Blueberry stem extract and stem active components prevent blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro.

Blue light causes retinal damage that can lead to ocular diseases such as age-related macular degeneration. In this study, we determined the protective effect of blueberry stem extract (BStEx) and active components on blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage in vitro. Photoreceptor cells cultured in the presence of BStEx or components were exposed to blue light to induce cell damage. BStEx, fractions of BStEx containing proanthocyanidins, chlorogenic acid, catechin, and epicatechin prevented the cell damage and/or inhibited the generation of reactive oxygen species (ROS). Furthermore, BStEx reduced apoptosis and cell death, and inhibited the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase leading to cellular apoptosis induced by blue light exposure. These findings suggest that BStEx and components exert a protective effect against blue light-induced photoreceptor cell damage through the inhibition of MAPK phosphorylation and ROS production.

[Advances in the therapy for von Willebrand disease].

Von Willebrand disease (VWD) is caused by quantitative or qualitative deficiencies in the von Willebrand factor (VWF). VWF concentrate replacement therapy is required in certain situations, such as severe VWD subtype or critical bleeding, even in mild VWD subtypes. A single plasma-derived factor VIII/VWF concentrate has been available for decades in Japan. However, it has a theoretical risk of infectious disease transmission, allergic reactions, and thrombosis. A recombinant VWF (vonicog alfa) was approved by the Japanese Pharmaceuticals and Medical Devices Agency in 2020. Vonicog alfa is the only VWF product that contains ultralarge multimer, suggesting both effective bleeding control and excessive platelet plug formation. The efficacy and safety of vonicog alfa have been confirmed by three phases of clinical studies for on-demand usage, elective surgery, and prophylaxis. We also have a successful experience with vonicog alfa with minimal adverse events in two cases (hemostatic treatment in a patient with recurrent epistaxis and prophylaxis for delivery in a pregnant woman).

High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs.

BACKGROUND: Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. METHODS: We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. RESULTS: A positive correlation between PLR and TIL was observed in TNBC (P = 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3+CD4+FOXP3+ T-cells (P = 0.049 and 0.019, respectively), while no trend was observed in CD8+ T-cells. TNBC patients had different patterns of outcomes according to TIL and PLR, with the TIL-high/PLR-low group having the lowest rate of disease relapse and death, and the longest distant metastasis-free and overall survivals, while the TIL-low/PLR-high group had the shortest survivals. CONCLUSIONS: Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting.

BACKGROUND: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. METHODS: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (

Highly polymerized proanthocyanidins (PAC) components from blueberry leaf and stem significantly inhibit SARS-CoV-2 infection via inhibition of ACE2 and viral 3CLpro enzymes.

With the current worldwide pandemic of COVID-19, there is an urgent need to develop effective treatment and prevention methods against SARS-CoV-2 infection. We have previously reported that the proanthocyanidin (PAC) fraction in blueberry (BB) leaves has strong antiviral activity against hepatitis C virus (HCV) and human T-lymphocytic leukemia virus type 1 (HTLV-1). In this study, we used Kunisato 35 Gou (K35) derived from the rabbit eye blueberry (Vaccinium virgatum Aiton), which has a high PAC content in the leaves and stems. The mean of polymerization (mDP) of PAC in K35 was the highest of 7.88 in Fraction 8 (Fr8) from the stems and 12.28 of Fraction 7 (Fr7) in the leaves. The composition of BB-PAC in K35 is that most are B-type bonds with a small number of A-type bonds and cinchonain I as extension units. A strong antiviral effect was observed in Fr7, with a high polymerized PAC content in both the leaves and stems. Furthermore, when we examined the difference in the action of BB-PAC before and after SARS-CoV-2 infection, we found a stronger inhibitory effect in the pre-infection period. Moreover, BB-PAC Fr7 inhibited the activity of angiotensin II converting enzyme (ACE2), although no effect was observed in a neutralization test of pseudotyped SARS-CoV-2. The viral chymotrypsin-like cysteine protease (3CLpro) of SARS-CoV-2 was also inhibited by BB-PAC Fr7 in leaves and stems. These results indicate that BB-PAC has at least two different inhibitory effects, and that it is effective in suppressing SARS-CoV-2 infection regardless of the time of infection.

Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity. METHODS: We retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138+ PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells. RESULTS: Greater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8+, T-bet+CD4+, and CD8+FOXP3+ T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034). CONCLUSIONS: We found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients.

Pretreatment Immature Platelet Fraction as a Surrogate of Reticulated Platelets Predicts the Response to Corticosteroids in Adults with Immune Thrombocytopenia.

OBJECTIVES: Reticulated platelets circulating in the blood reflect megakaryopoietic activity and platelet turnover and can be automatically and low-invasively measured as the immature platelet fraction (IPF) using a Sysmex XN hematocytometer. The present study retrospectively investigated whether or not the IPF can predict the treatment response to corticosteroids in adult patients with primary immune thrombocytopenia (ITP). METHODS: Forty-six patients who had been newly diagnosed with primary treatment-naïve ITP and started treatment with corticosteroids were analyzed. RESULTS: Among the 46 primary ITP patients, 33 (72%) responded to the treatment and 13 (28%) did not. The percentage of IPF (IPF%) among the nonresponders was significantly lower than that of the responders (6.6 vs. 16.0%; p < 0.001). In the receiver operating characteristics analysis, the optimum IPF% cut-off value for predicting the treatment response was 12%, with a specificity of 85% and a sensitivity of 76%. CONCLUSIONS: Our findings thus suggest that measuring the IPF% as a surrogate of reticulated platelets is useful to identify patients likely to respond to corticosteroids.

Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension.

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

Indoxyl Sulfate-induced Vascular Calcification is mediated through Altered Notch Signaling Pathway in Vascular Smooth Muscle Cells.

Introduction: The aim of this study was to determine the role of Notch in indoxyl sulfate (IS)-induced vascular calcification (VC). Materials and methods: VC and expression of Notch-related and osteogenic molecules were examined in Dahl salt-sensitive (DS), DS hypertensive (DH), and DH IS-treated rats (DH+IS). The effects of IS on expression of Notch receptors, apoptotic activity, and calcification were examined in cultured aortic smooth muscle cells (SMCs). Results: Medial calcification was noted only in aortas and coronary arteries of DH+IS rats. Notch1, Notch3, and Hes-1 were expressed in aortic SMCs of all rats, but only weakly in the central areas of the media and around the calcified lesions in DH+IS rats. RT-PCR and western blotting of DH+IS rat aortas showed downregulation of Notch ligands, Notch1 and Notch3, downstream transcriptional factors, and SM22, and conversely, overexpression of osteogenic markers. Expression of Notch1 and Notch3 in aortic SMCs was highest in incubation under 500 µM IS for 24hrs, and then decreased time- and dose-dependently. Coupled with this decrease, IS increased caspase 3/7 activity and TUNEL-positive aortic SMCs. In addition, pharmacological Notch signal inhibition with DAPT induced apoptosis in aortic SMCs. ZVAD, a caspase inhibitor abrogated IS-induced and DAPT-induced in vitro vascular calcification. Knockdown of Notch1 and Notch3 cooperatively increased expression of osteogenic transcriptional factors and decreased expression of SM22. Conclusion: Our results suggested that IS-induced VC is mediated through suppression of Notch activity in aortic SMCs, induction of osteogenic differentiation and apoptosis.

Contact with renal sinus is associated with poor prognosis in surgically treated pT1 clear cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of contact with the renal sinus in patients with clear cell renal cell carcinoma. METHODS: A total of 787 pT1N0M0 clear cell renal cell carcinoma patients who had undergone radical or partial nephrectomy were reviewed retrospectively. A tumor in contact with the renal sinus was defined as a tumor radiologically attached to the renal sinus. Metastatic-free survival rates were analyzed in the total and propensity score-matched cohorts. A risk score model for metastasis after surgery was developed. RESULTS: Of the 787 patients, 411 (52.2%) had tumors in contact with renal sinus. The contact with renal sinus group showed poorer metastatic-free survival in both total and matched cohorts. In multivariate analysis, contact with renal sinus was an independent prognostic factor of metastasis, as well as Fuhrman grade, microvascular invasion and age. The scoring model likewise consisted of Fuhrman grade, microvascular invasion, age and contact with renal sinus. Metastasis-free survival curves were clearly stratified according to risk, with 5-year metastasis-free survival rates of 95.7% and 65.2% in the low- and high-risk groups, respectively (P < 0.001). CONCLUSIONS: Contact with the renal sinus is a significant risk factor for metastasis in T1 clear cell renal cell carcinoma after surgery. More intensive follow up should be recommended for patients with renal cell carcinoma that is in contact with the renal sinus.

