Magnetic-Resonance-Imaging-Guided Cryoablation for Solitary-Biopsy-Proven Renal Cell Carcinoma: A Tertiary Cancer Center Experience.

BACKGROUND: Our purpose is to evaluate the long-term oncologic efficacy and survival rates of MRI-guided cryoablation for patients with biopsy-proven cT1a renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively reviewed our renal ablation database between January 2007 and June 2021 and only included patients with solitary-biopsy-proven cT1a RCC (≤4 cm) who underwent MRI-guided cryoablation. We excluded patients with genetic syndromes, bilateral RCC, recurrent RCC or benign lesions, those without pathologically proven RCC lesions and patients who underwent radiofrequency ablation or CT-guided cryoablation. For each patient, we collected the following: age, sex, lesion size, right- or left-sided, pathology, ablation zone tumor recurrence, development of new tumor in the kidney other than ablation zone, development of metastatic disease, patient alive or not, date and cause of death. We used the Kaplan and Meier product limit estimator to estimate the survival outcomes. RESULTS: Twenty-nine patients (median age 70 years) met our inclusion criteria. Twenty-nine MRI-guided cryoablation procedures were performed for twenty-nine tumor lesions with a median size of 2.2 cm. A Clavien-Dindo grade III complication developed in one patient (3.4%). Clear cell RCC was the most reported histology (n = 19). The median follow up was 4.5 years. No tumor recurrence or metastatic disease developed in any of the patients. Two patients developed new renal lesions separate from the ablation zone. The 5- and 10-year OS were 72% and 55.6%, respectively. The 5- and 10-year DFS were 90.5% and the 5-year and 10-year LRFS, MFS and CSS were all 100%. CONCLUSIONS: MRI-guided cryoablation is a safe treatment with a low complication rate. Long-term follow-up data revealed long-standing oncologic control.

Magnetic resonance imaging-guided renal biopsy shows high safety and diagnostic yield: a tertiary cancer center experience.

OBJECTIVES: To evaluate the technical success and outcomes of renal biopsies performed under magnetic resonance imaging (MRI) using a closed-bore, 1.5-Tesla MRI unit. MATERIALS AND METHODS: We retrospectively reviewed our institutional biopsy database and included 150 consecutive MRI-guided biopsies for renal masses between November 2007 and March 2020. We recorded age, sex, BMI, tumor characteristics, RENAL nephrometry score, MRI scan sequence, biopsy technique, complications, diagnostic yield, pathologic outcome, and follow-up imaging. Univariate logistic regression was used to assess the association between different parameters and the development of complications. McNemar's test was used to assess the association between paired diagnostic yield measurements for fine-needle aspiration and core samples. RESULTS: A total of 150 biopsies for 150 lesions were performed in 150 patients. The median tumor size was 2.7 cm. The median BMI was 28.3. The lesions were solid, partially necrotic/cystic, and predominantly cystic in 137, eight, and five patients, respectively. Image guidance using fat saturation steady-state free precession sequence was recorded in 95% of the biopsy procedures. Samples were obtained using both fine-needle aspiration (FNA) and cores in 99 patients (66%), cores only in 40 (26%), and FNA only in three (2%). Tissue sampling was diagnostic in 144 (96%) lesions. No major complication developed following any of the biopsy procedures. The median follow-up imaging duration was 8 years and none of the patients developed biopsy-related long-term complication or tumor seeding. CONCLUSIONS: MRI-guided renal biopsy is safe and effective, with high diagnostic yield and no major complications. CLINICAL RELEVANCE STATEMENT: Image-guided renal biopsy is safe and effective, and should be included in the management algorithm of patients with renal masses. Core biopsy is recommended. KEY POINTS: • MRI-guided biopsy is a safe and effective technique for sampling of renal lesions. • MRI-guided biopsy has high diagnostic yield with no major complications. • Percutaneous image-guided biopsy plays a key role in the management of patients with renal masses.

Comparison of Predictive Models for Prevention of Missed Endoscopy Appointments- failure of a Predictive Model to Outperform Overbooking Model.

