High prevalence of thrombocytopenia in SLE patients with a high level of anticardiolipin antibodies combined with lupus anticoagulant

The relationship between thrombocytopenia and the level of anticardiolipin antibodies (aCL) and/or the existence of lupus anticoagulant (LA) ware studied in 146 patients with systemic lupus erythematosus (SLE). These patients were divided into six groups: A, those LA positive with a high level of aCL (>10 U/ml) (10 cases); B, those LA positive with a low level of aCL (3–10 U/ml) (15 cases); C, those LA positive but aCL negative (<3 U/ml) (12 cases); D, LA negatives with a high level of aCL (12 cases); E, LA negatives with a low level of aCL (16 cases); and F, aCL and LA double negatives (81 cases). The prevalence of thrombocytopenia (platelet count ≦ 100 × 10⁹/L) was by far the highest in group A (9/10 cases, 90.0%, P < 0.005, Fisher's exact probability test) as compared with group B (4/15 cases, 26.7%), group C (4/12 cases, 33.3%), group D (1/12 cases, 8.3%), group E (4/16 cases, 25.5%), and group F (9/81 cases, 11.1%). When the relationship between moderate thrombocytopenia and arterial or venous thrombosis was studied in these patients with SLE, thrombocytopenia was detected in 10 (83.3%, P < 0.005, Fisher's exact probability test) of 12 patients with arterial thrombosis; however, it was present in only 4 (23.5%) of 17 patients with venous thrombosis and in 14 (12.3%) of 114 patients without thrombosis. These findings suggest that a high aCL activity combined with LA positively reflects a high risk for both thrombocytopenia and arterial thrombosis. Am. J. Hematol 58:55–60, 1998. © 1998 Wiley-Liss, Inc.     

Fatal Immune Checkpoint Inhibitor-related Pancreatitis

We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.     

Monitoring of CA19-9 and SPan-1 can facilitate the earlier confirmation of progressing pancreatic cancer during chemotherapy

BackgroundMeasurement of objective response to chemotherapy using imaging modalities is sometimes difficult in pancreatic cancer (PC). We aimed to verify whether monitoring of serum tumor markers (TMs), namely carcinoembryonic antigen, CA19-9, DUPAN-2, SPan-1, can facilitate earlier confirmation of treatment failure.MethodsMonitoring of serum TMs and computed tomography were performed every 4 weeks until progression of disease in 90 patients with PC undergoing gemcitabine therapy. In Group A (January 2006–October 2007), we analyzed the fluctuation rates of TMs with high pretreatment positive rates, and defined the criteria of progressive disease under TM monitoring (TM-PD). In Group B (November 2007–October 2008), we calculated the time to progression (TTP) under this TM-PD criteria, which was compared with the TTP under the RECIST criteria.ResultsCA19-9 and SPan-1 had the highest pretreatment positive rates: 83% and 90%, respectively. In Group A (CA19-9, n = 38; SPan-1, n = 36), TM-PD criteria were defined as follows: fluctuation rates were ≥25% for a month or ≥10% for 2 consecutive months in CA19-9, and ≥10% for a month in SPan-1. In Group B (CA19-9, n = 18; SPan-1, n = 17), under these criteria, one-month earlier confirmation of treatment failure was feasible in 61% by CA19-9 and 59% by SPan-1. Furthermore, the combination could facilitate this determination in 72% (35/49), significantly better than CA19-9 alone (P = 0.004).ConclusionMonitoring of serum CA19-9 and SPan-1 is helpful for earlier confirmation of treatment failure during gemcitabine therapy in PC.     

Effectiveness of Acute Phase Hybrid Assistive Limb Rehabilitation in Stroke Patients Classified by Paralysis Severity

The purpose of the present study was to investigate the effectiveness of acute phase hybrid assistive limb (HAL) rehabilitation training for patients after stroke by measuring the difference in the severity of paralysis. Fifty-three acute stroke patients were enrolled in this prospective cohort study. HAL training was administered about twice per week, and the mean number of sessions was 3.9 ± 2.7. The walking training was performed on a treadmill with individually adjustable body weight support and speed and there was a 10-m walk test (10MWT) before and after each session. Assessment at baseline and at endpoint consisted of the Glasgow Coma Scale (GCS), Revised Hasegawa’s Dementia Scale (HDS-R), Brunnstrom stage (Brs), Functional Independence Measure (FIM), Barthel index (BI), and 10MWT. We measured these assessments at the first walking training session and at the end of the final training session without the HAL. To evaluate the feasibility of training with the HAL, the outcome measures of BI, FIM, and speed and number of steps of 10MWT were compared before and after training using a paired Wilcoxon’s signed-rank test in different Brs. Except for Brs IV, the Brs III or higher subgroups displayed significant amelioration in BI, and the Brs III subgroup displayed significant amelioration in FIM. The Brs V and VI subgroups displayed significant amelioration in 10-m walking speed and steps. In acute phase rehabilitation after stroke, it is thought that the HAL is more effective for patients with less lower-limb paralysis, such as Brs III or higher.     

Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis

We evaluated intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis, with special reference to bone mineral density (BMD) and prevention of spinal fracture. The patients were 40 women, over 50 years of age, with lumbo-dorsal pain and low BMD (less than 0.70 g/cm²), measured by dual-energy X-ray absorptiometry (DXA). The patients were randomly assigned to two groups. The first group (HEBP) received 200 mg of HEBP per day for 2 weeks, followed by 2 g calcium lactate and 0.5 μg alphacalcidol per day for the next 10 weeks. This 12-week cycle was repeated eight times for 2 years. The second group (Ca · D) received 2 g calcium lactate and 0.5 μg alphacalcidol per day for 2 years. Lumbar BMD was measured before the treatment and every 6 months during the treatment until 24 months, and changes were evaluated. The number of fractured vertebrae was counted on X-ray films before treatment and at the final assessment. After 6 months of treatment, a significant and continuous increase in BMD was observed in the HEBP group. Moreover, the percentage of patients with new vertebral compression fractures in the HEBP group was one-tenth of that in the Ca · D group. These results suggest that intermittent cyclical treatment with HEBP and calcium plus alphacalcidol may be effective for increasing BMD and preventing fractures in postmenopausal osteoporosis. Received: May 19, 2000 / Accepted: October 18, 2000