Risk Factors For Poor Outcome Research Articles

Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.

Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.

Surgical Outcome of Intraventricular Tumors; A Retrospective Single Center Study in Addis Ababa, Ethiopia

Background: Intraventricular tumors (IVT) are rare clinical entities; surgical resection remains challenging for neurosurgeons. Knowledge about the surgical outcome of these tumors in resource-limited settings is scarce. The study aims to do quality control of surgical management of IVT in a single neurosurgical center in Ethiopia. Methods: This study employed a hospital-based retrospective review of 40 patients who underwent surgical treatment for intraventricular tumors (IVT) at Tikur Anbesa Specialized Hospital between January 2015 and December 2020. Descriptive statistics used to evaluate the clinical presentation, imaging, histology, surgical approach, complications, mortality, overall survival and risk factors for poor outcome. Results: The median age was 19 years (range: 1-52 years). Headache was the most common presenting symptom (95%), followed by visual disturbance (65%). Supratentorial tumors accounted for 52.5% of cases, with medulloblastomas being the most frequent subtype (n=11). The overall complication rate was 52.5%, with hydrocephalus (40%) and infections (25%) being the most common postoperative complications. The 30-day operative mortality rate was 27.5%. Risk factors for complications and mortality included infratentorial tumor location, subtotal resection, EVD insertion, and longer ICU stay. Postoperative hydrocephalus independently predicted operative mortality. Conclusion: This study reveals higher complication and mortality rates for Intraventricular tumor (IVT) surgeries, especially for infratentorial tumors. Limited resources and experience contribute to these concerning outcomes. Postoperative hydrocephalus is identified as an independent risk factor for 30-day mortality. The findings highlight the challenges of managing IVT surgically in resource-limited settings, emphasizing the need for serious consideration and proper management to achieve better outcomes.

Clinical features of omicron SARS-CoV-2 variants infection associated with co-infection and ICU-acquired infection in ICU patients.

Although the decreasing rate of hospital admission in the omicron wave has led countries to loosen control, still the patients requires ICU admission. It is common for viral respiratory infections to be co-infected with bacteria. However, the difference between co-infection and ICU-acquired infection on their clinical characteristics and outcomes during the Omicron wave was little reported. Clinical and microbiological data were collected from ICU patients with omicron infection between April 1st, 2022, and May 31th, 2022 and a comprehensive comparative study of the clinical characteristics and endpoint were conducted. The Omicron SARS-CoV-2 variants-infected patients requiring intensive care had high rates of co-infection (42.55%). Additionally, the ICU COVID-19 patients with co-infection showed more severe clinical features compared to those with ICU-acquired infection. Furthermore, Multivariate Cox analysis demonstrated that co-infection (hazard ratio: 4.670, p = 0.018) was a significant risk factor for poor outcomes in ICU patients with COVID-19. Besides, Kaplan-Meier survival curve analysis revealed that COVID-19 patients with co-infection had a significantly shorter 28-Day survival time compared to those with ICU-acquired infection (p < 0.001). Finally, our investigation identified a significant association between the presence of Candida app. in the broncho-alveolar lavage and an elevated risk of mortality (OR: 13.80, p = 0.002) and invasive ventilation (OR: 5.63, p = 0.01). Co-infection is prevalent among patients requiring intensive care and is linked to unfavorable outcomes in the Omicron wave. Consequently, more attention may be needed for the empirical antibacterial treatment in ICU patients within the COVID-19 Omicron variant, especially anti-fungi.

Risk predictors of race disparity in patients undergoing coronary artery bypass grafting: a propensity-matched analysis.

