Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19.

BACKGROUND & AIMS: Nutritional predisposition to severe coronavirus disease 2019 (COVID-19) remains unclear. Zinc deficiency could be critical since it is associated with a higher susceptibility to infections. We evaluated the prevalence of hypozincemia in the early stage of COVID-19, its association with risk factors for severe COVID-19 and its prognostic value for hospitalization for respiratory complications within 10 days. METHODS: For 152 COVID-19 patients and 88 non-COVID-19 patients admitted to COVID-19 screening centers, national early warning score for COVID-19 (NEWS) and laboratory analyses were performed to identify the risk for severe COVID-19. Multivariable logistic regression analysis assessed whether hypozincemia was an independent predictor of hospitalization for respiratory complications within 10 days (primary judgment criterion). The secondary judgment criteria were high NEWS score (≥7), comorbidities and biomarkers associated with severe COVID-19. RESULTS: Hypozincemia was more frequent in COVID-19 patients compared to non-COVID-19 patients (27.6% vs 11.4%; p = 0.003). Older patients (≥65 years) and medically assisted nursing home residents were at higher risk of hypozincemia (p < 0.01). Hypozincemia was associated with a worse NEWS score (p < 0.01) and lymphopenia (p < 0.001). Hypozincemia was independently associated with hospitalization for respiratory complications within 10 days (OR = 10.9, 95% CI = 2.3-51.6, p = 0.002). CONCLUSIONS: In the early stage of COVID-19, the prevalence of hypozincemia exceeded 20%. Hypozincemia was an independent predictor of hospitalization for respiratory complications within 10 days. This may suggest the importance of early detection and treatment of zinc deficiency in the nutritional management of COVID-19, especially in older people. Therefore, intervention and adjuvant treatment trials are strongly needed.

Troponins in scuba divers with immersion pulmonary edema.

Immersion pulmonary edema (IPE) is a serious complication of water immersion during scuba diving. Myocardial ischemia can occur during IPE that worsens outcome. Because myocardial injury impacts the therapeutic management, we aim to evaluate the profile of cardiac markers (creatine phosphokinase (CPK), brain natriuretic peptide (BNP), highly sensitive troponin T (TnT-hs) and ultrasensitive troponin I (TnI-us) of divers with IPE. Twelve male scuba divers admitted for suspected IPE were included. The collection of blood samples was performed at hospital entrance (T0) and 6 h later (T0 + 6 h). Diagnosis was confirmed by echocardiography or computed-tomography scan. Mean ± S.D. BNP (pg/ml) was 348 ± 324 at T0 and 223 ± 177 at T0 + 6 h (P<0.01), while mean CPK (international units (IUs)), and mean TnT-hs (pg/ml) increased in the same times 238 ± 200 compared with 545 ± 39, (P=0.008) and 128 ± 42 compared with 269 ± 210, (P=0.01), respectively; no significant change was observed concerning TnI-us (pg/ml): 110 ± 34 compared with 330 ± 77, P=0.12. At T0 + 6 h, three patients had high TnI-us, while six patients had high TnT-hs. Mean CPK was correlated with TnT-hs but not with TnI-us. Coronary angiographies were normal. The increase in TnT during IPE may be secondary to the release of troponin from non-cardiac origin. The measurement of TnI in place of TnT permits in some cases to avoid additional examinations, especially unnecessary invasive investigations.

Minimal residual disease testing in hematologic malignancies and solid cancer.

Minimal residual disease (MRD) assays are of a great value to assess treatment efficacy and may provide prognostic information. This is particularly relevant in the era of targeted therapy where the introduction of MRD monitoring has fundamentally transformed the way in which cancer patients are managed. While MRD guidelines are well-established for chronic myeloid leukemia, acute promyelocytic leukemia and acute lymphoblastic leukemia, areas for continuing development are available. High level of standardization and regular external quality control rounds and recommendations for data interpretation remain essential to improve MRD monitoring. In this review, we describe the different applications of MRD assays in most frequent hematologic malignancies and solid cancer and provide an overview of the strengths and potential weaknesses of each method.

Hypoxia-inducible factor-1α as prognostic marker.

INTRODUCTION: Hypoxia-inducible factor-1α (HIF-1α) is a key player in the signaling pathway that mediates a complex and pleiotropic range of adaptive responses to hypoxia. It serves as cellular hypoxia sensor and plays a critical role in physiologic processes including glucose metabolism, iron metabolism, erythropoiesis, angiogenesis, cell survival and apoptosis, but also, pathologic processes such as carcinogenesis, progression and metastasis of many cancers. With the recent advent of new molecular targeted therapies, there is a growing need of molecular understanding of physiology and physiopathology and increased demand of diagnosis, prognosis and follow-up markers. AREAS COVERED: This paper reviews the biology of regulation of HIF-1α, its physiological and physiopathological effects. EXPERT OPINION: The authors discuss the potential diagnosis and the prognosis significance of HIF-1α that was evaluated in recent studies.

Hypoxia-inducible factor (HIF1α) gene expression in human shock states.

INTRODUCTION: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients with shock. METHODS: 50 consecutive adult patients with shock and 11 healthy volunteers were prospectively included. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first 4 hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. RESULTS: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). The HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 [72-168] vs. 48 [38-54] normalized copies, p < 0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 [range 84-183] vs. 121 [range 72-185] normalized copies, p = 0.92), and did not significantly change within the study period. CONCLUSIONS: The present study is the first to demonstrate the increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.

Analysis of T-cell receptor-γ gene rearrangements using heteroduplex analysis by high-resolution microcapillary electrophoresis.

Determination of T-cell clonality has an important additional value for diagnosis of T-cell lymphomas. Various molecular methods have been developed, including polymerase chain reaction (PCR) of T-cell receptor γ (TCRγ). The detection of PCR products usually relies commonly on either GeneScan (GS) analysis or heteroduplex (HD) analysis by polyacrylamide gel electrophoresis (PAGE). These techniques have their disadvantages, being relatively time-consuming and laborious or requiring expensive equipment. Here, we propose an alternative method that combines multiplex PCR and HD analysis by microcapillary electrophoresis (ME) on the Agilent 2100 Bioanalyzer. The sensitivity of the method was determined with clonal PEER T-cell line DNA dilution in polyclonal DNA and was evaluated as 1-5%. Fifty-three samples from patients with T-cell lymphoproliferative disorders were analyzed by HD analysis using ME and GS analyses. Comparison of the two techniques showed them to be highly concordant (93% similarity). The rate of clonality detection by GS analysis was higher than HD analysis by ME, but none of the discordant patients (n=5) has yet developed lymphoma. HD analysis by ME to reveal TCRγ gene rearrangements in clinical specimens was consistent with clinical data and the outcome of patients. Detection of T-cell clonality by HD analysis with ME is sensitive, practical, safe and represents a potential alternative to PAGE and GS analysis.