Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

I've looked at gut from both sides now: Gastrointestinal tract involvement in the pathogenesis of SARS-CoV-2 and HIV/SIV infections.

The lumen of the gastrointestinal (GI) tract contains an incredibly diverse and extensive collection of microorganisms that can directly stimulate the immune system. There are significant data to demonstrate that the spatial localization of the microbiome can impact viral disease pathogenesis. Here we discuss recent studies that have investigated causes and consequences of GI tract pathologies in HIV, SIV, and SARS-CoV-2 infections with HIV and SIV initiating GI pathology from the basal side and SARS-CoV-2 from the luminal side. Both these infections result in alterations of the intestinal barrier, leading to microbial translocation, persistent inflammation, and T-cell immune activation. GI tract damage is one of the major contributors to multisystem inflammatory syndrome in SARS-CoV-2-infected individuals and to the incomplete immune restoration in HIV-infected subjects, even in those with robust viral control with antiretroviral therapy. While the causes of GI tract pathologies differ between these virus families, therapeutic interventions to reduce microbial translocation-induced inflammation and improve the integrity of the GI tract may improve the prognoses of infected individuals.

Enhanced Efficiency of Dye Sensitized Solar Cell Using Eu Doped TiO2-ZrO2 Nanocomposite.

BACKGROUND: Hydrothermal method was used to prepare TiO2-ZrO2 and Eu doped TiO2-ZrO2 nanocomposites for dye sensitized solar cell app lication. METHODS: X-ray diffraction was used to study the structural properties of prepared samples. Anatase and Rutile phases of TiO2 and Monoclinic and tetragonal phases of ZrO2 have been detected from XRD in prepared samples. The crystallite size of prepared samples lies between 6 to 18 nm. Absorption edge has been shifted to the longer wavelength region. The optical bandgap of TiO2-ZrO2 (2.15 eV) and Eu doped TiO2-ZrO2 nanocomposites (2.03 eV) have been calculated using Tauc's plot. A decrease in bandgap compared to pure TiO2 has been observed. The increased refractive index has been determined from UV -Visible spectra. RESULTS: Because of the high refractive index photons can stay for longer period of time inside the material and then they can be used to generate electrons in dye sensitized solar cell. An attempt was made to prepare an inexpensive dye sensitized solar cell by replacing synthetic organic dye with natural dye (pomegranate juice) and platinum coated counter electrode by carbon coated electrode. The improvement in efficiency has been recorded for prepared samples and it has been found to be 0.71%, 1.97% and 6.25% for TiO2, TiO2-ZrO2 nanocomposite and Eu doped TiO2-ZrO2 nanocomposite respectively. CONCLUSION: A simple and cost-effective DSSC prepared by materials is capable of producing a good amount photocurrent.

Factors Influencing the Valgus Cut Angle-during Total Knee Arthroplasty-in Indian Population.

The number of total knee arthroplasties performed in India and the world is increasing exponentially. The valgus cut angle (VCA) of the distal femur decides the final alignment achieved in the coronal plane. Little data are available regarding the ideal value for an Indian population and there is little consensus whether to use a single value for all knees or to individualize the angle for each patient. The parameters that can influence the value of this angle have not been evaluated thoroughly.Standard long leg X-ray (orthoscanogram) was used to calculate the VCA in 302 lower limbs (160 patients). Only Indian patients were included in the study; knees with bowed femurs were excluded. VCA, femoral length, medial hip offset, neck shaft angle, and hip knee ankle angle were measured manually. Demographic data such as gender, height, and weight were extracted from hospital charts. The correlation of VCA with the various parameters was evaluated using Pearson's correlation and its significance assessed using the independent Student's 't' test.The average VCA was 7.4 degrees (range: 4-11 degrees). Age, gender, height, hip knee ankle angle (alignment) and body mass index (BMI) had no influence on the VCA. The neck shaft angle (r = -0.520, p = < 0.0001) and hip medial offset (r = 0.223, p = < 0.0001) were the only two parameters significantly and independently influencing the value of VCA. There is a wide variation in the value of VCA in the Indian population. Choosing a fixed VCA will lead to significant number of knees aligned outside the ideal 0- to 3-degree hip knee ankle angle. The neck shaft angle and the medial hip offset are the only two factors that influence the VCA. The patients' height, preoperative deformity, gender, and BMI had no influence on the VCA.

A prospective comparative study of local infiltration versus adductor block versus combined use of the two techniques following knee arthroplasty.