The aim of this study was to compare long-term prognosis after isolated coronary artery bypass grafting between white and black patients and to investigate risk factors for poorer outcomes among the latest. All consecutive 4766 black and white patients undergoing isolated coronary artery bypass grafting between May 2005 and June 2021 at our institution were included. Primary outcomes were long-term incidence of all-cause death and major adverse cardiovascular and cerebrovascular events in black versus white patients. A propensity-matched analysis was used 2 compare groups. After matching, 459 patients were included in each black and white groups while groups were correctly balanced. The mean age was 70.4 vs 70.6 years old (P = 0.7) in black and white groups, respectively. Intraoperatively, mean operating room time and blood product transfusion, were higher in the black group while incidence of extubation in the operating room was higher in the white one. Postoperatively, hospital length of stay was higher in the black cohort. Thirty-day all-cause mortality was not different among groups. The median follow-up time was 4 years. Primary outcome of all-cause death was higher in the black versus the white, respectively. Major adverse cardiovascular and cerebrovascular events incidence was twice higher in the black compared to the white cohort (7.6% vs 3.7%, P = 0.013). Risk predictors for all-cause death and major adverse cardiovascular and cerebrovascular events in blacks were creatinine level, chronic obstructive pulmonary disease, ejection fraction <50% and preoperative atrial fibrillation. Racial disparities persist in a high-volume centre. Despite no preoperative difference, black minority has a higher incidence of major adverse cardiovascular and cerebrovascular events.

Predictors of Readmission and Reoperation Following Shoulder Arthroplasty in Patients Under 45 Years of Age.

The use of shoulder arthroplasty has increased among all age groups, albeit most prominently in older patients. While previous studies have investigated predictors of short-term readmission and reoperation in the general population, there is a paucity of literature available on these in patients under 45 years of age. This study aimed to identify the predictors of 30-day readmission and reoperation following shoulder arthroplasty in patients under 45 years of age. A retrospective query in the American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2019 was used to identify patients who underwent primary reverse and anatomic total shoulder arthroplasty and hemiarthroplasty. Multivariate logistic regression was used to identify predictors of 30-day readmission and reoperation. A total of 530 patients were included. Multivariate regression revealed that Black race and Hispanic ethnicity were independent predictors of readmission. Functional dependence, hypertension requiring medication, and prolonged length of stay predicted reoperation. Finally, low hematocrit and prolonged length of stay predicted morbidity. Identifying and accounting for these risk factors for poor outcomes may help improve perioperative risk stratification. As a result, these findings have the potential to reduce healthcare costs associated with readmission and reoperation following shoulder arthroplasty in young patients. Our results also highlight the underlying disparities in healthcare outcomes among racial and ethnic groups that must be considered.

Muscle wasting assessed by ultrasound versus scoring systems as early predictor of outcomes of intensive care unit stay in critically ill patients

ABSTRACT Background A lot of outcome predictive tools are already in use in critical care setting with different degrees of reliability aiming for possible prevention or minimization of bad outcome and better resource management. Some critical illness sequelae significantly affect patient’s outcome and currently not included in the in-use predictive scoring system. Muscle wasting/weakness is one of these sequelae, and it was found to be an independent risk factor of poor outcomes. Objective This study was conducted to evaluate the degree of muscle wasting estimated by ultrasonography during ICU stay as a predictor of mortality, successful weaning of mechanical ventilation, ICU stay and hospital stay. Patients and Methods A prospective observational study was conducted in critical care units in Ain Shams University Hospitals, Cairo, Egypt over a period of 12 months. Results Decrease in muscle measurements was found to correlated to mortality in ICU with cutoff points from area under the curve for right QMT, left QMT, right RFCSA, left RFCSA, IEDT and EEDT were supposed to be:>9.77,>15, >16.67, >12.5, >12.63, >12.5, respectively, with best specificity and positive predictive value was found in right RFCSA (95.45, 87.5, respectively) while best sensitivity and negative predictive value was found in left RFCSA (65.38, 82, respectively). Significant negative correlation between vasoactive agent free period and maximum daily reduction in RFCSA, QMT, EIDT, and EEDT (P value = 0.001). Conclusion Daily reduction of the RFCSA and to lesser extent the QMT has significant correlation to mortality, prolongation of mechanical ventilation days and reduction in the vasopressor free days but has a poor correlation to the ICU and hospital stay. Pneumonia and renal disease had significant correlation with the muscle mass reduction. The left RFCSA found to be comparable to SOFA score as mortality predictor.

Foot &amp; Ankle

The December 2023 Foot &amp; Ankle Roundup360 looks at: Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis; 3D-printed modular endoprosthesis reconstruction following total calcanectomy; Percutaneous partial bone excision in the management of diabetic toe osteomyelitis; Hemiepiphysiodesis is a viable surgical option for Juvenile hallux valgus; Ankle arthroplasty vs arthrodesis: which comes out on top?; Patient-related risk factors for poorer outcome following total ankle arthroplasty; The Outcomes in Ankle Replacement Study.

