High-flow cannula for frail patients with SARS-CoV-2 infection non-eligible for intensive care unit management.

OBJECTIVES: High-flow nasal cannula (HFNC) was widely used during the COVID-19 pandemic in intensive care units (ICU), but there is no recommendation for elderly patients non-eligible for ICU management. We aimed to describe the outcomes of HFNC treatment in patients with COVID-19 who are not eligible for ICU management. METHODS: Retrospective bicentric cohort study performed between September 1, 2020 and June 30, 2021 in two infectious diseases departments of Colmar Hospital and Antoine Beclere University Hospital, France. RESULTS: Sixty-four patients were treated with HFNC: 33 in Colmar and 31 in Beclere hospital (median age: 85 years; IQ, 82-92). Of these, 16 patients survived (25%). Surviving patients had a lower Charlson comorbidity index score than deceased patients (five vs six; p = 0.02). CONCLUSIONS: Despite a high death rate, with survivors being younger and having fewer comorbidities, HFNC is an easy tool to implement in non-ICU wards for the frailest patients.

Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care.

BACKGROUND: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. METHODS: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March-April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. RESULTS: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions>25% at admission (aHR: 2.2 [95% CI: 1.3-3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2-3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3-0.8]). CONCLUSION: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.

Posterior semicircular canal paroxysmal positional vertigo triggers a new type of windmill nystagmus.

BACKGROUND: Periodic alternating nystagmus is a rare condition characterised by spontaneous horizontal nystagmus that periodically reverses direction, indicating an alteration of the velocity storage mechanism. Windmill nystagmus is a peculiar and rare variant of periodic alternating horizontal nystagmus with a superimposed periodic alternating vertical nystagmus. It is generally observed in blind patients. CASE REPORT: This paper presents the unique case of a normally sighted patient with a windmill nystagmus triggered by an episode of benign paroxysmal positional vertigo due to bilateral posterior canalolithiasis. Videonystagmography revealed an anticlockwise up-beating nystagmus followed by a clockwise down-beating nystagmus with a cycle lasting 2 minutes, followed by a brief burst of horizontal left-beating nystagmus. CONCLUSION: This case report represents the first observation of a new type of windmill nystagmus, probably provoked by a malfunction of the velocity storage mechanism, gaze-stabilisation and short-adaptation networks, with a loss of cerebellar inhibition.

Effect of fish length and nutritional condition on the fecundity of distressed Atlantic cod Gadus morhua from the Baltic Sea.

The disappearance of larger individuals and the decrease in individual body condition suffered by Atlantic cod Gadus morhua in the eastern Baltic during the past two decades can be expected to affect the stock reproductive output. To investigate this, female G. morhua were collected during the spawning and pre-spawning period in 2015-2016. The current individual potential fecundity (FP ) of eastern Baltic G. morhua was estimated and analysed in relation to total length (LT ) and indices of nutritional status such as body condition (K) and hepato-somatic index (IH ) using generalized linear models. In addition, the current prevalence of atresia and its potential relation to K were investigated. Moreover, a calibration curve to estimate FP from oocyte diameter, based on the autodiametric oocyte counting method, was established for the first time for eastern Baltic G. morhua and can be used for future fecundity studies on this stock. The results showed that FP was mainly positively related to fish length, but K and IH also contributed significantly to the variation in FP . The model predicted that fish with K = 1·2 have a FP 51% higher than fish of the same LT with K = 0·8. The prevalence of fecundity regulation by atresia was 5·8%, but it was found only in fish in the pre-spawning maturity stage and with low K. Temporal changes in biological features such as the length composition and individual body condition of eastern Baltic G. morhua, should be accounted for when estimating stock reproductive potential.

Outcome predictors of treatment effectiveness for fungal malignant external otitis: a systematic review.