BACKGROUND: Pain management after total knee arthroplasty (TKA) is important as acute postoperative pain can affect patient's ability to walk and participate in rehabilitation required for good functional outcome. This is achieved by effective intra-operative and post-operative analgesia to facilitate early recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) are analgesic regimens and commonly used for effective post-operative analgesia after TKA. Our aim was to compare the efficacy and outcomes of these two methods, combined and independently. METHODS: Our study included 120 patients undergoing unilateral TKA, who were randomized into three groups: LIA (Group I), ACB (Group II) and combined LIA + ACB (Group III). Patients were operated by a single surgeon. The outcome was defined by post-operative analgesia achieved by the three techniques (measured by the NPRS) and amount of fentanyl consumed postoperatively. Secondary outcome was evaluated based on postoperative functional outcomes in terms of ability to stand, distance covered, range of motion of knee on the 1st post-operative day, complications and WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index) scores. RESULTS: All patients were available for analysis. Numerical Pain Rating Scale for pain showed significant differences at 24 h between Group I and Group II, with a p value of 0.018 (GroupI was better), significant differences were found at 24 h between Group III and Group II, with p values being 0.023 and 0.004 (GroupIII was better). No significant differences were found between Group I and Group III at 24 h. Total fentanyl consumption was significantly less in Group III than in Group I and Group II, with p value being 0.042 and 0.005, respectively (Group III was better and consumed less fentanyl). No significant differences were found in WOMAC scores between the three groups at baseline, 2 and 6 weeks after operation. CONCLUSION: In patients undergoing TKA, analgesic effect of combined ACB and LIA was superior, as indicated by reduced opioid consumption and no differences in functional outcomes and complications were observed as compared to separate use of the two techniques.

Tubercular esophagocutaneous fistula: Rare case report.

Tubercular esophagocutaneous fistula is a rare entity with only about five cases reported so far. It can be as a result of primary involvement of esophagus by tuberculosis or due to spread of infection from adjacent structures like lungs or mediastinal lymph nodes. The fistula usually heals with initiation of antitubercular therapy and surgery is rarely required. Here we report a case of 65-year-old diabetic male who developed esophagocutaneous fistula secondary to caseation of mediastinal lymph nodes and was successfully treated with antitubercular treatment.

Accuracy of urinary dipstick testing for pH manipulation therapy.

PURPOSE: To determine the accuracy of urinary dipstick testing for pH manipulation therapy. MATERIALS AND METHODS: Three commercial brands of dipstick paper were used to measure the pH of 100 fresh urine specimens from patients with urologic diseases. These were all read by an experienced medical technician. The pH of these specimens was also measured with an electrochemical pH meter ("gold standard") performed by another experienced technician. Both were blinded to each other's results. The influence of urinary microscopic findings was also assessed. Student t test and analysis of variance were used to analyze the data. RESULTS: The accuracies of the dipsticks for determining pH were as follows: 54.8% to 92.8% for less than 6, 45% to 97.5% for 6 to 7, 72.2% to 83.3% for greater than 7. One of the dipsticks assessed had the lowest accuracy for all three ranges. There was a statistically significant difference between the performances of the other two as compared with the least accurate one. There were no statistically significant differences between the two more accurate dipsticks. Urinary microscopic findings and other dipstick results did not influence results. CONCLUSION: The targeted pH range for urinary pH manipulation therapy is 6 to 7. These results indicate that dipstick testing may be applicable to monitor patients on pH manipulation therapy and modify treatment when necessary. The accuracy of the device used for this purpose, however, must be determined before use.

Role of laparoscopic stone surgery.

OBJECTIVES: To define the role of laparoscopic stone surgery in current urologic practice. METHODS: All cases of laparoscopic surgery for renal calculus disease performed at a single institution during a 2-year period were reviewed. A total of 449 stone-removing procedures were performed by one of us (D.G.A.) during this interval, of which 5 were laparoscopic (1.1%). Of the five laparoscopic procedures, three were pyelolithotomy/pyeloplasty, one was laparoscopic-assisted percutaneous nephrostolithotomy, and one was caliceal diverticular stone removal. RESULTS: All 5 patients were rendered stone free, and no patient had perioperative complications. CONCLUSIONS: A laparoscopic approach is rarely needed in patients requiring stone removal. However, it can be a safe and effective approach in the management of select patients with complex stone disease.

Management of cystinuria.

Cystinuria is a monogenic disorder in which there is a transepithelial transport defect of di-basic amino acids, including cystine, ornithine, lysine, and arginine (COLA). This results in diminished reabsorption of these amino acids in both the intestine and renal proximal tubule. This article describes the disorder, reviews the mechanisms of normal COLA renal transport, and summarizes issues related to the disorder, such as the role of mutations, associated diseases, clinical manifestations, therapies, the renal impact, and handling of pediatric patients.

Current opinion in urology: new insights into nephrolithiasis.

PURPOSE OF REVIEW: Recent studies in nephrolithiasis have investigated why stones form, improvements in medical therapy, and advances in surgical therapy. We outline recent research in these areas. RECENT FINDINGS: We describe a series of articles characterizing the histopathology of Randall's plaques and the renal papillae in patients with nephrolithiasis, detailing genetic discoveries related to uric acid stones, describing further uses of alpha-antagonists in nephrolithiasis, and reporting improvements in extracorporeal shockwave lithotripsy technique and outcomes. SUMMARY: Characterization of the renal papillae and Randall's plaques in different types of stones may guide the urologist in treating stones and may lead to further research into how and where stones of different compositions form.