An Analysis of the VELNEZ Nasal Pack's Acceptability and Safety for Use During Nasal Surgery: A Prospective Study.

The primary function of nasal packs is to modulate the bleeding, prevent adhesions and obstruction, with least discomfort to the subjects without risking secondary infection. However, both packing and removal of the pack is an unpleasant experience, with the latter being extremely painful. Therefore the need of the hour is a dressing which prioritizes subject comfort without compromising other desired nasal pack properties. Twenty subjects were enrolled in this interventional, open label study. The subjects had 10 hospital visits, starting from baseline (Visit 1) to postoperative day 28 (Visit 10), at regular intervals. The proportion of the population with postoperative pain alleviation and bleeding control failure (within 10 min) were the main objectives. Within 10 min of VELNEZ administration, all 20 participants got their bleeding under control. With VELNEZ, the painful nasal pack removal method was totally avoided because it was biodegradable. No moderate/severe pain, infection and adhesions were reported in any of the subjects, but few subjects reported moderate obstruction until Visit 3 (Discharge Day). In the present study, for participants undergoing nasal surgery, VELNEZ proved to be a secure and reliable nasal pack. Trial Registration: CTRI/2021/09/036437, prospectively registered.

Mesenchymal stem cells are prospective novel off-the-shelf wound management tools.

Chronic/non-healing cutaneous wounds pose a debilitating burden on patients and healthcare system. Presently, treatment modalities are rapidly shifting pace from conventional methods to advanced wound care involving cell-based therapies. Mesenchymal stem cells (MSCs) have come across as a prospective option due to its pleiotropic functions viz. non-immunogenicity, multipotency, multi-lineage plasticity and secretion of growth factors, cytokines, microRNAs (miRNA), exosomes, and microvesicles as part of their secretome for assisting wound healing. We outline the therapeutic role played by MSCs and its secretome in suppressing tissue inflammation, causing immunomodulation, aiding angiogenesis and assisting in scar-free wound healing. We further assess the mechanism of action by which MSCs contribute in manifesting tissue repair. The review flows ahead in exploring factors that influence healing behavior including effect of multiple donor sites, donor age and health status, tissue microenvironment, and in vitro expansion capability. Moving ahead, we overview the advancements achieved in extending the lifespan of cells upon implantation, influence of genetic modifications aimed at altering MSC cargo, and evaluating bioengineered matrix-assisted delivery methods toward faster healing in preclinical and clinical models. We also contribute toward highlighting the challenges faced in commercializing cell-based therapies as standard of care treatment regimens. Finally, we strongly advocate and highlight its application as a futuristic technology for revolutionizing tissue regeneration.

Ionic Liquid-Controlled Shape Transformation of Spherical to Nonspherical Polymersomes via Hierarchical Self-Assembly of a Diblock Copolymer.

Here, we report the self-assembly of poly(ethylene glycol) methyl ether-block-poly(ε-caprolactone) (PEG-b-PCL) copolymer in three ionic liquids (ILs) possessing different cations with common bis(trifluoromethylsulfonyl)imide anion. The observed polymeric nanostructures in ILs were directly visualized by room temperature conventional transmission and field emission scanning electron microscopy and were further examined for their size and shape by dynamic light scattering technique. The results show that through changes in the concentration of PEG-b-PCL and/or changing the solvent by using a different IL, we can effectively induce shape transformation of self-assembled PEG-b-PCL nanostructures in order to generate nonspherical polymersomes, such as worm-like aggregates, stomatocytes, nanotubes, large hexagonal and tubular-shaped polymersomes. These findings provide a promising platform for the design of biodegradable soft dynamic systems in the micro-/nano-motor field for cancer-targeted delivery, diagnosis and imaging-guided therapy, and controlled release of therapeutic drugs for treatment of many diseases. Non-spherical polymersome-based vaccines may be taken up more efficiently, especially against viruses for pulmonary drug delivery than the spherical polymersomes-based.

