Cryoglobulinemia vasculitis associated with adult-onset Still's disease.

Key Clinical Message: The present case indicates that cryoglobulinemia vasculitis should be considered in the differential diagnosis of purpura in patients with adult-onset Still's disease (AOSD). Abstract: The presence of purpura is suggested in adult-onset Still's disease (AOSD) hematological complications of hemophagocytic syndrome, disseminated intravascular coagulation, or thrombotic microangiopathy. We herein report a case of AOSD complicated by cryoglobulinemia vasculitis presenting with purpura.

Nephrotic syndrome with rectus sheath hematoma: a case report.

BACKGROUND: Rectus sheath hematoma is a rare presentation often associated with abdominal trauma and anticoagulant therapy. Here, we present a patient with severe rectus sheath hematoma accompanied by nephrotic syndrome who achieved significant clinical improvement without the need for invasive treatment. CASE PRESENTATION: A 72-year-old Japanese woman was referred to our hospital for the treatment of nephrotic syndrome. She was receiving steroid and anticoagulant therapy. Then she had abdominal pain and she was diagnosed with spontaneous rectus sheath hematoma by abdominal computed tomography. She received transfusion and was managed conservatively with bed rest, which led to improvement in abdominal pain. CONCLUSION: Despite the absence of trauma history, rectus sheath hematoma should be considered in patients at risk of vascular failure, including those receiving anticoagulant or steroid therapy, those who are elderly, and those with nephrotic syndrome.

Inflammation and malnutrition as markers of poor outcomes in head and neck cancer patients treated with nivolumab.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) are approved for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), the response to ICIs remains unclear. AIMS/OBJECTIVES: To summarize the clinical outcomes of patients with HNSCC treated with nivolumab (Nivo) in our institution, and provide a basis for research on biomarkers that can predict the efficacy of ICIs. MATERIAL AND METHODS: Forty-four patients with R/M HNSCC who received Nivo (2017-2022) were retrospectively analysed. RESULTS: Despite the older age of this cohort (median age of 72 years), we observed favourable long-term outcomes, with an overall survival of 24.1 months, which could be attributed to our aggressive nutritional intervention. Older age, poor performance status (≥1), and higher Glasgow Prognostic Scores, reflecting the chronic inflammation and malnutrition of patients, were associated with poor prognoses, with hazard ratios for death of 2.63 (95% confidence interval [CI]; 1.07-6.46, p = .016), 3.50 (95% CI; 1.28-9.55, p = .001), and 2.69 (95% CI; 1.17-6.21, p = .029), respectively. Peripheral blood biomarker analysis revealed that systemic inflammation may negatively affect the efficacy of Nivo. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that nutrition and inflammation must be the focus of future studies aiming to identify novel biomarkers.

Leukemic phase as the initial presentation of ALK-positive anaplastic large-cell lymphoma complicated by lactic acidosis.

The leukemic phase of ALK-positive anaplastic large cell lymphoma (ALCL) is reported to have a poor prognosis. We, herein, report a rare case of the common type of ALK-positive ALCL complicated by lactic acidosis.

Complete remission after concurrent single-agent S-1 chemoradiotherapy for stage IIIB esophageal cancer: an autopsy case report.

Chemoradiotherapy regimens for patients with esophageal cancer intolerant to standard therapies remain to be established. The standard therapy for patients with stage II-III esophageal squamous cell carcinoma, who are not surgical candidates, is definitive chemoradiotherapy with concomitant use of 5-fluorouracil and cisplatin; however, cisplatin can cause serious adverse events. An 83-year-old Japanese man developed a 2-month history of nausea and vomiting. Contrast-enhanced computed tomography revealed concentric wall thickening in the mid-to-lower esophagus with surrounding regional lymph node swelling. Upper gastrointestinal endoscopy revealed an ulcerated tumor with raised margins in the middle esophagus. He was diagnosed with stage IIIB (T3N2M0) esophageal squamous cell carcinoma, pathologically exhibiting squamous epithelium-like invasive abnormal structure with atypical cells. He underwent chemoradiotherapy involving four-dimensional conformal radiotherapy and single-agent S-1 rather than the standard chemoradiotherapy, and achieved clinical remission 2 months later on endoscopy and computed tomography. The patient died 1 year later due to pneumonia, and the autopsy did not reveal any evidence of squamous cell carcinoma in the esophagus, surrounding lymph nodes, or other organs, suggesting pathologically complete remission. Concurrent single-agent S-1 chemoradiotherapy may induce complete remission of stage IIIB esophageal cancer and is a possible alternative for older patients or those with multiple comorbidities.

