Development of a long-term care service integration self-assessment tool.

The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.

Impact of Mediating and Confounding Variables on the Volume-Outcome Association in the Treatment of Pancreatic Cancer.

BACKGROUND: High-volume centers (HVC), academic centers (AC), and longer travel distances (TD) have been associated with improved outcomes for patients undergoing surgery for pancreatic adenocarcinoma (PAC). Effects of mediating variables on these associations remain undefined. The purpose of this study is to examine the direct effects of hospital volume, facility type, and travel distance on overall survival (OS) in patients undergoing surgery for PAC and characterize the indirect effects of patient-, disease-, and treatment-related mediating variables. PATIENTS AND METHODS: Using the National Cancer Database, patients with non-metastatic PAC who underwent resection were stratified by annual hospital volume (< 11, 11-19, and ≥ 20 cases/year), facility type (AC versus non-AC), and TD (≥ 40 versus < 40 miles). Associations with survival were evaluated using multiple regression models. Effects of mediating variables were assessed using mediation analysis. RESULTS: In total, 19,636 patients were included. Treatment at HVC or AC was associated with lower risk of death [hazard ratio (HR) 0.90, confidence interval (CI) 0.88-0.92; HR 0.89, CI 0.86-0.91, respectively]. TD did not impact OS. Patient-, disease-, and treatment-related variables explained 25.5% and 41.8% of the survival benefit attained from treatment at HVC and AC, reducing the survival benefit directly attributable to each variable to 4.9% and 6.4%, respectively. CONCLUSIONS: Treatment of PAC at HVC and AC was associated with improved OS, but the magnitude of this benefit was less when mediating variables were considered. From a healthcare utilization and cost-resource perspective, further research is needed to identify patients who would benefit most from selective referral to HVC or AC.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

Hiding private information in private information protection liquid crystal displays using periodical waveplates and pixel quaternity.

A method to hide private information (PI) in private information protection liquid crystal displays (PIPLCDs) using periodical waveplates and pixel quaternity is reported in this study. The PIPLCD structure and its operation mechanism are conceptually elucidated. Users employing wide-view broadband circular polarizers (WVBCPs) can see PI hidden in images displayed on the PIPLCDs in PIP mode. However, people who do not use WVBCPs can only see the displayed images but not the PI at almost any viewing angles. The issues of the PIPLCD in PIP mode and possible fabrications of the periodical waveplates are also discussed.

Remdesivir and Mortality in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19. METHODS: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital. RESULTS: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049). CONCLUSION: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.

Cancer case trends following the onset of the COVID-19 pandemic: A community-based observational study with extended follow-up.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted health care delivery worldwide. Cancer is a leading cause of death, and the impact of the pandemic on cancer diagnoses is an important public health concern. METHODS: This cross-sectional study retrospectively analyzed the electronic medical records of 80,138 cancer patients diagnosed between January 1, 2019, and May 31, 2021. Outcome measures included weekly number of new cancer cases and trends in weekly cancer cases, before and after the pandemic; patient demographics; and positive COVID-19 test rates. RESULTS: Beginning March 4, 2020, defined as the onset of the pandemic, weekly cancer cases declined precipitously (-110.0 cases per week [95% confidence interval, -190.2 to -29.8]) for 4 weeks, followed by a moderate recovery (+23.7 cases per week [9.1 to 38.4]) of 10 weeks duration. Thereafter, weekly cancer cases trended slowly back toward pre-COVID-19 baseline levels. Following the pandemic onset, there was a cumulative year-over-year decline in cancer cases overall of 7.3%, including a 20.2%, 14.3%, and 12.8% decline in nonmelanoma skin cancer, breast cancer, and prostate cancer, respectively. Changes in case volumes were accompanied by variations in patient characteristics, including region, age, gender, race, insurance coverage, and COVID-19 positive test rates (P < .01 for all). Among patients tested for COVID-19, 5.3% had a positive result. CONCLUSIONS: The data in this study demonstrate a substantial reduction in cancer diagnoses following the onset of COVID-19, which appear to reach expected pre-COVID norms 12 months later. The largest reduction was noted among cancers that are typically screen-detected or identified as part of a routine wellness examination.

