Increases in drug-related infant mortality in the United States.

OBJECTIVES: We explored temporal trends in drug-related infant deaths in the United States (U.S.) from 2018 to 2022. METHODS: We used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER). A total of 295 drug-involved infant deaths were identified from 2018 to 2022 (provisional mortality data for year 2022) based on the underlying cause of death. RESULTS: In the U.S. from 2018 to 2022, there was a significant 2.2-fold increase in drug-involved infant mortality. The observed increases were higher in non-Hispanic White and Black infants. The findings show that drug-involved infant deaths were more likely to occur in the postneonatal period, defined as ages 28-364 days (81.4 %) compared to the neonatal period. The most prevalent underlying causes of death included assault (homicide) by drugs, medicaments and biological substances (35.6 %) followed by poisoning due to exposure to narcotics and psychodysleptics (hallucinogens) (15.6 %). The most common multiple causes of drug-involved infant deaths were psychostimulants with abuse potential of synthetic narcotics. CONCLUSIONS: Drug-related infant mortality has increased significantly from 2018 to 2022. These increases are particularly evident among White and Black infants and occurred predominantly in the postneonatal period. These findings require more research but also indicate the need to address drug-involved infant deaths as preventable clinical and public health issues. Effective strategies to reduce drug-involved infant deaths will require preventing and treating maternal substance use disorders, enhancing prenatal care access, and addressing broader social and behavioral risk factors among vulnerable maternal and infant populations.

Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8+ T-Cell Pathogenic Responses and Recognition of Type 1 Collagen in Rheumatic Heart Valve Disease.

BACKGROUND: Rheumatic heart valve disease (RHVD) is a leading cause of cardiovascular death in low- and middle-income countries and affects predominantly women. The underlying mechanisms of chronic valvular damage remain unexplored and regulators of sex predisposition are unknown. METHODS: Proteomics analysis of human heart valves (nondiseased aortic valves, nondiseased mitral valves [NDMVs], valves from patients with rheumatic aortic valve disease, and valves from patients with rheumatic mitral valve disease; n=30) followed by system biology analysis identified ProTα (prothymosin alpha) as a protein associated with RHVD. Histology, multiparameter flow cytometry, and enzyme-linked immunosorbent assay confirmed the expression of ProTα. In vitro experiments using peripheral mononuclear cells and valvular interstitial cells were performed using multiparameter flow cytometry and quantitative polymerase chain reaction. In silico analysis of the RHVD and Streptococcuspyogenes proteomes were used to identify mimic epitopes. RESULTS: A comparison of NDMV and nondiseased aortic valve proteomes established the baseline differences between nondiseased aortic and mitral valves. Thirteen unique proteins were enriched in NDMVs. Comparison of NDMVs versus valves from patients with rheumatic mitral valve disease and nondiseased aortic valves versus valves from patients with rheumatic aortic valve disease identified 213 proteins enriched in rheumatic valves. The expression of the 13 NDMV-enriched proteins was evaluated across the 213 proteins enriched in diseased valves, resulting in the discovery of ProTα common to valves from patients with rheumatic mitral valve disease and valves from patients with rheumatic aortic valve disease. ProTα plasma levels were significantly higher in patients with RHVD than in healthy individuals. Immunoreactive ProTα colocalized with CD8+ T cells in RHVD. Expression of ProTα and estrogen receptor alpha correlated strongly in circulating CD8+ T cells from patients with RHVD. Recombinant ProTα induced expression of the lytic proteins perforin and granzyme B by CD8+ T cells as well as higher estrogen receptor alpha expression. In addition, recombinant ProTα increased human leukocyte antigen class I levels in valvular interstitial cells. Treatment of CD8+ T cells with specific estrogen receptor alpha antagonist reduced the cytotoxic potential promoted by ProTα. In silico analysis of RHVD and Spyogenes proteomes revealed molecular mimicry between human type 1 collagen epitope and bacterial collagen-like protein, which induced CD8+ T-cell activation in vitro. CONCLUSIONS: ProTα-dependent CD8+ T-cell cytotoxicity was associated with estrogen receptor alpha activity, implicating ProTα as a potential regulator of sex predisposition in RHVD. ProTα facilitated recognition of type 1 collagen mimic epitopes by CD8+ T cells, suggesting mechanisms provoking autoimmunity.

Racial, ethnic and gender trends in lung cancer mortality rates in the United States-Mexico border and non-border areas.