Gain-of-function IKBKB mutation causes human combined immune deficiency.

Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in two separate kindreds in whom probands presented with immune dysregulation, combined T and B cell deficiency, inflammation, and epithelial defects. IKBKB encodes IKK2, which activates NF-κB signaling. IKK2V203I results in enhanced NF-κB signaling, as well as T and B cell functional defects. IKK2V203 is a highly conserved residue, and to prove causation, we generated an accurate mouse model by introducing the precise orthologous codon change in Ikbkb using CRISPR/Cas9. Mice and humans carrying this missense mutation exhibit remarkably similar cellular and biochemical phenotypes. Accurate mouse models engineered by CRISPR/Cas9 can help characterize novel syndromes arising from de novo germline mutations and yield insight into pathogenesis.

Differences in anti-phosphatidylserine-prothrombin complex antibodies and cutaneous vasculitis between regular livedo reticularis and livedo racemosa.

OBJECTIVES: We examined the prevalence of LAC, aCL antibodies (Abs), anti-beta(2)-glycoprotein I (anti-beta(2)GPI) Abs and anti-phosphatidylserine-prothrombin complex (anti-PS/PT) Abs in patients with regular livedo reticularis or with livedo racemosa to determine whether those Abs correlate with the clinical or serological features. Assuming that a correlation exists, early recognition of the serological features of the cutaneous manifestations may aid in the treatment and prediction of complications. METHODS: We examined the prevalence of LAC, aCL Abs, anti-beta(2)GPI Abs and anti-PS/PT Abs in 143 Japanese patients who presented at our department with regular livedo reticularis or livedo racemosa between 2003 and 2008. LAC was determined according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies. Levels of anti-PS/PT, aCL and anti-beta(2)GPI Abs in serum samples taken from patients were measured by specific ELISAs. RESULTS: Anti-PS/PT Abs were detected in 94 (65.7%) of the livedo patients. Further, IgM anti-PS/PT Abs were detected in 90 (62.9%) of the livedo patients. Serum IgM anti-PS/PT Ab levels were significantly higher in livedo racemosa patients compared with regular livedo reticularis (19.2 +/- 17.0 vs 8.93 +/- 8.48 U/ml, P = 0.0013). Cutaneous vasculitis was significantly more prevalent among patients with livedo racemosa compared with regular livedo reticularis (P = 0.0014). Livedo racemosa patients had significantly higher CRP serum levels than regular livedo reticularis patients. Livedo racemosa has a stronger association with skin ulceration and arthralgia compared with regular livedo reticularis. Overall, we found a statistically significant association between cutaneous vasculitis and ischaemic cerebrovascular events in our livedo patients. CONCLUSIONS: We speculate that IgM anti-PS/PT Abs could be implicated in disease susceptibility for livedo racemosa. We further suspect that cutaneous vasculitis could be closely related to pathogenic factors that trigger the development of livedo racemosa. Early detection of cutaneous vasculitis in skin biopsies of livedo patients should be useful for prognostic evaluation, including ischaemic cerebrovascular events.

Antiphosphatidylserine-prothrombin complex antibodies in 3 patients with Behçet disease involving superficial vein thrombophlebitis.

