Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming.

Stem cell division is linked to tumorigenesis by yet-elusive mechanisms. The hematopoietic system reacts to stress by triggering hematopoietic stem and progenitor cell (HSPC) proliferation, which can be accompanied by chromosomal breakage in activated hematopoietic stem cells (HSCs). However, whether these lesions persist in their downstream progeny and induce a canonical DNA damage response (DDR) remains unclear. Inducing HSPC proliferation by simulated viral infection, we report that the associated DNA damage is restricted to HSCs and that proliferating HSCs rewire their DDR upon endogenous and clastogen-induced damage. Combining transcriptomics, single-cell and single-molecule assays on murine bone marrow cells, we found accelerated fork progression in stimulated HSPCs, reflecting engagement of PrimPol-dependent repriming, at the expense of replication fork reversal. Ultimately, competitive bone marrow transplantation revealed the requirement of PrimPol for efficient HSC amplification and bone marrow reconstitution. Hence, fine-tuning replication fork plasticity is essential to support stem cell functionality upon proliferation stimuli.

A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Haplotype-aware pantranscriptome analyses using spliced pangenome graphs.

Pangenomics is emerging as a powerful computational paradigm in bioinformatics. This field uses population-level genome reference structures, typically consisting of a sequence graph, to mitigate reference bias and facilitate analyses that were challenging with previous reference-based methods. In this work, we extend these methods into transcriptomics to analyze sequencing data using the pantranscriptome: a population-level transcriptomic reference. Our toolchain, which consists of additions to the VG toolkit and a standalone tool, RPVG, can construct spliced pangenome graphs, map RNA sequencing data to these graphs, and perform haplotype-aware expression quantification of transcripts in a pantranscriptome. We show that this workflow improves accuracy over state-of-the-art RNA sequencing mapping methods, and that it can efficiently quantify haplotype-specific transcript expression without needing to characterize the haplotypes of a sample beforehand.

SPIRO - the automated Petri plate imaging platform designed by biologists, for biologists.

Phenotyping of model organisms grown on Petri plates is often carried out manually, despite the procedures being time-consuming and laborious. The main reason for this is the limited availability of automated phenotyping facilities, whereas constructing a custom automated solution can be a daunting task for biologists. Here, we describe SPIRO, the Smart Plate Imaging Robot, an automated platform that acquires time-lapse photographs of up to four vertically oriented Petri plates in a single experiment, corresponding to 192 seedlings for a typical root growth assay and up to 2500 seeds for a germination assay. SPIRO is catered specifically to biologists' needs, requiring no engineering or programming expertise for assembly and operation. Its small footprint is optimized for standard incubators, the inbuilt green LED enables imaging under dark conditions, and remote control provides access to the data without interfering with sample growth. SPIRO's excellent image quality is suitable for automated image processing, which we demonstrate on the example of seed germination and root growth assays. Furthermore, the robot can be easily customized for specific uses, as all information about SPIRO is released under open-source licenses. Importantly, uninterrupted imaging allows considerably more precise assessment of seed germination parameters and root growth rates compared with manual assays. Moreover, SPIRO enables previously technically challenging assays such as phenotyping in the dark. We illustrate the benefits of SPIRO in proof-of-concept experiments which yielded a novel insight on the interplay between autophagy, nitrogen sensing, and photoblastic response.

Identifying Spatial Co-occurrence in Healthy and InflAmed tissues (ISCHIA).

Sequencing-based spatial transcriptomics (ST) methods allow unbiased capturing of RNA molecules at barcoded spots, charting the distribution and localization of cell types and transcripts across a tissue. While the coarse resolution of these techniques is considered a disadvantage, we argue that the inherent proximity of transcriptomes captured on spots can be leveraged to reconstruct cellular networks. To this end, we developed ISCHIA (Identifying Spatial Co-occurrence in Healthy and InflAmed tissues), a computational framework to analyze the spatial co-occurrence of cell types and transcript species within spots. Co-occurrence analysis is complementary to differential gene expression, as it does not depend on the abundance of a given cell type or on the transcript expression levels, but rather on their spatial association in the tissue. We applied ISCHIA to analyze co-occurrence of cell types, ligands and receptors in a Visium dataset of human ulcerative colitis patients, and validated our findings at single-cell resolution on matched hybridization-based data. We uncover inflammation-induced cellular networks involving M cell and fibroblasts, as well as ligand-receptor interactions enriched in the inflamed human colon, and their associated gene signatures. Our results highlight the hypothesis-generating power and broad applicability of co-occurrence analysis on spatial transcriptomics data.

