A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

Effective Risk Assessment for Distal Radius Fractures: A Rigorous Multivariable Regression Analysis, Using a Novel 8-Item Modified Frailty Index.

Introduction Distal radius fractures (DRFs) are among the most common orthopaedic injuries. The prevalence of DRFs is increasing across all age groups but remains the second most common fracture in the elderly. The modified frailty index (MFI) often predicts morbidity and mortality in orthopaedic injuries. This study aims to determine the predictive value of MFI on complication rates following DRF and the patient length of stay and discharge outcomes. Methods We utilized our MFI to perform a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Results In a total of 22,313 patients, the average age was 46 ± 16. An increase in MFI led to an increase in the odds ratio of readmission and reoperation ( p < 0.001). MFI predicted complications, doubling the rate as the score increased from 1 to 2 ( p < 0.001). An MFI of 2 also led to a delayed hospital stay of 5 days ( p < 0.001), as well as an increase in the odds of patients not being sent home at discharge ( p < 0.001). Finally, life-threatening complications were also predicted with an increased MFI, the odds of a life-threatening complication increasing 488.20 times at an MFI of 3 ( p < 0.001). Discussion and Conclusion While surgical decision-making for frail patients with DRFs remains contentious, this novel 8-item MFI score was significantly associated with the probability of hospital readmission/reoperation, postoperative complications, and delayed hospital length of stay. Three new parameters were incorporated into our 8-item score compared with the conventional 5; hypoalbuminemia status (< 3.5 mg/dL), previous diagnosis of osteoporosis, and severe obesity (body mass index > 35) enhancing its sensitivity. Future studies are warranted for its prospective utility in ruling out postsurgical comorbidity.

Rates and Characteristics of Patients Leaving against Medical Advice after Spine Surgery.

Introduction: Leaving against medical advice (AMA) has been associated with higher rates of readmission and worse postoperative outcomes in various surgical fields. Patients who have undergone spine surgery often require careful postoperative follow-up to ensure an uncomplicated recovery. In this study, we aim to investigate the demographic and hospital variables that may have contributed to patients leaving the hospital AMA following spine surgery. Methods: We performed a retrospective analysis of patients receiving spine surgery; we used the data from the Healthcare Cost and Utilization Project (HCUP) database for the years 2011-2020. Demographics, household income status, insurance status, time from admission to operation, length of stay, length of recovery, and discharge disposition were collected and analyzed. Multivariate linear regression was used to determine the odds ratios of each factor and their association to patient decision of leaving AMA. Results: As per our findings, patients aged 30-49 had 1.666 times greater odds of leaving AMA following spine surgery (P<0.001), patients aged 50-64 had 1.222 times greater odds of leaving AMA (P=0.001), and patients older than 65 had 0.490 times lesser odds of leaving AMA (P<0.001). Additionally, black patients were 1.612 times more likely to leave AMA (P<0.001), whereas white patients were 0.675 times less likely to do so (<0.001). Women were 0.555 times less likely to leave AMA than the rest of the population (P<0.001). Moreover, patients with private insurance were 0.268 times less likely to leave AMA (P<0.001), while patients on Medicare and Medicaid were 1.692 times (P<0.001) and 3.958 times more likely to leave AMA (P<0.001) following spine surgery, respectively. Finally, patients in the lowest quartile of income were 1.691 times more likely to leave AMA (P<0.001), while patients in the higher quartile of income were 0.521 times less likely to do so (P<0.001). Conclusions: It is critical that spine surgeons are aware of the factors that predispose patients to leave AMA in order to mitigate postoperative complications.

Characterizing a panel of amino acid auxotrophs under auxotrophic starvation conditions.

Auxotrophic strains starving for their cognate nutrient, termed auxotrophic starvation, are characterized by a shorter lifespan, higher glucose wasting phenotype, and inability to accomplish cell cycle arrest when compared to a "natural starvation," where a cell is starving for natural environmental growth-limiting nutrients such as phosphate. Since evidence of this physiological response is limited to only a subset of auxotrophs, we evaluated a panel of auxotrophic mutants to determine whether these responses are characteristic of a broader range of amino acid auxotrophs. Based on the starvation survival kinetics, the panel of strains was grouped into three categories-short-lived strains, strains with survival similar to a prototrophic wild type strain, and long-lived strains. Among the short-lived strains, we observed that the tyrosine, asparagine, threonine, and aspartic acid auxotrophs rapidly decline in viability, with all strains unable to arrest cell cycle progression. The three basic amino acid auxotrophs had a survival similar to a prototrophic strain starving in minimal media. The leucine, tryptophan, methionine, and cysteine auxotrophs displayed the longest lifespan. We also demonstrate how the phenomenon of glucose wasting is limited to only a subset of the tested auxotrophs, namely the asparagine, leucine, and lysine auxotrophs. Furthermore, we observed pleiotropic phenotypes associated with a subgroup of auxotrophs, highlighting the importance of considering unintended phenotypic effects when using auxotrophic strains especially in chronological aging experiments.

Solid-to-liquid phase transition in the dissolution of cytosolic misfolded-protein aggregates.

