Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma

An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²), prednisone (100 mg days 3–7) and vincristine (1·4 mg/m²) (O‐CHOP), as frontline treatment for follicular lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) scores in the 500‐ and 1000‐mg dose groups, respectively. Overall response rate was 90% for the 500‐mg group and 100% for the 1000‐mg group. 62% of patients achieved complete response (CR)/unconfirmed CR (CRu). 76% of patients with FLIPI score 3–5 attained CR/CRu. Longer follow‐up time is needed for analysis of survival end points. The most common Common Terminology Criteria grade 3–4 investigator‐reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths have been reported. O‐CHOP was safe and efficacious in patients with previously untreated FL, including high‐risk FLIPI groups. This trial was registered at www.clinicaltrials.gov (NCT00494780).     

Surgical strategy in grade II astrocytoma: a population-based analysis of survival and morbidity with a strategy of early resection as compared to watchful waiting

Background

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods

Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n?=?169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results

Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p?<?0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5–7.6) if treated at the hospital favoring biopsy and watchful waiting (p?=?0.047). No difference in surgical-related neurological morbidity was seen (p?=?0.843).

Conclusions

Early 3D ultrasound guided resections improve survival, apparently without increased morbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.     

Treatment of frozen shoulder with subcutaneous TNF-alpha blockade compared with local glucocorticoid injection: a randomised pilot study

We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid injections administered every other week for a total of three administrations. The evaluation included validated scores. No effect of subcutaneous injections of adalimumab on frozen shoulder symptoms was demonstrated.     

Effect of acute changes in oxygen tension on flow-mediated dilation. Relation to cardiovascular risk

Objective. Oxygen-dependent changes in vascular diameters may be detrimental when the endothelium is dysfunctional. Design. Endothelial responsiveness was evaluated by brachial ultrasound and flow-mediated/nitroglycerin-mediated dilation (FMD/NMD). FMD/NMD was investigated in males with increased risk of cardiovascular disease (mean age 44±2 years, n =10) and matched controls without risk factors (44±2 years, n =10). FMD/NMD was assessed during normoxia (21% O₂, 79% N₂), while inhaling hypoxic gas (12.5% O₂, FMD_Hyp/NMD), and 100% O₂ supplementation (FMD_O2/NMD). In a second study we addressed the effect of lipid lowering. Twenty persons with cardiovascular risk (mean age 50±2 years) were treated with atorvastatin (80 mg/day) and FMD/NMD was measured during normoxia, hypoxia and oxygen supplementation before, after 1 day and 3 months. Results. Oxygen supplementation evoked vasoconstriction, while FMD_Hyp/NMD was reduced compared to FMD/NMD. Atorvastatin significantly lowered total cholesterol, LDL cholesterol, and ADMA after 1 day of treatment, while triglycerides, ApoB and hsCRP were lowered after 3 months. Atorvastatin did not change FMD/NMD irrespective of oxygen tension. Conclusion. Irrespective of risk factors or atorvastatin, hypoxia reduced endothelial vasodilation while oxygen supplementation evoked vasoconstriction.     

Gender Differences in the Electrophysiological Characteristics of Atrioventricular Conduction System and their Clinical Implications

Objective - The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff-Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. Design - The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. Results - The AH (83 &#45 15 ms) and His-ventricular intervals in men (42 &#45 6 ms) were significantly longer than in women (78 &#45 14, 38 &#45 6 ms, p < 0.05, respectively), as was the PR interval (160 &#45 17 vs 152 &#45 13 ms, p = 0.02). The effective refractory period of AV node in men (349 &#45 75 ms) was longer than in women (297 &#45 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 &#45 76 ms) than in women (330 &#45 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 &#45 107 vs 384 &#45 90 ms, p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). Conclusion - The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation.