Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients

Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02029443","term_id":"NCT02029443"}}NCT02029443, {"type":"clinical-trial","attrs":{"text":"NCT02475681","term_id":"NCT02475681"}}NCT02475681, {"type":"clinical-trial","attrs":{"text":"NCT02970318","term_id":"NCT02970318"}}NCT02970318 and {"type":"clinical-trial","attrs":{"text":"NCT02337829","term_id":"NCT02337829"}}NCT02337829). Acalabrutinib was given orally at total daily doses of 100–400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32–89]; median follow-up: 25.9 months [range, 0–58.5]) were analyzed. Cardiac AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with high-risk CLL (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02477696","term_id":"NCT02477696"}}NCT02477696) prospectively assess differences in CV toxicity between the two agents.     

Effects of inhaled ammonium sulfate on benzo[a]pyrene carcinogenesis

The effect of inhaled ammonium sulfate on benzo[a]pyrene carcinogenesis in the lungs of Syrian golden hamsters was studied. Exposure to ammonium sulfate at an airborne concentration 20 times average United States ambient levels resulted in a significant depression (p less than 0.05) of benzo[a]pyrene carcinogenesis in the first 6 mo of the study. However, at 2 yr, the termination of the study, there were no differences in cancer incidence between groups receiving benzo[a]pyrene and benzo[a]pyrene plus ammonium sulfate. In addition, at the concentration studied, inhaled ammonium sulfate did not significantly increase the incidence or severity of pneumonitis or pulmonary fibrosis in the hamster. However, this inhalation did increase the incidence of emphysema but not the severity. The decreased incidence of cancer during the first 6 mo of this study in animals receiving both benzo[a]pyrene and ammonium sulfate suggests that interaction between sulfate and benzo[a]pyrene does occur, but is insufficient to afford long-term protection against the development of cancer. No enhancement of carcinogenesis by benzo[a]pyrene occurs in the presence of inhaled sulfate.     

Pre-marriage prevention of thalassaemia: report of a 100 000 case experience in Isfahan

Background: Iran like other middle east countries has a large number of major thalassaemics. Due to religious restrictions on abortion, the routine prevention of the birth of thalassaemic children by this means is not possible. The aim of this study is to describe an alternative means to prevent the birth of thalassaemic children.Methods: From January 1993 to January 1996, 100 000 people preparing for marriage were screened for the thalassaemia trait, using CBC and HbA₂ level measurement. High risk couples were referred for further consultation regarding the disease and the means of its prevention. The proposed actions of the couples regarding thalassaemia prevention were evaluated immediately after consultation and then re-evaluated three months later. Result: After the project had been running for three years the average of high risk couple initially deciding not to marry was 90% and no new cases of thalassemia were detected in the children of the screened population.Conclusion: Where both members of the couple were trait-positive their preferred choice was not to marry, rather than to marry and use other or no methods of preventing a thalassemia affected child being born to them. Cultural and religious ideas can affect such decisions and in some Islamic countries the establishment and use of a genetic counselling centre can help prevent most of new thalassaemia cases.     

Opioid-Sparing Multimodal Analgesia Protocol for Lumpectomy Patients Results in Superior Postoperative Pain Control

Annals of Surgical Oncology - We sought to determine if lumpectomy patients who received perioperative opioid-sparing multimodal analgesia reported less pain when compared with those who received...     

Modic changes in the adjacent vertebrae due to disc material infection with <Emphasis Type="Italic">Propionibacterium acnes</Emphasis> in patients with lumbar disc herniation

Introduction

Modic changes (MCs) in vertebral bones are induced by two mechanisms of mechanical factors and infection. As Propionibacterium acnes (P. acnes) have been reported to be associated with LBP. The aim of this study is to evaluate the MCs in patients with disc herniation and positive for P. acnes.

Methods and material

A total of 120 patients with disc herniation surgery were enrolled into the study. The samples were excised during discectomy and then cultured in both anaerobic and aerobic incubations. Gram staining was employed for investigation of all colonies. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated.

Results

In this study, 120 subjects (69 male and 51 female) with mean age of 43.15 ± 12.62 years were investigated. Sixty disc samples and eight muscle samples were positive for microorganisms. Moreover, 16S rDNA gene was identified in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their sample had MCs.

Conclusion

According to the results and presence of 36/46 MCs in patients with lumbar disc herniation, positive for P. acnes suggests that P. acnes can lead to edema on the vertebrae endplates near to infected area.

     

Anatomical analysis of the relation between human ligamentum flavum and posterior spinal bony prominence

Background

Posterior spinal bony prominences are commonly used as landmarks during posterior spinal surgery; however, the exact relationship of these structures with ligamentum flavum (LF) borders and attachments has not been clarified.