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Abstract Background We investigated the relationship between cumulative, historical antibiotic therapy and the presence of ceftriaxone-resistant (CRO-R) Enterobacterales bloodstream infections (BSI) from urinary sources. Methods Adult patients established with primary care at Mayo Clinic with a first episode of monomicrobial Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis BSI from a urinary source from May 2019 to May 2023 were included. Antibiotic therapy over the year prior to BSI was quantified as days of therapy (DOT), cumulative modified Antibiotic Spectrum Index (mASI), and cumulative Days of Antibiotic Spectrum Coverage (DASC) using prescription data. Patients with CRO-R urinary pathogens prior to antibiotic therapy assessment were excluded. Results In total, 721 adults had monomicrobial gram-negative BSI, including 70 patients (9.7%) with a CRO-R pathogen and 651 patients (90.3%) with a ceftriaxone-susceptible (CRO-S) pathogen. In the 12 months prior to BSI, levels of antibiotic DOT, mASI, and DASC were significantly greater among patients with CRO-R BSI than CRO-S BSI (P < .001). The median time from blood culture collection to appropriate antibiotic therapy was significantly longer in the CRO-R group (24 hours, interquartile range [IQR] 16–48) than the CRO-S group (1 hour, IQR 0–2) (P < .001). Increasing cumulative antibiotic therapy prior to BSI, as quantified by the mASI, was significantly associated with increased risk of 1-year CDI after BSI (P = .027). Conclusions Patients with first episode CRO-R Enterobacterales BSI had significantly greater prior antibiotic exposure than patients with CRO-S BSI and experienced significant delay of appropriate therapy. Routine quantitation and reporting of prior antibiotic therapy may improve empiric prescribing.

Summary: Epilepsy neuromodulation treatment failure is a significant challenge, with multiple possible causes. The responsive neurostimulation (RNS) system delivers stimulation from a single current source, and the relative flow of the electrical current through each stimulating contact is inversely proportional to the relative impedance of each contact. Current shunting through low-impedance contacts (i.e., intraventricular contacts) can divert therapy away from the intended targets and may be a cause of treatment failure. We present a case of a patient with bitemporal epilepsy and bitemporal encephaloceles, with poor response to bilateral mesial temporal RNS, who completed stereotactic EEG (sEEG) monitoring to investigate the possible causes of treatment failure. The sEEG was safely completed without damaging the RNS device. The sEEG recorded independent bitemporal interictal epileptiform discharges and seizures, which did not arise from sampled encephalocele regions. The sEEG-recorded RNS stimulation artifact was reduced in the left mesial temporal region relative to the right, which suggested potential current shunting through the right-sided contacts. Impedance measurements confirmed several low-impedance contacts from the right lead, with associated intraventricular position on imaging. At last follow up, 161 days after replacement of the right lead, the patient experienced an additional 58% reduction in seizure burden. Effective therapy delivery by single-current-source neurostimulation systems, such as RNS, critically depends on relative electrode impedances. Current shunting through low-impedance contacts is an underappreciated potential cause of treatment failure. Routine impedance assessments and individualized stimulation programs are recommended to avoid unintended current diversion. Concurrent sEEG monitoring and active RNS are feasible and can characterize stimulation effects.

ABSTRACTObjectivesTo achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face.Materials and MethodsDelphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9‐point Likert scale (1 = strongly disagree; 9 = strongly agree) and optionally provided comments. The consensus meeting was supplemented by the results of a systematic review of the literature (from 2000 to 2023).ResultsTwo rounds of Delphi survey were completed by 34 participants across four countries. Represented specialties were dermatology, facial plastic surgery, plastic surgery, and oculoplastic surgery. The initial 105 statements from round 1 expanded to 112 in round 2, with 96 statements achieving consensus. These included possible adverse events (11 statements); absolute and relative contraindications to treatment (5 statements); preoperative care and antimicrobial prophylaxis precautions (16 statements); intraoperative precautions (17 statements); postoperative care (21 statements); monitoring for and management of infection (16 statements); management of pigmentation changes (6 statements); and management of scarring and incipient scarring (4 statements).ConclusionAn international consensus statement was developed for the prevention and management of complications associated with fully ablative laser resurfacing of the face. While expert practices vary, key factors for optimizing outcomes include careful patient selection, counseling, and meticulous pre‐ and postoperative care. Further research will improve our understanding of this treatment technique.

For over a century, scientists reported the disruption of normal nuclear shape and size in cancer. These changes have long been used as tools for diagnosis and staging of malignancies. However, to date, the mechanisms underlying these aberrant nuclear phenotypes and their biological significance remain poorly understood. Using a model of pancreatic ductal adenocarcinoma (PDAC), the major histological subtypes of pancreatic cancer, we found that oncogenic mutant KRAS reduces nuclear size. Transcriptomic and protein expression analysis of mutant KRAS–expressing PDAC cells revealed differential levels of several nuclear envelope–associated genes. Further analysis demonstrated the nuclear lamina protein, Emerin (EMD), acted downstream of KRAS to mediate nuclear size reduction in PDAC. Analysis of human PDAC samples showed that increased EMD expression associates with reduced nuclear size. Finally, in vivo genetic depletion of EMD in a mutant KRAS–driven PDAC model resulted in increased nuclear size and a reduced incidence of poorly differentiated PDAC. Thus, our data provide evidence of a potentially novel mechanism underlying nuclear size regulation and its effect in PDAC carcinogenesis.

Despite significant improvements in survival of patients with multiple myeloma (MM), outcomes remain heterogeneous, and a significant proportion of patients experience suboptimal outcomes. Importantly, traditional prognostic factors based on data from patients treated with older therapies no longer capture prognosis accurately in the contemporary era of novel triplet or quadruplet therapies. Therefore, risk stratification requires refinement in the context of available and investigational treatment options in routine practice and clinical trials, respectively. The current identification of high-risk MM (HRMM) in routine practice is based on the Revised International Staging System, which stratifies patients using a combination of widely available serum biomarkers and chromosomal abnormalities assessed via fluorescence in situ hybridization. In recent years, a substantial body of evidence concerning additional clinical, biological, and molecular/genomic prognostic factors has accumulated, along with new MM risk stratification tools and consensus reports. The International Myeloma Society, along with the International Myeloma Working Group, convened an Expert Panel with the primary aim of revisiting the definition of HRMM and formulating a practical and data-driven consensus definition, based on new evidence from molecular/genomic assays, updated clinical data, and contemporary risk stratification concepts. The Panel proposes the following Consensus Genomic Staging (CGS) of HRMM which relies upon the presence of at least one of these abnormalities: (1) del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation; (2) an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32); (3) monoallelic del(1p32) along with 1q+ or biallelic del(1p32); or (4) β2 microglobulin ≥5.5 mg/L with normal creatinine (<1.2 mg/dL).