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Nevin Manimala Statistics

Magnetic Resonance Imaging-based T-staging to Predict Biochemical Recurrence after Radical Prostatectomy: A Step Towards the iTNM Classification

Eur Urol Oncol. 2022 Oct 21:S2588-9311(22)00169-9. doi: 10.1016/j.euo.2022.09.005. Online ahead of print.

ABSTRACT

BACKGROUND: Local staging of prostate cancer (PCa) still relies on digital rectal examination (DRE), which therefore remains the standard for risk stratification in guideline recommendations, clinical trials, and patient counseling. This issue is increasingly controversial as multiparametric magnetic resonance imaging (mpMRI) has become the most influential diagnostic tool for local staging of PCa over the past two decades.

OBJECTIVE: To compare various models of T category based on DRE or mpMRI to predict early biochemical recurrence (BCR) after radical prostatectomy (RP).

DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study was conducted between 2014 and 2021. A total of 1436 patients were recruited across eight referral centers in France, Italy, Switzerland, and Belgium.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as two prostate-specific antigen values of ≥0.2 ng/ml during follow-up. Harrell’s concordance index (C index) was used to compare the discrimination of four models of T staging based on DRE (model 1: cT1 vs cT2 vs cT3) or mpMRI (model 2: organ-confined disease vs extracapsular extension [iECE] vs seminal vesicle invasion [iSVI]; model 3: Prostate Imaging-Reporting and Data System [PI-RADS] ≤3 vs PI-RADS 4 vs PI-RADS 5; and model 4: iT2a [PI-RADS ≤3] vs iT2b [PI-RADS 4] vs iT2c [PI-RADS 5 excluding ECE or SVI] vs iT3a [ECE] vs iT3b [SVI]) to predict BCR.

RESULTS AND LIMITATIONS: Overall, 74 (5%), 845 (59%), 482 (34%), and 35 (2%) patients had low-, intermediate-, high-, and very high-risk PCa, respectively, according to the Mazzone risk classification. After median follow-up of 16 mo, 113 patients experienced BCR. Although the new five-group mpMRI-based T classification system (model 4) had the highest prognostic discrimination (C index 0.694) for predicting early BCR on multivariable analysis, there was overlap between the 95% confidence intervals of the models. On sensitivity analysis, the new mpMRI-based T staging still had a higher C index than DRE for predicting BCR when excluding cN1 patients and comparing it with a five-group DRE-based T classification (cT1c vs cT2a vs cT2b vs cT2c vs cT3), but the overlap between the 95% confidence intervals of the models remained. The main limitation is the short follow-up.

CONCLUSIONS: We described an alternative mpMRI-based T staging for prediction of early BCR after RP for PCa. Our results need to be validated externally before they can be applied in clinical practice.

PATIENT SUMMARY: At present, digital rectal examination of the prostate is used to stage prostate cancer. We developed an alternative model for staging that uses information from magnetic resonance imaging (MRI) scans to predict cancer outcomes for men undergoing surgical removal of the prostate.

PMID:36280445 | DOI:10.1016/j.euo.2022.09.005

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Nevin Manimala Statistics

Subcortical and Cortical Electrophysiological Measures in Children With Speech-in-Noise Deficits Associated With Auditory Processing Disorders

J Speech Lang Hear Res. 2022 Oct 24:1-15. doi: 10.1044/2022_JSLHR-22-00094. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to analyze the subcortical and cortical auditory evoked potentials for speech stimuli in children with speech-in-noise (SIN) deficits associated with auditory processing disorder (APD) without any reading or language deficits.

METHOD: The study included 20 children in the age range of 9-13 years. Ten children were recruited to the APD group; they had below-normal scores on the speech-perception-in-noise test and were diagnosed as having APD. The remaining 10 were typically developing (TD) children and were recruited to the TD group. Speech-evoked subcortical (brainstem) and cortical (auditory late latency) responses were recorded and compared across both groups.

RESULTS: The results showed a statistically significant reduction in the amplitudes of the subcortical potentials (both for stimulus in quiet and in noise) and the magnitudes of the spectral components (fundamental frequency and the second formant) in children with SIN deficits in the APD group compared to the TD group. In addition, the APD group displayed enhanced amplitudes of the cortical potentials compared to the TD group.

CONCLUSION: Children with SIN deficits associated with APD exhibited impaired coding/processing of the auditory information at the level of the brainstem and the auditory cortex.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21357735.

PMID:36279585 | DOI:10.1044/2022_JSLHR-22-00094

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Nevin Manimala Statistics

Using a Business Model (the 4 Disciplines of Execution) to Improve Consistency, Efficiency, and Length of Stay in Microvascular Autologous Breast Reconstruction

Ann Plast Surg. 2022 Nov 1;89(5):532-537. doi: 10.1097/SAP.0000000000003292.

