Neutrophil NETosis is a unique form of cell death, characterized by the release of decondensed chromatin and antimicrobial contents to the extracellular space, which is involved in inflammation and thrombosis. However, the role of NETosis in the pathogenesis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and how a targeted therapy affects the accumulation of neutrophil extracellular traps (NETs) under flow remain unknown. Flow cytometry demonstrated that the percentage of neutrophils undergoing NETosis in whole blood from patients with iTTP on admission was significantly increased, with a concurrent decrease in the capacity of inducible NETosis by shigatoxin. After therapy, the percentage of H3Cit+MPO+ neutrophils was significantly reduced, with an improvement in inducible NETosis in these patients. Additionally, little to no NET and thrombus formation was detected underflow in the whole blood from patients with iTTP when platelet counts were very low, but the NET and thrombus formation was dramatically increased following therapy when platelet counts rose to ≥50 × 109/L or were restored to normal with donor platelets. Similarly, there was no thrombus or NET accumulation under flow in the whole blood from vwf-/- mice, but NET accumulation was significantly higher in Adamts13-/- mice than in wild-type mice. Finally, recombinant ADAMTS13 or caplacizumab (or anfibatide) prevented NET and thrombus formation under flow in whole blood from patients with iTTP or from Adamts13-/- mice. These results indicate that neutrophil NETosis and NET formation depend on platelets and von Willebrand factor (VWF) in iTTP, and a targeted therapy such as recombinant ADAMTS13 or caplacizumab may prevent NET and thrombus formation under flow in iTTP.

Giant cell arteritis (GCA) is a chronic vasculitis that primarily affects the elderly, and can cause visual impairment, requiring prompt diagnosis and treatment. The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been substantial. Although vaccination programs have been a key defense strategy, concerns have arisen regarding post-vaccination immune-mediated disorders and related risks. We present a case of GCA after COVID-19 vaccination with 2 years of follow-up. A 69-year-old woman experienced fever, headaches, and local muscle pain two days after receiving the COVID-19 vaccine. Elevated inflammatory markers were observed, and positron emission tomography (PET) revealed abnormal uptake in the major arteries, including the aorta and subclavian and iliac arteries. Temporal artery biopsy confirmed the diagnosis of GCA. Treatment consisted of pulse therapy with methylprednisolone, followed by prednisolone (PSL) and tocilizumab. Immediately after the initiation of treatment, the fever and headaches disappeared, and the inflammation markers normalized. The PSL dosage was gradually reduced, and one year later, a PET scan showed that the inflammation had resolved. After two years, the PSL dosage was reduced to 3 mg. Fourteen reported cases of GCA after COVID-19 vaccination was reviewed to reveal a diverse clinical picture and treatment response. The time from onset of symptoms to GCA diagnosis varied from two weeks to four months, highlighting the challenge of early detection. The effectiveness of treatment varied, but was generally effective similarly to that of conventional GCA. This report emphasizes the need for clinical vigilance and encourages further data collection in post-vaccination GCA cases.

In some cases, differentiating thrombotic thrombocytopenic purpura (TTP) from septic disseminated intravascular coagulation (DIC) without measuring ADAMTS13 activity is critical for urgent lifesaving plasma exchange. To investigate whether PLASMIC score without identifying the presence of schistocytes, D-dimer, fibrin/fibrinogen degradation products (FDP), FDP/D-dimer ratio, prothrombin time-international normalized ratio (PT-INR), lactate dehydrogenase (LD), hemoglobin (Hb), and LD/Hb ratio are useful in differentiating patients with TTP from those with septic DIC. Retrospective analysis was conducted on the medical records of the patients with septic DIC (32 patients) or TTP (16 patients). The PLASMIC score and other laboratory measurements all were helpful in differentiating TTP from septic DIC. When dichotomized between high risk (scores 6–7) and intermediate–low risk (scores 0–5), the PLASMIC score predicted TTP with a sensitivity of 75.0% and a specificity of 100%. However, 4 of 16 patients with TTP and 19 of 32 patients with septic DIC showed comparable PLASMIC scores of 4 or 5, making it difficult to distinguish between the two by PLASMIC score alone. Among the measurements examined, the LDH/Hb ratio was the most useful for differentiation. Receiver operating characteristic analysis of the LD/Hb ratio for predicting TTP revealed a cutoff of 53.7 (IU/10 g) (sensitivity 0.94, specificity 0.91). If the LD/Hb ratio was less than 53.7, it was unlikely that the patient had TTP. A combination of the LD/Hb ratio and the PLASMIC score may be useful for distinguishing between TTP and DIC and identifying patients who need rapid plasma exchange or caplacizumab administration.

