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Fungal infections are the fourth common cause of infection affecting around 50 million populations across the globe. Dermatophytes contribute to the majority of superficial fungal infections. Clotrimazole (CTZ), an imidazole derivative is widely preferred for the treatment of topical fungal infections. Conventional topical formulations enable effective penetration of CTZ into the stratum corneum, however, its low solubility results in poor dermal bioavailability, and variable drug levels limit the efficacy. The aim was to increase dermal bioavailability and sustain drug release, thereby potentially enhancing drug retention and reducing its side effects. This work evaluated the CTZ loaded solid lipid nanoparticles (SLN) consisting of precirol and polysorbate-80 developed using high pressure homogenization and optimized with QbD approach. Prior to release studies, CTZ-SLNs were characterized by different analytical techniques. The laser diffractometry and field emission scanning electron microscopy indicated that SLNs were spherical in shape with mean diameter of 450 ± 3.45 nm. DSC and XRD results revealed that the drug remained molecularly dispersed in the lipid matrix. The CTZ-SLNs showed no physicochemical instability during 6 months of storage at different temperatures. Further, the Carbopol with its pseudoplastic behavior showed a crucial role in forming homogenous and stable network for imbibing the CTZ-SLN dispersion for effective retention in skin. As examined, in-vitro drug release was sustained up to 24 h while ex-vivo skin retention and drug permeation studies showed the highest accumulation and lowest permeation with nanogel in comparison to pure drug and Candid® cream. Further, the in-vivo antifungal efficacy of nanogel suggested once-a-day application for 10 days, supported by histopathological analysis for complete eradication infection. In summary, the findings suggest, that nanogel-loaded with CTZ-SLNs has great potential for the management of fungal infections caused by Candida albicans.
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INTRODUCTION: Controversy exists regarding whether spinal implants need to be removed to treat postoperative deep wound infections (DWIs). This retrospective study aimed to determine whether the removal or retention of implants impacts the successful treatment of a DWI after spine surgery. METHODS: Postoperative spine surgery patients presenting with signs of infection who underwent irrigation and debridement (I&D) at Twin Cities Spine Surgeons at Abbott Northwestern Hospital, Minnesota, USA, were studied. First, the persistence of infection when implants were retained or removed was assessed. Second, we analyzed the persistence of infection with respect to the number of I&D, the use of vacuum-assisted closure (VAC) treatment, pseudoarthrosis status, and functional outcomes. RESULTS: One hundred thirty-five patients were included. Treatment of infection with retention of implants occurred in 64% (87/135); of these, 7% (6/87) had a persistent infection. Of patients with implant removal (36%, 48/135), 6% (3/48) had a persistent infection. Thus, we observed no difference between treatment with implants present compared to implants removed (p = 1.0). Fifty of the 135 patients (37%) received I&D and primary wound closure, and 85 (63%) patients received I&D and VAC treatment. There was no statistical difference between primary wound closure and VAC treatment (p = 0.15) with respect to persistence. Repeat I&D with VAC (three or more times) had a significantly lower rate of recurrence than those with two I&Ds. Pseudoarthrosis and persistent infection were unrelated. At minimum one-year follow-up, achieving a minimum clinically important difference in functional outcome was independent of persistent infection status. CONCLUSION: Persistent infection was unrelated to the retention of implants. When VAC treatment was deemed necessary, more than two I&Ds resulted in a significantly better cure for infection. Those with a persistent infection were no more likely to exhibit pseudoarthrosis than those with no persistent infection. All patients showed improvement in functional outcomes at minimum one-year follow-up.
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Background: The Ozaki procedure using autologous pericardium is an interesting but complex alternative for aortic valve replacement. We present a standardized approach to minimize the learning curve and confirm reproducibility. Methods: After careful preparation, from May 2015 to February 2021, an Ozaki procedure was performed on 46 patients age 51 ± 14 years. Seven had unicuspid (15%), 29 bicuspid (63%), and 10 tricuspid (22%) aortic valves, and 2 patients had endocarditis. Endpoints were operative learning curves, perioperative outcomes, intermediate-term valve hemodynamics, reintervention, health-related quality of life (MacNew Heart Disease Health-Related Quality of Life questionnaire), and mortality. Results: Cardiopulmonary bypass and aortic clamp times decreased from 145 to 125 âminutes and 120 to 100 âminutes, respectively, over the first 20 cases, reflecting the learning curve. There was no major perioperative morbidity or mortality. Median postoperative stay was 6.9 days. Aortic regurgitation was mild or less in all but 2 patients who developed moderate aortic regurgitation. Mean aortic valve gradient was 7.9 mmHg postoperatively, 9.2 mmHg by 6 months, and constant thereafter. Left ventricular ejection fraction was 58% preoperatively, 60% at 6 months, and remained stable thereafter. One patient developed infective endocarditis 7 months postoperatively, failed medical management, and underwent valve replacement at 14 months. Two-year survival was 96%, with 1 noncardiac death at 16 months. Health-related quality of life in mental, physical, and emotional domains was better than matched norms, global 6.2 vs. 5.0 (p < 0.0001). Conclusions: Using a well-prepared standardized approach, the Ozaki procedure is reproducible with a short learning curve, excellent hemodynamic performance, and good quality of life.
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BACKGROUND: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters. METHODS: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers (p53, mismatch repair proteins,MutS homolog6 and Postmeiotic seggregation 2 respectively[MSH6, and PMS2]), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA). RESULTS: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE, and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal (P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype (P = 0.001) and low-grade type (90.5%; P = 0.005). CONCLUSION: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.