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial

ObjectivesThis work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation.Setting and participantsThis study conducted...

416. Poor clinical outcomes of COVID-19 patients receiving rituximab during the Omicron era

Abstract Background Rituximab (RTX), a widely used anti-CD20 monoclonal antibody, has been suggested as a risk factor for poor outcomes of coronavirus disease 2019 (COVID-19). However, it remains largely unknown whether COVID-19 outcomes remain worse in patients receiving RTX compared to those not being treated with RTX during the Omicron-dominant period, when patient fatality has significantly decreased compared to the Delta-dominant period. Therefore, we aimed to investigate the outcomes of COVID-19 patients receiving RTX during the Omicron-dominant period. Methods Among all laboratory-confirmed COVID-19 patients who were admitted to Seoul National University Hospital from February 2022 to January 2023, those who had received RTX before diagnosis of COVID-19 were included in the RTX group, while those who had the same underlying diseases but had not received RTX were included in the non-RTX group. The COVID-19-related outcomes were compared between the RTX and non-RTX groups. Multivariate logistic regression analyses were used to identify factors associated with severe to critical COVID-19 and COVID-19-related mortality. Results The proportion of severe to critical COVID-19 and COVID-19-related mortality were significantly higher in the RTX group than in the non-RTX group (41.9% vs. 28.3%, P = 0.030; 11.8% vs. 2.8%, P = 0.005). RTX therapy (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21–4.04, P = 0.010) and chronic kidney disease (aOR 3.28, 95% CI 1.56–6.91, P = 0.002) were independent risk factors for severe to critical COVID-19, whereas being effectively vaccinated (aOR 0.47, 95% CI 0.25–0.85, P = 0.013) was a protective factor. In addition, only RTX therapy was independently associated with COVID-19-related mortality (aOR 4.03, 95% CI 1.17–13.86, P = 0.027). Conclusion RTX therapy was associated with poor clinical outcomes of COVID-19, even in the Omicron-dominant period. This suggests that RTX should be used with caution even during the Omicron-dominant period. Disclosures All Authors: No reported disclosures

1098. COVID-19 Reinfections in Older Adults: Risk Factors for Poor Outcomes

Abstract Background Older adults are at higher risk for hospitalization and death from COVID-19. The impact of COVID-19 reinfections on older adults is less clear. As more of the population experiences at least one COVID-19 infection, understanding risk factors associated with severe outcomes at reinfection is critical for improving patient care. Methods We examined the risk of hospitalization, ICU admission, and death among MN residents aged 65+ experiencing 2nd infections (reinfection) during the Omicron wave (12/26/2021-10/1/2022; n = 9311). We first performed log binomial regressions to examine risk of hospitalization, ICU admission, and death across the entire study period. We then stratified the sample by variant wave at 1st infection (Table 1). All models were adjusted for time from 1st infection to reinfection, gender (male vs. female), vaccination status at reinfection (vaccinated vs. unvaccinated), age group (65-74, 75-84, 85+), metro vs. outstate, and infection severity at 1st infection (hospitalized vs. not hospitalized). Results In the full model, people with 1st infections during each of subsequent variant waves were at increased risk of hospitalization during reinfection relative to people whose 1st infection occurred during the initial wild-type wave (Alpha: 1.27, 0.96-1.68, Delta: 1.29, 1.13-1.48, Omicron: 1.93, 1.72-2.18; Table 2). A similar effect was observed for ICU admission. In stratified analyses, age and severity at 1st infection were significant predictors of hospitalization, ICU admission and death across some variant waves (Tables 3 and 4). Conclusion In a preliminary examination of all Omicron reinfections, each subsequent variant wave of 1st infection was associated with an increase in hospitalization. However, given the lack of substantial temporal overlap between variant waves, it is not possible to distinguish whether characteristics of the variant or time between 1st and 2nd infections is impacting magnitude of risk. Stratifying by variant wave allowed us to examine whether potential risk factors varied by variant of 1st infection. Our stratified results indicate that greater age and hospitalization at 1st infection significantly increase negative outcomes at reinfection regardless of the variant of 1st infection. Disclosures All Authors: No reported disclosures

Trends in mortality risk of patients with congenital heart disease during the COVID-19 pandemic

