Unmatched Analysis Research Articles

HIV/AIDS patients undergoing total knee arthroplasty are at higher risk of acute renal failure and transfusion and incurred higher cost: a propensity-matched database study

IntroductionHuman immunodeficiency virus (HIV) is a retrovirus that can cause acquired immunodeficiency syndrome (AIDS). Total knee arthroplasty (TKA) in HIV-positive patients has not been well documented in the current literature. Thus, this study aimed to examine the early postoperative outcomes and complications of HIV-positive TKA patients as compared to TKA patients who are HIV-negative patients by utilizing the National Inpatient Sample (NIS) database.MethodsAdmissions data for TKA and HIV were analyzed from the NIS database using ICD-10-CM diagnosis codes. An extensive array of preoperative and postoperative variables was compared among HIV positive TKA patients and HIV negative TKA patients. An unmatched analysis and a matched analysis using a 1:1 propensity match algorithm were conducted to compare the two groups.ResultsThe average age of the HIV-positive group was lower than the HIV-negative group (59.0 vs 66.7, p < 0.001). The HIV-positive group had a smaller percentage of females (38.4% vs 61.5%, p < 0.001) and a lower incidence of tobacco-related disorders than the HIV-negative group (10.3% vs 15.8%, p = 0.032). The HIV-positive group had a longer mean length of stay (3.0 days vs 2.4 days, p < 0.001) and a greater mean total charge incurred (90,780.25 vs 64,801.55, p < 0.001). In the unmatched analysis, the incidence of acute renal failure (6.4% vs 2%, p < 0.001), transfusions (3.9% vs 1.5%, p = 0.004), and periprosthetic joint infection (3% vs 1%, p = 0.007) was higher in HIV positive group. The matched analysis showed a higher incidence of acute renal failure group (6.4% vs 0.5%, p = 0.01) and transfusions (3.9% vs 5%, p = 0.01) in the HIV-positive but a statistically insignificant difference in the rate of periprosthetic joint infection (3% vs 1%, p = 0.153).ConclusionHIV/AIDS is associated with an increased incidence of acute renal failure and transfusions, as well as a longer length of stay and higher incurred costs in TKA patients.

Association of Interpregnancy Interval With Adverse Birth Outcomes

Many studies have reported an association of interpregnancy interval (IPI) between 2 consecutive births with adverse birth outcomes in low- and middle-income countries. However, most of these studies ignore the implications of some unmeasured confounders. To explore the association of IPI with adverse perinatal outcomes. This large-scale cohort study used the Guangdong Provincial Women and Children Health Information System in Guangdong Province, China, to obtain birth data recorded between January 1, 2014, and December 31, 2020. Matched-sibling design was used. The final cohort included first-born and second-born sibling pairs delivered by mothers who were permanent residents of Guangdong Province. The exposure variable was IPI, which was categorized as follows: less than 6, 6 to 11, 12 to 17, 18 to 23, 24 to 29, 30 to 35, and 36 or more months. The outcome variables were adverse birth outcomes: preterm birth (PTB, gestational age <37 weeks), low birth weight (LBW, <2500 g), and small for gestational age (SGA). Adjusted odds ratio (OR) and interaction odds ratio (IOR) associated with IPI were calculated. The study consisted of 725 392 sibling pairs of multiparous mothers. Among these mothers, 718 111 (99.0%) were aged 20 to 34 years, and 715 583 (98.7%) were of Han Chinese ethnicity. Unmatched analysis showed that a short IPI of less than 6 months was associated with higher risks of PTB (adjusted OR, 1.96; 95% CI, 1.87-2.06), LBW (adjusted OR, 1.88; 95% CI, 1.79-1.98), and SGA (adjusted OR, 1.34; 95% CI, 1.30-1.38) compared with an IPI of 18 to 23 months. These associations were attenuated in the matched-sibling analysis. An association of short IPI (<6 months) with PTB (adjusted IOR, 1.40; 95% CI, 1.30-1.51), LBW (adjusted IOR, 1.30; 95% CI, 1.21-1.40), and SGA (adjusted IOR, 1.16; 95% CI, 1.11-1.22) remained in the matched analysis. For IPI of 36 months or more, the odds of PTB (adjusted OR, 1.08; 95% CI, 1.03-1.14) and LBW (adjusted OR, 1.13; 95% CI, 1.07-1.19) in the unmatched analysis were also greater than the reference interval (18-23 months), but not for SGA (adjusted OR, 0.96; 95% CI, 0.93-0.99). Associations between a long IPI (≥36 months) and PTB (adjusted IOR, 1.10; 95% CI, 1.02-1.19) and LBW (adjusted IOR, 1.16; 95% CI, 1.07-1.26) remained through the sibling comparisons. Results of this study indicated that mothers with a short (<6 months) or long (≥36 months) IPI had greater odds of adverse birth outcomes. The findings may inform family planning policies and guide individuals and families who are planning for another pregnancy in China.

