Double‐Filtration Plasmapheresis for the Treatment of Patients With Recalcitrant Atopic Dermatitis

The management of recalcitrant atopic dermatitis (AD) is a challenging issue for both clinicians and patients. In this study, we evaluate the clinical efficacy and safety of double‐filtration plasmapheresis (DFPP) in patients with recalcitrant AD. Eighteen patients with recalcitrant AD whose clinical condition had not been effectively controlled by current standard medical therapies were treated by either a single course of DFPP (N = 9) or with standard medical therapies only (N = 9). Clinical severity of AD was measured at baseline and at 1 and 4 weeks after treatment in patients in the DFPP group and at the corresponding time points in the control group using the standardized clinical severity scoring system for atopic dermatitis (SCORAD). In the nine patients who underwent DFPP, SCORAD values significantly decreased from 80.6 ± 16.7 (mean ± SD) at baseline to 65.9 ± 20.1 at 1 week and 69.8 ± 20.4 at 4 weeks after DFPP treatment (Wilcoxon signed‐rank test, P < 0.05). No significant side‐effects were observed during DFPP treatment. In the nine patients with recalcitrant AD who were treated with standard medical therapies, there were no significant differences between the SCORAD values at baseline (70.6 ± 13.9), 1 week (68.0 ± 14.4), and 4 weeks (69.8 ± 17.7) (P > 0.05). DFPP resulted in significant clinical improvements in patients with recalcitrant AD. Further studies are needed to evaluate the long‐term clinical usefulness of DFPP in the treatment of patients with recalcitrant AD.     

Tryptophan-immobilized column-based immunoadsorption as the choice method for plasmapheresis in Guillain-Barré syndrome

Plasmapheresis is widely performed as treatment for patients with Guillain-Barré syndrome (GBS) in the acute phase. As tryptophan-immobilized column-based immunoadsorption (Tr-IA) is a safer method than either double-filtration plasmapheresis (DFPP) or plasma exchange (PE), we investigated whether or not Tr-IA is as effective as other methods, and should be selected as the procedure of choice in patients with GBS. We retrospectively compared clinical outcomes, using Hughes grading, in GBS patients treated with Tr-IA, DFPP or PE. The outcome in the Tr-IA group was also compared historically with patients treated by PE in seven previous studies. We studied 34 patients with GBS: 20 were treated with Tr-IA, 11 with DFPP, and 3 with PE. The age, sex, duration from onset to initiation of treatment, and Hughes grade at entry did not differ among the Tr-IA, DFPP and PE groups. There was no significant difference in outcomes among these three groups, nor was there a significant difference between the outcomes in the Tr-IA and DFPP groups with respect to subgroups of Hughes grade at entry. Also, our Tr-IA group did not show a different outcome from the previously reported patients treated with PE. The frequency of complications in our Tr-IA group is significantly lower than that in both our DFPP group, and in the previously reported cases of patients treated with PE. Tr-IA, DFPP and PE have almost the same efficacy in patients with GBS, but Tr-IA is recommended as the plasmapheresis method of choice because of its safety.     

Ability to Remove Immunoglobulins and Antiganglioside Antibodies by Double Filtration Plasmapheresis in Guillain-Barré Syndrome: Is It Equivalent to Plasma Exchange?

Abstract: The value of plasma exchange (PE) in Guillain-Barré syndrome (GBS) is well established. In Japan, patients with GBS and related diseases often receive double filtration plasmapheresis (DFPP) as well as PE. No comparative trials between PE and DFPP, however, have been conducted. We compared their abilities to remove immunoglobulins and antiganglioside antibodies to find out whether DFPP is equivalent to PE. The ability to remove immunoglobulins and antiganglioside antibodies was compared between PE and DFPP using plasma samples from 41 patients with GBS and related diseases before and after each treatment session. The ability of DFPP to remove both IgGs and antiganglioside IgG antibodies were significantly inferior to those of PE. There is a less theoretical basis for selecting DFPP as the first choice of plasmapheresis for GBS and related disorders.—     

