Poor Clinical Course Research Articles

Perfusion Abnormalities on 24-Hour Perfusion Imaging in Patients With Complete Endovascular Reperfusion.

Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients. University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging. Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8]). In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

Respiratory microbiome and clinical course of carbapenem-resistant Acinetobacter baumannii pneumonia in critically Ill patients.

Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has been a serious problem in the intensive care unit (ICU). However, defined characteristics of respiratory microbiome in CRAB pneumonia are lacking nowadays. This study aimed to analyze respiratory microbiome of CRAB pneumonia compared to non-CRAB pneumonia and reveal the clinical significance of respiratory microbiome data in these patients. Patients diagnosed with severe pneumonia with mechanical ventilation were enrolled in the ICU of a tertiary care hospital. Respiratory specimens were collected on days 1, 4, 7, and 14 in each participant via tracheal aspiration. Clinical data and outcomes of each enrolled patient were collected via electronic medical records. Microbiome analysis was conducted with collected respiratory specimens undergone by next-generation sequencing of microbial 16S ribosomal DNA. Six CRAB pneumonia, 4 non-CRAB pneumonia and 5 healthy controls were enrolled. In CRAB pneumonia, CRAB was detected in 3 patients by sputum culture at day 1, while it was negative at day 1 and detected later in the others by follow-up sputum culture. Beta diversity plot analysis showed differences between each group. Shannon index was decreased markedly at day 4 in CRAB pneumonia compared to the others. Among CRAB pneumonia cases, 3 respiratory specimens were culture-negative, but positive by microbiome analysis. Lower respiratory microbiome in CRAB pneumonia had distinct characteristics and early loss of diversity compared to non-CRAB pneumonia, which might be related to poor clinical course. Moreover, CRAB acquisition and colonization would be predicted by preemptive microbiome analysis, which will contribute to effective infection control in the ICU.

Abernethy syndrome as a cause of liver transplantation.

Congenital portosystemic shunts are rare abnormalities in which blood flow from the liver is diverted to the systemic circulation. We would like to present the case of a 48-year-old male, during his neurological follow-up he was diagnosed with a congenital intrahepatic portosystemic shunt. Embolization of the portosystemic communicating veins was attempted on two occasions, but without success. Due to the poor clinical course, the patient was presented to our transplant committee and a liver transplant was decided upon.

(104) PREDICTORS OF LENGTH OF STAY IN PELVIC INFLAMMATORY DISEASE HOSPITALIZATION: INSIGHTS FROM THE NATIONAL INPATIENT SAMPLE

Abstract Introduction Pelvic inflammatory disease (PID) is a common and potentially serious reproductive health condition that may require hospitalization for proper management. Accurate prediction of the length of stay (LOS) for PID hospitalizations can aid clinicians in resource allocation, patient counseling, and improving overall patient care. Prior studies have explored potential risk factors for a poor clinical course among women hospitalized with PID, but to our knowledge, no study to date has explored potential predictors of LOS in PID hospitalization. Objective This study aims to characterize the predictors for LOS in PID hospitalizations based on patient and hospital characteristics using a large national database. Methods The National Inpatient Sample (NIS) database was queried from 2019 to 2020 for all female patients 18 years and older with a primary diagnosis of acute pelvic inflammatory disease using ICD-10 codes. Data on patient demographics, clinical characteristics, comorbidities, and hospital-related variables were collected using variables as defined by NIS and summarized using descriptive statistics. Bivariate and multivariable associations between LOS and covariates were assessed using linear regression models and estimates were reported as regression coefficients. Covariates that were statistically significant in the bivariate models were included as covariates during the multivariate regression analysis. Results A total of 14,505 hospitalized female patients with a principal diagnosis code for acute PID were included. Mean LOS for PID hospitalization was 5.8 days, with a range of 0 – 88 days. The average patient age was 42.9 years (age range 18 – 90 years old), with 55.1% White, 23.4% Black, 12.5% Hispanic, and 2.3% Asian or Pacific Islander. The main primary payers included Medicaid (40.0%), private insurance (36.1%), Medicare (19.1%), and self-pay (4.7%). About 34% of patients were in the lowest quartile for median household income, 45% in the middle two quartiles, and 19% in the highest quartile. In univariable analysis, increased LOS was associated with increasing age, larger hospital bed size, urban teaching hospital status, and the presence of hypertension, diabetes, obesity, or immunodeficiency. Decreased LOS was associated with Hispanic or Native American race and having a non-Medicare primary payer. In multivariable analysis, increased LOS was associated with increasing age (+0.06 days per increasing year, p < 0.0001) and large hospital bed size (+0.6 days compared to small bed size, p = 0.03). Decreased LOS was associated with Asian or Pacific Islander race (-1.1 days compared to White race, p = 0.02), Native American race (-1.4 days compared to White race, p = 0.03), and being billed as ‘no charge’ (-2.1 days compared to Medicare, p = 0.03). Conclusions This study identifies possible predictors of LOS in PID hospitalization, providing insights that may help optimize resource allocation and better characterize factors that may impact PID management. Several factors, including age, race, expected primary payer, and bed size of hospital were found to significantly impact LOS. Additionally, this study highlights the potential role of social determinants of health in PID hospitalization and management and can help guide future research and initiatives aimed at improving population health and addressing disparities in PID. Disclosure No.