Formation of water-in-oil microemulsions within a hydrophobic deep eutectic solvent.

Hydrophobic deep eutectic solvents (DESs) as neoteric, non-toxic, and inexpensive media have the potential to replace organic solvents in various aggregation processes. Conventional water-in-oil microemulsions are formed using mostly environmentally unfavorable toxic organic solvents as the bulk oil phase. Evidence of formation of water-in-DES microemulsions is presented. These novel assemblies are formed using a hydrophobic DES constituted of n-decanoic acid (DA) and tetra-n-butylammonium chloride (TBAC) in 2 : 1 mole ratio, termed TBAC-DA, as the bulk oil phase. It is observed that in the presence of a common and popular non-ionic surfactant Triton X-100 (TX-100), water pools are formed within TBAC-DA under ambient conditions with maximum water loading (w0 = [water]/[TX-100]) of 60 ± 3 for [TX-100] = 300 mM. The formation of the microemulsions is established by using fluorescence probe pyranine, which exhibited the appearance of a band characterizing the un-protonated form of the probe clearly implying onset of water-in-TBAC-DA microemulsion formation. The UV-vis absorbance of CoII further corroborates TX-100-assisted water pool formation within TBAC-DA via the appearance of the band that is assigned to the response of the probe in water. Dynamic light scattering (DLS) measurement suggests average aggregate sizes to be in the range of 72(±4) to 122(±7) nm. These unprecedented water-in-DES microemulsions may have far reaching implications due to their benign nature.

Chitosan and gelatin biopolymer supplemented with mesenchymal stem cells (Velgraft®) enhanced wound healing in goats (Capra hircus): Involvement of VEGF, TGF and CD31.

AIM: Cell-based therapy has emerged as promising strategy for chronic and impaired wounds treatment. Current research is focused on developing biomaterial systems that act as a niche for mesenchymal stem cells (MSCs) to promote wound healing through paracrine molecular cascading. This study was aimed to evaluate the wound healing potential of Velgraft, a ready-to-use biodegradable artificial skin substitute, on excision wound in goats. MATERIALS AND METHODS: Twelve male goats were randomized divided in to three groups of four animals each. After infliction of surgical wound, Velgraft and Soframycin were applied on wounds of the animals of Groups II and III while Group I (sham operated) served as control. Wound diameters were measured at pre-defined time-points for determination of progressive wound healing up to 28 days. Skin sections were stained using Hematoxylin and eosin (H&E) for examining the histoarchitectural changes, Masson trichome staining for ascertaining collagen synthesis and immunohistochemistry for expression of CD31, VEGF and TGF-ß1 proteins to determine post-treatment angiogenesis in the inflicted wounds. RESULTS: Velgraft application appreciably enhanced wound closure by day 21 which was confirmed through restoration of the normal skin architecture as evident based on histopathological examination and characterized by complete regeneration of epidermal layers, collagen fibers, blood capillaries and hair follicular formation. Stimulation of angiogenesis markers was also observed at different time-points post-Velgraft application; which is suggestive of the improved angiogenesis and vasculogenesis. CONCLUSION: Velgraft facilitates wound healing by augmenting early wound closure, enhancing collagen synthesis and deposition, trichosis development and promoting revascularization and epidermal layers restoration.

Advances and clinical challenges for translating nerve conduit technology from bench to bed side for peripheral nerve repair.

Injuries to the peripheral nervous system remain a large-scale clinical problem. These injuries often lead to loss of motor and/or sensory function that significantly affects patients' quality of life. The current neurosurgical approach for peripheral nerve repair involves autologous nerve transplantation, which often leads to clinical complications. The most pressing need is to increase the regenerative capacity of existing tubular constructs in the repair of large nerve gaps through development of tissue-engineered approaches that can surpass the performance of autografts. To fully realize the clinical potential of nerve conduit technology, there is a need to reconsider design strategies, biomaterial selection, fabrication techniques and the various potential modifications to optimize a conduit microenvironment that can best mimic the natural process of regeneration. In recent years, a significant progress has been made in the designing and functionality of bioengineered nerve conduits to bridge long peripheral nerve gaps in various animal models. However, translation of this work from lab to commercial scale has not been achieve. The current review summarizes recent advances in the development of tissue engineered nerve guidance conduits (NGCs) with regard to choice of material, novel fabrication methods, surface modifications and regenerative cues such as stem cells and growth factors to improve regeneration performance. Also, the current clinical potential and future perspectives to achieve therapeutic benefits of NGCs will be discussed in context of peripheral nerve regeneration.