BACKGROUND: Patient late cancelation and nonattendance for endoscopy appointments is an ongoing problem affecting the productivity and wait times of endoscopy units. Previous research evaluated a model for predictive overbooking and had promising results. STUDY: All endoscopy visits at an outpatient endoscopy unit during 4 nonconsecutive months were included in the data analysis. Patients who did not attend their appointment, or canceled with 48 hours of their appointment were considered nonattendees. Demographic, health, and prior visit behavior data was collected and the groups compared. RESULTS: 1780 patients attended 2331 visits in the study period. Comparing the attendee versus non-attendees, there were significant differences in mean age, prior absenteeism, prior cancelations, and total number of hospital visits. No significant differences were seen between groups in winter versus non-winter months, the day of the week, sex distribution, type of procedure booked, or whether the referral was from specialist clinic or direct to procedure. The visit cancelation proportion (calculated excluding current visit) was substantially higher in the absentee group ( P <0.0001). A predictive model was developed and compared to current booking as well as a straight overbooking of 7%. Both overbooking models performed better than the current practice, but the predictive overbooking model did not outperform straight overbooking. CONCLUSIONS: Developing an endoscopy unit specific predictive model may not be more beneficial than straight overbooking as calculated by missed appointment percentage.

Effectiveness of Thermal Ablation for Renal Cell Carcinoma after Prior Partial Nephrectomy.

Background: Repeat partial nephrectomy (PN) for tumors recurring in the ipsilateral kidney is associated with surgical complexity and a higher rate of complications. Objective: To evaluate the local oncologic efficacy of thermal ablation (TA) for renal cell carcinoma (RCC) in the ipsilateral kidney following PN. Design setting participation: We included patients who underwent ablation for renal tumors in the ipsilateral kidney after PN between January 2005 and December 2019. Demographics, tumor size, procedural details, complications, pathology, local oncologic outcomes, and survival outcomes are described. Outcome measurements and statistical analysis: The procedural, pathologic, and oncologic outcomes are described. Survival rates were estimated using the Kaplan-Meier method. Results and limitations: A total of 66 patients (46 male and 20 female) with a median age of 62 yr (interquartile range [IQR] 52-69) met our inclusion criteria. In these patients, 74 TA procedures were performed for 86 lesions (median tumor size 1.9 cm, IQR 1.6-2.5). Radiofrequency ablation and cryoablation accounted for 60 (81%) and 14 (19%) procedures, respectively. Three patients (3.7%) had Clavien-Dindo grade III complications. Of 65 lesion biopsies, 62 (95.5%) were diagnostic. The most common subtype was clear cell RCC (n = 37). The median imaging follow-up duration was 60 mo (IQR 43-88). Recurrence in the ablation zone occurred for four lesions (4.6%) at a median of 6.9 mo (IQR 6.4-10.7). The rates of overall, recurrence-free, and disease-free survival were 93.1%, 94.4%, and 65.6% at 5 yr, and 71.6%, 94.4%, and 60.1% at 10 yr, respectively. Limitations include the retrospective design and the lack of a control group. Conclusions: TA is effective for the treatment of RCC in the ipsilateral kidney following PN. Patient summary: Heat treatment to remove tumor tissue is an effective option for small kidney masses recurring after partial kidney removal for cancer. Long-term follow-up data revealed that this treatment resulted in low recurrence and complication rates.

YTHDF2/m6 A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs.

N6 -methyladenosine (m6 A) in messenger RNA (mRNA) regulates immune cells in homeostasis and in response to infection and inflammation. The function of the m6 A reader YTHDF2 in the tumor microenvironment (TME) in these contexts has not been explored. We discovered that the loss of YTHDF2 in regulatory T (Treg) cells reduces tumor growth in mice. Deletion of Ythdf2 in Tregs does not affect peripheral immune homeostasis but leads to increased apoptosis and impaired suppressive function of Treg cells in the TME. Elevated tumor necrosis factor (TNF) signaling in the TME promotes YTHDF2 expression, which in turn regulates NF-κB signaling by accelerating the degradation of m6 A-modified transcripts that encode NF-κB-negative regulators. This TME-specific regulation of Treg by YTHDF2 points to YTHDF2 as a potential target for anti-cancer immunotherapy, where intratumoral Treg cells can be targeted to enhance anti-tumor immune response while avoiding Treg cells in the periphery to minimize undesired inflammations.

