Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction.

OBJECTIVES: Among patients undergoing aortic valve surgery for chronic aortic regurgitation (AR), we sought to: 1) compare survival among those with and without severe left ventricular dysfunction (LVD); 2) identify risk factors for death, including LVD and date of operation; and 3) estimate contemporary risk for cardiomyopathic patients. BACKGROUND: Patients with chronic AR and severe LVD have been considered high risk for aortic valve surgery, with limited prognosis. Transplantation is considered for some. METHODS: From 1972 to 1999, 724 patients underwent surgery for chronic AR; 88 (12%) had severe LVD. They were propensity matched to patients with nonsevere LVD to compare hospital mortality, interaction of operative date with severity of LVD, and late survival. Propensity score-adjusted multivariable analysis was performed for all 724 patients to identify risk factors for death. RESULTS: Survival was lower (p = 0.04) among patients with severe LVD than among matched patients with nonsevere LVD (30-day, 1-, 5-, and 25-year survival estimates were 91% vs. 96%, 81% vs. 92%, 68% vs. 81%, and 5% vs. 12%, respectively). However, survival of patients with severe LVD improved dramatically across the study time frame (p = 0.0004): hospital mortality decreased from 50% in 1975 to 0% after 1985, and time-related survival in patients with severe LVD operated on since 1985 became equivalent to that of matched patients with nonsevere LVD (p = 0.96). CONCLUSIONS: Neutralizing risk of severe LVD has improved early and late survival such that aortic valve surgery for chronic AR and cardiomyopathy is no longer a high-risk procedure for which transplantation is the best option.     

Fabrication and statistical optimization of surface engineered PLGA nanoparticles for naso-brain delivery of ropinirole hydrochloride: in-vitro–ex-vivo studies

Ropinirole hydrochloride (RPN), a nonergot dopamine D₂-agonist used in the management of Parkinson’s disease, has poor oral bioavailability (52%) due to extensive hepatic metabolism. The intent of present research work was aimed at design and statistical optimization of RPN-loaded poly (lactic-co-glycolic acid) (PLGA)-based biodegradable nanoparticles (NPs) surface modified using natural emulsifier, vitamin E (d-α-tocopheryl polyethylene glycol 1000 succinate [TPGS]) for direct nose-to-brain delivery in order to avoid hepatic first-pass metabolism, and improve therapeutic efficacy with sustained drug release. RPN-NPs were prepared by modified nanoprecipitation technique and optimized using 2³ factorial design of experiment. The effect of polymer and emulsifier concentration was evaluated on particle size and entrapment efficiency (EE%). Formulation PL₆ was considered as desirable with highest EE% (72.3?±?6.1%), PS (279.4?±?1.8?nm), zeta potential (?29.4?±?2.6?mV), and cumulative drug diffusion of 96.43?±?3.1% in 24?h. The ANOVA results for the dependent variables demonstrated that the model was significant (p value?<?0.05) for response variables. Histopathological study of optimized batch (PL₆) demonstrated good retention of NPs with no severe signs of damage on the integrity of nasal mucosa. Differential scanning calorimetry revealed the absence of any chemical interaction between RPN, PLGA, and TPGS while SEM study confirmed spherical shape of optimized NPs. Accelerated stability studies of freeze-dried optimized batch demonstrated negligible change in the average PS and EE% after storage at 25?±?2?°C/60?±?5% (relative humidity (RH) for the period of three months. The promising results of optimized batch suggested practicability of investigated system for enhancement of bioavailability and brain targeting of CNS acting drugs like RPN.     

