Mesh-fixation method and pain and quality of life after laparoscopic ventral or incisional hernia repair: a randomized trial of three fixation techniques

Background: Persistent, activity-limiting pain after laparoscopic ventral or incisional hernia repair (LVIHR) appears to be related to fixation of the implanted mesh. A randomized study comparing commonly used fixation techniques with respect to postoperative pain and quality of life has not previously been reported. Methods: A total of 199 patients undergoing non-urgent LVIHR in our unit between August 2005 and July 2008 were randomly assigned to one of three mesh-fixation groups: absorbable sutures (AS) with tacks; double crown (DC), which involved two circles of tacks and no sutures; and nonabsorbable sutures (NS) with tacks. All operations were performed by one of two experienced surgeons, who used a standardized technique and the same type of mesh and mesh-fixation materials. The severity of the patients’ pain was assessed preoperatively and at 2 weeks, 6 weeks and 3 months postoperatively by using a visual analogue scale (VAS). Quality of life (QoL) was evaluated by administering a standard health survey before and 3 months after surgery. Results in the three groups were compared. Results: The AS, DC, and NS mesh-fixation groups had similar patient demographic, hernia and operative characteristics. There were no significant differences among the groups in VAS scores at any assessment time or in the change in VAS score from preoperative to postoperative evaluations. The QoL survey data showed a significant difference among groups for only two of the eight health areas analyzed. Conclusion: In this trial, the three mesh-fixation methods were associated with similar postoperative pain and QoL findings. These results suggest that none of the techniques can be considered to have a pain-reduction advantage over the others. Development of new methods for securing the mesh may be required to decrease the rate or severity of pain after LVIHR

Feasibility and efficacy of addition of individualized-dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m2 daily), rituximab (375 mg/m2 cycle 1 and 500 mg/m2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34

Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients

Construct validity of the assessment of balance in children who are developing typically and in children with hearing impairments

Background. Children with hearing impairments have a higher risk for deficits in balance and gross motor skills compared with children who are developing typically. As balance is a fundamental ability for the motor development of children, a valid and reliable assessment to identify weaknesses in balance is crucial. Objective. The purpose of this study was to investigate the construct validity of posturography and clinical balance tests in children with hearing impairments and in children who are developing typically. Methods. The study involved 53 children with typical development and 23 children with hearing impairments who were between 6 and 12 years of age and without neuromotor or orthopedic disorders. All participants completed 3 posturography tests (modified Clinical Test of Sensory Interaction of Balance [mCTSIB], unilateral stance, and tandem stance) and 4 clinical balance tests (one-leg stance with eyes open and with eyes closed, balance beam walking, and one-leg hopping). Results. Three conditions of the mCTSIB, unilateral stance, and 2 clinical balance tests were able to distinguish significantly between the 2 groups. Children with hearing impairments showed more difficulties in balance tasks compared with children who were developing typically when 1 or 2 types of sensory information were eliminated or disturbed. The study showed only low to moderate correlations among the different methods of evaluating balance. Conclusions. Clinical balance tests and posturography offer different but complementary information. An assessment protocol for balance consisting of posturography and clinical balance tasks is proposed. Static and dynamic balance abilities could not be differentiated and seem not to be a valid dichotomy

Feasibility and efficacy of addition of individualized dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m 2 daily), rituximab (375 mg/m 2 cycle 1 and 500 mg/m 2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2-and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34