Worse Outcomes Research Articles

Different but Equal: Outcomes of Prolonged Postanesthesia Care Unit Stay After Trauma Laparotomy

IntroductionHospital overcrowding is common and can lead to delays in intensive care unit (ICU) admission, resulting in increased morbidity and mortality in medical and surgical patients. Data on delayed ICU admission are limited in the postsurgical trauma cohort. Damage control laparotomy with temporary abdominal closure (DCL-TAC) for severely injured patients is often followed by an aggressive early resuscitation phase, usually occurring in the ICU. We hypothesized that patients who underwent DCL-TAC with initial postanesthesia care unit (PACU) stay would have worse outcomes than those directly admitted to ICU. MethodsA retrospective chart review identified all trauma patients who underwent DCL-TAC at a level 1 trauma center over a 5 y period. Demographics, injuries, and resuscitation markers at 12 and 24 h were collected. Patients were stratified by location after index laparotomy (PACU versus ICU) and compared. Outcomes included composite morbidity and mortality. Multivariable logistic regression was performed. ResultsOf the 561 patients undergoing DCL-TAC, 134 (24%) patients required PACU stay due to ICU bed shortage, and 427 (76%) patients were admitted directly to ICU. There was no difference in demographics, injury severity score, time to resuscitation, complications, or mortality between PACU and ICU groups. Only 46% of patients were resuscitated at 24 h; 76% underwent eventual primary fascial closure. Under-resuscitation at 24 h (adjusted odds ratio [AOR] 0.55; 95% confidence interval [CI] 0.31-0.95, P = 0.03), increased age (AOR 1.04; 95% CI 1.02-10.55, P < 0.0001), and increased injury severity score (AOR 1.04; 95% CI 1.02-1.07, P < 0.0001) were associated with mortality on multivariable logistic regression. The median time in PACU was 3 h. ConclusionsPACU hold is not associated with worse outcomes in patients undergoing DCL-TAC. While ICU was designed for the resuscitation of critically ill patients, PACU is an appropriate alternative when an ICU bed is unavailable.

Epidemiology of Adenosquamous Carcinomas.

Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs). In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6). Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.

Risk factors for acute kidney injury in patients hospitalized with COVID-19.

Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

Comparison of Postoperative Outcomes of Patients Undergoing Total Hip and Total Knee Arthroplasty Following a Diagnosis of Dementia: A TriNetX Database Study

BackgroundAs life expectancy improves for patients with dementia, the demand for mobility-improving surgeries such as total joint arthroplasty (TJA) will increase. There is little research on patients with dementia undergoing TJA, although dementia has been shown to be a risk factor for complications. The purpose of this study is to compare postoperative outcomes of patients with dementia undergoing TJA at 90 days, 2 years, and 5 years. MethodsThe TriNetX database was retrospectively queried for all patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients were divided into cohorts by preoperative diagnosis of dementia and propensity score matched. The following outcomes were evaluated between groups at 90 days, 2 years, and 5 years postoperatively: revision, resection arthroplasty, closed reduction (THA only), femur fracture plating, and prosthetic joint infection. Readmission and manipulation under anesthesia (TKA only) were evaluated at 90 days postoperatively. Univariate and multivariate analyses were performed. ResultsAfter matching, there were no differences in demographics or comorbidities between groups. TKA (odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.42-2.15, P < .001) and THA (OR = 2.17, 95% CI 1.92-2.45, P < .001) patients with dementia were more likely to be readmitted than patients without dementia. At 2 years (OR = 2.07, 95% CI 1.14-3.77, P = .015) and 5 years (OR = 2.14, 95% CI 1.32-3.48, P = .002) postoperatively, THA patients with dementia were more likely to have proximal femur fracture plating than patients without dementia. ConclusionsPatients undergoing THA with dementia had worse outcomes than patients undergoing THA without dementia and TKA with dementia. The overall rate of complications was low, and a diagnosis of dementia should not be an absolute contraindication to proceeding with TJA.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort

BackgroundThere is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). MethodsThis retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. ResultsOf 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). ConclusionIn NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

The effects of anaesthesia and analgesia on short- and long-term outcomes following colorectal cancer surgery

BACKGROUND Colorectal cancer (CRC) is the second most frequent cause of global cancer mortality. Most patients with CRC require surgical tumour resection, with certain stages of CRC (Stage II/III) also requiring postoperative chemotherapy. The timing of postoperative chemotherapy is largely determined by postoperative recovery. Delayed return to intended oncologic therapy (RIOT) by &gt;8 weeks results in worse oncologic outcomes. RIOT is thus an important surrogate marker of outcome for patients with stage II/III CRC. We will test the hypothesis that anaesthetic technique during CRC resection surgery may affect RIOT. OBJECTIVE To test the association between anaesthetic and analgesic technique during CRC surgery and RIOT. To document Short-term Secondary outcomes including individual postoperative complications and a composite of all postoperative complications, the Comprehensive Complications Index (CCI) and to measure the time to recurrence (TTR) of cancer at 3 years. DESIGN This is a prospective, international, multicentre, observational cohort study. SETTING Global healthcare setting, with &gt;140 centres in &gt;30 nations. PATIENTS Inclusion criteria: All patients age &gt;18 years, ASA I–III, with CRC stage I–III scheduled for elective CRC surgery (open or minimally invasive). Exclusion criteria: Uncontrolled renal or liver disease, restrictive (limiting mobility) heart failure or ischemic heart disease (ASA IV–V). Speech, language, or cognitive difficulties precluding signing informed consent to participate and Stage IV CRC. PRIMARY OUTCOME MEASURES Short -term: The duration from day of surgery to RIOT among patients expected to receive postoperative chemotherapy. Long-term: incidence of recurrence and time to recurrence (TTR) at 3 years after primary curative surgery SECONDARY OUTCOMES Postoperative complications within 30 days of surgery, length of hospital stay, Days at Home at 30 and 90 days (DAH-30, DAH-90) after surgery, and adverse events related to oncological treatment. We will also assess the burden of preoperative modifiable comorbid disease in patients. Exploratory endpoints will assess practice variation (including incidence of RIOT by demographic e.g. gender of patient, type of institution, country). RESULTS N/A. CONCLUSIONS N/A. TRIAL REGISTRATION The Effects of aNesthesia in COloREctal cancer outcome study: ENCORE, ClinicalTrials.gov Identifier: NCT04493905.

Ankle fracture surgery in patients experiencing homelessness: a national evaluation of one-year rates of reoperation.

To evaluate the impact of homelessness on surgical outcomes following ankle fracture surgery. Retrospective cohort study. Mariner claims database. Patients older than 18 years who underwent open reduction and internal fixation (ORIF) of ankle fractures between 2010 and 2021. A total of 345,759 patients were included in the study. Study patients were divided into two cohorts (homeless and nonhomeless) based on whether their patient record contained International Classification of Disease (ICD)-9 or ICD-10 codes for homelessness/inadequate housing. One-year rates of reoperation for amputation, irrigation and debridement, repeat ORIF, repair of nonunion/malunion, and implant removal in isolation. Homeless patients had significantly higher odds of undergoing amputation (adjusted odds ratio [aOR] 1.59, 95% confidence interval [CI] 1.08-2.27, P = 0.014), irrigation and debridement (aOR 1.22, 95% CI 1.08-1.37, P < 0.001), and repeat ORIF (aOR 1.16, 95% CI 1.00-1.35, P = 0.045). Implant removal was less common in homeless patients (aOR 0.65, 95% CI 0.59-0.72, P < 0.001). There was no significant difference between homeless and nonhomeless patients in the rate of nonunion/malunion repair (aOR 0.87, 95% CI 0.63-1.18, P = 0.41). Homelessness is a significant risk factor for worse surgical outcomes following ankle fracture surgery. The findings of this study warrant future research to identify gaps in surgical fracture care for patients with housing insecurity and underscore the importance of developing interventions to advance health equity for this vulnerable patient population. Prognostic Level III.

Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm

AimThe optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. MethodsBetween 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. ResultsAt 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5–12) vs 11 (7–16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4–6 min. ConclusionA longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Reliability and reference values for diaphragmatic excursion, thickness, and thickening fraction and quadriceps femoris muscle thickness in full-term newborns evaluated by ultrasound.

To determine the diaphragm thickness, thickening fraction, and excursion and thickness of the quadriceps femoris muscle in full-term newborns and to evaluate the intra- and interrater reliability of these measurements.This was a prospective, observational clinical study including full-term newborns born within the first 48h after birth. Serial measurements of the thickness, thickening fraction, and mobility of the diaphragm muscles and the thickness of the quadriceps muscle were obtained using ultrasound images. A total of 69 newborns with a mean gestational age of 39 weeks were included. The following measurements were obtained and are expressed as the mean (standard deviation): inspiratory diaphragm thickness, 0.19cm (0.04); expiratory diaphragm thickness, 0.16cm (0.04); diaphragm thickness fraction, 16.70cm (10.27); diaphragmatic excursion, 0.68cm (0.22); and quadriceps thickness, 0.99cm (0.14). Intrarater reliability was assessed using intraclass correlation coefficients (ICCs). Excellent intrarater agreement was observed for the two groups of operators (ICC > 0.86,p < 0.001) for all measurements except for the diaphragm thickening fraction, which showed good agreement for both operator groups (ICC = 0.70,p < 0.001). Regarding interrater reliability, moderate agreement between the raters was observed in the means of all measures (ICC > 0.49,p < 0.001), except for the diaphragm thickening fraction, which showed poor agreement. Conclusion: Good intrarater and moderate interrater reliability were achieved in ultrasound evaluations of the thickness and mobility of the diaphragm and quadriceps femoris muscles in full-term newborns, demonstrating the feasibility of this technique for clinical use. This pioneering study offers reference values for these muscles in a single study, allowing comparisons between different clinical conditions. What is Known: •Ultrasound is a highly reliable tool for muscle assessment that can be used to assess muscular atrophy in critically ill patients. • Muscle atrophy worsens the patient's condition and has been associated with worse outcomes. What is New: • To our knowledge, this is the first study to jointly evaluate the diaphragm and quadriceps muscle thickness and evaluate the reliability of all measurements. • Our study presents reference values for both muscles, enabling comparisons between different clinical conditions.

Effect of Cigarette Smoking on Postoperative Outcomes After Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the Talus.

Bone marrow stimulation (BMS) is presently considered first-line surgical treatment for osteochondral lesions of the talus (OLTs); however, some patients still experience pain or dysfunction after surgery, and the reasons for success or failure remain somewhat unclear. This study aimed to investigate the effect of smoking on postoperative outcomes after arthroscopic BMS for OLTs. Consecutive patients with OLTs who underwent BMS between January 2017 and January 2020 were included. Smokers were defined as patients who actively consumed cigarettes before surgery and postoperatively, whereas nonsmokers were patients who never smoked. Visual analog scale (VAS), American Orthopaedic Foot & Ankle Society ankle hindfoot score (AOFAS), Karlsson-Peterson, and Tegner scores were assessed preoperatively and at follow-up. Additionally, a general linear model (GLM) was performed, followed by the interaction analysis to explore the potential influence of smoking. The study enrolled 104 patients with a mean follow-up of 30.91 ± 7.03 months, including 28 smokers and 76 nonsmokers. There were no significant differences in patient age (35.2 ± 10.0 years vs 37.6 ± 9.7 years, P = .282) or OLT area (63.7 ± 38.7 mm2 vs 52.8 ± 37.0 mm2, P = .782). Both univariate analysis and GLM revealed that smoking was associated with worse postoperative pain levels, Karlsson-Peterson, and AOFAS scores (P < .05). The interaction analysis showed a significant interaction between smoking and OLT area for postoperative Karlsson-Peterson scores (general ankle function) (P = .031). Simple main effects analysis revealed that the negative effect of smoking on Tegner score significantly increased among patients >32 years old or with OLT area>50 mm2 (P < .05). Smoking was associated with worse clinical outcomes following BMS of OLTs. As the size of OLTs increased, the difference in general ankle function between smokers and nonsmokers also increased. Furthermore, smokers who were older than 32 years or had larger OLTs were less likely to resume participation in high-level activities.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Hypobaria During Aeromedical Evacuation and Systemic Inflammation after Porcine Traumatic Brain Injury.

Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is utilized by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation following TBI that could contribute to more severe TBI-related secondary injury. Thirty-six female pigs were used to test TBI vs. TBI sham, hypoxia vs. normoxia, and hypobaria vs. ground conditions. TBI was induced by controlled cortical injury, hypobaric conditions of 12,000 feet were established in an altitude chamber, and hypoxic exposure was titrated to 85% SpO2 while at altitude. Serum cytokines, UCH-L1 and TBI biomarkers were analyzed via ELISA. Gross analysis and staining of cortex and hippocampus tissue was completed for glial fibrillary acidic protein (GFAP) and phosphorylated tau (p-tau). Serum IL-1b, IL-6, and TNFα were significantly elevated following TBI in pigs exposed to altitude-induced hypobaria/hypoxia, as well as hypobaria alone, compared to ground level/normoxia. No difference in TBI biomarkers following TBI or hypobaric, hypoxic exposure was noted. No difference in brain tissue GFAP or p-tau when comparing the most different conditions of sham TBI+ground/normoxia to the TBI+hypobaria/hypoxia group was noted. The hypobaric environment of AE induces systemic inflammation following TBI. Severe inflammation may play a role in exacerbating secondary injury associated with TBI and contribute to worse neurocognitive outcomes. Measures should be taken to minimize barometric and oxygenation changes during AE following TBI.

Impact of inpatient geriatrics consultation on hospital outcomes in older adults with trauma.

Older adults presenting with trauma have worse outcomes than younger adults. Starting in 2016, we provided geriatrics consultation (GC) to older adults admitted to the trauma service. We aimed to analyze the impact of GC on patient outcomes. We performed a retrospective pre-post study and year-matched cohort study. We identified patients from the trauma registry at our level 1 trauma center. In the pre-post study, we compared patients who received GC (2016-2022) with controls (2011-2015). In the cohort study (2016-2022), we compared patients who received GC with controls. We matched for age, race, sex, and injury severity score (ISS) in both studies, as well as admission year in the cohort study. Outcome variables included mortality (in-hospital, 30-day, 90-day), length of stay (LOS), discharge disposition, and hospital readmission rates (30-day, 90-day). We analyzed 1968 patients in the pre-post study and 2544 patients in the cohort study. Patients were similar in age, race, and sex. GC patients had a slightly higher ISS score and a higher rate of ICU stay. Delirium occurrence was lower among GC patients. GC patients had lower in-hospital mortality compared to controls (pre-post OR 0.27, p < 0.001; cohort OR 0.31, p < 0.001) and increased LOS (6 days vs 4 days, p < 0.001; both studies). GC patients in the cohort study also had lower 30- and 90-day mortality (OR 0.52 and 0.65, p < 0.01) and were less likely to return home (OR 0.81, p < 0.01); similar trends, though not statistically significant, were noted in the pre-post study. Lower readmission rates (statistically non-significant) were noted in the GC group across both studies. GC in older adults with trauma has proven benefit with reduced mortality and a trend toward lower readmission rates but was associated with increased LOS and higher rates of discharge to skilled facility.

Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature.

The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

Immunohistochemical profile of triple negative breast cancers: SOX10 and AR dual negative tumors have worse outcomes.

