Use of Subfascial Passive Bile Bag Drainage for the Management of Durotomies in Spine Surgery.

INTRODUCTION: Historically, the use of subfascial drains for the management of durotomies was avoided due to concerns about the creation of cerebrospinal fluid (CSF) fistulas. Currently, there are limited series utilizing subfascial drainage for CSF leak management, many of which utilize suction drainage. We report our experience with the use of subfascial passive drainage in the management of such leaks. OBJECTIVE: To demonstrate the efficacy of a passive subfascial bile bag for diversion of CSF post-operatively in concert with a post-operative head of bed (HOB) protocol for the management of durotomies in spine surgery. METHODS: We performed a retrospective chart review of patients who underwent spinal surgery at a single institution performed by one surgeon. Cases utilizing a passive subfascial bile bag for durotomies were identified. A total of 1,882 consecutive surgeries were reviewed, and 108 met the inclusion criteria. The primary outcome was return to the operating room (OR) and/or the need for lumbar drain placement. Patient sociodemographic information and pre-, intra-, and post-operative clinical characteristics were reviewed. RESULTS: A total of 108 patients underwent subfascial bile bag CSF diversion after intra-operative durotomy. Four patients (3.7%) experienced post-operative CSF leakage requiring lumbar drain placement, while only two (1.9%) patients required a return to the OR. One patient returned to the OR for symptomatic pseudomeningocele and the other for ongoing CSF drainage from their wound. CONCLUSION:  Durotomies are known to increase complication rates, including reoperation. The use of subfascial passive bile bag drainage in concert with a post-operative HOB protocol is a safe and effective manner to manage durotomies while minimizing the need for reoperation.

Increasing Prevalence of Diagnosed Gestational Diabetes in South Carolina: 2015-2021.

Objective: To examine trends with a focus on racial and ethnic disparities in reported gestational diabetes mellitus (GDM) and related outcomes (macrosomia, large for gestational age infants) before and during the COVID-19 pandemic in South Carolina (SC). Methods: A retrospective cohort study of pregnancies resulting in livebirths from 2015 through 2021 was conducted in SC. Statewide maternal hospital and emergency department discharge codes were linked to birth certificate data. GDM was defined by ICD-9-CM (i.e., 648.01-648.02, 648.81-648.82) or ICD-10-CM codes (i.e., O24.4, O24.1, O24.9), or indication of GDM on the birth certificate without evidence of diabetes outside pregnancy (ICD-9-CM: 250.xx; ICD-10-CM: E10, E11, O24.0, O24.1, O24.3). Results: Our study included 194,777 non-Hispanic White (White), 108,165 non-Hispanic Black (Black), 25,556 Hispanic, and 16,344 other race-ethnic group pregnancies. The relative risk for GDM associated with a 1-year increase was 1.01 (95% confidence interval [CI]: 1.01-1.02) before the pandemic and 1.12 (1.09-1.14) during the pandemic. While there were race-ethnic differences in the prevalence of GDM, increasing trends were similar across all race-ethnic groups before and during the pandemic. From quarter 1, 2020, to quarter 4, 2021, the prevalence of reported GDM increased from 8.92% to 10.85% in White, from 8.04% to 9.78% in Black, from 11.2% to 13.65% in Hispanic, and from 13.3% to 16.16% in other race-ethnic women. Conclusion: An increasing prevalence of diagnosed GDM was reported during the COVID-19 pandemic. Future studies are needed to understand the mechanisms underlying increasing trends, to develop interventions, and to determine whether the increasing trend continues in subsequent years.

E-cigarette exposure disrupts antitumor immunity and promotes metastasis.

Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.

Time-resolved NMR detection of prolyl-hydroxylation in intrinsically disordered region of HIF-1α.

Prolyl-hydroxylation is an oxygen-dependent posttranslational modification (PTM) that is known to regulate fibril formation of collagenous proteins and modulate cellular expression of hypoxia-inducible factor (HIF) α subunits. However, our understanding of this important but relatively rare PTM has remained incomplete due to the lack of biophysical methodologies that can directly measure multiple prolyl-hydroxylation events within intrinsically disordered proteins. Here, we describe a real-time 13C-direct detection NMR-based assay for studying the hydroxylation of two evolutionarily conserved prolines (P402 and P564) simultaneously in the intrinsically disordered oxygen-dependent degradation domain of hypoxic-inducible factor 1α by exploiting the "proton-less" nature of prolines. We show unambiguously that P564 is rapidly hydroxylated in a time-resolved manner while P402 hydroxylation lags significantly behind that of P564. The differential hydroxylation rate was negligibly influenced by the binding affinity to prolyl-hydroxylase enzyme, but rather by the surrounding amino acid composition, particularly the conserved tyrosine residue at the +1 position to P564. These findings support the unanticipated notion that the evolutionarily conserved P402 seemingly has a minimal impact in normal oxygen-sensing pathway.

