Evaluating Patient Tolerability for Urological Procedures Under Conscious Sedation: A Prospective Study.

OBJECTIVE: To prospectively evaluate patient-reported tolerability and surgical outcomes of urologic procedures with conscious sedation with or without local anesthesia. Administration of general or spinal anesthesia is associated with anesthetic-related complications, long wait times, and high costs. Using intravenous conscious sedation and/or local anesthesia is an emerging alternative for a myriad of urologic procedures. METHODS: Patients were enrolled from June-August 2021 at a tertiary care hospital. All procedures were completed using fentanyl, midazolam, or both with patient and procedural data recorded upon completion. Patients were telephoned 4-6 weeks post-procedure with a standardized patient tolerability questionnaire. A multivariable adjusted logistic regression analysis was performed to evaluate whether a patient would opt for conscious sedation again as opposed to general anesthesia. RESULTS: A total of 196 procedures were performed by 6 attending urologists with an overall success rate of 98.5% and 0% intraoperative complication rate. At 4-6 weeks follow-up, 85.6% of patients reported they would opt for conscious sedation as opposed to general anesthesia. Predictors of opting for conscious sedation in the future were older age (Odds Ratio (OR): 1.049; P = .017) and surgeon perceived level of patient tolerability (OR: 2.124; P <.001, scored 1-10). CONCLUSION: Physician directed, nursing administered IV conscious sedation is a viable alternative for various urologic procedures and has minimal risk of perioperative complications.

Synergistic biodegradation of phenanthrene and fluoranthene by mixed bacterial cultures.

Polycyclic aromatic hydrocarbons (PAHs) are highly recalcitrant compounds and difficult to degrade. Therefore in this work, using a bioremediation approach, mixed bacterial cultures (ASPF) was developed and enriched from polluted marine sediments capable of degrading 400 mg/L of phenanthrene and fluoranthene in Bushnell Hass medium. ASPF consists of 22 bacterial genera dominated by Azoarcus and Chelativorans. The biostimulation effect of three water soluble fertilizers (NPK, urea, and ammonium sulfate) showed that NPK and ammonium sulfate have enhanced the degradation, whereas urea has decreased their degradation. ASPF was also able to degrade phenanthrene and fluoranthene in the presence of petroleum hydrocarbons. But degradation was found to decrease in the presence of pathway intermediates (phthalic acid and catechol) due to enzymatic feedback inhibition. Optimum degradation of both PAHs was observed under room temperature, suggesting the practical applicability of ASPF.

A novel vesicular transdermal delivery of nifedipine - preparation, characterization and in vitro/in-vivo evaluation.

Nifedipine is a calcium channel blocker extensively used in the treatment of anginal and hypertension. On oral administration it undergoes extensive first pass metabolism, which outweighs its absorbance through gastrointestinal tract (GIT) and bioavailability of the drug in systemic circulation. As an alternative to oral route transdermal route of drug delivery was developed. In the present investigation, proniosomes are prepared by varying the ratio of span-40, lecithin, aqueous phase and polymer. Formulation containing span-40, lecithin, isopropyl alcohol, 0.1% glycerol (5:5:4) and HPMC (2%) showed smaller vesicle size, high entrapment efficiency. The niosomal formation after hydration and their surface morphology of optimized formulation was studied by Motic and transmission electron microscopy. FTIR and differential scanning calorimetry studies were performed to unravel and understand the solid state properties of the drug and chemical interaction with formulation excipients. The ex-vivo Franz-diffusion studies were carried out in pH 6.8 using rat skin and the results showed better permeability of niosomes with good steady state flux and enhancement ratio suggesting the potential of proniosomal carriers for improved transdermal delivery of nifedipine. Skin irritation studies for 7 days, showed that the drug when formulated as proniosomes to be non-irritant with no erythemia development compared to pure drug. From the bio-distribution studies, the vesicles prepared with hydroxy propyl methyl cellulose with span-40 was found to be ideal batch as the concentration of drug at target site was higher.

Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS).

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The "atypia of undetermined significance/follicular lesion of undetermined significance" (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5-15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. METHODS: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan-Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. RESULTS: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4-31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1-42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032). CONCLUSIONS: In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26.6-37.8% of AUS/FLUS nodules harboring cancer. These data imply that Bethesda Category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration.

Modulation of cerebral malaria by curcumin as an adjunctive therapy

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Modulation of cerebral malaria by curcumin as an adjunctive therapy.

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Rechallenge with oxaliplatin and fluoropyrimidine for metastatic colorectal carcinoma after prior therapy.

OBJECTIVES: Patients with advanced colorectal cancer (CRC) who have received oxaliplatin, 5-fluoropyrimidine, and irinotecan chemotherapy (with or without bevacizumab) and antiepidermal growth factor receptor therapy (if KRAS is wild type) have no further standard treatment options. Although repeating a prior chemotherapy [in particular, oxaliplatin and fluoropyrimidine (FOX)] is an option, there is very little evidence in the literature for this approach; thus, we reviewed our registry to assess the frequency and outcome of rechallenging with FOX. METHODS: Patients who had been rechallenged with FOX were identified from the South Australian metastatic CRC database. Patient characteristics were analyzed, and tumor response was retrospectively assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Twenty patients were eligible for inclusion in this analysis. The number of prior lines of therapy received for metastatic CRC was 4 lines for 2 patients, 3 lines for 6 patients, 2 lines for 7 patients, and 1 line for 3 patients, with 3 patients having received oxaliplatin as adjuvant therapy. Four patients had received bevacizumab previously, 7 patients had undergone antiepidermal growth factor receptor treatment, and 4 patients had undergone liver resection earlier. Response rate was 18%, and 47% had stable disease. The median progression-free survival was 3.7 months, median overall survival was 7.8 months, and 1-year survival was 37%. CONCLUSIONS: In this selected population, there is evidence of modest activity of rechallenge with FOX chemotherapy, although radiologic response is uncommon.