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified. CASE PRESENTATION: We report 2 patients with metastatic melanoma who developed colitis, an irAEs caused by nivolumab. Both patients experienced colitis after nivolumab administration. Pathological examination of the colon showed robust infiltration of CD8+ cells and T-bet expressing CD4+ cells in both cases, indicating helper T cells (Th) 1 to be responsible for the dominant response. Additionally, we observed the serum C-reactive protein level (CRP) as well as interleukin-6 (IL-6) reflected the clinical course of irAEs clearly in the two cases. CONCLUSION: Our two cases suggested that the development of irAEs due to nivolumab is associated with Th1 dominant response. CRP as well as IL-6 was found to be a potential biomarker for irAEs. Our findings may help to understand the mechanisms underlying irAEs caused by nivolumab and manage irAEs in clinical practice.

Reduction in adverse transfusion reactions with increased use of washed platelet concentrates in Japan-A retrospective multicenter study.

Plasma removal by washing platelet concentrates (PCs) is effective in preventing adverse reactions to PC transfusions. The Japanese Red Cross Society (JRCS) started releasing washed PCs (WPCs) as a commercially approved blood product in September 2016. This retrospective multicenter study investigated the change in the number of transfused WPCs and the impact on the incidence of adverse reactions to PCs before and after the release. The numbers and types of transfused PCs and the adverse reactions to the PCs for a year before the start of the WPC release and for a year after the release were reported by 27 medical institutes in Japan. Transfusion information for approximately 8% of the amount of PCs supplied in Japan was analyzed during the study period. After the start of WPC release by the JRCS, the number of transfused WPCs doubled. The rate of adverse reactions to PCs decreased significantly (p = 0.0223), from 4.30% before the release to 4.05% after the release. The rates of adverse reactions to unwashed and WPCs were 4.13% and 0.84%, respectively. Allergic adverse reactions were significantly decreased after the release (3.60% before versus 3.37% after). No severe allergic reactions to WPCs were reported. The release of WPCs by the JRCS significantly reduced transfusion-related adverse reactions to PCs in Japan.

Case of mesenchymal tumor with the PPP6R3-USP6 fusion, possible nodular fasciitis with malignant transformation.

Nodular fasciitis (NF) is a self-limiting benign disease that is characterized by rapid proliferation of fibroblastic and myofibroblastic cells. The characteristic gene fusion containing the USP6 gene is a genetic hallmark of NF and MYH9-USP6 is the most frequent fusion, suggesting that NF is not a reactive condition but a neoplastic disease. Malignant transformation of NF has been reported rarely as a single case associated with the PPP6R3-USP6 fusion. Here we report a case of soft part tumor of which the histological feature was a typical NF but showed aggressive and non-regressing growth with local invasion. Targeted RNA sequencing and fluorescence in situ hybridization analysis identified PPP6R3-USP6 with gene amplification. These findings indicate that the present case is the second case of malignant NF, and we suggest potential malignant transformation in certain NF cases.

Immunotherapy for genitourinary tumors.

The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin-2 and interferon-alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.

Acute kidney injury and intermediate-term renal function after clampless partial nephrectomy.