Accumulation of protein aggregates is a hallmark of cellular aging and degenerative disorders. This could result from either increased protein misfolding and aggregation or impaired dissolution of aggregates formed under stress, the latter of which is poorly understood. In this study, we employed quantitative live-cell imaging to investigate the dynamic process of protein disaggregation in yeast. We show that protein aggregates formed upon heat stress are solid condensates, but after stress attenuation these protein aggregates first transition into a liquid-like state during their dissolution. This solid-to-liquid phase transition (SLPT) accompanies the reduction in aggregate number due to the fusion of the liquid condensates. The chaperone activity of Hsp104, a Clp/HSP100 family chaperone, is required for both SLPT and subsequent dispersal of the liquid condensates. Sse1, a yeast HSP110 chaperone, also facilitates SLPT. These results illuminate an unexpected mechanistic framework of cellular control over protein disaggregation upon stress attenuation.

Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.

Representing the most attractive and successful druggable receptors of the proteome, GPCRs regulate a myriad of physiological and pathophysiological functions. Although over half of present pharmaceuticals target GPCRs, the advancement of drug discovery is hampered by a lack of adequate screening tools, the majority of which are limited to probing agonist-induced G-protein and ß-arrestin-2-mediated events as a measure of receptor activation. Here, we develop Tango-Trio, a comprehensive cell-based high-throughput platform comprising cumate-inducible expression of transducers, capable of the parallelized profiling of both basal and agonist-dependent GPCR activities. We capture the functional diversity of GPCRs, reporting ß-arrestin-1/2 couplings, selectivities, and receptor internalization signatures across the GPCRome. Moreover, we present the construction of cumate-induced basal activation curves at approximately 200 receptors, including over 50 orphans. Overall, Tango-Trio's robustness is well-suited for the functional characterization and screening of GPCRs, especially for parallel interrogation, and is a valuable addition to the pharmacological toolbox.

A comparison of National Healthcare Safety Network surveillance definitions to physician review for central-line-associated bloodstream infections.

For 147 hospital-onset bloodstream infections, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the National Healthcare Safety Network surveillance definitions of central-line-associated bloodstream infections against the gold standard of physician review, examining the drivers of discrepancies and related implications for reporting and infection prevention.

Global analysis of the yeast knockout phenome.

Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae, enabled by its knockout collection, have produced the largest, richest, and most systematic phenotypic description of any organism. However, integrative analyses of this rich data source have been virtually impossible because of the lack of a central data repository and consistent metadata annotations. Here, we describe the aggregation, harmonization, and analysis of ~14,500 yeast knockout screens, which we call Yeast Phenome. Using this unique dataset, we characterized two unknown genes (YHR045W and YGL117W) and showed that tryptophan starvation is a by-product of many chemical treatments. Furthermore, we uncovered an exponential relationship between phenotypic similarity and intergenic distance, which suggests that gene positions in both yeast and human genomes are optimized for function.

National survey study of nirmatrelvir-ritonavir prescribing processes and access barriers during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron surge of the coronavirus disease 2019 (COVID-19) pandemic.

In this national survey, we found that individual patient assessments by pharmacists were more common at facilities using centralized prescribing for nirmetralvir-ritonavir (Paxlovid) than decentralized prescribing. Provider discomfort was initially less with centralized prescribing, but later, there was no difference in provider discomfort based on prescribing mechanism.

Disorders of hyperpigmentation. Part I. Pathogenesis and clinical features of common pigmentary disorders.

Disorders of hyperpigmentation are common and, depending on the extent and location of involvement, can affect the quality of life and pose a significant psychologic burden for patients. Given the similarities in presentation of the various causes of hyperpigmentation, it is often difficult to elucidate the etiology of these conditions, which is important to guide management. Furthermore, certain disorders, such as lichen planus pigmentosus and ashy dermatosis, have similar clinical and/or histologic presentations, and their classification as distinct entities has been debated upon, leading to additional confusion. In this review, the authors selected commonly encountered disorders of hyperpigmentation of the skin, subdivided into epidermal, dermal, or mixed epidermal-dermal disorders based on the location of pigment deposition, along with disorders of hyperpigmentation of the mucosa and nails. Melanocytic nevi, genetic disorders, and systemic causes of hyperpigmentation were largely excluded and considered to be outside the scope of this review. We discussed the pathogenesis of hyperpigmentation as well as the clinical and histologic features of these conditions, along with challenges encountered in their diagnosis and classification. The second article in this 2-part continuing medical education series focuses on the medical and procedural treatments of hyperpigmentation.

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

Graphene e-tattoos for unobstructive ambulatory electrodermal activity sensing on the palm enabled by heterogeneous serpentine ribbons.

