carcinoma with three different components (small-cell carcinoma, adenocarcinoma, and spindle-shaped cell tumor) after examination upon total removal of the lung nodule by lobectomy. In addition to the rarity of the three components in such a tumor, soft tissue metastasis also made it an unusual case.

Invasive fungal infections, a serious problem among cancer patients, are increasing in incidence, and can cause morbidity and mortality. Such infections may hinder additional treatment, especially for patients with leukemia. We report here our experiences in the management of invasive fungal infection in patients with acute leukemia. A total of 18 patients were enrolled in the study: 12 had microabscesses of the liver and/or spleen and/or kidneys; four had sinonasal infections; and two had pulmonary infections. Most of the patients (88.9%) received amphotericin B during treatment for fungal infection. Thirteen patients achieved complete response without evidence of fungal infection in follow-up. In the study, there were 11 mortalities, including five patients who died during therapy and six who later died as a result of relapse or refractoriness of the leukemia. We suggest that many patients may have a good response to antifungal therapy, and that fungal infection does not have to preclude additional chemotherapy after proper management. The state of the underlying disease has a strong impact on outcome.

Primary mediastinal germ-cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk-sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor-marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.

Pure red cell aplasia (PRCA) is a complication of ABO-incompatible allogeneic stem cell transplantation. The mechanism is not well known, although the isoagglutinin titer before transplantation or cyclosporine use is considered to be the cause. Patients with this complication require more blood transfusions than those without it. There is no standard treatment. We report two cases of PRCA after allogeneic peripheral blood stem cell transplantation that were successfully treated with plasma exchange and low-dose steroid.

This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia) who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years) or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years) from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001) and platelet engraftment (median, Day 9 vs Day 17, p < 0.001) was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001), but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD) (42.9% vs 33.3%, p = 0.72) or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57), and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67). No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3), and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death in both groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25); all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029), but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20). Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.