Cadaver Simulation is Associated with Increased Comfort in Performing Open Vascular Surgery Among Integrated Vascular Surgery (0+5) Residents and Recent Graduates

With the evolution in vascular surgery toward increased endovascular therapy and decreased open surgical training, comfort with open procedures by current trainees is declining. A proposed method to improve this discomfort is simulator training. We hypothesized that open, cadaver, and endovascular surgery simulation would be associated with increased self-perceived comfort in performing corresponding procedures. Integrated (0+5) vascular surgery residents and recent graduates in the United States were asked to complete a survey quantifying comfort via a Likert scale with procedures and experience with simulation training. Simulation groups were then matched using coarsened exact matching. Ordinal logistic regression assessed the association between simulation experience and comfort in performing procedures. Surveys were completed by 68 trainees and 20 attending surgeons in their first 5years of practice. On unmatched analyses, there were no significant differences in comfort in performing any open or endovascular aorto-mesenteric or peripheral vascular procedures between respondents who reported experience with open or endovascular simulation, respectively. However, respondents who reported cadaver simulation experience (58%, 51/88) had a significantly higher reported comfort score performing open juxtarenal aortic repair (2.4 vs. 1.7), superior mesenteric artery thrombectomy or bypass (2.5 vs. 1.9), inferior vena cava or iliac vein repair (2.2 vs. 1.7), axillary-femoral artery bypass (3.4 vs. 2.5), femoral-popliteal artery bypass (3.7 vs. 2.8), and inframalleolar artery bypass (2.8 vs. 2.1; all P<0.05). After matching on training level, number of abdominal cases completed, and number of open vascular cases completed, ordinal logistic regression demonstrated that previous cadaver simulation was significantly associated with increased comfort in performing open aortic repairs, venous repair, visceral revascularization, and peripheral bypasses. In this nationally representative sample, cadaver, but not open or endovascular, simulation was associated with increased comfort in performing open vascular surgery. Providing cadaver simulation to trainees may help to improve comfort levels in performing open surgery. Integrated vascular surgery training programs should consider implementing these experiences into their curriculum.

The survival benefit of anti-HER2 treatment in the management of small (T1mic, T1a, T1b, T1c), node-negative HER2+ breast cancer.

532 Background: Limited compelling prospective and retrospective data regarding the added benefit of anti-HER2 therapy in the management of small, node-negative HER2-positive breast cancer (HER2+BC) exists, in part due to differences in outcome reporting, unmatched analyses, and a lack of head-to-head comparisons. As a result, national guideline committees find themselves unable to confidently recommend anti-HER2 therapy and clinicians are left to exercise clinical judgement on whether the use of anti-HER2 therapy should be considered for such patients. Methods: Our team performed a multi-institutional retrospective analysis using the ASCO CancerLinQ database, with a focus on clinical data from small, node-negative HER2+BC patients diagnosed between 2010 to 2021. We compared clinical outcomes between those who received adjuvant trastuzumab therapy, with or without chemotherapy, to those who did not, with our primary outcomes being invasive disease-free survival (iDFS) and overall survival (OS). We performed both a univariate and multivariate analysis, using a Cox proportional hazard model to control for factors including age, ethnicity, body mass index, hormone status, tumor grade, histology type, BRCA status, region, and smoking history. Additionally, a three-arm univariate analysis was performed comparing untreated patients to trastuzumab alone versus combination therapy. Results: In total, 1206 patients met inclusion criteria, including 779 patients who received trastuzumab with or without chemotherapy. We found a statistically significant improvement in both iDFS (HR 0.73, p = 0.01) and OS (HR 0.63, p = 0.027) on univariate analysis for those receiving anti-HER2 therapy. Similarly on multivariate analysis, iDFS (HR 0.75, p = 0.030) and OS (HR 0.61, p = 0.029) were improved in those who received therapy, regardless of tumor size. Our three-arm univariate analysis involving no treatment (n = 427), trastuzumab monotherapy (n = 169), and combination therapy (n = 578) found that iDFS was significantly improved for both treatment arms compared to observation alone (p = 0.006), whereas OS trended towards significance in the treatment arms but did not reach this target (p = 0.061). No significant difference was noted between treatment arms. Conclusions: Our analysis found a statistically significant improvement in iDFS and OS when patients with small, node negative, HER2+BC received adjuvant anti-HER2 therapy with or without chemotherapy as compared to observation. From our univariate three-arm comparison, it appears that trastuzumab provides the majority of benefit to patients in terms of DFS, but this result is exploratory. Further investigation is warranted, including meta-analyses to better characterize the degree of benefit seen with anti-HER2 treatment. For now, this data adds to evidence suggesting added benefit with therapy over observation.

