Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial

Objective To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. Methods This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). Results No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. Conclusions ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. Trial registration: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964

Efficacy of a food supplement Lertal® as an adjuvant therapy of patients with moderate-to-severe seasonal allergic rhinoconjunctivitis

Background Lertal® is an oral food supplement containing 80 mg of dry extract of Perilla frutescens, 150 mg of bioflavonoid quercetin, and 5 μg of vitamin D3. The aim of this study was to evaluate the efficacy of Lertal® as a complementary therapy to topical therapy of patients with moderate-to-severe seasonal allergic rhinoconjunctivitis (SAR). Results Seventy (n=70) adult patients with moderate-to-severe SAR were included in this prospective study and treated by four different procedures: (1) 21 patients received azelastine intranasal spray for 30 days and, after that, azelastine spray and Lertal® tablets for the next 30 days; (2) 19 patients received combined azelastine with fluticasone intranasal spray for 30 days and azelastine with fluticasone spray and Lertal® tablets for the next 30 days; (3) 15 patients received azelastine spray only for 60 days; (4) 15 patients received combined azelastine with fluticasone spray only for 60 days. Levels of SAR symptoms (sneezing, tearing, ocular itching, rhinorrhea, nasal obstruction, hyposmia, and cough), as well as Total Symptom Scores (TSS), were evaluated at the start of this investigation (visit 0), after 30 days of treatment (visit 1), and after 60 days of treatment (visit 2) using a visual analog scale. After 30 days of treatment, better effects were achieved in groups in which patients were treated with combined (antihistamine with corticosteroid) spray. After 60 days of therapy, we found the best effects in procedure 2 and slightly worse effects in procedure 1. The high differences in the reduction of TSS between the 60th and 30th day were found for procedure 2 (p<0.001) and procedure 1 (p<0.001). The worse improvement of symptoms we found was in procedure 4 (p<0.01), and, for the procedure 3, we found no significant difference (p=0.140). None of the patients reported adverse effects during the therapy. Conclusion Our results suggest that addition of food supplement Lertal® to the standard topical therapy of patients with moderate-to-severe SAR increases the effects of intranasal therapy in reducing nasal and ocular symptoms.

Differences in the Genital Microbiota in Women Who Naturally Clear Chlamydia trachomatis Infection Compared to Women Who Do Not Clear; A Pilot Study

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that was treated with metronidazole at the Ct screening visit. The rate of natural Ct clearance was 23.6% by the Ct treatment visit (median 9 days). 16S rRNA gene sequencing revealed that metronidazole-treated women who had a Lactobacillus spp.-dominant vaginal microbiota (CST 2 or 3) at the Ct treatment visit, were more prevalent in the Ct clearing population than the non-clearing population (86% v. 50%). L. iners (CST2) was the major Lactobacillus spp. present in Ct clearers, and 33% still remained anaerobe-dominant (CST1). Vaginal IFNγ levels were not significantly different in Ct clearers and non-clearers and were several logs lower than that required for killing Ct in vitro. An expanded panel of IFNγ-induced and proinflammatory cytokines and chemokines also did not reveal differences between Ct clearers and non-clearers, but, rather, suggested signatures better associated with specific CSTs. Taken together, these findings suggest that BV-associated bacteria may impede Ct clearance, but a Lactobacillus spp.-dominant microbiome is not an absolute requirement to clear. Further, IFNγ may be required at lower concentrations than in vitro modeling indicates, suggesting it may act together with other factors in vivo. Data also revealed that the vaginal bacteria-driven inflammation add complexity to the genital cytokine milieu, but changes in this microbiota may contribute to, or provide cytokine biomarkers, for a shift to Ct clearance.

Comparison of single versus double versus triple site band ligation for haemorrhoids in a single visit: a case-controlled double blind randomized study

Background: Rubber band ligation is considered one of the most popular non-surgical procedures available, representing the most reasonable balance between efficacy, pain and potential of complication. The present study was a controlled double blinded randomized study to compare Single versus double versus triple site band ligation for haemorrhoids in single treatment visit with special regards to its safety and efficacy in our patient population.Methods: There were 78 patients equally randomized in three groups by closed enveloped method. The number of patients in each group was 26, In Group A, a single, in Group B, two, and in Group C three major haemorrhoidal groups were rubber band ligated, in a single treatment visit on outpatient basis under topical anaesthesia with lignocaine 2% jelly.Results: Rubber band ligation was effective with significant symptom improvement seen in all patients with 88% patient satisfaction at end of 30 days period. Post ligation pain score and number of analgesic requirement in immediate post band ligation period, at 12 hours, at 1,7,14, 21 and 30 days post band ligation were similar in all three groups with p value >0.05. Multiple site haemorrhoidal bandings was done safely at single session without severe discomfort, pain or bleeding or severe complications requiring hospitalization.Conclusions: The study finding shows that triple site band ligation in a single session is a safe way of treating symptomatic haemorrhoids with similar post-procedure pain and patient satisfaction as conventional single or double site band ligation.

Development and Validation of a Cisplatin Dose-Ototoxicity Model

Background: Cisplatin is effective in the treatment of several cancers but is a known ototoxin resulting in shifts to hearing sensitivity in up to 50–60% of patients. Cisplatin-induced hearing shifts tend to occur first within an octave of a patient’s high frequency hearing limit, termed the sensitive range for ototoxicity (SRO), and progress to lower frequencies. While it is currently not possible to know which patients will experience ototoxicity without testing their hearing directly, monitoring the SRO provides an early indication of damage. A tool to help forecast susceptibility to ototoxic-induced changes in the SRO in advance of each chemotherapy treatment visit may prove useful for ototoxicity monitoring efforts, patient counseling, and therapeutic planning. Purpose: This project was designed to (1) establish pretreatment risk curves that quantify the probability that a new patient will suffer hearing loss within the SRO during treatment with cisplatin and (2) evaluate the accuracy of these predictions in an independent sample of Veterans receiving cisplatin for the treatment of cancer. Study Sample: Two study samples were used. The Developmental sample contained 23 subjects while the Validation sample consisted of 12 subjects. Data Collection and Analysis: Risk curve predictions for SRO threshold shifts following cisplatin exposure were developed using a Developmental sample comprised of data from a total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone thresholds were obtained within each subject’s SRO at each treatment visit and compared with baseline measures. The risk of incurring an SRO shift was statistically modeled as a function of factors related to chemotherapy treatment (cisplatin dose, radiation treatment, doublet medication) and patient status (age, pre-exposure hearing, cancer location and stage). The model was reduced so that only statistically significant variables were included. Receiver-operating characteristic (ROC) curve analyses were then used to determine the accuracy of the risk curve predictions in an independent Validation sample of observations from over 62 treatment visits obtained in 24 ears of 12 Veterans. Results: Only cumulative cisplatin dose and pre-exposure hearing were found to be significantly related to the risk for hearing shift. The dose-ototoxicity risk curve predictions developed from the Developmental sample yielded area under the ROC curve accuracy estimates of 0.85 when applied to an independent Validation sample. Conclusions: Cumulative cisplatin dose in combination with pre-exposure hearing provides an indication of whether hearing will shift in the SRO in advance of cisplatin administration. The validated dose-ototoxicity risk curves described herein can be used before and during treatment to anticipate hearing loss. While having such a tool would not replace serial hearing testing, it would be of great benefit to an ototoxicity monitoring program. It would promote relevant pretreatment counseling. Furthermore, for those found to be at risk of SRO shifts within the speech frequencies, the oncology treatment plan could incorporate anticipated dosing adjustments that could stave off the impact that ototoxicity might bring.