Cardiovascular conditions are considered risk factors for poor outcomes associated with COVID-19. However, the effect of the COVID-19 pandemic on the mortality of patients with congenital heart disease (CHD) is unclear. Our study aims to examine the trends in mortality risk of CHD patients during the COVID-19 pandemic. This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for CHD. We included patients having US residence and direct identifiers; death events were captured by matching with the National Death Index. The observation window (2017-2022) was divided into pre-COVID-19 and COVID-19 era defined around the national onset of COVID-19 disease in 2020. Stratified Cox model was used to assess all-cause mortality between the pre- and the COVID-19 era. Among 45,130 patients with CHD (median age in 2017: 23.3 years, IQR: 19.0-28.4), 503 deaths occurred during the pandemic with 44 deaths (8.7%) attributed to COVID-19 (COVID-19 mortality rate of 0.09%). The overall risk of death for patients with all types of CHD during the pandemic was significantly higher compared to the pre-COVID-19 era (aHR 1.28, 95%CI: 1.08-1.53), with a differential trend towards increased risk in patients with two-ventricle (aHR 1.44, 95% CI: 1.19-1.76) vs unchanged risk for those with single ventricle CHD (aHR=0.83, 95% CI: 0.57-1.21). Adjusted subgroup analysis revealed a higher risk of death during the pandemic for CHD patients with male and chromosomal abnormalities. The excess deaths during the pandemic were attributed to COVID-19 itself rather than CHD or cardiovascular conditions. In this large CHD cohort study, there was a higher risk of death among CHD patients with male and chromosomal abnormalities. A differential trend towards higher risk for those with two vs. unchanged risk for single ventricle CHD was presented. The excess mortality was attributed to the COVID-19 itself and not to conditions potentially related to deferral of care. These results justify targeted protective measures towards the CHD population and may provide guidance for public health and medical care response in future epidemics.

Outcomes of BCMA-Directed Chimeric Antigen Receptor T-Cell (CART) Therapy in Patients with Relapse-Refractory Multiple Myeloma with Extramedullary Disease

Background: Presence of extramedullary disease (EMD) is associated with poor outcomes for patients with relapsed-refractory multiple myeloma (RRMM) and has been identified as a major risk factor for early progression (≤ 3 months) after CAR T-cell therapy. Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are B-cell maturation antigen (BCMA) targeting CAR T-cell therapies approved for patients with RRMM who have received ≥4 prior lines of therapy (LOT). This is a multicenter retrospective study on the real-world safety and efficacy of commercially available ide-cel and cilta-cel in heavily pretreated RRMM patients with EMD. Methods: Three U.S. academic centers, part of the U.S. Myeloma Innovations Research Collaborative (USMIRC), contributed data to this analysis, which included patients with RRMM who had received an ide-cel or cilta-cel infusion ≥30 days prior to data-cut off (7/1/2023). Baseline patient characteristics were outlined by descriptive analyses. Responses including overall response (ORR), and complete response or better (≥CR) rates were evaluated using the International Myeloma Working Group (IMWG) criteria. Statistical analysis was done with the Fisher's exact test and Kaplan Meier method for progression free (PFS) and overall survival (OS) calculations. Results: A total of 132 patients who received commercial (standard of care) BCMA-directed CAR T-cell therapy between 5/1/2021 and 5/30/2023 were included in this study. Out of these, 64 (48%) patients had a previous history or existing EMD prior to CART infusion. Table 1 summarizes the main patient characteristics and outcomes stratified as EMD and non-EMD groups. Both groups had comparable baseline patient and disease characteristics including median age, ECOG performance status, median bone marrow plasma cell percentage, high-risk cytogenetics, number of prior LOT, refractoriness status prior to CART and type of CAR T-cell product received. CART-related toxicities were comparable between the EMD and the non EMD groups. Cytokine release syndrome (CRS) was seen in 73% (≥ grade 3: 5%) of EMD patients vs 79% (≥ grade 3: 4%) of non-EMD patients (p=0.79). Likewise, immune effector cell-associated neurotoxicity syndrome (ICANS) was noted in 28% (≥ grade 3: 5%) of EMD patients vs 32% (≥ grade 3: 9%) of non-EMD patients (p=0.72). Infections were seen in 39% of the EMD group vs 28% of the non-EMD group (p=0.38). Response rates were also similar between the EMD vs non EMD cohorts: ORR 78% vs 96% (p=0.44); and ≥CR rate 42% vs 51% (p=0.54), respectively. With a median follow up of 7.2 (range 0.5-22.8) months for the entire patient cohort, the estimated median PFS was inferior for the EMD group (6.5 months [95% CI, 5.1-9.6]) compared to the non-EMD group (9.8 months [95% CI, 8.2-16.4]) (p=0.017) (Figure 1). At the time of data cut-off, 43 patients had died, 77% from disease progression, 11.5% from CART-related complications and 11.5% from unrelated causes. The estimated median OS was significantly worse for the EMD group (12.9 months [95% CI, 9.5-NA]) compared to the non-EMD group (19.4 months [95% CI, 1.2-NA]) (p=0.031). Conclusions: This is the largest multicenter retrospective study delineating the real-world outcomes of ide-cel and cilta-cel CAR T-cell therapies in RRMM patients with the high-risk disease feature of EMD. Based on our results, patients with prior history or presence of existing EMD at the time of CART infusion did not have any excessive treatment-related toxicities. However, these patients did experience shorter PFS and OS compared to patients without EMD highlighting the presence of EMD as a risk factor for poor outcomes after CART. Therefore, this group of patients should be considered for pre- and post-CART risk mitigation strategies aiming to prevent disease progression and improve survival outcomes.