Chemotherapy in patients with a solitary colorectal liver metastasis – A nationwide propensity score matched study

IntroductionChemotherapy is widely used as an adjunct to surgery in the treatment of patients with resectable colorectal liver metastases. The aim of this study was to examine whether chemotherapy confers a survival benefit in patients with a solitary colorectal liver metastasis. MethodsAll consecutive patients between 2009 and 2017 in Sweden who were resected for a solitary colorectal liver metastasis were included. Patients treated with chemotherapy were compared with patients who had surgery alone. Unmatched and propensity score matched analyses were performed to compare overall survival, morbidity and mortality. ResultsOf 1224 eligible patients, 641 (52.4%) patients had chemotherapy, and 583 (47.6%) had surgery alone. After propensity score matching, two balanced groups with 102 patients in each, were analyzed. There was no difference in readmission within 30-days (p = 0.250), or morbidity, defined as Clavien-Dindo 3a or greater, between the groups (p = 0.761). There were no mortalities within ninety days. Radical resection margins were achieved in 92 (n = 94) per cent in the chemotherapy group, and 77 (n = 78) per cent in the surgery alone group (p = 0.016). Median overall survival was 91 (95% CI 73–109) months in the chemotherapy group, and 78 (95% CI 37–119) months in the surgery-alone group (p = 0.652). ConclusionThis nationwide register-based study showed no difference in overall survival between patients treated with chemotherapy compared to surgery alone. Upfront surgery may be advisable in resectable solitary colorectal liver metastasis.

Dissecting Tissue Compartment-Specific Protein Signatures in Primary and Metastatic Oropharyngeal Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) often presents with locoregional or distant disease, despite multimodal therapeutic approaches, which include surgical resection, chemoradiotherapy, and more recently, immunotherapy for metastatic or recurrent HNSCC. Therapies often target the primary and nodal regional HNSCC sites, and their efficacy at controlling occult distant sites remains poor. While our understanding of the tumor microenvironment conducive to effective therapies is increasing, the biology underpinning locoregional sites remains unclear. Here, we applied targeted spatial proteomic approaches to primary and lymph node metastasis from an oropharyngeal SCC (OPSCC) cohort to understand the expression of proteins within tumors, and stromal compartments of the respective sites in samples of both matched and unmatched patients. In unmatched analyses of n = 43 primary and 11 nodal metastases, our data indicated that tumor cells in nodal metastases had higher levels of Ki-67, PARP, BAD, and cleaved caspase 9, suggesting a role for increased proliferation, DNA repair, and apoptosis within these metastatic cells. Conversely, in matched analyses (n = 7), pro-apoptotic markers BIM and BAD were enriched in the stroma of primary tumors. Univariate, overall survival (OS) analysis indicated CD25 in tumor regions of primary tumors to be associated with reduced survival (HR = 3.3, p = 0.003), while progesterone receptor (PR) was associated with an improved OS (HR = 0.33, p = 0.015). This study highlights the utility of spatial proteomics for delineating the tumor and stromal compartment composition, and utility toward understanding these properties in locoregional metastasis. These findings indicate unique biological properties of lymph node metastases that may elucidate further understanding of distant metastatic in OPSCC.

Metabolic bone disease and fracture risk after gastric bypass and sleeve gastrectomy: comparative analysis of a multi-institutional research network.

