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Not All Patient Reported Outcome Measures are Equivalent at Two- Compared to One-Year After Anterior Cruciate Ligament Reconstruction Based on a Retrospective Analysis

J ISAKOS. 2024 Mar 14:S2059-7754(24)00055-5. doi: 10.1016/j.jisako.2024.03.010. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess for clinically important differences in patient reported outcome measures (PROMs) at one- and two-years post anterior cruciate ligament reconstruction (ACLR).

METHODS: A retrospective comparison of prospectively collected PROMs for a single cohort who underwent a primary ACLR with or without associated meniscal surgery from 2016 to 2020 was assessed. Six externally validated PROMs were collected pre-operatively and at standardized times post-operatively. Descriptive statistics and paired equivalence testing of PROMs at one- and two-years after surgery was completed using previously published or calculated minimal clinically important differences as upper and lower equivalence limits. A repeated measures analysis of PROMs that were not clinically equivalent at one- and two-years after surgery was completed to assess for a clinically significant difference. Subgroup analyses based on sex, age and associated meniscal injury were completed.

RESULTS: One-hundred and forty-five participants with a mean age of 28.7 years (standard deviation: 9.9 years) were included in the final analysis. All PROMs were clinically equivalent at two- compared to one-year after ACLR except the Quality of Life and Sport and Recreation domains of the Knee Injury and Osteoarthritis Outcome Score (KOOS). The Quality of Life (mean difference (MD):12.3, P < 0.01, effect size (η2): 0.65) and Sport and Recreation (MD: 8.78, P < 0.01, η2: 0.50) domains of the KOOS were clinically different at two- compared to one-year post-operatively. No major differences were found in the subgroup analyses compared to the entire included sample.

CONCLUSION: While most PROMs were equivalent at two- compared to one-year after ACLR, the Quality of Life and Sport and Recreation domains of the KOOS, which reflect knee performance during higher demand activities exhibited a clinically significant difference.

LEVEL OF EVIDENCE: IV.

PMID:38492849 | DOI:10.1016/j.jisako.2024.03.010

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Poly(rC)-binding protein 1 alleviates neurotoxicity in 6-OHDA-induced SH-SY5Y cells and modulates glial cells in neuroinflammation

Brain Res. 2024 Mar 14:148863. doi: 10.1016/j.brainres.2024.148863. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons and neuroinflammation. Previous research has identified the involvement of Poly (rC)-binding protein 1 (PCBP1) in certain degenerative diseases; however, its specific mechanisms in PD remain incompletely understood.

METHODS: In this study, 6-OHDA-induced neurotoxicity in the cell lines SH-SY5Y, BV-2 and HA, was used to evaluate the protective effects of PCBP1. We assessed alterations in BDNF levels in SY5Y cells, changes in GDNF expression in glial cells, as well as variations in HSP70 and NF-κB activation. Additionally, glial cells were used as the in vitro model for neuroinflammation mechanisms.

RESULTS: The results indicate that the overexpression of PCBP1 significantly enhances cell growth compared to the control plasmid pEGFP/N1 group. Overexpression of PCBP1 leads to a substantial reduction in early apoptosis rates in SH-SY5Y, HA, and BV-2 cells, with statistically significant differences (p < 0.05). Furthermore, the overexpression of PCBP1 in cells results in a marked increase in the expression of HSP70, GDNF, and BDNF, while reducing NF-κB expression. Additionally, in SH-SY5Y, HA, and BV-2 cells overexpressing PCBP1, there is a decrease in the inflammatory factor IL-6 compared to the control plasmid pEGFP/N1 group, while BV-2 cells exhibit a significant increase in the anti-inflammatory factor IL-10.

CONCLUSION: Our findings suggest that PCBP1 plays a substantial role in promoting cell growth and modulating the balance of neuroprotective and inflammatory factors. These results offer valuable insights into the potential therapeutic utility of PCBP1 in mitigating neuroinflammation and enhancing neuronal survival in PD.

