Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Targeting the DNA damage response in hematological malignancies.

Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs.

A head-to-head comparison of the measurement properties of EQ-5D-3L and EQ-5D-5L in Chinese family caregivers of cancer patients.

BACKGROUND: Although both EQ-5D-3L(3L) and EQ-5D-5L(5L) have demonstrated good measurement properties in several patient populations, there is currently limited evidence comparing the measurement properties of 3L and 5L in family caregivers (FCs) of cancer patients. PURPOSE: This study aimed to compare the measurement properties of 3L and 5L in a sample of family caregivers of cancer patients. METHODS: A consecutive sample of FCs of cancer patients recruited from three tertiary hospitals were invited to complete the two versions of the EQ-5D in two rounds of interviews. We compared i) the ceiling effect using the McNemar's test, ii) test-retest reliability using intraclass correlation coefficient (ICC) and Cohen's Kappa, iii) convergent validity using Spearman's rank correlation coefficient, iv) known-group validity using F-statistic, v) and discriminant capacity using ordinal logistic regression. RESULTS: A total of 416 FCs completed the baseline questionnaire and 120 caregivers completed the follow-up questionnaire. Ceiling effects were smaller in 5L (12.5%) than in 3L (20.7%). The convergent validity (r = 0.344-0.771), known-groups validity (Fratio5L/3L = 2.06-4.09), discriminant capacity (ES = 0.341-0.396), and test-retest reliability (ICC = 0.725) of the 5L were slightly better than those of the 3L in China. CONCLUSION: The current study found both 3L and 5L to be suitable for use by FCs of cancer patients. However, 5L showed superior measurement properties compared to 3L and therefore could be the preferred instrument when EQ-5D data of cancer patients FCs is required.

Small extracellular vesicles from mesenchymal stromal cells: the next therapeutic paradigm for musculoskeletal disorders.

Musculoskeletal disorders are one of the biggest contributors to morbidity and place an enormous burden on the health care system in an aging population. Owing to their immunomodulatory and regenerative properties, mesenchymal stromal/stem cells (MSCs) have demonstrated therapeutic efficacy for treatment of a wide variety of conditions, including musculoskeletal disorders. Although MSCs were originally thought to differentiate and replace injured/diseased tissues, it is now accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly extracellular vesicles (EVs). Endowed with a diverse cargo of bioactive lipids, proteins, nucleic acids and metabolites, MSC-EVs have been shown to elicit diverse cellular responses and interact with many cell types needed in tissue repair. The present review aims to summarize the latest advances in the use of native MSC-EVs for musculoskeletal regeneration, examine the cargo molecules and mechanisms underlying their therapeutic effects, and discuss the progress and challenges in their translation to the clinic.

Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia.

Cancer cachexia is a multifactorial syndrome characterized by a significant loss of skeletal muscle, which negatively affects the quality of life. Inhibition of myostatin (Mstn), a negative regulator of skeletal muscle growth and differentiation, has been proven to preserve muscle mass in muscle atrophy diseases, including cachexia. However, myostatin inhibitors have repeatedly failed clinical trials because of modest therapeutic effects and side effects due to the poor efficiency and toxicity of existing delivery methods. Here, we describe a novel method for delivering Mstn siRNA to skeletal muscles using red blood cell-derived extracellular vesicles (RBCEVs) in a cancer cachectic mouse model. Our data show that RBCEVs are taken up by myofibers via intramuscular administration. Repeated intramuscular administrations with RBCEVs allowed the delivery of siRNAs, thereby inhibiting Mstn, increasing muscle growth, and preventing cachexia in cancer-bearing mice. We observed the same therapeutic effects when delivering siRNAs against malonyl-CoA decarboxylase, an enzyme driving dysfunctional fatty acid metabolism in skeletal muscles during cancer cachexia. We demonstrate that intramuscular siRNA delivery by RBCEVs is safe and non-inflammatory. Hence, this method is useful to reduce the therapeutic dose of siRNAs, to avoid toxicity and off-target effects caused by systemic administration of naked siRNAs at high doses.

