Comparative efficacy of balanced crystalloids versus 0.9% saline on delayed graft function and perioperative outcomes in kidney transplantation: a meta-analysis of randomised controlled trials.

BACKGROUND: Delayed graft function after kidney transplantation is linked to poor graft survival and increased chronic allograft injury. Recent guidelines suggest using balanced crystalloids over 0.9% saline owing to better metabolic profiles, but their impact on DGF remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Central Registry of Clinical Trials from inception until February 29, 2024, and included RCTs that randomised adult participants to receive either intravenous balanced fluids or 0.9% saline intraoperatively. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool and certainty of evidence using GRADE. Outcomes analysed were delayed graft function incidence, vasopressor requirements, length of hospital stay, and postoperative metabolic profiles. RESULTS: Of 106 publications identified, we included 11 RCTs (n=1717). Pooled analysis showed that the use of balanced fluids was associated with a lower incidence of delayed graft function compared with 0.9% saline (RR 0.82, 95% CI: 0.69 to 0.98, P=0.01, moderate certainty). Balanced crystalloids were associated with higher postoperative serum pH, higher serum bicarbonate, and lower serum chloride concentration, but effects on vasopressor requirements, length of hospital stay, and serum creatinine were uncertain. CONCLUSIONS: Balanced crystalloid intravenous fluid therapy reduced delayed graft function incidence and maintained more favourable serum chemistry profiles compared with 0.9% saline in patients undergoing kidney transplantation. However, crystalloid type did not significantly influence vasopressor requirements and length of hospital stay.

Score-based prediction model for severe vitamin D deficiency in patients with critical illness: development and validation.

BACKGROUND: Severe vitamin D deficiency (SVDD) dramatically increases the risks of mortality, infections, and many other diseases. Studies have reported higher prevalence of vitamin D deficiency in patients with critical illness than general population. This multicenter retrospective cohort study develops and validates a score-based model for predicting SVDD in patients with critical illness. METHODS: A total of 662 patients with critical illness were enrolled between October 2017 and July 2020. SVDD was defined as a serum 25(OH)D level of < 12 ng/mL (or 30 nmol/L). The data were divided into a derivation cohort and a validation cohort on the basis of date of enrollment. Multivariable logistic regression (MLR) was performed on the derivation cohort to generate a predictive model for SVDD. Additionally, a score-based calculator (the SVDD score) was designed on the basis of the MLR model. The model's performance and calibration were tested using the validation cohort. RESULTS: The prevalence of SVDD was 16.3% and 21.7% in the derivation and validation cohorts, respectively. The MLR model consisted of eight predictors that were then included in the SVDD score. The SVDD score had an area under the receiver operating characteristic curve of 0.848 [95% confidence interval (CI) 0.781-0.914] and an area under the precision recall curve of 0.619 (95% CI 0.577-0.669) in the validation cohort. CONCLUSIONS: This study developed a simple score-based model for predicting SVDD in patients with critical illness. TRIAL REGISTRATION: ClinicalTrials.gov protocol registration ID: NCT03639584. Date of registration: May 12, 2022.

Cardiac and Noncardiac Determinants of Exercise Capacity in CKD.

BACKGROUND: Impaired exercise capacity is a significant symptom of CKD and is associated with poor survival. Furthermore, there is a growing interest in applying exercise as a diagnostic tool or as therapy in CKD. However, an in-depth understanding of exercise physiology in CKD is still lacking. METHODS: To evaluate the role of cardiac (central) and noncardiac (peripheral) determinants of exercise capacity in CKD, we conducted a cross-sectional study of 70 male patients with CKD (stages 2-5) without diabetes or cardiac disease, 35 healthy controls, and 25 patients with heart failure. An integrated cardiopulmonary exercise test using a CO2 rebreathing technique was used to measure peak O2 consumption (VO2peak) and peak cardiac output simultaneously, and to calculate peak peripheral O2 extraction (C[a-v]O2), the peripheral determinant (the ability of exercising skeletal muscles to extract oxygen). We performed multiple regression analysis and used Bayesian information criteria (BIC) changes to quantitatively assess the individual contribution of central and peripheral factors. RESULTS: Compared with healthy controls, in patients with CKD, the VO2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO2peak in healthy controls and patients with heart failure, whereas C(a-v)O2 played a more significant role in determining VO2peak in CKD (ß=0.68, P<0.001) compared with cardiac output (ß=0.63, P<0.001). In addition, the magnitude of BIC reduction was greater for C(a-v)O2 compared with cardiac output (BIC, 298.72 versus 287.68) in CKD. CONCLUSIONS: In CKD, both peak cardiac output and peak C(a-v)O2 are independent predictors of VO2peak, and the more significant roleplayed by peak C(a-v)O2 highlights the importance of noncardiac factors in determining exercise capacity in CKD.

Factors affecting outcomes in patients with cardiac arrest who receive target temperature management: The multi-center TIMECARD registry.

BACKGROUND: Target temperature management (TTM) is a recommended therapy for patients after cardiac arrest (PCA). The TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry was established for PCA who receive TTM therapy in Taiwan. We aim to determine the variables that may affect neurologic outcomes in PCA who undergo TTM. METHODS: We retrieved demographic variables, resuscitation variables, and cerebral performance category (CPC) scale score at hospital discharge from the TIMECARD registry. The primary outcome was a favorable neurologic outcome, defined as a CPC scale of 1 or 2 at discharge. A total of 540 PCA treated between January 2014 and September 2019 were identified from the registry. Univariate and multivariate analyses were performed to identify significant variables. RESULTS: The mortality rate was 58.1% (314/540). Favorable neurologic outcomes were noted in 117 patients (21.7%). The factors significantly influencing the neurologic outcome (p < 0.05) were the presence of an initial shockable rhythm or pulseless electric activity, a witnessed cardiac-arrest event, bystander cardiopulmonary resuscitation, a smaller total dose of epinephrine, the diastolic blood pressure value at return of spontaneous circulation, a pre-arrest CPC score of 1, coronary angiography, new-onset seizure, and new-onset serious infection. Older patients and those with premorbid diabetes mellitus, chronic kidney disease, malignancy, obstructive lung disease, or cerebrovascular accident were more likely to have an unfavorable neurologic outcome. CONCLUSION: In the TIMECARD registry, some PCA baseline characteristics, cardiac arrest events, cardiopulmonary resuscitation characteristics, and post-arrest management characteristics were significantly associated with neurologic outcomes.

USING DENTAL PATIENT-REPORTED OUTCOMES (dPROs) IN META-ANALYSES: A SCOPING REVIEW AND METHODOLOGICAL INVESTIGATION.

Many studies use dental patient-reported outcomes (dPROs) to evaluate treatments and interventions. However, the consensus on the methodology for combining results of dPROs for meta-analysis has not yet been fully established or widely discussed. The aim of this study is to conduct a scoping review for the methodological issues and difficulties specific to meta-analysis of dPROs and to put forward recommendations for improving quality of meta-analyses of dPRO. We searched the Google Scholar and PubMed databases and identified meta-analysis with dPROs in English. A total of 22 meta-analyses were included in our scoping review, and their characteristics, such as reported outcomes, questionnaires, and effect measures, were extracted. We identified several methodological issues within current literature: (1) synthesizing results from studies with different rating scales; (2) meta-analyses with few studies; (3) the interpretation of standardized mean difference; (4) including studies of different cut-off values in a meta-analysis; and (5) systematic errors due to different instruments. According to each issue mentioned, we provided guidance and recommendations on how to resolve those issues, including using the same Likert scale, conducting an overall and subgroup meta-analysis, using a random-effects model in a meta-analysis, etc. More efforts are required to improve the conduct and interpretation of meta-analyses on dPROs.