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most performed bariatric procedures. Multiple studies have investigated the metabolic bone complications after bariatric surgery, but there is a paucity of data comparing bone health after RYGB and SG. To compare the rates of major fractures and osteoporosis after Roux-en-Y gastric bypass and sleeve gastrectomy. Data from TriNetX multi-institutional research network that includes data from multiple health care organizations in the USA was analyzed at West Virginia University. We conducted a retrospective cohort study using TriNetX, a federated multi-institutional research network. We identified patients who underwent RYGB or SG. Primary outcome was the rate of major fractures at 3 years after the procedure. Other outcomes includedthe rate of spine fracture, femur fracture, osteoporosis, and vitamin D deficiency at follow-up. In unmatched analysis, patients with SG were less likely to have major fractures or an osteoporosis diagnosis than RYGB patients at 3 years after the procedure (P < .05). After propensity-score matching, similar results were noted; patients with SG were less likely to have major fractures than RYGB patients at 3 years after procedure (2.85% versus 3.66%, risk ratio [RR]: .78, 95% confidence interval [CI]: .71-.85), and a lower rate of osteoporosis diagnosis was noted in the SG group. High rates of vitamin D deficiency were noted in both cohorts. The incidence of spine fractures was significantly lower in the SG group than in the RYGB group (.76% versus 1.18%, RR: .65, 95% CI: .54-.77). Similarly, the incidence of femur fracture was significantly lower after SG (RR: .62, 95% CI: .44-.88). Female sex, higher age, smoking history, and diabetes were independently associated with osteoporosis diagnosis during follow-up (all P values <.05). Our analyses showed that RYGB is associated with a higher risk of osteoporosis, vitamin D deficiency, and osteoporotic fractures. Thus, in patients with a higher baseline osteoporotic risk, SG may be preferred option; however, further studies are needed.

Patient related outcomes of mechanical lead extraction techniques (PROMET) study: A comparison of two professions.

With an increasing number of cardiac implantable electronic devices (CIEDs), there has been a paralleled increase in demand for transvenous lead extraction (TLE). Cardiac surgeons (CS) and cardiologists perform TLE; however, data comparing the two groups of operators is scarce. We compared the outcomes of TLE performed by cardiologists and CS from six European lead extraction units. Data was collected retrospectively of 2205 patients who had 3849 leads extracted (PROMET) between 2005 and 2018. Patient demographics and procedural outcomes were compared between the CS and cardiologist groups, using propensity score matching. A multivariate regression analysis was also performed for variables associated with 30-day mortality. CS performed the majority of extractions (59.8%), of leads with longer dwell times (90 [57-129 interquartile range (IQR)] vs. 62 [31-102 IQR] months, CS vs. cardiologists, p<.001) and with pre-dominantly non-infectious indications (57.4%vs. 50.2%, CS vs. cardiologists, p<.001). CS achieved a higher complete success per lead than the cardiologists (98.1%vs. 95.7%, respectively, p<.01), with a higher number of minor complications (5.51%vs. 2.1%, p<.01) and similar number of major complications (0.47%vs. 1.3%, p=.12). Thirty-day mortality was similarly low in the CS and cardiologist groups (1.76%vs. 0.94%, p=.21). Unmatched data multivariate analysis revealed infection indication (OR 6.12 [1.9-20.3], p<.01), procedure duration (OR 1.01 [1.01-1.02], p<.01) and CS operator (OR 2.67, [1.12-6.37], p=.027) were associated with 30-day mortality. TLE by CS was performed with similar safety and higher efficacy compared to cardiologists in high and medium-volume lead extraction centers.

Are Survival Outcomes Different for Young and Old Patients with Oral and Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis.

Simple SummaryOral cancer was considered a disease of old age. However, there has been a recent surge in the incidence of oral cancer in young individuals. Age dependence on survival outcomes such as overall survival, disease-free survival, recurrence, distant metastasis and second primary in surgically treated oral cancer has been investigated several times and the results differ. This systematic review and meta-analysis has been conducted to address this concern. The results of the present research may facilitate age-dependent prognosis stratification, which would assist in treatment planning in oral cancer patients.This systematic review and meta-analysis aims to address whether age can be a determinant of overall survival (OS), disease-free survival (DFS), recurrence, distant metastasis (DM) and second primary (SP) in surgically treated oral and oropharyngeal squamous cell carcinoma (OOPSCC). A total of 4981 cases and 44254 controls from 25 comparative observational studies were included in the analysis. A significantly better OS (matched subgroup analysis: OR 1.64; 95% CI 1.31–2.04, overall analysis: OR 1.48; 95% CI 1.09–2.01) was observed in young patients compared to older adults, with heterogeneity ranging from moderate to severe. Worse DFS (unmatched subgroup analysis OR 0.43; 95% CI 0.27–0.68) was observed in young patients compared to older adults with minimal to moderate heterogeneity. The frequency of recurrence (OR 1.49; 95% CI 1.10–2.02) and DM (OR 1.83; 95% CI 1.10–3.03) was significantly higher in the young patients, as found in unmatched and matched subgroup analysis, with the least heterogeneities. Young age can be considered as an independent prognostic factor for recurrence and distant metastases in OOP-SCC. Larger and methodologically robust observational studies with longer follow-up are needed to establish the definitive role of age as an independent prognostic factor on OS and DFS in OOPSCC.

