Bcl-2 gene rearrangements and apoptosis rates in patients with non-Hodgkin's lymphoma during chemotherapy

OBJECTIVES: Overexpression of the bcl-2 gene as a result of the t(14,18) translocation leads to neoplastic transformation by suppressing apoptosis. However, apoptotic cell death in response to chemotherapy has not been investigated. This study was planned with the aim to investigate the association between bcl-2 gene rearrangements and apoptotic changes during chemotherapy in patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: Lymphocytes from 33 patients were collected before and during chemotherapy. Bcl-2 gene rearrangements were investigated by PCR. Apoptotic cell death was analyzed by enzyme immunoassay. RESULTS: In 24 cases, mbr gene rearrangements were detected. Apoptosis was successfully induced by chemotherapy in 48% of patients. Two characteristic, clearly distinguishable apoptotic response patterns with transient peaks either following the first or the third course were observed. It was found that apoptosis rates measured after the first course exactly reflect the final response. No correlation was found between bcl-2 gene rearrangements and apoptosis. CONCLUSIONS: Apoptotic cell death rates show transient changes during chemotherapy. Because the midterm response can be misleading, the apoptotic response should be evaluated following the first course of chemotherapy.     

Angiolipoma located inside the obturator canal and supplied by the umbilical artery

During dissection of the retropubic region of a 55-year-old female cadaver, we encountered an angiolipoma located inside the obturator canal which was connected to the wall of the urinary bladder by a fibrous cord. The angiolipoma was supplied by a branch originating from the umbilical artery. Microscopically the benign soft tissue tumor was characterized by lobules of mature adipocytes and densely distributed networks of small and larger blood vessels, thus resembling typical histological features of an angiolipoma. Both the uncommon location of the angiolipoma and the abnormal branch of the umbilical artery entering the obturator canal should be taken into account during surgical procedures in this region, such as for orthopedic pelvic procedures, hernia repair or bladder/urethra-related interventions (e.g. transobturator tape, tension-free vaginal tape, colposuspension).     

Unmet need in Behcet’s disease: most patients in routine follow-up continue to have oral ulcers

The clinical course of Behcet’s disease (BD) as a multisystemic disorder with a remitting-relapsing nature is insufficiently explored. As complete remission should be aimed in all inflammatory diseases, we investigated the frequency of complete remission in patients with BD followed in long-term, routine practice. In this retrospective study, 258 patients with BD who were regularly followed in outpatient clinics were assessed. The demographic and clinical data for active organ manifestations and treatment protocols were evaluated, and “complete remission” for this study was defined as no sign of any disease manifestation in the current visit and the preceding month. Two hundred fifty-eight patients with BD (F/M 130/128, mean age 41.1?±?11.5 years) were included to the study. Mucocutaneous disease was present in 48.4 % (n?=?125). Mean visit number was 6.8?±?2.7, and mean follow-up duration was 45.8?±?36.5 months. Patients were clinically active in 67.2 % (n?=?1,182) of the total visits (n?=?1,757), which increased to 75.6 % (68.1–90.3) when the month preceding the visit was also included. The most common active manifestation was oral ulcers (39.4–63.2 %) followed by other mucocutaneous manifestations and musculoskeletal involvement. When multivariate analysis was performed, oral ulcers, which are the main cause of the clinical activity, negatively correlated with immunosuppressive treatments (β?=??0.356, p?β?=??0.183, p?=?0.04). It is fairly difficult to achieve complete remission in BD with current therapeutic regimens. The reluctance of the clinician to be aggressive for some BD manifestations with low morbidity, such as mucocutaneous lesions and arthritis, might be influencing the continuous, low-disease activity state, especially due to oral ulcers, in BD patients.     

Economic Evaluation of Lupus Nephritis in the Systemic Lupus International Collaborating Clinics Inception Cohort Using a Multistate Model Approach

Objective

Little is known about the long‐term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling.

Methods

Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10‐year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration.

Results

A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten‐year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day).

Conclusion

Patients with estimated GFR <30 ml/minute incurred 10‐year costs 15‐fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost‐effectiveness evaluations of novel therapies.

     

Favorable first-pass recanalization rates with NeVa™ thrombectomy device in acute stroke patients: Initial clinical experience

BackgroundThe NeVa™ thrombectomy device (Vesalio LLC, Nashville, USA) has been reported to succeed in large vessel occlusion thrombectomy in animal, in-vitro, and clinical studies. Designed with Drop Zone technology, a closed distal tip, and strong expansive radial force, the device demonstrated particular efficiency in resistant “white” thrombi in preclinical research. Our goal is to determine the safety and performance of this novel stent retriever on first-pass rates and overall recanalization.MethodsThe Interventional Neurology Database is a prospectively maintained database of anterior and posterior circulation stroke thrombectomy cases. We retrospectively analyzed cases where the NeVa™ thrombectomy device was used as the first-line treatment strategy. Data collection occurred between January 2019 and January 2020. First-pass recanalization, final recanalization, 90-day functional outcome, complication, and bleeding rates are reported.ResultsOne hundred eighteen patients were treated with the NeVa™ thrombectomy device. The mean patient age was 69 ± 14 years, the median baseline National Institutes of Health Stroke Scale was 14, and the median initial Alberta Stroke Program Early Computed Tomography score was 8. The median time from groin puncture to successful recanalization was 29 min (interquartile range (IQR): 20–40). First-pass recanalization rates were 56.8% (modified treatment in cerebral infarction (mTICI) 2b/3) and 44.9% (mTICI 2c/3). Final successful recanalization rate was 95.8% (thrombolysis in cerebral infarction 2b/3). Favorable functional outcome (modified Rankin Scale 0–2) was 53% in the “first-pass” subgroup and 42.4% in the total patient population. The median number of passes to achieve the final recanalization score was 1 (IQR 1–2). The rate of embolization into new territory was 1.7%. Four patients (3.3%) had symptomatic hemorrhage.ConclusionsIn our experience, the NeVa™ device demonstrated high first-pass and overall recanalization rates along with a good safety profile.     

An objective evaluation of lens transparency after vitrectomy surgery with different intravitreal tamponades

International Ophthalmology - To evaluate and compare the effects of different intraocular tamponade agents on lens density after vitrectomy. The participating patients were divided into four...     

Systemic Sclerosis Quality of Life Questionnaire (SScQoL): translation into Turkish and assessing its psychometric properties

Clinical Rheumatology - Systemic sclerosis (SSc) is a chronic autoimmune disease that affects the connective tissues and leads to physical, emotional, and social challenges for patients. Evaluating...     

Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: Post-hoc analysis of clinical trials

Aim

Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels.

Methods

This post-hoc analysis included data from 6 trials: C-OPERA (NCT01451203), pooled RAPID trials (RAPID-1 [NCT00152386], RAPID-2 [NCT00160602], J-RAPID [NCT00791999], RAPID-C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR).

Results

Overall, 316, 1537, and 908 patients were included in C-OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28-ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28-ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles.

Conclusion

CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis.