Non-pulmonary Infections Research Articles

Machine learning-based model for predicting the occurrence and mortality of nonpulmonary sepsis-associated ARDS.

The objective was to establish a machine learning-based model for predicting the occurrence and mortality of nonpulmonary sepsis-associated ARDS. 80% of sepsis patients selected randomly from the MIMIC-IV database, without prior pulmonary conditions and with nonpulmonary infection sites, were used to construct prediction models through machine learning techniques (including K-nearest neighbour, extreme gradient boosting, support vector machine, deep neural network, and decision tree methods). The remaining 20% of patients were utilized to validate the model's accuracy. Additionally, local data were employed for further model validation. A total of 11,409 patients were included, with the most common type of infection being bloodstream infection. A total of 7,632 (66.9%) patients developed nonpulmonary sepsis-associated ARDS (NPS-ARDS). Patients with NPS-ARDS had significantly longer ICU stays (6.2 ± 5.2 days vs. 4.4 ± 3.7 days, p < 0.01) and higher 28-day mortality rates (19.5% vs. 14.9%, p < 0.01). Both internal and external validation demonstrated that the model constructed with the extreme gradient boosting method had high accuracy. In the internal validation, the model predicted NPS-ARDS and mortality in such patients with accuracies of 77.5% and 71.8%, respectively. In the external validation, the model predicted NPS-ARDS and mortality in these patients with accuracies of 78.0% and 81.4%, respectively. The model established via the extreme gradient boosting method can predict the occurrence and mortality of nonpulmonary sepsis-associated ARDS to a certain extent.

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review.

Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate). We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Features of the course of the new coronavirus infection COVID-19 in patients with chronic kidney disease

BACKGROUND: CKD is one of the main comorbidities in those who die from COVID-19. Renal injury is the most common nonpulmonary infection of SARS-CoV-2 and has a wide range of manifestations, ranging from mild proteinuria and hematuria to progressive acute kidney injury (AKI) requiring renal replacement therapy (RRT).THE AIM: to study the features of the course of the new coronavirus infection COVID-19 in patients with chronic kidney disease.PATIENTS AND METHODS: The study included 79 patients with confirmed new coronavirus infection COVID-19 who hospitalized. The first group consisted of people with a history of CKD (44 people), the second group included people without a history of CKD (35 people). The diagnosis of CKD established based on the calculation of glomerular filtration rate using the CKD-EPI formula. The comorbidity index calculated using two scales: Charlson and CIRS-G. Statistical data analysis carried out using the Statistica 12.0 application package (StatSoft Inc., USA).RESULTS: Patients with COVID-19 and CKD had a higher comorbidity index: according to the Charlson index in one group of patients the indicator was 7 [5.0-9.0], and in group 2 it was 5 [4.0-6.0] (p&lt;0.001). According to the CIRS-G index, in one group the indicator was 9 [7-11.5], in two group it was 4 [2-6] (p &lt;0.001). Patients in one group had a greater degree of damage to the lung tissue according to MSCT of the OGK; in laboratory tests, the levels of CRP, ferritin, LDH, and d-dimer were higher; leukocytosis with a neutrophil shift in the leukocyte count observed.CONCLUSION: Patients with a history of chronic kidney disease (CKD) had more severe COVID-19 and higher mortality.

1895. Omadacycline for the Treatment of Non-Pulmonary Mycobacterial Infections: a Single-Center Retrospective Review

Abstract Background Infections due to rapidly growing mycobacteria (RGM) such as M. abscessus, M. chelonae and M. fortuitum typically require long and toxic regimens, with complex resistance patterns and limited oral options further producing suboptimal efficacy. Since its approval in 2018, however, the tetracycline derivative omadacycline has established new options in antibiotic management. We report here clinical experience with the use of omadacycline for non-pulmonary RGM infections within the Mass General Brigham (MGB) system. Methods The study was approved by the MGB Institutional Review Board (2022P001578). Electronic ambulatory notes in the MGB Research Patient Data Registry (RPDR) from 2012-present were filtered by the term “omadacycline,” and manual chart review was conducted for individuals treated for non-pulmonary RGM infections. Flow diagram of chart review procedure for identification of non-pulmonary RGM patients Results Chart review revealed 25 patients with omadacycline-treated non-pulmonary RGM infections. The median age was 50, 52% female and 48% male. In total, 16 were infected with M. abscessus (64%), 8 with M. chelonae (32%), and 1 with M. immunogenum. 18 cases were skin and soft tissue infections (72%), 4 cases were bone and joint infections (16%), and 3 cases were disseminated infections (12%). Most patients (88%) received omadacycline as part of a step-down or a salvage regimen; 3 (12%) received omadacycline in initial treatment. 17 patients (68%) had completed regimens as of April 2023. Among these cases, the median duration of omadacycline use was 5 months (range=0.25-16). Patients within this cohort generally experienced clinical improvement. Adverse effects–most commonly nausea–were noted in 6 (24%) cases. No patients were discontinued due to the severity of these effects, though one regimen was temporarily paused due to hyperlipasemia. Non-pulmonary RGM patient cohort demographics, Mycobacterial species, and site of infection. Conclusion Omadacycline is an increasingly common component of the treatment of RGM infections, with use in multidrug regimens appearing generally effective and well-tolerated. Limitations of this study include its retrospective nature and evaluation within a single health system. To our knowledge, however, this is the largest series on omadacycline in RGM infections reported to-date. This analysis provides support for the further evaluation of omadacycline outcomes among patients with RGM infections. Disclosures All Authors: No reported disclosures

819. Experience with Isavuconazole Use for Treatment of Invasive Fungal Infections

Abstract Background The treatment of invasive fungal infections (IFI) is often complicated by drug-drug interactions, toxicities, and host comorbidities. Isavuconazole (ISA) has a favorable side effect profile and has FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data on its efficacy for other microbes and non-pulmonary infections. We report our experience of ISA in IFI treatment, with a particular focus on non-pulmonary sites and other microbial etiologies. Methods We identified patients who received ISA as part of IFI treatment from 1/1/2015–4/1/2020 at Mayo Clinic. We categorized them by organ involvement and by pathogens, and identified patterns of ISA use and clinical outcomes. Results A total of 131 patients were identified. Similar to the existing literature, the majority were pulmonary infections (60%), with 12% invasive sinus infection, 12% central nervous system (CNS) infection, and 7% fungemia. Aspergillus was the most common pathogen (39%), yeast comprised 19%, dimorphic fungi 15%, Mucormycosis 12%, phaeohyphomycosis 5%, and other molds 3%. ISA was used as secondary/salvage therapy in 89% of cases. The response rate varied by organ involvement and pathogen. ISA had complete/partial resolution or achieved stability in 57% of fungemia cases, 63% of invasive sinus infections, 64% of pulmonary infections, and 73% of CNS infections. Aspergillus species had a 67% response rate, with 72% response in yeast infections, 65% rate in dimorphic fungi, 53% for mucormycosis, and 86% in dematiaceous molds. Conclusion Although limited by a small sample size, the subgroup review based on organ site and microbial etiology did seem to show roughly similar results to approved uses. The CNS infections treated with ISA were particularly of interest, given the limited options available with reliable CNS penetration. The current available literature has little to say on the efficacy of ISA in these off-label uses, with the majority being similar case series. This report highlights the importance of prospective trials comparing ISA to other antifungals in a greater variety of indications to better identify when this better-tolerated agent can be safely used. Disclosures Courtney E. Harris, MD, Dynamed: Advisor/Consultant

Comparison of quality/quantity mNGS and usual mNGS for pathogen detection in suspected pulmonary infections.

Improved metagenomic next-generation sequencing (mNGS), for example, quality/quantity mNGS (QmNGS), is being used in the diagnosis of pulmonary pathogens. There are differences between QmNGS and the usual mNGS (UmNGS), but reports that compare their detection performances are rare. In this prospective study of patients enrolled between December 2021 and March 2022, the bronchoalveolar lavage fluid of thirty-six patients with suspected pulmonary infection was assessed using UmNGS and QmNGS. The sensitivity of QmNGS was similar to that of UmNGS. The specificity of QmNGS was higher than that of UmNGS; however, the difference was not statistically significant. The positive likelihood ratios (+LR) of QmNGS and UmNGS were 3.956 and 1.394, respectively, and the negative likelihood ratios (-LR) were 0.342 and 0.527, respectively. For the co-detection of pathogens, the depth and coverage of the QmNGS sequencing were lower than those of UmNGS, while for the detection of pathogens isolated from patients with pulmonary infection, the concordance rate was 77.2%. In the eleven patients with nonpulmonary infection, only viruses were detected using QmNGS, while UmNGS detected not only viruses but also bacteria and fungi. This study provides a basis for the selection of mNGS for the diagnosis of suspected pulmonary infection.

Assessing functional recovery for individuals with spinal cord injury post-discharge from inpatient rehabilitation

Objective To determine the associations between trauma variables, acute phase-related variables, and patient-level characteristics with functional recovery during the first-year post-discharge from inpatient rehabilitation facilities (IRF) for individuals with spinal cord injury (SCI). Design Retrospective cohort analysis. Setting Two SCI Model Centers in Pennsylvania, United States. Methods We were able to link 378 individuals with traumatic SCI between the Pennsylvania Trauma Systems Outcomes Study and the National SCI Model Systems databases. Nineteen individuals with SCI were excluded due to missing data. We estimated functional recovery based on changes in functional independence measure (FIM) total motor score during the first-year post-discharge from IRF in 359 individuals with SCI, who did not have any missing data, using ordinary least squares regression (OLS). Results After discharge from IRF the majority of individuals with SCI improved over the first-year post-injury. Individuals with cervical A-C (injury severity group) who were older had a slight decrease in motor FIM at 1-year post-injury. Regression analysis indicated that lower functional recovery was associated with being of Black and Hispanic race and ethnicity, higher injury severity group, occurrence of non-pulmonary infection during acute care, and longer length of stay at IRF (R 2 = 0.36). Conclusions Patient-level characteristics, trauma variables, and acute phase-related variables were associated with functional recovery post-discharge from IRF. Further research is necessary to collect and assess post-rehabilitation and socio-economic factors that play a critical role in continued functional recovery in the community.

Pneumonia panel results and antibiotic prescribing in COVID-19 patients in 2020 versus 2022

Background: Antibiotics are frequently prescribed in patients with COVID-19 infections to treat secondary bacterial pneumonia. The pneumonia panel (PNP) is a molecular diagnostic tool that rapidly detects 33 bacterial and viral targets. The utility of this panel in COVID-19 patients and how it may direct antibiotic use is unknown. We sought to understand the utilization of PNP in patients with COVID-19 pneumonia over time by comparing clinical parameters, microbiologic results, and antibiotic use between May–December 2020 and January–July 2022. Methods: We implemented the PNP in May 2020 with antimicrobial stewardship guidance, provider education, and order restriction to critical care and infectious disease clinicians. From February–July 2021 prescribers received regular structured antimicrobial stewardship feedback regarding PNP results; from August 2021 to January 2022, no antimicrobial stewardship feedback was provided; from February to July 2022, intermittent feedback was provided. We compared PNP and culture results from sputum or bronchoalveolar lavage samples and antibiotic use and modification within 24 hours of PNP result from patients with confirmed COVID-19 pneumonia between May–December 2020 and January–July 2022. Clinical data and antibiotic use were abstracted through chart review. We excluded patients who died within 72 hours of PNP, those who had concurrent nonpulmonary infections, and those whose COVID-19 test was &gt;30 days prior. Results: We included 114 patients in 2020 and 71 patients in 2022. The overall median age was 61 years, 71% were male, and 66% were mechanically ventilated without statistical differences between the cohorts, including their comorbidities. Acute or worsening hypoxia remained the predominant indication for PNP (77% in 2020 vs 75% in 2022, NS). The median number of days between admission and PNP was 4 (IQR, 1–8) in 2020 versus 3 (IQR, 1–7), and the difference was not significant. PNP and culture results in Table 1 show that Staphylococcus aureus and Hemophilus influenzae were the pathogens most commonly identified. Table 2 describes empiric prescribing and modifications for commonly prescribed antibiotics. Prescribers used empiric cefepime and ceftriaxone more in 2020 and vancomycin more in the 2022 group; however, these were not statistically significant. Cefepime de-escalation was more common in 2022 (53% vs 28%; P = .03). Antibiotic modifications within 24 hours of PNP remained similar in 2020 vs 2022. Although vancomycin cessation was more common in 2020 (78%) versus 2022 (57%), the difference was not statistically significant. Conclusions: With ASP guidance, PNP may be a useful tool to stop or target antibiotics for secondary bacterial pneumonia in COVID-19 pneumonia. Early vancomycin cessation (prior to culture results) may be an enduring consequence of PNP implementation.Disclosures: None

A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients

ObjectivesTo develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients. MethodsHospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS). Population PK analysis and Monte Carlo simulations were performed to determine the probability of target attainment (PTA). ResultsOne hundred and forty-two patients received intravenous polymyxin B (1.33–6 mg/kg/day), providing 681 plasma samples. Twenty-four patients were on renal replacement therapy, including 13 on continuous veno-venous hemodiafiltration (CVVHDF). A 2-compartment model adequately described the PK with body weight as a covariate on the volume of distribution that affected Cmax, but it did not impact clearance or exposure. Creatinine clearance was a statistically significant covariate on clearance, although clinically relevant variations of dose-normalized drug exposure were not observed across a wide creatinine clearance range. The model described higher clearance in CVVHDF patients than in non-CVVHDF patients. Maintenance doses of ≥2.5 mg/kg/day or ≥150 mg/day had a PTA ≥90% (for non-pulmonary infections target) at a steady state for minimum inhibitory concentrations ≤2 mg/L. The PTA at a steady state for CVVHDF patients was lower. DiscussionFixed loading and maintenance doses of polymyxin B seemed to be more appropriate than weight-based dosing regimens in patients weighing 45–90 kg. Higher doses may be needed in patients on CVVHDF. Substantial variability in polymyxin B clearance and volume of distribution was found, suggesting that therapeutic drug monitoring may be indicated.

The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: A nationwide study.

Lactic dehydrogenase reflects target organ damage, and is associated with mortality in patients with infectious diseases. The purpose of this study was to examine associations of serum lactic dehydrogenase levels with mortality, target organ damage and length of hospital stay in adults with pulmonary and non-pulmonary infections. This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. Patients with available serum lactic dehydrogenase levels on admission and one week after were included, and stratified by the source of their infection: pulmonary vs. non-pulmonary. Associations of lactic dehydrogenase levels with mortality and target organ damage were analyzed using multivariable logistic regression models. Quantile regression was used for multivariable analysis of the median length of stay. The study included 103,050 patients (45.4% male, median age: 69 years); 44,491 (43.1%) had pulmonary infections. The median serum lactic dehydrogenase levels on admission were higher in patients with pulmonary than non-pulmonary infections (418 vs. 385 units per liter (U/L), p<0.001). In a multivariable logistic regression model, elevated serum lactic dehydrogenase levels (480-700 U/L, 700-900 U/L and >900 U/L), compared with <480 U/L, were associated with in-hospital mortality (OR = 1.81, 2.85 and 3.69, respectively) and target organ damage (OR = 1.19, 1.51 and 1.80, respectively). The median stay increased with increasing elevated lactic dehydrogenase levels (+0.3, +0.5 and +0.4 days, respectively). Among patients with lactic dehydrogenase levels >900 U/L, mortality, but none of the other examined outcomes, was greater among those with pulmonary than non-pulmonary infections. Among hospitalized patients with infectious diseases, lactic dehydrogenase levels were associated with mortality and target organ damage, and were similar in patients with pulmonary and non-pulmonary infections. Among patients with lactic dehydrogenase levels >900 U/L, mortality was prominently higher among those with pulmonary than non-pulmonary infections.

Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients

ObjectivesPulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis.Methods140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated.ResultsThe patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p < 0.05, respectively), and more changes in pulmonary CT scanning images in terms of patched/striped compact opacity, alveolar hemorrhage, bronchiectasis, pleural effusion, as well as mediastinal lymphadenopathy (89.71% vs 52.00%, 11.76% vs 2.00%, 22.06% vs 8.00%, 50.00% vs 20.00%, 48.53% vs 24.00%, p < 0.05, respectively). In addition, patients in the lung infection group had significantly higher levels of serum pro-calcitonin (PCT), C-reactive protein (CRP), amyloid A (SAA), blood neutrophil-to-lymphocyte ratio (NLCR), erythrocyte sedimentation rate (ESR), as well as Birmingham vasculitis activity score (BVAS) than patients in the other two groups (p < 0.05). Among all biomarkers, PCT exhibited the highest diagnostic efficacy (0.928; 95%CI 0.89–0.97) for pulmonary infected AAV patients at a cut-off score of 0.235 ng/ml with 85.3% sensitivity and 84% specificity. Moreover, the composite biomarker of PCT-CRP-NLCR showed more diagnostic efficacy (0.979; 95% CI 0.95–1.00) in distinguishing the infectious and non-infectious lung injuries in AAV patients.ConclusionsAAV patients with lung infection manifested more clinical symptoms and prominent lung image changes. The PCT and composite biomarker PCT-CRP-NLCR showed high diagnostic efficacy for a lung infection in AAV patients. Pulmonary lesion caused by either infection or AAV involvement is commonly seen and difficult to distinguish. We aim to identify the biomarkers that can be applied in the differentiation diagnosis of pulmonary lesions in AAV patients.

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection.

BackgroundClara cell 16 kDa protein (CC16) is a secretory protein primarily expressed in epithelial cells in the lungs. Previous studies show that CC16 exerts anti-inflammatory and immune-modulatory properties in both acute and chronic pulmonary diseases. However, despite the evidence of CC16’s high biomarker potential, evaluation of its role in infectious diseases is yet very limited.MethodsSerum CC16 concentrations were measured by ELISA and assessed in two different types of severe infections. Using a case-control study design, patients treated for either severe SARS-CoV-2 or severe non-pulmonary sepsis infection were compared to age- and sex-matched healthy human subjects.ResultsSerum CC16 was significantly increased in both types of infection (SARS-CoV-2: 96.22 ± 129.01 ng/ml vs. healthy controls: 14.05 ± 7.48 ng/ml, p = 0.022; sepsis: 35.37 ± 28.10 ng/ml vs. healthy controls: 15.25 ± 7.51 ng/ml, p = 0.032) but there were no distinct differences between infections with and without pulmonary focus (p = 0.089). Furthermore, CC16 serum levels were positively correlated to disease duration and inversely to the platelet count in severe SARS-CoV-2 infection.ConclusionsIncreased CC16 serum levels in both SARS-CoV-2 and sepsis reinforce the high potential as a biomarker for epithelial cell damage and bronchoalveolar−blood barrier leakage in pulmonary as well as non-pulmonary infectious diseases.

Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study.

The concentration-time profile of linezolid varies considerably in critically ill patients. Question of interest is, if the site of infection influences linezolid serum concentrations. 68 critically ill patients, treated with linezolid, were included. The concentration-time-profile for linezolid was determined using maximum a-posteriori predictions. A trough concentration (Cmin) between 2 and 10 mg/L was defined as the target. A generalized linear model (GLM) was established to evaluate potential covariates. The indications for linezolid therapy were in descending order: peritonitis (38.2%), pneumonia (25.0%), infectious acute respiratory distress syndrome (ARDS) (19.1%), and other non-pulmonary infection (17.7%). 27.2 and 7.9% of Cmin were subtherapeutic and toxic, respectively. In the GLM, ARDS (mean: -2.1 mg/L, CI: -3.0 to -1.2 mg/L) and pneumonia (mean: -2.2 mg/L, CI: -2.8 to -1.6 mg/L) were significant (p < 0.001) determinants of Cmin. Patients with ARDS (mean: 2.3 mg/L, 51.2% subtherapeutic, 0.0% toxic) and pneumonia (mean: 3.5 mg/L, 41.5% subtherapeutic, 7.7% toxic) had significantly (p < 0.001) lower Cmin than those with peritonitis (mean: 5.5 mg/L, 14.4% subtherapeutic, 9.3% toxic) and other non-pulmonary infection (mean: 5.2 mg/L, 3.3% subtherapeutic, 16.5% toxic). Linezolid serum concentrations are reduced in patients with pulmonary infections. Future studies should investigate if other linezolid thresholds are needed in those patients due to linezolid pooling in patients´ lung.

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent

Treatment of newly diagnosed multiple myeloma (NDMM) with a quadruplet regimen consisting of a monoclonal antibody, proteasome inhibitor, immunomodulatory imide, and corticosteroid has been associated with improved progression-free survival (PFS) compared with triplet regimens. The optimal quadruplet combination, and whether this obviates the need for frontline autologous stem cell transplant (ASCT), remains unknown. We evaluated elotuzumab and weekly carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) without ASCT in NDMM. To investigate the efficacy of Elo-KRd using a measurable residual disease (MRD)-adapted design in NDMM regardless of ASCT eligibility. This multicenter, single-arm, phase 2 study enrolled patients between July 2017 and February 2021. Median follow-up was 29 months. Twelve to 24 cycles of Elo-KRd; consecutive MRD-negative results at 10-6 by next-generation sequencing (NGS) after cycles 8 (C8) and 12 determined the duration of Elo-KRd. This was followed by Elo-Rd (no carfilzomib) maintenance therapy until disease progression. The primary end point was the rate of stringent complete response (sCR) and/or MRD-negativity (10-5) after C8 Elo-KRd. Secondary end points included safety, rate of response, MRD status, PFS, and overall survival (OS). As an exploratory analysis, MRD was assessed using liquid chromatography mass spectrometry (MS) on peripheral blood samples. Forty-six patients were enrolled (median age 62 years, 11 [24%] aged >70 years). Overall, 32 (70%) were White, 6 (13%) were Black, 3 (6%) were more than 1 race, and 5 (11%) were of unknown race. Thirty-three (72%) were men and 13 (28%) were women. High-risk cytogenetic abnormalities were present in 22 (48%) patients. The rate of sCR and/or MRD-negativity after C8 was 26 of 45 (58%), meeting the predefined statistical threshold for efficacy. Responses deepened over time, with the MRD-negativity (10-5) rate increasing to 70% and MS-negativity rate increasing to 65%; concordance between MRD by NGS and MS increased over time. The most common (>10%) grade 3 or 4 adverse events were lung and nonpulmonary infections (13% and 11%, respectively). There was 1 grade 5 myocardial infarction. The estimated 3-year PFS was 72% overall and 92% for patients with MRD-negativity (10-5) at C8. An MRD-adapted design using elotuzumab and weekly KRd without ASCT showed a high rate of sCR and/or MRD-negativity and durable responses. This approach provides support for further evaluation of MRD-guided deescalation of therapy to decrease treatment exposure while sustaining deep responses. ClinicalTrials.gov Identifier: NCT02969837.