Impact of Locoregional Treatment on Survival in Young Patients with Early-Stage Breast Cancer undergoing Upfront Surgery.

BACKGROUND: Randomized, controlled trials comparing breast-conserving therapy (BCT) with mastectomy have demonstrated equivalent overall survival (OS), but recent observational studies have shown improved OS in patients undergoing BCT. These studies provide limited data on young patients who are traditionally offered mastectomy due to perceived higher disease risk. This study examines the OS in a contemporary series of young women with breast cancer undergoing upfront BCT compared with mastectomy. METHODS: Women ≤40 years old with primary invasive T1-T2, N0-N1 breast cancer were identified from the National Cancer Database between 2006 and 2016. Patient cohorts were based according to locoregional treatment: BCT, mastectomy alone (Mx), and mastectomy with radiotherapy (Mx/RT). Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability of treatment weighting (IPTW) were performed to account for treatment selection bias effects in OS. RESULTS: A total of 15,611 patients met the study criteria; 9,509 patients (60.9%) had BCT, 4,020 (25.8%) had Mx/RT, and 2,082 (13.3%) had Mx alone. The median follow-up was 4.6 years (interquartile range [IQR] 3.0-6.4). After IPTW-adjustment, the 5-year OS was similar for BCT (95%), Mx (95%), and Mx/RT (94%), and there was no significant difference in OS in Mx (hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.90-1.51) and Mx/RT (HR = 1.08, 95% CI 0.88-1.34) compared with BCT. Mx/RT was associated with decreased survival in patients with pT2N0 (HR = 1.78, 95% CI 1.12-2.84). CONCLUSIONS: Among young patients with early-stage breast cancer, overall survival was equivalent regardless of surgical approach. Breast-conserving therapy remains a safe option in young women despite the clinical tendency to offer upfront mastectomy in young patients.

Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.

Preoperative Risk Prediction for Pancreatectomy: A Comparative Analysis of Three Scoring Systems.

INTRODUCTION: Pancreatectomy is associated with high morbidity and mortality. Therefore, patient selection and risk prediction is paramount. In this study, three validated perioperative risk scoring systems were compared among patients undergoing pancreatectomy to identify the most clinically useful model. MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried for pancreatectomy patients. Three models were evaluated: National Surgical Quality Improvement Program Universal Risk Calculator (URC), Model for End-Stage Liver Disease (MELD), and Modified Frailty Index-5 Factor (mFI-5). Outcomes were 30-d mortality and complications. Predictive performance of the models was compared using area under the receiver operating characteristic curve (AUC) and Brier scores. RESULTS: Twenty two thousand one hundred twenty three pancreatectomy patients were identified. The 30-d mortality rate was 1.4% (n = 319). Complications occurred in 6020 cases (27.2%). AUC (95% CI) for 30-d mortality were 0.70 (0.67-0.73), 0.63 (0.60-0.67), and 0.60 (0.57-0.63) for URC, MELD, and mFI-5, respectively, with Brier score of 0.014 for all three models. AUC (95% confidence interval) for any complication was 0.59 (0.58-0.59) for URC, 0.53 (0.52-0.54) for MELD, and 0.53 (0.52-0.54) for mFI-5, with Brier scores 0.193 (URC), 0.200 (MELD), and 0.197 (mFI-5). For individual complications, URC was more predictive than MELD or mFI-5. CONCLUSIONS: Of the validated preoperative risk scoring systems, URC was most predictive of both complications and 30-d mortality. None of the models performed better than fair to good. The lack of predictive accuracy of currently existing models highlights the need for development of improved perioperative risk models.

Utilization of palliative care resource remains low, consuming potentially avoidable hospital admissions in stage IV non-small cell lung cancer: a community-based retrospective review.

