Univariate Subgroup Research Articles

A prediction model for secondary invasive fungal infection among severe SARS-CoV-2 positive patients in ICU.

The global COVID-19 pandemic has resulted in over seven million deaths, and IFI can further complicate the clinical course of COVID-19. Coinfection of COVID-19 and IFI (secondary IFI) pose significant threats not only to healthcare systems but also to patient lives. After the control measures for COVID-19 were lifted in China, we observed a substantial number of ICU patients developing COVID-19-associated IFI. This creates an urgent need for predictive assessment of COVID-19 patients in the ICU environment for early detection of suspected fungal infection cases. This study is a single-center, retrospective research endeavor. We conducted a case-control study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. The cases consisted of patients who developed any secondary IFI during their ICU stay at Jilin University China-Japan Union Hospital in Changchun, Jilin Province, China, from December 1st, 2022, to August 31st, 2023. The control group consisted of SARS-CoV-2 positive patients without secondary IFI. Descriptive and comparative analyses were performed, and a logistic regression prediction model for secondary IFI in COVID-19 patients was established. Additionally, we observed an increased incidence of COVID-19-associated pulmonary aspergillosis (CAPA) during this pandemic. Therefore, we conducted a univariate subgroup analysis on top of IFI, using non-CAPA patients as the control subgroup. From multivariate analysis, the prediction model identified 6 factors that are significantly associated with IFI, including the use of broad-spectrum antibiotics for more than 2 weeks (aOR=4.14, 95% CI 2.03-8.67), fever (aOR=2.3, 95%CI 1.16-4.55), elevated log IL-6 levels (aOR=1.22, 95% CI 1.04-1.43) and prone position ventilation (aOR=2.38, 95%CI 1.15-4.97) as independent risk factors for COVID-19 secondary IFI. High BMI (BMI ≥ 28 kg/m2) (aOR=0.85, 95% CI 0.75-0.94) and the use of COVID-19 immunoglobulin (aOR=0.45, 95% CI 0.2-0.97) were identified as independent protective factors against COVID-19 secondary IFI. The Receiver Operating Curve (ROC) area under the curve (AUC) of this model was 0.81, indicating good classification. We recommend paying special attention for the occurrence of secondary IFI in COVID-19 patients with low BMI (BMI < 28 kg/m2), elevated log IL-6 levels and fever. Additionally, during the treatment of COVID-19 patients, we emphasize the importance of minimizing the duration of broad-spectrum antibiotic use and highlight the potential of immunoglobulin application in reducing the incidence of IFI.

Exploring Socioeconomic Disparities in Surgical Site Infections

Introduction: Social disparities have been shown to impact a wide variety of healthcare outcomes. Surgical site infections (SSIs) are associated with substantial patient morbidity, but studies on the intersection of social disparity and SSI are limited. We sought to evaluate the association between SSI and the Center for Disease Control and Prevention’s social vulnerability index (SVI). Methods: Patients with National Health Safety Network (NHSN) procedure codes for colon, abdominal hysterectomy, hip prosthesis, knee prosthesis and spinal fusion surgeries were retrieved from the electronic medical records of 20 hospitals across 4 geographic markets. SSIs were identified by trained infection preventionists using NHSN definitions. Descriptive statistics were used for baseline demographic and clinical characteristics. Univariate logistic regression was performed to assess the association of demographic, clinical, and procedural factors with the outcome of SSI. Further univariate subgroup analysis was completed by procedure. To account for the nonlinear relationship between the social vulnerability index and SSIs, smoothing splines were used in a Bayesian hierarchical logistic regression model, with random effects to account for the different market practices. Nonlinear effects of procedure duration were also investigated while adjusting for the patient age, procedure type, and health system market. Results: 23,864 surgical procedures among 22,319 unique patients identified between 1 August 2022 and 31 August 2023. 96 patients with infection present at time of surgery were excluded. The study population was mostly white (74%) and female (65%) (Table 1). Less than 13% of the patients had more than one procedure during this time. In a univariate analysis, we found evidence of market and procedure effects, with colon surgery being associated with the highest odds of SSI. Procedure duration was significantly associated with SSI in both univariate and multivariable models, with a drastic increase in the odds of SSI for procedures &gt; 150 mins. In the multivariable model we found that SVIs lower than 0.4 (95% CI 0.28 to 0.55) are associated with an adjusted odds ratio (aOR) &lt; 1. (Figure 1) Conclusions: Our study shows that the relationship of social vulnerability and adverse outcomes is highly complex with nonlinear dynamics at play. After adjusting for procedure type, duration, patient age, gender and health system market the odds of SSIs increase sharply in patients with higher SVI until leveling off at an elevated risk.