Inflammation-Triggered Enlargement of Choroid Plexus in Subacute COVID-19 Patients with Neurological Symptoms.

OBJECTIVE: To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID-19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association with clinical data. METHODS: Choroid plexus volumes were measured in 28 subacute COVID-19 patients via cerebral magnetic resonance imaging (MRI), compared with those in infection-triggered non-COVID-19 encephalopathy patients (n = 25), asymptomatic individuals after COVID-19 (n = 21), and healthy controls (n = 21). Associations with inflammatory serum markers (peak counts of leukocytes, C-reactive protein [CRP], interleukin 6), an MRI-based marker of barrier dysfunction (CSF volume fraction [V-CSF]), and clinical parameters like olfactory performance and cognitive scores (Montreal Cognitive Assessment) were investigated. RESULTS: COVID-19 patients showed significantly larger choroid plexus volumes than control groups (p < 0.001, η2 = 0.172). These volumes correlated significantly with peak leukocyte levels (p = 0.001, Pearson's r = 0.621) and V-CSF (p = 0.009, Spearman's rho = 0.534), but neither with CRP nor interleukin 6. No significant correlations were found with clinical parameters. INTERPRETATION: In patients with subacute COVID-19, choroid plexus volume is a marker of central nervous system inflammation and barrier dysfunction in the presence of neurologic symptoms. The absence of plexus enlargement in infection-triggered non-COVID-19 encephalopathy suggests a specific severe acute respiratory syndrome coronavirus 2 effect. This study also documents an increase in choroid plexus volume for the first time as a parainfectious event. ANN NEUROL 2024.

Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.

DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination activates an error-free pathway, elusive in mammals, enabling damage bypass by template switching. Fork reversal is driven in vitro by multiple enzymes, including the DNA translocase ZRANB3, shown to bind polyubiquitinated PCNA. However, whether this interaction promotes fork remodeling and template switching in vivo was unknown. Here we show that damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance. Fork reversal in vivo also requires ZRANB3 translocase activity and its interaction with polyubiquitinated PCNA, pinpointing ZRANB3 as a key effector of error-free DNA damage tolerance. Mutations affecting fork reversal also induced unrestrained fork progression and chromosomal breakage, suggesting fork remodeling as a global fork slowing and protection mechanism. Targeting these fork protection systems represents a promising strategy to potentiate cancer chemotherapy.

Structural-functional brain network coupling predicts human cognitive ability.

Individual differences in general cognitive ability (GCA) have a biological basis within the structure and function of the human brain. Network neuroscience investigations revealed neural correlates of GCA in structural as well as in functional brain networks. However, whether the relationship between structural and functional networks, the structural-functional brain network coupling (SC-FC coupling), is related to individual differences in GCA remains an open question. We used data from 1030 adults of the Human Connectome Project, derived structural connectivity from diffusion weighted imaging, functional connectivity from resting-state fMRI, and assessed GCA as a latent g-factor from 12 cognitive tasks. Two similarity measures and six communication measures were used to model possible functional interactions arising from structural brain networks. SC-FC coupling was estimated as the degree to which these measures align with the actual functional connectivity, providing insights into different neural communication strategies. At the whole-brain level, higher GCA was associated with higher SC-FC coupling, but only when considering path transitivity as neural communication strategy. Taking region-specific variations in the SC-FC coupling strategy into account and differentiating between positive and negative associations with GCA, allows for prediction of individual cognitive ability scores in a cross-validated prediction framework (correlation between predicted and observed scores: r = 0.25, p < .001). The same model also predicts GCA scores in a completely independent sample (N = 567, r = 0.19, p < .001). Our results propose structural-functional brain network coupling as a neurobiological correlate of GCA and suggest brain region-specific coupling strategies as neural basis of efficient information processing predictive of cognitive ability.

Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM.

OBJECTIVE: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases. SUMMARY BACKGROUND DATA: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS). METHODS: In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months. RESULTS: The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group. CONCLUSIONS: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

Local adaptation of Pinus leiophylla under climate and land use change models in the Avocado Belt of Michoacán.