PURPOSE: Early referral of patients with stage IV non-small cell lung cancer (NSCLC) to outpatient palliative care has been shown to increase survival and reduce unnecessary healthcare resource utilization. We aimed to determine outpatient palliative care referral rate and subsequent resource utilization in patients with stage IV NSCLC in a multistate, community-based hospital network and identify rates and reasons for admissions within a local healthcare system of Washington State. METHODS: A retrospective chart review of a multistate hospital network and a local healthcare system. Patients were identified using ICD billing codes. In the multistate network, 2844 patients diagnosed with stage IV NSCLC between January 1, 2013, and March 1, 2018, were reviewed. In the state healthcare system, 283 patients between August 2014 and June 2017 were reviewed. RESULTS: Referral for outpatient palliative care was low: 8% (217/2844) in the multistate network and 11% (32/283) in the local healthcare system. Early outpatient palliative care (6%, 10/156) was associated with a lower proportion of patients admitted into the intensive care unit in the last 30 days of life compared to no outpatient palliative care (15%, 399/2627; p = 0.003). Outpatient palliative care referral was associated with improved overall survival in Kaplan Meier survival analysis. Within the local system, 51% (104/204) of admissions could have been managed in outpatient setting, and of the patients admitted in the last 30 days of life, 59% (87/147) experienced in-hospital deaths. CONCLUSION: We identified underutilization of outpatient palliative care services within stage IV NSCLC patients. Many patients with NSCLC experience hospitalization the last month of life and in-hospital death.

Prognostic indicators for undifferentiated carcinoma with/without osteoclast-like giant cells of the pancreas.

BACKGROUND: Undifferentiated carcinoma of the pancreas (UPC) is a rare malignancy. There are no standardized guidelines for treatment. Current management has been extrapolated from smaller reviews. METHODS: 858 patients with UPC were identified in the 2004-2017 NCDB. Kaplan-Meier method followed by Cox proportional-hazards regression examined independent prognostic factors associated with overall survival (OS). Logistic regression analyses were performed to determine independent predictors of surgical intervention and the status of surgical resection by histologic subtype. RESULTS: Patients with osteoclast-like giant cells (OCLGC) had a longer median OS compared to those without (aHR 0.52: 95% CI 0.41-0.67). Of the non-OCLGC subtypes, pleomorphic large cell demonstrated the shortest median OS (2.4 months). Surgical resection was associated with improved survival in all histologies except for pleomorphic cell carcinoma. R0 resection and negative lymph nodes were independently associated with an improved OS. CONCLUSION: This is the largest database review published to date on UCP. OCLGC histology is associated with an improved survival compared to those without OCLGC. Of the non-OCLGC subtypes, pleomorphic large cell is associated with the shortest overall survival. Surgical resection is associated with a significant survival advantage for all histologies except for pleomorphic cell carcinoma.

Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer.

BACKGROUND: The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents. METHODS: Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power. RESULTS: mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p < .001). Hierarchical linear modeling resulted in more precise estimates of treatment-related increases in sTIL, PD-L1, and other metrics such as CD8+ tumor nest infiltration. Statistical precision was dependent on adequate tissue sampling, with at least 15 high-powered fields recommended per specimen. Compared to conventional t-testing of means, hierarchical linear modeling was associated with substantial reductions in enrollment size required (n = 25➔n = 13) to detect the observed increases in sTIL/PD-L1. CONCLUSION: mIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials. TRIAL REGISTRATION: NCT02950259 .

Is the 21-Gene Recurrence Score on Core Needle Biopsy Equivalent to Surgical Specimen in Early-Stage Breast Cancer? A Comparison of Gene Expression Between Paired Core Needle Biopsy and Surgical Specimens.