OBJECTIVES: To evaluate the incidence and predictors of acute kidney injury after clampless partial nephrectomy, and its impact on intermediate-term renal function. METHODS: The incidence and severity of acute kidney injury were assessed for 262 patients undergoing clampless partial nephrectomy between 2010 and 2015. The association between perioperative covariates and acute kidney injury was evaluated using multivariate logistic regression analysis. An annual change in estimated glomerular filtration rate from 1 year after surgery was calculated according to the presence or absence of acute kidney injury. An impact of acute kidney injury on postoperative renal impairment, defined as a ≥25% estimated glomerular filtration rate decrease, was evaluated. RESULTS: Overall, 21 (8.0%) patients experienced grade 1 acute kidney injury after clampless partial nephrectomy, and grade ≥2 acute kidney injury was not observed. High tumor complexity was the only independent predictor of acute kidney injury. Estimated glomerular filtration rate in patients with acute kidney injury improved within 1 year, and annual estimated glomerular filtration rate changes were similar among patients with or without acute kidney injury. Ultimately, 13 (5.0%) patients showed postoperative renal impairment during the median follow-up period of 37 months. Advanced age and diabetes mellitus were independent risk factors for renal impairment, but acute kidney injury was not. CONCLUSIONS: The incidence and severity of acute kidney injury after clampless partial nephrectomy are low. Low-grade acute kidney injury after clampless partial nephrectomy does not seem to affect intermediate-term renal function.

Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice.

Stress is associated with pathophysiology of both irritable bowel syndrome (IBS) and hypertension. Angiotensin receptor blockers (ARB) have anti-inflammatory properties via inhibition of angiotensin II (Ang II)/Ang II type I receptor axis (AT1). Inhibition of the classical RAS pathway is also involved in upregulation of angiotensin converting enzyme-2 (ACE2), which activates the Ang-(1-7)/Mas pathway to counteract inflammatory signaling and acts as a partner of the amino acid transporter, B0AT-1, to absorb tryptophan for regulation of microbiota-gut-brain axis. In this study, we determined the effects of ARB irbesartan on stress-induced intestinal inflammation. C57BL/6J mice were subjected to 2-week intermittent restraint stress. They were orally treated during the stress with either vehicle, 3 or 10 mg/kg/day irbesartan. Restraint stress resulted in colon inflammation with higher histological damage scores, increased expression of Nox4, TLR-4 and IL1-ß, accumulation of reactive oxygen species (ROS), and activation of the ACE-angiotensin II-AT1 receptor axis. Stress also downregulated intestinal amino acid transporter, ACE2/B0AT-1, and activity of intestinal mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K), resulting in decrease in α-defensins, changes in intestinal microbial contents, and perturbation of tryptophan metabolism with activation of the kynurenine pathway. Administration of irbesartan inhibited activation of stress-induced AT1 pathway to reduce intestinal ROS accumulation and inflammation, restored expression of ACE2/B0AT-1, activity of mTOR and p70S6K, dysbiosis and tryptophan metabolism. Our results suggest that AT1 is a potentially suitable therapeutic target in stress-induced intestinal inflammation, and that irbesartan could be beneficially suitable for the treatment of stressed patients with IBS.

pqiABC and yebST, Putative mce Operons of Escherichia coli, Encode Transport Pathways and Contribute to Membrane Integrity.

The membranes of single-cell organisms are crucial as the first line of defense. The outer membrane of Gram-negative bacteria is an asymmetric bilayer in which lipopolysaccharides (LPSs) and phospholipids are localized in the outer and inner leaflet, respectively. This asymmetry is important for membrane integrity. In Escherichia coli, the Mla transport pathway maintains this asymmetry by removing phospholipids from the outer leaflet. The MlaD component of this system is a mammalian cell entry (MCE) domain protein, and E. coli has two other MCE domain proteins of unknown function (PqiB and YebT). Here, we show that these two proteins are components of novel transport pathways that contribute to membrane integrity. The pqiAB operon is regulated by SoxS and RpoS. The yebST operon contains pqiAB homologues. Here, we found a third member of the pqi operon, ymbA (pqiC). A PqiB-PqiC complex bridges the inner and the outer membrane, and in other bacteria, pqiBC genes are located in operons together with transporter proteins. We show here that simultaneous deletion of pqiABC and yebST operons in an Δmla background rendered cells more sensitive to SDS-EDTA, and the SDS-EDTA sensitivity of mla mutants was rescued by additional copies of pqiABC We also found that the yebST operon was induced by a defect in LPS molecules. In conclusion, PqiABC and YebST are novel transport pathways related to the Mla transport pathway and important for membrane integrity. IMPORTANCE: Membranes of bacteria are crucial for stress resistance. The composition of the E. coli outer membrane is asymmetric, with asymmetry maintained by the Mla ABC transport pathway. We propose that the stress-inducible pqiABC operon and homologous yebST operon, both of previously unknown function, encode transport pathway proteins related to the Mla transport pathway. Deletion of these operons rendered cells more sensitive to membrane stress, and additional copies of pqiABC suppressed the SDS-EDTA sensitivity of mla mutant strains. We found that yebS'-'lacZ fusion was activated in mutant strains with defective LPS molecules.