#1378 A single-center retrospective study on clinical characteristics and outcomes of extended-spectrum beta-lactamases positive acute pyelonephritis

Abstract Background and Aims The increase of extended-spectrum beta-lactamases (ESBL) releasing bacteria in acute pyelonephritis (APN) is a growing problem world-wide. Recently, little is known about the incidence, clinical features and outcomes of ESBL positive APN. This study intends to describe the epidemiology and clinical outcomes of ESBL positive APN. Method A retrospective study of 1631 culture positive patients with APN admitted from Jan, 2011 to Dec, 2019 in a single-center was performed. Adults over 18 years of age were included, and outpatient treatment, pregnant women, and transplant patients were excluded. Result A total of 2818 patients were diagnosed as APN during this period and causative bacteria was confirmed in1631 patients among them (57.9%). ESBL positive bacteria were found in 553 patients (33.9%). There were no differences in baseline characteristics between ESBL positive and negative groups. Most common strain was Escherichia coli, followed by Klebsiella and Pseudomonas species. The proportion of ESBL positive APN increased when evaluated at one-year intervals for 8 years (from 4.9% in 2011 to 20.9% in 2019). The rate of positive blood culture was higher in ESBL positive patients (39.2% vs 21.1%, p<0.001). Hospital stay was longer in ESBL positive patients (12.3 ± 2.2 vs. 5.4 ± 5.2, p<0.001) and the number of re-admission is higher (1.7 ± 1.3 vs. 1.2 ± 0.6, p<0.001). The incidence of acute kidney injury according to KDIGO was higher in ESBL positive groups (25.4% vs 12.3%, p<0.001). There was no hospital mortality between two groups. Conclusion We should attempt to detect ESBL positive bacteria through timely performing blood and urine culture and administer appropriate antibiotics if APN is clinically suspected because of poor clinical courses.

Vitamin D Supplementation in Functional Recovery of Subjects with Severe Acquired Brain Injury: A Pilot Controlled Randomized Study.

Low vitamin D (VD) has been associated with poor clinical course in several neurological diseases. Supplementation has been suggested to improve outcomes. Severe acquired brain injury (sABI) subjects have low VD levels and disabling conditions requiring rehabilitation. The aim of the present study was to evaluate if VD supplementation produced a better clinical course and a better functional outcome in sABI during rehabilitation. A randomized single-blind study was performed. sABI subjects were randomized to the VD supplementation group (VDsG) (initial dose of 50.000 UI and 1.000 daily) and usual care control group (CG). Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS), and Level of Cognitive Functioning (LCF) were used in assessing disability. A total of 73 subjects (42 M and 31 F; mean age 53.2 ± 15.7) were randomized: 36 (21 M and 15 F; mean age 57.52 ± 14.88) to VDsG and 37 (20 M and 17 F; mean age 48.28 ± 17.47) to CG. Both groups significantly improved after rehabilitation, and no between-group difference was observed. The mean score values for DRS, GOS, and LCF in VDsG were 18.83 ± 4.27 and 9.42 ± 5.83; 2.89 ± 0.32 and 3.78 ± 0.80; and 4.81 ± 1.70 and 7.53 ± 1.28, at admission and discharge, respectively. Likewise, mean values for DRS, GOS, and LCF in CG were 18.57 ± 4.80 and 9.84 ± 6.34; 2.84 ± 0.37 and 3.81 ± 0.94; and 4.97 ± 2.01 and 7.41 ± 1.32, respectively. VD supplementation did not improve functional outcomes in sABI during rehabilitation treatment.