Managed Care after Acute Myocardial Infarction (MC-AMI) improves prognosis in AMI survivors with pre-existing heart failure: A propensity score matching analysis of Polish nationwide program of comprehensive post-MI care.

Despite improvement in acute myocardial infarction (AMI) treatment, post-discharge mortality remains high. The outcomes are supposed to be even worse in patients with post-MI heart failure (HF), as only a half of patients with newly diagnosed HF survive four years. The study aimed to analyze whether managed care after acute myocardial infarction (MC-AMI) is associated with better survival in AMI survivors with a pre-existing diagnosis of HF. The study included 7228 patients with a pre-existing diagnosis of HF who survived the hospitalization for AMI in Poland between November 2017 and December 2020, of whom 2268 (31.4%) were referred for the MC-AMI program. The median follow-up was 1.5 (0.7-2.3) years. In the unmatched analysis, patients without MC-AMI had more than twice higher 12-month mortality (21.8% vs. 9.9%; P <0.01) than MC-AMI participants. The difference remained significant after propensity score matching (16,8% vs. 10.0%; P <0.01). In multivariable analysis, participation in MC-AMI was an independent factor of 12-month survival. MC-AMI participants had a lower stroke rate (1.5% vs. 3.0%; P <0.01) and fewer hospital admissions due to HF (22.9% vs. 27.6%; P <0.01). After propensity score matching, participation in MC-AMI was associated with lower rates of stroke, HF hospitalizations, and all-cause mortality in the 12-month follow-up and was an independent factor of 12-month survival in AMI survivors with pre-existing HF.

Education, income, and obesity: A nationwide Chinese twinstudy.

This study aimed to examine the association of socioeconomic status with obesity. A total of 39,262 twin individuals were included from the Chinese National Twin Registry (CNTR). Generalized estimating equation models for unmatched twin individual analyses and conditional logistic regression for the co-twin matched design were used. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was used to explore the evidence of a causal relationship. In general estimating equation models, high education level and income were associated with lower risk of obesity (odds ratio [OR]=0.74 [95% CI: 0.65 to 0.84] and 0.86 [95% CI: 0.77 to 0.96]). In conditional logistic regression analysis, the association with education was significant (OR=0.50 [95% CI: 0.34 to 0.74]) but the association with income was insignificant (OR=0.74 [95% CI: 0.48 to 1.15]). From the ICE FALCON analysis, a twin's obesity was associated with the co-twin's education and income. After adjusting for the twin's own education, the association disappeared ( =-0.10 [95% CI: -0.26 to 0.07]), whereas the twin's obesity was still associated with the co-twin's income but attenuated toward the null ( =-0.21 [95% CI: -0.36 to -0.06]). Socioeconomic status is negatively associated with obesity. Education may have a causal effect on obesity, whereas the association between income and obesity is confounded by familial factors.

Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population

Early features of Parkinson disease (PD) have been described through population-based studies that overrepresent White, affluent groups and may not be generalizable. To investigate the association between risk factors and prediagnostic presentations of PD in an ethnically diverse UK population with high socioeconomic deprivation but universal access to health care. A nested case-control study was conducted using electronic health care records on 1 016 277 individuals from primary care practices in East London to extract clinical information recorded between 1990 and February 6, 2018. The data were analyzed between September 3, 2020, and September 3, 2021. Individuals with a diagnosis of PD were compared with controls without PD or other major neurological conditions. A matched analysis (10 controls matched for each patient with PD according to age and sex) and an unmatched analysis (adjusted for age and sex) were undertaken using multivariable logistic regression to determine associations between risk factors and prediagnostic presentations to primary care with subsequent diagnosis of PD. Three time periods (<2, 2-<5, and 5-10 years before diagnosis) were analyzed separately and together. Of 1 016 277 individuals included in the data set, 5699 were excluded and 1055 patients with PD and 1 009 523 controls were included in the analysis. Patients with PD were older than controls (mean [SD], 72.9 [11.3] vs 40.3 [15.2] years), and more were male (632 [59.9%] vs 516 862 [51.2%]). In the matched analysis (1055 individuals with PD and 10 550 controls), associations were found for tremor (odds ratio [OR], 145.96; 95% CI, 90.55-235.28) and memory symptoms (OR, 8.60; 95% CI, 5.91-12.49) less than 2 years before the PD diagnosis. The associations were also found up to 10 years before PD diagnosis for tremor and 5 years for memory symptoms. Among midlife risk factors, hypertension (OR, 1.36; 95% CI, 1.19-1.55) and type 2 diabetes (OR, 1.39; 95% CI, 1.19-1.62) were associated with subsequent diagnosis of PD. Associations with early nonmotor features, including hypotension (OR, 6.84; 95% CI, 3.38-13.85), constipation (OR, 3.29; 95% CI, 2.32-4.66), and depression (OR, 4.69; 95% CI, 2.88-7.63), were also noted. Associations were found for epilepsy (OR, 2.5; 95% CI, 1.63-3.83) and hearing loss (OR, 1.66; 95% CI, 1.06-2.58), which have not previously been well reported. These findings were replicated using data from the UK Biobank. No association with future PD diagnosis was found for ethnicity or deprivation index level. This study provides data suggesting that a range of comorbidities and symptoms are encountered in primary care settings before PD diagnosis in an ethnically diverse and deprived population. Novel temporal associations were observed for epilepsy and hearing loss with subsequent development of PD. The prominence of memory symptoms suggests an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally underrepresented groups.

Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis.

The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. We compared blood gene expression (whole‐genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total, 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up‐ and downregulation of canonical signalling pathways. In the matched analysis, the top upregulated gene was cold‐inducible mRNA binding protein (CIRBP) which plays a role in cold‐induced suppression of cell proliferation. In addition, we found three signalling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. In conclusion, there are distinct signalling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression, providing a possible link to the modulation of body temperature and early immunosuppression. Future studies may focus on the canonical signalling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis.

Carfilzomib 56 mg/m2 twice-weekly in combination with dexamethasone and daratumumab (KdD) versus daratumumab in combination with bortezomib and dexamethasone (DVd): a matching-adjusted indirect treatment comparison

Given the increasing use of frontline lenalidomide-based therapies in multiple myeloma (MM), there is an emerging need for lenalidomide-sparing regimens at relapse. Carfilzomib plus dexamethasone and daratumumab (KdD) and daratumumab plus bortezomib and dexamethasone (DVd) are lenalidomide-sparing triplet regimens that are approved for relapsed and/or refractory MM (R/RMM). In the absence of a head-to-head trial comparing these treatments, a matching-adjusted indirect treatment comparison (MAIC) was conducted to assess the efficacy and safety of KdD versus DVd. Results showed that treatment with KdD decreases the risk of progression or death versus DVd (HR 0.64; 95% confidence interval (CI): 0.46–0.90). Time-dependent analysis demonstrated a larger benefit for KdD after the first eight cycles. Unmatched subgroup analysis indicated that KdD may be particularly effective in lenalidomide-exposed and -refractory patients. The present analysis suggests that KdD improves outcomes compared with DVd in patients with R/RMM and may provide a rationale for a preferential treatment.

Inpatient versus outpatient shoulder arthroplasty outcomes: A propensity score matched risk-adjusted analysis demonstrates the safety of outpatient shoulder arthroplasty

