Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes.

BACKGROUND: While 'immuno-competence' is a well-known term, it lacks an operational definition. To address this omission, this study explored whether the temporal and structured data of the complete blood cell count (CBC) can rapidly estimate immuno-competence. To this end, one or more ratios that included data on all monocytes, lymphocytes and neutrophils were investigated. MATERIALS AND METHODS: Longitudinal CBC data collected from 101 COVID-19 patients (291 observations) were analyzed. Dynamics were estimated with several approaches, which included non-structured (the classic CBC format) and structured data. Structured data were assessed as complex ratios that capture multicellular interactions among leukocytes. In comparing survivors with non-survivors, the hypothesis that immuno-competence may exhibit feedback-like (oscillatory or cyclic) responses was tested. RESULTS: While non-structured data did not distinguish survivors from non-survivors, structured data revealed immunological and statistical differences between outcomes: while survivors exhibited oscillatory data patterns, non-survivors did not. In survivors, many variables (including IL-6, hemoglobin and several complex indicators) showed values above or below the levels observed on day 1 of the hospitalization period, displaying L-shaped data distributions (positive kurtosis). In contrast, non-survivors did not exhibit kurtosis. Three immunologically defined data subsets included only survivors. Because information was based on visual patterns generated in real time, this method can, potentially, provide information rapidly. DISCUSSION: The hypothesis that immuno-competence expresses feedback-like loops when immunological data are structured was not rejected. This function seemed to be impaired in immuno-suppressed individuals. While this method rapidly informs, it is only a guide that, to be confirmed, requires additional tests. Despite this limitation, the fact that three protective (survival-associated) immunological data subsets were observed since day 1 supports many clinical decisions, including the early and personalized prognosis and identification of targets that immunomodulatory therapies could pursue. Because it extracts more information from the same data, structured data may replace the century-old format of the CBC.

From numbers to medical knowledge: harnessing combinatorial data patterns to predict COVID-19 resource needs and distinguish patient subsets.

Background: The COVID-19 pandemic intensified the use of scarce resources, including extracorporeal membrane oxygenation (ECMO) and mechanical ventilation (MV). The combinatorial features of the immune system may be considered to estimate such needs and facilitate continuous open-ended knowledge discovery. Materials and methods: Computer-generated distinct data patterns derived from 283 white blood cell counts collected within five days after hospitalization from 97 COVID-19 patients were used to predict patient's use of hospital resources. Results: Alone, data on separate cell types-such as neutrophils-did not identify patients that required MV/ECMO. However, when structured as multicellular indicators, distinct data patterns displayed by such markers separated patients later needing or not needing MV/ECMO. Patients that eventually required MV/ECMO also revealed increased percentages of neutrophils and decreased percentages of lymphocytes on admission. Discussion/conclusion: Future use of limited hospital resources may be predicted when combinations of available blood leukocyte-related data are analyzed. New methods could also identify, upon admission, a subset of COVID-19 patients that reveal inflammation. Presented by individuals not previously exposed to MV/ECMO, this inflammation differs from the well-described inflammation induced after exposure to such resources. If shown to be reproducible in other clinical syndromes and populations, it is suggested that the analysis of immunological combinations may inform more and/or uncover novel information even in the absence of pre-established questions.

Disseminated mycobacterial infections after tumor necrosis factor inhibitor use, revealing inborn errors of immunity.

Tumor necrosis factor-a inhibitors can be associated with increased risk of infections, particularly reactivation of latent tuberculosis or nontuberculous mycobacterium (NTM). However, because disseminated NTM is rare, inborn errors of immunity should be considered. We present three patients with disseminated NTM after tumor necrosis factor-a inhibitor use who were found to have inborn errors of immunity.

A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis.

