Cancer procoagulant in acute lymphoblastic leukemia

In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.     

Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca²⁺ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca²⁺ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca²⁺ entry and coupling to Ca²⁺ release microdomains at the intercalated disc, resulting in enhanced Ca²⁺ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca²⁺ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.     

Detection of human cytomegalovirus in transbronchial biopsies from lung transplant recipients

The role of human cytomegalovirus (HCMV) in lung transplantation (LT) and drawbacks related to viral quantification in bronchoalveolar lavage (BAL) underline the potential usefulness of investigating other specimens. Thirty-three LT recipients were prospectively studied by HCMV quantitative real time PCR on matched transbronchial biopsy (TBB), BAL, and whole blood specimens. Overall, 27/33 patients turned out HCMV-positive in at least one specimen: 7.1 %, 37.1 %, and 13.5 % of TBB, BAL, and blood samples, respectively. No significant association between HCMV on all types of specimens and acute rejection, lymphocytic bronchiolitis, bronchiolitis obliterans and bronchiolitis obliterans syndrome was found. HCMV pneumonia was associated to HCMV detection on TBB (p = 0.003) and whole blood (p = 0.008), not on BAL (p = 0.47). The highest mean viral load was detected in TBB from cases with HCMV pneumonia in comparison to all other cases, suggesting the potential use of HCMV investigation in TBB for evaluating posttransplant complications.     

Open-source open-access reaction time test (OORTT): an easy tool to assess reaction times

Neurological Sciences - The speed of information processing is one of the most reliable indices of cognitive efficiency. The most common way to evaluate this ability is to assess reaction times...     

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis

European Journal of Clinical Microbiology & Infectious Diseases - This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all...     

Video Laryngoscopy-guided Nasal Intubation: One More Bullet in Our Rifle

How to cite this article: Cittadini A, Marsigli F, Sica A, Santonastaso DP, Russo E, Gamberini E, et al. Video Laryngoscopy-guided Nasal Intubation: One More Bullet in Our Rifle. Indian J Crit Care Med 2021;25(3):351.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

A Paradigm Shift for Torsional Stiffness of Nickel-Titanium Rotary Instruments: A Finite Element Analysis

IntroductionThe aim of this study was to investigate the influence of mass and the polar moment of inertia on the torsional behavior of nickel-titanium rotary instruments to understand which parameter of cross-sectional design had a key role in terms of torsional resistance.MethodsFour different instrument models were designed and meshed using computer-aided engineering software (SolidWorks; Dassault Systems, Waltham, MA). Instrument models shared the same characteristics, except for cross-sectional design; triangle, rectangle, square, and hollow square geometry was selected. Finite element analysis was performed simulating a static torsional test using the FEEPlus internal solver (Solid Works). Von Mises stress and torsional load at fracture were calculated by the software. Linear regression analysis was performed to investigate the relationship of the polar moment of inertia, cross-sectional area, inner core radius, and mass per volume on the torsional resistance of nickel-titanium rotary instruments.ResultsThe polar moment of inertia positively affected the maximum torsional load with the highest level of correlation (R² = 0.917). It could be stated that the higher the polar moment of inertia is, the more maximum torsional load at fracture is present. Mass and cross-sectional area had a lower level of correlation compared with the polar moment of inertia (R² = 0.5533). According to this, 2 instruments with the same mass/mm and/or cross-sectional area could have different torsional resistance.ConclusionsThe polar moment of inertia can be considered as the most important cross-sectional factor in determining the torsional resistance of rotary instruments over metal mass and cross-sectional area.     

Influence of shaft length on torsional behavior of endodontic nickel–titanium instruments

Odontology - Torsional stresses are one of the most frequent causes of intracanal separation of nickel–titanium endodontic instruments, which represents a great concern of endodontists. For...