The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure

OBJECTIVES: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated. BACKGROUND: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF). METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 +/- 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h. Left ventricular function was measured using echocardiography and oxidative metabolism using [(11)C]acetate positron emission tomography. Both measurements were performed at rest and during dobutamine-induced stress (5 microg/kg/min). Basal- and adenosine-stimulated (140 microg/kg/min) myocardial blood flow were quantitated using [(15)O]water. RESULTS: During CRT off, LV stroke volume was significantly reduced at rest (72 +/- 18 ml vs. 63 +/- 15 ml, p < 0.05), but LV oxidative metabolism (K(mono)) remained unchanged (0.046 +/- 0.008 vs. 0.054 +/- 0.016 min(-1)) leading to a significant deterioration of myocardial efficiency of forward work (from 48.2 +/- 16.7 to 36.6 +/- 11.7 mm Hg.l/g, p < 0.05). During dobutamine-induced stress, stroke volume and K(mono) values were not different whether CRT was on or off. However, myocardial efficiency (56.1 +/- 16.1 vs. 49.8 +/- 18.0 mm Hg.ml.g(-1).min(-1), p = 0.099) and metabolic reserve, the response of K(mono) to dobutamine (0.023 +/- 0.014 vs. 0.013 +/- 0.014 min(-1), p = 0.09), tended to reduce when CRT was switched off. Cardiac resynchronization therapy had no effects on myocardial perfusion. Natriuretic peptides increased significantly during CRT-off period. CONCLUSIONS: Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.     

Mycobacterium bovis Infection in Humans and Cats in Same Household,Texas, USA, 2012

Mycobacterium bovis infection of cats is exceedingly rare in regions where bovine tuberculosis is not endemic. We describe the diagnosis and clinical management of pulmonary M. bovis infection in 2 indoor-housed cats and their association with at least 1 M. bovis–infected human in Texas, USA, in September 2012.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Automated preparation for identification and antimicrobial susceptibility testing: evaluation of a research use only prototype,the BD Kiestra IdentifA/SusceptA system

ObjectiveThe current BD Kiestra? total laboratory automation (TLA) system automates specimen inoculation, incubation, and digital visualization of cultures prior to initiation of manual or semi-automated identification (ID) and antimicrobial susceptibility testing (AST). The current study aimed to compare the performance, in a clinical setting, of a fully automated research-use-only prototype, BD Kiestra? IdentifA/SusceptA (automated system), to our current BD Kiestra? TLA which utilizes manual or semi-automated IDs and ASTs (current system).MethodsClinical samples yielding significant growth after processing by the BD Kiestra? TLA were tested in parallel for ID and AST by both systems. IDs and ASTs were determined by Bruker matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and BD Phoenix, respectively, with data stored and managed in the BD EpiCenter?. The automated system used a common inoculum preparation for both tests, whereas the current system used separate inocula. Results were compared to assess agreement between the systems.ResultsOn initial testing, 89% of IDs (466/523) and 92.4% of IDs (484/523) for the automated and current ID systems, respectively, yielded acceptable MALDI-TOF log scores of ≥1.7. On repeat testing, the respective acceptable scores were 97.1% (508/523) and 98.1% (513/523). For initial ASTs, the automated and current systems yielded 97.5% categorical agreement for 7325 drug–organism tests. After omitting discrepant MICs that differed by only one dilution and categorical discrepancies that were not reproducible, 0.2% unresolved discrepancies remained thus (99.8% categorical agreement).ConclusionsThe automated prototype is suitable for development into technology that will provide clinical microbiology laboratories with significant advantages such as improved efficiency, standardization, reproducibility, reduced technical error and greater safety.     

Functional Assessment of TSC2 Variants Identified in Individuals with Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Here, we investigate the effects of 78 TSC2 variants identified in individuals suspected of TSC, on the function of the TSC1–TSC2 complex. According to our functional assessment, 40 variants disrupted the TSC1–TSC2‐dependent inhibition of TORC1. We classified 34 of these as pathogenic, three as probably pathogenic and three as possibly pathogenic. In one case, a likely effect on splicing as well as an effect on function was noted. In 15 cases, our functional assessment did not agree with the predictions of the SIFT amino acid substitution analysis software. Our data support the notion that different, nonterminating TSC2 mutations can have distinct effects on TSC1–TSC2 function, and therefore, on TSC pathology.     

High incidence of subclinical peripheral neuropathy in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis): an electrophysiological study

OBJECTIVE: To study subclinical involvement of the peripheral nerves in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis: AM). MATERIAL AND METHODS: We carried out a nerve conduction study of the median, ulnar, tibial, and sural nerves in 21 patients with AM and in 28 patients with clinically definite or laboratory-supported definite multiple sclerosis (MS). RESULTS: The patients with AM showed a significantly higher frequency of abnormal records than the MS patients in the sensory nerve conduction study (52.4% vs. 14.3%, p = 0.0106). The frequency of abnormal records in the motor nerve conduction study in AM patients was twice as high as in MS patients (38.1% vs. 17.9%), but the difference was not statistically significant. Abnormality in the F-wave-evoked frequency in the median nerve was also significantly more common in AM patients than in MS patients (57.9% vs. 10.7%, p = 0.0016). CONCLUSIONS: These findings suggest that subclinical peripheral neuropathy is frequent in patients with AM.