Pancreatic neck transection using a harmonic scalpel increases risk of biochemical leak but not postoperative pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: The effect of a harmonic scalpel on postoperative pancreatic fistula (POPF) has not been addressed. This study assessed the effect of pancreatic neck transection using a harmonic scalpel on rate and severity of POPF after pancreaticoduodenectomy (PD). METHODS: This retrospective analysis included patients who underwent PD at National Taiwan University Hospital between July 2015 and March 2019. We compared rate and severity of POPF between patients who underwent pancreatic neck transection using a harmonic scalpel versus electrosurgical unit. RESULTS: Of 422 consecutive PDs, the pancreatic neck was transected using a harmonic scalpel or electrosurgical unit in 144 and 278 patients, respectively. Use of a harmonic scalpel significantly increased risk of biochemical leak (25.7% versus [vs] 10.8%; P < 0.05) but not clinically relevant POPF (CR-POPF; 30.2% vs 26.4%; P = 0.41). Harmonic transection was an independent predictor of biochemical leak (odds ratio [OR] = 2.93; P < 0.05) but not CR-POPF (OR = 0.83; P = 0.41) or other major complications (OR = 0.72; P = 0.27). There was no significant intergroup difference in postoperative hospital stay. CONCLUSION: Pancreatic neck transection using a harmonic scalpel increased risk of biochemical leak but not CR-POPF or other major complications.

Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses.

BACKGROUND: Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients. METHODS: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence. RESULTS: Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74-0.95) and L-HES (OR 0.81; 95% CI 0.69-0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65-0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35-0.87). CONCLUSIONS: Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients. TRIAL REGISTRATION: PROSPERO website, registration number: CRD42018115641).

Systematic review and sequential network meta-analysis on the efficacy of periodontal regenerative therapies.

AIMS: We aimed to update a previous network meta-analysis comparing the efficacy of periodontal regenerative therapies on the treatment of infrabony lesions. MATERIALS AND METHODS: Seven clinical trials were added after literature research for studies published between January 2011 and September 2019. We conducted network meta-analysis (NMA) to compare the effects of guided tissue regeneration (GTR), enamel matrix derivatives (EMD) and their combination therapies on probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain. Sequential network meta-analysis (SNMA) was also used to control the type-I error rate due to multiple testing. RESULTS: A total of 60 studies were included. For both PPD reduction and CAL gain, the flap operation (FO) was the least effective treatment. Although the differences between periodontal regenerative therapies were small, GTR attained the greatest reduction in PPD, and EMD with bone graft the greatest CAL gain compared to other therapies. SNMA used stricter efficacy criteria, yielding slightly different results from NMA. CONCLUSIONS: EMD, GTR, and their combined therapies were more effective than flap operation, although the differences between regenerative therapies remain small in this updated study. SNMA reduces the risk of false-positive findings, thereby providing more robust evidence on the superiority of treatments.

Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET imaging in node-positive esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: Our purpose was to examine the prognostic value of post-CRT PET based on the presence or absence of FDG-avid metastatic lymph node(s) and metabolic response of the primary tumor in patients with clinically node-positive ESCC treated with definitive chemoradiotherapy (dCRT). METHODS: We identified 108 eligible patients treated by chemoradiotherapy (CRT) with or without resection from our prospectively collected database. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox regression were performed for survival analyses and multivariable analysis, respectively. RESULTS: The study cohort was comprised of 59 patients receiving dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the comparative group and four patients were excluded from further analyses for developing interval distant metastasis detected on post-CRT PET scan. The median follow-up for the study cohort was 41 months. On K-M analysis of the study cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%, p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In multivariable analysis, yPET-F remained as a strong independent favorable prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p > 0.99) and DMFS (p = 0.92) between these three groups. CONCLUSIONS: Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.

Reassessing the management of uncomplicated urinary tract infection: A retrospective analysis using machine learning causal inference.

