Citations

Background This study aimed to evaluate outcomes of different antibiotic durations in patients with severe diverticulitis. Methods Initial electronic medical record review identified 2437 adult patients who underwent sigmoid colectomy. Manual chart review identified 133 patients who underwent sigmoid resection and proximal diversion for Hinchey stage 3 or 4 diverticulitis. Patients who received a short antibiotic course (SAC, ≤5 days) were compared with those who received a long antibiotic course (LAC, >5 days). The primary composite outcome included superficial, incisional, organ-space infections or death within 30 days post procedure. Results A total of 53 SAC patients and 55 LAC patients were identified. The composite outcome occurred more frequently in LAC patients than in SAC patients (40% vs 15%; P = .005). Organ-space infection occurred more frequently in LAC patients than in SAC patients (31% vs 13%; P = .04). Conclusions Extended duration of antibiotics after adequate source control does not improve outcomes even in the setting of extensive intra-abdominal contamination.

Objectives: To evaluate evolving management, ICU admission, and outcomes for critically ill chimeric antigen receptor (CAR) T-cell patients over a 6-year period. Design: Multicenter retrospective cohort study from January 2018 to September 2023. Setting: Eight U.S. centers. Patients: Adult CAR T-cell patients requiring ICU admission. Interventions: None. Methods: Summary statistics included mean, sd , median, and interquartile range (IQR). Fisher exact test or chi-square test were used to evaluate association between year treated and other categorical variables. Cochran-Armitage test was performed to assess significance of trends across years. Multivariable logistic regression was performed to assess covariates associated with mortality. Measurements and Main Results: Demographics, toxicity management, ICU admission, support modalities, toxicity severity, and survival (ICU, hospital, and 3-mo) were compared year-to-year. From 2018 to 2023, 2238 patients received CAR T cells, with increasing number of patients treated yearly; 398 (17.8%) required ICU care. Of those admitted to the ICU, 66.1% were male, 89.2% had lymphoma, and median age was 64 years (53–71 yr). ICU admission rates declined from 38.5% (95% CI, 31.6–45.8%) in 2018 to 16.4% in 2023 (95% CI, 13.5–19.7%; p < 0.0001). Cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was the reason for ICU admission in 87.9%. In 2023 vs. 2018, ICU patients were older (median, 65 yr [IQR, 55–73 yr] vs. 58 yr [48–67 yr]; p = 0.003) with higher comorbidity indices (4 [4–6] vs. 3 [2–4]; p = 0.005) and more severe toxicities (≥ grade 3: 90.1% vs. 69.9%; p = 0.004). Corticosteroid use for less severe toxicities (≤ grade 2 toxicity: 73.8% vs. 40.6%; p = 0.0001) and anakinra use (56% vs. 5.5%; p < 0.0001) increased throughout the years. Mortality from cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome remained low (5.5%). Age, Sequential Organ Failure Assessment greater than or equal to 10 at ICU admission, and ICU admission for noncytokine release/neurotoxicity syndrome reasons were associated with hospital mortality (odds ratios, 1.02 [95% CI, 1–1.04; p = 0.046], 4.69 [2.44–9.01; p < 0.0001], and 3.74 [1.91–7.3; p = 0.0001], respectively). Conclusions: ICU admission rates after CAR T-cell treatment are declining. Although ICU patients are older with higher severity of illness and toxicity grades, ICU mortality after CAR T-cell therapy remains low.

Abstract Background Prior studies of Alzheimer's disease (AD) biomarker disclosure have answered important questions about individuals’ experiences learning amyloid results. In comparison, the experiences of individuals performing AD biomarker disclosure have been under characterized. The present study examines the clinician experience disclosing amyloid positron emission tomography (PET) results within the Alzheimer's Disease Neuroimaging Initiative's ADNI‐4 study. Methods The ADNI‐4 longitudinal cohort study includes a pragmatic process for amyloid PET disclosure for participants across the cognitive spectrum. Disclosing clinicians complete a short questionnaire after each disclosure session, reporting on the visit length, the clinician's rating of participant and study partner understanding and emotional reactions, topics discussed, challenges, assessment of the visit overall, and any feedback about the process. Results Across the first 100 disclosures (48 cognitively normal, 35 Mild Cognitive Impairment (MCI), 17 dementia) in ADNI‐4, visits lasted an average of 29.4 minutes (SD 13.9, range 10‐90). Most cognitively impaired participants had a loved one present at the disclosure visit (dementia 94%, MCI 80%) but the majority of cognitively normal participants (73%) did not. Clinicians rated understanding of the result as adequate for all study partners and the vast majority (94%) of participants. Clinicians reported feeling “very confident” in their ability to assess readiness to receive result (70%), disclose (73%), and answer questions (77%). Clinicians rated all visits as “good” or better, with two‐thirds (65%) rated as “excellent.” Frequently discussed topics included meaning of result (99%), other risk factors (72%), and emotional impact of result (49%). Stigma and discrimination were rarely discussed, coming up in 12% and 3% of disclosure sessions, respectively. Challenges were infrequent (7%) and primarily included desire for additional information and challenges related to the participant's impairment. Clinicians provided the study team feedback about the disclosure process for 25% of disclosure visits. Comments included the desire for additional information or resources, positive feedback, and the importance of the study partner. Conclusions Clinicians disclosing amyloid PET results in ADNI‐4 report high confidence, adequate participant and study partner understanding, and few challenges. These data from clinicians, in combination with participant data, will inform future disclosure practices in both research and care.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