Atlantoaxial Subluxation Secondary to SARS-CoV-2 Infection: A Rare Orthopedic Complication from COVID-19

Patient: Male, 86-year-old Final Diagnosis: Atlantoaxial subluxation Symptoms: Neck pain Medication:— Clinical Procedure: — Specialty: Rehabilitation Objective: Rare coexistence of disease or pathology Background:There are several reports of atlantoaxial subluxation caused by upper respiratory tract infections. Although, there are many known non-pulmonary complications COVID-19 infection, to date there have been no reported cases of orthopedic complications in the peer-reviewed literature. Diagnosis and management of atlantoaxial subluxation is currently limited. Therefore, it is important to explore other methods of identifying and treating patients suffering from atlantoaxial subluxation.Case Report:Our patient was an 86-year-old man with right-sided neck pain and reduced range of neck motion for the past 6 months, shortly after a mild case of COVID-19. Autoimmune and inflammatory workup was unremarkable. Patient’s symptoms persisted despite 3 weeks of conservative therapy with analgesics, cervical collar, and physical therapy. He received low-frequency kinetically directed impulse wave (al-Kindi wave) treatment administered by the KKT device after 3-dimensional digital X-ray analysis of the atlas. After receiving the treatment over a period of 13 days, patient showed significant improvement in symptoms and follow-up X-rays.Conclusions:For patient’s having neck stiffness or pain with COVID-19, it is important to consider atlantoaxial subluxation as a potential cause, especially if the patient requires intubation, as the technique should be adjusted to reduce spinal injury. Atlas X-ray analysis with Spinalytics provides very precise measurements of the atlas in relation to the skull and cervical spine, and improvement in angles were seen before and after treatment. The al-Kindi wave treatment was also effective in reducing the patient’s symptoms and improving cervical X-ray results, but further studies are required for confirmation.

Evaluation of the relationships between procalcitonin and neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with pneumonia.

The aim of this study is to examine whether there is a relationship between procalcitonin and neutrophil/lymphocyte ratio or platelet/lymphocyte ratio in patients with pneumonia. The data of 54 patients hospitalized in the respiratory unit of the Adıyaman University Faculty of Medicine Hospital (Adıyaman, Turkey) with the diagnosis of pneumonia between January 2018 and July 2019 were reviewed retrospectively. The patients' complete blood count, procalcitonin, erythrocyte sedimentation rate, and C-reactive protein data were obtained. Diagnosis was made by chest X-ray and, for some patients, by thorax computed tomography together with appropriate clinical findings. Patients with a history of tumors, trauma, burns, surgery, kidney failure, inflammatory diseases or non-pulmonary infections were excluded from the study. The mean age of the patients was 59.04±20.00 years in the group with normal procalcitonin and 66.04±18.28 years in the group with elevated procalcitonin (p: 0.186). The female/male sex ratio of the patients was 15/13 in the group with normal procalcitonin and 8/18 in the group with elevated procalcitonin (p: 0.090). Neutrophil/lymphocyte ratio was 3.97 (1.20-10.77) in the group with normal procalcitonin and 7.21 (0.60-29.50) in the group with elevated procalcitonin (p: 0.012). Platelet/lymphocyte ratio was 155.54±68.89 in the group with normal procalcitonin and 157.48±81.38 in the group with elevated procalcitonin (p: 0.925). In ROC analysis performed to predict elevated levels of procalcitonin, cut-off values were 16.4 ×103/mm3 for white blood cells (p: 0.003), 11.7 ×103/mm3 for neutrophils (p: 0.001), 5.47 for neutrophil/lymphocyte ratio (p: 0.005), and 7.4 mg/dL for C-reactive protein (p: 0.005). In our study, white blood cell, neutrophil, neutrophil/lymphocyte ratio, and C-reactive protein values were found to be significantly higher in patients with elevated procalcitonin. The neutrophil/lymphocyte ratio was also significantly correlated with white blood cell count and platelet/lymphocyte ratio.

