Improved all-cause mortality with left bundle branch area pacing compared to biventricular pacing in cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative pacing strategy to biventricular pacing (BIVP) in cardiac resynchronization therapy (CRT). We aimed to assess the impact of LBBAP vs. BIVP on all-cause mortality and heart failure (HF)-related hospitalization in patients undergoing CRT. METHODS: Studies comparing LBBAP and BIVP for CRT in patients with HF with reduced left ventricular ejection fraction (LVEF) were included. The coprimary outcomes were all-cause mortality and HF-related hospitalization. Secondary outcomes included procedural and fluoroscopy time, change in QRS duration, and change in LVEF. RESULTS: Thirteen studies (12 observational and 1 RCT, n = 3239; LBBAP = 1338 and BIVP = 1901) with a mean follow-up duration of 25.8 months were included. Compared to BIVP, LBBAP was associated with a significant absolute risk reduction of 3.2% in all-cause mortality (9.3% vs 12.5%, RR 0.7, 95% CI 0.57-0.86, p < 0.001) and an 8.2% reduction in HF-related hospitalization (11.3% vs 19.5%, RR 0.6, 95% CI 0.5-0.71, p < 0.00001). LBBAP also resulted in reductions in procedural time (mean weighted difference- 23.2 min, 95% CI - 42.9 to - 3.6, p = 0.02) and fluoroscopy time (- 8.6 min, 95% CI - 12.5 to - 4.7, p < 0.001) as well as a significant reduction in QRS duration (mean weighted difference:- 25.3 ms, 95% CI - 30.9 to - 19.8, p < 0.00001) and a greater improvement in LVEF of 5.1% (95% CI 4.4-5.8, p < 0.001) compared to BIVP in the studies that reported these outcomes. CONCLUSION: In this meta-analysis, LBBAP was associated with a significant reduction in all-cause mortality as well as HF-related hospitalization when compared to BIVP. Additional data from large RCTs is warranted to corroborate these promising findings.

Predicting Extubation Readiness in Preterm Infants Utilizing Machine Learning: A Diagnostic Utility Study.

OBJECTIVE: The objective of this study was to predict extubation readiness in preterm infants using machine learning analysis of bedside pulse oximeter and ventilator data. STUDY DESIGN: This is an observational study with prospective recordings of oxygen saturation (SpO2) and ventilator data from infants <30 weeks of gestation age. Research pulse oximeters collected SpO2 (1 Hz sampling rate) to quantify intermittent hypoxemia (IH). Continuous ventilator metrics were collected (4-5-minute sampling) from bedside ventilators. Data modeling was completed using unbiased machine learning algorithms. Three model sets were created using the following data source combinations: (1) IH and ventilator (IH + SIMV), (2) IH, and (3) ventilator (SIMV). Infants were also analyzed separated by postnatal age (infants <2 or ≥2 weeks of age). Models were compared by area under the receiver operating characteristic curve (AUC). RESULTS: A total of 110 extubation events from 110 preterm infants were analyzed. Infants had a median gestation age and birth weight of 26 weeks and 825 g, respectively. Of the 3 models presented, the IH + SIMV model achieved the highest AUC of 0.77 for all infants. Separating infants by postnatal age increased accuracy further achieving AUC of 0.94 for <2 weeks of age group and AUC of 0.83 for ≥2 weeks group. CONCLUSIONS: Machine learning analysis has the potential to enhance prediction accuracy of extubation readiness in preterm infants while utilizing readily available data streams from bedside pulse oximeters and ventilators.

Effect of Speaking Valves on Tracheostomy Decannulation.