Recurrent nephrolithiasis and loss of kidney function: a cohort study.

PURPOSE: To evaluate whether symptomatic recurrent nephrolithiasis leads to loss of kidney function. METHODS: Adults who presented to the Emergency Department at least twice with symptomatic and radiologically confirmed nephrolithiasis were retrospectively recruited. Primary endpoint was the change in glomerular filtration rate (GFR) between baseline and at the time of data collection. Secondary endpoints include GFR slope defined as the mean rate of change in GFR from baseline to the end of the study period. RESULTS: 240 patients had recurrent symptomatic nephrolithiasis. Median follow-up was 5.4 years. The median age of first acute presentation was 51.6 years and the median baseline serum creatinine (bsCr) was 85.5 umol/l. 17.5% (n = 42) had worsening GFR, with the average change in GFR of - 8.64 ml/min/1.73 m2 per year. Four patients progressed to ESKD requiring haemodialysis. 14.5% (n = 35) had calcium oxalate stones. Univariate analysis showed older patients (p < 0.001), more symptomatic stone episodes (p < 0.001) and non-calcium-containing stones (p < 0.001) were strongly associated with deteriorating kidney function. Age (p = 0.002) and number of acute stone episodes (p = 0.011) were significant predictive factors when unadjusted to co-morbidities. Age (p = 0.018) was the only predictive factor of worsening GFR when adjusted for co-morbidities. Average mean GFR slope was - 2.83/min/1.73 m2 per year. CONCLUSIONS: Recurrent symptomatic nephrolithiasis is associated with loss of kidney function, in older patients, increased episodes of symptomatic nephrolithiasis and non-calcium-containing stones. Age is the only predictive factor for progression to chronic kidney disease in this subgroup.

Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells.

A rare sub-population of mouse embryonic stem cells (mESCs), the 2-cell-like cell, is defined by the expression of MERVL and 2-cell-stage-specific transcript (2C transcript). Here, we report that the ribosomal proteins (RPs) RPL14, RPL18, and RPL23 maintain the identity of mESCs and regulate the expression of 2C transcripts. Disregulation of the RPs induces DUX-dependent expression of 2C transcripts and alters the chromatin landscape. Mechanically, knockdown (KD) of RPs triggers the binding of RPL11 to MDM2, an interaction known to prevent P53 protein degradation. Increased P53 protein upon RP KD further activates its downstream pathways, including DUX. Our study delineates the critical roles of RPs in 2C transcript activation, ascribing a novel function to these essential proteins.

Dominant Negative TRAF3 Variant With Recurrent Mycobacterium abscessus Infection and Bronchiectasis.

Host factors leading to pulmonary nontuberculous mycobacteria (PNTM) disease are poorly understood compared with disseminated NTM disease, which is linked to the interleukin 12-interferon gamma signaling pathway. We investigated the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection, demonstrating TRAF3- and TNF-α-deficient phenotypes via ex vivo immune and cloning-transfection cellular studies.

Murine Soft Tissue Infection Model to Study Group A Streptococcus (GAS) Pathogenesis in Necrotizing Fasciitis.

Group A streptococcus (GAS) necrotizing fasciitis (NF) causes high morbidity and mortality despite prompt intravenous administration of antibiotics, surgical soft-tissue debridement, and supportive treatment in the intensive care unit. Since there is no effective vaccine against GAS infections, a comprehensive understanding of NF pathogenesis is required to design more efficient treatments. To increase our understanding of NF pathogenesis, we need a reliable animal model that mirrors, at least in part, the infectious process in humans. This chapter describes a reliable murine model of human NF that mimics the histopathology observed in humans, namely the destruction of soft tissue, a paucity of infiltrating neutrophils, and the presence of many gram-positive cocci at the center of the infection.