PMID:38492841 | DOI:10.1016/j.brainres.2024.148863

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Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the pancreas

Int J Radiat Oncol Biol Phys. 2024 Mar 14:S0360-3016(24)00429-2. doi: 10.1016/j.ijrobp.2024.03.013. Online ahead of print.

ABSTRACT

BACKGROUND: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

METHODS: SBRT (6.6 Gy x 5) was intended, although hypofractionated RT (5 Gy x 5) (HIGRT) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, 3) based on adequacy. A score of 1 indicated no deviation, a 2 indicated minor deviation, and a 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score.

RESULTS: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic, 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets, while 4 were approved for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT, and 7 (17.9%) with HIGRT. Five cases (13%) required revision prior to treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2 and 11 cases (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded.

CONCLUSION: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. While clinical outcomes did not appear to be impacted, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

PMID:38492812 | DOI:10.1016/j.ijrobp.2024.03.013

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Further Interventions After Root Canal Treatment Are Most Common in Molars and Teeth Restored with Direct Restorations: A 10-11-Year Follow-Up of the Adult Swedish Population

J Endod. 2024 Mar 14:S0099-2399(24)00164-X. doi: 10.1016/j.joen.2024.03.005. Online ahead of print.

ABSTRACT

INTRODUCTION: The aims were to investigate 1) the frequency of nonsurgical retreatment, root-end surgery, extraction, and further restorative treatment during a follow-up of 10 to 11 years after root filling and compare the frequencies according to tooth group and type of coronal restoration, and 2) the timing of nonsurgical retreatment, root-end surgery, and extraction.

METHODS: Data were collected from the Swedish Social Insurance Agency’s register. A search for treatment codes identified teeth root filled in 2009 and the type of coronal restoration (direct, indirect, unspecified) registered within 6 months of root filling. The root-filled teeth were followed 10-11 years, and further interventions were recorded. Descriptive statistics and Chi-square tests were used for statistical analysis.

RESULTS: In 2009, root fillings were registered for 215,611 individuals/teeth. Nonsurgical retreatment, root-end surgery, and extraction were undertaken in 3.5%, 1.4%, and 20% teeth, respectively. The frequency of further interventions varied with respect to tooth group and type of coronal restoration, but only slightly for endodontic retreatments. Further interventions, except for root-end surgery, were registered more often for molars and directly restored teeth (P < 0.001). The majority of endodontic retreatments were undertaken within 4 years, while extractions were evenly distributed over 10-11 years.

CONCLUSIONS: The frequency numbers of nonsurgical retreatment and root-end surgery were low, despite one in five root-filled teeth registered as extracted. Further interventions were most common in molars and directly restored teeth. Endodontic retreatments were performed more often during the first 4 years.

PMID:38492798 | DOI:10.1016/j.joen.2024.03.005

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Prophylactic Enoxaparin Dosing Using Anti-Factor Xa Levels in Hepatic Surgery Patients: A Pilot Study

Am Surg. 2024 Mar 15:31348241239926. doi: 10.1177/00031348241239926. Online ahead of print.

ABSTRACT

This study examines the safety and efficacy of using peak anti-Xa levels to achieve prophylactic enoxaparin (Lovenox, Sanofi-Aventis) levels in patients who underwent hepatic surgery. Prospectively enrolled patients undergoing major and minor hepatic procedures received postoperative enoxaparin dosing. The enoxaparin dose was adjusted to attain a peak anti-Xa level ≥ 0.20 U/ml. This group was compared to a historical cohort of patients who underwent similar procedures and received standard postoperative VTE chemoprophylaxis dosing. Inpatient postoperative VTE rates were higher in the control group when compared to the experimental group (0 patients [0.00%] vs 4 patients [8.16%]; P = .035). There was no statistically significant difference in number of postoperative blood transfusions, discharge hemoglobin, or in-hospital bleeding events. Adjusting enoxaparin dosing to achieve prophylactic peak anti-Xa levels of ≥0.20 IU/ml was associated with a reduced incidence of symptomatic inpatient postoperative VTE in patients who underwent hepatic surgery without increasing postoperative bleeding events.