Introduction Despite several pediatric tracheostomy decannulation protocols there remains tremendous variability in practice. The effect of tracheostomy capping on decannulation has been studied but the role of speaking valves (SVs) is unknown. Objective Given the positive benefits SVs have on rehabilitation, we hypothesized that SVs would decrease time to tracheostomy decannulation. The purpose of the present study was to evaluate this in a subset of patients with chronic lung disease of prematurity (CLD). Methods A retrospective chart review was performed at a tertiary care children's hospital. A total of 105 patients with tracheostomies and CLD were identified. Data collected included demographics, gestational age, congenital cardiac disease, airway surgeries, granulation tissue excisions, SV and capping trials, tracheitis episodes, and clinic visits. Statistics were performed with logistic and linear regression. Results A total of 75 patients were included. The mean gestational age was 27 weeks (standard deviation [SD] = 3.6) and the average birthweight was 1.1 kg (SD = 0.6). The average age at tracheostomy was 122 days (SD = 63). A total of 70.7% of the patients underwent decannulation and the mean time to decannulation (TTD) was 37 months (SD = 19). A total of 77.3% of the patients had SVs. Those with an SV had a longer TTD compared to those without (52 versus 35 months; p = 0.008). Decannulation was increased by 2 months for every increase in the number of hospital presentations for tracheitis ( p = 0.011). Conclusion The present study is the first, to our knowledge, to assess the effect of SVs on tracheostomy decannulation in patients with CLD showing a longer TTD when SVs are used.

Left Bundle Branch Pacing vs Left Ventricular Septal Pacing vs Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are considered to be acceptable as LBBAP strategies. Differences in clinical outcomes between LBBP and LVSP are yet to be determined. OBJECTIVES: The purpose of this study was to compare the outcomes of LBBP vs LVSP vs BIVP for CRT. METHODS: In this prospective multicenter observational study, LBBP was compared with LVSP and BIVP in patients undergoing CRT. The primary composite outcome was freedom from heart failure (HF)-related hospitalization and all-cause mortality. Secondary outcomes included individual components of the primary outcome, postprocedural NYHA functional class, and electrocardiographic and echocardiographic parameters. RESULTS: A total of 415 patients were included (LBBP: n = 141; LVSP: n = 31; BIVP: n = 243), with a median follow-up of 399 days (Q1-Q3: 249.5-554.8 days). Freedom from the primary composite outcomes was 76.6% in the LBBP group and 48.4% in the LVSP group (HR: 1.37; 95% CI: 1.143-1.649; P = 0.001), driven by a 31.4% absolute increase in freedom from HF-related hospitalizations (83% vs 51.6%; HR: 3.55; 95% CI: 1.856-6.791; P < 0.001) without differences in all-cause mortality. LBBP was also associated with a higher freedom from the primary composite outcome compared with BIVP (HR: 1.43; 95% CI: 1.175-1.730; P < 0.001), with no difference between LVSP and BIVP. CONCLUSIONS: In patients undergoing CRT, LBBP was associated with improved outcomes compared with LVSP and BIVP, while outcomes between BIVP and LVSP are similar.

Effect of Speaking Valves on Tracheostomy Decannulation

Abstract Introduction Despite several pediatric tracheostomy decannulation protocols there remains tremendous variability in practice. The effect of tracheostomy capping on decannulation has been studied but the role of speaking valves (SVs) is unknown. Objective Given the positive benefits SVs have on rehabilitation, we hypothesized that SVs would decrease time to tracheostomy decannulation. The purpose of the present study was to evaluate this in a subset of patients with chronic lung disease of prematurity (CLD). Methods A retrospective chart review was performed at a tertiary care children's hospital. A total of 105 patients with tracheostomies and CLD were identified. Data collected included demographics, gestational age, congenital cardiac disease, airway surgeries, granulation tissue excisions, SV and capping trials, tracheitis episodes, and clinic visits. Statistics were performed with logistic and linear regression. Results A total of 75 patients were included. The mean gestational age was 27 weeks (standard deviation [SD] =3.6) and the average birthweight was 1.1 kg (SD = 0.6). The average age at tracheostomy was 122 days (SD = 63). A total of 70.7% of the patients underwent decannulation and the mean time to decannulation (TTD) was 37 months (SD = 19). A total of 77.3% of the patients had SVs. Those with an SV had a longer TTD compared to those without (52 versus 35 months; p = 0.008). Decannulation was increased by 2 months for every increase in the number of hospital presentations for tracheitis (p =0.011). Conclusion The present study is the first, to our knowledge, to assess the effect of SVs on tracheostomy decannulation in patients with CLD showing a longer TTD when SVs are used.