The outcomes of different regimens depend on the molecular subtypes of pulmonary large-cell neuroendocrine carcinoma: A retrospective study in China.

The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains controversial, and recent advances in LCNEC molecular subtype classification have provided potential strategies for assisting in treatment decisions. Our study aimed to investigate the impact of treatment regimens, molecular subtypes and their concordance on clinical outcomes of patients diagnosed with LCNEC. All patients diagnosed with advanced pulmonary LCNEC in Peking Union Medical College Hospital (PUMCH) between January 2000 and October 2021 were enrolled in this retrospective study. The tumor samples were collected and sequenced using a tumor-specific gene panel, while clinical information was retrieved from the medical records system. The survival and therapeutic response were analyzed and compared between different subgroups classified by treatment regimen (SCLC or NSCLC-based), molecular subtype (type I or II) or the combination. In univariate subgroup analysis categorized only by treatment regimen or molecular subtype, there were no differences identified in DCR, ORR, PFS, or OS. Nevertheless, the group with consistent treatment regimen and molecular subtype exhibited significantly longer OS than that of the inconsistent group (median OS 37.7 vs. 8.3 months; p = 0.046). Particularly, the OS of patients with type II LCNEC treated with SCLC-based regimen was significantly prolonged than that of others (median 37.7 vs. 10.5 months; p = 0.039). Collectively, our study revealed the clinical outcomes of different treatment regimens for LCNEC patients highly depend on their molecular subtypes, highlighting the need for sequencing-guided therapy.

Prevalence of delayed antiretroviral therapy initiation among people living with HIV: A systematic review and meta-analysis.

HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally. This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran's Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis. Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7-42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2-46.4%) than female (36.5%, 95% CI: 26.9-50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%). Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation.

Predictors of the inability to achieve full oral feeding in postoperative infants with CHD.

Poor oral feeding is a known contributor to growth challenges in neonates with complex CHD who require early surgery. Almost 60% of these infants do not achieve full oral feeding by hospital discharge. This study's objective was to identify predictors of the inability to achieve full oral feeding by discharge in neonates with complex CHD following surgical intervention with cardiopulmonary bypass. A retrospective analysis of a prospective study of 192 full-term neonates with complex CHD was performed. A stepwise selection logistic regression model was developed to predict oral feeding status at hospital discharge. Univariate subgroup analysis was performed with groups determined based on a CHD classification system. 58% of neonates (112/192) failed to achieve full oral feeding by hospital discharge. A logistic regression model identified duration of deep hypothermic circulatory arrest and reintubation as predictors of the inability to achieve full oral feeding. Among neonates who achieved full oral feeding by discharge (42%), only 7.5% did so after postoperative day 10. Brain maturation, brain injury, and preoperative oral feeding were not predictors of full postoperative oral feeding. Many infants with CHD fail to achieve full oral feeding by time of hospital discharge. Longer duration of deep hypothermic circulatory arrest and increased number of intubations were predictive of poor feeding after surgery. Prolonging hospitalisation solely to achieve full oral feeding after postoperative day ten is of limited utility; earlier discharge should be promoted to avoid negative impacts on neonatal neurodevelopment as unintended consequences of lengthy hospitalisations.

Seroprevalence and risk factors of Borrelia burgdorferi sensu lato and Rickettsia species infection in humans in Mongolia, 2016-2020.

Borrelia burgdorferi sensu lato and Rickettsia spp. are worldwide causes of tick-borne infections. We aimed to estimate the seroprevalence of immunoglobulin G (IgG) antibodies against different tick-borne diseases (TBDs) and determine risk factors among Mongolians from 2016 to 2020. Blood samples were obtained from voluntary participants with a history of suspected tick bite who visited our hospital, and IgG antibodies against Rickettsia and Borrelia were detected using enzyme-linked immunosorbent assay (ELISA). The IgG antibody seropositivity rate against Rickettsia was 21.8% (1032/4724), while 3.4% (162/4724) of participants tested positive for serum IgG antibodies against Borrelia by ELISA.Binary logistic regression analysis was performed to evaluate risk factors for tick-borne rickettsiosis (TBR) and tick-borne borreliosis (TBB) using IgG serum sample. Age, occupation, and residence were significantly associated with these diseases; however, sex did not show any significant association. Seroprevalence was significantly higher among herders (40.6%, 95% confidence interval [CI]: 35.5-45.8; odds ratio [OR] 0.61; P < 0.001) and students (32.8%, 95% CI: 30.2-35.4; OR 0.75; P < 0.001) than among individuals with other occupations. The 25-29 age group had a slightly higher seroprevalence (35.1%, 95% CI: 28.1-42.6; OR 0.61; P < 0.006) than those in other age groups. Province was a stronger predictor of TBR than occupation and age group. In univariate subgroup analysis by age group, occupation, and residence were significantly associated with TBR seroprevalence, whereas age and province were associated with TBB seroprevalence. Thus, risk factors for TBD include residence, occupation, and age group. This study was conducted using samples from all Mongolian provinces and the capital city, and the risk factors and prevalence of Rickettsia and Borreliaare highlighted.