BACKGROUND: Superficial vein thrombophlebitis is the common vascular symptom in Behçet disease and is characterized as erythema nodosum-like eruptions. Some studies have reported the presence of antiphospholipid antibodies (Abs) in patients with Behçet disease. OBSERVATIONS: We measured lupus anticoagulant, anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine-prothrombin complex antibody (Ab) levels in 3 patients with Behçet disease involving superficial vein thrombophlebitis. High levels of IgM antiphosphatidylserine-prothrombin complex Abs were found (mean [SD], 50.3 [43.1] U/mL; normal, <10 U/mL). One of the patients with Behçet disease was positive for both IgM and IgG antiphosphatidylserine-prothrombin complex Abs, and 2 were positive for lupus anticoagulant. Two patients were also positive for IgM anticardiolipin Abs, but the titers were low. In contrast, none of the patients with Behçet disease was positive for IgG anticardiolipin Abs or IgG or IgM anti-beta(2)-glycoprotein I Abs. CONCLUSIONS: A high titer of IgM antiphosphatidylserine-prothrombin complex Abs was found in our patients with Behçet disease involving superficial vein thrombophlebitis. We speculate that there is a relationship between the antiphospholipid Abs, especially IgM antiphosphatidylserine-prothrombin complex Abs, and superficial vein thrombophlebitis complications in Behçet disease. This study suggests that elevated serum antiphosphatidylserine-prothrombin complex Ab levels might play some role in the development of the vascular manifestations in Behçet disease.

Increased macrophage colony-stimulating factor levels in patients with Graves' disease.

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.

Changes in molecular markers of hemostatic and fibrinolytic activation under various sampling conditions using vacuum tube samples from healthy volunteers.

Molecular makers such as thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), and D-dimer, are useful markers in the diagnosis and assessment of various thrombotic conditions. These markers are measured in plasma after blood sampling. Difficult blood sampling is known to falsely elevate plasma TAT levels. However, it is not known exactly why this occurs. In the present study, we examined how levels of molecular markers of haemostatic and fibrinolytic activation change under various sampling conditions using vacuum tube samples from healthy volunteers. When blood was sampled continuously by taking 10 consecutive vacuum tube samples following application of a tourniquet, blood sampling resulted in an accurate assessment of these molecular makers. When blood was sampled continuously by taking vacuum tube samples every one minute over a total of 9 minutes to investigate possible changes in the levels of the molecular markers over time, plasma levels of TAT, SF, and F1+2 gradually increased with time. Plasma levels of TAT, F1+2, and SF increased beyond the normal range over the course of nine minutes. When blood was sampled using three alternative methods, which varied in terms of the duration of needle puncture (sampling B), duration of tourniquet use (sampling C), or both (sampling A), plasma TAT and SF levels were significantly increased with all three methods, compared to control samples. Plasma F1+2 levels were significantly increased with sampling methods A and B, compared to control samples, but not with sampling method C. On the other hand, plasma D-dimer levels were not significantly altered by any of the sampling methods. In conclusion, the results suggest that molecular markers of haemostatic and fibrinolytic activation, except for D-dimer, may be affected by sampling method, particularly the duration of needle puncturing. Therefore, care needs to be taken when using TAT, F1+2, and SF levels to diagnose and estimate activation of the coagulation system.

Expression of annexin II in human atherosclerotic abdominal aortic aneurysms.

BACKGROUND: Annexin II is a receptor for tissue-type plasminogen activator (t-PA) that converts plasminogen to plasmin. Although the fibrinolytic system is known to play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs), the relationship between annexin II and AAA development is unknown. Therefore, we examined annexin II localization in the wall of human atherosclerotic AAAs. METHODS AND RESULTS: Specimens from 13 patients undergoing elective repair of an AAA were taken. Annexin II expression was evaluated by immunohistochemical analysis. Immunostaining results were semiquantitatively analyzed using histology scores and WinROOF software based on staining intensity. The expression of annexin II was increased and the histology score was higher in the shoulder region of the atheromatous plaque than in the atheroma and fibrous plaque regions. Annexin II appeared to have greater expression and the histology score was higher in regions where the media was preserved. Furthermore, there was a significant inverse correlation between AAA size and histology score in the fibrous plaque region. CONCLUSIONS: The present work demonstrates various levels of annexin II expression within the aneurysm wall. Therefore, we suggest that alteration of annexin II expression within the aortic wall may be associated with the development of an aneurysm.