PMID:38490954 | DOI:10.1177/00031348241239926

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MRI Investigation of the Association of Left Atrial and Left Atrial Appendage Hemodynamics with Silent Brain Infarction

J Magn Reson Imaging. 2024 Mar 15. doi: 10.1002/jmri.29349. Online ahead of print.

ABSTRACT

BACKGROUND: Left atrial (LA) myopathy is thought to be associated with silent brain infarctions (SBI) through changes in blood flow hemodynamics leading to thrombogenesis. 4D-flow MRI enables in-vivo hemodynamic quantification in the left atrium (LA) and LA appendage (LAA).

PURPOSE: To determine whether LA and LAA hemodynamic and volumetric parameters are associated with SBI.

STUDY TYPE: Prospective observational study.

POPULATION: A single-site cohort of 125 Participants of the multiethnic study of atherosclerosis (MESA), mean age: 72.3 ± 7.2 years, 56 men.

FIELD STRENGTH/SEQUENCE: 1.5T. Cardiac MRI: Cine balanced steady state free precession (bSSFP) and 4D-flow sequences. Brain MRI: T1- and T2-weighted SE and FLAIR.

ASSESSMENT: Presence of SBI was determined from brain MRI by neuroradiologists according to routine diagnostic criteria in all participants without a history of stroke based on the MESA database. Minimum and maximum LA volumes and ejection fraction were calculated from bSSFP data. Blood stasis (% of voxels <10 cm/sec) and peak velocity (cm/sec) in the LA and LAA were assessed by a radiologist using an established 4D-flow workflow.

STATISTICAL TESTS: Student’s t test, Mann-Whitney U test, one-way ANOVA, chi-square test. Multivariable stepwise logistic regression with automatic forward and backward selection. Significance level P < 0.05.

RESULTS: 26 (20.8%) had at least one SBI. After Bonferroni correction, participants with SBI were significantly older and had significantly lower peak velocities in the LAA. In multivariable analyses, age (per 10-years) (odds ratio (OR) = 1.99 (95% confidence interval (CI): 1.30-3.04)) and LAA peak velocity (per cm/sec) (OR = 0.87 (95% CI: 0.81-0.93)) were significantly associated with SBI.

CONCLUSION: Older age and lower LAA peak velocity were associated with SBI in multivariable analyses whereas volumetric-based measures from cardiac MRI or cardiovascular risk factors were not. Cardiac 4D-flow MRI showed potential to serve as a novel imaging marker for SBI.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PMID:38490945 | DOI:10.1002/jmri.29349

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Clinical characteristics associated with pediatric traumatic intracranial hemorrhage

Chin J Traumatol. 2024 Mar 7:S1008-1275(24)00029-4. doi: 10.1016/j.cjtee.2024.03.003. Online ahead of print.

ABSTRACT

PURPOSE: Traumatic brain injury (TBI) can cause significant morbidity and mortality in the pediatric population. Brain CT is the mainstay in the diagnosis of intracranial hemorrhage (ICH). The aim of this study was to explore the clinical characteristics that can predict ICH on brain CT in pediatric TBI patients, to assist physicians in deciding on the use of brain CT.

METHODS: A total of 475 pediatric TBI patients who underwent brain CT within 24 h after injury from January 2012 to December 2021 in the level 1 trauma center in Thailand were included in this cross-sectional study. Clinical data and brain CT findings were collected. Logistic regression analysis was applied to evaluate clinical characteristics that could predict ICH on brain CT in pediatric TBI patients. A p value was less than 0.05 being indicated that the difference is statistically significant. R software version 3.6.1 was used to statistical analysis.