Sensitive 1,4-Disubstituted Nitro-Containing Cubanes: Structures and Properties.

The cubane cage system is characteristic and well known for its high strain energy, qualifying it as a promising precursor for energetic materials. 1,4-Disubstituted cubanes are the easiest accessible derivatives. A further developed laboratory-scale procedure for cubane-1,4-dicarboxylic acid dimethyl ester is presented. From this central precursor, the bis-trinitroethyl and bis-nitromethyl esters as well as the bis-methylcarbamate and bis-methylnitrocarbamate were synthesized and characterized by multinuclear NMR spectroscopy and X-ray crystallography. In addition, their physical and energetic properties were determined and studied.

Left Bundle Branch Area Pacing Versus Biventricular Pacing as Initial Strategy for Cardiac Resynchronization.

BACKGROUND: Left bundle branch area pacing (LBBAP) for cardiac resynchronization therapy (CRT) is an alternative to biventricular pacing (BiVp). OBJECTIVES: The purpose of this study was to compare the outcomes between LBBAP and BiVp as an initial implant strategy for CRT. METHODS: In this prospective multicenter, observational, nonrandomized study, first-time CRT implant recipients with LBBAP or BiVp were included. The primary efficacy outcome was a composite of heart failure (HF)-related hospitalization and all-cause mortality. The primary safety outcomes were acute and long-term complications. Secondary outcomes included postprocedural New York Heart Association functional class and electrocardiographic and echocardiographic parameters. RESULTS: A total of 371 patients (median follow-up of 340 days [IQR: 206-477 days]) were included. The primary efficacy outcome occurred in 24.2% in the LBBAP vs 42.4% in the BiVp (HR: 0.621 [95% CI: 0.415-0.93]; P = 0.021) group, driven by a reduction in HF-related hospitalizations (22.6% vs 39.5%; HR: 0.607 [95% CI: 0.397-0.927]; P = 0.021) without significant difference in all-cause mortality (5.5% vs 11.9%; P = 0.19) or differences in long-term complications (LBBAP: 9.4% vs BiVp: 15.2%; P = 0.146). LBBAP resulted in shorter procedural (95 minutes [IQR: 65-120 minutes] vs 129 minutes [IQR: 103-162 minutes]; P < 0.001) and fluoroscopy times (12 minutes [IQR: 7.4-21.1 minutes] vs 21.7 minutes [IQR: 14.3-30 minutes]; P < 0.001), shorter QRS duration (123.7 ± 18 milliseconds vs 149.3 ± 29.1 milliseconds; P < 0.001), and higher postprocedural left ventricular ejection fraction (34.1% ± 12.5% vs 31.4% ± 10.8%; P = 0.041). CONCLUSIONS: LBBAP as an initial CRT strategy resulted in a lower risk of HF-related hospitalizations compared to BiVp. A reduction in procedural and fluoroscopy times, shorter paced QRS duration, and improvements in left ventricular ejection fraction compared with BiVp were observed.

Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production.