5-year adherence to adjuvant endocrine treatment in Dutch women with early stage breast cancer: A population-based database study (2006-2016).

Hormonal receptor (HR) positive breast tumors are common. Adjuvant hormonal therapy (AHT) with tamoxifen or Aromatase Inhibitors (AIs) is beneficial depending on the stage of the tumor. Despite the fact that AHT has been shown to improve survival and recurrence, Dutch adherence rates, which were mostly dependent on Tamoxifen prescriptions until 2006, plummeted from 80% after one year to 50% after five years. Nonadherence with AHT reduces its effectiveness. This research presents more recent adherence statistics (from 2006 to 2016), on a larger sample (7,996 vs 1,451), as well as factors that influence AHT adherence. In addition to tamoxifen data, AIs are now included. As low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome, it is important to monitor the rate as an indicator of women's burden of disease and the direction of adherence trends. The Netherlands Cancer Registry (NCR) was used to find women with early-stage breast cancer who started AHT within a year of surgery and were linked to the PHARMO Database Network (n =8,679). The Kaplan-Meier approach was used to measure AHT adherence five years after treatment was started, with a 60-day gap between refills as our primary outcome. Furthermore, the Medication Possession Rate (MPR) was determined using a cutoff of ≥80%. Analysis was performed on influential factors of adherence. The proportion of persistent women declined over time to reach 46.6% at the end of the fifth year and 53.3% of the women had a MPR ≥80% during the fifth year. Older and being diagnosed in 2006-2010 were associated with AHT adherence. Dutch 5-year AHT adherence appears to remain poor. Improving AHT adherence in HR+ breast cancer survivors is a critical medical need.

Sex differences in post-operative outcomes following non-cardiac surgery.

It is uncertain whether sex is an independent risk factor for poor outcomes after non-cardiac surgery. We examined sex differences in short- and long-term mortality and morbidity in patients undergoing non-cardiac surgery in Alberta, Canada. Using linked administrative databases, we identified patients undergoing one of 45 different non-cardiac surgeries who were hospitalized between 2008 and 2019. Adjusted odds ratios (95% CI) were reported for mortality at 30-days, 6-months, and 1-year stratified by sex. Secondary outcomes including all-cause hospitalization, hospitalization for heart failure (HF), hospitalization for acute coronary syndrome (ACS), hospitalization for infection, hospitalization for stroke, and hospitalization for bleeding were also analyzed. Multivariate logistic regression was adjusted for age, sex, surgery type, the components of the Charlson Comorbidity Index, and the Revised Cardiac Risk Index. We identified 552,224 unique patients who underwent non-cardiac surgery of which 304,408 (55.1%) were female. Male sex was a predictor of mortality at 30-days (aOR 1.25 (1.14, 1.38), p<0.0001), 6-months (aOR 1.26 (1.20, 1.33), p<0.0001), and 1-year (aOR 1.25 (1.20, 1.31), p<0.0001). Similarly, male sex was a predictor of hospital readmission at 30-days (1.12 (1.09, 1.14), p<0.0001), 6-months (aOR 1.11 (1.10, 1.13), p<0.0001), and 1-year (aOR 1.06 (1.04, 1.07), p<0.0001). When the results were stratified by age, the effect of male sex on clinical outcome diminished for age ≥ 65years compared to younger patients. In conclusion, male patients undergoing non-cardiac surgery have higher risks of all-cause mortality and readmission after adjustment for baseline risk factor differences, particularly in those under 65-years-old. The overall incidence of readmission for stroke, bleeding, HF and ACS after non-cardiac surgery was low. The impact of male sex on clinical outcomes decreases with increasing age, suggesting the importance of considering the effect of both sex and age on clinical outcomes after non-cardiac surgery.

