ORAl iMmunosuppressive therapy to prevent in-Stent rEstenosiS (RAMSES) cooperation: A patient-level meta-analysis of randomized trials

Objective: The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis. Methods: We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics. Results: Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24–0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21–0.67], P < 0.001) and late lumen loss (−0.39 mm [−0.67, −0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29–1.53], P = 0.34), death (0.82 [0.25–2.69], P = 0.71), MI (0.58 [0.24–1.39], P = 0.22) and stent thrombosis (0.43 [0.10–1.87], P = 0.26). Conclusion: In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.     

Hemodynamic and antiischemic effects of intravenous elgodipine,a new dihydropyridine calcium channel blocker,in patients with chronic stable angina

Summary Elgodipine is a new second-generation dihydropyridine calcium antagonist. Its hemodynamic and antiischemic properties were evaluated in a single-blind, placebocontrolled trial in 22 males with chronic stable angina. Coronary artery disease was angiographically confirmed. Measurements were performed with a Swan-Ganz thermodilution catheter during a 30-minute period of rest and before the end of a 4-minute bicycle exercise test at maximum individual workload, both with placebo (IV infusion of 5 ml saline over 30 minutes) and elgodipine (10 µg/kg/2 min bolus IV, then IV infusion of 1 µ/kg/min for 28 minutes. Elgodipine caused very similar hemodynamic changes at rest and during exercise. Its major hemodynamic modification was the marked decrease in systemic vascular resistance, which was accompanied by an increase in cardiac index and stroke volume. Mean arterial blood pressure was slightly reduced, whereas the opposite small increase in heart rate meant that the double product remained unchanged. Contrary to resting conditions, pulmonary capillary wedge pressure, pulmonary artery pressures, pulmonary vascular resistance, and mean right atrial pressure remained normal or increased to a lesser extent during exercise after elgodipine. After elgodipine ischemic ST depression during exercise was diminished, and 11 of 16 assessable patients remained free from angina pectoris. We conclude that elgodipine is an efficacious antianginal drug. Its major mechanism of action is lowering of systemic vascular resistance. Thus elgodipine improves systolic cardiac function in patients with chronic stable angina and may delay the onset of ischemic diastolic dysfunction during exercise, as indicated by a normal left ventricular end-diastolic pressure (LVEDP). The data also suggest an improvement in coronary blood flow during exercise.     

Molecular targeting agents in renal cell carcinoma: present strategies and future perspectives

Treatment options for metastatic renal cell carcinoma (RCC) have been limited due to its resistance to chemotherapy and radiotherapy. Benefits from immunotherapeutic agents provide only a small subset of patients. During the past decade major advances have been made toward understanding the molecular basis of RCC development. Such acquired knowledge has offered unique opportunities for the development of molecular targeting agents. These agents are predominately small molecules or monoclonal antibodies that exert their action through modulation of protein activity or inhibition of amplified signals directly implicated in disease mechanism. To date, some of newly molecular targeted agents have entered advanced phases of clinical development, received marketing authorization by regulatory agencies and have opened a possibility of multiple treatment options. This article overviews current knowledge in RCC molecular pathology with recent clinical data, and discuss present strategies for future development of targeted therapies.     

Comparison of benzydamine hydrochloride and Salvia officinalis as an adjuvant local treatment to systemic nonsteroidal anti-inflammatory drug in controlling pain after tonsillectomy, adenoidectomy, or both: an open-label, single-blind, randomized clinical trial

Background

Benzydamine hydrochloride (BNZD) is a nonsteroidal anti-inflammatory drug (NSAID) used in an oral rinse formulation as an adjuvant to other NSAIDs in controlling postoperative pain after tonsillectomy, adenoidectomy, or both. Salvia officinalis (SO) is a topically applied herbal preparation frequently used for the same indication. Pain, bleeding, and infection are the most common postoperative complications of tonsillectomy.

Objective

The aim of this study was to compare the efficacy and tolerability of BNDZ with those of SO as adjuvant treatments in controlling postoperative pain.