Background: The Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer's (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer's lactate in a cohort of sepsis patients. Method: We performed a retrospective cohort analysis of patients visiting the ED of 19 different Mayo Clinic sites between August 2018 to November 2020 with sepsis and receiving at least 30 mL/kg fluid in the first 6 h. Patients were divided into two cohorts based on the type of resuscitation fluid (LR vs. NS) and propensity-matching was done based on clinical characteristics as well as fluid amount (with 5 ml/kg). Single variable logistic regression (categorical outcomes) and Cox proportional hazards regression models were used to compare the primary and secondary outcomes between the 2 groups. Results: Out of 2022 patients meeting our inclusion criteria; 1,428 (70.6%) received NS, and 594 (29.4%) received LR as the predominant fluid (>30 mL/kg). Patients receiving predominantly NS were more likely to be male and older in age. The LR cohort had a higher BMI, lactate level and incidence of septic shock. Propensity-matched analysis did not show a difference in 30-day and in-hospital mortality rate, mechanical ventilation, oxygen therapy, or CRRT requirement. We did observe longer hospital LOS in the LR group (median 5 vs. 4 days, p = 0.047 and higher requirement for ICU post-admission (OR: 0.70; 95% CI: 0.51-0.96; p = 0.026) in the NS group. However, these did not remain statistically significant after adjustment for multiple testing. Conclusion: In our matched cohort, we did not show any statistically significant difference in mortality rates, hospital LOS, ICU admission after diagnosis, mechanical ventilation, oxygen therapy and RRT between sepsis patients receiving lactated ringers and normal saline as predominant resuscitation fluid. Further large-scale prospective studies are needed to solidify the current guidelines on the use of balanced crystalloids.

Data structuring may prevent ambiguity and improve personalized medical prognosis.

Topics expected to influence personalized medicine (PM), where medical decisions, practices, and treatments are tailored to the individual patient, are reviewed. Lack of discrimination due to different biological conditions that express similar values of numerical variables (ambiguity) is regarded to be a major potential barrier for PM. This material explores possible causes and sources of ambiguity and offers suggestions for mitigating the impacts of uncertainties. Three causes of ambiguity are identified: (1) delayed adoption of innovations, (2) inadequate emphases, and (3) inadequate processes used when new medical practices are developed and validated. One example of the first problem is the relative lack of medical research on "compositional data" -the type that characterizes leukocyte data. This omission results in erroneous use of data abundantly utilized in medicine, such as the blood cell differential. Emphasis on data output ‒not biomedical interpretation that facilitates the use of clinical data‒ exemplifies the second type of problems. Reliance on tools generated in other fields (but not validated within biomedical contexts) describes the last limitation. Because reductionism is associated with these problems, non-reductionist alternatives are reviewed as potential remedies. Data structuring (converting data into information) is considered a key element that may promote PM. To illustrate a process that includes data-information-knowledge and decision-making, previously published data on COVID-19 are utilized. It is suggested that ambiguity may be prevented or ameliorated. Provided that validations are grounded on biomedical knowledge, approaches that describe certain criteria - such as non-overlapping data intervals of patients that experience different outcomes, immunologically interpretable data, and distinct graphic patterns - can inform, at personalized bases, earlier and/or with fewer observations.

Clinical and laboratory profiles of the SARS-CoV-2 Delta variant compared with pre-Delta variants.

OBJECTIVES: The emergence of SARS-CoV-2 variants of concern has led to significant phenotypical changes in transmissibility, virulence, and public health measures. Our study used clinical data to compare characteristics between a Delta variant wave and a pre-Delta variant wave of hospitalized patients. METHODS: This single-center retrospective study defined a wave as an increasing number of COVID-19 hospitalizations, which peaked and later decreased. Data from the United States Department of Health and Human Services were used to identify the waves' primary variant. Wave 1 (August 8, 2020-April 1, 2021) was characterized by heterogeneous variants, whereas Wave 2 (June 26, 2021-October 18, 2021) was predominantly the Delta variant. Descriptive statistics, regression techniques, and machine learning approaches supported the comparisons between waves. RESULTS: From the cohort (N = 1318), Wave 2 patients (n = 665) were more likely to be younger, have fewer comorbidities, require more care in the intensive care unit, and show an inflammatory profile with higher C-reactive protein, lactate dehydrogenase, ferritin, fibrinogen, prothrombin time, activated thromboplastin time, and international normalized ratio compared with Wave 1 patients (n = 653). The gradient boosting model showed an area under the receiver operating characteristic curve of 0.854 (sensitivity 86.4%; specificity 61.5%; positive predictive value 73.8%; negative predictive value 78.3%). CONCLUSION: Clinical and laboratory characteristics can be used to estimate the COVID-19 variant regardless of genomic testing availability. This finding has implications for variant-driven treatment protocols and further research.