Optimal timing for the first cystoscopic follow-up using time-to-treatment initiation analysis of oncologic outcomes in primary non-muscle invasive bladder cancer

Various guidelines recommend the first follow-up cystoscopy at 3 months; however, no data exist on the optimal timing for initial follow-up cystoscopy. We tried to provide evidence on the timing of the first cystoscopy after the initial transurethral resection of bladder tumor (TUR-BT) for patients with non-muscle invasive bladder cancer (NMIBC) using big data. This was a retrospective National Health Insurance Service database analysis. The following outcomes were considered: recurrence, progression, cancer-specific mortality, and all-cause mortality. Exposure was the time-to-treatment initiation (TTI), a continuous variable representing the time to the first cystoscopy from the first TUR-BT within 1 year. Additionally, we categorized TTI (TTIc) into five levels: < 2, 2–4, 4–6, 6–8, and 8–12 months. A landmark time of 1 year after the initial TUR-BT was described to address immortal-time bias. We identified the optimal time for the first cystoscopy using Cox regression models with and without restricted cubic splines (RCS) for TTI and TTIc, respectively. Among 26,660 patients, 16,880 (63.3%) underwent cystoscopy within 2–4 months. A U-shaped trend of the lowest risks at TTI was observed in the 2–4 months group for progression, cancer-specific mortality, and all-cause mortality. TTI within 0–2 months had a higher risk of progression (aHR 1.36; 95% confidence intervals [CI] 1.15–1.60; p < 0.001) and cancer-specific mortality (aHR 1.29; 95% CI 1.05–1.58; p = 0.010). Similarly, TTI within 8–12 months had a higher risk of progression (aHR 2.09; 95% CI 1.67–2.63; p < 0.001) and cancer-specific mortality (aHR 1.96; 95% CI 1.48–2.60; p < 0.001). Based on the RCS models, the risks of progression, cancer-specific mortality, and all-cause mortality were lowest at TTI of 4 months. The timing of the first cystoscopy follow-up was associated with oncologic prognosis. In our model, undergoing cystoscopy at 4 months has shown the best outcomes in clinical course. Therefore, patients who do not receive cystoscopy at approximately 4 months for any reason need more careful follow-up to predict a poor clinical course.

Efficacy and safety of topical corticosteroid treatment under occlusion for severe alopecia areata in children: asingle-centre retrospective analysis.

Alopecia areata (AA) has a poor clinical course in children. There are no reliable therapeutic options for children with severe AA, including alopecia totalis (AT) and alopecia universalis (AU). We evaluated the efficacy and adverse effects of a potent topical corticosteroid (TCS) under occlusion in paediatric patients with severe AA. We reviewed records of 23 patients under the age of 10 years with AT or AU treated with a potent TCS (0.05% clobetasol propionate or 0.3% diflucortolone valerate) for 8 h under occlusion with a plastic film. We used the Severity of Alopecia Tool (SALT) to measure clinical improvement. The primary endpoint was a SALT score of ≤ 20 at 6 months. We analysed the change in cortisol levels to identify the long-term safety of TCS therapy on the hypothalamus-pituitary-adrenal axis. Nineteen of the 23 patients (83%) reached SALT ≤ 20 at 6 months. Six patients relapsed over the 6-month follow-up period. Four patients were suspected of having adrenal insufficiency. However, the cortisol levels of the patients recovered to normal within 1 month of lowering the TCS potency or changing to nonsteroidal treatments. Limitations include the retrospective design and small sample size. This study shows that a potent TCS occlusion may be a safe treatment option in paediatric patients with severe AA. Further long-term studies are required to evaluate the safety and recurrence of TCS occlusion therapy for paediatric AA.