BACKGROUND: Molecular testing on surgical specimens predicts disease recurrence and benefit of adjuvant chemotherapy in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (EBC). Testing on core biopsies has become common practice despite limited evidence of concordance between core/surgical samples. In this study, we compared the gene expression of the 21 genes and the recurrence score (RS) between paired core/surgical specimens. METHODS: Eighty patients with HR+/HER2- EBC were evaluated from two publicly available gene expression datasets (GSE73235, GSE76728) with paired core/surgical specimens without neoadjuvant systemic therapy. The expression of the 21 genes was compared in paired samples. A microarray-based RS was calculated and a value ≥ 26 was defined as high-RS. The concordance rate and kappa statistic were used to evaluate the agreement between the RS of paired samples. RESULTS: Overall, there was no significant difference and a high correlation in the gene expression levels of the 21 genes between paired samples. However, CD68 and RPLP0 in GSE73235, AURKA, BAG1, and TFRC in GSE76728, and MYLBL2 and ACTB in both datasets exhibited weak to moderate correlation (r < 0.5). There was a high correlation of the microarray-based RS between paired samples in GSE76728 (r = 0.91, 95% confidence interval [CI] 0.81-0.96) and GSE73235 (r = 0.82, 95% CI 0.71-0.89). There were no changes in RS category in GSE76728, whereas 82% of patients remained in the same RS category in GSE73235 (κ = 0.64). CONCLUSIONS: Gene expression levels of the 21-gene RS showed a high correlation between paired specimens. Potential sampling and biological variability on a set of genes need to be considered to better estimate the RS from core needle biopsy.

Impact of Hepatic Metastasectomy in the Multimodal Treatment of Metastatic Breast Cancer.

BACKGROUND: Surgical management of hepatic metastases in patients with stage IV breast cancer remains controversial. The purpose of this study was to examine the impact of hepatic metastasectomy on long-term outcomes. METHODS: The 2004-2015 National Cancer Database was queried for all patients diagnosed with stage IV breast cancer with metastases isolated to the liver. Patient demographics, disease-, treatment- and outcome-related data were analyzed. RESULTS: Of 2,895 patients, only 90 (3.1%) underwent hepatic resection. Compared to patients who did not undergo metastasectomy, patients treated with metastasectomy tended to be younger (52 ± 12.7 versus 59.2 ± 14.6; P < 0.001) and have private insurance (74.4% versus 45.3%; P < 0.001). Independent predictors of metastasectomy included younger age (OR 0.98; CI 0.96-0.99; P = 0.01), lobular carcinoma (OR 2.26; CI 1.06-4.82; P = 0.03), and prior surgery of the primary site (partial mastectomy (OR 6.96; CI 3.47-13.95; P < 0.001) or total mastectomy (OR 5.74; CI 3.06-10.76; P < 0.001)). Compared to no metastasectomy, hepatic metastasectomy was independently associated with a 37% reduction in the risk of death (HR 0.63; CI 0.44-0.91; P = 0.01). CONCLUSIONS: Stage IV breast cancer with metastases to the liver is rare and few patients undergo hepatic resection. However, in this select patient population, hepatic metastasectomy was associated with a significant survival advantage when included in the multimodal treatment of synchronous stage IV breast cancer.

Delay in surgery is associated with axillary upstaging of clinically node negative breast cancer patients.

BACKGROUND AND OBJECTIVES: Most breast cancer (BC) patients present with early disease and clinically negative lymph nodes (cN0). Timing of surgery has not been standardized. We hypothesized that surgical delay results in an increased likelihood of nodal metastasis. METHODS: Patients diagnosed with cN0 BC undergoing surgery with sentinel lymph node biopsy as initial therapy between 2006 and 2014 were identified in the NCDB and divided into four groups based on time intervals between diagnosis and surgery (<4 weeks, 4-8 weeks, 8-12 weeks, and >12 weeks). Regression analysis evaluated the independent impact of surgical timing on axillary upstaging and survival. RESULTS: Of 355,443 patients with cN0 BC, 39.6% had surgery within 4 weeks and 5.4% more than 12 weeks from diagnosis. After controlling for relevant factors, a month delay in surgery was associated with an increased likelihood of nodal positivity (odds ratio: 1.04; 95% confidence interval [CI]: 1.04-1.05; p < .001) and decreased overall survival (hazard ratio: 1.03; 95% CI: 1.02-1.04; p < .001). When compared to patients who underwent surgery less than 4 weeks from diagnosis, the absolute increase in nodal positivity and relative risks were 5.3% (95% CI: 0.047-0.059) and 1.34 (95% CI: 1.30-1.38), respectively, in the more than 12 weeks group. CONCLUSIONS: Delay in BC surgery in cN0 patients was associated with an increased likelihood of axillary upstaging and decreased survival.