Multi-Cellular Immunological Interactions Associated With COVID-19 Infections.

To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a "reductionist" one, which analyzes each cell type separately, and (ii) a "non-reductionist" method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern's immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations.

BACKGROUND: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge. METHODS: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders. RESULTS: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients. CONCLUSIONS: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.

Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.

After more than a year of the COVID-19 pandemic, SARS-CoV-2 infection rates with newer variants continue to devastate much of the world. Global healthcare systems are overwhelmed with high positive patient numbers. Silent hypoxia accompanied by rapid deterioration and some cases with septic shock is responsible for COVID-19 mortality in many hospitalized patients. There is an urgent need to further understand the relationships and interplay with human host components during pathogenesis and immune evasion strategies. Currently, acquired immunity through vaccination or prior infection usually provides sufficient protection against the emerging variants of SARS-CoV-2 except Omicron variant requiring recent booster. New strains have shown higher viral loads and greater transmissibility with more severe disease presentations. Notably, COVID-19 has a peculiar prognosis in severe patients with iron dysregulation and hypoxia which is still poorly understood. Studies have shown abnormally low serum iron levels in severe infection but a high iron overload in lung fibrotic tissue. Data from our in-silico structural analysis of the spike protein sequence along with host proteolysis processing suggests that the viral spike protein fragment mimics Hepcidin and is resistant to the major human proteases. This functional spike-derived peptide dubbed "Covidin" thus may be intricately involved with host ferroportin binding and internalization leading to dysregulated host iron metabolism. Here, we propose the possible role of this potentially allogenic mimetic hormone corresponding to severe COVID-19 immunopathology and illustrate that this molecular mimicry is responsible for a major pathway associated with severe disease status. Furthermore, through 3D molecular modeling and docking followed by MD simulation validation, we have unraveled the likely role of Covidin in iron dysregulation in COVID-19 patients. Our meta-analysis suggests the Hepcidin mimetic mechanism is highly conserved among its host range as well as among all new variants to date including Omicron. Extensive analysis of current mutations revealed that new variants are becoming alarmingly more resistant to selective human proteases associated with host defense.

Alkaline Urine in the Emergency Department Predicts Nitrofurantoin Resistance.

BACKGROUND: The Proteeae group (i.e., Proteus species, Morganella morganii, and Providencia species) frequently causes urinary tract infections (UTIs) and is generally resistant to nitrofurantoin. Proteeae species can produce urease, which can increase urine pH. OBJECTIVE: Our aim was to determine whether higher urine pH in the emergency department is associated with nitrofurantoin resistance. METHODS: A single health system database of emergency department patients aged 18 years and older who received urinalysis between April 18, 2014, and March 7, 2017, was examined using χ2 test and multivariable regression analysis. RESULTS: Of 67,271 urine samples analyzed, 13,456 samples grew a single bacterial species. Urine cultures growing the Proteeae group were associated with significantly more alkaline urine than other bacteriuria cultures (odds ratio [OR] 2.20, 95% confidence interval [CI] 2.06-2.36; p < 0.001). The Proteeae species represented 4.4% of urine samples at pH 5-7, 24.4% at pH 8-9, and 40.0% at pH 9. At urine pH 5-7, 80.4% of urine samples were sensitive to nitrofurantoin; however, this percentage decreased to 66.1% for urine pH 8-9 and 54.6% for urine pH 9. Nitrofurantoin had the highest OR (2.10, 95% CI 1.85-2.39) among cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole for bacteriuria sensitive to those antibiotics at urine pH 5-7. At urine pH 8-9 and 9, nitrofurantoin had the lowest OR among the antibiotics: 0.48 (95% CI 0.42-0.54) and 0.31 (95% CI 0.24-0.40), respectively (p < 0.001 for both). CONCLUSIONS: Urine pH of 8 or higher is associated with high rates of nitrofurantoin resistance.

