Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

<div><p>Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.</p></div

Measuring Outcome after Wrist Injury: Translation and Validation of the Swedish Version of the Patient-Rated Wrist Evaluation (PRWE-Swe)

<p>Abstract</p> <p>Background</p> <p>There is a need for outcome measurement instruments for evaluation of disability after trauma. The Patient-Rated Wrist Evaluation (PRWE) is a self-administered region-specific outcome measuring instrument developed for use in evaluating disability and pain of the wrist. The aim of this study is to translate and to cross-culturally adapt the PRWE for use in a Swedish patient population. Moreover, we aim at investigating the PRWE in terms of validity, reliability and responsiveness.</p> <p>Methods</p> <p>We performed a translation and cross-cultural adaptation of the PRWE to Swedish (PRWE-Swe), utilising the process recommended by the American Association of Orthopedic Surgeons. A total of 124 patients with an injury to the wrist were included in the study. They filled in the PRWE and the DASH questionnaires at two separate occasions.</p> <p>Results</p> <p>Reliability of the PRWE in terms of internal consistency (Cronbach's alpha 0.97) and test-retest stability (intraclass correlation coefficient 0.93) were excellent. Face validity and content validity were judged as good. Criterion validity assessed as the correlation between the PRWE and the DASH was also good (Spearman's rho = 0.9). Responsiveness measured by the standardized response mean (SRM) was good with an SRM_PRWEof 1.29.</p> <p>Conclusion</p> <p>This Swedish version of the PRWE is a short and easily understood self-administered questionnaire with good validity, reliability, and responsiveness. Our results confirm that the PRWE is a valuable tool in evaluating the results after treatment of a wrist injury.</p

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

The effect of flurbiprofen and tiaprofenic acid on serum cytokine levels of patients with osteoarthrosis

39 patients with active knee osteoarthrosis, chosen according to ACR criteria, were assigned to receive flurbiprofen (n 12, 2 x 100 mg), tiaprofenic acid (n 14, 2 x 300 mg) and placebo (n 13) in a 3-week, placebo-controlled study. All patients completed the study, and both medications were found to be effective: improvement occurred in the clinical signs. These drugs reduced the TNF-a levels. Flurbiprofen especially affected the IL-6 levels. Our findings indicate that NSAIDs may be effective in the etiopathogenesis of osteoarthrosis

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1-4 were not significantly different among the subgroups (0.920 +/- 0.08 g/cm(2), 0.801 +/- 0.09 g/cm(2), and 0.910 +/- 0.05 g/cm(2), for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 +/- 0.1 g/cm(2)) was significantly lower than the values in untreated patients (1.080 +/- 0.2 g/cm(2); P < 0.01) and in controls (1.028 +/- 0.17 g/cm(2); P < 0.05). For postmenopausals, the BMD value at L1-4 in controls (1.019 +/- 0.07 g/cm(2)) was significantly higher than the values in untreated patients (0.783 +/- 0.01 g/cm(2)) and in treated patients (0.751 +/- 0.08 g/cm(2); P < 0.001 for both). The BMD value at the femoral neck in controls (0.890 +/- 0.1 g/cm(2)) was higher than the values in untreated patients (0.745 +/- 0.08 g/cm(2)) and treated patients (0.747 +/- 0.1 g/cm(2)), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss

Congenital dyserythropoietic anemia type I with ringed sideroblasts

A 25-year-old male with anemia, jaundice and liver dysfunction was admitted to our institution. Anisopoikilocytosis with tear-drop forms, polychromasia, basophilic stippling in peripheral blood smear, erythroid hyperplasia with megaloblastoid changes, binucleated cells and intranuclear bridging in bone marrow aspirate and spongy, unevenly condensed nuclear chromatin in electron microscopy studies indicated that he had congenital dyserythropoietic anemia (CDA) type I. As a rare finding in CDA, ringed sideroblasts were noted. It is proposed that this patient is an example for the designation 'variant congenital dyserythropoietic anemia with ringed sideroblasts'