IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA 1 PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA 1 PCs with mild versus severe smIgA 1 MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA 1 and smIgG 1 MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27 1 MBCs with almost normal IgG 3 1 MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG 2 1 MBCs; and (6) with IgA 1 1 MBCs. Conclusion: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles. (J

AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells.

Hypokalemia in opiate overdose is an event concerning which no previous references have been made. Twenty-four addicts to parenteral drugs without recent withdrawal, admitted consecutively to the emergency room of University Hospital of Salamanca, were studied. All patients had the clinical criteria of acute opiate intoxication (acute alteration of mental status, respiration of 12 or less per minute, miotic pupils); the questionnaire study, conducted after recovery, confirmed the diagnosis of intravenous heroin overdose, which nine cases coexisted with intravenous cocaine administration. No other psychodepressant drugs, such as benzodiazepines, alcohol, or barbiturates, were associated. All the subjects were treated with the opiate antagonist naloxone, given at an initial dose of 0.4 mg intravenously; this was repeated after 3-10 minutes if no response occurred. No supplements of potassium were added. Blood samples were obtained from all subjects before naloxone administration. Values are expressed as means_+ SE. Pair-wise comparisons were analyzed using the Wilcoxon or Mann-Whitney tests for paired or unpaired observations, respectively.The mean plasma potassium concentration of all patients at admission was 3.43 +0.12 mmol/1 (range 2.30-5.10 mmol/1); 14 patients (58.3%) were hypokalemic (K+< 3.5 mmol/1). Arterial blood gases and the acid-base balance measured at admission showed a decrease in both pH (7.20_+0.04) and bicarbonate (22.40 _+ 2.11 mmol/1), with hypoxemia (pO2 = 56.4 ± 3.35 mmHg) and hypercapnia (pCO2 = 57.2_+ 4.42 mmHg). There was a relationship between the level of consciousness and kalemia: the deep coma patients (n= 17) had plasma potassium concentrations that were significantly lower than patients with obnubilation, but who responded to painful stimuli (n=7; 3.21_+0.11 mmol/1 vs 4.01 _+ 0.28 mmol/1, P <0.01); also, significantly lower plasma potassium concentrations were observed in the patients who needed more than 0.8 mg naloxone for recovery of consciousness than those who needed lower doses of the antagonist (2.95_+0.16 mmol/1 vs 3.60_+0.42 mmol/1, P<0.02). Plasma potassium concentrations were higher in combined heroin and cocaine overdose than in heroin overdose alone. In six patients it was possible to determine plasma potassium concentrations just after recovery of consciousness after naloxone administration, showing a decrease of kalemia with respect to its values at admission (Fig. 1); spontaneous normalization -without potassium supplements of kalemia in these patients was verified 4-6 h after recovery from the overdose episode.Experimental studies have shown a dissociation of the sympathetic nervous system and adrenal medullary responses fol-lowing sympathoadrenal stimulus in acute hypoxia [2] and after the administration of naloxone to rats chronically treated with morphine [1]. The hypokalemiant action of epinephrine due to stimulation of 132-adrenergic receptors and the hyperkalemiant action of norepinephrine (cz-adrenergic stimulus) [3]. These observations led us to hypothesize t...

Background: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. Methods: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400–600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. Results: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. Conclusions: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.