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial.

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.

Investigating the association of bed bugs with infectious diseases: A retrospective case-control study.

Bed bugs are common urban pests. Unlike many other blood-feeding human ectoparasites, bed bugs are not known to be vectors of human infectious diseases, but clinical and epidemiological studies to directly interrogate this link have been limited. Here, we aimed to determine whether bed bugs were associated with infectious diseases in a set of infested patients presenting to emergency departments (ED) in the greater Cleveland, OH area. We performed a retrospective case-control study involving 332 ED patients with bed bugs and 4,952 control patients, seen from February 1, 2011, through February 1, 2017. Cases and controls were matched by age, sex, and the presenting ED. Additionally, data were adjusted for ≥20 sociodemographic variables, triage data, and comorbidities in multivariable regression analyses. Seventeen laboratory values, ten different ED and inpatient diagnoses, chest radiographs, infectious disease consults, and blood cultures were examined. The odds of bed bug infestation were significantly higher for patients that had positive blood cultures, had blood cultures growing coagulase-negative Staphylococcus, were diagnosed with pneumonia, were diagnosed with cellulitis, received an infectious disease consult, received a chest radiograph, and had higher percentages of eosinophils in the blood (P < .05 for all). Additional investigations are needed to determine whether bed bugs directly contribute to disease by transmitting causative agents, whether bed bug exposure contributes secondarily contributes to infections, or whether these associations are better explained by other environmental and social determinants of health.

Minimal change disease and subacute interstitial nephritis in association with Edwardsiella tarda gastroenteritis following oyster consumption.

Edwardsiella tarda (E. tarda) is a gram-negative, facultatively anaerobic bacillus that is associated with gastroenteritis and a host of other extra-intestinal manifestations in humans. However, its impact on the kidneys is unclear. Most literature that has explored this association involves fish, marine life in which E. tarda inhabits. We report a rare case of a 72-year-old female who presented with an acute kidney injury (AKI) associated with newfound minimal change disease, subacute interstitial nephritis, and a severe E. tarda infection. Her clinical course resolved with antibiotics and glucocorticoids.

A Comparison of Interobserver Reliability Between Orthopedic Surgeons Using the Centers for Disease Control Surgical Wound Class Definitions.

BACKGROUND: The Centers for Disease Control (CDC) created a classification to help stratify surgical wounds based on contamination and risk of developing a surgical site infection. The classification includes four options (I to IV) depending on the level of contamination present. Although universally applied to a variety of surgical specialties, it is unknown whether the current system is reliable when considering orthopaedic surgeries. The purpose of this study was to compare the degree of interobserver reliability between orthopaedic surgeons using the current CDC wound class definitions. METHODS: A questionnaire containing 30 clinical vignettes was completed by 39 orthopaedic surgeons at our institution. After each vignette, respondents were asked to determine the appropriate wound class based on information provided in the vignette. The overall interobserver agreement among all participants was analyzed. In addition, respondents were queried about the adequacy of the current classification system in describing orthopaedic surgical wound class. RESULTS: Interobserver agreement was poor at 66%, with a coefficient of concordance of 0.48. Only six physicians (15.4%) thought that the current wound classification system adequately covered orthopaedic surgery. CONCLUSIONS: There is poor interobserver reliability using the CDC surgical wound class definitions for orthopaedic surgeries. Alternate definitions are needed to improve the validity of the system for subspecialty procedures.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Serologic screening and infectious diseases consultation in renal transplant candidates for measles, mumps, rubella and varicella.