COMPARISON OF CLINICAL CHARACTERISTICS OF PATIENTS HOSPITALIZED DUE TO SARS-COV-2, INFLUENZA AND RESPIRATORY SYNCYTIAL VIRUS PNEUMONIA

OBJECTIVE: Influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are agents that spread through droplets, have similar symptoms and radiological findings, and can cause respiratory failure. This study was conducted to compare the clinical features and mortality rates of patients with novel coronavirus disease (COVID-19), influenza, and respiratory syncytial virus pneumonia. MATERIAL AND METHODS: A total of 182 patients who were hospitalized at Baskent University Medical Faculty Hospital due to COVID-19, influenza, and RSV were included in the study. Patients were grouped according to their clinical status. Demographic characteristics, comorbidities, laboratory and radiological findings, respiratory support treatments and mortality rates of the patients were recorded and compared between the groups. RESULTS: The mean age was 69.4±7 years in the COVID-19 group (n:115), 72.9±17.1 years in the influenza group (n:33), and 66.5±22.4 years in the RSV group (n:34). There was no difference in age between the groups (p=0.305). The hospitalization rate was higher for male patients in the COVID-19 group (p=0.036). There was no difference between the groups in terms of comorbidities (p&amp;gt;0.05). There was no difference in mortality rates between the COVID-19, RSV, and influenza patient groups (p=0.260). CONCLUSIONS: Viral infections with pulmonary involvement require special attention because they can have a poor clinical course. The severity of the clinical course of COVID-19 pneumonia, which causes deaths in the current century, is not different from the clinical course of viral infections such as influenza and RSV.

Management of cytomegalovirus reactivation in patient with immunotherapy-induced gastritis.

We present the case of a 52-year-old woman diagnosed with stage IV clear cell renal cell carcinoma who received combination of surgery and systemic therapy with nivolumab (anti-PD1) and ipilimumab (anti-CTLA-4). During treatment, patient presented oral intolerance, vomiting and abdominal pain. Computed tomography (CT) and gastroscopy (EGD) were performed, identifying findings suggestive of severe gastro-duodenitis with friability and diffuse oedema of the mucosa and deep ulcers. A gastrointestinal immunotherapy-induced toxicity was suspected so patient was managed with proton pump inhibitors (PPIs) and intravenous corticosteroids 1mg/Kg. Three weeks later, corticosteroid treatment failed. EGD was repeated and gastric biopsies were taken for histological and microbiological tests. Gastric biopsies revealed the presence of cytomegalovirus (CMV) inclusion bodies by immunohistochemistry (IHC). CMV viral load by quantitative PCR in plasma was 2,000 IU/mL so intravenous ganciclovir was prescribed. Then, the patient presented poor clinical course with persistent vomiting due to a failure of first-line corticosteroid and antiviral treatment. Another EGD was performed. Last IHC reveals a low CMV viral load. Second-line treatment with Anti-TNF was performed using a single-dose regimen of intravenous infliximab 5 mg/Kg. Finally, the patient presented a clinical and endoscopic response and a negative CMV DNA test in the blood after completing the antiviral treatment.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis.

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.

Correlation of Measurable Body Fat and Muscle Composition Parameters and Visceral Adipose Tissue on Computed Tomography with COVID-19 Severity

Background/Aims: Obesity increases the risk of having COVID-19. To evaluate the relationship between body fat, muscle composition, and visceral adipose tissue on computed tomography (CT) with COVID-19 outcome. Materials and Methods: 149 patients were included who had chest CT and a positive reverse transcriptase-polymerase chain reaction test. We measured the epicardial adipose tissue thickness (EAT) and liver density (LD), thoracic subcutaneous adipose tissue /pectoralis major (TSAT/PMJ), abdominal subcutaneous adipose tissue /psoas major muscle (ASAT/PSM), abdominal subcutaneous adipose tissue/erector spina muscle (ASAT/ESM) thickness ratios from thorax CT. Lymphocyte, platelet, neutrophil count, lymphocyte/neutrophil ratio, and CRP were recorded. Results: The mean EAT was high in the patients with a poor clinical course (in severe patients: 7.06±2.39 mm, in critical patients: 7.89±2.08 mm). The mean EAT of the ICU group was 7.70±2.14 mm, it was 8.50±2.10 mm in the deceased patients. TSAT/PMJ was lower in deceased patients (0.90±0.36, p=0.038). ASAT/PSM and ASAT/ESM were also higher in the moderate group (2,27±1,60 and 0,51±0,25) (p=0.003. and p=0.019) than mild one (1.59±1.80, and 0.40±0.26). There was no difference in terms of DM, malignancy, or gender. Conclusion: EAT was high in ICU-admitted and deceased patients and can be used as a predictor of poor prognosis.

