Marked hyperferritinemia in critically ill cancer patients.

OBJECTIVES: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia. METHODS: A single-center retrospective analysis comprising cancer patients with a ferritin level >10.000 µg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted. RESULTS: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15-86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 µg/L (range: 10.300-426.073 µg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH-2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90-day and 1-year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p = .001); the survival of patients who fulfilled the HLH-2004 criteria did not differ from those who did not (p = .88). CONCLUSION: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group.

Measuring capillary blood glucose concentration: Is the first blood drop really the right blood drop?

BACKGROUND: Capillary blood glucose (CBG) is fundamental for diabetes mellitus management. However, it is still unclear whether the first or the subsequent blood drops most accurately reflect patients' blood glucose levels. METHODS: 128 healthy volunteers were included in this prospective cohort study from November 2021 to December 2021. Capillary blood glucose concentrations of the first four blood drops, measured using glucose meters were compared with venous blood concentrations of the respective donors, measured using an in-lab hexokinase method. ANOVA, the Spearman correlation coefficient and Bland-Altman plots were used to analyze the data. RESULTS: The mean plasma glucose concentration was 90.46 mg/dl with an SD of ± 14.416 (5.02 ± 0.8 mmol/l). There were statistically strong correlations among the glucose concentrations of all capillary blood drops (correlation coefficients of r > 0.8). The first capillary blood drops showed the lowest mean difference to plasma blood glucose concentrations (+4.92 mg/dl; +0.27 mmol/l), followed by the third drop (+7.28 mg/dl; +0.4 mmol/l), second drop (+7.30 mg/dl; +0.4 mmol/l) and fourth drop (+8.87 mg/dl; +0.49 mmol/l). CONCLUSION: There is a strong correlation and good agreement between the different capillary blood drops, making all blood drops equally suitable for blood glucose monitoring. In practice, the given setting (clinical or patient self-monitoring) should be considered upon choosing a specific blood drop.

C-Reactive Protein and Lymphocyte-to-Monocyte Ratio Predict Recurrence in Stage III Melanoma Patients with Microscopic Sentinel Lymph Node Metastasis.

Although adjuvant therapies with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors improve recurrence-free survival (RFS) in stage III melanoma patients significantly, prognostic factors are needed to identify patients with a high risk of disease recurrence. Therefore, the aim of our study was to investigate the prognostic potential of routinely collected blood parameters for stage III melanoma patients with microscopic sentinel lymph node (SLN) metastasis. Altogether, we retrospectively analyzed 138 stage III melanoma patients who were diagnosed with microscopic SLN metastasis at the skin cancer center of the University Hospital Cologne between 2011 and 2020 and who did not receive prior adjuvant therapy with ICI or BRAF/MEK-inhibitors. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analyses and receiver operating characteristic (ROC) curves were performed to assess the impact of preoperatively collected blood parameters and blood ratios on recurrence-free survival (RFS; primary endpoint) and overall survival (OS). A high neutrophil-to-lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR) and high C-reactive protein (CRP) value were significantly associated with shorter RFS in multivariate analysis. For LMR (cut-off 3.5) and for CRP (cut-off 3.0) this effect remained after dichotomization. CRP showed a stronger association with RFS than NLR or LMR, with the highest association being detected for the combination of low LMR and high CRP. Additionally, derived NLR ≥ 2.0 was significantly associated with shorter OS in multivariate analysis. In summary, our data suggest that CRP in combination with LMR should be considered as a marker for melanoma recurrence in stage III melanoma patients with microscopic SLN metastasis.

Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients.

INTRODUCTION: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. METHODS: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. RESULTS: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations. CONCLUSION: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans.

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these "elite neutralizers" also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.

Evaluation of a New Spike (S)-Protein-Based Commercial Immunoassay for the Detection of Anti-SARS-CoV-2 IgG.

Background: The investigation of the antibody response to SARS-CoV-2 represents a key aspect in facing the COVID-19 pandemic. In the present study, we compared the new Immundiagnostik IDK® anti-SARS-CoV-2 S1 IgG assay with four widely-used commercial serological assays for the detection of antibodies targeting S (spike) and NC (nucleocapsid) proteins. Methods: Serum samples were taken from an unbiased group of convalescent patients and from a negative control group. Sample were simultaneously analyzed by the new Immundiagnostik IDK® anti-SARS-CoV-2 S1 IgG assay, by the DiaSorin LIAISON® SARS-CoV-2 S1/S2 IgG assay, and by the Euroimmun anti-SARS-CoV-2 S1 IgG ELISA. Antibodies binding NC were detected by the Abbott SARS-CoV-2 IgG assay and by the pan-immunoglobulin immunoassay Roche Elecsys® anti-SARS-CoV-2. Moreover, we investigated samples of a group of COVID-19 convalescent subjects that were primarily tested S1 IgG non-reactive. Samples were also tested by live virus and pseudovirus neutralization tests. Results: Overall, the IDK® anti-SARS-CoV-2 S1 IgG assay showed the highest sensitivity among the evaluated spike (S) protein-based assays. Additionally, the Immundiagnostik assay correlated well with serum-neutralizing activity. Conclusions: The novel IDK® anti-SARS-CoV-2 S1 IgG assay showed high sensitivity and specificity, representing a valid option for use in the routine diagnostic.