Background: Uncomplicated urinary tract infection (UTI) is a common indication for outpatient antimicrobial therapy. National guidelines for the management of uncomplicated UTI were published by the Infectious Diseases Society of America in 2011, however it is not fully known the extent to which they align with current practices, patient diversity, and pathogen biology, all of which have evolved significantly in the time since their publication. Objective: We aimed to re-evaluate efficacy and adverse events for first-line antibiotics (nitrofurantoin, and trimethoprim-sulfamethoxazole), versus second-line antibiotics (fluoroquinolones) and versus alternative agents (oral ß-lactams) for uncomplicated UTI in contemporary clinical practice by applying machine learning algorithms to a large claims database formatted into the Observational Medical Outcomes Partnership (OMOP) common data model. Outcomes: Our primary outcome was a composite endpoint for treatment failure, defined as outpatient or inpatient re-visit within 30 days for UTI, pyelonephritis or sepsis. Secondary outcomes were the risk of 4 common antibiotic-associated adverse events: gastrointestinal symptoms, rash, kidney injury and C. difficile infection. Statistical methods: We adjusted for covariate-dependent censoring and treatment indication using a broad set of domain-expert derived features. Sensitivity analyses were conducted using OMOP-learn, an automated feature engineering package for OMOP datasets. Results: Our study included 57,585 episodes of UTI from 49,037 patients. First-line antibiotics were prescribed in 35,018 (61%) episodes, second-line antibiotics were prescribed in 21,140 (37%) episodes and alternative antibiotics were prescribed in 1,427 (2%) episodes. After adjustment, patients receiving first-line therapies had an absolute risk difference of -2.1% [95% CI -2.9% to -1.6%] for having a revisit for UTI within 30 days of diagnosis relative to second-line antibiotics. First-line therapies had an absolute risk difference of -6.6% [95% CI -9.4% to -3.8%] for 30-day revisit compared to alternative ß-lactam antibiotics. Differences in adverse events were clinically similar between first and second line agents, but lower for first-line agents relative to alternative antibiotics (-3.5% [95% CI -5.9% to -1.2%]). Results were similar for models built with OMOPlearn. Conclusion: Our study provides support for the continued use of first-line antibiotics for the management of uncomplicated UTI. Our results also provide proof-of-principle that automated feature extraction methods for OMOP formatted data can emulate manually curated models, thereby promoting reproducibility and generalizability.

Prognostic Value and Clinical Implication of Lymph Node-to-Primary Tumor SUV Ratio in Node-Positive Hypopharyngeal Squamous Cell Carcinoma Treated With Radiotherapy With or Without Chemotherapy.

PURPOSE: The aim of this was to evaluate the prognostic significance of the nodal-to-primary tumor SUVmax ratio (NTR) in patients with node-positive hypopharyngeal squamous cell carcinoma (HPSCC) treated with radiotherapy with or without concurrent chemotherapy. The study aims to enhance prognostic accuracy by incorporating NTR into the American Joint Committee on Cancer (AJCC) staging system. PATIENTS AND METHODS: This retrospective study included 191 patients with biopsy-proven node-positive HPSCC treated from 2005 to 2013. NTR was calculated as the ratio of SUVmax of metastatic lymph nodes to the primary tumor's SUVmax. Survival analyses were conducted using Cox regression models and Kaplan-Meier analysis. Receiver operating characteristic analysis compared the prognostic performance of the modified and AJCC staging systems. RESULTS: The median follow-up was 8.27 years, with 135 deaths (70.7%). High NTR (≥0.63) was significantly associated with worse overall survival (OS) and was an independent prognostic factor in multivariable analysis (adjusted hazards ratio [HR] = 1.63, P = 0.007). Median OS for high NTR was 17.4 months, compared with 75.2 months for low NTR. High NTR significantly predicted worse OS within AJCC stage IVA patients (HR = 6.09, P = 0.014). Patients in modified stage IVA (AJCC stage IVA with low NTR) had significantly longer OS than those in modified stage IVB (AJCC stage IVA with high NTR and AJCC stage IVB) (HR = 8.62, P = 0.003). The modified staging system incorporating NTR showed superior prognostic performance compared with the AJCC staging system. CONCLUSIONS: NTR is a significant independent prognostic factor for OS in node-positive HPSCC patients. Integrating NTR into the AJCC staging system improves prognostic accuracy.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Effect of early dexamethasone on outcomes of COVID-19: A quasi-experimental study using propensity score matching.

BACKGROUND: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. METHODS: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. RESULTS: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98). CONCLUSION: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Graphical evaluation of evidence structure within a component network meta-analysis.

Component network meta-analysis (CNMA) compares treatments comprising multiple components and estimates the effects of individual components. For network meta-analysis, a standard network plot with nodes for treatments and edges for direct comparisons between treatments is drawn to visualize the evidence structure and the connections between treatments. However, the standard network plot does not effectively illustrate the connections between components for a CNMA. For example, the comparison between linear combinations of components within a trial is not shown directly in a standard network plot, and whether all components are identifiable cannot be deduced directly from the plot. Therefore, we need a new approach to visualizing the evidence structure of a CNMA. In this article, we proposed a new graph, a modified signal-flow graph representing a system of equations, to evaluate the evidence structure for CNMA. In our new graph, each node represents a component, and arrows are used to show linear relationships between components. We used two examples to demonstrate how to draw and interpret the graph and how to use it to identify components that require more evidence.