ABSTRACT

BACKGROUND: Autologous free tissue transfer is a common method of breast reconstruction in the United States, but it involves many care teams and can incur a large cost on an institution. The consistency and efficiency of performing these procedures can be improved with a method called the 4 disciplines of execution (4DX).

METHODS: Patients that underwent autologous breast reconstruction between 2015 and 2020 were included. Midway through the collection period, several preoperative and intraoperative interventions were implemented using the 4DX. Then, 2 cohorts of patients were analyzed for differences in operative times, length of stay (LOS), and major complications.

RESULTS: Thirty-two total patients were included. The median operative time before interventions were implemented was 828 minutes, and the median operative time after interventions was 619 minutes (P < 0.05). The median LOS in days before interventions was 5 days, and the median LOS after interventions was 3 days (P < 0.05). There were no statistically significant differences in complications before or after the interventions.

CONCLUSIONS: The 4DX successfully improved consistency and efficiency in the process of performing autologous breast reconstruction at our institution, as evidenced by a faster median operative time and shorter patient LOS in the hospital.

PMID:36279579 | DOI:10.1097/SAP.0000000000003292

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Nevin Manimala Statistics

Closed-Incision Negative Pressure Therapy Prevents Major Abdominal Donor-Site Complications in Autologous Breast Reconstruction

Ann Plast Surg. 2022 Nov 1;89(5):529-531. doi: 10.1097/SAP.0000000000003285. Epub 2022 Sep 9.

ABSTRACT

BACKGROUND: Outcomes in autologous breast reconstruction continue to improve with refinements in microsurgical techniques; however, donor-site morbidity remains a concern. Closed-incision negative pressure therapy (ciNPT) has been shown to reduce wound complications. Limited evaluation in abdominal donor sites has shown promising results. We hypothesize that ciNPT will reduce abdominal donor-site complications.

METHODS: A retrospective chart review was performed of patients who underwent abdominally based autologous free tissue transfer for breast reconstruction by 4 microsurgeons at an academic institution from 2015 to 2020. The application of a commercial ciNPT for donor-site management was at the discretion of the operating surgeon. Demographics, operative details, and management of donor-site complications were analyzed.

RESULTS: Four hundred thirty-three patients underwent autologous breast reconstruction; 212 abdominal donor sites were managed with ciNPT and 219 with standard dressings. Demographics were statistically similar between groups. Abdominal wound healing complications were noted in 30.2% of ciNPT patients (64/212) and 22.8% of control patients (50/219, P = 0.08); however, overall wound complications were attributed to obesity on multivariable analysis. Closed-incision negative pressure therapy significantly decreased complications requiring reoperation (ciNPT 6.2%, 4/64; control 26.5%, 13/51; P = 0.004). There were no significant differences in surgical site infection rates (P = 0.73) and rates of abdominal scar revisions (ciNPT 11.8%, 25/212; control 9.1%, 20/219; P = 0.37).

CONCLUSIONS: Use of ciNPT in abdominal donor-site management significantly decreases the incidence of delayed wound healing requiring surgical intervention, with one major wound healing complication prevented for every 6 donor sites managed with ciNPT.

PMID:36279578 | DOI:10.1097/SAP.0000000000003285

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Nevin Manimala Statistics

Hippocampal gamma and sharp wave/ripples mediate bidirectional interactions with cortical networks during sleep

Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2204959119. doi: 10.1073/pnas.2204959119. Epub 2022 Oct 24.

ABSTRACT

Hippocampus-neocortex interactions during sleep are critical for memory processes: Hippocampally initiated replay contributes to memory consolidation in the neocortex and hippocampal sharp wave/ripples modulate cortical activity. Yet, the spatial and temporal patterns of this interaction are unknown. With voltage imaging, electrocorticography, and laminarly resolved hippocampal potentials, we characterized cortico-hippocampal signaling during anesthesia and nonrapid eye movement sleep. We observed neocortical activation transients, with statistics suggesting a quasi-critical regime, may be helpful for communication across remote brain areas. From activity transients, we identified, in a data-driven fashion, three functional networks. A network overlapping with the default mode network and centered on retrosplenial cortex was the most associated with hippocampal activity. Hippocampal slow gamma rhythms were strongly associated to neocortical transients, even more than ripples. In fact, neocortical activity predicted hippocampal slow gamma and followed ripples, suggesting that consolidation processes rely on bidirectional signaling between hippocampus and neocortex.

PMID:36279469 | DOI:10.1073/pnas.2204959119

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Nevin Manimala Statistics

Estimating the total treatment effect in randomized experiments with unknown network structure

Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2208975119. doi: 10.1073/pnas.2208975119. Epub 2022 Oct 24.