A novel interactive educational system in the operating room--the IE system.

BACKGROUND: The shortage of surgeon is one of the serious problems in Japan. To solve the problem, various efforts have been undertaken to improve surgical education and training. However, appropriate teaching methods in the operating room have not been well established. The aim of this study is to assess the utility of a novel interactive educational (IE) system for surgical education on urologic surgeries in the operating room. METHODS: A total of 20 Japanese medical students were educated on urologic surgery using the IE system in the operating room. The IE system consists of two parts. The first is three-dimensional (3D) magnified vision of the operative field using a 3D head-mounted display and a 3D endoscope. The second is interactive educative communication between medical students and surgeons using a small-sized wireless communication device. The satisfaction level with the IE system and the physical burden on medical students was examined via questionnaire. RESULTS: All students utilized the IE system in urologic surgery and responded to the survey. Most students were satisfied with the IE system. They also felt more welcomed by the surgeon when using the IE system than when not using it. No major unpleasant symptoms were observed but five students (25 %) experienced mild eye fatigue as a result of viewing the medical images. CONCLUSIONS: The IE system has the potential to motivate students to become interested in surgery and could be an efficient method of surgical education in the operating room.

Predictive risk factors of postoperative urinary incontinence following holmium laser enucleation of the prostate during the initial learning period.

PURPOSE: To determine the predictive factors for postoperative urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP) during the initial learning period. PATIENTS AND METHODS: We evaluated 127 patients with benign prostatic hyperplasia who underwent HoLEP between January 2011 and December 2013. We recorded clinical variables, including blood loss, serum prostate-specific antigen levels, and the presence or absence of UI. Blood loss was estimated as a decline in postoperative hemoglobina levels. The predictive factors for postoperative UI were determined using a multivariable logistic regression analysis. RESULTS: Postoperative UI occurred in 31 patients (24.4%), but it cured in 29 patients (93.5%) after a mean duration of 12 weeks. Enucleation time >100 min (p=0.043) and blood loss >2.5g/dL (p=0.032) were identified as significant and independent risk factors for postoperative UI. CONCLUSIONS: Longer enucleation time and increased blood loss were independent predictors of postoperative UI in patients who underwent HoLEP during the initial learning period. Surgeons in training should take care to perform speedy enucleation maneuver with hemostasis.

Repeated exposure rather than the total volume of transfused components may influence the incidence of allergic transfusion reactions.

BACKGROUND: The plasma fraction of blood components has an essential role in the etiology of allergic transfusion reactions (ATRs). The difference of incidences of ATRs between fresh-frozen plasma (FFP) and platelet concentrates (PCs), in which plasma is the main component, is not clearly understood. This study compares the frequency of ATRs to FFP versus PCs on both first and subsequent (nonfirst) transfusions and considers the factors influencing the risk of ATRs. STUDY DESIGN AND METHODS: Five hospitals agreed to systematically collect and share 2 years of data (January 2010 through December 2011). This was a retrospective observational analysis of data including the number of transfusion episodes and ATRs for FFP and PCs on first-transfusion patients (without transfusion history) and previously transfused patients. RESULTS: The incidence of ATRs to PCs (2.51%) was significantly higher than to FFP (1.68%) on subsequent transfusions (p < 0.001). On the other hand, there were no significant differences in the incidences of ATRs to FFP (2.67%) and PCs (2.82%) on first transfusions. This discrepancy was most pronounced among males: FFP versus PCs on first transfusions, 2.02% versus 2.60% (p = 0.30); and on subsequent transfusions, 1.58% versus 2.46% (p = 0.0007). Among females, FFP versus PCs on first transfusions was 3.59% versus 3.13% (p = 0.61) and on subsequent transfusions was 1.87% versus 2.61% (p = 0.029). CONCLUSION: Repeated exposure rather than the total volume of transfused components may influence the incidence of ATRs.