Seroprevalence and risk factors of tick-borne encephalitis in Mongolia between 2016 and 2022

The tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes severe encephalitis in humans and is transmitted through the bites of infected ticks. Ixodes ticks are the primary vector for TBEV in Mongolia, and approximately 3.4% carry the TBEV. The ticks are capable of not only transmitting these viruses but also serve as excellent reservoir hosts. The Dermacenter tick species may have similar properties. TBEV is a significant cause of virus-related diseases of the central nervous system in many European countries as well as in China, Russia, and Mongolia. Our objectives were to investigate TBEV seroprevalence and infection risk factors in different biogeographical zones and provinces, especially in the highly endemic areas of Mongolia. Serum samples were collected from individuals who experienced tick bites (n = 993) in Mongolia between 2016 and 2022. Enzyme-linked immunosorbent assay of the samples was performed to evaluate for TBEV-specific immunoglobulin (Ig)M and IgG. We analyzed the risk factors and seroprevalence of TBEV infection among these individuals using a cross-sectional, questionnaire-based study. Statistical analyses were performed using a multistage cluster sampling survey design, and all data were analyzed using the R software. TBEV IgM and IgG antibodies were detected in 8.1% (80/993) and 20.2% (201/993) of all serum samples, respectively. The seroprevalence was significantly higher in men (68%, 95% confidence interval [CI]: 1.63–3.13, odds ratio [OR]: 2.25) than in women (p < 0.001). Additionally, the seroprevalence was significantly higher among unemployed (35.0%, 95% CI: 0.31–0.84, OR: 0.51) than employed individuals (p < 0.001). The seroprevalence was the highest among the 25–29 and 35–39-year age groups (11%, 95% CI: 1.29–5.51, OR: 2.65 and 11%, 95% CI: 0.94–3.87, OR: 1.9, respectively), and the lowest in the 65–69-year age group (4%, 95% CI: 0.46–6.15, OR: 1.83) (p < 0.001). Furthermore, the seroprevalence was the highest in Selenge province and the capital city Ulaanbaatar (40%, 95% CI: 1.73–21.7, OR: 5.07 and 28%, 95% CI: 0.51–6.89, OR: 1.57, respectively) and the lowest in Bayan-Ulgii and Dornod provinces (0.5%, 95% CI: 0.06–12.4, OR: 1.33 and 0.5%, 95% CI: 0.03–6.24, OR: 0.72, respectively). TBEV infection incidence remained low in most regions of Mongolia but increased in endemic areas. Furthermore, in the univariate subgroup analysis, age, occupation status, and residential area were significantly associated with TBEV seroprevalence.

Efficiency of endovascular management with a combination of Onyx and coils for direct and indirect carotid cavernous fistula treatment: Experience of a single center

BackgroundTo evaluate the safety and efficacy of endovascular treatment with a combination of Onyx and coils for carotid cavernous fistulas (CCFs), and to characterize the factors associated with clinical and angiographic outcomes for direct and indirect CCFs. MethodsThis retrospective study included 31 patients with CCF treated with an endovascular procedure between December 2017 and March 2022. ResultsDirect and indirect CCFs were found in 14 (45.2%) and 17 (54.8%) cases, respectively. Direct CCFs included eleven traumatic carotid cavernous fistulas. The most common symptom on admission was chemosis, which was seen in 17 (54.8%) patients. Eight (25.7%) cases were treated by the transarterial approach. Fourteen (45.2%) cases were treated using the femoral vein-inferior petrosal sinus approach. Seven (22.6%) were treated by direct puncture of the superior ophthalmic vein. Two (6.5%) were treated by the femoral vein-facial vein approach. Immediate complete occlusion and follow-up rates were 93.5% and 96.7%, respectively. Twenty-nine (96.7%) patients experienced an improvement in their symptoms at clinical follow-up. Chemosis was significantly improved or resolved in 15 patients. Ophthalmoplegia was improved or resolved in 10 patients. Visual impairment was improved in 6 patients. Proptosis was improved or resolved in 5 patients. One case (3.2%) experienced procedure-related complication presented with transient oculomotor nerve palsy. In univariate subgroup analysis, use of balloon, treatment approach, and history of head trauma were significantly different between the direct and indirect CCF groups. ConclusionsEndovascular treatment with a combination of Onyx and coils is a safe and effective therapy for CCFs. In this study, the transarterial approach was a favorable option for embolization of direct CCFs. In contrast, the transvenous approach may be the first choice of treatment for indirect CCFs.