Climate change and land use change are two main drivers of global biodiversity decline, decreasing the genetic diversity that populations harbour and altering patterns of local adaptation. Landscape genomics allows measuring the effect of these anthropogenic disturbances on the adaptation of populations. However, both factors have rarely been considered simultaneously. Based on a set of 3660 SNPs from which 130 were identified as outliers by a genome-environment association analysis (LFMM), we modelled the spatial turnover of allele frequencies in 19 localities of Pinus leiophylla across the Avocado Belt in Michoacán state, Mexico. Then, we evaluated the effect of climate change and land use change scenarios, in addition to evaluating assisted gene flow strategies and connectivity metrics across the landscape to identify priority conservation areas for the species. We found that localities in the centre-east of the Avocado Belt would be more vulnerable to climate change, while localities in the western area are more threatened by land conversion to avocado orchards. Assisted gene flow actions could aid in mitigating both threats. Connectivity patterns among forest patches will also be modified by future habitat loss, with central and eastern parts of the Avocado Belt maintaining the highest connectivity. These results suggest that areas with the highest priority for conservation are in the eastern part of the Avocado Belt, including the Monarch Butterfly Biosphere Reserve. This work is useful as a framework that incorporates distinct layers of information to provide a more robust representation of the response of tree populations to anthropogenic disturbances.

Patient-Reported Outcomes in Patients Undergoing Lumpectomy With and Without Defect Closure.

BACKGROUND: The effect of lumpectomy defect repair (a level 1 oncoplastic technique) on patient-reported breast satisfaction among patients undergoing lumpectomy has not yet been investigated. METHODS: Patients undergoing lumpectomy at our institution between 2018 and 2020 with or without repair of their lumpectomy defect during index operation, comprised our study population. The BREAST-Q quality-of-life questionnaire was administered preoperatively, and at 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between those who did and did not have closure of their lumpectomy defect, and compared with surgeon-reported outcomes. RESULTS: A total of 487 patients met eligibility criteria, 206 (42%) had their partial mastectomy defect repaired by glandular displacement. Median breast volume, as calculated from the mammogram, was smaller in patients undergoing defect closure (826 cm3 vs. 895 cm3, p = 0.006). There were no statistically significant differences in satisfaction with breasts (SABTR), physical well-being of the chest (PWB-CHEST), or psychosocial well-being (PsychWB) scores between the two cohorts at any time point. While patients undergoing defect closure had significantly higher sexual well-being (SexWB) scores compared with no closure (66 vs. 59, p = 0.021), there were no predictors of improvement in SexWB scores over time on multivariable analysis. Patients' self-reported scores positively correlated with physician-reported outcomes. CONCLUSIONS: Despite a larger lumpectomy-to-breast volume ratio among patients undergoing defect repair, satisfaction was equivalent among those whose defects were or were not repaired at 2 years postsurgery. Defect repair was associated with clinically relevant improvement in patient-reported sexual well-being.

Examining Race and Patient-Reported Outcomes After Contralateral Prophylactic Mastectomy with Reconstruction.

BACKGROUND: Little is known regarding racial differences in satisfaction and quality of life (QOL) after contralateral prophylactic mastectomy (CPM). In this study, we aim to characterize associations between race, and postoperative satisfaction and well-being, utilizing the validated BREAST-Q patient-reported outcome measure. PATIENTS AND METHODS: Patients were eligible if they were diagnosed with stage 0-III unilateral breast cancer and underwent mastectomy with immediate reconstruction at our institution between 2016 and 2022. BREAST-Q surveys were administered in routine clinical care preoperatively and postoperatively to assess QOL. We assessed whether the relationship between race, and domains of satisfaction with breasts and psychosocial well-being differed by receipt of CPM compared with unilateral mastectomy at 6 months, 1 year, 2 years, and 3 years following reconstruction. RESULTS: Of 3334 women, 2040 (61%) underwent unilateral mastectomy and 1294 (39%) underwent CPM. Compared with White and Asian women who received CPM, Black women who underwent CPM were more likely to have higher BMI (p < 0.001), undergo autologous reconstruction (p = 0.006), and receive postmastectomy radiation (PMRT) (p < 0.001). There was no association between race and domains of satisfaction of breasts or psychosocial well-being for women who underwent unilateral mastectomy (p = 0.6 and p > 0.9, respectively) or CPM (p = 0.8 and p = 0.9, respectively). PMRT was negatively associated with both satisfaction with breasts (p < 0.001) and psychosocial well-being (p = 0.007). CONCLUSIONS: Differences in satisfaction with breasts and psychosocial well-being at 3-year follow-up were not associated with race but rather treatment variables, particularly the receipt of PMRT. Further investigations with a larger and more diverse population are needed to validate these findings.