The impact of menopause and serum DHEA-S level on the severity of Covid-19

ObjectivesWe aimed to demonstrate the difference between premenopausal and postmenopausal women in respect of the clinical course and outcomes of Covid-19. We investigated the epidemiological and hormonal factors which influence the severity of the disease. Study designThis observational cross-sectional study included the female patients admitted to a Covid-19 outpatient clinic between July 2020 and June 2021 and diagnosed with a positive polymerase chain reaction test. Blood samples were obtained to determine the serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, total testosterone and dehydroepiandrosterone sulfate. Main outcome measureOur primary outcome was the poor clinical course of the disease in postmenopausal women. Our secondary outcome was the contribution of hormonal status to the clinical course of the disease. ResultsOur cohort consisted of 253 female patients (85 with mild, 125 with moderate and 43 with severe disease; 101 at the premenopausal and 152 at the postmenopausal stage). There was a statistically significant difference between the patients in different severity groups regarding clinical data and serum levels of luteinizing hormone, follicle stimulating hormone, estradiol and dehydroepiandrosterone sulfate. Being one year younger decreased the odds of having severe Covid-19 0.338-fold relative to the group with mild disease. A decrease in the serum dehydroepiandrosterone sulfate level was associated with a 2.604-fold increase in the odds of having severe Covid-19 relative to the group with mild disease. Being postmenopausal increased the odds of having severe disease compared with mild disease by 2.687-fold. ConclusionsThe prognosis of Covid-19 is more favorable in premenopausal women compared with postmenopausal women. Age, postmenopausal status and serum levels of dehydroepiandrosterone sulfate are important predictors of the severity of Covid-19 for women.

Etiology and Factors Affecting Severe Complications and Mortality of Febrile Neutropenia in Children with Acute Leukemia

Febrile neutropenia (FN) is an important complication that causes high rates of morbidity and mortality in patients with malignancies. We aimed to investigate the etiology, epidemiological distribution and its change over the years, clinical courses, and outcomes of FN in children with acute leukemia. We retrospectively analyzed the demographic data, clinical characteristics, laboratory results, severe complications, and mortality rates of pediatric patients with FN between January 2010 and December 2020. In 153 patients, a total of 450 FN episodes (FNEs) occurred. Eighty-four (54.9%) of these patients were male, the median age of the patients was 6.5 (range: 3-12.2) years, and 127 patients (83%) were diagnosed with acute lymphoblastic leukemia. Fever with a focus was found in approximately half of the patients, and an etiology was identified for 38.7% of the patients. The most common fever focus was bloodstream infection (n=74, 16.5%). Etiologically, a bacterial infection was identified in 22.7% (n=102), a viral infection in 13.3% (n=60), and a fungal infection in 5.8% (n=26) of the episodes. Twenty-six (23.2%) of a total of 112 bacteria were multidrug resistant (MDR) The rate of severe complications was 7.8% (n=35) and the mortality rate was 2% (n=9). In logistic regression analysis, refractory/relapsed malignancies and high C-reactive protein (CRP) at first admission were found to be the most important independent risk factors for mortality. Prolonged neutropenia after chemotherapy, diagnosis of acute myeloid leukemia, identification of fever focus or etiological agents, invasive fungal infections, polymicrobial infections, and need for intravenous immunoglobulin treatment increased the frequency of severe complications. We found that there was no significant change in the epidemiological distribution or frequency of resistant bacteria in our center in the last 10 years compared to previous years. Prolonged duration of fever, relapsed/refractory malignancies, presence of fever focus, and high CRP level were significant risk factors for poor clinical course and outcome.

Oxidative stress-related markers as prognostic factors for patients with primary sclerosing cholangitis in Japan.

Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors. We recruited 58 patients with PSC (mean age; 37.4years, mean observation period; 1382days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY). The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival. High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis.