RESULTS: The mean age of included cases was 7.7 years (interquartile range (IQR) 3.5 – 12.6 years). ICH was found in 98 (20.63%) pediatric patients based on brain CT findings. On multivariable analysis, high blunt energy injury (odds ratio (OR) = 2.79, 95% CI 1.27 – 6.11, p = 0.010), motor vehicle accidents (OR = 2.04, 95% CI: 1.14 – 3.67, p = 0.017), Glasgow coma scale score <13 (OR = 4.28, 95% CI: 1.87 – 9.78, p < 0.001), palpable skull fractures (OR = 7.30, 95% CI: 1.44 – 37.04, p = 0.016), signs of basilar skull fracture (OR = 6.10, 95% CI: 2.16 – 17.24, p < 0.001), and vomiting ≥ 3 times (OR = 2.60, 95% CI: 1.17 – 5.77, p = 0.022) were statistically significant predictive factors for ICH in pediatric TBI patients.

CONCLUSION: These factors might aid clinicians in making an appropriate decision regarding the use of brain CT in pediatric TBI cases.

PMID:38490943 | DOI:10.1016/j.cjtee.2024.03.003

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Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis

J Cyst Fibros. 2024 Mar 14:S1569-1993(24)00030-4. doi: 10.1016/j.jcf.2024.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID.

METHODS: In a multicenter retrospective cohort study across 4 United States CF centers 2012-2022, the association between modulator therapies and ID laboratory outcomes was estimated using multivariable linear mixed effects models overall and by key subgroups. Summary statistics describe the prevalence and trends of ID, defined a priori as transferrin saturation (TSAT) <20 % or serum iron <60 μg/dL (<10.7 μmol/L).

RESULTS: A total of 568 patients with 2571 person-years of follow-up were included in analyses. Compared to off modulator therapy, HEMT was associated with +8.4 % TSAT (95 % confidence interval [CI], +6.3-10.6 %; p < 0.0001) and +34.4 μg/dL serum iron (95 % CI, +26.7-42.1 μg/dL; p < 0.0001) overall; +5.4 % TSAT (95 % CI, +2.8-8.0 %; p = 0.0001) and +22.1 μg/dL serum iron (95 % CI, +13.5-30.8 μg/dL; p < 0.0001) in females; and +11.4 % TSAT (95 % CI, +7.9-14.8 %; p < 0.0001) and +46.0 μg/dL serum iron (95 % CI, +33.3-58.8 μg/dL; p < 0.0001) in males. Ferritin was not different in those taking modulator therapy relative to off modulator therapy. Hemoglobin was overall higher with use of modulator therapy. The prevalence of ID was high throughout the study period (32.8 % in those treated with HEMT).

CONCLUSIONS: ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin).

PMID:38490920 | DOI:10.1016/j.jcf.2024.03.002

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Carbon Footprint of Total Intravenous and Inhalation Anesthesia in the Transcatheter Aortic Valve Replacement Procedure

J Cardiothorac Vasc Anesth. 2024 Feb 22:S1053-0770(24)00124-1. doi: 10.1053/j.jvca.2024.02.027. Online ahead of print.

ABSTRACT

OBJECTIVES: To quantify and compare the emissions for deep sedation with total intravenous anesthesia (TIVA) and general anesthesia with inhaled agents during the transcatheter aortic valve replacement procedure.

DESIGN: A retrospective study.

SETTING: A tertiary hospital in Boston, Massachusetts.

PARTICIPANTS: The anesthesia records of 604 consecutive patients who underwent the transcatheter aortic valve replacement procedure between January 1, 2018, and March 31, 2022, were reviewed and analyzed.

INTERVENTIONS: Data were examined and compared in the following 2 groups: general anesthesia with inhaled agents and deep sedation with TIVA.