Bias propagation in network meta-analysis models.

Network meta-analysis combines direct and indirect evidence to compare multiple treatments. As direct evidence for one treatment contrast may be indirect evidence for other treatment contrasts, biases in the direct evidence for one treatment contrast may affect not only the estimate for this particular treatment contrast but also estimates of other treatment contrasts. Because network structure determines how direct and indirect evidence are combined and weighted, the impact of biased evidence will be determined by the network geometry. Thus, this study's aim was to investigate how the impact of biased evidence spreads across the whole network and how the propagation of bias is influenced by the network structure. In addition to the popular Lu & Ades model, we also investigate bias propagation in the baseline model and arm-based model to compare the effects of bias in the different models. We undertook extensive simulations under different scenarios to explore how the impact of bias may be affected by the location of the bias, network geometry and the statistical model. Our results showed that the structure of a network has an important impact on how the bias spreads across the network, and this is especially true for the Lu & Ades model. The impact of bias is more likely to be diluted by other unbiased evidence in a well-connected network. We also used a real network meta-analysis to demonstrate how to use the new knowledge about bias propagation to explain questionable results from the original analysis.

The Interpretation of Standard Cardiopulmonary Exercise Test Indices of Cardiac Function in Chronic Kidney Disease.

BACKGROUND AND AIMS: As there is growing interest in the application of cardiopulmonary exercise test (CPX) in chronic kidney disease (CKD), it is important to understand the utility of conventional exercise test parameters in quantifying the cardiopulmonary fitness of patients with CKD. Merely extrapolating information from heart failure (HF) patients would not suffice. In the present study, we evaluated the utility of CPX parameters such as the peak O2-pulse and the estimated stroke volume (SV) in assessing the peak SV by comparing with the actual measured values. Furthermore, we compared the anaerobic threshold (AT), peak circulatory power, and ventilatory power with that of the measured values of the peak cardiac power (CPOpeak) in representing the cardiac functional reserve in CKD. We also performed such analyses in patients with HF for comparison. METHOD: A cross sectional study of 70 asymptomatic male CKD patients [CKD stages 2-5 (pre-dialysis)] without primary cardiac disease or diabetes mellitus and 25 HF patients. A specialized CPX with a CO2 rebreathing technique was utilized to measure the peak cardiac output and peak cardiac power output. The peak O2 consumption (VO2peak) and AT were also measured during the test. Parameters such as the O2-pulse, stroke volume, arteriovenous difference in O2 concentration [C(a-v)O2], peak circulatory power, and peak ventilatory power were all calculated. Pearson's correlation, univariate, and multivariate analyses were applied. RESULTS: Whereas there was a strong correlation between the peak O2-pulse and measured peak SV in HF, the correlation was less robust in CKD. Similarly, the correlation between the estimated SV and the measured SV was less robust in CKD compared to HF. The AT only showed a modest correlation with the CPOpeak in HF and only a weak correlation in CKD. A stronger correlation was demonstrated between the peak circulatory power and CPOpeak, and the ventilatory power and CPOpeak. In HF, the central cardiac factor was the predominant determinant of the standard CPX-derived surrogate indices of cardiac performance. By contrast, in CKD both central and peripheral factors played an equally important role, making such indices less reliable markers of cardiac performance per se in CKD. CONCLUSION: The results highlight that the standard CPX-derived surrogate markers of cardiac performance may be less reliable in CKD, and that further prospective studies comparing such surrogate markers with directly measured cardiac hemodynamics are required before adopting such markers into clinical practice or research in CKD.

The Impact of Sinus Floor Elevation Techniques on Sinus Membrane Perforation: A Systematic Review and Network Meta-analysis.

