Publications by authors named "Johnny W Huang"

9 Publications

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What Are the Burden, Causes, and Costs of Early Hospital Readmissions After Kidney Transplantation?

Prog Transplant 2021 Jun 24;31(2):160-167. Epub 2021 Mar 24.

Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Introduction: Kidney transplant recipients are at risk for complications resulting in early hospital readmission. This study sought to determine the incidences, risk factors, causes, and financial costs of early readmissions.

Design: This single-centre cohort study included 1461 kidney recipients from 1 Jul 2004 to 31 Dec 2012, with at least 1-year follow-up. Early readmission was defined as hospitalization within 30 or 90-days postdischarge from transplant admission. Associations between various parameters and 30 and 90-days posttransplant were determined using multivariable Cox proportional hazards models. The hospital-associated costs of were assessed.

Results: The rates of early readmission were 19.4% at 30 days and 26.8% at 90 days posttransplant. Mean cost per 30-day readmission was 11 606 CAD. Infectious complications were the most common reasons and resulted in the greatest cost burden. Factors associated with 30 and 90-days in multivariable models were recipient history of chronic lung disease (hazard ratio or HR 1.78 [95%CI: 1.14, 2.76] and HR 1.68 [1.14, 2.48], respectively), median time on dialysis (HR 1.07 [95% CI: 1.01, 1.13]and HR 1.06 [95% CI: 1.01, 1.11], respectively), being transplanted preemptively (HR 1.75 [95% CI: 1.07, 2.88] and HR 1.66 [95% CI: 1.07, 2.57], respectively), and having a transplant hospitalization lasting of and more than 11 days (HR 1.52 [95% CI: 1.01, 2.27] and HR 1.65 [95% CI: 1.16, 2.34], respectively).

Discussion: Early hospital readmission after transplantation was common and costly. Strategies to reduce the burden of early hospital readmissions are needed for all patients.
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http://dx.doi.org/10.1177/15269248211003563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182333PMC
June 2021

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

Kidney Int Rep 2021 Feb 3;6(2):396-403. Epub 2020 Dec 3.

The Ottawa Hospital, Ottawa, Ontario, Canada.

Introduction: N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.

Methods: A literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).

Results: Six studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 μmol/L [95% confidence interval {CI} -5.6 to 0.0];  = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 μmol/L [95% CI -6.29 to -0.28];  = 0.04) than Jaffe (WMD, -0.51 μmol/L [95% CI -7.56 to 6.53];  = 0.89) and in particular with intravenous (WMD, -31.10 μmol/L [95% CI -58.37 to -3.83];  = 0.03) compared with oral NAC (WMD, -2.5 μmol/L [95% CI -5.32 to 0.32];  = 0.08). There was no change in cystatin C after NAC administration.

Discussion: NAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.
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http://dx.doi.org/10.1016/j.ekir.2020.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879108PMC
February 2021

A systematic review on the efficacy and safety of low molecular weight heparin as an anticancer therapeutic in preclinical animal models.

Thromb Res 2020 11 8;195:103-113. Epub 2020 Jul 8.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Box 511, Ottawa, ON K1H 8L6, Canada; Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Room B307, 1053 Carling Avenue, Mail Stop 249, Ottawa, ON K1Y 4E9, Canada; Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Box 511, Ottawa, ON K1H 8L6, Canada. Electronic address:

Objective: The therapeutic effects of low molecular weight heparins (LMWH) may extend past thrombosis prevention, with preclinical evidence demonstrating anti-metastatic properties. Clinical evidence on the topic, however, remains controversial. A systematic review of preclinical evidence may help elucidate reasons for this contradictory evidence. The objective of our systematic review is to assess the anti-metastatic properties of LMWHs in solid tumour animal models.

Methods: MEDLINE, Embase, Web of Science and PubMed were searched from inception to May 12th, 2020. All articles were screened independently and in duplicate. Studies that compared LMWH to a placebo or no treatment arm in solid tumour animal models were included. The primary outcome was the burden of metastasis. Secondary outcomes included primary tumour growth and mortality. The risk of bias was assessed in duplicate using a modified Cochrane Risk of Bias tool.

