A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

Adhesive fragment reattachment after orthodontic extrusion: a case report

Abstract –  In the treatment of crown fractures, adhesive fragment reattachment provides a good alternative to other restorative techniques, offering several advantages. The present paper reports a case in which the treatment of a cervical crown fracture was accomplished by reattaching the tooth fragment with a flowable resin composite. Orthodontic root extrusion was performed with a modified Hawley appliance prior to fragment reattachment. The clinical and radiographic results after 2.5 years were successful.     

Vascular lesions in Beh?et's disease

Vascular lesions in Beh?et's disease are generally localized in the venous system: up to 24% of the cases reported in the literature are accompanied by thrombosis/thrombophlebitis. Reports of arterial involvement are rare but have increased during the last decade. Surgical treatments of arterial aneurysms and occlusions are often followed by recurrences due to progression or relapses of the inflammatory vessel wall lesions. Aneurysms of the pulmonary artery are rare. They may be complicated by thrombosis within the aneurysm and massive hemoptysis due to bronchial erosion and formation of an arterio-bronchial fistula. 27 cases of Beh?et's disease are reported.     

Effect of N-acetylcysteine on blood and tissue lipid peroxidation in lipopolysaccharide-induced obstructive jaundice.

In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg- 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ +/- LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.     

Access-site thrombosis after placement of inferior vena cava filters with 12-14-F delivery sheaths.

Inferior vena cava filters were placed in 60 patients. Ultrasound (US) of the venous access site was performed before and 3-5 days after filter placement to determine the prevalence of occlusive and nonocclusive access-site thrombosis (AST). Prevalence of symptoms attributable to AST was also evaluated at 1-month clinical follow-up in 58 of the 60 patients. All filters were placed with delivery sheaths with outer diameters of 12-14 F. US depicted development of occlusive AST in six of the 60 patients (10%). Nonocclusive AST developed in 15 (25%). Symptoms related to AST occurred in two of 58 patients (3%). There was a substantially increased prevalence of occlusive thrombus in patients in whom partially occluding thrombus or extrinsic compression in the inferior vena cava or ipsilateral iliofemoral veins was demonstrated on vena cavograms obtained before filter placement. The prevalence of both symptoms attributable to AST and US-detected occlusive thrombus in this series with smaller delivery systems is lower than that reported after percutaneous placement of stainless steel Greenfield filters via 29.5-F (outer diameter) sheaths.     

Intracoronary shunt reduces postoperative troponin leaks: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate whether intracoronary shunt usage reduced the myocardial damage on the basis of the cardiac markers when compared with the shuntless anastomosis in off-pump coronary artery bypass grafting (OPCABG) surgery of isolated left anterior descending artery lesions. METHODS: Forty patients who had stable angina with isolated left anterior descending (LAD) coronary artery lesion undergoing OPCABG surgery were randomized into two groups. Shunt group consisted of 20 patients who had OPCABG using intracoronary shunt, whereas the shuntless group consisted of 20 patients who underwent OPCABG without using intracoronary shunt. Cardiac troponin I, CK, and CK-MB before and 24h after the surgery were assessed in the groups. RESULTS: There were no deaths in the study. The two groups were similar with respect to sex and age. Duration of LIMA-LAD anastomosis was significantly higher in the shunt group (p=0.01). There was no significant difference between the groups concerning the preoperative and postoperative CK and CK-MB levels. The preoperative troponin I levels of the groups were not different (p=0.238; NS), whereas postoperative levels of this marker was significantly higher in the shuntless group (p=0.003). CONCLUSION: Intracoronary shunt reduced the postoperative troponin I levels significantly, so it may be indicated in the patients who are thought to be susceptible to transient ischemia.     

Three dimensional computed tomographic imaging in planning the surgical approach for redo cardiac surgery after coronary revascularization.

OBJECTIVE: Reoperative cardiac surgery after previous coronary artery bypass grafting represents a surgical challenge due to the potential for injury to patent coronary grafts, aorta or right ventricle. Standard preoperative imaging using a coronary angiogram and chest radiograph (CXR) often results in inaccurate assessment of mediastinal anatomy. We aimed to evaluate 3D volume rendered computed tomographic imaging as an adjunct to standard preoperative assessment of patients requiring cardiac surgery in whom coronary artery revascularization had been performed in the past. METHODS: Between January 2003 and January 2004, 33 patients with previous coronary revascularization referred for reoperative cardiac surgery underwent preoperative 3D CT imaging in order to optimize the surgical approach. The mean age in this patient population was 72+/-8 years. The combined evaluation of CXR and conventional angiography offered incomplete insight into pertinent mediastinal topography in 85% of patients (28/33). RESULTS: The correlations for distances of the left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft from the midline and posterior sternum obtained by CT angiography (CTA) and CXR were poor, R=0.56 and 0.49, respectively. The correlation coefficients for distances between the right ventricle and the aorta to the sternum obtained by the same methods were similarly marginal, 0.58 and 0.48, respectively. The correlation coefficients for distances between the LIMA to LAD, circumflex and right coronary artery grafts from the midline obtained by CTA and conventional angiography were 0.54, -0.13 and 0.43, respectively. In seven patients (21%) the surgical strategy was modified based on the location of patent grafts in the mediastinum. The hospital mortality was 17% (5/29). Intraoperative injuries to vital structures were encountered in two patients (7%). No injuries to patent LIMA or the aorta were encountered. CONCLUSIONS: The 3D CT imaging technique is useful in defining the optimal surgical strategy for reoperative cardiac surgery. We found that CTA is superior to CXR and conventional angiography in defining the position of patent grafts and vital structures in relation to the midline and posterior sternum. Preoperative mapping of patent coronary grafts and other vital mediastinal structures reduces the morbidity of the reoperation through modification of surgical approaches.     

Noonan syndrome associated with central giant cell granuloma

We report a case of Noonan syndrome associated with central giant cell granuloma. The patient was a 101/2-year-old boy with the chief complaint of proptosis of the right eye. He also had various malformations such as short stature, webbed neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent foramen ovale, a characteristic face appearance and cryptorchidism and so on. Chromosome analysis showed a 46, XY karyotype. A computed tomographic scan and magnetic resonance imaging showed a mass originated from the lateral wall of the right maxillary sinus. The patient underwent Caldwell-Luc operation. Histological examination of the mass showed the characteristics of central giant cell granuloma. This case report describes a patient with the features of the recently described Noonan-like/multiple giant cell lesion syndrome.