The aim of this review is to summarise literature data on clinical aspects and traditional management of fungal malignant external otitis (FMEO), and to identify potential predictive factors of positive treatment outcome. Articles were initially selected based on their titles or abstracts. Full articles were then retrieved and further scrutinised according to predetermined criteria. Reference lists of selected articles were searched for any missed publications. The selected articles were methodologically evaluated. Of an initial 143 references, 14 were selected that focalised on the management of FMEO. The majority of studies demonstrated a correlation between treatment effectiveness, assessed as symptom resolution, and clinical and management variables: abstention from surgical debridement, absence of facial palsy, Aspergillus spp. as causative pathogen and absence of imaging findings at diagnosis and follow-up. The effectiveness of FMEO treatment depends on the assessment of cranial nerve state, the causative pathogen and imaging findings. Above all, absence of facial nerve palsy, Aspergillus spp. and absence of radiological signs at diagnosis and during follow-up correlate with symptom resolution. The fact that conservative treatment may be associated with a better outcome than surgical debridement could purely reflect that patients with more aggressive and advanced illness required debridement, whereas milder disease was treated conservatively. Thus, caution should be advised in the interpretation of data due to the need for further trials on the topic.

The eminent anatomists who discovered the upper oesophageal sphincter.

OBJECTIVE: To discover the anatomist who first identified the upper oesophageal sphincter. METHOD: The authors searched dozens of antique anatomy textbooks kept in the old section of the 'Vincenzo Pinali' Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter. RESULTS: The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as 'An Anatomical History on the Organs of Voice and Hearing …'), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… ('Treatise on the Human Ear …'). CONCLUSION: Anatomists Casserius and Valsalva can be considered the discoverers of the 'oesophageal sphincter'.

Performance characteristics of laboratory testing and clinical outcomes.

In order to demonstrate the relationship between performance characteristics of laboratory tests and clinical outcomes, diabetes seems to represent a paradigmatic disease: diagnosis, monitoring of therapeutic efficacy and prognosis are adequately achieved by means of laboratory testing. Starting from a simple molecule, glucose, used for the diagnosis of diabetes, continuing with creatinine, used for monitoring renal function in diabetic patients and concluding with cardiac troponins, a recognised gold standard for the diagnosis and risk stratification of cardiovascular diseases, several criticisms may be stressed considering the current methodological state-of-the art. Finally, an often overlooked aspect of performance, the analytical interferences, being responsible of unexpected results, that in turn depend from unknown or undisclosed factors will be discussed, concerning in particular, in our paper, the macroprolactin and the heterophilic antibodies aspects.

Creatine-kinase MB mass: age and sex-associated reference limits in two different platforms that use the same method.

BACKGROUND: Recent updated NACB guidelines suggest that troponins are the biomarker of choice for the detection of myocardial necrosis, but the CK-MB mass is still considered an effective and alternative indicator when troponin assays are not available. The aim of the present study was to compare the reliability of two different analytical platforms in establishing the gender-specific 99th percentile for the CK-MB mass. METHODS: Serum samples collected from healthy subjects were investigated in two different laboratories, LAB 1 (354 subjects: 222 men, 132 women; median age, 40 years, range 19-64 years) and LAB 2 (330 subjects: 224 men, 106 women; median age, 41 years, range 18-71 years), in order to determine the CK-MB mass (microg/L) using the Access((R)) CKMB method (Beckman Coulter), a two-site immunoenzymatic sandwich assay, on UniCel DxI 800 (LAB 1) and Access((R)) 2 (LAB 2) analyzers (Beckman Coulter). The related plasma samples (lithium-heparin) were also evaluated in LAB 2. RESULTS: Total imprecision (CV%), calculated in control materials, ranged from 6.00 to 9.05 (concentration range, 3.82-36.37) in LAB 1 and from 7.05 to 5.02 in LAB 2 (concentration range, 3.63-34.18). A statistically significant gender-related difference (p<0.05) was found in the whole population studied, values in men being higher than those in women: median=1.86 vs 1.22; 99th percentile=7.64 vs 5.19. The median values in subjects aged 18-28 years (group 1) were lower than those in the other 4 groups (2-5): 1.12 vs 1.59, vs 1.78, vs 1.95 and vs 2.03. The same age-related trend was also observed for CK-MB plasma values, which were comparable to those observed in the matched-serum samples: median 1.12 vs 1.10 (group 1), 1.45 vs 1.50, (group 5). CONCLUSIONS: The two different analytical platforms provide comparable results. The finding that CK-MB mass values are significantly higher in males than in females represents a relevant information, that will impact on patient classification when a myocardial necrosis has been suspected. Actually, however, numerous assays commercially available, lack of this information.