Comparative Study of Efficacy of Plasma Exchange Versus Intravenous Gammaglobulin Treatment on Acute Postinfectious Polyradiculoneuropathy: A Preliminary Report

Abstract: We tried to compare the efficacy of plasma exchange (PE) with that of intravenous immunoglobulin (IVIG) in patients with postinfectious polyneuritis (Guil-lain-Barre syndrome [GBS] and cranial neuritis). Fifteen patients with postinfectious polyneuritis were divided into 2 groups. The IVIG group included 5 cases of GBS and 2 cases of postinfectious cranial neuritis (ophthalmoplegic type). The PE group included 5 cases of GBS and 3 cases of postinfectious cranial neuritis (ophthalmoplegic type). The changes and incidences of improvement of muscle strength scores (MSSs) and ocular movement scores (OMSs) were evaluated before treatment and 1, 2, 3, and 4 weeks after treatment. No significant differences between the IVIG and PE groups were found in the MSSs or OMSs at any time after treatment. These data suggested that PE and IVIG had equivalent efficacy. In the IVIG group, the proportion of suppressor-inducer T cells significantly increased (p ≤ 0.01) (before versus after treatment), and the proportion of suppressor-effector cells also increased but not significantly (before versus after treatment). In the PE group, the percentage of suppressor-inducer T cells significantly decreased (p ≤ 0.05) (before versus after treatment) while the proportion of suppressor/ cytotoxic T cells significantly increased (p ≤ 0.05) (before versus after treatment). The percentage of suppressor-effector T cells also increased (before versus after treatment) but not significantly.     

Comparison of Citrate Anticoagulation During Plasma Exchange With Different Replacement Solutions

The aim of our retrospective study was to compare the application of regional citrate anticoagulation and citrate‐related side‐effects in plasma exchange (PE) with different replacement solutions. We included 35 patients treated with PE with regional citrate anticoagulation and divided them into three groups according to the replacement solution used: human albumin (HA) group (40 PE treatments), fresh frozen plasma (FFP) group (86 PE treatments), or a combination of the two (63 PE treatments). The citrate anticoagulation parameters, ionized calcium and metabolic consequences of citrate were compared. The blood flow and citrate infusion rates were similar in all groups. To maintain comparable values of ionized calcium during PE, significantly more calcium was replaced in the combination group (7.6 ± 1.3 vs. 6.2 ± 2.7 mL/h, P < 0.001) and even more in the FFP group (10.8 ± 1.7 vs. 6.2 ± 2.7 mL/h, P < 0.001) as compared to the HA group. The pH increased significantly and comparably in all groups, but the increase in bicarbonate was significantly higher in the FFP group (4.4 ± 3.0 vs. 2.6 ± 2.1 mmol/L, P = 0.01). A short, heparin‐free hemodialysis session was performed after the PE treatment, because of significant metabolic alkalosis (mainly with pH ≥ 7.5), significantly more often in the FFP group (14/86 PE, P < 0.01) as compared to the HA group (0/40), and only rarely in the combination group (2/63). To conclude, when FFP is used as a replacement solution during PE with citrate anticoagulation, significantly more calcium needs to be replaced and the increase in bicarbonate is greater during PE. The additional citrate contained in FFP, combined with frequent PE treatments, often causes significant metabolic alkalosis, which can be efficiently corrected with a short heparin‐free hemodialysis.     

More Selective Removal of Myeloperoxidase‐Anti‐Neutrophil Cytoplasmic Antibody From the Circulation of Patients With Vasculitides Using a Novel Double‐Filtration Plasmapheresis Therapy