The long-term observation of the rotation of implantable collamer lens as the management of high postoperative vault.

Purpose: This study aimed to describe the effectiveness and stability of implantable collamer lens (ICL) rotation in reducing high postoperative vault. Setting: This study was conducted in the Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. Design: This is a retrospective case series. Methods: Twenty-two eyes from 22 patients who had ICL (V4c EVO) implantation with high postoperative vault (>=750 µm) were recruited for our study. All the lenses were rotated from a horizontal to an oblique position. The vault, SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° were measured pre-rotation, 1-week post-rotation, and in the at-least 1-year-follow-up. Results: Twenty female patients and two male patients were recruited, with a mean age of 28.68 ± 6.08 years. The mean vault had declined significantly from 951.81 ± 154.26 µm pre-rotation to 772.27 ± 119.40 µm 1 week post-rotation (p < 0.001). The SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° pre-rotation and 1-week post-rotation were 30.40 ± 7.91° and 45.14 ± 6.75°, 32.37 ± 7.48° and 46.23 ± 6.39°, 303.27 ± 87.99 and 522.45 ± 122.16 µm, 323.81 ± 89.15 and 536.13 ± 121.66 µm, 387.95 ± 99.43 and 630.81 ± 133.59 µm, 435.68 ± 106.72 and 643.36 ± 132.82 µm, 0.109 ± 0.034 and 0.202 ± 0.053 mm2, 0.123 ± 0.034 and 0.212 ± 0.051 mm2, 0.194 ± 0.056 and 0.345 ± 0.083 mm2, and 0.216 ± 0.055 and 0.358 ± 0.079 mm2 (all p < 0.001). The mean vault value had changed from 747.50 ± 116.07 µm 1-week post-rotation to 586.87 ± 132.65 µm in the 1-year follow-up. However, the SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° had remained stable (p > 0.05). Conclusion: Non-toric ICL rotation is a novel and effective technique in the treatment of high postoperative vault. Our results are more robust given the extended period of follow-up.

Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience.

BACKGROUND: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan-Meier method. RESULTS: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien-Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. CONCLUSIONS: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes.

Endogenous Interleukin-10 Contributes to Wound Healing and Regulates Tissue Repair.

INTRODUCTION: Interleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well-established. We sought to determine the function of endogenous IL-10 in murine full thickness excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure. METHODS: Full-thickness excisional wounds were made in wildtype (WT) and IL-10-/- mice on a C57BL/6J background (F/M, 8 wk old). In a subset of wounds, contraction was prevented by splinting with silicone stents (stenting) and maintaining a moist wound microenvironment using a semiocclusive dressing. Wounds were examined for re-epithelialization, granulation tissue deposition, and inflammatory cell infiltrate at day 7 and fibrosis and scarring at day 30 postwounding. RESULTS: We observed no difference in wound healing rate between WT and IL-10-/- mice in either the stented or unstented group. At day 7, unstented IL-10-/- wounds had a larger granulation tissue area and more inflammatory infiltrate than their WT counterparts. However, we did observe more F4/80+ cell infiltrate in stented IL-10-/- wounds at day 7. At day 30, stented wounds had increased scar area and epithelial thickness compared to unstented wounds. CONCLUSIONS: These data suggest that endogenous IL-10 expression does not alter closure of full thickness excisional wounds when wound hydration and excessive contraction of murine skin are controlled. However, the loss of IL-10 leads to increased inflammatory cell infiltration and scarring. These new findings suggest that IL-10 contributes to the regulation of inflammation without compromising the healing response. These data combined with previous reports of increased rates of healing in IL-10-/- mice wounds not controlled for hydration and contraction suggest an important role for murine wound healing models used in research studies of molecular mechanisms that regulate healing.