Evaluation of a collapsed-cone convolution algorithm for esophagus and surface mold 192Ir brachytherapy treatment planning

PurposeTG43 does not account for a lack of scatter and tissue and applicator heterogeneities. The advanced collapsed-cone engine (ACE) algorithm available for use in the Oncentra Brachy treatment planning system (Elekta AB, Stockholm, Sweden) can model these conditions more accurately and is evaluated for esophageal and surface mold brachytherapy treatments.Methods and MaterialsACE was commissioned for use then compared against TG43 for five esophageal and five surface mold treatment plans. Dosimetric differences between each algorithm were assessed using superimposed comparisons and dose-volume histogram statistics.ResultsEsophagus (6 Gy per fraction): Compared with TG43, ACE demonstrated up to a 0.63% and 0.05 Gy reduction in planning target volume (PTV) V100% and PTV D98, respectively. Lung D2cc and bone D2cc deviated by up to 0.09 Gy and 0.03 Gy, respectively. Lung D0.1 cc and bone D0.1 cc both deviated by up to 0.12 Gy.Surface mold (4.5 Gy per fraction): Compared with TG43, ACE demonstrated up to a 12.5% and 0.18 Gy reduction in PTV V80% and PTV D98, respectively. Bone D2cc and D0.1 cc both reduced by up to 0.2 Gy when modeled with ACE. Increasing mold size laterally increased the dosimetric differences between TG43 and ACE.ConclusionsTG43 generally overestimated dose delivered to the target volume and organs at risk for the sites investigated. Dosimetric differences observed for esophageal treatments were minimal; however, surface mold treatments would benefit from the increased dosimetric accuracy offered by ACE.Implementation should be considered for surface mold ¹⁹²Ir treatment planning, but increased calculation time, additional contouring, and mass density assignment requirements should be scrutinized with regard to their potentially negative impact on current clinical practice.     

Use of knotless barbed sutures for closure of intraoral incisions for maxillofacial trauma: a randomised controlled trial

The objective of this study was to assess the efficacy of knotless barbed sutures in intraoral wound closure for maxillofacial trauma in comparison with conventional (vicryl) sutures. This was a randomised controlled clinical trial involving 40 patients with isolated mandibular angle fractures who required intraoral incisions for open reduction and internal fixation (ORIF). The sample was randomised into the study group (20 patients) and control group (20 patients). Following fracture fixation by a standardised surgical protocol, the wound closure was done with bidirectional knotless barbed suture and vicryl for the study and control groups, respectively. The wounds were closed in layers (periosteum and mucosa). All operations were performed by a single surgeon. Outcome parameters measured were intraoperative wound closure time and wound healing using ‘Landry’s wound healing index’ on the first, third, and seventh postoperative days. Statistically significant difference in suturing time was noted between the study and control group (p value <0.001). The study group demonstrated a mean (SD) suturing time of 9.46 (2.01) minutes, compared with the 17.61 (2.57) minutes in the control group. Wound healing was found to be better and statistically significant in the study group than the control group (p value<0.001). Knotless barbed suture is a promising alternative to vicryl for intraoral wound closure.     

Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

Carcinogenesis in the human colon is associated with a marked increase of urokinase type plasminogen activator and a decrease of tissue type plasminogen activator. This study was performed to determine the concentrations of urokinase type plasminogen activator and tissue type plasminogen activator in normal tissue and carcinomas along the upper part of the gastrointestinal tract. Activity and antigen levels of both activators were determined in homogenates of endoscopically obtained biopsies from normal and carcinomatous tissues. Although the concentrations of tissue type plasminogen activator and urokinase type plasminogen activator in normal squamous epithelium of the oesophagus were low compared with those in columnar epithelium from the stomach, the urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio of the different locations showed hardly any difference. Significant but heterogeneous increases were found in urokinase type plasminogen activator concentrations of biopsy specimens originating from carcinomas of both epithelial cell types. A decrease in tissue type plasminogen activator concentrations, as found in human colon carcinomas, could only be shown in carcinomas of columnar epithelium origin but not in squamous cell carcinomas of the oesophagus. The increase of urokinase type plasminogen activator and urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio and the decrease of tissue type plasminogen activator in the carcinomas did not show a significant correlation with known prognostic determinants as differentiation grade, TNM classification, intestinal metaplasia, inflammation, and ulceration. The heterogeneous increase of urokinase type plasminogen activator in oesophageal and stomach carcinomas, together with the recently described association of urokinase type plasminogen activator in tissue extracts of breast carcinomas with aggressiveness and prognosis, may be relevance to prognostic studies, may be of relevance to prognostic studies in oesophageal and gastric cancer.