Mortality after radiotherapy or surgery in the treatment of early-stage non-small-cell lung cancer: a population-based data analysis in the clinical cancer registry of Brandenburg-Berlin

PurposeStereotactic body radiotherapy (SBRT) is an established treatment method with favorable toxicity for inoperable early-stage non-small-cell lung cancer (NSCLC) patients. This paper aims to evaluate the importance of SBRT in the treatment of early-stage lung cancer patients compared to surgery as standard of care.MethodsThe German clinical cancer register of Berlin-Brandenburg was assessed. Cases of lung cancer were considered if they had a TNM stage (clinical or pathological) of T1-T2a and N0/x and M0/x, corresponding to UICC stages I and II. In our analyses, cases diagnosed between 2000 and 2015 were included. We adjusted our models with propensity score matching. We compared patients treated with SBRT or surgery regarding age, Karnofsky performance status (KPS), sex, histological grade, and TNM classification. Further, we assessed the association of cancer-related parameters with mortality; hazard ratios (HR) from Cox proportional hazards models were computed.ResultsA total of 558 patients with UICC stages I and II NSCLC were analyzed. In univariate survival models, we found similar survival rates in patients who underwent radiotherapy compared with surgery (HR 1.2, 95% confidence interval [CI] 0.92–1.56; p = 0.2). Our univariate subgroup analyses of patients > 75 years showed a statistically nonsignificant survival benefit for patients treated with SBRT (HR 0.86, 95% CI 0.54–1.35; p = 0.5). Likewise, in our T1 subanalysis, survival rates were similar between the two treatment groups regarding overall survival (HR 1.12, 95% CI 0.57–2.19; p = 0.7). The availability of histological data might be slightly beneficial in terms of survival (HR 0.89, 95% CI 0.68–1.15; p = 0.4). This effect was also not significant. Regarding the availability of histological status in our subgroup analyses of elderly patients, we could show similar survival rates as well (HR 0.70, 95% CI 0.44–1.23; p = 0.14). T1-staged patients also had a statistically nonsignificant survival benefit if histological grading was available (HR 0.75, 95% CI 0.39–1.44; p = 0.4). Concerning adjusted covariates, better KPS scores were associated with better survival in our matched univariate Cox regression models. Further, higher histological grades and TNM stages were related to a higher mortality risk.ConclusionUsing population-based data, we observed an almost equal survival of patients treated with SBRT compared to surgery in stage I and II lung cancer. The availability of histological status might not be decisive in treatment planning. SBRT is comparable to surgery in terms of survival.

Comparing the effects of variable and traditional resistance training on maximal strength and muscle power in healthy adults: A systematic review and meta-analysis.

The aim of the study was to aggregate different effects between variable resistance training and traditional resistance training on maximal muscle strength and muscle power and identify potential sex- and training program-related moderator variables. Meta-analysis. A systematic literature search was conducted in SPORTDiscus, PubMed, and Web of Science. Interventions were included if they compared variable resistance training and traditional resistance training in healthy adults and examined the effects on measures of maximal muscle strength and/or muscle power of the lower and/or upper body. A random-effects model was used to calculate weighted and averaged standardized mean differences. Additionally, univariate sub-group analyses were independently computed for sex and training-related moderator variables. Seventeen studies comprising a total of 491 participants (341 men and 150 women, age 18-37 years) were included in the analyses. In terms of maximal muscle strength, there were no statistically significant differences between variable resistance training and traditional resistance training for the lower (p = 0.46, standardized mean difference = -0.10) or the upper body (p = 0.14, standardized mean difference = -0.17). Additionally, there were no significant training-related differences in muscle power for the lower (p = 0.16, standardized mean difference = 0.21) or upper body (p = 0.81, standardized mean difference = 0.05). Sub-group analyses showed a significant moderator effect for training period and repetitions per set for maximal muscle strength in the lower body (p = 0.03-0.04) with larger strength gains following traditional resistance training when performing more repetitions per set (p = 0.02, standardized mean difference = 0.43). No other significant sub-group effects were found (p = 0.18-0.82). Our results suggest that variable resistance training and traditional resistance training are equally effective in improving maximal muscle strength and muscle power in healthy adults.

