Removal Characteristics of Immunoadsorption with the Tryptophan-Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis.

Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan-immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan-immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were performed (five sessions of IA and 14 sessions of SeIA) when the processed plasma volume was 2 L. The corresponding reductions were 52.5% ± 6.2% for AChRAb, 58.8% ± 4.2% for fibrinogen, and 36.9% ± 5.5% for FXIII after one session of IA. The corresponding reductions were 45.2% ± 9.9% for AChRAb, 3.5% ± 6.9% for fibrinogen, and -4.6% ± 11.1% for FXIII after one session of SeIA. The removal rates for AChRAb, fibrinogen, and FXIII in IA were significantly higher than those in SeIA. IA could effectively remove AChRAb, and SeIA could retain fibrinogen and FXIII. IA can be combined with SeIA, resulting in both IgG autoantibodies removal by IA and retention of coagulation factors by SeIA.

Removal Dynamics of Autoantibodies, Immunoglobulins, and Coagulation Factors by Selective Plasma Exchange on Three Consecutive Days.

Selective plasma exchange has been shown to be effective in various diseases, but no studies have assessed the benefits of daily treatment. We aimed to investigate the removal dynamics of immunoglobulins, fibrinogen, and factor XIII on three consecutive days in three patients. For mean processed plasma volumes of 1.06 × plasma volume, reductions of 79.6%, 49.3%, and 8.6% were seen for immunoglobulins G, A, and M, respectively. The reductions for fibrinogen and factor XIII were 18.4% and 13.0%, respectively. Removal dynamics were similar for immunoglobulin G-related autoantibodies and immunoglobulin G when using daily selective plasma exchange. Moreover, daily use effectively removed the immunoglobulin G while retaining the coagulation factors. When disease-specific autoantibodies are limited to immunoglobulin G, daily selective plasma exchange may be a useful and safe method of intensive induction treatment for plasmapheresis. However, further study is required in larger cohorts to confirm these findings.

Selective Plasma Exchange for the Removal of Pemphigus Autoantibodies, Fibrinogen, and Factor XIII in Pemphigus Vulgaris.

Pemphigus vulgaris is a serious autoimmune skin disorder associated with desmoglein 1 and 3. Selective plasma exchange (SePE) for pemphigus vulgaris remains unknown. We investigated the removal characteristics of pemphigus autoantibodies, immunoglobulins, and fibrinogen in three cases. When the mean processed volume for SePE was 1.2 plasma volumes, the mean percent reduction was 50.7% for desmoglein 1, 48.9% for desmoglein 3, 50.3% for IgG, 29.8% for IgA, 1.9% for IgM, and 17.6% for fibrinogen. In one case, the percent reduction after four sessions of SePE within eight days was 87.0% for desmoglein 1, 85.1% for desmoglein 3, 76.6% for IgG, 53.5% for IgA, 7.9% for IgM, 41.6% for fibrinogen, and 31.4% for factor XIII. SePE can effectively remove pemphigus autoantibodies and retain coagulation factors, e.g. factor XIII and fibrinogen. In severe cases, SePE can be useful and safe for induction therapy.

Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration.

Hyperbaric oxygen therapy for a refractory skin ulcer after radical mastectomy and radiation therapy: a case report.

BACKGROUND: Radiation therapy is performed as an adjuvant therapy when indicated following surgical resection of malignant tumors. However, radiation exposure induces acute or chronic dermatitis, depending on the radiation dose, interval, tissue volume, or irradiated area of the body. Radiation-induced skin ulcers and osteomyelitis of the underlying bone are intractable late-stage complications of radiation therapy, and often require reconstructive surgery to cover exposed tissue. Hyperbaric oxygen therapy has been suggested as a treatment for delayed radiation injury with soft tissue and bony necrosis. CASE PRESENTATION: A 74-year-old Japanese female underwent left radical mastectomy for breast cancer (T3N3M0, stage IIIB) in 1987. Radiation therapy was initiated 6 weeks after the surgery. She received telecobalt-60 in a total dose of 50 Gy with 25 fractions to the left supraclavicular, parasternal and left axillary regions, and electron treatment (9 MeV) in a total dose of 50 Gy in 25 fractions to the left chest wall. After irradiation, her skin became thinner and more fragile on the left chest wall, but no severe infections were observed. She noticed a small ulcer that repeatedly healed and recurred in 2000. She visited the hospital where she received radiation therapy and was treated for a skin ulcer on the left chest wall in December 2012. A fistula developed and then pus was discharged in January 2013. She was referred to the hyperbaric medical center in February 2013, and the fistula (1.5 × 3 cm) with pus discharge was observed. She was diagnosed with a late-onset radiation-induced skin ulcer that developed 25 years after radical mastectomy. HBO2 (2.5 atmospheres absolute with 100% oxygen for 60 minutes) was indicated for the refractory ulcer and osteomyelitis of the ribs. The patient was treated with HBO2 a total of 101 times over the course of 1 year and completely recovered. CONCLUSIONS: Hyperbaric oxygen therapy can be performed safely for even more than 100 sessions in patients with radiation-induced skin ulcers and osteomyelitis. Hyperbaric oxygen therapy can be considered as an alternative, conservative treatment when surgical resection for late-onset, radiation-induced skin ulcers is not indicated because of fragile skin in the irradiated areas.

Removal Dynamics of Immunoglobulin and Fibrinogen by Conventional Plasma Exchange, Selective Plasma Exchange, and a Combination of the Two.