Effects of dietary nitrate on the O2 cost of submaximal exercise: Accounting for "noise" in pulmonary gas exchange measurements.

Dietary nitrate (NO3-) supplementation can reduce the oxygen cost of submaximal exercise, but this has not been reported consistently. We hypothesised that the number of step transitions to moderate-intensity exercise, and corresponding effects on the signal-to-noise ratio for pulmonary V˙ O2, may be important in this regard. Twelve recreationally active participants were assigned in a randomised, double-blind, crossover design to supplement for 4 days in three conditions: 1) control (CON; water); 2); PL (NO3--depleted beetroot juice); and 3) BR (NO3--rich beetroot juice). On days 3 and 4, participants completed two 6-min step transitions to moderate-intensity cycle exercise. Breath-by-breath V˙ O2 data were collected and V˙ O2 kinetic responses were determined for a single transition and when the responses to 2, 3 and 4 transitions were ensemble-averaged. Steady-state V˙ O2 was not different between PL and BR when the V˙ O2 response to one-, two- or three-step transition was compared but was significantly lower in BR compared to PL when four-step transitions was considered (PL: 1.33 ± 0.34 vs. BR: 1.31 ± 0.34 L·min-1, P < 0.05). There were no differences in pulmonary V˙ O2 responses between CON and PL (P > 0.05). Multiple step transitions may be required to detect the influence of NO3- supplementation on steady-state V˙ O2.

Reactive Strength as a Metric for Informing Return-to-Sport Decisions: A Case-Control Study.

OBJECTIVE: Current return-to-sport decisions are primarily based on elapsed time since surgery or injury and strength measures. Given data that show rates of successful return to competitive sport at around 55%, there is strong rationale for adopting tools that will better inform return to sport decisions. The authors' objective was to assess reactive strength as a metric for informing return-to-sport decisions. DESIGN: Case-control design. METHODS: Fifteen elite athletes from national sports teams (23 [6.0] y) in the final phase of their return-to-sport protocol following a unilateral knee injury and 16 age-matched control athletes (22 [4.6] y) performed a unilateral isometric strength test and 24-cm drop jump test. Pairwise comparisons were used to determine differences between legs within groups and differences in interleg asymmetry between groups. RESULTS: Strength measures did not distinguish the control from the rehabilitation group; however, clear differences in the degree of asymmetry were apparent between the control and rehabilitation groups for contact time (Cohen d = 0.56; -0.14 to 1.27; 8.2%; P = .113), flight time (d = 1.10; 0.44 to 1.76; 16.0%; P = .002), and reactive strength index (d = 1.27; 0.50 to 2.04; 22.4%; P = .002). CONCLUSION: Reactive strength data provide insight into functional deficits that persist into the final phase of a return-to-sport protocol. The authors' findings support the use of dynamic assessment tools to inform return-to-sport decisions to limit potential for reinjury.

Moving beyond inclusion: Methodological considerations for the menstrual cycle and menopause in research evaluating effects of dietary nitrate on vascular function.

Recent reports have acknowledged the underrepresentation of women in the field of dietary nitrate (NO3-) research. Undoubtedly, greater participation from women is warranted to clarify potential sex differences in the responses to dietary NO3- interventions. However, careful consideration for the effects of sex hormones - principally 17ß-estradiol - on endogenous nitric oxide (NO) synthesis and dietary NO3- reductase capacity is necessary for improved interpretation and reproducibility of such investigations. From available literature, we present a narrative review describing how hormonal variations across the menstrual cycle, as well as with menopause, may impact NO biosynthesis catalyzed by NO synthase enzymes and NO3- reduction via the enterosalivary pathway. In doing so, we address methodological considerations related to the menstrual cycle and hormonal contraceptive use relevant for the inclusion of premenopausal women along with factors to consider when testing postmenopausal women. Adherence to such methodological practices may explicate the utility of dietary NO3- supplementation as a means to improve vascular function among women across the lifespan.