Background. Renal transplant recipients are at increased risk for developing complications of vaccine-preventable diseases. They benefit from a comprehensive pre-transplant evaluation when they might safely receive live vaccines. The primary aim of our study was to investigate the number of renal transplant recipients who were evaluated for serologic status against measles, mumps, rubella (MMR), and varicella. Secondarily, we investigated if pre-transplant Infectious Diseases consultation (IDC) improved vaccination rates.Methods. We retrospectively analyzed 282 kidney-alone and kidney-plus adult transplant recipients who were born in or after 1957. Patients were evaluated at Mayo Clinic, Florida Transplant Center between January 2015 and December 2017. Serologic status evaluation and vaccination rates were compared in two groups created based on IDC and no ID consultation (NIDC).Results. 235 (83%) of a total 282 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 235 IDC candidates. Among the IDC patients, mumps, measles and rubella IgG serologies were performed in 7 (3%), 143 (61%) and 144 (61%), respectively. Among 44 patients seronegative for any of MMR, 24 (55%) were vaccinated. Ten (66%) of 15 varicella seronegative patients were vaccinated. Zostavax was not given to 18% of IDC patients. Zostavax and MMR were administered more frequently in the IDC group compared to NIDC (p < .001 and p = 0.0016, respectively).Conclusion. Although the majority of patients had IDC, the screening rate for MMR serologies was lower than varicella. A protocol-driven serologic screening similar to the one for VZV is required for MMR. Pre-transplant IDC increases vaccination rates.

Establishing best practices in measles, mumps, and rubella serologic screening for kidney transplant candidates.

Optimizing immunity against vaccine-preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al, World J Transplant, 2019, 9:1; Sester et al, Transplant Rev, 2008, 22:274; Fishman, N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live-attenuated vaccines are contraindicated post-transplantation (Malinis et al, Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan-Do-Study-Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol-driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre-KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre-KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%-87.4% post-PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol-driven orders combined with our pre-existing IDCs.

Bed bugs are associated with anemia.

INTRODUCTION: Bed bugs are hematophagous insects that can be problematic in some urban emergency departments. The objective was to determine if red blood cell (RBC) and coagulation indices of bed bug-infested emergency department (ED) patients differed from those of noninfested control patients. METHODS: A chart review from a single health system was performed for ED patients between February 1, 2011, and February 1, 2017. Bed bug-infested patients were matched to noninfested control patients on the basis of age, sex, and the presenting ED. Variables were analyzed with the t-test and Pearson χ2 test and were modeled with multivariable logistic regression. RESULTS: The study had 332 bed bug-infested patients and 4952 controls. Infested patients had lower hemoglobin (11.7 g/dL vs 12.8 g/dL), hematocrit (35.0% vs 37.9%), RBC counts (4.1 × 109/L vs 4.4 × 109/L), mean corpuscular volume (86.0 vs 87.5 fL/cell), and mean corpuscular hemoglobin concentrations (33.2 vs 33.7 g/dL) and higher RBC distribution width-coefficient of variation (RDW-CV) (15.2% vs 14.2%) than noninfested patients (all P ≤ .003). Infested patients were more likely to be anemic (59.5% vs 36.9%) and to have severe anemia (4.4% vs 0.7%) (P < .001 for both). Blood transfusions were more common in those with bed bugs (5.1%) than those without bed bugs (2.3%) (P < .001). CONCLUSION: Bed bug infestated patients in the ED are associated with anemia.

Three-tier stratification for CNS COVID-19 to help decide which patients should undergo lumbar puncture with CSF analysis: a case report and literature review.

The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study.

OBJECTIVE: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death. RESULTS: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. CONCLUSION: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).