Triple negative breast cancer (TNBC) refers to an estrogen receptor negative, progesterone receptor negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor (LAR) subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding post-neoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR, INPP4B), basal (SOX10, Nestin, CK5, EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, TRPS1) markers. Survival analysis was performed to assess the significance of clinical pathologic variables including age, histology, grade, lymphovascular invasion [LVI], Nottingham prognostic index [NPI] category, AJCC stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15 while no special type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on univariable as well as multivariable analysis. LVI and higher NPI category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage, and chemotherapy status.

Kidney-sparing surgery has equivalent oncological outcomes to radical nephroureterectomy for ureteral urothelial carcinoma.

Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large prospective international UTUC registry. The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included UTUC patients who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumour features' differences between groups. Of 391 patients with ureteral UTUC, 309 (79.0%) received RNU, and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n=28) or segmental resection (n=54). After PSM, there were no differences in OS (p=0.525), CSS (p=0.487), upper tract RFS (p=0.147), intravesical RFS (p=0.989), PFS (p=0.617), and MFS (p=0.336) between KSS and RNU. Both ureteroscopic ablation and segmental resection had similar OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumour locations following segmental resection. In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumour locations following segmental resection.

Abstract A021: The role of MGAT5 in sex-dependent regulation of CD8+ T cells in muscle-invasive bladder cancer

Abstract Biological sex significantly affects bladder cancer incidence and outcome. Although men have much greater incidence of bladder cancer than women, females tend to be diagnosed with more advanced tumors and have worse outcomes. The mechanisms driving these differences are likely multifactorial, with biological factors playing an important role, however, much of the biology underlying these differences is unknown. The immune system is a critical regulator of cancer biology, and immune features have been associated with bladder cancer grade, stage, progression, and response to therapies. Sex dramatically affects the immune system including anti-tumor immunity. However, how sex and immunity intersect to affect clinical outcomes in bladder cancer patients remains unclear. CD8+ T cells are a key part of anti-tumor immune responses and the importance of inhibitory receptors such as programmed cell death-1 (PD-1), is now well established as a mechanism restricting T cell responses in MIBC. However, there are a variety of other regulatory pathways that restrict their anti-tumor function, which have yet to be investigated. One such pathway involves alterations in protein glycosylation, which can affect T cell function at many levels. The activity of the glycosyltransferase N-acetylglucosaminyltransferase V (MGAT5), responsible for complex N-glycan branching, has been shown to regulate T cell function in autoimmunity and chronic viral infections, however, its role in regulating anti-tumor CD8+ T cell responses has yet to be explored. We assessed the activity of MGAT5 in circulating and tumor-infiltrating CD8+ T cells in mice using a panel of cell lines in a syngeneic orthotopic model of muscle-invasive bladder cancer (MIBC). We found that in all tumor models, MGAT5 activity was upregulated in tumor infiltrating CD8+ T cells compared with circulating cells. Furthermore, using high parameter flow cytometry, we assessed the activity of MGAT5 in CD8+ T cells from mice with bladder cancer induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and in patients with MIBC. In both mice and humans, we found that sex affects MGAT5 activity in memory CD8+ T cells, with females exhibiting decreased MGAT5 activity in these cells compared to males. The functional significance of altering MGAT5 activity in T cells was also assessed in vivo. To do this, chimeric mice were generated by mixed bone-marrow transplant resulting in mice with loss of Mgat5 in T cells. Bladder cancer was then induced using BBN, and morbidity (defined as either 10% weight loss in one week, 10% weight loss post-BBN, or humane endpoint), as a proxy for mortality, was assessed over time. In this model, male mice were protected from BBN-induced morbidity compared to female mice, and this protection was abrogated by homozygous or heterozygous loss of Mgat5 in T cells. Overall, our data suggest that sex-dependent regulation of MGAT5 activity in CD8+ T cells may be an important underlying factor affecting outcomes in bladder cancer. Citation Format: Morgan E. Roberts, Igor Moskalev, Peter C. Black. The role of MGAT5 in sex-dependent regulation of CD8+ T cells in muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A021.

Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary disease.

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.