BACKGROUND: Geographic patterns of lung cancer mortality rate differ in the region bordering Mexico in contrast to the US. This study compares lung cancer mortality between border and non-border counties by race/ethnicity and gender. METHODS: This study utilized population-level death certificate data from US Centers for Disease Control and Prevention Public Internet Wide-Ranging Online Data for Epidemiologic Research dataset between 1999 and 2020. Established algorithms were implemented to examine lung cancer deaths among US residents. We analyzed the age-adjusted data by year, race/ethnicity, gender, and geographic region. Joinpoint regression was used to determine mortality trends across time. RESULTS: Lung cancer mortality rates were lower in border counties compared to non-border counties across time (p < 0.05). Hispanic lung cancer mortality rates were not different in border counties compared to non-border counties during the same period (p > 0.05). Lung cancer mortality among non-Hispanic White living in border counties was lower than non-Hispanic White residing in non-border counties (p < 0.01), and non-Hispanic Black living in border counties had lower lung cancer mortality than non-Hispanic Black in non-border counties in all but three years (p < 0.05). Both female and male mortality rates were lower in border counties compared to non-border counties (p < 0.05). CONCLUSION: Differences in lung cancer mortality between border counties and non-border counties reflect lower mortality in Hispanics overall and a decline for non-Hispanic White and non-Hispanic Black living in border counties experiencing lower lung cancer mortality rates than non-border counties. Further studies are needed to identify specific causes for lower mortality rates in border counties.

Temporal trends and geographic variations in mortality rates from tobacco and firearms in the United States.

We explored temporal trends and geographic variations in United States of America (US) mortality rates from smoking and firearms from 1999 to 2019. To do so, we used the publicly available Centers for Disease Control and Prevention (CDC) Wide Ranging Online Data for Epidemiologic Research (WONDER) with Multiple Cause of Death files from 1999 to 2019. Using age-specific rates and ArcGIS Pro Advanced software for Optimized Hot Spot Analyses from Esri, we generated maps of statistically significant spatial clusters with 90-99% confidence intervals with the Getis-Ord Gi* statistic for mortality from smoking-related causes and firearms. These data show temporal trends and geographic variations in mortality from smoking and firearms in the US. Smoking and firearm-related mortality from assault and suicide increased throughout the US and clustered in the Southeast. Firearm-related suicide also clustered in the continental West and Alaska. These descriptive data generate many hypotheses which are testable in analytic epidemiologic studies designed a priori to do so. The trends suggest smoking and firearm-related causes pose particular challenges to the Southeast and firearms also to the West and Alaska. These data may aid clinicians and public health authorities to implement evidence-based smoking avoidance and cessation programs as well as address firearm mortality, with particular attention to the areas of highest risks. As has been the case with cigarettes, individual behavior changes as well as societal changes are likely to be needed to achieve decreases in premature mortality.

Group 4 ITI Consensus Report: Patient benefits following implant treatment in partially and fully edentulous patients.

OBJECTIVES: The aim of Working Group 4 was to address patient benefits associated with implant dentistry. Focused questions on (a) dental patient-reported outcomes (dPROs), (b) improvement in orofacial function, and (c) preservation of orofacial tissues in partially and fully edentulous patients following provision of implant-retained/supported dental prostheses were addressed. MATERIALS AND METHODS: Three systematic reviews formed the basis for discussion. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary of the 7th ITI Consensus Conference, taking place in 2023 in Lisbon, Portugal. RESULTS: Edentulous patients wearing complete dentures (CD) experience substantial improvements in overall dPROs and orofacial function following treatment with either complete implant-supported fixed dental prostheses (CIFDP) or implant overdentures (IODs). With respect to dPROs, mandibular IODs retained by two implants are superior to IODs retained by one implant. However, increasing the number of implants beyond two, does not further improve dPROs. In fully edentulous patients, rehabilitation with CIFDP or IOD is recommended to benefit the preservation of alveolar bone and masseter muscle thickness. CONCLUSIONS: Completely edentulous patients benefit substantially when at least the mandible is restored using an CIFDP or an IOD compared to CD. In fully edentulous patients, implant prostheses are the best option for tooth replacement. The availability of this treatment modality should be actively promoted in all edentulous communities, including those with limited access and means.

Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

Relative Impact of Surgical Mitral Repair and MitraClip on Annular Remodeling-A Potential Mechanism for Therapeutic Response to Mitral Repair for Degenerative Mitral Regurgitation.