Our aim was to investigate the removal of myeloperoxidase‐anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) from the circulation of patients with vasculitides by double‐filtration plasmapheresis (DFPP) using various primary separator and secondary separator combinations. Nineteen patients diagnosed with vasculitides positive for serum MPO‐ANCA were enrolled and received 56 sessions of DFPP. One patient received three sessions of DFPP using MPS07 (the primary filter)/EC50W (the secondary filter), nine patients received 27 sessions of DFPP using MPS07/EC20W, and the other nine patients received 26 sessions of DFPP using EC50W/EC20W. The sieving coefficients (SC) of albumin, immunoglobulin (Ig)A, IgG and IgM were measured, as well as the reduction ratio in plasma protein concentrations and MPO‐ANCA titer after a single session of DFPP. The MPS07 filter was well permeable for all the above‐mentioned plasma proteins; the EC50W and EC20W filters were permeable for albumin and IgG, less for IgA and IgM. During DFPP using MPS07/EC50W, the reduction ratio of IgG was much lower than IgM and IgA (30.5 ± 9.0% vs. 89.7 ± 5.4% and 61.7 ± 14.8%). During DFPP using MPS07/EC20W, the decline in IgM, IgA, and IgG was 94.2 ± 3.1%, 96.2 ± 2.3%, and 64.7 ± 21.0%, respectively. During DFPP using EC50W/EC20W, the decline in IgM, IgA, and IgG was 2.8 ± 12.9%, 90.9 ± 4.4%, and 43.5 ± 13.8%, respectively. The percentage reduction in MPO‐ANCA titer after a single session of DFPP using EC50W/EC20W was 34.6 ± 14.3%. DFPP using EC50W/EC20W filters may be more selective for the removal of pathogens such as IgG, with subsequently effective reduction of serum ANCA titer.     

Effects of dextromethorphan as add‐on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized,placebo‐controlled,double‐blinded,multiple crossover,single‐dose clinical trial

In this clinical trial, we investigated the blood glucose (BG)‐lowering effects of 30, 60 and 90 mg dextromethorphan (DXM) as well as 100 mg sitagliptin alone versus combinations of DXM and sitagliptin during an oral glucose tolerance test (OGTT) in 20 men with T2DM. The combination of 60 mg DXM plus 100 mg sitagliptin was observed to have the strongest effect in the OGTT. It lowered maximum BG concentrations and increased the baseline‐adjusted area under the curve for serum insulin concentrations in the first 30 min of the OGTT (mean ± standard deviation 240 ± 47 mg/dl and 8.1 ± 6.1 mU/l/h, respectively) to a significantly larger extent than did 100 mg sitagliptin alone (254 ± 50 mg/dl and 5.8 ± 2.5 mU/l/h, respectively; p < 0.05) and placebo (272 ± 49 mg/dl and 3.9 ± 3.0 mU/l/h, respectively; p < 0.001). All study drugs were well tolerated, alone and in combination, without serious adverse events or hypoglycaemia. Long‐term clinical trials are now warranted to investigate the potential of the combination of 30 or 60 mg DXM and dipeptidyl peptidase‐4 inhibitors in the treatment of individuals with T2DM, in particular as preclinical studies have identified the β‐cell protective properties of DXM.     

Community‐based exercise program reduces chronic knee pain in elderly Japanese women at high risk of requiring long‐term care: A non‐randomized controlled trial

Aim: To estimate the prevalence of low back pain and/or knee pain among the elderly at high risk of requiring long‐term care, and to determine the effectiveness of a community‐based exercise program provided in accordance with the Motor Function Improvement Program for improving low back and/or knee pain. Methods: The target population of this study was 320 residents aged ≥65 years who were eligible for the exercise program. For the intervention group, weekly exercise classes of 120 min duration were held 12 times over 3 months. The main outcome measures were changes between the baseline and 3‐month follow up in visual analog scale (VAS) scores for pain and in the Western Ontario McMaster Osteoarthritis Index (WOMAC) pain for severity of knee pain. Results: The number of participants reporting chronic low back and/or knee pain was 252 with a prevalence of 78.8%. Among them, 68 who were allocated to the intervention group and 125 to the control group completed the study, and were stratified by sex. In women, change in the VAS scores of low back pain was −17.5 ± 23.2 for the intervention group and −7.2 ± 23.4 for the control group (between‐group differences P = 0.03). For knee pain, significant changes in the VAS scores (between‐group differences P = 0.04) and WOMAC pain (P < 0.001) were observed; −14.9 ± 24.9 and −0.6 ± 3.1 for the intervention group, and −0.2 ± 28.5 and 2.2 ± 3.2 for the control group, respectively. No significant difference was observed in men. Conclusion: Community‐based exercise programs might reduce prevalent knee pain in elderly women at high risk of requiring long‐term care. Geriatr Gerontol Int 2013; 13: 167–174.     