While plasma exchange (PE) can eliminate plasma proteins, including all immunoglobulin (Ig) and coagulation factors, selective plasma exchange (SePE) can retain fibrinogen (Fbg). Here, we investigated the removal dynamics of Ig and Fbg in 53 patients with immunological disorders by PE, SePE, and a combination of the two. When the mean processed plasma volume (PPV) was 0.9 plasma volume (PV), the mean percent reductions of Ig and Fbg by PE were both approximately 62%-65%. When the mean PPV was 1.1 PV, the mean percent reductions by SePE were 53.1% for IgG, 30.1% for IgA, 3.6% for IgM, and 19.0% for Fbg, respectively. In the three plasmapheresis sessions performed on alternate days, we classified treatments into three categories: PE group (PE-PE-PE, N = 2), SePE group (SePE-SePE-SePE, N = 14), and PE/SePE group (PE-SePE-SePE, N = 4). The mean percent reductions of IgG, IgA, IgM, and Fbg were 82.0%, 80.4%, 87.3%, and 80.9%, respectively, for the PE group; 76.4%, 57.7%, 43.3%, and 35.9%, respectively, for the PE/SePE group; and 75.4%, 50.6%, 3.2%, and 29.3%, respectively, for the SePE group. Plasmapheresis modalities can be combined according to clinical conditions, for instance, to achieve both the unspecific removal of pathogens by PE and retention of coagulation factors, such as Fbg, by SePE.

Removal Characteristics of Immunoadsorption With the Immusorba TR-350 Column Using Conventional and Selective Plasma Separators.

In Japan, immunoadsorption (IA) is performed using a conventional plasma separator and Immusorba TR-350 column (TR-350) for the treatment of neurological immune diseases. By this method, TR-350 has the limited maximal capacity of the immunoglobulin G (IgG) adsorption, and fibrinogen (Fbg) is reduced remarkably. Evacure EC-4A10 (EC-4A) is a selective plasma separator and the sieving coefficients of IgG and Fbg using EC-4A were 0.5 and 0, respectively. Here, we investigated the removal characteristics of IgG and Fbg in IA by TR-350 using two different plasma membrane separators: conventional plasma separator (PE-IA) and EC-4A (EC-IA). In vitro filtration using plasma effluent was performed with a closed circuit. When the processed volume was 3 L, estimated removal amounts by PE-IA were 3172 mg for IgG and 3329 mg for Fbg, respectively. When the processed volume was 3 L, estimated removal amounts by EC-IA were 4946 mg and 1916 mg, respectively. EC-IA can be considered useful for the removal of IgG, including auto-antibodies, while retaining Fbg, thereby allowing even daily use.

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange.

Selective plasma exchange (SePE) using a selective membrane separator is a modified method of simple plasma exchange (PE). Immunoglobulin G (IgG) subclass distribution is one of the important immunological characteristics of IgG. However, there is little information regarding the removal characteristics of IgG subclasses by SePE and conventional PE. Here, we investigated the removal ratio of IgG subclasses by PE and SePE in seven patients with immunological disorders. When the mean processed volume was 0.88 plasma volume (PV) (corresponding to 2.12 L), the mean percent reductions by PE were as follows: IgG, 63.2%; IgG1, 64.5%; IgG2, 64.0%; IgG3, 61.4%; and IgG4, 69.5%. When the mean processed volume was 1.18 PV (corresponding to 2.98 L), the mean percent reductions by SePE were as follows: IgG, 51.6%; IgG1, 55.3%; IgG2, 52.0%; IgG3, 53.7%; and IgG4, 64.6%. In both PE and SePE, using albumin solution as the supplementary fluid, IgG was effectively eliminated regardless of IgG subclasses.

Removal kinetics of antibodies against glutamic acid decarboxylase by various plasmapheresis modalities in the treatment of neurological disorders.

Plasmapheresis is one of the acute treatment modalities for neurological disorders associated with antibodies against glutamic acid decarboxylase (anti-GAD). However, there is little information about the removal kinetics of anti-GAD by various plasmapheresis modalities. Here, we investigated the removal rate of anti-GAD and fibrinogen (Fib) by immunoadsorption (IA), plasma exchange using a conventional plasma separator (OP-PE), and plasma exchange using a high cut-off selective membrane plasma separator (EC-PE) in two cases of anti-GAD-associated neurological diseases. In case 1, IA and OP-PE were used, and the percent reductions were as follows: anti-GAD: 38.2% and 69.1% and Fib: 67.7% and 68.2%, respectively. In case 2, OP-PE and EC-PE were used, and the percent reductions were as follows: anti-GAD: 65.8% and 48.5% and Fib: 68.5% and 19.8%, respectively. OP-PE could remove anti-GAD more efficiently than IA. Further, EC-PE could maintain coagulation factors such as Fib better than IA and OP-PE. It is important to select the appropriate plasmapheresis modality on the basis of the removal kinetics.

Solute removal capacity of high cut-off membrane plasma separators.

In vitro blood filtration was performed by a closed circuit using high cut-off membrane plasma separators, EVACURE EC-2A10 (EC-2A) and EVACURE EC-4A10 (EC-4A). Samples were obtained from sampling sites before the plasma separator, after each plasma separator, and from the ultrafiltrate of each separator. The sieving coefficient (S.C.) of total protein (TP), albumin (Alb), IgG, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), fibrinogen (Fib), antithrombin III (AT-III), and coagulation factor XIII (FXIII) were calculated. The S.C. of each solute using EC-2A and EC-A4 were as follows; TP: 0.25 and 0.56, Alb: 0.32 and 0.73, IgG: 0.16 and 0.50, IL-6:0.73 and 0.95, IL-8:0.85 and 0.82, TNF-α: 1.07 and 0.99, Fib: 0 and 0, FXIII: 0.07 and 0.17, respectively. When compared with the conventional type of membrane plasma separators, EVACURE could efficiently remove cytokines while retaining coagulation factors such as fibrinogen. Moreover, EC-2A prevented protein loss, whereas EC-4A could remove approximately 50% of IgG.