Frail but Resilient: Frailty in Autologous Breast Reconstruction is Associated with Worse Surgical Outcomes but Equivalent Long-Term Patient-Reported Outcomes.

BACKGROUND: Frailty is associated with higher risk of complications following breast reconstruction, but its impact on long-term surgical and patient-reported outcomes has not been investigated. We examined the association of the five-item modified frailty index (MFI) score with long-term surgical and patient-reported outcomes in autologous breast reconstruction. PATIENTS AND METHODS: We conducted a retrospective cohort study of consecutive patients who underwent mastectomy and autologous breast reconstruction between January 2016 and April 2022. Primary outcome was any flap-related complication. Secondary outcomes were patient-reported outcomes and predictors of complications in the frail cohort. RESULTS: We identified 1640 reconstructions (mean follow-up 24.2 ± 19.2 months). In patients with MFI ≥ 2, the odds of surgical [odds ratio (OR) 2.13, p = 0.023] and medical (OR 17.02, p < 0.001) complications were higher than in nonfrail patients. We found no significant difference in satisfaction with the breast (p = 0.287), psychosocial well-being (p = 0.119), or sexual well-being (p = 0.314) according to MFI score. Chronic obstructive pulmonary disease was an independent predictor of infection (OR 3.70, p = 0.002). Tobacco use (OR 7.13, p = 0.002) and contralateral prophylactic mastectomy (OR 2.36, p = 0.014) were independent predictors of wound dehiscence. Dependent functional status (OR 2.36, p = 0.007) and immediate reconstruction (compared with delayed reconstruction; OR 3.16, p = 0.026) were independent predictors of skin flap necrosis. Dependent functional status was also independently associated with higher odds of reoperation (OR 2.64, p = 0.011). CONCLUSION: Frailty is associated with higher risk of complications in breast reconstruction, but there is no significant difference in long-term patient-reported outcomes. MFI should be considered in breast reconstruction to improve outcomes in high-risk frail patients.

BREAST-Q REACT: Qualitative Assessment of the Design, Functionality, and Clinical Utility of a New Score Interpretation Tool.

BACKGROUND: The BREAST-Q real-time engagement and communication tool (REACT) was developed to aid with BREAST-Q score interpretation and guide patient-centered care. OBJECTIVE: The purpose of this qualitative study was to examine the perspectives of patients and providers on the design, functionality, and clinical utility of REACT and refine the REACT based on their recommendations. METHODS: We conducted three patient focus groups with women who were at least 6 postoperative months from their postmastectomy breast reconstruction, and two provider focus groups with plastic surgeons, breast surgeons, and advanced practice providers. Focus groups were audio-taped, transcribed verbatim, and analyzed thematically. RESULTS: A total of 18 breast reconstruction patients and 14 providers participated in the focus groups. Themes identified by thematic analysis were organized into two categories: (1) design and functionality, and (2) clinical utility. On the design and functionality of REACT, four major themes were identified: visual appeal and usefulness; contextualizing results; ability to normalize patients' experiences, noting participants' concerns; and suggested modifications. On the clinical utility of REACT, three major themes were identified: potential to empower patients to communicate with their providers; increase patient and provider motivation to engage with the BREAST-Q; and effective integration into clinical workflow. CONCLUSION: Patients and providers in this qualitative study indicated that with some modifications, REACT has a great potential to elevate the clinical utility of the BREAST-Q by enhancing patient-provider communication that can lead to patient-centered, clinically relevant action recommendations based on longitudinal BREAST-Q scores.

Regional Blocks Benefit Patients Undergoing Bilateral Mastectomy with Immediate Implant-Based Reconstruction, Even After Discharge.

BACKGROUND: There is limited evidence that regional anesthesia reduces pain in patients undergoing mastectomy with immediate implant-based reconstruction. We sought to determine whether regional blocks reduce opioid consumption and improve post-discharge patient-reported pain in this population. METHODS: We retrospectively reviewed patients who underwent bilateral mastectomy with immediate implant-based reconstruction with and without a regional block. We tested for differences in opioid consumption by block receipt using multivariable ordinal regression, and also assessed routinely collected patient-reported outcomes (PROs) for 10 days postoperatively and tested the association between block receipt and moderate or greater pain. RESULTS: Of 754 patients, 89% received a block. Non-block patients had an increase in the odds of requiring a higher quartile of postoperative opioids. Among block patients, the estimated probability of being in the lowest quartile of opioids required was 25%, compared with 15% for non-block patients. Odds of patient-reported moderate or greater pain after discharge was 0.54 times lower in block patients than non-block patients (p = 0.025). Block patients had a 49% risk of moderate or greater pain compared with 64% in non-block patients on postoperative day 5. There was no indication of any reason for these differences other than a causal effect of the block. CONCLUSION: Receipt of a regional block resulted in reduced opioid use and lower risk of self-reported moderate and higher pain after discharge in bilateral mastectomy with immediate implant-based reconstruction patients. Our use of PROs suggests that the analgesic effects of blocks persist after discharge, beyond the expected duration of a 'single shot' block.