Physiological and performance effects of dietary nitrate and N-acetylcysteine supplementation during prolonged heavy-intensity cycling.

The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC  and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC  and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions  but was better preserved in PL+NAC  compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.

LL-37-mediated activation of host receptors is critical for defense against group A streptococcal infection.

Group A Streptococcus (GAS) causes diverse human diseases, including life-threatening soft-tissue infections. It is accepted that the human antimicrobial peptide LL-37 protects the host by killing GAS. Here, we show that GAS extracellular protease ScpC N-terminally cleaves LL-37 into two fragments of 8 and 29 amino acids, preserving its bactericidal activity. At sub-bactericidal concentrations, the cleavage inhibits LL-37-mediated neutrophil chemotaxis, shortens neutrophil lifespan, and eliminates P2X7 and EGF receptors' activation. Mutations at the LL-37 cleavage site protect the peptide from ScpC-mediated splitting, maintaining all its functions. The mouse LL-37 ortholog CRAMP is neither cleaved by ScpC nor does it activate P2X7 or EGF receptors. Treating wild-type or CRAMP-null mice with sub-bactericidal concentrations of the non-cleavable LL-37 analogs promotes GAS clearance that is abolished by the administration of either P2X7 or EGF receptor antagonists. We demonstrate that LL-37-mediated activation of host receptors is critical for defense against GAS soft-tissue infections.

A head-to-head comparison of measurement properties of the EQ-5D-3L and EQ-5D-5L in acute myeloid leukemia patients.

PURPOSE: This study aimed to compare the measurement properties of EQ-5D-3L(3L) and EQ-5D-5L(5L) in patients with acute myeloid leukemia (AML) in China. METHODS: We consecutively recruited 168 patients with AML from three tertiary hospitals to complete two rounds of interviews using the two versions of the EQ-5D. We compared (i) the ceiling effect using the McNemar's test, (ii) test-retest reliability using intraclass correlation coefficient (ICC) and Cohen's weighted Kappa, (iii) convergent validity using Spearman's rank correlation coefficient (r) and iv) discriminatory ability using F statistic and area under the receiver operating characteristics curve (AUROC) of the 5L and the 3L. RESULTS: The 5L descriptive system showed significantly lower ceiling effects in comparison to the 3L descriptive system (p < 0.001). While 5L showed superior reproducibility (Cohen's weighted Kappa = 0.56-0.67 and ICC = 0.89), both instruments exhibited good test-retest reliability. Even though both 3L and 5L showed good convergent and known-groups validity, 5L showed better convergent validity and discriminatory ability. CONCLUSION: The current study found both 3L and 5L to be suitable for use in AML patients. However, 5L showed superior measurement properties compared to 3L. Thus, 5L could be the preferred instrument over 3L for use in AML patients.

Measurement Properties of the EQ-5D-5L and EQ-5D-3L in Six Commonly Diagnosed Cancers.

BACKGROUND: This study aimed to compare the measurement properties of the EQ-5D-3L (3L) and EQ-5D-5L (5L) in cancer patients. METHODS: A consecutive sample of inpatients with lung, breast, colorectal, liver, gastric, or thyroid cancer were interviewed using the 3L, 5L, and Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires, and a subgroup was invited to complete the 3L and 5L again. Kappa and intraclass correlation coefficient were used to assess test-retest reliability, and Spearman's correlation between the EQ-5D and FACT-G was evaluated to assess convergent validity. Comparison of subgroups defined using Eastern Cooperative Oncology Group status and cancer stage were performed to assess known-group validity and discriminatory power using the F-statistic and area under the receiver-operating characteristics curve. All analyses were also performed for each subgroup of cancer patients. RESULTS: A total of 416 cancer patients completed the baseline questionnaire and 90 patients also completed the follow-up survey after 2 days. Ceiling effects were smaller in 5L (10.1%) than in 3L (17.8%). The test-retest reliability and convergent validity of the 5L were slightly better than those of the 3L. Both the 3L and 5L showed known-group validity; however, the 5L index showed better discriminatory power. Similar trends were found in the six types of cancers. CONCLUSION: In general, 5L appears to have better measurement properties than 3L for measuring the health-related quality of life of cancer patients. While both the 3L and 5L are suitable, 5L should be preferable to 3L for use in cancer outcomes research.