Retinal Nerve Fibre Layer Thickness Change Following Femtosecond Laser-Assisted in situ Keratomileusis.

Purpose: To evaluate the effect of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) on retinal fovea thickness, volume, and retinal nerve fibre layer (RNFL) thickness. Methods: Thirty-seven eyes (37 patients) undergoing FS-LASIK were included in this prospective study. Optical coherence tomography (OCT) was performed 1 day before, 1 h and 1 day after FS-LASIK surgery. Result: Eighteen male and nineteen females were enrolled. Mean patient age was 22.94 ± 4.22 years. One hour postoperatively, macula fovea thicknesses, macula fovea volume, macula parafovea thickness, macula parafovea volume, macula perifovea thickness, macula perifove volume, temporal RNFL thickness, and superior RNFL thickness measures showed significant decrease (t = 6.171, 6.032, and 9.837, 9.700, 2.532, 4.393, 4.926, 2.265; p = 0.000, 0.000, 0.000, 0.000, 0.016, 0.000, 0.000, and 0.011). Day 1 post-operation, macula fovea thicknesses, macula fovea volume, macula parafovea thickness, macula parafovea volume, and inferior RNFL thickness measures showed significant change compared to preoperative measures (t = 3.620, 3.220, 2.901, 2.910, 3.632; p = 0.001, 0.003, 0.006, 0.006, and 0.001). Conclusion: Our data suggest there are alterations in retinal foveal and RNFL measurements by OCT 1 h and 1 day after FS-LASIK surgery.

High myopia and macular vascular density: an optical coherence tomography angiography study.

OBJECTIVE: To investigate whether there are differences inmacular vascular density (VD) between patients with high-myopia (HM) and those with non-high myopia (NHM) using Optical Coherence Tomography Angiography (OCTA). METHOD: OCTA was performed on 35 eyes with HM with spherical equivalence (SE) > - 6.00D and 35 eyes with NHM with SE ≤ -6.00D. Vascular densities of the macula (overall macula, fovea, parafovea, superior hemi and inferior hemi) were measured in each of the superficial, deep and choriocapillaris layers of the retina. RESULTS: In the superficial retinal layer, overall macular VFD was significantly higher in the NHM compared to the HM group (51.27 ± 3.74 vs. 48.07 ± 5.69, p < 0.05). There were significant differences between the NHM and HM in parafovea (52.58 ± 5.78 vs. 49.4 ± 6.43, p < 0.05), superior-hemi (53.38 ± 4.03 vs 49.78 ± 6.84, p < 0.05) and inferior-hemi regions (53.49 ± 4.61 vs 49.05 ± 6.41, p < 0.05), but not in the fovea region. Similarly, in the deep retinal layer, overall macular VFD was significantly higher in the NHM group compared to the HM group (58.69 ± 2.46 vs. 56.90 ± 4.08, p < 0.05). There was significant differences between the HM and NHM in superior-hemi region (61.97 ± 2.68 vs. 60.08 ± 3.98, p < 0.05), but not in the fovea, parafovea, and inferior-hemi region. In the choriocapillaris, there was no difference in the overall macular VFD, nor any of the individual sectors between the HM and the NHM groups. CONCLUSION: VFD in the superficial and deep retinal layers of the macula are significantly increased in the NHM compared to HM eyes. This is not the case in the choroidal capillary layers of the retina.

Separation of color channels from conventional colonoscopy images improves deep neural network detection of polyps.