The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleTJE. Herein, we describe OleTPRN, a poly-unsaturated alkene-producing decarboxylase that outrivals the functional properties of the model enzyme and exploits a distinct molecular mechanism for substrate binding and chemoselectivity. In addition to the high conversion rates into alkenes from a broad range of saturated FAs without dependence on high salt concentrations, OleTPRN can also efficiently produce alkenes from unsaturated (oleic and linoleic) acids, the most abundant FAs found in nature. OleTPRN performs carbon-carbon cleavage by a catalytic itinerary that involves hydrogen-atom transfer by the heme-ferryl intermediate Compound I and features a hydrophobic cradle at the distal region of the substrate-binding pocket, not found in OleTJE, which is proposed to play a role in the productive binding of long-chain FAs and favors the rapid release of products from the metabolism of short-chain FAs. Moreover, it is shown that the dimeric configuration of OleTPRN is involved in the stabilization of the A-A' helical motif, a second-coordination sphere of the substrate, which contributes to the proper accommodation of the aliphatic tail in the distal and medial active-site pocket. These findings provide an alternative molecular mechanism for alkene production by P450 peroxygenases, creating new opportunities for biological production of renewable hydrocarbons.

Prevalence of phalangeal bone marrow edema on MRI before and during the COVID-19 pandemic and correlation with chilblain skin lesions.

OBJECTIVE: The purpose of this study is to establish the prevalence bone marrow edema of the phalanges of the feet and hands before and during the COVID-19 pandemic on MRI studies and correlate with clinically chilblain skin lesions and epidemiological data. METHODS: This observational retrospective study. In patients with confirmed bone marrow edema of the phalanges, epidemiological data and clinical findings were collected, including the history of current or remote COVID-19 infection and vaccination status. The two-proportion test was used to compare the frequency of bone marrow edema in the phalanges before and during the pandemic, and the comparison between the categories variables was performed using the one-proportion test. RESULTS: Of the total of 7215 patients, only 20 presented isolated bone marrow edema of the digits in MRI studies; 2 (0.05%) were found two years before the pandemic's beginning, and 18 (0.64%) after the pandemic's onset, demonstrating an increase of 13-fold in this period. 16 were women with a mean age of 40.3 years and 4 were men with a mean age of 53.5 years. The most frequently reported clinical symptoms by the patients were pain (85.0%), and erythema of the skin (45.0%). Of the 18 patients found after the pandemic's onset, only 27.8% had COVID-19 infections confirmed by RT-PCR before the imaging study, and all cases were mild. CONCLUSION: This study demonstrated a significant increase in the prevalence of bone marrow edema of the phalanges after the onset of the COVID-19 pandemic, particularly in middle-aged and younger women.

Flexor Tendon Repair in Zone II Augmented With an Externalized Detensioning Suture: Protected Flexor Tendon Repair.

Flexor tendon repair in zone II benefits from early finger motion to prevent stiffness. This article presents a technique that serves to augment a zone II flexor tendon repair with an externalized detensioning suture that can be used following any commonly employed repair method. This simple technique enables early active motion and is suited for patients who are less likely to be compliant after surgery or when the soft-tissue injury to the finger and hand is substantial. Although this technique substantially strengthens the repair, a possible drawback is that the tendon excursion distal to the repair is limited until the externalized suture is removed, which may lead to less motion of the distal interphalangeal than what may have occurred without the detensioning suture.

Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation.

Age is the main risk factor for the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction, and cognitive disabilities in humans, primates, rodents, and invertebrates. Necroptosis mediates degeneration of injured axons, but whether necroptosis triggers neurodegeneration and cognitive impairment along aging is unknown. Here, we show that the loss of the necroptotic effector Mlkl was sufficient to delay age-associated axonal degeneration and neuroinflammation, protecting against decreased synaptic transmission and memory decline in aged mice. Moreover, short-term pharmacologic inhibition of necroptosis targeting RIPK3 in aged mice, reverted structural and functional hippocampal impairment, both at the electrophysiological and behavioral level. Finally, a quantitative proteomic analysis revealed that necroptosis inhibition leads to an overall improvement of the aged hippocampal proteome, including a subclass of molecular biofunctions associated with brain rejuvenation, such as long-term potentiation and synaptic plasticity. Our results demonstrate that necroptosis contributes to age-dependent brain degeneration, disturbing hippocampal neuronal connectivity, and cognitive function. Therefore, necroptosis inhibition constitutes a potential geroprotective strategy to treat age-related disabilities associated with memory impairment and cognitive decline.