Factors Impacting the Yield of Image-Guided Biopsy in Native Vertebral Osteomyelitis: A 10-Year Retrospective Study.

Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39-7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16-.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0-3 days and higher rates as duration increased (P = .017). Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.

PATH-15. THE PROGNOSTIC IMPLICATION OF MGMT PROMOTER METHYLATION IN IDH-MUTANT GLIOMAS

Abstract BACKGROUND MGMT promoter methylation in IDH-mutant gliomas was associated with improved survival in a recent study (PMID 35386566) but did not account for the updated WHO classification of CNS tumors. We evaluated the prognostic value of MGMT methylation in IDH-mutant gliomas incorporating the 2021 WHO classification. METHODS We retrospectively identified 431 patients with IDH-mutant gliomas treated at a single institution from 2010-2020. Kaplan-Meier method was used to estimate OS and PFS rates. Log-Rank test was used to evaluate differences between groups. RESULTS Median age was 36.2 years. MGMT promoter was methylated in 49.6%, unmethylated in 17.2%, partially methylated in 6.7%, and untested in 26.5%. Histological diagnosis was consistent with astrocytoma in 45.7%, oligodendroglioma in 33.9%, glioblastoma in 16.4%, and oligoastrocytoma in 4%. After accounting for 1p/19q and CDKN2A statuses, 190 patients had an integrated diagnosis of astrocytoma, grade 2 or 3; 94 had astrocytoma, grade 4; and 147 had oligodendroglioma, grade 2 or 3. There were 101 death events. Median OS was 33.36 years and median PFS was 5.67 years in MGMT methylated gliomas, compared to median OS of 12.54 years (p=0.0064) and median PFS of 3.91 years (p=0.0034) in unmethylated tumors. Upon univariate subgroup analysis, MGMT methylation was associated with significantly longer OS in histological astrocytomas, grade 2 or 4. However, when stratifying patients according to 2021 WHO classification of CNS tumors, there was no significant difference in OS between MGMT methylated and unmethylated astrocytomas or oligodendrogliomas, irrespective of WHO grade. CONCLUSION MGMT promoter methylation was associated with prolonged OS in histological astrocytomas, IDH-mutant. However, MGMT status did not impact survival after incorporating 2021 WHO classification of CNS tumors, suggesting that 1p/19q co-deletion and CDKN2A homozygous deletion are stronger prognostic factors in our cohort. The number of survival events was limited; larger datasets are required for more definitive conclusions.

Impact of Medicaid expansion on postoperative mortality in women with gynecologic cancer: a difference-in-difference analysis (020)