SIGNIFICANCE: Colorectal cancer incidence has decreased largely due to detection and removal of polyps. Computer-aided diagnosis development may improve on polyp detection and discrimination. AIM: To advance detection and discrimination using currently available commercial colonoscopy systems, we developed a deep neural network (DNN) separating the color channels from images acquired under narrow-band imaging (NBI) and white-light endoscopy (WLE). APPROACH: Images of normal colon mucosa and polyps from colonoscopies were studied. Each color image was extracted based on the color channel: red/green/blue. A multilayer DNN was trained using one-channel, two-channel, and full-color images. The trained DNN was then tested for performance in detection of polyps. RESULTS: The DNN performed better using full-colored NBI over WLE images in the detection of polyps. Furthermore, the DNN performed better using the two-channel red + green images when compared to full-color WLE images. CONCLUSIONS: The separation of color channels from full-color NBI and WLE images taken from commercially available colonoscopes may improve the ability of the DNN to detect and discriminate polyps. Further studies are needed to better determine the color channels and combination of channels to include and exclude in DNN development for clinical use.

The influence of proton pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: a patient-level meta-analysis of randomised controlled studies.

OBJECTIVE: In treating patients with inflammatory bowel disease (IBD), how concomitant medications influence the response to infliximab is largely unexplored. We aim to evaluate whether proton pump inhibitors (PPIs) affect the response to infliximab therapy in patients with IBD. DESIGN: Patient-level data of adult patients with moderate-to-severe IBD treated with infliximab were obtained from the Yale Open Data Access Framework. Multivariable analysis and propensity score-matched analysis were performed to assess week 30 remission rates, week 54 remission rates and hospitalisation rates in patients on infliximab therapy with and without PPI exposure. RESULTS: Among the five randomised controlled studies, there were 147 and 889 patients on infliximab with and without PPI therapy, respectively. Patients on PPI were older, more likely to be Caucasian and were less likely to be on immunomodulator therapy. Patients on PPI were significantly less likely to achieve week 30 remission on multivariable analysis (OR 0.45, p<0.001). Following propensity score matching adjusting for baseline difference in patient characteristics, the week 30 remission rates were 30% and 49% in patients with and without PPI therapy, respectively (p<0.001). Analysing separately for disease, the findings remained statistically significant in Crohn's disease but did not reach significance in UC. Similar results were seen with week 54 remission rates. Patients on PPI were also more likely to be hospitalised (15% vs 8%, p=0.007). Rates of adverse events such as gastroenteritis were not different between the two groups. CONCLUSION: In this patient-level meta-analysis of randomised controlled studies, we found that patients with IBD taking PPI were less likely to achieve remission while on infliximab therapy. The results of our study warrant further investigation into the effect of PPI on IBD outcomes and therapies.

Contraction Reserve With Ineffective Esophageal Motility on Esophageal High-Resolution Manometry is Associated With Lower Acid Exposure Times Compared With Absent Contraction Reserve.

INTRODUCTION: Ineffective esophageal motility (IEM) is a minor motor disorder with potential reflux implications. Contraction reserve, manifested as augmentation of esophageal body contraction after multiple rapid swallows (MRS), may affect esophageal acid exposure time (AET) in IEM. METHODS: Esophageal high-resolution manometry (HRM) and ambulatory reflux monitoring studies were reviewed over 2 years to identify patients with normal HRM, IEM (≥50% ineffective swallows), and absent contractility (100% failed swallows). Single swallows and MRS were analyzed using HRM software tools (distal contractile integral, DCI) to determine contraction reserve (mean MRS DCI to mean single swallow DCI ratio >1). Univariate analysis and multivariable regression analyses were performed to determine motor predictors of abnormal AET in the context of contraction reserve. RESULTS: Of 191 eligible patients, 57.1% had normal HRM, 37.2% had IEM, and 5.8% had absent contractility. Contraction reserve had no affect on AET in normal HRM. Nonsevere IEM (5-7 ineffective swallows) demonstrated significantly lower proportions with abnormal AET in the presence of contraction reserve (30.4%) compared with severe IEM (8-10 ineffective swallows) (75.0%, P = 0.03). Abnormal AET proportions in nonsevere IEM with contraction reserve (32.7%) resembled normal HRM (33.0%, P = 0.96), whereas that in severe IEM with (46.2%) or without contraction reserve (50.0%) resembled absent contractility (54.5%, P ≥ 0.6). Multivariable analysis demonstrated contraction reserve to be an independent predictor of lower upright AET in nonsevere (odds ratio 0.44, 95% confidence interval 0.23-0.88) but not severe IEM. DISCUSSION: Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

A New Model of Spontaneous Colitis in Mice Induced by Deletion of an RNA m6A Methyltransferase Component METTL14 in T Cells.