Clinical Characteristics Associated with Poor Prognosis of Acquired Immunodeficiency Syndrome Patients Complicated with Disseminated Talaromycosis marneffei.

To analyze the clinical characteristics of AIDS with dTSM, especially in patients with poor prognosis. One hundred and seventy AIDS patients were enrolled in this single-center retrospective study. The epidemiological characteristics, clinical manifestations, laboratory tests, imaging examination, and treatment outcome were collected. Logistic regression analysis was used to estimate the risk of mortality in AIDS patients with dTSM. The predictive value was evaluated using the receiver operating characteristic (ROC) curve. From 2015 to 2022, the incidence of AIDS with dTSM in the Wenzhou region increased yearly, mainly in young adults. The mortality rate was 16.47%. The most common clinical manifestations were lymph-node enlargement (92.35%) and fever (78.24%). Multivariate logistic regression analysis showed that procalcitonin (PCT), blood urea nitrogen (BUN), shock, and antiretroviral therapy (ART) were the risk factors for poor outcomes. The model comprised four risk factors and showed an excellent prediction performance, with an AUC of 0.987 in the training cohort (95% CI: 0.946-0.999) and 0.976 in the validation cohort (95% CI: 0.887-0.999). This study suggested that PCT, BUN, shock, and ART were associated with the prognosis and outcome of AIDS with dTSM and had a specific predictive value.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial

BackgroundSphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathological damages in models of viral pneumonia. Research QuestionIs it feasible to administer an SRL therapy, here ozanimod, to acutely ill SARS-CoV-2-infected patients? Study Design and MethodsThe prospective, randomized, open-label, COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care (SOC), or to standard of care plus ozanimod (OZA). Ozanimod (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary endpoint investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the WHO-adapted 6-points ordinal scale for clinical improvement analyzed under the intention-to-treat principle. ResultsTwenty-three patients were randomized to SOC arm and 20, in the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed non-significant reductions of median duration of respiratory support (6 (3-10) vs 9 (4-12) days, P=0.34), median duration of hospitalization (9 (6-12) vs 10 (6-18) days, P=0.20) and median time to clinical improvement (4 (3-7) vs 7 (3-11) days, P=0.12) for OZA compared to SOC. Heart rate was significantly lower with ozanimod (65 (63-67) vs. 71 (69-72) bpm, P<0.0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. InterpretationSRLs utility in severe pneumonia had never been tested in patients. We show for the first time that this new pharmacological agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. Clinical Trial RegistrationClinicalTrials.gov number NCT04405102

Production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in Klebsiella pneumoniae infection.

To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of Klebsiella pneumoniae infection, once adjusted by clinical syndrome and baseline risk factors. We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing K. pneumoniae (OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome). Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 [35.0%] vs. 17 [14.5%]; P-value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 [41.9%] vs. 95 [81.2%]; P-value < 0.001), whereas 30-day all-cause mortality was higher (33 [28.2%] vs. 18 [15.4%]; P-value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio [aHR]: 0.45; 95% confidential interval [95%CI]: 0.29-0.70; P-value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92-2.94; P-value = 0.093). Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in K. pneumoniae infection as compared to episodes due to non-carbapenemase-producing strains.