Unprecedented formation of reverse micellar vesicles from psuedopeptidic bottlebrush polymers.

Spherical assemblies named "reverse micellar vesicles" from self-assembling psuedopeptidic bottlebrush polymers are reported. These assemblies exhibited the combined features of both micelles and vesicles viz. molecular arrangement of classical micelles and dimensions similar to that of classical vesicles. Comprehensive ultramicroscopic and spectroscopic analyses were performed to delineate the hierarchical mechanism of their formation.

Cartilage repair using stem cells & biomaterials: advancement from bench to bedside.

Osteoarthritis (OA) involves gradual destruction of articular cartilagemanifested by pain, stiffness of joints, and impaired movement especially in knees and hips. Non-vascularity of this tissue hinders its self-regenerative capacity and thus, the application of reparative or restorative modalities becomes imperative in OA treatment. In recent years, stem cell-based therapies have been explored as potential modalities for addressing OA complications. While mesenchymal stem cells (MSCs) hold immense promise, the recapitulation of native articular cartilage usingMSCs remains elusive. In this review, we have highlighted the chondrogenic potential of MSCs, factors guiding in vitro chondrogenic differentiation, biomaterials available for cartilage repair, their current market status, and the outcomes of major clinical trials. Our search on ClinicalTrials.gov using terms "stem cell" and "osteoarthritis" yielded 83 results. An analysis of the 29 trials that have been completed revealed differences in source of MSCs (bone marrow, adipose tissue, umbilical cord etc.), cell type (autologous or allogenic), and dose administered. Moreover, only 02 out of 29 studies have reported the use of matrix for cartilage repair. From future perspective, aconsensus on choice of cells, differentiation inducers, biomaterials, and clinical settings might pave a way for concocting robust strategies to improve the clinical applicability of biomimetic neocartilage constructs.

Assessment of long term outcomes after buccal mucosal graft urethroplasty: the impact of chronic kidney disease

ABSTRACT Objectives To compare and assess various outcomes and success of buccal mucosal graft urethroplasty (BMGU) in patients with CKD versus patients having normal renal function. Material and Methods This was a retrospective, single centre study, during period 2013 to 2017. Patients were grouped into two groups. Group 1 had patients with estimated Glomerular Filtration Rate (eGFR)>60mL/min/1.73m2 while group 2 had patients with eGFR <60mL/min/1.73m2. eGFR was calculated according to the MDRD equation. The two groups were compared with regard to various outcomes like length, location of stricture, technique of graft placement, intra-operative blood loss (haemoglobin drop), duration of hospital stay, post-operative complications and recurrence. Results A total of 223 patients were included in study with group 1 had 130 patients and group 2 had 93 patients. Mean age of patients with CKD were higher (47.49 years versus 29.13 years). The mean follow-up period was comparable between both groups (23.29 months and 22.54 months respectively). Patients with CKD had more post-operative Clavien Grade 2 or higher complications (p=0.01) and a greater recurrence rates (p<0.001) than in non-CKD patients. On multivariate analysis, age and CKD status was significant predictor of urethroplasty success (p=0.004) (OR= 14.98 (1.952-114.94, 95% CI). Conclusions CKD patients are more prone to post-operative complications in terms of wound infection, graft uptake and graft failure and higher recurrence rates following BMGU.

Changing profiles of patients undergoing transurethral resection of the prostate over a decade: A single-center experience.

