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.

TMErisk score: a tumor microenvironment-based model for predicting prognosis and immunotherapy in patients with head and neck squamous cell carcinoma

Tumor microenvironment (TME) is closely associated with the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). To investigate potential biomarkers for predicting therapeutic outcomes in HNSCC, we analyzed the immune and stromal status of HNSCC based on the genes associated with TME using the ESTIMATE algorithm. Immune and stromal genes were identified with differential gene expression and weighted gene co-expression network analysis (WGCNA). From these genes, 118 were initially selected through Cox univariate regression and then further input into least absolute shrinkage and selection operator (LASSO) regression analysis. As a result, 11 genes were screened out for the TME-related risk (TMErisk) score model which presented promising overall survival predictive potential. The TMErisk score was negatively associated with immune and stromal scores but positively associated with tumor purity. Individuals with high TMErisk scores exhibited decreased expression of most immune checkpoints and all human leukocyte antigen family genes, and reduced abundance of infiltrating immune cells. Divergent genes were mutated in HNSCC. In both high and low TMErisk score groups, the tumor protein P53 exhibited the highest mutation frequency. A higher TMErisk score was found to be associated with reduced overall survival probability and worse outcomes of immunotherapy. Therefore, the TMErisk score could serve as a valuable model for the outcome prediction of HNSCC in clinic.

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumors.

The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumors. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. The expression and clinical significance of isoform "A" of SALL4 was evaluated in 124 testicular germ cell tumors (TGCTs) subtypes, adjacent normal tissues and 22 benign tumors, using immunohistochemistry on tissue microarrays (TMA). A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumors compared to the normal tissues. Seminoma and yolk sac tumors had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumor recurrence (P= 0.04) and invasion of the epididymis (P = 0.011). SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty.

The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.

Donor genetic burden for cerebrovascular risk and kidney transplant outcome.

Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient. Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes. We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1year. Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function.

HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is one of the deadliest forms of cancer with limited therapy options. Overexpression of the heat shock protein 70 (HSP70) is a hallmark of cancer that is strongly associated with aggressive disease and worse clinical outcomes. However, the underlying mechanisms by which HSP70 allows tumor cells to thrive under conditions of continuous stress have not been fully described. Here, we report that PDAC has the highest expression of HSP70 relative to normal tissue across all cancersanalyzed. Furthermore, HSP70 expression is associated with tumor grade and is further enhanced in metastatic PDAC. We show that genetic or therapeutic ablation of HSP70 alters mitochondrial subcellular localization, impairs mitochondrial dynamics, and promotes mitochondrial swelling to induce apoptosis. Mechanistically, we find that targeting HSP70 suppresses the PTEN-induced kinase 1 (PINK1) mediated phosphorylation of dynamin-related protein 1 (DRP1). Treatment with the HSP70 inhibitor AP-4-139B was efficacious as a single agent in primary and metastatic mousemodels of PDAC. In addition, we demonstrate that HSP70 inhibition promotes the AMP-activated protein kinase (AMPK) mediated phosphorylation of Beclin-1, a key regulator of autophagic flux. Accordingly, we find that the autophagy inhibitor hydroxychloroquine (HCQ) enhances the ability of AP-4-139B to mediate anti-tumor activity in vivo. Collectively, our results suggest that HSP70 is a multi-functional driver of tumorigenesis that orchestrates mitochondrial dynamics and autophagy. Moreover, these findings support the rationale for concurrent inhibition of HSP70 and autophagy as a novel therapeutic approach for HSP70-driven PDAC.

Clinical Relevance of Resection Margins in Patients with Total Laryngectomy or Laryngopharyngectomy

Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin &gt; 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins &lt; 1 mm are related to significantly worse outcomes and should be avoided.

Georg Schmorl Prize of the German Spine Society (DWG) 2023: the influence of sarcopenia and paraspinal muscle composition on patient-reported outcomes: a prospective investigation of lumbar spinal fusion patients with 12-month follow-up.

