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.

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.

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.

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.

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.

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.

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.

Maneuvering Clinical Pathways for Crohn's Disease.

PURPOSE OF REVIEW: Crohn's disease management has changed significantly with increasing use of biologics. We review the recent literature on the clinical management of Crohn's disease and new approaches in selecting and optimizing therapy. RECENT FINDINGS: Recent studies have addressed the efficacy of proactive anti-TNFα trough level monitoring, the efficacy of biosimilars, and the efficacy and immunogenicity of newer biologics including anti-integrin therapy and anti-IL12/23 therapy. Optimizing anti-TNFα therapy according to trough concentrations correlates with improved remission rates. Patients can be switched from the reference drug to a biosimilar, or vice versa, without a measurable change in efficacy, safety, or immunogenicity. Immunomodulators are effective in decreasing immunogenicity and boosting anti-TNFα drug level. The anti-integrin and anti-IL12/23 therapies are effective as induction and maintenance therapy with low immunogenicity and excellent safety profiles. Patients at high risk for post-operative recurrence should be started on a biologic therapy within 4 weeks post-op. Multiple biologic therapies are currently available for treatment of Crohn's disease including anti-TNFα therapy, anti-integrin therapy, and anti-IL12/23 therapy. The choice of first-line therapy should be based on individual risk-benefit analysis, route of administration, and patient preference. Patient with inadequate response should have their trough level checked and therapy optimized. Therapeutic prophylaxis for post-operative recurrence should be based on patient's risk factors for recurrence.

Determining patient preferences in a glaucoma service: A discrete choice experiment.

IMPORTANCE: Patient perspectives are crucial in informing design of acceptable services. BACKGROUND: This study determined patient preferences in glaucoma care. DESIGN: A discrete choice experiment was used to evaluate the relative importance of out-of-pocket costs, waiting time, continuity of care, service location and expertise. PARTICIPANTS: Ninety-eight glaucoma suspects or glaucoma patients were recruited from one public and two private clinics in Sydney. METHODS: Twelve choice-tasks were presented in random order and forced-choice preferences were elicited. Choice data were analysed using a multinominal logit model (NLOGIT 4.0). MAIN OUTCOME MEASURES: The relative importance and the likelihood of choosing services with each attribute were determined. Willingness-to-pay and willingness-to-wait were calculated. Analyses were stratified by whether the patient attended a public or private glaucoma clinic and other demographic features. RESULTS: Choice was influenced by four or five attributes: greater clinician expertise, the same clinician each visit, lower out-of-pocket costs and shorter wait times (all P < .05). Respondents were willing to pay an additional (Australian dollars) $325 (95% confidence interval [CI] 188-389) to see a senior eye doctor, and $87 (95% CI 60-116) to see the same clinician each visit. Respondents were willing to wait for these attributes; however, the estimates had wide confidence intervals and were beyond the range tested. Private patients had a stronger preference for expertise and continuity of care compared to public patients. CONCLUSIONS AND RELEVANCE: Expertise and continuity of care were important to glaucoma patients in this setting, and they were willing to pay out-of-pocket and concede longer waiting times to secure these preferences.

MicroRNA.

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are crucial regulators of gene expression and promising candidates for biomarker development. MiRNA mimics and miRNA inhibitors currently in preclinical development have shown promise as novel therapeutic agents. Multiple technological platforms have been developed for miRNA isolation, miRNA quantitation, miRNA profiling, miRNA target detection, and modulating miRNA levels in vitro and in vivo. Here we will review the major technological platforms with consideration given for the advantages and disadvantages of each platform.

MiR-223 deficiency increases eosinophil progenitor proliferation.

Recently, microRNAs have been shown to be involved in hematopoietic cell development, but their role in eosinophilopoiesis has not yet been described. In this article, we show that miR-223 is upregulated during eosinophil differentiation in an ex vivo bone marrow-derived eosinophil culture system. Targeted ablation of miR-223 leads to an increased proliferation of eosinophil progenitors. We found upregulation of a miR-223 target gene, IGF1R, in the eosinophil progenitor cultures derived from miR-223(-/-) mice compared with miR-223(+/+) littermate controls. The increased proliferation of miR-223(-/-) eosinophil progenitors was reversed by treatment with an IGF1R inhibitor (picropodophyllin). Whole-genome microarray analysis of differentially regulated genes between miR-223(+/+) and miR-223(-/-) eosinophil progenitor cultures identified a specific enrichment in genes that regulate hematologic cell development. Indeed, miR-223(-/-) eosinophil progenitors had a delay in differentiation. Our results demonstrate that microRNAs regulate the development of eosinophils by influencing eosinophil progenitor growth and differentiation and identify a contributory role for miR-223 in this process.

Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases.

Allergic inflammation is accompanied by the coordinated expression of a myriad of genes and proteins that initiate, sustain, and propagate immune responses and tissue remodeling. MicroRNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and have been shown to fine-tune gene transcriptional networks because single miRNAs can target hundreds of genes. Considerable attention has been focused on the key role of miRNAs in regulating homeostatic immune architecture and acquired immunity. Recent studies have identified miRNA profiles in multiple allergic inflammatory diseases, including asthma, eosinophilic esophagitis, allergic rhinitis, and atopic dermatitis. Specific miRNAs have been found to have critical roles in regulating key pathogenic mechanisms in allergic inflammation, including polarization of adaptive immune responses and activation of T cells (eg, miR-21 and miR-146), regulation of eosinophil development (eg, miR-21 and miR-223), and modulation of IL-13-driven epithelial responses (eg, miR-375). This review discusses recent advances in our understanding of the expression and function of miRNAs in patients with allergic inflammation, their role as disease biomarkers, and perspectives for future investigation and clinical utility.

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.

MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity.

An altered balance between Th1 and Th2 cytokines is responsible for a variety of immunoinflammatory disorders such as asthma, yet the role of posttranscriptional mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. In this study, we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome and significantly increased levels of the Th1 cytokine IFN-γ. Biological network-based transcriptome analysis of OVA-challenged miR-21(-/-) mice identified an unexpected prominent dysregulation of IL-12/IFN-γ pathways as the most significantly affected in the lungs, with a key role for miR-21 in IFN-γ signaling and T cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation and OVA-challenged CD4(+) T lymphocytes to produce increased IFN-γ and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new mechanism for regulating polarized immunoinflammatory responses.

Central masking with bilateral cochlear implants.

Across bilateral cochlear implants, contralateral threshold shift has been investigated as a function of electrode difference between the masking and probe electrodes. For contralateral electric masking, maximum threshold elevations occurred when the position of the masker and probe electrode was approximately place-matched across ears. The amount of masking diminished with increasing masker-probe electrode separation. Place-dependent masking occurred in both sequentially implanted ears, and was not affected by the masker intensity or the time delay from the masker onset. When compared to previous contralateral masking results in normal hearing, the similarities between place-dependent central masking patterns suggest comparable mechanisms of overlapping excitation in the central auditory nervous system.

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers.

BACKGROUND: The role of microRNAs (miRNAs), a key class of regulators of mRNA expression and translation, in patients with eosinophilic esophagitis (EoE) has not been explored. OBJECTIVE: We aimed to identify miRNAs dysregulated in patients with EoE and assess the potential of these miRNAs as disease biomarkers. METHODS: Esophageal miRNA expression was profiled in patients with active EoE and those with glucocorticoid-induced disease remission. Expression profiles were compared with those of healthy control subjects and patients with chronic (noneosinophilic) esophagitis. Expression levels of the top differentially expressed miRNAs from the plasma of patients with active EoE and patients with EoE remission were compared with those of healthy control subjects. RESULTS: EoE was associated with 32 differentially regulated miRNAs and was distinguished from noneosinophilic forms of esophagitis. The expression levels of the most upregulated miRNAs (miR-21 and miR-223) and the most downregulated miRNA (miR-375) strongly correlated with esophageal eosinophil levels. Bioinformatic analysis predicted interplay of miR-21 and miR-223 with key roles in the polarization of adaptive immunity and regulation of eosinophilia, and indeed, these miRNAs correlated with key elements of the EoE transcriptome. The differentially expressed miRNAs were largely reversible in patients who responded to glucocorticoid treatment. EoE remission induced a single miRNA (miR-675) likely to be involved in DNA methylation. Plasma analysis of the most upregulated esophageal miRNAs identified miR-146a, miR-146b, and miR-223 as the most differentially expressed miRNAs in the plasma. CONCLUSIONS: We have identified a marked dysregulated expression of a select group of miRNAs in patients with EoE and defined their reversibility with glucocorticoid treatment and their potential value as invasive and noninvasive biomarkers.

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.

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.