Hierarchical compound topology uncovers complex structure of species interaction networks.

Nestedness and modularity have been found in many species interaction networks. Despite being conceptually distinct, negatively correlated and having different causes, these patterns often co-occur. A realistic but seldom investigated alternative to these simple topologies is hierarchical compound networks, in which the entire network is modular, and modules are internally nested. In compound networks, nestedness is suppressed by modularity at higher network hierarchical levels, but prevails at lower levels, within modules. The aims of this study are (i) to evaluate the prevalence of simple and hierarchical compound topologies in binary and weighted networks describing different kinds of species interactions and (ii) to probe the relationships between modularity and nestedness at different network hierarchical levels. With a procedure that discriminates between simple and compound structures, we re-analysed the topology of 142 well-studied binary networks including seed dispersal, host-parasite, pollination and plant-herbivore interactions; 68 of these also had quantitative information. Additionally, we tested the relationship between robustness and topology of binary networks and compared the robustness of networks with compound topologies to different sequences of species removals. Compound topologies were detected in 34% of binary and 71% of weighted networks of all interaction kinds. These results establish the hierarchical compound topology as a widespread network architecture, often undetected without quantitative data. Furthermore, they disentangle an apparent paradox: despite conflicting with overall nestedness, modularity usually co-occurs with high values of low-level nestedness. Nestedness progressively decreased, while modularity increased, from seed dispersal to host-parasite, pollination and plant-herbivore networks. There were no consistent differences in the robustness of networks with nested and compound topologies. However, compound topologies were especially vulnerable to removal sequences that accelerate the exclusion of entire modules. Compound topologies improve the depiction of ecological networks and differentiate ecological and evolutionary processes that operate at different hierarchical levels, with the potential to advance our understanding of network dynamics, stability and response to species loss or change. Quantitative data often reveal specialization patterns that are indistinguishable in binary networks, strongly improving the detection of modular and compound topologies.

Insect decline in Brazil: an appraisal of current evidence.

Recent reviews of data on worldwide insect decline include almost no information on Brazil. We gathered evidence from literature searches and a survey sent to researchers, to which 96 replied and 56 provided information and publications. We present 75 instances of trends recorded over an average span of 11 years for aquatic and 22 years for terrestrial insects. These include time-replicated samples and expert opinion based on long-term local collections. Most terrestrial data are for butterflies, bees and scarab beetles. Aquatic studies include several insect orders, usually sorted to genus or family. Terrestrial insects showed significantly more cases of declines than increases, both in abundance (17 : 3) and in diversity (11 : 1). In aquatic cases, no tendency was detected in abundance (2 : 2) or diversity (3 : 4), not counting cases with no trend. Differences in these results among habitats may be due to the shorter span and less change in environmental conditions in the aquatic surveys, which included sites already degraded before sampling. We offer guidelines for future long-term assessments, including resampling of legacy collection sites.

Health care in pregnancy during the COVID-19 pandemic and pregnancy outcomes in six low- and-middle-income countries: Evidence from a prospective, observational registry of the Global Network for Women's and Children's Health

Objective: To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID-19) pandemic in relationship to pregnancy outcom. Results: Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID-19 and COVID-19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05­1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight infants in the COVID-19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89­0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. Conclusions: Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID-19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period

Meniscal Root Tears: An Update Focused on Preoperative and Postoperative MRI Findings.