Influence of Atorvastatin Versus Simvastatin on Fibrinogen and Other Hemorheological Parameters in Patients with Severe Hypercholesterolemia Treated with Regular Low‐Density Lipoprotein Immunoadsorption Apheresis

Abstract: Low‐density lipoprotein (LDL) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is more effective when combined with strong lipid‐lowering drugs, such as atorvastatin. However, conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration. Therefore, we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis. Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male, 54.0 ± 8.9 years) with coronary artery disease treated by weekly LDL immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma and blood viscosity at different shear rates, parameters of red cell aggregation at stasis and shear rate 3/s, and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks. Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin (3.09 ± 0.36 g/L) compared to simvastatin (3.13 ± 0.77 g/L). Plasma and blood viscosity as well as erythrocyte filterability were also unchanged. The increase in red cell aggregation at stasis during atorvastatin treatment (5.82 ± 1.00 U versus 4.89±0.48 U during simvastatin; p < 0.05) was inversely correlated with a lower high‐density liprotein (HDL) cholesterol concentration (1.17 ± 0.21 mmol/L versus 1.31 ± 0.30 mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to lower concentrations during atorvastatin (4.14 ± 0.61 mmol/L versus 4.56 ± 0.66 mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated (3,547 ± 1,239 ml during atorvastatin versus 3,888 ± 1,206 mL during simvastatin; p < 0.05). In conclusion, fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis. Therefore, with respect to hemorheology, we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption.     

Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β‐cell protection in individuals with type 2 diabetes

Aim: Postprandial release of intact proinsulin (IP) is an independent marker for β‐cell dysfunction in patients with type 2 diabetes. This open‐label, parallel‐group, two‐arm, pilot study compared the β‐cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin. Material and methods: Overall, 28 insulin‐naive type 2 diabetes subjects (mean ± SD age, 61.5 ± 6.7 years; diabetes duration, 9.8 ± 6.5 years; HbA1c, 7.1 ± 0.5%; BMI, 30.7 ± 4.3 kg/m²) treated with metformin and sulfonylurea were randomized to add once‐daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre‐ and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG). Results: Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 ± 13.4 vs. 23.3 ± 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 ± 19 to 121 ± 23 mg/dl; NPH: 156 ± 34 to 119 ± 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups. Conclusions: Adding basal insulin to metformin reduces postprandial β‐cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces β‐cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.     

Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case–control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10–21) and 13 (10–29) days respectively. Although the cumulative incidence of II–IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT.     

Long‐term outcomes of direct acting antivirals in post‐transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Long‐term functional outcomes of sofosbuvir‐based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post‐transplant hepatitis C virus (HCV) recurrence. Seventy‐three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24‐week sofosbuvir with ribavirin±pegylated interferon or interferon‐free sofosbuvir‐based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82‐112) weeks. Twelve of 73 (16.4%) died (10 non‐FCH, 2 FCH) and two underwent re‐LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non‐FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow‐up, MELD and Child‐Turcotte‐Pugh scores improved both in non‐FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short‐treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long‐term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child‐Turcotte‐Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals‐based treatments for severe post‐transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long‐term survival. The setting of severe HCV recurrence may require the identification of “too‐sick‐to‐treat patients” to avoid futile treatments.     

Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma

Background/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC. Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored. Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each). Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.     