Risk of nonpulmonary infections requiring hospitalization in spondyloarthritis.

ObjectivesTo compare the risk of five nonpulmonary infections leading to hospitalization between spondyloarthritis (SpA) and nonspecific back pain (NSBP), and to identify the risk factors.MethodsA total of 3018 patients with SpA and 2527 patients with NSBP were identified. Data from December 1995 to June 2019 was retrieved from a centralized electronic medical record system. The date of onset of five types of nonpulmonary infections including: urinary tract infection (UTI), skin infection, gastroenteritis (GE), septic arthritis, and pancreato‐hepatobiliary tract infection were identified. Demographic data, comorbidities, and medications used were also retrieved. Comparative risk of each type of infection between SpA and NSBP was determined using propensity score adjustment method. Cox regression model was used to identified risk factors.ResultsPatients with SpA were younger in age, predominantly male, with fewer comorbid diabetes mellitus (DM), renal impairment, and depression. Compared with NSBP, patients with SpA had higher risk of UTI (hazard ratio [HR] 1.91; p < .001), skin infection (HR 1.79; p < .001), and septic arthritis (HR 4.57; p = .04). Risk of GE (HR 1.42; p = 1.00), and pancreato‐hepatobiliary tract infection (HR 1.67; p = .06) were not increased. Infliximab was an independent risk factor for UTI (HR 2.21; p = .04). Duration of steroid therapy >6 months (HR 2.22; p < .001), smoker (HR 1.81; p < .001), and psoriasis (HR 2.47; p < .001) were risk factors for skin infection.ConclusionSpA was associated with increased risk of UTI, skin infection, and septic arthritis. Infliximab, prolonged steroid therapy, smoking, and psoriasis were associated risk factors.

Antibiotic use for respiratory syncytial virus in the Middle East: A surveillance study in hospitalized Jordanian children.

IntroductionIn developing countries where point-of-care testing is limited, providers rely on clinical judgement to discriminate between viral and bacterial respiratory infections. We performed a cross-sectional cohort study of hospitalized Jordanian children to evaluate antibiotic use for respiratory syncytial virus (RSV) infections.Materials and methodsAdmitting diagnoses from a prior viral surveillance cohort of hospitalized Jordanian children were dichotomized into suspected viral-like, non-pulmonary bacterial-like, and pulmonary bacterial-like infection. Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) for antibiotic use during hospitalization. Sensitivity and specificity of admission diagnoses and research laboratory results were compared.ResultsChildren with a suspected viral-like admission diagnosis, compared to those with suspected non-pulmonary bacterial-like, were 88% and 86% less likely to be administered an empiric/first-line antibiotic (male, aPOR: 0.12; female, aPOR: 0.14; p-value = <0.001). There were slight differences by sex with males having a lower prevalence than females in being administered an expanded coverage antibiotic; but they had a higher prevalence of macrolide administration than males with non-pulmonary bacterial-like infection. Overall, children with RSV had a 34% probability (sensitivity) of being assigned to a suspected viral-like diagnosis; whereas RSV-negative children had a 76% probability (specificity) of being assigned to a suspected pulmonary bacterial-like diagnosis.ConclusionsHospitalized children with a suspected viral-like admission diagnosis were less likely to receive an empiric/first-line and expanded coverage antibiotic compared to suspected non-pulmonary and pulmonary infections; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.

Nonpulmonary Infections of the Thorax

In this paper, we provide a brief overview of the history, organizational structure, and current operational state of our blended academic and community-model breast service. We review the challenges inherent to governance and management of a "matrix" organization practice model such as ours, and discuss the ways in which the leadership of our evolving blended practice are addressing those challenges collaboratively.

High-Dose versus Standard-Dose Tigecycline Treatment of Secondary Bloodstream Infections Caused by Extensively Drug-Resistant Acinetobacter baumannii: An Observational Cohort Study.

BackgroundExtensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.MethodsAn observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.ResultsOf the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.ConclusionA tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.