Outcomes by best response with hypomethylating agent plus venetoclax in adults with previously untreated acute myeloid leukemia.

INTRODUCTION: We aimed to compare outcomes of patients with AML treated with frontline hypomethylating agent and venetoclax (HMA + Ven) who achieved complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) as defined by ELN 2022. METHODS: Patients with AML seen at Moffitt Cancer Center between 2018 and 2022 and treated with HMA + Ven were retrospectively evaluated. RESULTS: About 120 patients achieved blast clearance with best response of CR in 52 (43.3%), CRh in 22 (18.3%), CRi in 31 (25.8%) and MLFS in 15 (12.5%) patients. Greater proportion of patients with MLFS had a prior myeloid malignancy (p = 0.003) and were treated with prior HMA (p < 0.001). Patients that achieved MLFS as their best response had inferior OS compared to the CR/CRh/CRi cohort (8 months vs. 27 months; p < 0.001). RFS was also worse for the MLFS cohort. CONCLUSION: To the best of our knowledge, this is the largest study analyzing differences in outcomes of AML patients treated with HMA + Ven based on best response. We noted that prior myeloid malignancy and use of HMA led to more MLFS as best response compared to CR/CRi. The OS and RFS were inferior for MLFS cohort.

Purpose in life and stress: Momentary associations from a micro-longitudinal study.

Purpose in life is an aspect of well-being associated with less subjective stress. The present research sought to expand this literature by testing the association between both dispositional and momentary purpose with stress in daily life using a micro-longitudinal study design. Participants (N = 303) reported their dispositional purpose at baseline and reported their momentary purpose and stress three times a day for 8 days. Between-person, dispositional purpose was associated with less momentary stress across the 8 days tested with linear regression (ß = -0.29, 95% CI = -0.39, -18, p < 0.001); it was unrelated to variability in stress (ß = 0.05, 95% CI = -0.05, 0.14, p = 0.310). In contrast, the within-person analysis tested with multilevel modelling indicated that in moments when participants felt more purpose-driven than their average, they felt more stressed (b = 0.09, 95% CI = 0.06, 0.12, SE = 0.01, p < 0.001). This association was slightly stronger among participants with relatively lower dispositional purpose (binteraction = -0.04, SE = 0.02, 95% CI = -0.08, -0.01, p = 0.032). This study replicated the negative association between dispositional purpose and subjective stress when stress was measured at moments in daily life. It also found that feeling more purpose-driven than usual in the moment is stressful, a counterintuitive finding that, if replicated, suggests that striving for purpose can be stressful in the moment, even if feeling more purposeful in general is associated with lower stress.

One-step genome engineering in bee gut bacterial symbionts.

Mechanistic understanding of interactions in many host-microbe systems, including the honey bee microbiome, is limited by a lack of easy-to-use genome engineering approaches. To this end, we demonstrate a one-step genome engineering approach for making gene deletions and insertions in the chromosomes of honey bee gut bacterial symbionts. Electroporation of linear or non-replicating plasmid DNA containing an antibiotic resistance cassette flanked by regions with homology to a symbiont genome reliably results in chromosomal integration. This lightweight approach does not require expressing any exogenous recombination machinery. The high concentrations of large DNAs with long homology regions needed to make the process efficient can be readily produced using modern DNA synthesis and assembly methods. We use this approach to knock out genes, including genes involved in biofilm formation, and insert fluorescent protein genes into the chromosome of the betaproteobacterial bee gut symbiont Snodgrassella alvi. We are also able to engineer the genomes of multiple strains of S. alvi and another species, Snodgrassella communis, which is found in the bumble bee gut microbiome. Finally, we use the same method to engineer the chromosome of another bee symbiont, Bartonella apis, which is an alphaproteobacterium. As expected, gene knockout in S. alvi using this approach is recA-dependent, suggesting that this straightforward procedure can be applied to other microbes that lack convenient genome engineering methods. IMPORTANCE: Honey bees are ecologically and economically important crop pollinators with bacterial gut symbionts that influence their health. Microbiome-based strategies for studying or improving bee health have utilized wild-type or plasmid-engineered bacteria. We demonstrate that a straightforward, single-step method can be used to insert cassettes and replace genes in the chromosomes of multiple bee gut bacteria. This method can be used for investigating the mechanisms of host-microbe interactions in the bee gut community and stably engineering symbionts that benefit pollinator health.

Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community.

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.

Planar Disk µ-Aptasensors by Monolayer Assembly in a Dissolving Microdroplet.

Electrochemical aptamer-based sensors provide a highly modular platform for real-time monitoring of small molecules. Their ability to selectively recognize target molecules in complex environments like biological fluids makes them an attractive technology for the analysis of micro- and nanoscale systems. The signal-to-noise of the measurement depends on the electroactive surface (i.e., how many aptamers one can place), which has previously precluded miniaturization of aptamer-based sensors to planar disk ultramicroelectrodes (r ∼ 5-10 µm). Here, we employ a concentration enrichment strategy based on the active dissolution of an aqueous, aptamer-containing microdroplet on an ultramicroelectrode submerged in an organic continuous phase (1,2-dichloroethane). We show consistent voltammetric signal increase as a function of droplet lifetime, indicating the successful immobalization of the thiol-terminated aminoglycoside aptamers to the electrode surface. We observe a diagnostic methylene blue peak and 10-fold increase in current magnitude as compared to bare microelectrodes. We report robust sensor behavior with a linear dynamic range extending from milli- to micromolar concentrations of kanamycin in buffer. This research offers a successful method for optimized electrochemical aptamer-based sensor fabrication and miniaturization on ultramicroelectrodes without the need for electrode surface area enhancement.

An Update on the Independent Plastic Surgery Match (2019-2022): Trends, Predictors, and Program Leaders' Perspectives.

Background: A previous study by the authors noted a decline in independent plastic surgery residency programs and rising applicant participation. This study provides updates on match trends and influential predictors, and gathers program leaders' views on the future of the independent track. Methods: Match data (2019-2022) were obtained from the San Francisco match after American Council of Educators in Plastic Surgery approval. Variables influencing match success were analyzed, and program leaders were surveyed about desirable applicant traits and program trajectories. Results: From 2019 to 2022, 243 of 428 applicants matched. Programs and positions declined by 10% and 9.5%, respectively. Applicants rose to 42.3%, but match rates fell from 82% to 56%. Osteopathic graduates doubled, whereas international graduates increased to 53.8%. Successful matches were associated with US allopathic medical school graduates, university-affiliated general surgery residencies, eight or more interviews, United States Medical Licensing Examination scores greater than 230, and high post graduate year (PGY)1-3 American Board of Surgery In-service Training Examination scores (PGY1-64.7%, PGY2-61.2%, PGY3-60.7%; P < 0.05). Of surveyed programs, 55.6% aimed to continue running the independent track in the next year. Conversely, 7.4% planned to discontinue in the next year, 22.2% within 2-5 years, 7.4% within the next decade, and 7.4% were unsure. Conclusions: Although support for the independent plastic surgery track remains, program participation diminishes as applicant interest increases, intensifying match challenges. Increasing number of interviews improves match potential. Program leaders display varied commitments, with looming plans for some programs to discontinue offering this track. Applicant evaluation pivots on strong recommendations, research, and test scores.

Medical tattooing as a complementary cosmetic intervention to reduce body-image distress and mental health symptoms in U.S. breast cancer survivors.

PURPOSE: A review of the literature revealed a high incidence of body-image distress among breast cancer survivors who had surgery. This cross-sectional study examined the relationship between medical tattooing as a complementary cosmetic intervention and body-image distress and mental health outcomes among breast cancer survivors following surgery. METHODS: We examined 330 post-surgical breast cancer survivors collected through a nationwide online survey in the U.S., pursuing two main objectives. First, we investigated body-image distress, depression and anxiety symptoms, and perceived stress in survivors who underwent breast cancer surgery, comparing those with medical tattooing (n = 89) and those without (n = 226). Second, we assessed the influence of the participant's surgery type on body-image distress, depression and anxiety symptoms, and perceived stress. Additionally, we evaluated whether individual factors, such as appearance investment, satisfaction with decision, and cosmetic expectation discrepancy, predicted the participant's body-image distress. RESULTS: Findings suggest that participants with medical tattoos reported significantly lower body-image distress, depression and anxiety symptoms, and perceived stress compared to those without medical tattoos. The participant's surgery type did not significantly predict body-image distress, depression or anxiety symptoms, or perceived stress. However, participants who reported greater appearance investment endorsed higher body-image distress. Participants who reported higher satisfaction with their treatment decisions and lower cosmetic expectation discrepancy endorsed lower body-image distress. CONCLUSION: Medical tattooing may be a valuable tool in improving body-image distress and mental health for those who wish to pursue it, but more research is needed. Empirical studies supporting the mental health benefits of medical tattooing among survivors are crucial to standardize insurance coverage and promote its inclusion as a complementary intervention across insurance providers nationwide. This complementary intervention should be considered using a patient-centered approach that aligns with the patient's values and preferences.