Purpose: To compare the risk of sinus membrane perforation (SMP) among lateral window sinus floor elevation (LSFE) and transcrestal sinus floor elevation (TSFE) techniques in prospective and retrospective studies for patients who underwent sinus augmentation for dental implant placement. Materials and Methods: A database search was conducted to screen the literature published from January 1960 to August 2021. The associations between SMP and surgical techniques as well as other clinical factors were evaluated via network meta-analysis. The impact of SMP on vertical ridge gain and implant survival was also evaluated. Results: Eighty-five studies with 5,551 SFE procedures were included. In LSFE techniques, using rotary burs showed the highest risk of SMP (surface under the cumulative ranking area [SUCRA] = 0.0745). In TSFE techniques, using reamers had the lowest risk of SMP (SUCRA = 0.9444). Increased SMP prevalence was significantly associated with reduced implant survival rate (odds ratio [OR] = 0.45 per 10% increase of SMP rate [95% credible interval (CreI): 0.21, 0.71], P < .001). Conclusions: With the inherent limitations, this network meta-analysis suggested that some techniques within either the LSFE or TSFE group may reduce SMP risk. Additional randomized controlled trials and better assessment of SMP are required to directly compare the risk of SMP between LSFE and TSFE.

To Treat or Not to Treat? Effect of Urate-Lowering Therapy on Renal Function, Blood Pressure and Safety in Patients with Asymptomatic Hyperuricemia: A Systematic Review and Network Meta-Analysis.

PURPOSE: Hyperuricemia is associated with increased cardiovascular risk. Because patients with asymptomatic hyperuricemia (AH) experience no immediate discomfort and there are possible side effects of urate-lowering drugs, treatment for AH is controversial. We aimed to perform a network meta-analysis (NMA) to investigate the effects of different urate-lowering therapies (ULTs) on serum uric acid level, renal function, blood pressure (BP), and safety in AH patients. METHODS: This NMA focused on AH patients. The intervention group (patients receiving urate-lowering drugs) was compared with others using other types of drugs, placebo, or usual care. We undertook a NMA under the frequentist framework by R. RESULTS: Thirteen eligible trials were identified. The interventions included allopurinol, febuxostat, and benzbromarone, which are not approved in the United States. Benzbromarone and allopurinol had the best efficacy on lowering serum uric acid level in short-term and long-term follow-up (mean difference [MD] = -3.05; 95% CI, -5.19 to -0.91 vs MD = -3.17; 95% CI, -5.19 to -1.15). Patients using allopurinol had significantly higher eGFR than using placebo in both short-term and long-term follow-up (MD = 3.07; 95% CI, 0.18 to 5.95 vs MD = 4.10; 95% CI, 2.66 to 5.54). No difference in BP was found between groups, except for febuxostat to diastolic BP after long-term treatment (MD = -1.47; 95% CI, -2.91 to -0.04). No statistically increased odds of safety events were found with the use of ULT. CONCLUSIONS: Our result showed that in AH patients, allopurinol has a renoprotective effect. Febuxostat has a significant impact in lowering diastolic BP. ULT does not result in a higher risk of safety events.

Complications of sinus floor elevation procedure and management strategies: A systematic review.

AIM: This systematic review aimed to investigates the types and incidences of complications following sinus floor elevations (SFE) along with their prevention and management strategies. MATERIALS AND METHODS: Electronic database and hand search were conducted to screen the literature published from January 1960 to June 2021. The selected studies had to report well-described SFE techniques, complications during, and post-SFE. Data extraction included types of SFE techniques, complications, and their treatment strategies. RESULTS: A total of 74 studies with 4411 SFE procedures met the inclusion criteria. Different SFE techniques demonstrated varying patterns for both complications and complication rates. Postoperative pain, swelling, and edema were widely reported. The most common complications that required intervention following Lateral SFE (LSFE) were sinus membrane perforation (SMP), wound dehiscence, graft exposure and failure, and sinusitis. LSFE had more SMPs and sinusitis cases compared with a transcrestal SFE (TSFE). The presence of benign paroxysmal positional vertigo following TSFE was significant in certain selected studies. CONCLUSION: Given the inherent limitations, this systematic review showed distinct features of complications in SFE using varying techniques. Treatment planning for these procedures should incorporate strategies to avoid complication occurrence.