Surge effects and survival to hospital discharge in critical care patients with COVID-19 during the early pandemic: a cohort study.

BACKGROUND: The early months of the COVID-19 pandemic were fraught with much uncertainty and some resource constraint. We assessed the change in survival to hospital discharge over time for intensive care unit patients with COVID-19 during the first 3 months of the pandemic and the presence of any surge effects on patient outcomes. METHODS: Retrospective cohort study using electronic medical record data for all patients with laboratory-confirmed COVID-19 admitted to intensive care units from February 25, 2020, to May 15, 2020, at one of 26 hospitals within an integrated delivery system in the Western USA. Patient demographics, comorbidities, and severity of illness were measured along with medical therapies and hospital outcomes over time. Multivariable logistic regression models were constructed to assess temporal changes in survival to hospital discharge during the study period. RESULTS: Of 620 patients with COVID-19 admitted to the ICU [mean age 63.5 years (SD 15.7) and 69% male], 403 (65%) survived to hospital discharge and 217 (35%) died in the hospital. Survival to hospital discharge increased over time, from 60.0% in the first 2 weeks of the study period to 67.6% in the last 2 weeks. In a multivariable logistic regression analysis, the risk-adjusted odds of survival to hospital discharge increased over time (biweekly change, adjusted odds ratio [aOR] 1.22, 95% CI 1.04-1.40, P = 0.02). Additionally, an a priori-defined explanatory model showed that after adjusting for both hospital occupancy and percent hospital capacity by COVID-19-positive individuals and persons under investigation (PUI), the temporal trend in risk-adjusted patient survival to hospital discharge remained the same (biweekly change, aOR 1.18, 95% CI 1.00-1.38, P = 0.04). The presence of greater rates of COVID-19 positive/PUI as a percentage of hospital capacity was, however, significantly and inversely associated with survival to hospital discharge (aOR 0.95, 95% CI 0.92-0.98, P < 0.01). CONCLUSIONS: During the early COVID-19 pandemic, risk-adjusted survival to hospital discharge increased over time for critical care patients. An association was also seen between a greater COVID-19-positive/PUI percentage of hospital capacity and a lower survival rate to hospital discharge.

Cumulative radiation dose incurred during the management of complex pleural space infection.

BACKGROUND: Complex pleural space infections are commonly managed with antibiotics, pleural drainage, intrapleural fibrinolytic therapy, and surgery. These strategies often utilize radiographic imaging during management, however little data is available on cumulative radiation exposure received during inpatient management. We aimed to identify the type and quantity of radiographic studies along with the resultant radiation exposure during the management of complex pleural space infections. METHODS: Retrospective review of community network healthcare system from January 2015 to July 2018. Patients were identified through billing databases as receiving intrapleural fibrinolytic therapy and/or surgical intervention. Patient demographics, clinical outcomes, and inpatient radiographic imaging was collected to calculate cumulative effective dose. RESULTS: A total of 566 patients were identified with 7275 total radiographic studies performed and a median cumulative effective dose of 16.9 (IQR 9.9-26.3) mSv. Multivariable linear regression analysis revealed computed tomography use was associated with increased cumulative dose, whereas increased age was associated with lower cumulative dose. Over 74% of patients received more than 10 mSv, with 7.4% receiving more than 40 mSv. CONCLUSIONS: The number of radiographic studies and overall cumulative effective dose in patients hospitalized for complex pleural space infection was high with the median cumulative effective dose > 5 times normal yearly exposure. Ionizing radiation and modern radiology techniques have revolutionized medical care, but are likely not without risk. Additional study is warranted to identify the frequency and imaging type needed during complex pleural space infection management, attempting to keep ionizing radiation exposure as low as reasonably possible.