Concomitant malnutrition and frailty are significant risk factors for poor outcome following two-stage revision for chronic periprosthetic joint infection

BackgroundTwo-stage revision remains the gold standard for periprosthetic joint infection (PJI) treatment. Although previous studies have examined malnutrition and frailty independently, their cumulative effects are not clear. Therefore, this study aimed to assess the individual and combined influence of malnutrition and frailty on the two-stage revision surgery.MethodsPatients with chronic PJI undergoing two-stage revision were retrospectively included. The definition of PJI is completely consistent with the evidence-based definition of PJI recorded by the MSIS in 2018. Preoperative serum albumin levels and 11-item modified frailty index scores were collected. Four cohorts were created: (1) Normal (N), (2) Frail (F), (3) Malnourished (M), and (4) Malnourished and frail (MF). Demographic data, comorbidities, and postoperative complications were collected and compared between the four cohorts.ResultsA total of 117 consecutive patients were enrolled, 48% of patients were healthy (27.4% F, 16.2% M, and 9.4% MF). MF group showed lower scores on the physical composite scale of the 12-item short-form health survey (SF12-PCS), mental composite summary (SF12-MCS), Harris hip score (HHS), and knee society score (KSS) (P < 0.05). The incidence of reinfection in the MF group was higher than that in all other groups (MF vs. N; odds ratio [OR] 3.7, 95% confidence interval [CI] 1.37 − 8.82, P = 0.032). The incidence of complications in the MF group was higher than that in all other groups (MF vs. N; OR 4.81, 95% CI 1.58–9.26, P = 0.018). Postoperative transfusion events (OR 2.92, 95% CI 1.27–3.09, P = 0.021), readmission at 60 days after the operation (OR 4.91, 95% CI 1.82–13.80, P = 0.012) was higher in the MF patients. In addition, the extended length of stay after the operation was highest in the MF patients, with an OR of 5.78 (95% CI 2.16–12.04, P = 0.003).ConclusionThe concurrent presence of concomitant malnutrition and frailty in patients with PJI is related to poor prognosis and may be a predictor of the efficacy of two-stage revision. Future research will be needed to describe the benefits of improving these risk factors for patients with PJI.

COVID-19 hip fracture outcomes: The role of Ct values and D-dimer levels?

IntroductionThe COVID-19 pandemic has caused high mortality rates in hip fracture patients, but data for Asian patients are lacking. Whilst Cycle threshold (Ct) values and D-dimer have been reported as predictors of mortality in COVID-19 patients, their prognostic roles in those with concomitant hip fracture remain unknown. The objectives of this study were to i) assess the clinical outcomes of COVID-19 hip fractures patients in the Chinese population, ii) identify risk factors of mortality and complications, and iii) determine the prognostic roles of Ct values and D-dimer levels. MethodologyThis cohort study was conducted during the 5th wave of the COVID-19 pandemic. Inclusion criteria were 1) hip fracture 2) ​≥ ​60 years old 3) low-energy trauma. Outcomes were 90-day all-cause mortality, complications, length of stay, discharge destination and mobility status. Logistic regression analysis was performed to identify risk factors for mortality and complications. Subgroup analysis was performed for patients with Ct ​< ​30 and Ct ​> ​30, comparing their outcomes of operations performed within 48 ​h vs beyond 48 ​h. Results159 hip fracture patients were included, 42 patients were COVID-19 positive. COVID-19 group had significantly higher 90-day mortality rates (21.4% vs 9.4%), complication rates (45.2% vs 28.2%) and longer length of stay (17.06 vs 10.84 nights). COVID-19 was an independent risk factor for mortality and complications. Amongst the COVID-19 group, risk factors for poor outcomes were advanced age, steroids use, conservative treatment and American Society of Anaesthesiologists (ASA) score ≥ 3. Conservative treatment was associated with higher mortality (OR ​= ​16.00; p ​= ​0.025) in COVID-19 hip fracture patients. There was no significant difference between Ct values ​< ​30 and >30 regarding mortality and complication rate. D-dimer and timing to operation did not affect outcomes. ConclusionsPatients with concomitant COVID-19 and hip fracture are at high risk of mortality and complications. Ct values and D-dimer levels have no prognostic roles for hip fracture outcomes. Early operative treatment is recommended as soon as patients are medically fit.

Systematic Literature Review of Risk Factors for Poor Outcomes Among Adults With Respiratory Syncytial Virus Infection in High-Income Countries.

PROSPERO (CRD42022315239).