ABSTRACT

Randomized experiments are widely used to estimate the causal effects of a proposed treatment in many areas of science, from medicine and healthcare to the physical and biological sciences, from the social sciences to engineering, and from public policy to the technology industry. Here we consider situations where classical methods for estimating the total treatment effect on a target population are considerably biased due to confounding network effects, i.e., the fact that the treatment of an individual may impact its neighbors’ outcomes, an issue referred to as network interference or as nonindividualized treatment response. A key challenge in these situations is that the network is often unknown and difficult or costly to measure. We assume a potential outcomes model with heterogeneous additive network effects, encompassing a broad class of network interference sources, including spillover, peer effects, and contagion. First, we characterize the limitations in estimating the total treatment effect without knowledge of the network that drives interference. By contrast, we subsequently develop a simple estimator and efficient randomized design that outputs an unbiased estimate with low variance in situations where one is given access to average historical baseline measurements prior to the experiment. Our solution does not require knowledge of the underlying network structure, and it comes with statistical guarantees for a broad class of models. Due to their ease of interpretation and implementation, and their theoretical guarantees, we believe our results will have significant impact on the design of randomized experiments.

PMID:36279463 | DOI:10.1073/pnas.2208975119

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Nevin Manimala Statistics

Sea ice fluctuations in the Baffin Bay and the Labrador Sea during glacial abrupt climate changes

Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2203468119. doi: 10.1073/pnas.2203468119. Epub 2022 Oct 24.

ABSTRACT

Sea ice decline in the North Atlantic and Nordic Seas has been proposed to contribute to the repeated abrupt atmospheric warmings recorded in Greenland ice cores during the last glacial period, known as Dansgaard-Oeschger (D-O) events. However, the understanding of how sea ice changes were coupled with abrupt climate changes during D-O events has remained incomplete due to a lack of suitable high-resolution sea ice proxy records from northwestern North Atlantic regions. Here, we present a subdecadal-scale bromine enrichment (Brenr) record from the NEEM ice core (Northwest Greenland) and sediment core biomarker records to reconstruct the variability of seasonal sea ice in the Baffin Bay and Labrador Sea over a suite of D-O events between 34 and 42 ka. Our results reveal repeated shifts between stable, multiyear sea ice (MYSI) conditions during cold stadials and unstable, seasonal sea ice conditions during warmer interstadials. The shift from stadial to interstadial sea ice conditions occurred rapidly and synchronously with the atmospheric warming over Greenland, while the amplitude of high-frequency sea ice fluctuations increased through interstadials. Our findings suggest that the rapid replacement of widespread MYSI with seasonal sea ice amplified the abrupt climate warming over the course of D-O events and highlight the role of feedbacks associated with late-interstadial seasonal sea ice expansion in driving the North Atlantic ocean-climate system back to stadial conditions.

PMID:36279448 | DOI:10.1073/pnas.2203468119

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Nevin Manimala Statistics

Mercury isotopic evidence for the importance of particles as a source of mercury to marine organisms

Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2208183119. doi: 10.1073/pnas.2208183119. Epub 2022 Oct 24.

ABSTRACT

The origin of methylmercury in pelagic fish remains unclear, with many unanswered questions regarding the production and degradation of this neurotoxin in the water column. We used mercury (Hg) stable isotope ratios of marine particles and biota to elucidate the cycling of methylmercury prior to incorporation into the marine food web. The Hg isotopic composition of particles, zooplankton, and fish reveals preferential methylation of Hg within small (< 53 µm) marine particles in the upper 400 m of the North Pacific Ocean. Mass-dependent Hg isotope ratios (δ202Hg) recorded in small particles overlap with previously estimated δ202Hg values for methylmercury sources to Pacific and Atlantic Ocean food webs. Particulate compound specific isotope analysis of amino acids (CSIA-AA) yield δ15N values that indicate more-significant microbial decomposition in small particles compared to larger particles. CSIA-AA and Hg isotope data also suggest that large particles (> 53 µm) collected in the equatorial ocean are distinct from small particles and resemble fecal pellets. Additional evidence for Hg methylation within small particles is provided by a statistical mixing model of even mass-independent (Δ200Hg and Δ204Hg) isotope values, which demonstrates that Hg within near-surface marine organisms (0-150 m) originates from a combination of rainfall and marine particles. In contrast, in meso- and upper bathypelagic organisms (200-1,400 m), the majority of Hg originates from marine particles with little input from wet deposition. The occurrence of methylation within marine particles is supported further by a correlation between Δ200Hg and Δ199Hg values, demonstrating greater overlap in the Hg isotopic composition of marine organisms with marine particles than with total gaseous Hg or wet deposition.