Characterization of self-anticipated pain score prior to elective surgery - a prospective observational study.

BACKGROUND: Current principles of postoperative pain management are primarily based on the types and extent of surgical intervention. This clinical study measured patient's self-anticipated pain score before surgery, and compared the anticipated scores with the actual pain levels and analgesic requirements after surgery. METHODS: This prospective observational study recruited consecutive patients who received elective surgery in the E-Da Hospital, Taiwan from June to August 2018. Patients were asked to subjectively rate their highest anticipated pain level (numeric rating scale, NRS 0-10) for the scheduled surgical interventions during their preoperative anesthesia assessment. After the operation, the actual pain intensity (NRS 0-10) experienced by the patient in the post-anesthesia care unit and the total dose of opioids administered during the perioperative period were recorded. Pain scores ≥4 on NRS were regarded as being unacceptable levels for anticipated or postoperative pain that required more aggressive intervention. RESULTS: A total of 996 patients were included in the study. Most of the patients (86%) received general anesthesia and 73.9% of them had a history of previous operation. Female anticipated significantly higher overall pain intensities than the male patients (adjusted odd ratio 1.523, 95% confidence interval 1.126-2.061; P = 0.006). Patients who took regular benzodiazepine at bedtime (P = 0.037) and those scheduled to receive more invasive surgical procedures were most likely to anticipate for higher pain intensity at the preoperative period (P < 0.05). Higher anticipated pain scores (preoperative NRS ≥ 4) were associated with higher actual postoperative pain levels (P = 0.007) in the PACU and higher total equivalent opioid use (P < 0.001) for acute pain management during the perioperative period. CONCLUSION: This observational study found that patients who are female, use regular benzodiazepines at bedtime and scheduled for more invasive surgeries anticipate significantly higher surgery-related pain. Therefore, appropriate preoperative counseling for analgesic control and the management of exaggerated pain expectation in these patients is necessary to improve the quality of anesthesia delivered and patient's satisfaction.

Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy.

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel. METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed. RESULTS: CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF-mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (P = 0.03) and overall survival (P = 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (CTNNB1) overexpression (P <0.01) compared to nondisease donor blood. CTC-CTNNB1 was associated with progressive disease/stable disease compared to complete-responder patient status (P = 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment/follow-up. CONCLUSIONS: CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.

Inaccurate pretreatment staging can impact survival in early stage esophageal adenocarcinoma.

BACKGROUND: Given the survival advantage of neoadjuvant treatment for locally advanced esophageal cancer, accurate clinical staging is necessary. The aim of this study was to assess the clinical (c) and pathologic (p) staging concordance rates for presumably early stage esophageal adenocarcinoma patients that had upfront esophagectomy (UFE) and evaluate if survival (OS) was negatively affected by inaccurate preoperative staging and subsequent treatment selection. METHODS: An NCDB retrospective review of nonmetastatic esophageal adenocarcinoma patients that had UFE. The rates of concordance between c and p staging system and OS were calculated. RESULTS: Of 2775 patients, most patients presented with cN0 (82.8%) and cT1 tumors (53.6%). The overall concordance between c and p staging was 78.8% for T-classification (moderate agreement; weighted κ = 0.729; P < .001) and 78.8% for N-classification (weak agreement; weighted κ = 0.448; P < .001). Patients that were upstaged due to a lack of concordance between T-classification had decreased 5- and 10-year OS (30% and 16%, P < .001) and those upstaged due to discordant N-classification had decreased 5- and 10-year OS (28% and 23%, P < .001)." CONCLUSIONS: Preoperative staging of esophageal adenocarcinoma has moderate reliability and accuracy for predicting pT and pN classification. Up to 25% of patients have discordant clinical and pathological staging, which impacts OS.