Progress in drug delivery and diagnostic applications of carbon dots: a systematic review.

Carbon dots (CDs), which have particle size of less than 10 nm, are carbon-based nanomaterials that are used in a wide range of applications in the area of novel drug delivery in cancer, ocular diseases, infectious diseases, and brain disorders. CDs are biocompatible, eco-friendly, easy to synthesize, and less toxic with excellent chemical inertness, which makes them very good nanocarrier system to deliver multi-functional drugs effectively. A huge number of researchers worldwide are working on CDs-based drug delivery systems to evaluate their versatility and efficacy in the field of pharmaceuticals. As a result, there is a tremendous increase in our understanding of the physicochemical properties, diagnostic and drug delivery aspects of CDs, which consequently has led us to design and develop CDs-based theranostic system for the treatment of multiple disorders. In this review, we aim to summarize the advances in application of CDs as nanocarrier including gene delivery, vaccine delivery and antiviral delivery, that has been carried out in the last 5 years.

Preclinical evaluation of a microparticle-based transdermal vaccine patch against metastatic breast cancer.

Breast cancer is the number one cause of cancer-related deaths among females. Current chemotherapy targets both tumor and normal cells, leading to pronounced side effects. Therefore, therapeutic vaccines acting against specific cancer cells would be the choice of treatment. We prepared microparticles entrapping the antigens obtained from a murine metastatic breast cancer cell line, 4 T1 using the spray drying technology. These microparticles were incorporated into microneedle patches to deliver to the animals for the efficacy study. An antineoplastic drug, cyclophosphamide, in a very low dose has been found to inhibit the immunosuppressive regulatory T cells (Treg) (Le and Jaffee, 2012). In-vivo efficacy of the microparticulate vaccine given along with a low dose of cyclophosphamide was evaluated in a murine breast cancer model. Animals immunized with vaccine microparticles showed considerably slower tumor growth than animals that did not receive the vaccine. The results of the study showed that the Tumor-Associated Antigens (TAAs) within the microparticles were responsible for the delayed tumor growth in vaccinated animals. Vaccinated animals also showed an increase in the population of CD4 and CD8 T cells. Overall, our results demonstrated that immunotherapy with vaccine microparticles encapsulating TAA's could potentially be an effective treatment for metastatic breast cancer.

Trifecta and Pentafecta Outcomes in Laparoscopic and Robotic Nephron-Sparing Surgery for Highly Complex Renal Tumors: A Propensity Score-Matched Cohort Analysis.

Purpose: To compare the trifecta and pentafecta outcomes of laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy (RPN) in highly complex renal tumors (RENAL nephrometry score ≥10) using a matched cohort analysis. Methods: Patients undergoing LPN or RPN for renal tumors with RENAL score ≥10 between January 2014 and December 2019 were matched using 1:2 propensity score match analysis based on age, body mass index, gender, laterality of tumor, RENAL score, and American Society of Anesthesiologists (ASA) score. The two groups were compared for trifecta and pentafecta outcomes. Results: Thirty patients undergoing LPN (Group A) were matched with 60 patients undergoing RPN (Group B). The mean age (standard deviation) was 53.7 (12.9) years. The median (interquartile range) RENAL score was 10 (10-11). In comparison, the mean warm ischemia time in Group A was significantly longer than that in Group B (26.2 vs 23.0 minutes, p = 0.013). The overall complication rate was 36.7% in Group A as compared with 20% in Group B (p = 0.440). The trifecta outcomes could be achieved in 11 patients (36.7%) in Group A compared with 40 patients (66.7%) in Group B (p = 0.012). Moreover, 10 patients (33.3%) in Group A and 28 patients (46.7%) in Group B achieved pentafecta outcomes (p = 0.227). Conclusions: In a matched cohort of patients undergoing nephron-sparing surgery for highly complex renal tumors (RENAL score ≥10), the robotic approach offers a superior advantage in the achievement of trifecta outcomes as compared with the laparoscopic approach. However, both LPN and RPN can achieve similar pentafecta outcomes.

Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.

Establishing a Robot-Assisted Kidney Transplant Program: Independent Evaluation of the Learning Curve and Surgical Nuances.

