Nevin Manimala

J Pediatr Surg. 2022 Sep 26:S0022-3468(22)00610-8. doi: 10.1016/j.jpedsurg.2022.09.022. Online ahead of print.

ABSTRACT

PURPOSE: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown to impact pulmonary vascular development and remodeling in experimental congenital diaphragmatic hernia (CDH), with secondary structural cardiac effects. We sought to determine whether TRASCET has any functional impact on term fetal pulmonary hemodynamics in the nitrofen model.

METHODS: Time-dated pregnant rat dams (n = 13) received nitrofen on gestational day 9 (E9) to induce fetal CDH. Fetuses (n = 155) were divided into three groups: untreated (n = 45), and two groups receiving volume-matched intra-amniotic injections on E17 of either saline (sham; n = 46), or a suspension of amniotic fluid-derived MSCs (afMSCs) (TRASCET; n = 64). Donor afMSCs were syngeneic, phenotyped by flow cytometry, and “primed” by exposure to interferon-gamma and interleukin-1beta prior to administration in vivo. At term (E21), fetuses underwent Doppler flow assessment at the mid-pulmonary artery and 4-chamber echocardiogram. Pulmonary vascular resistance was estimated by pulmonary artery acceleration time (PAAT), max velocity (MaxV) and velocity time integral (VTI). Cardiac function was assessed by global longitudinal strain (GLS) and ejection fraction (EF) using speckle analyses. Healthy fetuses (n = 11) served as additional controls. Statistical analysis was by the Mann-Whitney U test RESULTS: High resolution ultrasound data could be obtained from 8 to 13 fetuses per group. The PAAT and the PAAT normalized to cardiac cycle time were significantly improved by TRASCET compared to both untreated and sham-treated CDH (p = 0.004 to <0.001 in all pairwise comparisons). The flow profile sharpness (MaxV:VTI) was increased in untreated (p = 0.06) and sham (p = 0.01) groups but normalized by TRASCET (p<0.01). There was no difference in GLS between TRASCET and either the untreated or sham groups (p = 0.25 to p = 0.93).

CONCLUSION: Transamniotic stem cell therapy improves pulmonary vascular resistance in early term fetuses in the Nitrofen model of congenital diaphragmatic hernia. Further focus on the functional pulmonary hemodynamic impact of this therapy is justified.

LEVEL OF EVIDENCE: N/A (animal and laboratory study).

PMID:36280468 | DOI:10.1016/j.jpedsurg.2022.09.022

J Pediatr Surg. 2022 Sep 26:S0022-3468(22)00628-5. doi: 10.1016/j.jpedsurg.2022.09.035. Online ahead of print.

ABSTRACT

INTRODUCTION: There are existing healthcare disparities in pediatric surgery today. Identity and racial incongruity between patients and providers contribute to systemic healthcare inequities and negatively impacts health outcomes of minoritized populations. Understanding the current demographics of the American Pediatric Surgical Association and therefore the cognitive diversity represented will help inform how best to strategically build the organization to optimize disparity solutions and improve patient care.

METHODS: 1558 APSA members were sent an anonymous electronic survey. Comparative data was collected from the US Census Bureau and the Association of American Medical Colleges. Results were analyzed using standard statistical tests.

RESULTS: Of 423 respondents (response rate 27%), the race and ethnicity composition were 68% non Hispanic White, 12% Asian American and Pacific Islander, 6% Hispanic, 5% multiracial, and 4% Black/African American. Respondents were 35% women, 63% men, and 1% transgender, androgyne, or uncertain. Distribution of sexual identity was 97% heterosexual and 3% LGBTQIA. Religious identity was 50% Christian, 22% Agnostic/Atheist, 11% Jewish, 3% Hindu, and 2% Muslim. 32% of respondents were first-generation Americans. Twenty-four different primary languages were spoken, and 46% of respondents were conversational in a second language. These findings differ in meaningful ways from the overall American population and from the population of matriculants in American medical schools.

CONCLUSION: There are substantial differences in the racial, gender, and sexual identity composition of APSA members compared with the overall population in the United States. To achieve excellence in patient care and innovate solutions to existing disparities, representation, particularly in leadership is essential.

TYPE OF STUDY: Survey; original research.

LEVEL OF EVIDENCE: Level IV.

PMID:36280465 | DOI:10.1016/j.jpedsurg.2022.09.035

Trends Neurosci. 2022 Oct 21:S0166-2236(22)00188-6. doi: 10.1016/j.tins.2022.09.009. Online ahead of print.

ABSTRACT

The correlation coefficient gauges linear association between two variables. However, interpreting its value depends on the question at hand. This article argues that relying on the correlation coefficient may be irrelevant for many neuroscience research tasks. When the experimental dataset is contextually suitable for binning-averaging, other indicators of statistical association could prove more suitable.

PMID:36280457 | DOI:10.1016/j.tins.2022.09.009

Eur Urol Oncol. 2022 Oct 21:S2588-9311(22)00170-5. doi: 10.1016/j.euo.2022.09.006. Online ahead of print.

ABSTRACT

BACKGROUND: Approximately 20-40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020).

OBJECTIVE: To evaluate and validate the updated NRG 2020 guideline with our established LN atlas.

DESIGN, SETTING, AND PARTICIPANTS: We screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10-90%), or outside (<10%).

RESULTS AND LIMITATIONS: In comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results.

CONCLUSIONS: The updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread.

PATIENT SUMMARY: We compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

PMID:36280446 | DOI:10.1016/j.euo.2022.09.006

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

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

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

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

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

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