CONTEXT: Patients with benign prostatic hyperplasia (BPH) usually form the bulk in urology outpatient departments. The management options include medical therapy or surgery. Transurethral resection of the prostate (TURP) has been the mainstay of surgical management. The use of medical therapy has increased over the years. This has led to a shift in the profiles of patients undergoing surgical management of BPH. AIMS: We conducted this study to analyze the differences in profiles of patients undergoing TURP over a decade. SETTINGS AND DESIGN: This was a retrospective study. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent TURP from January 1 to December 31 in 2006 and 2016. The age, preexisting comorbidities, prostate volume, operative time, mean prostatic tissue removed, duration of hospitalization, and complications were evaluated among the two groups of patients. Charlson comorbidity index was used to evaluate the preexisting comorbidities, and the modified Clavien classification system was used for evaluating the perioperative and postoperative complications. RESULTS: A total of 114 and 125 patients underwent TURP in 2006 and 2016, respectively. The mean age of the patients was 62.1 ± 8.22 and 66.94 ± 9.12 years in 2006 and 2016, respectively. The serum prostate-specific antigen levels increased from 4.39 ± 4.425 to 5.59 ± 7.61 ng/ml a decade apart. A number of patients taking medical therapy before surgical intervention increased from 62.23% to 75.2% (P < 0.05). There was a significant increase in the mean prostatic volume and weight. There was only a modest increase of 1.94% in the total number of complications (P > 0.05) and no significant change in the rates of complications. CONCLUSIONS: Medical therapy for BPH patients has resulted in delayed surgical interventions. The complication rates have not increased. Thus, the increased use of medical therapy in BPH patients is justified though TURP may still be considered the gold standard.

Laparoscopic transperitoneal heminephrectomy for treatment of the nonfunctioning moiety of duplex kidney in adults: A case series.

Purpose: We report the results and experience of a tertiary care center in laparoscopic transperitoneal heminephrectomy for the treatment of a non-functioning upper pole moiety of duplex kidney in adults. Materials and Methods: The key point of the technique included the placement of a 6-Fr ureteric catheter in the healthy ureter at the beginning of the procedure under fluoroscopic guidance cystoscopically. A standard laparoscopic 3- to 4-port placement was done after placing the patient in a 45 to 90 degrees lateral decubitus position. The upper pole was mobilized transperitoneally and transected using a harmonic scalpel. Results: A total of 17 patients aged 19 to 44 years underwent laparoscopic upper pole heminephrectomy. All patients had a complete duplicated renal collecting system on the ipsilateral side. Three patients were found to have ureterocele. The average blood loss was minimal (50-150 mL) with a mean of 95 ml. None of the patients required any blood transfusions. The mean operative time was 220 minutes (range, 160-315 minutes). The average length of hospital stay was 3 days (range, 2-4 days). Only 2 patients had Clavien-Dindo grade 3a complications, which were managed by double J stenting and percutaneous aspiration, respectively. Conclusions: Laparoscopic heminephrectomy is playing a cornerstone role in the treatment of the non-functioning moiety of duplex kidneys. The procedure is safe, efficient and offers the typical preoperative and postoperative benefits of laparoscopic surgery. The rate of complications in adults is acceptable and is similar to that reported in pediatric patients.

Transvaginal Repair of Vesico Vaginal Fistula: A 10-Year Experience with Analysis of Factors Affecting Outcomes.