Objectives: To compare 30 and 90-day postoperative mortality after surgery for gynecologic malignancy before and after the advent of Medicaid expansion in 2014 in states which did and did not expand Medicaid using a difference-in-difference (DID) analysis. Methods: We included women aged 40-64 years diagnosed with a primary endometrial, ovarian, or cervical malignancy in the National Cancer Database between 2010 and 2016 who underwent surgery. The outcome variables were 30-day and 90-day postoperative mortality. We used logistic regression to evaluate mortality between pre-2014 (2010-2013) and post-2014 (2014-2016) time periods for states which did expand (“expansion states”) and did not expand (“non-expansion states”) Medicaid in January 2014. We further used a quasi-experimental DID logistic regression to compare postoperative mortality after 2014 between expansion and non-expansion states. Our main regression models adjusted for cancer stage, age, race, ethnicity, comorbidity score, health insurance, geographic location, income, education, and urban-rural location. Subgroup analyses were unadjusted, odds ratios (ORs) were reported for logistic regression models, and DID ORs were reported for difference-in-difference analyses. Results: Among 169,731 women, 30-day postoperative mortality improved for endometrial cancer in expansion compared to nonexpansion states after 2014 (DID OR: 0.54, 95% CI: 0.31-0.96) on adjusted regression. There was no significant DID change in 30-day postoperative mortality for ovarian and cervical cancer between expansion and non-expansion states. However, the 30-day postoperative mortality in expansion states after 2014 significantly decreased for endometrial cancer (OR: 0.42, 95% CI: 0.26-0.67) and ovarian cancer (OR: 0.67, 95% CI: 0.46-0.99) and significantly increased for cervical cancer (OR: 3.82, 95% CI: 1.12-13.01). Univariable subgroup analysis demonstrated improved 30-day postoperative mortality for Black women with endometrial cancer in expansion compared to non-expansion states after 2014 (DID OR: 0.22, 95% CI: 0.05-0.95). There were no significant DID changes in 90-day postoperative mortality after 2014 based on expansion status for any primary cancer site. However, 90-day postoperative mortality decreased significantly for endometrial (OR: 0.66, 95% CI: 0.50-0.85) cancer in expansion states after 2014. There was improved 90-day postoperative mortality for women with ovarian cancer in the Midwest in expansion compared to non-expansion states after 2014 on univariable subgroup analysis (DID OR: 0.48, 95% CI: 0.26-0.91). Objectives: To compare 30 and 90-day postoperative mortality after surgery for gynecologic malignancy before and after the advent of Medicaid expansion in 2014 in states which did and did not expand Medicaid using a difference-in-difference (DID) analysis. Methods: We included women aged 40-64 years diagnosed with a primary endometrial, ovarian, or cervical malignancy in the National Cancer Database between 2010 and 2016 who underwent surgery. The outcome variables were 30-day and 90-day postoperative mortality. We used logistic regression to evaluate mortality between pre-2014 (2010-2013) and post-2014 (2014-2016) time periods for states which did expand (“expansion states”) and did not expand (“non-expansion states”) Medicaid in January 2014. We further used a quasi-experimental DID logistic regression to compare postoperative mortality after 2014 between expansion and non-expansion states. Our main regression models adjusted for cancer stage, age, race, ethnicity, comorbidity score, health insurance, geographic location, income, education, and urban-rural location. Subgroup analyses were unadjusted, odds ratios (ORs) were reported for logistic regression models, and DID ORs were reported for difference-in-difference analyses. Results: Among 169,731 women, 30-day postoperative mortality improved for endometrial cancer in expansion compared to nonexpansion states after 2014 (DID OR: 0.54, 95% CI: 0.31-0.96) on adjusted regression. There was no significant DID change in 30-day postoperative mortality for ovarian and cervical cancer between expansion and non-expansion states. However, the 30-day postoperative mortality in expansion states after 2014 significantly decreased for endometrial cancer (OR: 0.42, 95% CI: 0.26-0.67) and ovarian cancer (OR: 0.67, 95% CI: 0.46-0.99) and significantly increased for cervical cancer (OR: 3.82, 95% CI: 1.12-13.01). Univariable subgroup analysis demonstrated improved 30-day postoperative mortality for Black women with endometrial cancer in expansion compared to non-expansion states after 2014 (DID OR: 0.22, 95% CI: 0.05-0.95). There were no significant DID changes in 90-day postoperative mortality after 2014 based on expansion status for any primary cancer site. However, 90-day postoperative mortality decreased significantly for endometrial (OR: 0.66, 95% CI: 0.50-0.85) cancer in expansion states after 2014. There was improved 90-day postoperative mortality for women with ovarian cancer in the Midwest in expansion compared to non-expansion states after 2014 on univariable subgroup analysis (DID OR: 0.48, 95% CI: 0.26-0.91).

Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection

BackgroundEfficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens.MethodsAn adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3–5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed.ResultsBaseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.ConclusionsThis analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.Trial registration: NCT02938520, NCT02951052, NCT03299049.

Medicaid expansion and 2-year survival in women with gynecologic cancer: a difference-in-difference analysis