Knot Security 101: A Comprehensive Practical Review to Optimal Knot Configuration, Pulling Direction, Throw Count, and Tail Length.

Background: Knots are the weakest structural point in a suture line and inevitably weaken almost all suture materials. This practical review critically evaluates the factors, such as suture material properties, gauge, configuration, throw count, and tail length, that affect knot security. Methods: A PubMed search between the years 1934 and 2023 identified relevant studies that addressed factors relating to knot security. Studies that investigated knots and sutures solely used in laparoscopic and arthroscopic surgery were excluded. Knot configurations assessed were the Aberdeen, sliding, square, and surgeon's. Results: Eighty-six articles were included in this review article and demonstrated that knot security varies greatly between suture materials and gauge. Knot security also varies by configuration, throw count, conditions, tail length, and stitch type. Throw count differs by knot configuration, with the Aberdeen knot being most secure with three throws and one to two turns compared with three to five throws for surgeon's and square knots. The optimal tail length was 3 mm. Conclusions: This practical review demonstrates that there are significant differences in knot security based on a variety of factors. It is challenging to propose an ideal knot because most studies did not evaluate knot security using a broad variety of suture materials, gauges, and throws for each of the most common knots. Although this review article demonstrated several applicable findings, additional robust studies are needed to simplify proposals.

Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.

Label-free, real-time monitoring of membrane binding events at zeptomolar concentrations using frequency-locked optical microresonators.

G-protein coupled receptors help regulate cellular function and communication, and are targets of small molecule drug discovery efforts. Conventional techniques to probe these interactions require labels and large amounts of receptor to achieve satisfactory sensitivity. Here, we use frequency-locked optical microtoroids for label-free characterization of membrane interactions in vitro at zeptomolar concentrations for the kappa opioid receptor and its native agonist dynorphin A 1-13, as well as big dynorphin (dynorphin A and dynorphin B) using a supported biomimetic membrane. The measured affinity of the agonist dynorphin A 1-13 to the κ-opioid receptor was also measured and found to be 3.1 nM. Radioligand assays revealed a dissociation constant in agreement with this value (1.1 nM). The limit of detection for the κOR/DynA 1-13 was calculated as 180 zM. The binding of Cholera Toxin B-monosialotetrahexosyl ganglioside was also monitored in real-time and an equilibrium dissociation constant of 1.53 nM was found. Our biosensing platform provides a method for highly sensitive real-time characterization of membrane embedded protein binding kinetics that is rapid and label-free, for drug discovery and toxin screening among other applications.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.

BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Level of evidence in high impact surgical literature: the way forward.

Evidence-based medicine stipulates that clinical decision-making should revolve around scientific evidence. The goal of the present study is to evaluate the methodological quality of surgical research recently published in JAMA Surgery, International Journal of Surgery, and British Journal of Surgery, the three surgical journals with the highest impact factor. An electronic search of the PUBMED database was performed to retrieve all articles published in the JAMA Surgery, International Journal of Surgery, and British Journal of Surgery in the year 2022. Three authors independently reviewed all retrieved articles and methodological designs of the publications were analyzed and rated using a modification of the Oxford Centre for Evidence-Based Medicine Levels of Evidence (Oxford Levels of Evidence scale). The initial search identified 1236 articles of which 809 were excluded after title and abstract screening. The remaining 427 underwent full text/methods read, of which 164 did not meet the inclusion/exclusion criteria. A total of 273 studies were included in the analysis. The average level of evidence was 2.5 ± 0.8 across all studies assessed. The majority of study designs were comprised of retrospective cohorts (n = 119), prospective cohorts (n = 47), systematic reviews of non RCTs (n = 39), and RCTs (n = 37). There was no significant difference in the average level of evidence between the top three journals (p = 0.50). Most clinical studies in the highest impact factor surgical journals are of level III evidence, consistent with earlier literature. However, our analysis demonstrates a relatively higher percentage of LOE I and II compared to what was previously published in the literature.