Background and Objectives: The Dix–Hallpike test (DHT) is the standard diagnostic maneuver for posterior semicircular canal benign paroxysmal positional vertigo (BPPV). However, some patients present with positional symptoms compatible with BPPV yet show no observable nystagmus on the DHT. We introduced the Head Rotation Sit-up Test (HRST) as a symptom-based maneuver and hypothesized that it would identify DHT-negative patients who nonetheless benefit from canalith repositioning. This study aimed to explore the potential role of the HRST. It was introduced as a complementary, symptom-based maneuver for evaluating non-classical vertigo presentations. Materials and Methods: We retrospectively reviewed patients clinically suspected of having BPPV by the attending physicians at Nara Medical University Hospital (August 2018–July 2022). All underwent both the DHT and HRST; those positive on either test received the Epley maneuver and were included. Patients were categorized as Group 1: DHT(−)/HRST(+), and Group 2: DHT(+), irrespective of the HRST, for the purpose of comparing patients who were positive on the HRST with those positive on the DHT. Post-treatment symptom severity was assessed on a 0–10 scale, with the patient’s most severe pre-treatment symptom defined as 10, and responder rates (post-Epley score < 5) were compared. Results: Among 179 patients with suspected BPPV, 80 were test-positive and were treated with the Epley maneuver. Group 1 comprised 31 patients, who more commonly reported non-rotational symptoms such as floating or unsteadiness, whereas rotational vertigo predominated in Group 2 (n = 49). Median post-Epley scores were significantly lower after treatment in both groups (Group 1: 2 [IQR 0–3]; Group 2: 3 [IQR 0–5]). Group 1 demonstrated a higher responder rate than Group 2 (90.3% vs. 65.3%, p = 0.016). Within Group 2, outcomes did not differ significantly between DHT(+)/HRST(+) and DHT(+)/HRST(−) subgroups. Conclusions: The HRST identified a clinically relevant subgroup of DHT-negative patients who nevertheless responded favorably to the Epley maneuver. Incorporating the HRST alongside the DHT may expand the diagnostic reach for BPPV, particularly among patients with non-classical symptoms or without observable nystagmus. These findings support the HRST as a useful complementary maneuver for detecting Epley responsive, symptom based positional vertigo.

Objective: This study aimed to evaluate treatment outcomes, complications, and the clinical course of thrombocytopenia in patients with TAFRO syndrome. Methods: We conducted a retrospective analysis of patients treated at Nara Medical University Hospital from 2015 to 2023. Diagnosis of TAFRO syndrome was made according to the 2015 or 2019 criteria, and disease severity was assessed based on the updated disease severity classification. Clinical characteristics and laboratory and histological data were analysed. Results: Seven patients were included, with four classified as very severe, two as severe, and one as slightly severe. All the patients received early combination therapy (various combinations of glucocorticoids, tocilizumab, cyclosporine, and rituximab), with the second therapy added a median of 5 days after the first. Six patients received eltrombopag. Despite intensive treatment, thrombocytopenia persisted for a prolonged period, with a median time to platelet count normalization of 54 days. Cytomegalovirus reactivation occurred in six patients during treatment but resolved with appropriate antiviral therapy. All the patients achieved remission and survived. Conclusions: Thrombocytopenia in TAFRO syndrome persists long term despite intensive combination therapy. Early combination therapy was associated with excellent survival outcomes, suggesting that intensifying treatment solely for thrombocytopenia may not be necessary given its prolonged course.

Purpose: This study aims to investigate the characteristics of Epstein–Barr virus associated-hemophagocytic lymphohistiocytosis (EBV-HLH) and HLH caused by a severe form of infectious mononucleosis (IM-HLH) compared to IM by EBV, and thus also to assist in early diagnosis and providing appropriate treatment. Methods: Data for this analysis were collected from patients at the Department of General Medicine, Nara Medical University, between April 1, 2012, and August 1, 2020. EBV infection was diagnosed using clinical presentation and laboratory tests. HLH diagnosis followed the HLH-2004 protocol, supplemented by plasma EBV DNA detection. A range of clinical and laboratory parameters were collected, including age, sex, clinical outcomes, blood cell counts, hemoglobin, platelets, and various serum values. Plasma EBV DNA levels and flow cytometric analysis (FCM) of bone marrow were performed for HLH cases. Results: Among 1850 hospitalized patients, 14 cases were identified, including 2 HLH cases and 12 IM cases. Comparative analysis revealed distinctive features of HLH, including lower lymphocyte and platelet counts and higher levels of ferritin, soluble interleukin 2 receptor (sIL-2R), and D dimer compared to IM. Notably, one HLH case responded well to corticosteroid monotherapy, while the other case did not, resulting in a fatal outcome. Detection of a cluster of CD5-CD7 lymphocytes in bone marrow is a hallmark of EBV-HLH and useful to distinguish from IM-HLH. Conclusion: This study underscores the importance of early differentiation among EBV-HLH, IM-HLH, and IM in adults to guide appropriate treatment strategies. While specific laboratory markers help distinguish HLH from IM, a more detailed analysis of FCM is crucial for precise diagnosis of HLH cases and tailored therapeutic interventions.