Immune Responses to SARS-CoV-2 Infection and Vaccination in Dialysis Patients and Kidney Transplant Recipients.

Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.

COMP does not directly modify the expression of genes involved in cartilage homeostasis in contrast to several other cartilage matrix proteins.

OBJECTIVE: We investigated whether COMP may modify cartilage metabolism and play a role as an endogenous disease aggravating factor in OA. MATERIALS AND METHODS: Full-length and momomeric COMP was recombinantly expressed in human embryonic kidney cells and purified it via affinity chromatography. Purified COMP was used to stimulate either primary human chondrocytes or cartilage explants. Changes in the expression profiles of inflammatory genes, differentiation markers and growth factors were examined by immunoassay and by quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Incubation of primary human chondrocytes or cartilage explants in the presence of COMP did not induce statistically significant changes in the expression of IL-6, MMP1, MMP13, collagen I, collagen II, collagen X, TGF-ß1 and BMP-2. CONCLUSIONS: In contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a proinflammatory response in chondrocytes, although it carries an RGD motif and can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but increased COMP levels do not necessarily correlate with inflammation.

Anti-glycolipid antibodies in patients with neuropathy: a diagnostic assessment.

Anti-glycolipid antibodies are associated with immune-mediated neuropathies and screening is often performed as part of the diagnostic assessment for patients presenting with peripheral neuropathy. We report our experience in testing for immunoglobulin (Ig) G and IgM anti-glycolipid (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, sulfatides) antibodies in 290 consecutive patients presenting with neuropathy. Anti-glycolipid antibodies were detected significantly more often (43%) in patients who were diagnosed with definite immune-mediated neuropathy than in patients without a final diagnosis of immune-mediated neuropathy (control group) (23%). With positive and negative predictive values of 22% and 90%, respectively, anti-glycolipid antibodies are not a very reliable diagnostic tool in early patient contact. Certain antibodies (IgM to GM2, GT1a and IgG to GM3, GD3 and GT1b) were equally or more prevalent in the control group; clinicians should be aware of this distribution when receiving positive screening results for these antibodies. Concomitant IgG and IgM reactivities were found for GM1, GM2, GD1b and sulfatides, and were detected more frequently in patients with definite immune-mediated neuropathies.

Gamma heavy chain disease in a patient with rheumatoid arthritis--a laboratory evaluation.

INTRODUCTION: Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. Being rare and probably underdiagnosed diseases the aim of this report is to show an additional case of gamma heavy chain disease in a 48 year old female patient with rheumatoid arthritis focusing on the laboratory presentation. MATERIALS AND METHODS: Laboratory work-up included agarose gel electrophoresis (AGE), capillary zone electrophoresis (CZE), immunofixation and nephelometrically determined immunoglobulin and immunoglobulin subclasses of the patient's serum. Urine samples were also subjected to immunofixation and to a SDS-PAGE with consecutive immunoblot. RESULTS: Nephelometrically measured elevated IgG concentrations were noted in combination with a decreased gamma globulin region and an increased beta globulin region on AGE. A definite monoclonal spike was not identified on AGE but at least suspected on CZE; finally serum and urine immunofixation demonstrated a monoclonal gamma heavy chain devoid of any corresponding light chains confirming the diagnosis of HCD. Analysis of the gamma heavy chain (HC) with means of SDS-PAGE revealed proteins of 40 kD and 80 kD most likely presenting a truncated HC in its monomeric and dimeric form and possibly leading to the failure of IgG-subclass typing with the applied IgG subclass antisera. CONCLUSION: This case report illustrates a new case of gamma HCD demonstrating variable laboratory manifestations and therefore the need for heightened awareness concerning this disease when confronted with abnormal and discrepant protein profiles in routinely applied laboratory tests.

Ma2 antibodies: an evaluation of commercially available detection methods.

BACKGROUND: Ma2 antibodies belong to the onconeuronal antibodies which define a "definite" paraneoplastic neurological syndrome (PNS). Because of the clinical relevance, use of two separate methods (indirect immunofluorescence technique--IFT--and immunoblot) is advocated; however, with an increasing number of commercially available assay systems, usually only one assay is performed. METHODS: We compared IFT and three commercially available immunoblots (ravo Diagnostika, Euroimmun, Milenia Biotec) on sera from 35 patients with clinically suspected PNS. 17 were Ma2 antibody associated as defined by consensus result (showing positive reactivity in 2 assays), 18 were Ma2 antibody negative controls. RESULTS: Sensitivity/specificity for single assays were for IFT 94%/94%, for ravo Diagnostika PNS blot 88%/100%, for Euroimmun Neuronal Antigens Profile blot 100%/89%, and for Milenia Biotec MTR blot 94%/100%. CONCLUSIONS: Our data confirm, although all tests performed well, a combination of 2 independent assays is still advisable for Ma2 antibody detection in order to achieve higher sensitivity and specificity rates.