Background: Robot-assisted kidney transplantation (RAKT) is a technically challenging procedure and there has been limited reporting of its learning curve (LC), mostly by a single surgical working group. The aim of the current study was to perform an independent analysis of LC and describe our modifications in the technique of RAKT. Materials and Methods: All consecutive cases performed at our center from April 2016 to March 2020 were reviewed. LC was analyzed by using the cumulative summation method for total anastomosis time (technical outcome) and serum creatinine at days 7 and 30 (functional outcome). Patient safety was assessed by using Shewhart control charts, and a comparison of safety outcomes before and after achieving LC was done by using Chi-square or Fischer exact test as appropriate. A descriptive review of technical modifications made during our experience was conducted. Results: Ninety patients underwent robot-assisted renal transplant during the study period. LC was crossed at 24 cases (total anastomosis time) and 15 to 25 cases (serum creatinine). Shewhart control charts showed that total anastomosis time remained below alert/alarm line in 94.4%/98.9% cases, with the alert line being crossed a significantly greater number of times before the LC. Serum creatinine values remained below alert/alarm line in 85.5%/90% cases at day 7 and 92.2%/96.7% cases at day 30, with no difference made due to LC. Key technical modifications included arterial and ureteric spatulation at bench, use of polypropylene 5 to 0 holding stitch in graft vessels to facilitate intraoperative handling, keeping anterior arterial wall smaller to visualize posterior arterial wall anastomosis, and leaving a small amount of fatty tissue on the supero-lateral surface of the kidney for handling after jacket removal. Conclusion: Our LC of RAKT was crossed at 24 cases (technical outcome) and 15 to 25 cases (functional outcome). We have also detailed valuable technical modifications in the procedure.

Comparative analysis of outcomes and long-term follow-up of robot-assisted pediatric kidney transplantation, with open counterpart.

How does the robotic kidney transplant fare against the open technique, in pediatric patients? No one knows. To address this question, this study compares the outcomes of robotic kidney transplants, with those of open transplant in these patients. This study was a retrospective analysis of outcomes (renal function and complications), of all pediatric patients (<18 years of age), who underwent kidney transplant at our institute, after 2014, till their last follow-up. Fisher's exact test was used to compare proportions. Continuous variables were analyzed using Mann-Whitney test. P value of <.05 was considered significant. Of the twenty-five patients included, 21 belonged to open group, and 4 to the robotic group. Patients in the robotic group had significantly higher Re-WIT (P value .002) and had lower analgesia requirement (P value .04). Median follow-up period was 31 months. Both groups were comparable in terms of length of hospital stay, blood transfusion, and renal function post-operatively till their last follow-up. Three patients in the open group had surgical site infection as compared to none in the robotic group. All the patients had functioning grafts till their last follow-up. Robotic transplant is safe and delivers functional results similar to open technique, with lesser pain and better cosmesis. Longer Re-WIT in robotic transplant has no impact on post-operative renal function. Ours is the first known effort to compare robotic technology with the established open technique of transplant in this population. A prospective randomized controlled trial should refine the results of the present study.

Clinico-Radiological Evaluation of Modified Stoppa Approach in Treatment of Acetabulum Fractures.

Background The aim of our study was to evaluate the efficacy of Modified Stoppa approach for surgical treatment of acetabulum fractures by analyzing clinical and radiological outcomes. Also, we assess intraoperative and postoperative complications of fracture treated by using Modified Stoppa approach. Objectives To evaluate clinical outcomes of Modified Stoppa approach by using Merle d'Aubigne hip score. To evaluate the radiological reduction quality of Modified Stoppa approach by using the criteria of Matta, and to assess complications of Modified Stoppa approach.  Method Thirty-two patients participated in this study (mean age 40 years; range 18-60 years) and the male to female ratio was 4:1, patients who underwent surgical intervention for acetabular fracture by using Modified Stoppa approach from Oct 2017 to April 2019 were included. Out of 32 patients, two were lost in follow up, leaving 30 of 32 patients for clinico-radiological analysis. We classified the fracture pattern according to Judet and Letournel classification based on preoperative X-ray AP view, Judet View, and 3D-CT pelvis. Operative time, blood loss, reduction quality, and perioperative complications were assessed in each patient. Clinical outcomes were assessed by Merle d'Aubigne hip score and radiological outcomes by criteria of Matta.  Results Out of 30 acetabulum fractures in 30 patients, three (10%) were categorized as anterior column fracture, one (3.3%) as transverse with posterior wall, one (3.33%) as T-type, six (20%) as anterior column with posterior hemi-transverse and 19 (63.33%) as both column fractures. In our study, most patients have trauma due to road traffic accident (RTA) in 25 (83.3%) and fall from stairs in three (10%) patients. Timing of surgery after trauma was average 5.83 days (range three to 15 days), Mean surgical time determined to be 214.66 min (range 150-350 min) and mean intraoperative loss 683.33 ml (range 230-1250 ml). Clinical outcomes by Merle d'Aubigne hip score was excellent in 13 (43.33%), good in 15 (50%), fair in two (6.66%) patients whereas poor results in 0 (0%) patient (p=0.001). Quality of reduction by Matta criteria was found to be an anatomical reduction in 26 (86.6%), imperfect reduction in three (10%), and poor reduction in one patient (3.33%) (p<0.001). Radiological grading by Matta criteria was excellent in 24 (80%), good in five (16.66%), and fair in one (3.33%) patient, and no patients met criteria for poor results (p<0.001). In operative complications one patient developed an external iliac vein injury which was repaired by a vascular surgeon, one patient had a superficial infection for which debridement, regular dressing, and IV antibiotics given and resolve in one month, obturator nerve injury in one patient which was resolve in five to six months, lateral femoral cutaneous nerve injury in one patient which resolved within three months and one patient urinary bladder injury which was repaired by a general surgeon.  Conclusion Our experience with Modified Stoppa approach for surgical treatment of acetabulum fracture in 30 patients is excellent and effective for better visualization to anterior column, quadrilateral plate, and up to sacroiliac joint. This approach provides better visibility of the fracture site which allows for good to an excellent reduction of fracture and fixation. Although Stoppa approach is cosmetic surgery in terms of scar size, there is less complication rate than the ilioinguinal approach.