Abstract Background Self‐administered and remote digital cognitive assessments provide a scalable method for screening and longitudinal cognitive monitoring. Mayo Test Drive (MTD) is one such assessment with previously demonstrated usability, reliability, validity and multi‐device compatibility. MTD includes a computer‐adaptive word list memory test (Stricker Learning Span) and a measure of processing speed/executive functioning (Symbols Test) that combine to provide an MTD Composite. This study aimed to develop a conditional normative model predicting longitudinal cognitive change for MTD, and to validate the model in two independent samples of cognitively unimpaired (CU) and mild cognitive impairment (MCI)/dementia (DEM) participants. Method 1355 CU participants at initial MTD assessment with 2‐4 consecutive MTD assessments every 7.5 months comprised the development dataset. Linear mixed effects models were used to construct a conditional normative model for MTD assessments 2‐4. The baseline model was chosen a priori , consisting of age, sex, education, baseline score, number of assessments, and time. Device type, race, and baseline score by time interactions were also considered. Variables were only added if a >1% increment in r‐squared was observed. The models were externally validated in 113 CU and 51 MCI/DEM patients. Following model development, the data were updated and additional follow‐up MTD assessments were added for many participants, including the addition of additional CU validation data at test 3 ( N = 126) and 4 ( N = 279). T‐tests compared observed and predicted differences and residual z‐scores between development and validation at each follow‐up assessment. Result Table 1 presents demographic variables. No additional variables increased the r‐squared by >1%. The final models are presented in Table 2. Age, baseline score, sex, and education were significant. Residual z‐scores were not significantly different between CU development and CU validation cohorts, indicating observed scores were in line with model predicted scores. Residual z‐scores were significantly worse among MCI/DEM compared to CU development in 11/12 comparisons (Figure 1), indicating observed scores were below model predicted expectations and implying sensitivity to longitudinal cognitive decline. Conclusion These longitudinal normative models can be used to identify individuals with follow‐up scores outside of expected predicted ranges, signifying abnormal longitudinal cognitive decline.

Abstract Background Amyloid related imaging abnormality edema (ARIA‐E) occurs in about 19% of individuals with autosomal dominant Alzheimer disease (ADAD) treated with an anti‐amyloid‐b monoclonal antibody (Salloway et al., 2021). In a previously reported case, ARIA‐E appeared to colocalize with decreases in PiB‐PET uptake (Joseph‐Mathurin, Llibre‐Guerra, et al, 2022), suggesting an association between amyloid‐b (Aβ) removal and ARIA‐E. Here, we compare longitudinal neuroimaging and corresponding neuropathology in an ADAD individual treated with gantenerumab, who experienced multiple ARIA‐E episodes as sulcal effusions that resolved by the end of the four‐year trial. Methods PiB‐PET and MRI were collected pre‐ and post‐randomization (2 and 4 years). The participant consented to brain donation, which was received a year after trial completion. Four tissue samples were taken from the location of the ARIA‐E in the parieto‐occipital left hemibrain as identified by MRI (one block contained the sulcus affected by ARIA‐E; the rest of the coronal section was captured in the remaining three blocks). Area fractions (AFs) of Aβ (10D5 immunohistochemistry (IHC)), tauopathy (PHF1), microglia (Iba1), and astrocytes (GFAP) in one sulcal region of interest (ROI) from each block and PiB‐PET SUVRs of corresponding ROIs were extracted ( n = 4, Figure 1). Additionally, we included PiB‐PET SUVRs corresponding to ARIA‐E findings observed in the right hemisphere at baseline, two‐year, and four‐year visits ( n = 6). Results Overall PiB‐PET uptake increased during the first two years (before ARIA‐E) and decreased during the last two years (including ARIA‐E episodes) (0.03±0.05 vs. ‐0.04±0.04 SUVR/year, p ‐value=0.01, Figure 2). The decrease seemed more pronounced in ARIA‐E ROIs versus normal‐appearing sulcus ROIs (‐0.05±0.04 vs. ‐0.02±0.03 SUVR/year). Lower PiB uptake at last visit appeared associated with lower Aβ AF (estimates=0.03±0.01, p ‐value=0.07). The ARIA‐E ROI had an Aβ AF of 0.009 while normal‐appearing sulcus ROIs had a mean of 0.02+0.003 (Figure 3). AFs for tauopathy, microglia, and astrocytes were within the range of those of normal‐appearing sulcus ROIs, suggesting an Aβ‐specific effect, although unexamined markers may play a role. Conclusions Our preliminary findings indicated that ARIA‐E is associated with longitudinal PiB‐PET decrease and Aβ AF, supporting the link between ARIA‐E, changes in PiB‐PET, and local Aβ removal observed at autopsy. Funding : K01AG080123; U01AG042791; R01AG046179; R01AG053267

