Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab / 대한내과학회지

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, which results from uncontrolled complement activation. Delayed diagnosis and treatment of aHUS may result in end-stage renal disease (ESRD) and an associated dependence on dialysis. In extreme cases, it may cause death due to multi-organ failure. Eculizumab, a humanized monoclonal antibody against C5, inhibits the formation of the terminal membrane attack complex and is used to treat aHUS. Here, we report a 46-year-old male patient who suffered from aHUS relapse, despite prior treatment with repeated plasma exchange and hemodialysis. Eculizumab therapy improved his hematologic findings without use of hemodialysis.

Aspirin for Primary Prevention of Cardiovascular Disease

Aspirin has been used for decades for the primary and secondary prevention of cardiovascular disease (CVD). The effect of aspirin in secondary prevention is well-known but is still debatable for primary prevention. Despite the controversy, aspirin is believed to have a beneficial effect in primary prevention and has been widely used. However, whether the doubts concerning the wide use of aspirin are correct has resulted in the publication of data from several large clinical trials recently. There are several clinical guidelines from various international organizations on the use of aspirin for the primary prevention of CVD, and they offer some conflicting recommendations. A reduction in the overall incidence of CVD with the development of modern prevention therapies has weakened the impact of aspirin in primary prevention. Large randomized clinical trials have found decreased or no difference in CVD events but a significant increase in the risk of bleeding. Taking aspirin for the primary prevention of CVD is no longer recommended, especially for patients who have a low to moderate risk. An assessment of the balance between the benefits and risks of aspirin use should be considered.

Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. METHODS: We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. RESULTS: The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). CONCLUSION: These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients.

Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. MATERIALS AND METHODS: This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. RESULTS: The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. CONCLUSION: Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

Metastatic Thyroid Gland Tumor Presenting as an Initial Manifestation of Recurrent Uterine Cervical Cancer / 대한내과학회지

Most patients with recurrent uterine cervical cancer have intra-pelvis metastasis with adjacent lymph node involvement, while a lone, distant metastasis is extremely rare. We report a 79-year-old woman with recurrent uterine cervical cancer that presented as thyroid mass with no intra-pelvic recurrence. Four years earlier, the patient had been diagnosed with uterine cervical cancer. She had undergone a course of concurrent chemoradiotherapy to the pelvis and had no subsequent evidence of recurrence. Several weeks before presenting, she had noticed a foreign body sensation in her throat and a palpable mass in the left side of her neck. Clinically, this was metastatic squamous cell carcinoma from the uterine cervix. Patients who present with swelling or palpable nodules in the neck with a previously diagnosed malignancy must be evaluated for metastatic disease, although metastasis from uterine cervical carcinoma to the thyroid gland is rare.

Characterization of anti-factor VIII antibody in a patient with acquired hemophilia A

Acquired hemophilia A (AHA) is a bleeding disorder caused by the development of an auto-antibody against endogenous factor VIII (FVIII). In this study, the epitope of the autoantibody was identified in a 67-year-old female patient with AHA. A prolonged activated partial thromboplastin time (77.4 s) that failed to correct in an incubation mixing test (68.2 s), a decreased FVIII activity, and a high FVIII inhibitor (14.6 Bethesda units/mL) were observed. Enzyme-linked immunosorbent assay demonstrated that the antibody belonged to the immunoglobulin G4 subclass. An immunoblotting assay revealed the light chain (A3/C1/C2 domain) of FVIII as the binding region of the antibody. The bleeding experienced by our patient resulted from the interference of FVIII binding to both FIX by anti-A3 antibodies and phospholipids and von Willebrand factor by anti-C2 antibodies. To the best of our knowledge, this is the first study in Korea characterizing an autoantibody in the context of AHA.

Characterization of anti-factor VIII antibody in a patient with acquired hemophilia A

Acquired hemophilia A (AHA) is a bleeding disorder caused by the development of an auto-antibody against endogenous factor VIII (FVIII). In this study, the epitope of the autoantibody was identified in a 67-year-old female patient with AHA. A prolonged activated partial thromboplastin time (77.4 s) that failed to correct in an incubation mixing test (68.2 s), a decreased FVIII activity, and a high FVIII inhibitor (14.6 Bethesda units/mL) were observed. Enzyme-linked immunosorbent assay demonstrated that the antibody belonged to the immunoglobulin G4 subclass. An immunoblotting assay revealed the light chain (A3/C1/C2 domain) of FVIII as the binding region of the antibody. The bleeding experienced by our patient resulted from the interference of FVIII binding to both FIX by anti-A3 antibodies and phospholipids and von Willebrand factor by anti-C2 antibodies. To the best of our knowledge, this is the first study in Korea characterizing an autoantibody in the context of AHA.

Asymptomatic pneumatosis intestinalis following chemotherapy for B lymphoblastic leukemia with recurrent genetic abnormalities in an adolescent patient / 대한혈액학회지

Pneumatosis intestinalis (PI) is a rare condition characterized by multiple pneumocysts in the submucosa or subserosa of the bowel. Here, we report a rare case of asymptomatic PI after chemotherapy induction in an 18-yr-old man with B lymphoblastic leukemia with recurrent genetic abnormalities. The patient was treated conservatively and recovered without complications. The possibility of PI should be considered as a complication during or after chemotherapy for hematologic malignancies. Conservative treatment should be considered unless there are complications, including peritonitis, bowel perforation, and severe sepsis.