BACKGROUND AND AIMS: Mouse models of colitis have been used to study the pathogenesis of inflammatory bowel disease (IBD) and for pre-clinical development of therapeutic agents. Various epigenetic pathways have been shown to play important regulatory roles in IBD. Reversible N6-methyladenosine (m6A) methylation represents a new layer of post-transcriptional gene regulation that affects a variety of biological processes. We aim to study how deletion of a critical component of m6A writer complex, METTL14, in T cells affects the development of colitis. METHODS: Conditional Mettl14 was lineage specifically deleted with CD4-regulated Cre in T cells. Colitis phenotype was determined by H&E staining, colon weight-to-length ratio and cytokine expression. We additionally utilized T cell transfer model of colitis and adoptive transfer of regulatory T cells. Mice were treated with antibiotics to determine if the colitis could be attenuated. RESULTS: METTL14 deficiency in T cells induced spontaneous colitis in mice. This was characterized by increased inflammatory cell infiltration, increased colonic weight-to-length ratio and increased Th1 and Th17 cytokines. The colitis development was due to dysfunctional regulatory T (Treg) cells, as adoptive transfer of WT Treg cells attenuated the colitis phenotype. The METTL14-deficient Treg cells have decreased RORγt expression compared with WT controls. METTL14 deficiency caused impaired induction of naïve T cells into induced Treg cells. Antibiotic treatment notably attenuated the colitis development. CONCLUSION: Here we report a new mouse model of spontaneous colitis based on perturbation of RNA methylation in T cells. The colitis is T cell-mediated and dependent on the microbiome. This model represents a new tool for elucidating pathogenic pathways, studying the contribution of intestinal microbiome and preclinical testing of therapeutic agents for inflammatory bowel disease.

High-molecular weight hyaluronan attenuates tubulointerstitial scarring in kidney injury.

Renal fibrosis features exaggerated inflammation, extracellular matrix (ECM) deposition, and peritubular capillary loss. We previously showed that IL-10 stimulates high-molecular weight hyaluronan (HMW-HA) expression by fibroblasts, and we hypothesize that HMW-HA attenuates renal fibrosis by reducing inflammation and ECM remodeling. We studied the effects of IL-10 overexpression on HA production and scarring in mouse models of unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R) to investigate whether IL-10 antifibrotic effects are HA dependent. C57BL/6J mice were fed with the HA synthesis inhibitor, 4-methylumbelliferone (4-MU), before UUO. We observed that in vivo injury increased intratubular spaces, ECM deposition, and HA expression at day 7 and onward. IL-10 overexpression reduced renal fibrosis in both models, promoted HMW-HA synthesis and stability in UUO, and regulated cell proliferation in I/R. 4-MU inhibited IL-10-driven antifibrotic effects, indicating that HMW-HA is necessary for cytokine-mediated reduction of fibrosis. We also found that IL-10 induces in vitro HMW-HA production by renal fibroblasts via STAT3-dependent upregulation of HA synthase 2. We propose that IL-10-induced HMW-HA synthesis plays cytoprotective and antifibrotic roles in kidney injury, thereby revealing an effective strategy to attenuate renal fibrosis in obstructive and ischemic pathologies.

Electro-Tactile Stimulation Enhances Cochlear-Implant Melody Recognition: Effects of Rhythm and Musical Training.