Quality specifications for biochemical markers of myocardial injury.

BACKGROUND: The current approach to the diagnosis and monitoring of myocardial damage, recognizes to biochemical markers, and in particular to troponins, a key role being well demonstrated that all elevated values were associated with a worsened prognosis. In 2001, the IFCC Committee on Standardization of Markers of Cardiac Damage published guidelines addressing the quality specifications for troponin assays in order to guarantee an analytical performance satisfying medical requirements and to standardize the quality of commercial methods. We describe how the application of quality specifications may be useful in daily practice, in order to provide advice to clinicians in the investigations of complex clinical cases of patients suffering from myocardial damage. MATERIALS AND METHODS: The samples from three patients (cases 1-3) admitted to the hospital with symptoms suggestive of cardiac disease, showing high troponin I (cTnI) values not correlated with clinical condition, were investigated in order to verify the accuracy of the laboratory data. The standard of quality specifications related to assay specificity, imprecision and interferences were evaluated using different platforms for cTnI assays, carrying out imprecision profile and specific studies on more common interferents in immunoassays. RESULTS: The obtained results allow us to demonstrate two cases of false-positive cTnI values attributable to a macrocomplex between a modified "in vivo" cTnI and immunoglobulin G (case 1) and to a presence of heterophilic antibodies affecting the RxL Dimension procedure (case 3). Instead, the accuracy of data obtained in case 2 was evidenced by the imprecision profile obtained in our laboratory and by the comparison of results between different laboratories using same platform. CONCLUSIONS: The lack of standardization as well as the wide differences in the development of each assay give rise to major concerns regarding cTnI determinations. The laboratory must therefore check the compliance between the analytical characteristics of the method utilised against recommended quality specifications for a reliable understanding of the frequency of false-positive results as well as other serious analytical errors.

[General anaesthesia for Caesarean section in a patient with pulmonary atresia and an intact intraventricular septum]. / Anesthésie pour césarienne chez une patiente atteinte d'une atrésie pulmonaire à septum interventriculaire intact.

We report the case of a 22-year-old primigravida patient presenting pulmonary atresia with intact ventricular septum, a rare congenital heart disease. Caesarean delivery was performed at 32 weeks of gestation because of moderate maternal function deterioration and foetal growth restriction. General anaesthesia was used because of the presence of lumbar Harrington rods. The administration of etomidate, celocurine and a continuous perfusion of remifentanil right from induction ensured haemodynamic stability and a rapid emergence and recovery.

Point-of-care testing of cardiac markers: results from an experience in an Emergency Department.

AIM: An experimental approach to the use of point-of-care testing for cardiac markers in the Emergency Department (ED) of our Institution has been carried out using two devices (SCS, Dade Behring and Triage Cardiac Panel, Biosite Diagnostics) for the measurement of cardiac markers. RESULTS: (1) From the analytical point of view, a fundamental tool for an efficient management of patients was the agreement between results from point-of-care testing and from the instruments located in STAT lab and/or central laboratory: in about 5% of patients, a lack of comparability of data, resulted in an inappropriate admission of patients (medical vs. intensive care unit). (2) The actual total turnaround time (TAT) in the management of samples sent to STAT lab was estimated to be equal to 82.5 min (50th percentile). (3) In the same organizational setting, the use of a point-of-care device produced a turnaround time equal to 17 min (50th percentile). (4) The reduction in turnaround time resulted in a faster discharge for five patients who had normal ECG findings and cardiac marker values, the Delta time (POCT-STAT lab) ranging from -10 to -70 min. CONCLUSIONS: The point-of-care option evaluated also in relation to personnel issues for staff working in the ED, brought some interesting questions about the characteristics of POCT devices (easy to use 100%, safety for operator 91%) and the obtained results (quantitative and correlated to STAT lab, 91%), as well as the need of other options such as the implementation of rapid tube sample delivery.