The Affordable Care Act implemented optional Medicaid expansion starting in 2014, but the association between Medicaid expansion and gynecologic cancer survival is unknown. To evaluate the impact of Medicaid expansion by comparing 2-year survival among gynecologic cancers before and after 2014 in states that did and did not expand Medicaid using a difference-in-difference analysis. We searched the National Cancer Database for women aged 40 to 64 years, diagnosed with a primary gynecologic malignancy (endometrial, ovarian, cervical, vulvar, and vaginal) between 2010 and 2016. We used a quasiexperimental difference-in-difference multivariable Cox regression analysis to compare 2-year survival between states that expanded Medicaid in January 2014 and states that did not expand Medicaid as of 2016. We performed univariable subgroup difference-in-difference Cox regression analyses on the basis of stage, income, race, ethnicity, and geographic location. Adjusted linear difference-in-difference regressions evaluated the proportion of uninsured patients on the basis of expansion status after 2014. We evaluated adjusted Kaplan-Meier curves to examine differences on the basis of study period and expansion status. Our sample included 169,731 women, including 78,669 (46.3%) in expansion states and 91,062 (53.7%) in nonexpansion states. There was improved 2-year survival on adjusted difference-in-difference Cox regressions for women with ovarian cancer in expansion than in nonexpansion states after 2014 (hazard ratio, 0.88; 95% confidence interval, 0.82-0.94; P<.001) with no differences in endometrial, cervical, vaginal, vulvar, or combined gynecologic cancer sites on the basis of expansion status. On univariable subgroup difference-in-difference Cox analyses, women with ovarian cancer with stage III-IV disease (P=.008), non-Hispanic ethnicity (P=.042), those in the South (P=.016), and women with vulvar cancer in the Northeast (P=.022), had improved 2-year survival in expansion than in nonexpansion states after 2014. In contrast, women with cervical cancer in the South (P=.018) had worse 2-year survival in expansion than in nonexpansion states after 2014. All cancer sites had lower proportions of uninsured patients in expansion than in nonexpansion states after2014. There was a significant association between Medicaid expansion and improved 2-year survival for women with ovarian cancer in states that expanded Medicaid after 2014. Despite improved insurance coverage, racial, ethnic, and regional survival differences exist between expansion and nonexpansion states.

Oncologic outcomes of fertility-sparing surgery in early stage epithelial ovarian cancer: a population-based propensity score-matched analysis.

To evaluate the safety of fertility-sparing surgery (FSS) in reproductive women (younger than 50years) with early epithelial ovarian cancer (EOC). Reproductive women diagnosed with stage I EOC in the Surveillance, Epidemiology and End Results (SEER) database were identified. Surgeries that did not undergo hysterectomy and/or bilateral salpingo-oophorectomy were categorized as FSS, whereas non-FSS included bilateral salpingo-oophorectomy and hysterectomy. Propensity-score matching (PSM) was conducted to balance the covariates. Risk factor was identified by COX analysis. Kaplan-Meier curves were performed to evaluate the overall survival (OS) and cancer-specific survival (CSS). 3556 patients with stage I EOC were identified and divided into non-FSS group and FSS group. After PSM, 625 pairs of patients with stage I EOC were included. FSS was not inferior to non-FSS in the OS curve [HR 0.9127, 95% CI (0.6971 ~ 0.1.195), P = 0.5174; HR: 0.9378, 95% CI (0.6358 ~ 0.1.383), P = 0.7460] and the CSS curve [HR 0.8284, 95% CI (0.5932 ~ 1.157), P = 0.2949; HR 0.9003, 95% CI (0.5470 ~ 1.482), P = 0.6803] both in overall cohort and in matched cohort. Univariate COX analysis identified older age (45-49), moderate-differentiated to un-differentiation grade, IC stage, bigger tumor size (> 10cm) and chemotherapy as risk factors of prognostic outcome (P < 0.1). Not only in univariate subgroup analyses but also in bivariate factors subgroup analysis, the evidence was not enough to regard FSS as a harmful factor compared with non-FSS. Fertility-sparing surgery was comparable to non-FSS in terms of survival in reproductive women with stage I EOC. Patients with high-risk factors could also consider FSS as an effective alternative compared with non-FSS.

Prognostic value of O 6-methylguanine-DNA methyltransferase methylation in isocitrate dehydrogenase mutant gliomas.

BackgroundPatients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those that are IDH wild-type. Previous studies have shown the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma multiforme (GBM), which are predominantly IDH wild-type. Little is known of the prognostic value of MGMT methylation status for IDH mutant gliomas.MethodsWe retrospectively identified IDH mutant gliomas patients between 2011 and 2020 that were tested for MGMT promoter methylation. We generated Kaplan–Meier estimator curves and performed Cox proportional hazard models for overall survival (OS) and progression-free survival (PFS) to compare the outcomes of MGMT promoter methylated versus MGMT unmethylated patients.ResultsOf 419 IDH mutant gliomas with MGMT promoter methylation testing, we identified 54 GBMs, 223 astrocytomas, and 142 oligodendrogliomas. 62.3% patients had MGMT methylated tumors while 37.7% were MGMT unmethylated. On Kaplan–Meier analysis, median OS for all MGMT methylated patients was 17.7 years and 14.6 years for unmethylated patients. Median PFS for all MGMT methylated patients was 7.0 years and for unmethylated patients 5.2 years. After univariate subgroup analysis, MGMT methylation is only prognostic for OS and PFS in GBM, and for OS in anaplastic oligodendroglioma and anaplastic oligodendroglioma for OS. In multivariate analysis, MGMT unmethylated GBM patients carry a higher risk of death (HR 7.72, 95% CI 2.10–28.33) and recurrence (HR 3.85, 95% CI 1.35–10.96).Conclusions MGMT promoter methylation is associated with better OS and PFS for IDH mutant GBM. MGMT promoter methylation testing for other IDH mutant glioma subtypes may not provide additional information on prognostication.