This study aimed to investigate the impact of sarcopenia and lumbar paraspinal muscle composition (PMC) on patient-reported outcomes (PROs) after lumbar fusion surgery with 12-month follow-up (12M-FU). A prospective investigation of patients undergoing elective lumbar fusion was conducted. Preoperative MRI-based evaluation of the cross-sectional area (CSA), the functional CSA (fCSA), and the fat infiltration(FI) of the posterior paraspinal muscles (PPM) and the psoas muscle at level L3 was performed. Sarcopenia was defined by the psoas muscle index (PMI) at L3 (CSAPsoas [cm2]/(patients' height [m])2). PROs included Oswestry Disability Index (ODI), 12-item Short Form Healthy Survey with Physical (PCS-12) and Mental Component Scores (MCS-12) and Numerical Rating Scale back and leg (NRS-L) pain before surgery and 12months postoperatively. Univariate and multivariable regression determined associations among sarcopenia, PMC and PROs. 135 patients (52.6% female, 62.1years, BMI 29.1kg/m2) were analyzed. The univariate analysis demonstrated that a higher FI (PPM) was associated with worse ODI outcomes at 12M-FU in males. Sarcopenia (PMI) and higher FI (PPM) were associated with worse ODI and MCS-12 at 12M-FU in females. Sarcopenia and higher FI of the PPM are associated with worse PCS-12 and more leg pain in females. In the multivariable analysis, a higher preoperative FI of the PPM (β = 0.442; p = 0.012) and lower FI of the psoas (β = -0.439; p = 0.029) were associated with a worse ODI at 12M-FU after adjusting for covariates. Preoperative FI of the psoas and the PPM are associated with worse ODI outcomes one year after lumbar fusion. Sarcopenia is associated with worse ODI, PCS-12 and NRS-L in females, but not males. Considering sex differences, PMI and FI of the PPM might be used to counsel patients on their expectations for health-related quality of life after lumbar fusion.

Do time preferences predict diabetes outcomes? A combined survey and register-based study.

Identifying determinants of heterogeneity in health outcomes continues to be a focus in the health economic literature. In this study, we analyze whether time preferences predict health outcomes in individuals with type 1 diabetes (T1D) who use insulin pump therapy to manage their condition. We collect data on time preferences using a hypothetical matching task and estimate aggregate as well as individual-level discounting parameters using the exponential, hyperbolic, and quasi-hyperbolic discounting models. These parameters are then regressed against essential diabetes-related health outcomes obtained from registries and medical records, including glycemic control, kidney function, BMI, and number of hospital contacts. Our analyses indicate that all three discounting models fit the data equally well. Except for hospital contacts, we find robust evidence that impatience, as reflected by higher discounting, predicts worse health outcomes. Additionally, present bias is associated with worse kidney function. Our findings suggest that time preferences can explain some of the heterogeneity in health among individuals with T1D and call for increased attention on the role of time preferences in the design of disease management programs for individuals with chronic conditions.

Assessing Functional Outcomes of Partial Versus Radical Nephrectomy for T1b-T2 Renal Masses: Results from a Multi-institutional Collaboration.

Deterioration of renal function is associated with increased all-cause mortality. In renal masses larger than 4 cm, whether partial versus radical nephrectomy (PN vs. RN) might affect long-term functional outcomes is unknown. This study tested the association between PN versus RN and postoperative acute kidney injury (AKI), recovery of at least 90% of the preoperative estimated glomerular filtration rate (eGFR) at 1 year, upstaging of chronic kidney disease (CKD) one stage or more at 1 year, and eGFR decline of 45 ml/min/1.73 m2 or less at 1 year. Data from 23 high-volume institutions were used. The study included only surgically treated patients with single, unilateral, localized, clinical T1b-2 renal masses. Multivariable logistic regression analyses were performed. Overall, 968 PN patients and 325 RN patients were identified. The rate of AKI was lower in the PN versus the RN patients (17% vs. 58%; p < 0.001). At 1 year after surgery, for the PN versus the RN patients, the rate for recovery of at least 90% of baseline eGFR was 51% versus 16%, the rate of CKD progression of ≥ 1 stage was 38% versus 65%, and the rate of eGFR decline of 45 ml/min/1.73 m2 or less was 10% versus 23% (all p < 0.001). Radical nephrectomy independently predicted AKI (odds ratio [OR], 7.61), 1-year ≥ 90% eGFR recovery (OR, 0.30), 1-year CKD upstaging (OR, 1.78), and 1-year eGFR decline of 45 ml/min/1.73 m2 or less (OR, 2.36) (all p ≤ 0.002). For cT1b-2 masses, RN portends worse immediate and 1-year functional outcomes. When technically feasible and oncologically safe, efforts should be made to spare the kidney in case of large renal masses to avoid the hazard of glomerular function loss-related mortality.