Results: Forty-two studies were included in the review. Administration of a LMWH was associated with a significant decrease in the burden of metastasis (SMD -2.18; 95% CI -2.66 to -1.70). Additionally, the administration of a LMWH was also associated with a significant reduction in primary tumour growth (SMD -1.95; 95% CI -2.56 to -1.34) and risk of death (RR 0.39; 95% CI 0.16-0.97). All included studies were deemed to be at an unclear risk of bias for at least one methodological criterion.

Conclusions: Our results demonstrate that LMWH can effectively reduce metastatic burden and reduce tumour growth in preclinical animal models of solid tumour malignancies. Reasons for the contradiction with clinical evidence require further exploration.
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http://dx.doi.org/10.1016/j.thromres.2020.07.008DOI Listing
November 2020

Approach to treatment of cicatricial ectropion: a systematic review and meta-analysis comparing surgical and minimally invasive options.

Arch Dermatol Res 2020 Apr 4;312(3):165-172. Epub 2019 Oct 4.

Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Cicatricial ectropion can involve the skin, subcutaneous tissue, muscle, and septum to result in chronic tearing and keratopathy. Surgery involving the orbital rim or eyelid is a common cause. Minimally invasive techniques may provide alternative options for correction, but the comparative benefit to surgery is unknown. To compare the efficacy of surgical and minimally invasive minimally invasive treatment options for cicatricial ectropion. A comprehensive literature search of Medline, EMBASE, and the Cochrane Library published from 1960 to August 2019 was performed for studies that described any treatment of cicatricial ectropion. 1391 studies were found, of which 31 had extractable data for 299 patients. Pooling of outcome data occurred for the primary and secondary outcomes. The complete and partial response rates to treatment (primary outcomes) as well as the recurrence rate and physician global assessment of cosmesis (secondary outcomes) were analyzed. Surgical correction resulted in complete correction in 79% of patients compared to 63% of hyaluronic acid treated patients. Hyaluronic acid injection had a better aesthetic outcome, but a higher recurrence rate overall. Hyaluronic acid filler with a high G' along with delayed dissolution trended toward a lower recurrence rate. Other minimally invasive treatments had little data. The literature found was limited to mostly single-center, observational studies. Hyaluronic acid may be a viable alternative for cicatricial ectropion in those patients who cannot undergo surgery. Further prospective studies are required to routinely recommend minimally invasive techniques.
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http://dx.doi.org/10.1007/s00403-019-01983-0DOI Listing
April 2020

Photoprotection in the Immunosuppressed Pediatric Population.

J Cutan Med Surg 2018 Nov/Dec;22(6):639-642

1 Division of Rheumatology and Dermatology, Department of Pediatrics, Children's Hospital of Eastern Ontario Division of Dermatology, Ottawa, ON, Canada.

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http://dx.doi.org/10.1177/1203475418782151DOI Listing
September 2019

The Effect of N-Acetylcysteine on Creatinine Measurement: Protocol for a Systematic Review.

Can J Kidney Health Dis 2018 24;5:2054358118801017. Epub 2018 Sep 24.

The Ottawa Hospital, University of Ottawa, ON, Canada.

Background: N-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, a systematic review of the literature will be conducted to determine whether there is an effect of NAC on kidney function measured with serum creatinine.

Objective: To determine the effect of NAC on kidney function.

Design: A systematic review and meta-analysis.

Settings: Prospective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery).

Patients: Adult humans aged 18 years old or more, either healthy volunteers or with chronic kidney disease, were administered with NAC. Populations having little to no kidney function such as in end-stage kidney disease will be excluded.

Measurements: Serum creatinine and/or cystatin C measurements before and after NAC administration.

Methods: An information specialist will assist in searching MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify all study types including randomized controlled trials, and prospective cohort studies reporting change in serum creatinine after NAC administration. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using predefined inclusion criteria and will then extract data from the full texts of selected studies. The weighted mean difference will be calculated for change in creatinine with NAC, using random-effects analysis. Quality assessment will be done with the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies.

Results: The outcome of interest is kidney function as reported by either change in serum creatinine and/or serum cystatin C measurement for randomized trials or comparing baseline (pre-NAC dose) values and those following the NAC dose.

Limitations: Possible heterogeneity and publication bias and lack of mechanistic data.

Conclusions: This systematic review will provide a synthesis of current evidence on the effect of NAC on serum creatinine measurement. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field.

