Elevated serum vasohibin-1 levels in atopic dermatitis: Implications for disease chronicity.

Atopic dermatitis (AD) is often characterized by chronic skin changes of dermal fibrosis, typically regulated by inflammatory and angiogenic factors. However, the significance of angiogenesis inhibitory factors in the development of AD is poorly understood. The present study investigated the potential role of an angiogenesis inhibitory factor, vasohibin-1 (VASH1), in AD by evaluating serum and skin VASH1 levels and their correlation with clinical features. The results showed that VASH1 expression levels in both the serum and skin of patients with AD were significantly elevated compared to healthy controls. Immunohistochemical staining of AD skin showed increased VASH1 expression in dermal vascular endothelial cells. Notably, there was a significant correlation between serum VASH1 levels and disease duration as well as VASH1 and vascular endothelial growth factor A expression levels in the skin tissue of patients with AD. These results may suggest a pathogenesis of increased angiogenesis and associated elevated inhibitory processes accompanying inflammation in the chronic phase of AD.

Impact of Pretreatment Systemic Inflammatory Markers on Treatment Persistence with Biologics and Conventional Systemic Therapy: A Retrospective Study of Patients with Psoriasis Vulgaris and Psoriatic Arthritis.

Systemic inflammation plays a central role in the pathophysiology of psoriasis. This study examined accessible systemic inflammatory markers in patients with psoriasis vulgaris and psoriatic arthritis. We aimed to evaluate their association with psoriasis severity, the presence of arthritis, and drug continuation rates. The findings revealed that neutrophil, monocyte, and platelet count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, systemic inflammation response index, systemic immune/inflammation index (SII), and CRP were positively correlated with Psoriasis Area and Severity Index scores. Patients presenting with higher platelet/lymphocyte ratio (PLR) or CRP values were more likely to be diagnosed with psoriatic arthritis than with psoriasis vulgaris in the multivariate regression analysis. Importantly, patients with higher pretreatment neutrophil or platelet count, PLR, and SII were associated with lower treatment continuation rates of conventional systemic agents. Higher pretreatment scores of systemic inflammatory markers did not affect treatment retention rates of biologics. These findings suggest that several accessible systemic inflammatory markers may effectively assess underlying systemic inflammation and may provide an indication for a therapeutic approach in patients with psoriasis vulgaris and psoriatic arthritis.

[Acquired factor V inhibitor associated with apixaban].

Acquired factor V inhibitor is an acquired coagulation disorder that is rare. We report the case of a patient who was treated with apixaban and developed acquired factor V inhibitor. The patient was a 76-year-old man who has been on long-term treatment with aspirin and clopidogrel after undergoing percutaneous coronary intervention (PCI) and carotid artery stenting. In June, he developed a cerebral infarction six days after the second PCI. Apixaban was added to his treatment regimen for cariogenic cerebral embolism. Three months later, intramuscular hemorrhage occurred in his left leg after a fall. However, the hemorrhage improved upon aspirin withdrawal. Unexpectedly, subcutaneous and intramuscular hemorrhage recurred three months after the patient commenced anticoagulation therapy. At this time, the APTT was 242.5 seconds and the PT was over the reference range. Although clopidogrel and apixaban were discontinued, these abnormalities did not improve. However, a cross-mixing test showed an inhibitor pattern, with factor V activity being less than 1% and its inhibitor level being 8.0 BU/ml. Based on these findings, the patient was finally diagnosed of acquired factor V inhibitor. One month after prednisolone administration at 20 mg/day, the PT and APTT were normalized, and prednisolone was tapered off. Although the use of dabigatran has been associated with iatrogenic acquired factor V inhibitor, we describe the first case of acquired factor V inhibitor associated with direct Xa inhibitor.

Pathological changes in the lymphatic system of patients with secondary upper limb lymphoedema.

Secondary upper limb lymphoedema is usually caused by lymphatic system dysfunction. Diagnosis is primarily based on clinical features. However, there are no distinct diagnostic criteria for lymphoedema. Although conventional lymphoscintigraphy is a useful technique to diagnose the severity of lymphoedema, the resultant data are two-dimensional. In this study, we examined the pathology of lymphoedema using single photon emission computed tomography-computed tomography lymphoscintigraphy (SPECT-CT LSG), a new technique that provides 3-dimensional information on lymph flow. We observed lymph flow pathways in the subcutaneous and muscle layers of the upper limbs. A significant positive correlation was found between the dermal back flow (DBF) type and the visualization of lymph nodes around the clavicle (p = 0.000266), the type of lymph flow pathways and the visualization of lymph nodes around the clavicle (p = 0.00963), and the DBF type and the lymph flow pathway (p = 0.00766). As the severity of lymphoedema increased, the DBF appeared more distally in the upper limb and the flow into the lymph nodes around the clavicle decreased, whereas the lymph flow pathways in the muscle layer became dominant. These findings demonstrate the features of lymphoedema pathology and the functional anatomy and physiology of the lymphatic system without the need for cadaver dissection.