OBJECTIVES: Electro-acoustic stimulation (EAS) enhances speech and music perception in cochlear-implant (CI) users who have residual low-frequency acoustic hearing. For CI users who do not have low-frequency acoustic hearing, tactile stimulation may be used in a similar fashion as residual low-frequency acoustic hearing to enhance CI performance. Previous studies showed that electro-tactile stimulation (ETS) enhanced speech recognition in noise and tonal language perception for CI listeners. Here, we examined the effect of ETS on melody recognition in both musician and nonmusician CI users. DESIGN: Nine musician and eight nonmusician CI users were tested in a melody recognition task with or without rhythmic cues in three testing conditions: CI only (E), tactile only (T), and combined CI and tactile stimulation (ETS). RESULTS: Overall, the combined electrical and tactile stimulation enhanced the melody recognition performance in CI users by 9% points. Two additional findings were observed. First, musician CI users outperformed nonmusicians CI users in melody recognition, but the size of the enhancement effect was similar between the two groups. Second, the ETS enhancement was significantly higher with nonrhythmic melodies than rhythmic melodies in both groups. CONCLUSIONS: These findings suggest that, independent of musical experience, the size of the ETS enhancement depends on integration efficiency between tactile and auditory stimulation, and that the mechanism of the ETS enhancement is improved electric pitch perception. The present study supports the hypothesis that tactile stimulation can be used to improve pitch perception in CI users.

Journey to glaucoma care - trusting but uncertain and uninformed: a qualitative study.

BACKGROUND: This study aims to explore patient perspectives regarding their journey to glaucoma care and sought to understand the determinants that guide their access to tertiary glaucoma care. METHODS: Twenty-nine patients who are glaucoma suspects or had definitive diagnosis of glaucoma were recruited from a large public glaucoma clinic and a private ophthalmology clinic in Sydney. Face-to-face, in-depth semi-structured interviews were conducted between April and December 2017. Interviews were recorded and transcribed verbatim. A framework method was used for thematic analysis of the data. RESULTS: Thematic analysis resulted in the emergence of eight main themes. There was limited patient participation in decision making in their journey to glaucoma care. Consequently, there was great trust placed in the referring clinician. Patients valued their vision and therefore expressed a desire for high-quality care. They placed considerable trust in their specialist but were often unsure how to evaluate the quality of care received. Patients lacked an understanding of the cost of glaucoma care and for some, cost remained a barrier to the access of private care. There were variable experiences with waiting times and the journey to clinic, with many patients making concessions and requiring support to access care. CONCLUSION: This study is the first qualitative study exploring the perspectives of glaucoma patients in Australia and the determinants of access to care. These findings support and can inform development of patient-centred models of care furthering patient trust and empowerment.

Prognostic Differences in ISUP Grade Group 4: a Systematic Review and Meta-Analysis.

The ISUP (Internal Society of Urologic Pathology) recently adopted a five-tiered prognostication system. There is evidence to suggest that the ISUP grade group 4 is a heterogeneous entity regarding prognosis. Our aim was to systematically examine the existing evidence to determine if outcome differences exist within the ISUP grade group 4. A systematic search of the literature for all studies examining the heterogeneity of the ISUP grade group 4 was conducted. Available studies were combined with meta-analysis to evaluate prognostic differences within the ISUP grade group 4 measured by all-cause mortality (ACM) and the prostate cancer-specific mortality (PCSM). Eight studies were identified and utilised a variety of outcome measures to answer the question of heterogeneity within the ISUP grade group 4. Four of these studies examined prognosis using both ACM and PCSM. These were combined into a meta-analysis. The combined group of 5 + 3/3 + 5 had statistically significant higher ACM (hazard ratio [HR] 1.23, 95% confidence internal [Cl] 1.08-1.41) when compared to the 4 + 4 group. There was no difference in the PCSM between the two groups (HR 1.34, 95% CI 0.89-2.01). However, heterogeneity was high for this analysis secondary to a range of methodological differences. Our meta-analysis showed that Gleason grade 3 + 5/5 + 3 had higher ACM than Gleason grade group 4 + 4. Measures of PCSM were statistically insignificant, although heterogeneity was high. Evidence suggests that heterogeneity is likely, although inconclusive. Further studies with consistent methodologies are required to answer this question.