OBJECTIVES: To highlight the transvaginal route as an excellent approach for repair of a simple trigonal, supra-trigonal vesico-vaginal and urethrovaginal fistulae without compromising on the successful patient outcomes. We also determine factors affecting outcomes in such patients. MATERIALS AND METHODS: A retrospective analysis was carried out on 58 patients with simple trigonal, supra trigonal and urethrovaginal fistula who underwent transvaginal repair in the last 10 years. Simple fistulas were defined as fistula less than 3 cm in size or recurrent fistulae less than 1.5-2 cm in size and located either supra-trigonally (above the bar of mercier) or sub-trigonally (below the bar of mercier) as determined by cystoscopy. RESULTS: Obstetric cause, due to obstructed labour, was the most common cause of fistula formation (68.96%), while remaining (29.31%) were attributed to hysterectomy. Primary fistulae were found in 68.9% of patients and recurrent fiistulae in 31.1% patients. The mean age of patients was 33.4 years. Average fistula size was 1.5 cm. The success rate of primary operation was 84.12% (50/58). On using a multivariate regression model, the underlying aetiology (OR 2.2), fistula location (OR 2.5) and history of previous repair (OR 2.4) were found to be significant factors affecting outcome. CONCLUSION: The transvaginal approach is less invasive and achieves comparable success rates as compared to other methods of vesico-vaginal fistula repair. This surgery with Foley catheter has a high success rate with reduced morbidity. We postulate that vaginal approach should be preferred over abdominal approach for repair of all vaginally accessible vesico vaginal fistulae, both of obstetrical and gynaecological origin.

Implications of the Fracture Risk Assessment Algorithm for the assessment and improvement of bone health in patients with prostate cancer: A comprehensive review.

OBJECTIVE: Maintaining the optimum bone health is one of the important concerns in patients with prostate cancer, but it usually remains neglected. Failure to screen these patients is detrimental to both the length and the quality of life. The estimation of bone mineral density (BMD) and more recently the World Health Organization's fracture risk assessment (FRAX) algorithm in appropriate patients is recommended by several specialty organizations/associations at the time of instituting androgen deprivation therapy (ADT) for metastatic and high-risk individuals. It provides a 10-year risk evaluation of hip and major osteoporotic fractures (MOF). Using this web-based new investigating tool, candidates at high risk of fractures can be predicted more accurately according to clinical risk factors (CRF) alone or in combination with the femoral neck BMD. The FRAX application for senile osteoporosis has been studied and reviewed extensively, but no systematic review has ever been conducted for assessing the implication of FRAX in prostate cancer. This review article will give insight about the validity, role, and utility of this investigating tool in clinical practice for fracture risk assessment in these individuals. MATERIAL AND METHODS: This systematic review was carried out as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and Cochrane review principles. We searched the PubMed, Cochrane database of systematic reviews, and the EMBASE electronic database until December 2018 using the medical subject heading terms prostate cancer and FRAX. RESULTS: A total of nine studies meet the inclusion criteria and were included in the review. These studies enrolled a total of 3704 patients (sample size range, 78-1220) of localized, metastatic, castration resistant prostate cancer with or without ADT and/or on photon or radiotherapy. The factors that influenced FRAX included age, ethnicity, baseline BMD, duration of ADT, presence of CRF, and measurement methods (CRF, with/without BMD, computed tomography based). An advanced age and duration of ADT were the most robust risk factors. A 10-year MOF and hip fracture risk estimation was higher when the femoral neck BMD was not incorporated in the FRAX measurement. Despite several well-known strengths of using FRAX in the fracture risk assessment of suitable candidates with prostate cancer, several risk factors such as the mode/duration of ADT, mode of radiotherapy, Vitamin D levels, bone remodeling markers, and recent/recurrent fractures need to be incorporated in the FRAX calculator for improving the predictive ability. In contrast to senile osteoporosis with a longer life expectancy, the fracture risk in patients with prostate cancer need to be measured more frequently and for a shorter time. Therefore, models like Garvan calculator with both 5- and 10-year risk estimates have to be developed for these patients. Additionally, its utilization is of limited value in the presence of recurrent fractures or falls. CONCLUSION: The FRAX algorithm is beneficial in identifying patients who require early intervention or bone-directed therapy as an early step to decrease skeletal-related events and other morbidity. Several risk factors need to be added for improving the FRAX predictive value. This model is still underutilized in the clinical practice and increasing the awareness among treating physicians will help in optimizing the bone health and the quality of life of this important population subgroup.