CBCT Evaluation of the Vital Mandibular Interforaminal Anatomical Structures.

BACKGROUND: Oral implants are considered safe in the mandibular anterior region, but complications often occur if vital structures such as inferior alveolar nerve, mandibular incisive canal (MIC), anterior mental loop (AL), or mental foramen (MF) are not properly identified. AIM: The aim was to evaluate vital anatomical structures in the mandibular interforaminal region and to investigate sexual dimorphism and differences with respect to left and right side regions using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Eighty CBCT scans (forty male and forty female) were analyzed for MF position and shape, presence and measurement of AL and MIC (both in mm), emergence patterns of mandibular canal, and symmetry of MF and AL. A pilot study was conducted on five patients to determine interobserver reliability among two oral and maxillofacial radiologists, considered for interpretation of CBCT images. All the scans were taken by CS 9300, CBCT machine adjusted at 80 kVp, 15 mA, voxel size 0.3 × 0.3 × 0.3, and field of view of 10 × 5 (mandible only). The acquired images were reconstructed into multiplanar views (axial, panoramic, and cross-sectional) for evaluation. RESULTS: The mean age of the study population was 42.64 ± 16.22 years, with males noted with slightly higher age. Position 4 of MF (below the apex of the second premolar) was noted the most on the right side, whereas position 3 (between the first and second premolars) was noted on the left side, with 75% of symmetrical MF position. The oval-shaped MF was most common among both genders and sides. The prevalence of MIC was noted in 93.75% of patients with a mean length of 12.09 ± 5.95 mm. The prevalence of AL was 53.13%, with a mean length of 1.07 ± 1.42 mm. No statistically significant sexual dimorphism (P > 0.05) was found between genders or sides for all the evaluated interforaminal parameters. CONCLUSION: CBCT evaluation of vital anatomical structures needs to be elicited before planning an interforaminal placement of implants, and no sexual dimorphism was found regarding them.

Clinical utility of procalcitonin in bacterial infections in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Infections are major contributor to morbidity and mortality in patients undergoing bone marrow transplant (BMT). OBJECTIVE: To assess role of serum procalcitonin (PCT) as a useful biomarker for the infections and outcomes in these patients. METHODS: Retrospective observational study. RESULTS: Total 47 patients with febrile episodes were enrolled. Twenty patients underwent autologous BMT and 27 underwent allogeneic BMT. Bacterial infections were documented in 18/47 (38%) patients. Forty patients were neutropenic. The median fever duration was 10 days (range 3-30 days) in positive procalcitonin level group whereas it was 4 days (range 1-18) in negative group. This was statistically significant (P=0.000). Procalcitonin levels were high in 8/9 episodes of sepsis (P=0.029). Intensive care unit transfers and death were significantly higher in PCT positive group as compared to PCT negative group. CONCLUSION: Serum procalcitonin levels provide prognostic information of worse outcome in patients undergoing HSCT.

Paraneoplastic hepatic dysfunction with jaundice in a case of primary renal synovial sarcoma: A very rare scenario.

Nonmetastatic hepatic dysfunction known as Stauffer's syndrome is a rare entity. It is commonly associated with clear cell carcinoma of kidney. Rarely it has been reported in cases of prostatic carcinoma, bronchogenic tumor and lymphoproliferative diseases. Stauffer s syndrome presents as elevated alkaline phosphatase, aminotransferases, and prolonged prothrombin time without jaundice. However a very rare variant of Stauffer's syndrome presenting with jaundice has been reported in few case reports of clear cell carcinoma of kidney. But such a presentation in cases of renal sarcomas has not been reported so far. Here we report a unique case of primary synovial sarcoma of kidney presenting as nonmetastatic cholestatic jaundice.

Reducing Phlebotomy Utilization With Education and Changes to Computerized Provider Order Entry.