ObjectivesBeginning January 1, 2021 total shoulder arthroplasty (TSA) was removed from the Medicare (U.S national healthcare for patients ≥ 65years of age) inpatient-only list. Furthermore, there is limited data comparing outpatient and inpatient TSA among recent contemporary large population databases. This study aimed to analyze shoulder arthroplasty outcomes between inpatient and outpatient procedures at the national level. MethodsThe American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was utilized (2015–2019). Cases with a current procedural terminology of 23472 indicative of primary TSA and reverse total shoulder arthroplasty were included (N = 22,452). Outcomes were then analyzed in two approaches: unmatched analysis and propensity score matched risk-adjusted analysis. ResultsOverall, 9.7% (N = 2,185) of cases were performed outpatient and 90.3% (N = 20,357) of cases were performed inpatient. The rate of outpatient procedures has been steadily increasing (2015: 8.3%, 2016: 14.7%, 2017: 15.8%, 2018: 26.5%, 2019: 34.6%; P < 0.001). Outpatients were more likely to be male (50.7% vs. 43.7%) and younger (age < 65; 37.0% vs. 27.9%) and less likely to be ASA class 3 or 4 (49.5% vs. 58.3%). Outpatients had fewer comorbidities including obesity (46.1% vs. 51.9%), hypertension (60.5% vs. 67.4%), diabetes (15.1 vs. 18.2%), chronic obstructive pulmonary disease (4.8% vs. 7.0%), bleeding disorders (1.3% vs. 2.5%), or chronic steroid use (3.5% vs. 5.0%; all P < 0.001). In a non-risk matched analysis of outcomes, outpatient procedures displayed lower rates of any adverse event (3.5% vs. 5.3%; P < 0.001), minor adverse events (1.5% vs. 3.0%; P = 0.001), and readmission (2.2% vs. 2.8%; P = 0.025). Following a propensity score matched analysis, two risk matched cohorts of outpatient (N = 2,172) and inpatient (N = 2,172) procedures were identified. Subsequent analysis of outcomes revealed no significant differences in outcome metrics between risk-matched outpatient and inpatient procedures. ConclusionsFrom 2015 to 2019, there has been a four-fold increase in the proportion of outpatient shoulder arthroplasty cases in the ACS-NSQIP database. This study shows that outpatient shoulder arthroplasty may be safely performed in a select cohort of patients without increased risk of adverse events. After adjusting for comorbidities, there were no differences in clinical outcomes or rates of adverse outcomes between inpatient and outpatient shoulder arthroplasty. Level of evidenceRetrospective Observational Study, Level IV.

P231 Emergency Colectomy for IBD Is Not Associated with Increased Risk of Postoperative Infection, Reoperation or Readmission

Abstract Background The current literature suggests that IBD patients have worse outcomes after emergency surgery when compared to elective surgery. We hypothesized that this association will be lost after matching cohorts of emergency and elective patients. We aimed to confirm the current emergency IBD surgery literature in a large cohort of unmatched IBD patients. We then aimed to determine if postoperative outcomes are worse in matched patients undergoing elective vs emergency colectomy. Methods We utilized the NSQIP PUF IBD Cohort 2005–2019 to assess 30-day outcomes in adult IBD patients undergoing emergency vs elective colectomy. Our primary outcome was any complication. Our secondary endpoints were readmission, reoperation, and mortality. Univariable and multivariable logistic regression models were used to examine the association between emergency surgery and complications in the unmatched cohort. Propensity-score matching was performed to match emergency patients to non-emergency patients on a 1:1 basis. A logistic regression model was used to assign a propensity score to each patient using emergency surgery as the outcome. All preoperative and perioperative characteristics were included in the model except those with &amp;gt; 20% missing data. The probability of emergency surgery based on these factors was used as the propensity score. A greedy matching algorithm was used to find the best controls matches for each case. A Love plot was used to show the covariate balance. Conditional logistic regression were used to evaluate the association between outcomes and emergency surgery on the matched sample. Results A total of 16,790 patients (15,849 elective, 941 emergency) were included in the unmatched cohort analysis. 30-day outcomes in 21 categories including length of stay, surgical site infection, sepsis, death and cardiovascular, renal and thrombotic complications were worse in the emergency cohort (Table 1). After matching, 632 sets were constructed. The majority of adverse outcomes demonstrated in the unmatched cohort lost significance. Only unplanned intubation (OR 2.6, p=.006), &amp;gt;48 hours on a ventilator (OR 2.8, p&amp;lt;.001), septic shock (OR 3.6, p&amp;lt;.001) and any complication (OR 1.3, p=.03) retained significance (Table 2). Conclusion In concordance with the current literature, we demonstrated increased rates of postoperative infection, cardiovascular and renal complications, reoperation and length of stay in unmatched groups of IBD patients undergoing emergency vs elective surgery. However, the majority of these complications were not significantly different after propensity matching. This suggests that emergency surgery is not associated with poorer outcomes in terms of length of stay, mortality and most morbidities as previously thought.

Association of depression with mortality in nationwide twins: The mediating role of dementia.

The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association. From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45-64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively. In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46-2.00) for depression at any age, 1.72 (1.36-2.17) for early-life, 1.51 (1.19-1.90) for midlife, and 4.10 (2.02-8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09). Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study.

17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9-1.4). We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. · We observed higher risk for sPTB in the group receiving 17-OHP in the unmatched analysis. · After propensity-score matching, we still failed to identify a beneficial effect of 17-OHP on sPTB. · Sensitivity analyses demonstrated robustness to the inclusion criteria and modeling assumptions..