[Pleural mesothelioma in women in the Veneto Region who used to work as rag sorters for textile recycling and paper production]. / Mesoteliomi pleurici insorti in donne, residenti in Veneto, addette alla cernita di stracci presso "robe vecchie" e cartiere.

The paper reports 9 cases of mesothelioma diagnosed by means of histology or cytology that were observed among women resident in the Veneto Region, Northern Italy, whose only activity that could involve exposure to asbestos was as rag sorter. These cases are part of a group of about 260 subjects with mesothelioma whose entire working and residential history has been collected. The women worked as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or (one case) at a paper mill where cotton was used for paper production. The work as rag sorter helps to explain the high proportion of mesotheliomas among women with an occupational exposure to asbestos.

Mutator phenotype in human hematopoietic neoplasms and its association with deletions disabling DNA repair genes and bcl-2 rearrangements.

As mice carrying mutations of the DNA mismatch repair genes MSH2 and MSH6 often develop lymphoid neoplasms, we addressed the prevalence of the replication error (RER(+)) phenotype, a manifestation of an underlying defect of DNA mismatch repair genes, in human lymphoid tumors. We compared microsatellite instability (MSI) at 10 loci in 37 lymphoid tumors, including 16 acute lymphoid leukemias (ALL) and 21 non-Hodgkin's lymphomas (NHL), and in 29 acute myeloid leukemias (AML). Significant differences in MSI prevalence between AMLs and ALLs emerged, and MSI occurrence was more frequent in the NHLs versus AMLs. Indeed, only 3 of 29 (10%) AMLs exhibited MSI, thus confirming its paucity in myeloid tumors, while 10 of 37 (27%) lymphoid tumors, 6 ALLs and 4 NHLs, disclosed an RER(+) phenotype. In 1 ALL patient, the same molecular alterations were observed in correspondence with a relapse, but were not detected during remission over a 14-month follow-up; in another ALL patient, findings correlated with impending clinical relapse. These results suggest that the study of MSI in lymphoid tumors might provide a useful molecular tool to monitor disease progression in a subset of ALLs. To correlate MSI with other known genetic abnormalities, we investigated the status of the proto-oncogene, bcl-2, in the lymphoma patients and found that 4 of 4 NHL patients with MSI carried bcl-2 rearrangements, thus linking genomic instability to enhanced cell survival in NHL; moreover, no p53 mutations were found in these patients. Finally, we addressed the putative cause of MSI in hematopoietic tumors by searching for both mutations and deletions affecting DNA repair genes. A limited genetic analysis did not show any tumor-specific mutation in MLH1 exons 9 and 16 and in MSH2 exons 5 and 13. However, loss of heterozygosity (LOH) of markers closely linked to mismatch repair genes MLH1, MSH2, and PMS2 was demonstrated in 4 of 6 ALLs and 1 of 3 AMLs with MSI. These observations indicate that chromosomal deletions might represent a mechanism of inactivation of DNA repair genes in acute leukemia.

Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. IV. Differential activation of human Th1 and Th2 lymphocytes and influence of the atopic status on lymphoma development.