PMID:36279440 | DOI:10.1073/pnas.2208183119

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Nevin Manimala Statistics

Decadal migration phenology of a long-lived Arctic icon keeps pace with climate change

Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2121092119. doi: 10.1073/pnas.2121092119. Epub 2022 Oct 24.

ABSTRACT

Animals migrate in response to seasonal environments, to reproduce, to benefit from resource pulses, or to avoid fluctuating hazards. Although climate change is predicted to modify migration, only a few studies to date have demonstrated phenological shifts in marine mammals. In the Arctic, marine mammals are considered among the most sensitive to ongoing climate change due to their narrow habitat preferences and long life spans. Longevity may prove an obstacle for species to evolutionarily respond. For species that exhibit high site fidelity and strong associations with migration routes, adjusting the timing of migration is one of the few recourses available to respond to a changing climate. Here, we demonstrate evidence of significant delays in the timing of narwhal autumn migrations with satellite tracking data spanning 21 y from the Canadian Arctic. Measures of migration phenology varied annually and were explained by sex and climate drivers associated with ice conditions, suggesting that narwhals are adopting strategic migration tactics. Male narwhals were found to lead the migration out of the summering areas, while females, potentially with dependent young, departed later. Narwhals are remaining longer in their summer areas at a rate of 10 d per decade, a similar rate to that observed for climate-driven sea ice loss across the region. The consequences of altered space use and timing have yet to be evaluated but will expose individuals to increasing natural changes and anthropogenic activities on the summering areas.

PMID:36279424 | DOI:10.1073/pnas.2121092119

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Nevin Manimala Statistics

Sugammadex Versus Neostigmine for Recovery of Respiratory Muscle Strength Measured by Ultrasonography in the Postextubation Period: A Randomized Controlled Trial

Anesth Analg. 2022 Oct 24. doi: 10.1213/ANE.0000000000006219. Online ahead of print.

ABSTRACT

BACKGROUND: Although sugammadex is well known for its use in reducing the incidence of residual neuromuscular blockade, this has not always been translated to improved clinical measures of postoperative respiratory muscle strength. Expiratory muscles play an important role in airway clearance and inspiratory muscle capacity augmentation, yet they have not been well studied. Therefore, we tested the hypothesis on whether sugammadex could enhance expiratory muscle strength recovery more completely than neostigmine in the immediate postextubation period.

METHODS: Adult patients having microlaryngeal surgery under total intravenous anesthesia were randomized to receive sugammadex or neostigmine. The thickening fraction of internal oblique abdominal muscle (TFIO) and diaphragm excursion, respectively, reflecting expiratory and inspiratory muscle strength, were measured via ultrasonography at 3 time points: before induction (baseline), train-of-four ratio (TOFR) recovery to 0.9, and 30 minutes after postanesthesia care unit (PACU) arrival. The primary outcome was the change in TFIO from baseline to TOFR ≥0.9. The postoperative changes of diaphragm excursion from baseline, incidences of TFIO and diaphragm excursion returning to baseline levels, and the time from TOFR 0.9 to 0.95 and 1 were also measured.

RESULTS: Among 58 patients, a significant difference in the change in TFIO from baseline to TOFR ≥0.9 between the sugammadex and neostigmine groups was observed: mean ± standard deviation, 9% ± 6% vs 16% ± 9%; difference in means: -6% (95% confidence interval [CI], -10 to -2); and adjusted P =.005 (adjusting for imbalanced variables between 2 groups). Sugammadex resulted in smaller changes in diaphragm excursion from baseline to TOFR ≥0.9 compared with neostigmine: difference in means: -0.83 cm (99.4% CI, -1.39 to -0.28 cm; Bonferroni-corrected P < .001). After 30 minutes in the postanesthesia care unit (PACU),33% of patients reversed with sugammadex versus 14% of those receiving neostigmine reached baseline TFIO levels (99.4% CI, -14 to 52; Bonferroni-corrected P > .999). The incidences of TFIO and diaphragm excursion returning to baseline were relatively low (<40%) in both groups despite TOFR reaching 1. The median time from TOFR of 0.9 to 0.95 and to 1 among patients receiving sugammadex was 7 and 10× faster than those receiving neostigmine (0.3 vs 2 minutes, Bonferroni-corrected P = .003; 0.5 vs 5.3 minutes, Bonferroni-corrected P < .001, respectively).

CONCLUSIONS: Sugammadex provides a more complete recovery of expiratory muscle strength than neostigmine at TOFR ≥0.9. Our data suggest that the respiratory muscle strength might still be impaired despite TOFR reaching 1.

PMID:36279410 | DOI:10.1213/ANE.0000000000006219