Early Application of Palbociclib Plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer: A Better Choice Based on Data From the Chinese Population.

Background: Palbociclib is the most widely used cyclin-dependent kinase 4/6 inhibitor in China, but its early application efficacy on Chinese metastatic breast cancer (MBC) patients was reported deficiently. Methods: Between February 2019 to December 2021, 95 female hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) patients with MBC received palbociclib combined with AI or fulvestrant were retrospectively analyzed in our center. The primary outcome was progression-free survival (PFS). The objective response rate and clinical benefit rate (CBR) were evaluated. Results: The median follow-up period was 15 months (range from 2 to 37). Palbociclib performed superiorly when applicated in first-and-second line therapy than in later lines (P = .002). Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively. Univariate subgroup analysis showed that the previous history of salvage chemotherapy (P = .015) and the presence of liver metastases (P < .001) significantly affected the efficacy of palbociclib. Despite the existence of liver metastases and primary endocrine resistance, which are two independent predictors of poor prognosis, early application of palbociclib in advanced stage can bring further benefits to these two groups of patients, rather than choosing salvage chemotherapy in the first place. Conclusion: Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2- Chinese MBC patients. Better performance can be seen when palbociclib was applicated in the early stage.

Selective inference for effect modification via the lasso.

Effect modification occurs when the effect of the treatment on an outcome varies according to the level of other covariates and often has important implications in decision-making. When there are tens or hundreds of covariates, it becomes necessary to use the observed data to select a simpler model for effect modification and then make valid statistical inference. We propose a two-stage procedure to solve this problem. First, we use Robinson's transformation to decouple the nuisance parameters from the treatment effect of interest and use machine learning algorithms to estimate the nuisance parameters. Next, after plugging in the estimates of the nuisance parameters, we use the lasso to choose a low-complexity model for effect modification. Compared to a full model consisting of all the covariates, the selected model is much more interpretable. Compared to the univariate subgroup analyses, the selected model greatly reduces the number of false discoveries. We show that the conditional selective inference for the selected model is asymptotically valid given the rate assumptions in classical semiparametric regression. Extensive simulation studies are conducted to verify the asymptotic results and an epidemiological application is used to demonstrate the method.

Benefit of Adjuvant Chemotherapy After Radical Cystectomy for Treatment of Urothelial Carcinoma of the Bladder in the Elderly -An International Multicenter Study.

Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer, but approximately half of all patients will ultimately succumb to disease progression despite apparent cure with extirpative surgery. Elderly patients are at especially high risk of advanced disease and may benefit from perioperative systemic therapy. To assess the real-world benefit of adjuvant chemotherapy (AC) in patients ≥75 years old. We retrospectively reviewed patients who underwent RC for non-metastatic urothelial carcinoma of the bladder (UCB) from 12 participating international medical institutions. Kaplan-Meier survival curves and Cox regression models were used to assess the association between age groups, administration of AC and oncological outcome parameters such as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). 4,335 patients were included in the analyses, of which 820 (18.9%) were ≥75 years old. These elderly patients had a higher rate of adverse pathologic features. In an univariable subgroup analysis in patients ≥75 years with lymph node metastasis, 5-year OS was significantly higher in patients who had received AC (41% vs. 30.9%, p = 0.02). In a multivariable Cox model that was adjusted for several established outcome predictors, there was a significant favorable association between the administration of AC in elderly patients and OS, but no RFS or CSS. In this large observational study, the administration of AC was associated with improved OS, but not RFS or CSS, in elderly patients treated with RC for UCB. This is of clinical importance, as elderly patients are more likely to have adverse pathologic features and experience worse survival outcomes. Treatment of UCB should include both a multidisciplinary approach and a geriatric evaluation to identify patients who are most likely to tolerate and benefit from AC.