Capnocytophaga canimorsus sepsis in a methotrexate-treated patient with rheumatoid arthritis.

Capnocytophaga canimorsus is a gram-negative rod that can be transmitted primarily by dog bites. This life-threatening organism commonly causes sepsis in patients with splenectomy or alcoholism. A 53-year-old rheumatoid arthritis male treated with methotrexate (MTX) for 5 years was admitted for a 4-day history of fever and dyspnea. He had been bitten on a finger by the family dog 4 days before onset. Laboratory tests revealed pancytopenia, acute renal failure, and evidence of disseminated intravascular coagulation, and he subsequently developed acute respiratory distress syndrome. Furthermore, blood cultures grew gram-negative bacilli and despite intensive treatment, he died 5 days after admission. Later, C. canimorsus was identified from his culture samples using a species-specific polymerase chain reaction. C. canimorsus infections should be considered in the differential diagnosis of sepsis for immunocompromised hosts following animal bites.

Splenic marginal zone lymphoma uncovered after a 10-year follow up as anemia of unknown cause.

A 75-year-old man was referred to our hospital for evaluation of persistent anemia. Despite repeated diagnostic tests, including bone marrow aspiration, the cause of his anemia remained unknown. On each occasion, computed tomography had revealed neither swollen lymph nodes nor splenomegaly. After a 10-year follow-up period, he was admitted with general fatigue and had developed splenomegaly as well as the anemia. Bone marrow biopsy revealed increased abnormal lymphocytes with short villi that were positive for CD11c, CD19, CD20, and kappa chain, but not for CD5, CD10, CD23, or cyclin D1, according to flow cytometry. The bone marrow biopsy sample showed nodular proliferation of small to medium-sized abnormal lymphocytes. Based on these findings, the patient was diagnosed as having splenic marginal zone lymphoma, a rare indolent B-cell neoplasm. Although his splenomegaly diminished after eight cycles of weekly rituximab monotherapy, the anemia did not improve, and abnormal lymphocytes remained detectable in his bone marrow. The patient was then treated with bendamustine monotherapy for six cycles, after which the anemia resolved, and he has since been in good condition. Although rare, it is important to consider splenic marginal zone lymphoma during the differential diagnosis of patients with a long history of anemia of unknown cause.

[Hemolytic Anemia with Excessively Elevated Lactic Dehydrogenase Levels].

It has become easier to acquire patients' clinical information from clinical laboratories using the electronic medical record system. However, it is possible that clinical laboratories do not consider abnormal laboratory data when elucidating the pathological mechanism of diseases in patients when their clinical information is obtained from the electronic medical records. In this reversed clinicopathological conference, we analyzed the laboratory data of a patient with elevated lactate dehydrogenase (LD) levels and anemia. Although the presence of hemolysis was clear from the elevated LD levels, anemia, and decreased haptoglobin levels, the ,excessive increase in the LD level suggested a particular mechanism of hemolysis. Drug intake was sus- pected on the basis of a prolonged prothrombin time with a normal activated partial thromboplastin time. At the conference, these findings led to in-depth discussions. We elucidated the pathological mechanism in this patient based only on the laboratory data, with intentionally restricted clinical information, and again recog- nized the importance of analyzing laboratory data thoroughly. Training modules for medical technologists and doctors in clinical laboratories that provide information regarding elucidating pathological mechanisms using laboratory data may prove useful for improving the nature of comments in laboratory data reports. In addition, clinicians should also receive training to elucidate the pathological mechanism of a disease on the basis of only laboratory data, as well as training for diagnosing patients on the basis of clinical information and physical examination findings. [Review].

Successful bortezomib/dexamethasone induction therapy with lenalidomide in an elderly patient with primary plasma cell leukemia complicated by renal failure and pulmonary hypertension.

Primary plasma cell leukemia (PPCL) is a rare disease that progresses rapidly. In such cases, it is difficult to achieve remission, and early intensive chemotherapy is recommended. We herein describe the case of a 76-year-old man with PPCL complicated by renal failure and pulmonary hypertension. Bortezomib/dexamethasone induction therapy with lenalidomide was administered in association with continuous hemodiafiltration (CHDF). Complete remission was achieved after a single course of treatment, resulting in the cessation of CHDF. With the patient in remission, the administration of beraprost and bosentan resulted in improvements in the pulmonary hypertension. The results of this case report support the use of bortezomib/lenalidomide/dexamethasone combination therapy as an effective treatment for elderly PPCL patients with various complications.