Intraperitoneal transfer of PBMC from EBV+ donors into SCID mice leads to high human Ig levels in mouse serum and B cell lymphoproliferative disease. As these events depend on the activation of coinjected human T cells, we addressed the behavior of the Th1 and Th2 subsets in this model. Production of IFN-gamma, but not of Th2 cytokines such as IL-4, was detected in culture supernatants of PBMC stimulated in vitro with mouse splenocytes. Moreover, anti-CD3 stimulation of the human cells recovered from mice brought about IFN-gamma, but not IL-4, synthesis; on the other hand, PCR and in situ hybridization analysis of ex vivo-recovered cells disclosed the presence of mRNA for both cytokines following in vitro restimulation, thus suggesting posttranscriptional regulation of IL-4 gene expression. When SCID mice were inoculated with PBMC from atopic donors, whose Th1/Th2 profile displays an imbalance toward Th2 cells, tumor development rates were lower, and tumor latency was higher, compared with those in mice injected with PBMC from normal donors. Isotypic analysis of human Ig in mouse serum showed the exclusive presence of IFN-gamma-driven IgG subclasses; in addition, human IgE were low or undetectable in most cases. These findings indicate that following transfer into SCID mice, human Th1 lymphocytes undergo preferential activation, whereas Th2 function is down-regulated. Th1 lymphocytes probably are a major component in promoting EBV+ B cell expansion and tumor development; the individual Th1/Th2 profile could in part account for the as yet unexplained donor variability in tumor generation in this experimental model.

DNA immunization of mice against SIVmac239 Gag and Env using Rev-independent expression plasmids.

Simian immunodeficiency virus (SIV) structural gene expression, including gag and env, strictly depends on the interaction of the viral posttranscriptional regulator Rev with its target RNA, the Rev-responsive element (RRE). A small RNA element, termed the constitutive transport element (CTE), located in the 3' portion of simian retrovirus 1 (SRV-1) mRNA, can efficiently substitute for the human immunodeficiency virus (HIV) Rev-RRE interaction, and thus render HIV expression and replication Rev independent. We tested the ability of the SRV-1 CTE to drive the expression of SIVmac239 env and gag from subgenomic constructs designed for possible use in vaccine trials. In vitro expression studies showed that when the SRV-1 sequence is coupled to the SIV gag and env mRNAs, it functions in an orientation-dependent fashion, and leads to strong expression of SIV Gag and Env in human and monkey cell lines; levels of CTE-mediated protein expression were similar to those obtained with a functional Rev-RRE system. On the other hand, in murine fibroblast-like cells, SIV Gag and Env were expressed from constructs at relatively high levels even in the absence of Rev-RRE; nevertheless, their expression was increased by the presence of the SRV-1 CTE. As reported previously for HIV, the murine cell lines appeared to be defective for Rev-RRE activity, and required overexpression of Rev to induce a Rev response. Intramuscular injection of the gag-CTE and env-CTE constructs in BALB/c mice resulted in the expression of the corresponding mRNAs, and the production of anti-Gag and anti-Env antibodies, thus suggesting that these vectors might be used for genetic immunization approaches.

TCR expression and clonality analysis in peripheral blood and lymph nodes of HIV-infected patients.

We compared the T cell receptor (TCR) V beta gene family repertoire in peripheral blood mononuclear cells (PBMC) and lymph node (LN) cells from 7 human immunodeficiency virus (HIV)-infected patients and 3 seronegative healthy controls. Virtually all the V beta family specificities were represented in patient PBMC and LN cells, and mean values for each specificity were comparable to figures in seronegative controls. In 4 patients, however, some V beta gene segment transcripts were overrepresented in the LN compartment, compared to the peripheral blood counterpart. To ascertain whether this phenomenon was due to polyclonal or oligoclonal expansion of T cells bearing the relevant V beta gene product, we sequenced the entire CDR3 region of a panel of 238 PCR clones corresponding to the V beta transcripts expanded in LN; as control, the same regions were cloned and sequenced in patient's PBMC, and in PBMC and LN cells from seronegative individuals. This analysis disclosed preferential usage of J beta 2 genes in PBMC and LN cells from both seropositive patients and controls, regardless of the V beta gene segment considered, thus indicating that this skewness in the V beta-J beta repertoire could be a consistent feature of at least a part of the V beta repertoire in different lymphoid compartments, regardless of the pathologic conditions. In addition, in LN from HIV seropositive patients we found the presence of recurrent TCR rearrangements, accounting for 8-23% of the generated clones, in each of the 4 V beta specificities analyzed; recurrent sequences were not found in PBMC from patients nor in PBMC and LN cells from seronegative controls. These findings suggest that antigen-driven oligoclonal T cell expansions may occur in vivo in lymphoid organs of HIV seropositive patients.