Revisiting En Bloc Resection Versus Piecemeal Resection for the Treatment of Giant Cell Tumor of the Spine

Surgery for spinal giant cell tumors (GCTs) is challenging because these tumors often exhibit a poor clinical course owing to their locally aggressive features. This study aimed to investigate the prognostic factors of GCT recurrence in the spine by focusing on surgical factors. We retrospectively reviewed patients who underwent surgery for spinal GCTs between January 2005 and December 2016. Using the Kaplan-Meier method, surgical variables were evaluated for disease-free survival (DFS). Since tumor violation may occur at the pedicle during en bloc resection of the spine, it was further analyzed as a separate variable. Multivariate Cox proportional hazard regression analysis was performed for other clinical and radiographic variables. A total of 28 patients (male:female= 8:20) were included. The mean follow-up period was 90.5months (range, 15-184 months). Among the 28 patients, gross total resection (GTR) was the most important factor for DFS (P= 0.001). Any form of tumor violation was also correlated with DFS (P= 0.049); however, use of en bloc resection technique did not show a significant DFS gain compared to piecemeal resection (P= 0.218). In the patient group that achieved GTR, the mode of resection was not a significant factor for DFS (P= 0.959). In the multivariate analysis, the extent of resection was the only significant variable that affected DFS (P= 0.016). Conflicting results on tumor violation from univariate and multivariate analyses suggest that GTR without tumor violation should be the treatment goal for spinal GCTs. However, when tumor violation is unavoidable, it would be important to prioritize GTR over adhering to en bloc resection.

Identification of a sub-group of critically ill patients with high risk of intensive care unit-acquired infections and poor clinical course using a transcriptomic score

BackgroundThe development of stratification tools based on the assessment of circulating mRNA of genes involved in the immune response is constrained by the heterogeneity of septic patients. The aim of this study is to develop a transcriptomic score based on a pragmatic combination of immune-related genes detected with a prototype multiplex PCR tool.MethodsAs training cohort, we used the gene expression dataset obtained from 176 critically ill patients enrolled in the REALISM study (NCT02638779) with various etiologies and still hospitalized in intensive care unit (ICU) at day 5–7. Based on the performances of each gene taken independently to identify patients developing ICU-acquired infections (ICU-AI) after day 5–7, we built an unweighted score assuming the independence of each gene. We then determined the performances of this score to identify a subgroup of patients at high risk to develop ICU-AI, and both longer ICU length of stay and mortality of this high-risk group were assessed. Finally, we validated the effectiveness of this score in a retrospective cohort of 257 septic patients.ResultsThis transcriptomic score (TScore) enabled the identification of a high-risk group of patients (49%) with an increased rate of ICU-AI when compared to the low-risk group (49% vs. 4%, respectively), with longer ICU length of stay (13 days [95% CI 8–30] vs. 7 days [95% CI 6–9], p < 0.001) and higher ICU mortality (15% vs. 2%). High-risk patients exhibited biological features of immune suppression with low monocytic HLA-DR levels, higher immature neutrophils rates and higher IL10 concentrations. Using the TScore, we identified 160 high-risk patients (62%) in the validation cohort, with 30% of ICU-AI (vs. 18% in the low-risk group, p = 0.06), and significantly higher mortality and longer ICU length of stay.ConclusionsThe transcriptomic score provides a useful and reliable companion diagnostic tool to further develop immune modulating drugs in sepsis in the context of personalized medicine.

The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

Macrophages are a representative cell type in the tumor microenvironment. Macrophages that infiltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related to invasion, metastasis, and immunosuppression, and an increased density of TAMs is associated with a poor clinical course in many cancers. Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional secreted phosphorylated glycoprotein. Although SPP1 is produced in a variety of organs, at the cellular level, it is expressed on only a few cell types, such as osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid cells, and mononuclear cells. SPP1 is also expressed by cancer cells, and previous studies have demonstrated correlations between levels of circulating SPP1 and/or increased SPP1 expression on tumor cells and poor prognosis in many types of cancer. We recently revealed that SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma. In this review, we summarize the significance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of monocyte-derived TAMs in lung adenocarcinoma. Several studies have shown that the SPP1/CD44 axis contribute to cancer chemoresistance in solid cancers, so the SPP1/CD44 axis may represent one of the most critical mechanisms for cell-to-cell communication between cancer cells and TAMs.