INTRODUCTION: Daily phlebotomy is often a standard procedure in hospitalized patients. Recently, this practice has begun receiving attention as a potential target for efforts focused on eliminating overuse. Several organizations have published their efforts in this arena. Interventions have included education, feedback, and changes to computerized provider order entry (CPOE) but have yielded mixed results. METHODS: A quality improvement initiative to reduce the utilization of daily phlebotomy was conducted at a 505-bed Academic Medical Center. This project involved a combination of educational interventions and changes to CPOE. The primary end point evaluated was the daily performance of complete blood counts (CBCs) and basic metabolic profiles (BMPs) on medical and surgery units relative to the corresponding hospital census. RESULTS: Over the course of this project from August 1, 2013, to September 23, 2016, there was a 15.2% reduction in CBCs (p < .001 for linear trend) and 13.1% reduction in BMPs. DISCUSSION: Our results suggest that layering multimodal interventions that involve both "hard-wired" changes to CPOE and education and performance feedback can result in decreased utilization of phlebotomy.

Centchroman vs tamoxifen for regression of mastalgia: a randomized controlled trial.

INTRODUCTION: Several agents have been tried in the management of mastalgia. Centchroman (Ormeloxifene), a novel non-steroidal selective estrogen receptor modulator (SERM), has also been recently used in the management of mastalgia. METHODS: Eligible patients, who had mastalgia for more than 3 months, were randomized into two groups - Group A received centchroman 30 mg daily and Group B received tamoxifen 10 mg daily. Treatment was continued for a total of 12 weeks; thereafter, patients were followed for another 12 weeks without medication to assess the continuum of relief. Pain severity was measured with VAS score. Patients were considered to have complete pain relief if their VAS score decreased to 3 or less. RESULTS: Patients, in both the groups, showed gradual improvement in mastalgia with passage of time up to 12 weeks. Following cessation of treatment at 12 weeks, partial relapse of pain was observed at 24 weeks. There was no significant difference between Group A and Group B in terms of mean VAS Score and proportion of women reporting pain relief at 4, 8, 12, and 24 weeks. Fifteen patients in Group A had side effects namely dizziness, menstrual irregularities and development of ovarian cysts. There was no side effect noted in group B. CONCLUSION: Centchroman and tamoxifen were found to be of similar effectiveness in providing pain relief in mastalgia. High frequency of side effects, particularly development of ovarian cyst, in patients receiving centchroman is a matter of concern.

Safety and acceptance of non-sedated upper gastrointestinal endoscopy: a prospective observational study.

BACKGROUND: The study was conducted to assess the patient acceptability of non-sedated upper gastrointestinal (GI) endoscopy and to study cardiorespiratory changes during the procedure. SUBJECTS AND METHODS: This study was conducted in the outpatient endoscopy room of Department of Surgery of a teaching tertiary-care hospital in North India. The patients underwent diagnostic GI endoscopy under topical pharyngeal anesthesia using 5% lidocaine. No sedation was used. Pulse rate (PR), respiratory rate (RR), oxygen saturation (SpO(2)), and mean blood pressure (BP) were recorded immediately prior to endoscopy, during endoscopy, and 5, 15, and 30 minutes after endoscopy. Using a 10-point Likert scale, all the patients were asked to record their expected discomfort for the endoscopy as a pre-test score and their actual level of discomfort during endoscopy as a post-test score. Patients were also asked about whether they would opt for non-sedated upper GI endoscopy again in the future if required. RESULTS: Sixty patients underwent diagnostic upper GI endoscopy during the study period. Post hoc tests using Bonferroni's correction revealed that mean PR, RR, and mean BP changed significantly during endoscopy. However, these parameters normalized at 30 minutes following endoscopy. Mean SpO(2) did not differ significantly at the different time points. Pre- and post-endoscopy mean visual analog scale scores to assess the expected level of discomfort during endoscopy were not statistically different. Forty-four patients (73.3%) indicated their willingness to undergo repeat non-sedated endoscopy in the future if required. Binary logistic regression analysis identified young age, male gender, and long duration of procedure as significant factors for unwillingness to undergo repeat non-sedated endoscopy. CONCLUSION: Non-sedated endoscopy is a feasible, safe, and fast office procedure and seems well tolerated by most patients.

Design and development of paclitaxel-loaded bovine serum albumin nanoparticles for brain targeting.

Bovine serum albumin (BSA) nanoparticles loaded with paclitaxel (PTX) were prepared using a desolvation technique. A 32 full factorial design (FFD) was employed to formulate nanoparticles. Nanoparticles were characterized for particle size by photon correlation spectroscopy and surface morphology by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Encapsulation efficiency, zeta potential and particle yield were also determined. Response surface linear modelling (RSLM) was used to predict the optimal formulation. Various models were applied to determine the release mechanism from PTX nanoparticles. The effect of drug-polymer ratio on the release profile of formulations was observed and was applied to determine the suitability of the predicted optimal formulation. A preliminary study to determine the feasibility of targeting the prepared nanoparticles to brain was also carried out using mice as in vivo models.