Factors associated with postsurgical wound infections among breast cancer patients: A retrospective case-control record review.

Women with non-metastatic breast cancer will be offered surgery as their first option. Unfortunately, studies have shown that the most common postoperative complication is surgical wound infection (SWI). We investigated the prevalence of SWI in breast cancer patients and identified the factors predictive of its development. The study was conducted at the breast cancer centre in Singapore. A retrospective case-control review of medical records was used. During the 2013 to 2016 study period, there were 657 postsurgical breast cancer patients with only 105 records eligible for the study. The sample consisted of one to four case:control (21:84), matched according to their age at the time of their surgery. Patients presenting with SWI were grouped into cases, while those without SWI were grouped into the controls. Chi-square test and Mann-Whitney U test were used to identify risk factors associated with SWI. Regression analysis of predictive variables from the univariate analyses was included. These variables were type of breast surgery, implants, comorbidities, previous surgery, previous chemotherapy, surgical drains, seroma, blood transfusion, surgeon department, and length of stay. The prevalence of SWI was 9%. Demographic, clinical, and comorbidities were not associated with SWI. However, multivariate analysis found that "surgeon department," "discharged with surgical drains," and "postoperative seroma" were predictive of SWI. Monitoring SWI is indispensable to minimise burdens on individuals and institutions. Health care professionals should identify high-risk patients based on the identified predictive variables. A cross-institutional record review of SWI in postoperative breast cancer patients should be conducted.

A vision 'bolt-on' increases the responsiveness of EQ-5D: preliminary evidence from a study of cataract surgery.

OBJECTIVES: (1) To evaluate the effect of adding a vision dimension ('bolt-on') to the 5-level EQ-5D (EQ-5D-5L) and 3-level EQ-5D (EQ-5D-3L) on their responsiveness, and (2) to compare the responsiveness of a vision 'bolt-on' EQ-5D-3L (EQ-5D-3L + V) with SF-6D and Health Utilities Index Mark 3 (HUI3) to the benefit of cataract surgery. METHODS: Sixty-three patients were assessed before and after their cataract surgery using the EQ-5D-3L, EQ-5D-5L, SF-6D, HUI3, as well as a 3-level and a 5-level vision dimension. Preference-based indices were calculated using available value sets for EQ-5D-3L, EQ-5D-3L + V, EQ-5D-5L, SF-6D, and HUI3, and non-preference-based indices were calculated using the sum-score method for EQ-5D-5L and EQ-5D-5L + V (vision bolt-on EQ-5D-5L). Responsiveness was assessed using the standardized response mean (SRM) and F-statistic. RESULTS: Among preference-based indices, mean changes from pre to post-surgery in EQ-5D-3L + V and EQ-5D-3L indices were 0.031 and 0.018, respectively. The mean changes for EQ-5D-5L, SF-6D and HUI3 indices were 0.020, 0.012 and 0.105, respectively. The SRM (F-statistic) for EQ-5D-3L + V and EQ-5D-3L indices were 0.458 (13.2) and 0.098 (0.6), respectively. The responsiveness of EQ-5D-3L + V was better than EQ-5D-5L, SF-6D; the responsiveness of HUI3 was better than all other measures. Using non-preference-based indices, mean change for EQ-5D-5L + V and EQ-5D-5L were 0.067 and 0.017, respectively. The corresponding SRM (F-statistic) were 0.709 (31.7) and 0.295 (5.4). CONCLUSIONS: Preliminary evidence from our study suggests that a vision 'bolt-on' may increase the responsiveness of EQ-5D-3L and EQ-5D-5L to change in health outcomes experienced by patients undergoing cataract surgery. In absence of the preference-based vision bolt-on EQ-5D-5L index, HUI3 was the most responsive measure.