Psychiatric Inpatient Healthcare Resource Utilization and Treatment Patterns Among Patients With Predominant Negative Symptoms in Schizophrenia

AbstractIntroductionCurrently approved treatments for schizophrenia (antipsychotics) have demonstrated effectiveness for treating positive symptoms; however, these agents are largely ineffective in treating other domains. Negative symptoms, including avolition, alogia, blunted affect, and asociality, are difficult to treat, and often persist despite adequate control of positive symptoms. Additionally, some patients experience “predominant” (moderate-to-severe negative symptoms that have greater relative severity than co-occurring positive symptoms) or “prominent” (severity of negative symptoms [moderate-to-severe] without any reference to positive symptoms) negative symptoms. These symptoms are known to have great impact on patient social functioning and quality of life, and are associated with poorer clinical course and outcomes for patients. Here, we examined inpatient healthcare resource utilization in patients with schizophrenia experiencing predominantly negative symptoms (PNS).MethodsDe-identified data were extracted from electronic health records in the NeuroBlu Database across 25 US mental healthcare providers. Positive and negative symptom data were derived from free-text records using natural language processing. PNS was defined as the presence of three or more negative symptoms and three or fewer positive symptoms at first clinical contact following schizophrenia diagnosis. Groups were balanced for baseline demographic and clinical characteristics by minimizing the generalized Mahalanobis distance and compared using chi-square and t-tests. Treatment patterns were visualized using Sankey diagrams.ResultsA total of 4444 patients with schizophrenia were identified and 8% were classified as PNS. A balanced cohort of 720 patients (50% PNS) was generated. Patients with PNS were more likely to be hospitalized in the 12 months following diagnosis (PNS: 76%, non-PNS: 60%, χ2: 22.5, p &lt; 0.001) and were switched to a second-line antipsychotic after a shorter first-line treatment duration. The most frequently prescribed antipsychotics differed between groups (PNS: risperidone, aripiprazole, haloperidol; non-PNS: risperidone, olanzapine, other atypical).DiscussionThis study demonstrates that negative symptoms in schizophrenia may be associated with worse illness course and higher healthcare resource utilization. There remains a need for new treatment options for patients with persistent, prominent, or predominant negative symptoms which specifically improve this historically hard-to-treat and assess symptom domain.FundingSunovion Pharmaceuticals, Inc.

Abstract P5-03-11: The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer

Abstract Background Return-to-work (RTW) after breast cancer may be challenging for breast cancer survivors, especially those who experience adverse effects. Neuropathies are common adverse effect of taxane-based chemotherapy. Single nucleotide polymorphisms (SNPs) in genes related to taxane metabolism and transport, neural function, and neural- or DNA-repair may influence the risk of taxane-induced adverse effects, potentially impacting patient recovery and RTW. We examined the association of such SNPs with RTW in premenopausal breast cancer survivors. Methods We used Denmark’s nationwide population-based health registries to ascertain data on premenopausal women aged 18‒55 years diagnosed with non‒distant metastatic breast cancer during 2007‒2011, who were candidates for adjuvant combination chemotherapy including cyclophosphamide and docetaxel. Only women employed at diagnosis were included. We collected archived tumor tissue from nationwide pathology departments and genotyped 26 SNPs in 20 genes using TaqMan assays. For each SNP, we categorized the women as wildtype, homozygote or heterozygote. Follow-up continued from the date of primary surgery to the first of RTW (defined as 4 consecutive weeks of work), recurrence, maternity leave/childbirth, other malignancy, retirement, death, emigration or 25th September 2017. We computed the cumulative incidence of RTW and used Cox regression models to calculate unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of RTW. Results We included 1,963 women. Women who were homozygotes for the phase 1 metabolizer CYP3A5 rs776746 (n=15) had lower cumulative incidence of RTW than wildtypes (n=1,600) and heterozygotes (n=249), 7%, 25% and 17% at six months, 57%, 87% and 88% at two years, and 82%, 94% and 94% at end of follow-up, respectively. Compared with wildtypes, CYP3A5 rs776746 homozygotes had delayed RTW throughout follow-up (HR 0-10 years: 0.48, 95% CI: 0.26, 0.86). No other SNPs were associated with RTW. Conclusions Among 26 SNPs, CYP3A5 rs776746 was associated with delayed RTW after breast cancer among premenopausal women. Our findings may help identify women at risk of a poor clinical course, who may benefit from enhanced supportive care during treatment and follow-up. Citation Format: Cathrine Hjorth, Per Damkier, Tore B. Stage, Søren Feddersen, Stephen Hamilton-Dutoit, Bent Ejlertsen, Timothy L. Lash, Henrik Bøggild, Henrik Sørensen, Deirdre Cronin-Fenton. The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-11.