MEASUREMENTS AND MAIN RESULTS: The gases, drugs, airway management devices, and anesthesia machine electricity were collected and converted into carbon dioxide emissions (CO2e). The carbon emissions of intravenous medications were converted with the CO2e data for anesthetic pharmaceuticals from the Parvatker et al. study. For inhaled agents, inhaled anesthetics and oxygen/air flow rate were collected at 15-minute intervals and calculated using the anesthetic gases calculator provided by the Association of Anesthetists. The airway management devices were converted based on life-cycle assessments. The electricity consumed by the anesthesia machine during general anesthesia was estimated from the manufacturer’s data (Dräger, GE) and local Energy Information Administration data. The data were analyzed in the chi-squared test or Wilcoxon rank-sum test. There were no significant differences in the patients’ demographic characteristics, such as age, sex, weight, height, and body mass index. The patients who received general anesthesia with inhaled agents had statistically higher total CO2e per case than deep sedation with TIVA (16.188 v 1.518 kg CO2e; p < 0.001), primarily due to the inhaled agents and secondarily to airway management devices. For deep sedation with TIVA, the major contributors were intravenous medications (71.02%) and airway management devices (16.58%). A subgroup study of patients who received sevoflurane only showed the same trend with less variation.

CONCLUSIONS: The patients who received volatile anesthesia were found to have a higher CO2e per case. This difference remained after a subgroup analysis evaluating those patients only receiving sevoflurane and after accounting for the differences in the duration of anesthesia. Data from this study and others should be collectively considered as the healthcare profession aims to provide the best care possible for their patients while limiting the harm caused to the environment.

PMID:38490897 | DOI:10.1053/j.jvca.2024.02.027

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Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Göteborg-2 Prostate Cancer Screening Trial

Eur Urol. 2024 Mar 14:S0302-2838(24)00052-6. doi: 10.1016/j.eururo.2024.01.017. Online ahead of print.

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) and targeted biopsies reduce overdiagnosis of prostate cancer (PC). It is uncertain how this strategy performs for low prostate-specific antigen (PSA) levels.

OBJECTIVE: To investigate the Prostate Imaging Reporting and Data System (PI-RADS) distribution, frequency, and characteristics of screen-detected PC with PSA of 1.8-<3 ng/ml and 3-<10 ng/ml.

DESIGN, SETTING, AND PARTICIPANTS: In the population-based Göteborg-2 screening study, 17974 men choose to participate by having a PSA test (2015-2020). One-third of the participants (n = 6006) were randomized to arm 3, men with a PSA value of ≥1.8 ng/ml were recommended for MRI. Men with positive MRI (PI-RADS 3-5) had four targeted biopsies from each MRI-visible lesion.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinically significant PC was defined as Gleason score ≥3 + 4.

RESULTS AND LIMITATIONS: A total of 6006 men were included. The median age was 55.9 yr (interquartile range [IQR] 52.6-59.6). Of them, 4929 (82%) had PSA of <1.8 ng/ml, 670 (11%) had PSA of 1.8-<3 ng/ml (low-PSA group, median PSA 2.1 ng/ml [IQR 1.9-2.5]), and 377 (6.3%) had PSA of 3-<10 ng/ml (high-PSA group, median PSA 3.9 ng/ml [IQR 3.3-5.0]). PI-RADS scores of 3, 4, and 5 were observed in 7.8%, 15%, and 1.0% of men in the low-PSA group, and in 6.9%, 17%, and 5.3% of men in the high-PSA group, respectively. PC was found in 64 men (41%, 95% confidence interval [CI] 0.33-0.49) with positive MRI findings in the low-PSA group, of whom 33 (21%) had Gleason 6 (insignificant PC) and 31 (20%) had Gleason ≥7 (significant PC). In the high-PSA group, PC was detected in 61 men (56%, 95% CI 0.46-0.66), of whom 26 (24%) had Gleason 6 (insignificant PC) and 35 (32%) had Gleason ≥7 (significant PC). Limitations include results from only a single screening round.

CONCLUSIONS: A non-negligible number of men with PSA 1.8-3 ng/ml have clinically significant PC. Whether a delay in the diagnosis of these tumors until they reached PSA ≥3 ng/ml would impair their chance of cure remains to be evaluated.

PATIENT SUMMARY: We studied screening using prostate-specific antigen (PSA) and magnetic resonance imaging in men with PSA 1.8-3 ng/ml. We found a non-negligible number of potentially harmful prostate cancers in these men.

PMID:38490856 | DOI:10.1016/j.eururo.2024.01.017