A Multiparameter Flow Cytometry Analysis Panel to Assess CD163 mRNA and Protein in Monocyte and Macrophage Populations in Hyperinflammatory Diseases.

CD163 facilitates regulation and resolution of inflammation and removal of free hemoglobin and is highly expressed in myeloid cells from patients with inflammatory disorders, such as systemic juvenile idiopathic arthritis (SJIA) and macrophage activation syndrome (MAS). Our recent studies indicate that regulation of CD163 mRNA expression is a key functional property of polarized monocytes and macrophages and is mediated at the transcriptional and posttranscriptional level, including via microRNAs. The goal of the current study is to develop a multiparameter flow cytometry panel incorporating detection of CD163 mRNA for polarized monocyte and macrophage populations in disorders such as SJIA and MAS. THP-1 cells and CD14+ human monocytes were stained using fluorochrome-conjugated Abs to myeloid surface markers, along with CD163 mRNA. Staining for mRNA could reliably detect CD163 expression while simultaneously detecting different macrophage populations using Abs targeting CD14, CD64, CD80, CD163, and CD209. This approach was found to be highly sensitive for increased mRNA expression when macrophages were polarized with IL-10 [M(IL-10)], with a strong signal over a broad range of IL-10 concentrations, and showed distinct kinetics of CD163 mRNA and protein induction upon IL-10 stimulation. Finally, this panel demonstrated clear changes in polarization markers in unstimulated monocytes from patients with SJIA and MAS, including upregulated CD163 mRNA and increased CD64 expression. This approach represents a robust and sensitive system for RNA flow cytometry, useful for studying CD163 expression as part of a multimarker panel for human monocytes and macrophages, with broad applicability to the pathogenesis of hyperinflammatory diseases.

EQ-5D-5L is More Responsive than EQ-5D-3L to Treatment Benefit of Cataract Surgery.

BACKGROUND: It is not clear whether 5-level EQ-5D (EQ-5D-5L) utilities based on recently developed value sets are more responsive than 3-level EQ-5D (EQ-5D-3L) utilities. OBJECTIVES: The study aims were to compare (1) the responsiveness of EQ-5D-5L and EQ-5D-3L utilities and (2) the responsiveness of these utilities with the Short Form-6 Dimension (SF-6D) and Health Utilities Index Mark 3 (HUI3) utilities to the treatment benefit of cataract surgery. METHODS: A total of 148 patients were interviewed before and after their cataract surgery using EQ-5D-3L, EQ-5D-5L, SF-6D, and HUI3. Responsiveness was assessed for all measures using the mean change (post-treatment-pre-treatment), standardized effect size (SES), standardized response mean (SRM), and F-statistic. RESULTS: Using the Singapore value sets, mean change for EQ-5D-3L and EQ-5D-5L utilities was 0.016 and 0.028, SES was 0.097 and 0.199; SRM was 0.091 and 0.196; and F-statistic was 1.2 and 5.7, respectively. Similar trends were observed using the UK/England EQ-5D value sets, although the magnitude was slightly smaller. The mean change, SES, SRM and F-statistics for SF-6D (UK value set) were 0.020, 0.234, 0.249, and 9.2, respectively. The values of mean change, SES, SRM and F-statistics for HUI3 (Canada value set) were 0.080, 0.472, 0.474, and 33.3, respectively. CONCLUSIONS: The EQ-5D-5L utilities tend to be more responsive than the EQ-5D-3L utilities to treatment benefits of cataract surgery. The HUI3 utilities are more responsive than both the EQ-5D-5L and SF-6D, and SF-6D utilities may be slightly more responsive than the EQ-5D-5L for assessing patients undergoing cataract surgery.