P-OGC41 Survival after curative chemoradiotherapy or neoadjuvant therapy and surgery converges in higher-risk patients with oesophageal cancer

Abstract Background Both curative chemoradiotherapy (cCRT) and neoadjuvant chemoradiotherapy and surgery (nCRTS) can be considered as treatments for potentially curable oesophageal squamous cell carcinoma (OSCC). Whilst this equipoise does not exist in oesophageal adenocarcinoma (OAC), there are patients in whom treatment decisions are not straightforward, creating an overlapping group in which cCRT might be considered in preference to neoadjuvant chemotherapy or chemoradiotherapy and surgery (nC(R)TS). We aim to see how survival changes between unmatched and matched cohorts of patients with OAC and OSCC treated with cCRT or nC(R)TS, to reflect difficult multidisciplinary team treatment decisions. Methods Patients treated with nC(R)TS or cCRT for OSCC and OAC were identified on an intention-to-treat basis from April 2016 to April 2019, allowing a minimum 2-year follow up from diagnosis. Upper third tumours were excluded due to clear preference for cCRT. Preoperative variables were compared using descriptive statistics, with OSCC and OAC analysed separately. Significantly different variables were used to generate propensity scores. Cohorts were then matched and analysis repeated to assess cohort symmetry. Overall survival and 2-year survival were investigated using Kaplan-Meier survival curves and log-rank testing. Analysis was performed in R. Results 60 and 231 patients with OSCC and OAC were treated with cCRT or nC(R)TS. In the unmatched analysis, nC(R)TS had superior overall and 2-year survival, however there were significant differences in age, Charlson comorbidity index and cancer stage in OSCC and OAC cohorts, and in tumour site for the OAC cohort. After propensity score matching, differences in overall and 2-year survival reduced, though no results reached significance (OSCC: nCRTS 2y survival 58% vs 51% and 54% in unmatched and matched cCRT cohorts, respectively; OAC: cCRT 2y survival 51% vs 60% and 56% in unmatched and matched nC(R)TS cohorts, respectively). Conclusions These data suggest that as patient and cancer related factors increase the difficulty of treatment decisions, the survival benefit of surgery reduces in both OSCC and OAC. These results underline the need for randomised controlled trials using current treatment and staging strategies, as there have been considerable advances since original comparisons of neoadjuvant and curative chemoradiotherapy. This study is limited by relatively short follow up and unpowered sample sizes, however the coded nature of the analysis provides a structure for regular review of outcomes in our unit using routinely collected data, and could be easily applied more widely.

Association of life‐course depression with the risk of dementia in late life: A nationwide twin study

AbstractBackgroundDepression in later life has been linked to dementia, yet whether depression is a prodromal phase or risk factor for dementia is still under debate. Thus, looking into the time window of depression occurrence may help unveil the nature of this link. We aimed to examine the association of depression with dementia from a life‐course perspective, and to explore the roles of genetic and early‐life environmental factors shared by twins, and education in this association.MethodWithin the Swedish Twin Registry, 41,727 dementia‐free twin individuals (mean age 60 years) were observed for 18 years to detect incident dementia. Life‐course depression was ascertained from the Patient Registry and divided as early‐, mid‐, late‐, early‐ to mid‐life, mid‐ to late‐life, and lifelong depression according to the age of occurrence. Dementia was ascertained based on the same registry. Generalized estimating equation (GEE) model was used for unmatched case‐control analysis and conditional logistic regression was used for co‐twin matched case‐control analysis.ResultOf all participants, 2,832 (6.8%) had depression and 3,258 (7.8%) developed dementia. In the multi‐adjusted GEE model of unmatched analysis, the odds ratio (OR) of dementia was 1.93 [95% confidence interval (CI): 1.69–2.21] for depression at any age. In stratified analyses, the ORs (95% CIs) of dementia were 0.98 (0.51–1.90) for early‐life, 1.46 (1.09–1.95) for mid‐life, 2.16 (1.82–2.56) for late‐life, 1.62 (0.60–4.35) for early‐ to mid‐life, 2.24 (1.49–3.36) for mid‐ to late‐life, and 2.65 (1.17–5.98) for lifelong depression respectively. No statistically significant difference in ORs from the unmatched and co‐twin matched analyses was observed (P = 0.60). In joint exposure analysis, the dementia risk associated with mid‐life depression was attenuated by education ≥8 years.ConclusionNot only late‐life depression, but also depression beginning from midlife is associated with dementia. Genetic and early‐life environmental factors seem not to account for the association. Higher education might buffer the impact of mid‐life depression on dementia.