Methods

This open-label, single-blind, randomized clinical trial was conducted at the Department of Otorhinolaryngology, Clinical Hospital Center “Dr. Dragiša Mišović—Dedinje” (Belgrade, Serbia and Montenegro). Pediatric and adult patients undergoing tonsillectomy, adenoidectomy, or both were enrolled. Patients were randomized to receive BNZD or SO, in addition to ibuprofen 20 mg/kg·d (children) or diclofenac 100 mg/d (adults). The primary end point was the proportion of patients with mild or no pain on postoperative days 1, 2, 4, and 7. Secondary end points were the incidences of infection, hemorrhage, and other adverse events.

Results

A total of 420 patients were enrolled (217 females, 203 males; 278 children, 142 adults; mean [SD] age, 6.2 [2.1] years [children] and 24.1 [9.8] years [adults] [range, 3–45 years]). One hundred thirty-eight children received BNZD; 140 received SO (both in addition to ibuprofen 20 mg/kg·d). Seventy-two adults received BNZD; 70 received SO (both in addition to diclofenac 100 mg/d). A significantly lower proportion of children treated with adjuvant BNZD experienced moderate or severe pain than those treated with SO at each time point (P < 0.01 at days 1 and 4; P < 0.001 at days 2 and 7). In children, the risk for postoperative infection was similar between BNZD and SO (absolute risk reduction [ARR], 6.9%; 95% CI, 6.4%–7.6%); however, the risk was reduced in adults (ARR, 19.0%; 95% CI, 16.5%–21.9%; P = 0.008).

Conclusions

In this clinical trial of children and adults who underwent tonsillectomy, adenoidectomy, or both, BNZD, as an adjuvant to an NSAID, was more effective than SO in controlling postoperative pain and infection. The pain-reducing effect of BNZD was of quick onset and persisted for 1 week after surgery. The safety profile of BNZD was comparable to that of SO, with the exception of postoperative infection in adults, for which BNZD was more efficacious. In particular, the use of BNZD was not associated with a high risk for early postoperative hemorrhage.     

Impact of concomitant tricuspid regurgitation on outcome after edge-to-edge mitral valve repair

Aims

To evaluate the impact of tricuspid regurgitation (TR) on echocardiographic and functional outcome after mitral valve transcatheter edge-to-edge-repair (M-TEER).

Methods and Results

A total of 740 patients underwent M-TEER at our center from 2010 to 2021. Patients were analyzed according to severity of concomitant TR at the time of M-TEER procedure: low-grade TR (grade ≤I [trace–mild], 279 patients [37.7%]), moderate TR (grade II, 170 patients [23.0%]) and high-grade TR (grade III-V [severe–torrential], 291 patients [39.3%]). Patients with moderate to high-grade TR had higher morbidity. Procedural success of M-TEER was achieved similarly in all groups (98.2% vs. 97.6% vs. 95.9%, p = 0.22). TR severity decreased rapidly and consistently after M-TEER to only 48.0% of high-grade TR patients after 3 months (p < 0.001) and to 46.8% after 12 months (p = 0.99). High-grade TR patients had significantly higher mortality (21.5% vs. 18.2% vs. 11.1%, p = 0.003) up to 12 months after M-TEER. However, high-grade TR did not independently predict mortality (HR 1.302, 95% CI 0.937–1.810; p = 0.116). Echocardiographic and functional outcome was similar in both secondary and primary MR patients.

Conclusions

High-grade concomitant TR did not independently predict adverse outcome following M-TEER. A wait-and-observe approach for these patients is reasonable.     

Natural killer T cells in pulmonary disorders

Natural killer T (NKT) cells, a unique subgroup of lymphocytes with features of both T and natural killer (NK) cells, represent a bridge between innate and adaptive immunity. They have the ability to either promote or suppress immune responses. With these immunoregulatory functions, NKT cells have emerged as an important subset of lymphocytes with a protective role in some disorders, such as infections, cancer, and possibly sarcoidosis, and a pathogenic role in others, such as asthma, chronic obstructive pulmonary disease and hypersensitivity pneumonitis. Immunotherapeutic interventions to modulate the immune response by targeting iNKT cell functions has become a challenging field and has shown promising results for the development of new therapies.