How well do participants in clinical trials represent the U.S. population with chronic neck or back pain?

Randomized clinical trials (RCTs) are the gold standard for assessing treatment effectiveness; however, they have been criticized for generalizability issues such as how well trial participants represent those who receive the treatments in clinical practice. We assessed the representativeness of participants from eight RCTs for chronic spine pain in the U.S., which were used for an individual participant data meta-analysis on the cost-effectiveness of spinal manipulation for spine pain. In these clinical trials, spinal manipulation was performed by chiropractors. We conducted a retrospective secondary analysis of RCT data to compare trial participants' socio-demographic characteristics, clinical features, and health outcomes to a representative sample of (a) U.S. adults with chronic spine pain and (b) U.S. adults with chronic spine pain receiving chiropractic care, using secondary data from the National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS). We assessed differences between trial and U.S. spine populations using independent t-tests for means and z-tests for proportions, accounting for the complex multi-stage survey design of the NHIS and MEPS. We found the clinical trials had an under-representation of individuals from health disparity populations with lower percentages of racial and ethnic minority groups (Black/African American 7% lower, Hispanic 8% lower), less educated (No high school degree 19% lower, high school degree 11% lower), and unemployed adults (25% lower) with worse health outcomes (physical health scores 2.5 lower and mental health scores 5.3 lower using the SF-12/36) relative to the U.S. population with spine pain. While the odds of chiropractic use in the U.S. are lower for individuals from health disparity populations, the trials also under-represented these populations relative to U.S. adults with chronic spine pain who visit a chiropractor. Health disparity populations are not well represented in spine pain clinical trials. Embracing key community-based approaches, which have shown promise for increasing participation of underserved communities, is needed.

Structural and functional effects of C5aR1 antagonism in a rat model of neonatal hypoxic-ischemic encephalopathy.

Introduction The complement response activates upon reperfusion in neonatal hypoxic-ischemic encephalopathy (HIE) and contributes to excessive neuroinflammation and worse outcomes. C5a is a powerful anaphylatoxin central to each of the complement pathways, and its engagement with C5aR1 is directly tied to brain injury and neuronal death. Reasoning C5aR1 antagonism can decrease excessive neuroinflammation and thereby improve neurological and functional outcomes, we tested this hypothesis in a rat model of HIE with PMX205, a small molecule that inhibits C5a-C5aR1 interaction. Methods Term-equivalent pups (P10-12) were subjected to mild-moderate HIE by Vannucci's method and treated with PMX205. We compared motor and cognitive outcomes with two behavioral tests each [food-handling and accelerod; novel object recognition (NOR) and open field] to improve the accuracy of our conclusions. Results Improvements were observed in fine motor function, balance and exploratory behaviors, but little to no improvement in recognition memory and gross motor function. Lesion area and histological assessments showed robust cortical neuroprotection from treatment but persistent injury to the CA1 region of the hippocampus. Better structural and functional outcomes were seen with 1 day of treatment, suggesting C5aR1 antagonism beyond the latent injury phase may impair recovery. In a dose-response experiment, cerebral area loss from injury was improved only in female rats, suggesting underlying sexual dimorphisms in the complement response. Conclusion These results demonstrate proof-of-concept for targeting C5aR1 signaling in neonatal HIE with PMX205 and underscore the role of sex in hypoxic-ischemic injury.