Health status and hypoglycaemia with insulin degludec versus insulin glargine: a 2‐year trial in insulin‐naïve patients with type 2 diabetes

Insulin degludec (IDeg) is a new basal insulin with an ultra‐long and stable glucose‐lowering effect. We compared once‐daily IDeg and insulin glargine (IGlar), both in combination with metformin ± dipeptidyl peptidase‐4 inhibitors, in a 52‐week, open‐label, treat‐to‐target trial in patients with type 2 diabetes followed by a 52‐week extension trial in which subjects [n = 725/1030 (70.4%)] maintained their initial randomised treatment. Health status was assessed at baseline and 105 weeks using the Short Form‐36 (SF‐36 v2) questionnaire. SF‐36 scores were analysed (ITT population) using anova , with adjustments for covariates. At 105 weeks, the overall physical component score was significantly better with IDeg versus IGlar [treatment contrast (TC): 1.1 (0.1; 2.1)_95%CI, p < 0.05]. This was largely because of significantly better physical functioning [TC: 1.1 (0.0; 2.3)_95%CI, p < 0.05] and bodily pain sub‐domain scores [TC: 1.5 (0.2; 2.9)_95%CI, p < 0.05]. Improvements in health status with IDeg compared to IGlar were maintained after 2 years.     

Avaliação das propriedades dinâmicas da pressão arterial em mulheres com antecedentes de pré‐eclâmpsia

BackgroundWe investigated viscoelastic properties of the arterial wall in women with previous preeclampsia (PE) compared to those with normal pregnancy (NP).MethodsIn a cross‐sectional study 45 women with previous PE and 55 with NP were included, matched for age (PE 38±6 vs. NP 38±5 years, NS) and body mass index: (PE 25±4 vs. NP 26±4 kg/m², NS) studied, respectively, 76±34 and 86±48 months after delivery. We assessed arterial distensibility – pulse wave velocity (PWV, Complior) and reflected waves (augmentation pressure [AP], mmHg) and augmentation index (AIx) – in the central pressure wave and blood pressure (BP) on 24‐h ambulatory BP monitoring (ABPM).ResultsPE showed higher (p<0.01) peripheral systolic blood pressure (SBP): PE 131±18 vs. NP 121±19, and central SBP: PE 122±18 vs. NP 110±19 mmHg, with less amplification of central‐peripheral pressure: PE 10±4 vs. NP 12±5, p=0.041, and higher (p<0.05) AP: PE 10±3 vs. NP 8±2, and AIx: PE 26±5 vs. NP 20±5 mmHg, but PE and NP did not differ in pulse wave velocity. On ABPM, PE (n=39) vs. NP (n=33) had higher nighttime SBP: PE 121±10 vs. NP 108±10 mmHg and lower percentage nocturnal SBP fall: PE 11±6 vs. NP 18±11%, both p<0.02. During follow‐up, the need for antihypertensive medication was seven times higher in PE than in NP.ConclusionWomen with previous PE have a greater risk of hypertension, higher nighttime BP values, blunted nocturnal BP fall and changes in central pressure suggestive of increased reflected waves and peripheral vascular resistance. These factors may contribute to their higher cardiovascular risk after pregnancy.     

Recent Advances of Therapeutic Apheresis in Guillain‐Barré Syndrome

Abstract: Acute idiopathic demyelinating polyneuritis (AIDP), commonly known as the Guillain‐Barré syndrome (GBS), is an immune‐mediated demyelinating disease of the peripheral nerve and nerve roots. A number of immunological mechanisms were described, but the exact pathomechanism has not been explained fully. Presumably, a variety of immunological processes lead to a relatively uniform clinical phenotype. Two large multicenter studies showed that plasma exchange (PE) was significantly superior to supportive treatment only. Selective adsorption (SA) also was employed as a method of therapeutic apheresis, and various smaller studies established that both PE and SA are equally effective treatments for GBS. Recently, it was demonstrated that the number of apheresis treatments should be adapted to the severity of disease. A large multicenter controlled study established equal efficacy of PE and intravenous immunoglobulin treatment (IVIg) as well as the combination of PE and IVIg. Since that time, the use of apheresis for the treatment of GBS declined in many countries due to the easier application of IVIg. The number of patients treated in larger hospitals with long‐standing experience in the treatment of GBS also has declined.     