Meniscal root tears represent radial tears or avulsions of the meniscal cartilage at the tibial attachment site that profoundly affect meniscal biomechanics and kinematics. Meniscal root tears have the functional effect of a total meniscectomy and can lead to rapid degenerative change with development of early knee osteoarthritis (OA). A growing range of arthroscopic surgical techniques have been developed to repair meniscal root tears with the aim of restoring joint kinematics and contact pressures and delaying the development of OA. With increased understanding of the anatomy and biomechanics of the meniscal root, meniscal root injury repair has become the treatment of choice in knees with nonadvanced OA. This article reviews the anatomy and biomechanics of the meniscal roots, clinical and imaging diagnostic criteria of meniscal root tears, correlation between arthroscopy and MRI in the diagnosis and classification of meniscal root tears, and expected and abnormal MRI findings after meniscal root repair. Familiarity with MRI signs and classifications of meniscal root tears, as well as with root repair surgical techniques, can aid radiologists in correctly reporting preoperative and postoperative MRI findings.

An integrative re-evaluation of Typhlatya shrimp within the karst aquifer of the Yucatán Peninsula, Mexico.

The Yucatán Peninsula, Mexico is a carbonate platform well-known for extensive karst networks of densely stratified aquifer ecosystems. This aquifer supports diverse anchialine fauna, including species of the globally distributed anchialine shrimp genus Typhlatya (Atyidae). Four species (T. campecheae, T. pearsei, T. dzilamensis and T. mitchelli) are endemic to the Peninsula, of which three are federally listed in Mexico. This first integrative evaluation (i.e., molecular, morphological, broad geographic and type locality sampling, and environmental data) of Yucatán Typhlatya reveals considerable species identity conflict in prior phylogenetic assessments, broad species ranges, syntopy within cave systems and five genetic lineages (of which two are new to science). Despite sampling from the type locality of endangered T. campecheae, specimens (and molecular data) were indistinguishable from vulnerable T. pearsei. Ancestral/divergence reconstructions support convergent evolution of a low-salinity ancestor for a post-Paleogene arc Yucatán + Cuba Typhlatya clade within the anchialine Atyidae clade. A secondary adaptation for the coastal-restricted euryhaline (2-37 psu), Typhlatya dzilamensis (unknown conservation status) was identified, while remaining species lineages were low-salinity (< 5 psu) adapted and found within the meteoric lens of inland and coastal caves. This study demonstrates the need for integrative/interdisciplinary approaches when conducting biodiversity assessments in complex and poorly studied aquifers.

Depression in Female Adolescents with Heavy Menstrual Bleeding.

OBJECTIVE: To assess the degree to which heavy menstrual bleeding is associated with depression, independent of hormonal contraception. STUDY DESIGN: We performed a retrospective cohort study of 1168 female adolescents 9-18 years old presenting to general pediatricians for heavy menstrual bleeding or well visits. Depression was the primary outcome and defined as a diagnosis in the health record. Univariable and multivariable regression models were fit to the data to identify factors associated with depression diagnosis. RESULTS: In total, 581 adolescents with heavy menstrual bleeding and 587 without heavy menstrual bleeding were included. Depression diagnoses occurred with greater frequency in youth with heavy menstrual bleeding compared with those without heavy menstrual bleeding (50.9% vs 24.2% P < .001; risk ratio 1.67, 95% CI 1.39-2.01) but did not significantly differ between those taking vs not taking hormonal contraception (risk ratio 0.99; 95% CI 0.84-1.17). Most patients with depression and heavy menstrual bleeding developed depression following or concurrent with heavy menstrual bleeding (261/296, 88%). Of these, 199 of 261 (76%) were treated with hormonal contraception, but the majority (168/199; 84%) were diagnosed with depression before initiation. CONCLUSIONS: Heavy menstrual bleeding is associated with depression diagnosis in female adolescents. The use of hormonal contraception was not associated with depression diagnosis in multivariable analysis, covarying heavy menstrual bleeding, age, body mass index, anxiety, sexual activity, and substance use. As hormonal contraception is often used to treat heavy menstrual bleeding, heavy menstrual bleeding may be partially driving previous reports of increased depression risk in those taking hormonal contraception.