Systematic Review Registration: This review is registered with PROSPERO, CRD42017055984.
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http://dx.doi.org/10.1177/2054358118801017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156188PMC
September 2018

Cancer recurrence after solid organ transplantation: A systematic review and meta-analysis.

Transplant Rev (Orlando) 2017 10 10;31(4):240-248. Epub 2017 Aug 10.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Surgery, St. Michael's Hospital, Toronto, Canada; Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada. Electronic address:

Solid organ transplant recipients (SOTR) with a pre-transplant malignancy (PTM) have been thought to be at high risk of cancer recurrence. However, recent population-based studies report cancer recurrence rates in SOTR similar to those of non-transplant patients. A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies reporting cancer recurrence in SOTR with PTM. Quality assessment was performed using a validated tool for assessing the quality of an observational study with no control group designed by the Institute of Health Economics. Overall and site-specific recurrence rates per person-year were pooled using generalized linear random/mixed-effects meta-analysis models and an exact likelihood approach based on a binomial and Poisson distribution. Meta-regressions, subgroup and sensitivity meta-analyses were used to explore sources of heterogeneity. Fifty-seven eligible studies were identified and 39 were included in the meta-analysis. The pooled recurrence rate was 1.6 (95% CI 1.0-2.6) per 100 person-year for all studies, and 1.1 (95% CI 0.5-2.7) when restricted to population-based studies. The recurrence rate was higher for kidney (2.4 per 100 person-year, 95% CI 1.0-5.6) compared with liver (1.0 per 100 person-year, 95% CI 0.4-2.6), and cardiothoracic recipients (1.3 per 100 person-year, 95% CI 0.6-2.7). Time from cancer diagnosis to transplantation (TCT) ≤ 5 years was associated with greater risk of cancer recurrence compared to TCT > 5 years (risk ratio: 2.80, 95% CI 1.12-7.01). In conclusion, the risk of cancer recurrence in recipients with PTM is considerably lower than historic reports used to establish recommendations for listing patients with PTM. Evidence to support minimum cancer remission times before transplantation is limited.
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http://dx.doi.org/10.1016/j.trre.2017.08.003DOI Listing
October 2017

Outcomes of Solid Organ Transplant Recipients With Preexisting Malignancies in Remission: A Systematic Review and Meta-Analysis.

Transplantation 2017 Mar;101(3):471-481

1 Institute of Health Policy, Management and Education, University of Toronto, Toronto, ON, Canada. 2 Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. 3 Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada. 4 Departments of Paediatrics, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada. 5 Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada. 6 Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

Background: Solid organ transplant recipients (SOTR) with a pretransplant malignancy (PTM) are at increased risk for cancer recurrence. However, it is unclear whether differences in survival and incidence of posttransplant de novo malignancies exist between recipients with PTM and those without PTM. We designed a systematic review to synthesize all available evidence assessing these outcomes.

Methods: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies comparing the following outcomes in SOTR by PTM status: (1) all-cause mortality, (2) cancer-specific mortality, and (3) incidence of posttransplant de novo malignancy. Risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: Thirty-two cohort studies were included. Recipients with PTM were at increased risk of all-cause mortality compared to recipients without PTM (pooled hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.27-1.81). Similarly, recipients with PTM were 3 times more likely to die of cancer (pooled HR, 3.13; 95% CI, 2.29-4.27). The pooled HR for developing posttransplant de novo malignancy was also increased (HR, 1.92; 95% CI, 1.52-2.42). The association of all-cause mortality and SOTR with PTM did not vary by transplanted organ.

Conclusions: Pretransplant malignancy is associated with increased risk of all cause-mortality, cancer-specific mortality and of developing de novo malignancies after transplantation compared with those without PTM. These results reaffirm the need for careful selection of transplant recipients with PTM. Tailored screening and management strategies should be developed for this group of patients.
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http://dx.doi.org/10.1097/TP.0000000000001192DOI Listing
March 2017

Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation.

J Am Soc Nephrol 2016 06 8;27(6):1793-800. Epub 2015 Oct 8.

Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology and the Renal Transplant Program, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.
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http://dx.doi.org/10.1681/ASN.2015040391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884111PMC
June 2016
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