Electrodermal activity (EDA) is a popular index of mental stress. State-of-the-art EDA sensors suffer from obstructiveness on the palm or low signal fidelity off the palm. Our previous invention of sub-micron-thin imperceptible graphene e-tattoos (GET) is ideal for unobstructive EDA sensing on the palm. However, robust electrical connection between ultrathin devices and rigid circuit boards is a long missing component for ambulatory use. To minimize the well-known strain concentration at their interfaces, we propose heterogeneous serpentine ribbons (HSPR), which refer to a GET serpentine partially overlapping with a gold serpentine without added adhesive. A fifty-fold strain reduction in HSPR vs. heterogeneous straight ribbons (HSTR) has been discovered and understood. The combination of HSPR and a soft interlayer between the GET and an EDA wristband enabled ambulatory EDA monitoring on the palm in free-living conditions. A newly developed EDA event selection policy leveraging unbiased selection of phasic events validated our GET EDA sensor against gold standards.

Preparing for colorectal surgery: a qualitative study of experiences and preferences of patients in Western Canada.

OBJECTIVES: The burden and costs of abdominal surgery for chronic conditions are on the rise, but could be reduced through self-management support. However, structured support to prepare for colorectal surgery is not routinely offered to patients in Canada. This study aimed to describe experiences and explore preferences for multimodal prehabilitation among colorectal surgery patients. METHODS: A qualitative descriptive study using three focus groups (FG) was held with 19 patients who had a surgical date for abdominal surgery (April 2017-April 2018) and lived close (≤ 50 km radius) to a tertiary hospital in Western Canada (including a Surgical Lead for the British Columbia Enhanced Recovery After Surgery (ERAS) Collaborative). FGs were audio-taped and verbatim transcribed with coding and pile-and-sort methods performed by two independent reviewers, confirmed by a third reviewer, in NVivo v9 software; followed by thematic analysis and narrative synthesis. RESULTS: Four themes emerged: support, informed decision-making, personalization of care, and mental/emotional health, which patients felt was particularly important but rarely addressed. Patient preferences for prehabilitation programming emphasised regular support from a single professional source, simple health messages, convenient access, and flexibility. CONCLUSIONS: There is an unmet need for structured preoperative support to better prepare patients for colorectal surgery. Future multimodal prehabilitation should be flexible and presented with non-medical information so patients can make informed decisions about their preoperative care and surgical outcomes. Healthcare providers have an important role in encouraging healthy lifestyle changes before colorectal surgery, though clearer communication and accurate advice on self-care, particularly mental health, are needed for improving patient outcomes.

SARS-COV-2 as potential microRNA sponge in COVID-19 patients.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA that can downregulate their targets by selectively binding to the 3' untranslated region (3'UTR) of most messenger RNAs (mRNAs) in the human genome. MiRNAs can interact with other molecules such as viruses and act as a mediator for viral infection. In this study, we examined whether, and to what extent, the SARS-CoV-2 virus can serve as a "sponge" for human miRNAs. RESULTS: We identified multiple potential miRNA/target pairs that may be disrupted during SARS-CoV-2 infection. Using miRNA expression profiles and RNA-seq from published studies, we further identified a highly confident list of 5 miRNA/target pairs that could be disrupted by the virus's miRNA sponge effect, namely hsa-miR-374a-5p/APOL6, hsa-let-7f-1-3p/EIF4A2, hsa-miR-374a-3p/PARP11, hsa-miR-548d-3p/PSMA2 and hsa-miR-23b-3p/ZNFX1 pairs. Using single-cell RNA-sequencing based data, we identified two important miRNAs, hsa-miR-302c-5p and hsa-miR-16-5p, to be potential virus targeting miRNAs across multiple cell types from bronchoalveolar lavage fluid samples. We further validated some of our findings using miRNA and gene enrichment analyses and the results confirmed with findings from previous studies that some of these identified miRNA/target pairs are involved in ACE2 receptor network, regulating pro-inflammatory cytokines and in immune cell maturation and differentiation. CONCLUSION: Using publicly available databases and patient-related expression data, we found that acting as a "miRNA sponge" could be one explanation for SARS-CoV-2-mediated pathophysiological changes. This study provides a novel way of utilizing SARS-CoV-2 related data, with bioinformatics approaches, to help us better understand the etiology of the disease and its differential manifestation across individuals.

Active Tuberculosis After Solid Organ Transplantation in Individuals With Negative Pretransplant QuantiFERON-TB Gold Testing: A Case Series.

Active tuberculosis (TB) in solid organ transplant (SOT) recipients most commonly occurs due to reactivation of latent infection and is associated with poor clinical outcomes, including allograft loss and death. National transplant societies, including the American Society of Transplantation, recommend screening for latent TB prior to transplant, with treatment in the peritransplant setting to reduce the subsequent risk of TB reactivation. Though screening is traditionally conducted using laboratory-based assays, such as the QuantiFERON-TB Gold, false negatives may occur in SOT candidates due to anergy from end-stage organ dysfunction, highlighting the need for a multimodal diagnostic approach. In this case series, we describe the clinical characteristics and outcomes of 3 SOT recipients at the University of Pennsylvania with negative pretransplant QuantiFERON-TB Gold testing who subsequently developed active TB in the posttransplant setting, contributing to a growing body of knowledge regarding this challenging population. Each patient experienced a complicated clinical course that arose in part from the lack of diagnosis of TB prior to transplant. Because all had epidemiologic risk factors for TB, the findings of our study highlight the need for more individualized approaches to pretransplant TB screening.