Reducing Disparities: Regional Anesthesia Blocks for Mastectomy with Reconstruction Within Standardized Regional Anesthesia Pathways.

BACKGROUND: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways. PATIENTS AND METHODS: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure. RESULTS: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal. CONCLUSIONS: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations.

Remote Symptom Monitoring with Clinical Alerts Following Mastectomy: Do Early Symptoms Predict 30-Day Surgical Complications.

BACKGROUND: Electronic patient-reported outcome measures (ePROMs) for real-time remote symptom monitoring facilitate early recognition of postoperative complications. We sought to determine whether remote, electronic, patient-reported symptom-monitoring with Recovery Tracker predicts 30-day readmission or reoperation in outpatient mastectomy patients. METHODS: We conducted a retrospective review of breast cancer patients who underwent outpatient (< 24-h stay) mastectomy with or without reconstruction from April 2017 to January 2022 and who received the Recovery Tracker on Days 1-10 postoperatively. Of 5,130 patients, 3,888 met the inclusion criteria (2,880 mastectomy with immediate reconstruction and 1,008 mastectomy only). We focused on symptoms concerning for surgical complications and assessed if symptoms reaching prespecified alert levels-prompting a nursing call-predicted risk of 30-day readmission or reoperation. RESULTS: Daily Recovery Tracker response rates ranged from 45% to 70%. Overall, 1,461 of 3,888 patients (38%) triggered at least one alert. Most red (urgent) alerts were triggered by pain and fever; most yellow (less urgent) alerts were triggered by wound redness and pain severity. The 30-day readmission and reoperation rates were low at 3.8% and 2.4%, respectively. There was no statistically significant association between symptom alerts and 30-day reoperation or readmission, and a clinically relevant increase in risk can be excluded (odds ratio 1.08; 95% confidence interval 0.8-1.46; p = 0.6). CONCLUSIONS: Breast cancer patients undergoing mastectomy with or without reconstruction in the ambulatory setting have a low burden of concerning symptoms, even in the first few days after surgery. Patients can be reassured that symptoms that do present resolve quickly thereafter.

Early Complications in Prepectoral Tissue Expander-Based Breast Reconstruction.

BACKGROUND: Prepectoral implant placement for postmastectomy breast reconstruction has increased in recent years. Benefits of prepectoral reconstruction may include lack of animation deformities and reduced postoperative pain, but its complication profile is currently unclear. This study aimed to examine the complication profile of prepectoral tissue expanders (TEs) to determine factors associated with TE loss. METHODS: A retrospective review was performed to identify all patients who underwent immediate prepectoral TE reconstruction from January 2018 to June 2021. The decision to use the prepectoral technique was based on mastectomy skin quality and patient comorbidities. Patient demographics, comorbidities, and operative details were evaluated. Outcomes of interest included TE loss, seroma, hematoma, infection/cellulitis, mastectomy skin flap necrosis requiring revision, and TE exposure. Logistic regression analysis was performed to identify factors associated with TE loss. RESULTS: The study identified 1225 TEs. The most frequent complications were seroma (8.7%, n = 106), infection/cellulitis (8.2%, n = 101), and TE loss (4.2%, n = 51). Factors associated with TE loss in the univariate analysis included ethnicity, history of smoking, body mass index, mastectomy weight, and neoadjuvant chemotherapy. In the multivariate regression analysis, only mastectomy weight had a positive association with TE loss (odds ratio, 1.001; p = 0.016). CONCLUSION: Prepectoral two-stage breast reconstruction can be performed safely with an acceptable early complication profile. The study data suggest that increasing mastectomy weight is the most significant factor associated with TE loss. Further research examining the quality of the soft tissue envelope and assessing patient-reported outcomes would prove beneficial.