Effect of age on atrioventricular conduction in patients with chronic bifascicular block

Five hundred thirty-one patients with chronic bifascicular block and intact atrioventricular (A-V) conduction were studied and prospectively followed up to ascertain the effect of age on both severity of conduction defect and life history. The patients were subdivided into a younger group, aged 18 to 59 years, and an older group, aged 60 and above. They were further separated into those with primary conduction disease (118 patients) and those with organic heart disease (413 patients). In the patients with primary conduction disease, the findings were as follows (younger group, 60 patients, versus older group, 58 patients) (mean ± standard error of the mean): age 43 ± 1.4 versus 73 ± 1.1 (p < 0.001); A-H Interval 92 ± 3.8 versus 100 ± 3.8 ms (not significant); H-V interval 48 ± 1.6 versus 49 ± 1.6 ms (not significant). Progression to spontaneous A-V block was noted in no younger patient and one older patient (not significant) over a mean follow-up period of 3.5 ± 0.3 years. The 5 year total cumulative mortality was significantly higher in the older group with no difference in the incidence of sudden death in the two groups.In patients with organic heart disease, the findings were as follows (younger group, 170 patients, versus older group, 243 patients): age 48 ± 0.9 versus 71 ± 0.5 (p < 0.001); A-H interval 105 ± 2.3 versus 114 ±3.1 ms (p < 0.05); H-V interval 54 ± 1.3 versus 55 ± 0.9 ms (not significant). Progression to spontaneous A-V block was seen in six patients (3 percent) in the younger group and 15 (5 percent) in the older group (not significant). The 5 year total cumulative mortality was significantly higher in the older group with no difference in the incidence of sudden death in the two groups. With the exception of the A-H interval in the group with organic heart disease, the severity and progression of conduction disease were independent of advanced age in patients with chronic bifascicular block.     

Left atrial function and ventricular filling in hypertensive patients with paroxysmal atrial fibrillation

Objectives. We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation.Background. In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias.Methods. Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender.Results. The EH and EHf groups had similar systolic arterial pressures ([mean ± SD] group EH 185 ± 27, group EHf 173 ± 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 ± 55, group EHf 131 ± 57.8 g/m², p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 ± 6, group EH 37.9 ± 4.6, group EHf 44.6 ± 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 ± 3.6, group EH 34.5 ± 5, group EHf 40.4 ± 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 ± 4.4%, group EH 14.6 ± 5.5%, group EHf 9.3 ± 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals × mitral annulus area) was lower than normal in group EH (group N 2.9 ± 2.2, group EH 1.75 ± 0.8, group EHf 2.8 ± 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was “normalised” in group EHf, early flow being increased in this group (group N 42 ± 13, group EH 39 ± 29, group EHf 60 ± 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05).Conclusions. These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and “normalization” of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined.     

Effect of diuresis on the performance of the failing left ventricle in man

To determine the effect of diuresis on the performance of the failing left ventricle, we measured cardiac output, pulmonary wedge pressure and M-mode echo left ventricular diastolic dimension before and after diuresis in 13 patients with heart failure. Diuresis increased stroke volume (43 ± 23 ml to 50 ± 18 ml (p < 0.05) and decreased pulmonary wedge pressure (28 ± 3 mm Hg to 19 ± 5 mm Hg (p < 0.01)), mean blood pressure (100 ± 14 mm Hg to 88 ± 10 mm Hg (p < 0.01)) and systemic vascular resistance (2,059 ± 622 dynes-sec-cm^?5 to 1,783 ± 556 dynes-sec-cm^?5 (p < 0.05)). Echo left ventricular diastolic dimension was not changed by diuresis (6.0 ± 0.8 cm to 6.0 ± 0.8 cm). Percent change in stroke volume correlated with systemic vascular resistance (r = 0.60, p < 0.05) and with left ventricular diastolic dimension (r = 0.62, p < 0.05) but not with pulmonary wedge pressure (r = 0.12) or right atrial pressure (r = 0.04). Thus, diuresis improved the performance of the failing ventricle and reduced afterload, but it did not alter left ventricular diastolic dimension, an index of preload. These data suggest that diuresis improves ventricular function by decreasing afterload.