Comparison of outcomes in malignant vs. non-malignant ischemic priapism: 12-year experience from a tertiary center.

OBJECTIVE: Data on outcome of patients with ischemic priapism (IP) due to malignant causes are scant. In this study, we compared outcome of patients with malignant vs. non-malignant IP in adult North Indian men. MATERIAL AND METHODS: We analyzed medical records of patients with IP who presented to a large tertiary care referral center from August 2005 to July 2017. RESULTS: Data of 71 patients were analyzed. The median age was 30 years (range 17-65). The average duration of symptoms was 4.39 days (range 1-10). Most common etiology was idiopathic in 29 (40.84%), chronic myeloid leukemia (CML) in 24 (33.80%), and drug-induced in 15 patients. Thirty-eight patients underwent distal shunts, while nine patients underwent proximal shunt procedure. Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications (p<0.05). Most complications after shunt surgery were minor (Clavein grade 1 and 2). After shunt surgery, bleeding at shunt site was observed in 14 cases, and wound infection developed in five patients. Prevalence of erectile dysfunction in patients at follow-up was high. CONCLUSION: Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications than men with non-malignant priapism.

Evaluation of resistive index of the prostate and bladder sonomorphologic parameters as replacements for urodynamics to predict bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: This study investigated whether the resistive index (RI) of prostate and bladder sonomorphologic parameters (total prostate volume [TPV], detrusor wall thickness [DWT], intraprostatic protrusion [IPP]) can be used instead of urodynamic studies (UDS) to predict bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). METHODS: Men aged ≥50 years with clinical BPH/LUTS were prospectively enrolled included. Basic evaluations, measurement of sonomorphologic parameters, and UDS were performed in accordance with the International Continence Society's Good Urodynamics Practices protocol. RESULTS: Data of 240 patients were divided into two groups based on the BOO index(BOOI). Group 1 consisted of patients negative for BOO (BOOI <40), whereas Group 2 consisted of patients positive for BOO (BOOI > 40). Patient age, International Prostate Symptom Score (IPSS), quality of life score and post-void residual volume were comparable between the two groups, whereas significant differences were evident in peak flow rate, TPV, DWT, RI, and IPP (P < 0.01 for all). Pearson correlation analysis revealed a significant correlation between BOOI and DWT (r = 0.198, P = 0.002), IPP (r = 0.450, P = 0.000), and RI (r = 0.334, P = 0.000). Multiple regression analysis revealed a significant correlation between BOOI and IPP (ß = 0.382, P = 0.000) and RI (ß = 0.226, P = 0.000). Receiver operating characteristic analysis showed that the area under curve was 0.785 for RI (95% confidence interval [CI] 0.703-0.867, P < 0.001) and 0.905 for IPP (95% CI 0.850-0.961, P < 0.001). At a cut-off value of 7.5 mm for IPP, the sensitivity was 86.9%, specificity was 83.3% and positive predictive value was 92.41%. CONCLUSION: IPP and RI may be the best non-invasive predictors for BOO in selected patients with LUTS/BPH.

Medullary sponge kidney and Caroli's disease in a patient with stricture urethra: look for the hidden in presence of the apparent.

Caroli's disease is a rare congenital disorder with incidence rate of approximately 1 in 1 000 000 population. Renal anomalies which may be associated with Caroli's disease include medullary sponge kidney (MSK), cortical cysts, adult recessive polycystic kidney disease and rarely autosomal dominant polycystic kidney disease. Exact incidence of MSK in patients of Caroli's disease is not known. There are only a handful of reported cases of this association in literature. We hereby report a case of Caroli's disease with MSK with nephrocalcinosis. He presented to primary health centre with symptoms of urethral stricture due to lichen sclerosus et atrophicus and was managed with repeated co-axial dilatation but was never evaluated for underlying chronic renal insufficiency due to MSK. The thorough clinical examination and proper evaluation is important in patient of urethral stricture with underlying chronic renal insufficiency to avoid delayed diagnosis, management and related complications.