Study Design. Modified Delphi consensus process Objective. To establish a standardized, consensus-driven definition for postoperative spine infection (PSI) for research, diagnosis, and management. Summary of Background Data. Postoperative infection is a devastating and common complication following spine surgery. Rates of PSI in the literature range from 0% to over 20% depending on surgical indication and invasiveness. Despite the implications of PSI, there is no universally accepted diagnostic standard or consensus definition for infection following spine surgery, hindering research and treatment of this challenging clinical condition. Methods. A multispecialty workgroup convened by the Musculoskeletal Infection Society (MSIS) conducted a systematic literature review. Using data from the systematic review, an expert panel completed a modified Delphi process to achieve consensus. The panel included nine fellowship-trained, board-certified physicians with expertise in infectious diseases, orthopaedic and neurologic spine surgery, and musculoskeletal radiology. Iterative rounds focused on criterion selection, importance ranking, categorical grouping, and final constellation development for PSI diagnosis. Consensus was defined as a 2/3 majority, with a target of 100%. Results. The workgroup achieved 100% consensus on a new PSI definition, which incorporates six clinical domains: wound features, microbiology, imaging, inflammatory biomarkers, intraoperative findings, and histology. A single microbiological stand-alone criterion—identification of a phenotypically indistinguishable organism from two or more deep operative site specimens—was established as pathognomonic for postoperative spine infection. Additional primary and secondary supporting criteria were defined, with specific combinations required to classify cases as definite or probable PSI. Final definitions were ratified by the boards of MSIS and the European Bone & Joint Infection Society (EBJIS) Conclusion. This consensus-based definition provides a standardized framework for diagnosing postoperative spine infection, facilitating research and clinical management. The criteria balance sensitivity and specificity across diverse clinical scenarios and represent the first multispecialty, society-endorsed definition for PSI.

Introduction: Adult hepatitis B vaccination coverage in the United States remains low despite updated national recommendations supporting universal adult immunization. Many adults remain unaware of their susceptibility to hepatitis B virus (HBV) infection. This quality improvement (QI) study evaluated a stepwise “Offer–Offer–Test–Vaccinate” workflow designed to improve hepatitis B vaccine uptake among vaccine-hesitant adults in a primary care setting. Methods: This retrospective QI study was conducted at a single primary care clinic in Rochester, Minnesota. Adult patients (≥19 years) seen between October 1, 2022, and October 1, 2024, were routinely offered hepatitis B vaccination during rooming. Two participating physicians implemented an enhanced workflow in which patients who declined vaccination were counseled and then offered serologic screening using the 2023 CDC-recommended triple panel (HBsAg, anti-HBs, and total anti-HBc). Patients with negative serology were notified via the patient portal and reoffered vaccination along with a link to the CDC Vaccine Information Statement. The primary endpoint was initiation of the hepatitis B vaccine series following receipt of negative serology results. Preliminary series-completion data through October 1, 2025, were also assessed. Results: Among 501 eligible adults, 104 (20.8%) accepted vaccination at the initial offer. Of the 397 who declined, 106 (26.7%) agreed to serologic testing; 91 (85.8%) were seronegative. Among seronegative patients, 41 (45.1%) subsequently accepted vaccination. Integrating serologic testing increased overall vaccination uptake from 20.8% to 28.9%, an absolute increase of 8.2 percentage points and a relative increase of 39.4%. Approximately 2.6 serologic tests were required to generate 1 additional first-dose vaccination. Preliminary series-completion rates were 74.0% among those vaccinated at the initial offer and 87.8% among those vaccinated following serologic testing. Discussion: In this primary care setting, incorporating serologic testing into the workflow was associated with modestly improved hepatitis B vaccination uptake among vaccine-hesitant adults. Serologic results may help re-engage patients by providing personalized immunity information. Implementation considerations include staffing needs, laboratory access, patient portal engagement, and insurance coverage. Conclusion: The “Offer–Offer–Test–Vaccinate” strategy was associated with a modest increase in hepatitis B vaccine uptake among hesitant adults. This EMR-integrated, stepwise approach may offer a feasible and scalable strategy to reduce missed vaccination opportunities and support HBV prevention in adult primary care.

Abstract Introduction Periacetabular osteotomy (PAO) is performed in the setting of hip dysplasia to increase acetabular coverage of the femoral head and improve joint biomechanics and longevity. PAO fixation is generally achieved with two or three 4.5 mm screws, as compared to the generally more substantial plate and screw constructs used in the setting of acetabular fractures or pelvic ring injuries. The purpose of this study was to evaluate postoperative changes in hip joint center medialization and lateral acetabular coverage following PAO, understanding that these radiographic measures are generally used to guide intra-operative assessment of correction. Methods A retrospective chart review of 100 consecutive PAOs during 2021-2023 at a single academic institution by four surgeons was performed. Perioperative radiographs and fluoroscopy images were evaluated to measure lateral center edge angle (LCEA), Tönnis angle, and medialization of the hip joint center. The hip joint center was measured at one-third of the diameter of the femoral head from inferior to superior, to the ilioischial line, as previously validated by Fowler and colleagues. Results One hundred PAOs in 87 patients (87% female, mean age: 23.0 years) were included. Average preoperative radiographic parameters were 19.9° for LCEA, 12.5° for Tönnis angle, and 12.6 mm for distance from the femoral head to ilioischial line. Ninety-four cases (94%) used three screws, and 6 cases (6%) used two screws for unstable fragment fixation. On immediate postoperative films, average correction was to 28.3° for LCEA, 4.9° for Tönnis angle, and 1.9 mm of pre- to postoperative femoral head medialization (p≤0.001). Patients were radiographically followed for an average of 13.3 months, with an average time to radiographic union of 7.1 months. During the course of follow-up, LCEA increased to 29.3°, Tönnis angle remained to 5.0° (p=0.47), and medialization increased to 2.7 mm (p≤0.02), suggesting further significant but clinically modest increases in lateral coverage and femoral head medialization. Conclusion While the majority of lateral acetabular coverage and femoral head medialization occurs intra-operatively at the time of PAO, patients undergo modest but statistically significant postoperative increases in lateral coverage and medialization prior to radiographic union.

Abstract Purpose Acetabular overcoverage (pincer morphology) has been suggested to be both a source of pain and dysfunction as well as potentially protective against osteoarthritic change. The purpose of this study was to compare minimum 5-year clinical outcomes of patients undergoing primary hip arthroscopic labral repair with a lateral center edge angle (LCEA) of ≥ 40° as compared to non-dysplastic controls with an LCEA of 25-40°. Methods We identified all patients that underwent primary hip arthroscopy with labral repair between 2009-2019 at a single academic institution. Patients with LCEA ≥ 40° (pincer) were propensity matched to non-dysplastic controls with LCEA 25-40° on a 1:2 basis by sex, age, body mass index (BMI), and year of surgery. Patient-reported outcome measures (PROMs) including Visual Analog Scale (VAS) for pain, Tegner activity score, modified Harris Hip Score (mHHS), International Hip Outcome Tool (iHOT-12), and Hip Outcome Score (HOS) were analyzed, as were reoperations and conversions to total hip arthroplasty (THA). Results Fifty-five patients with pincer morphology (mean preoperative LCEA: 41.9°, Tonnis angle: -7.3°, alpha angle: 58.8°) were matched to 110 non-dysplastic controls (LCEA: 31.2°, Tonnis angle: 2.2°, alpha angle: 58.9°), resulting in a total of 165 hips in 163 patients (67% females, mean age: 37.7 years, BMI: 26.8 kg/m2). Pincer patients were corrected to a mean postoperative LCEA of 38.7° (p&lt;0.0001), with 22 pincer patients having residual overcoverage, namely a postoperative LCEA ≥ 40° (range: 40.0-45.8°). At mean 7.8 years follow-up (range: 5.1-13.2), there was no difference in any postoperative PROMs between pincers and controls (p&gt;0.15) and no difference in PROMs between patients with residual overcoverage and pincer patients with a postoperatively normalized LCEA (p&gt;0.25). At final follow-up, 4 patients in the pincer cohort (7%) and 21 controls (19%) had converted to THA (p=0.046). Conclusion Patients with lateral acetabular overcoverage demonstrated similar and satisfactory postoperative PROMs at a minimum of 5-year follow-up compared to propensity-matched non-dysplastic controls, regardless of if the LCEA was corrected to &lt;40°. Of note, non-dysplastic controls demonstrated an increased rate of conversion to THA, supporting the potentially chondroprotective role of acetabular overcoverage.