OBJECTIVES: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair. The relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area. DESIGN: This was a retrospective observational study of patients who underwent mitral intervention between 2016 and 2020. SETTING: Weill Cornell Medicine, a single, large, academic medical center. PARTICIPANTS: The population comprised 50 patients with degenerative mitral regurgitation (MR) undergoing MVr. INTERVENTIONS: Elective MVr and TEE. MEASUREMENTS AND MAIN RESULTS: Patients undergoing MitraClip or surgical MVr were matched (1:1) for sex and coronary artery disease. Mitral annular geometry indices were quantified on intraprocedural three-dimensional TEE. Mild or less MR on follow-up transthoracic echocardiography defined optimal response. Patients undergoing MitraClip were older (80 ± eight v 66 ± six years; p < 0.001) but were otherwise similar to surgical patients. Patients undergoing MitraClip had larger baseline left atrial and ventricular sizes, increased tenting height, and volume (p < 0.01), with a trend toward increased annular area (p = 0.23). MitraClip and surgery both induced immediate mitral annular remodeling, including decreased area, circumference, and tenting height (p < 0.001), with greater remodeling with surgical repair. At follow-up (4.1 ± 9.0 months) optimal response (≤ mild MR) was ∼twofold more common with surgery than MitraClip (81% v 46%; p = 0.02). The relative reduction in annular circumference (odds ratio [OR] 1.05 [1.00-1.09] per cm; p = 0.04) and area (OR 1.03 [1.00-1.05] per cm2; p = 0.049) were both associated with optimal response. CONCLUSIONS: Surgical MVr and MitraClip both reduce annular size, but repair-induced remodeling is greater with surgery and associated with an increased likelihood of optimal response.

Mixed reality simulation for peripheral intravenous catheter placement training.

BACKGROUND: Despite the advantages of simulation-based training, trainees are typically unable to view internal anatomical structures. This limitation can be overcome by using mixed reality (MR) wherein 3-D virtual anatomical images can be projected. This study was designed to evaluate the efficacy of an MR trainer for peripheral intravenous catheter (PIVC) placement. METHODS: Sixty-two participants used projected images of arm veins to place a PIVC in a mannequin arm. Participants were evaluated using a checklist on their ability to successfully place the PIVC. Participants completed a survey to elicit demographic information and perceptions of the trainer. A follow-up survey at two-weeks assessed clinical experiences with PIVC placement since using the MR trainer. RESULTS: First attempt catheter placement was successful in 48 (77.4%) cases. Only 11 (17.7%) and 3 (4.8%) of participants caused 'extravasation' and 'hematoma' formation on their first attempt, respectively. Fifty-nine participants (95.2%) agreed that ability to see internal structures was useful, and 58 (93.5%, respectively) agreed that the interactivity promoted learning and that MR should be included in training. CONCLUSIONS: Results of this study showed that use of a novel MR trainer for PIVC placement appears to provide an environment conducive to successful learning. Most participants were successful at PIVC placement on their first attempt and an overwhelming number found it helpful in identifying landmarks and confirming correct needle angles for insertion. Given the increasing emphasis on simulation training, highly immersive MR tools appear to offer promise to close the gap between classroom instruction and clinical experience.

Key Informants' Perspectives on Implementing a Comprehensive Lung Cancer Screening Program in a Safety Net Healthcare System: Leadership, Successes, and Barriers.

Implementing evidence-based practice (EBP) in a safety net healthcare system is challenging. This study examined factors associated with feasibility and potential facilitators and barriers which might affect the implementation of a new evidence-based comprehensive primary care and community health-based program aiming to promote efficient and equitable delivery of Lung Cancer Screening and Tobacco Cessation (LCS-TC). Fifty-three key informants were interviewed. Informants discussed their perceptions of adoption of screening and appropriate referral practices across 15 community health centers. They also identified barriers and facilitators to implementing the LCS-TC program. Interview data were analyzed using inductive thematic analysis. Three major themes representing facilitators and barriers were identified: (1) Allocation of resources and services coverage; (2) need for a collaborative process to engage stakeholders and identify champions; and (3) stakeholders need different types of evidence to support implementation. The top three activities identified as essential for success included provision of sufficient resources for radiologic screening (30%); using non-physician staff for screening (30%); and minimizing the time healthcare providers need to contribute (23%). Conversely, the top three barriers were lack of resources for screening and treatment (60%); insufficient time to address complex patient problems (36%); and perceived lack of patient buy-in (30%). Models for EBP implementation provide stepwise guidance; however, particular contextual factors act as facilitators or barriers to the process. Findings inform EBP implementation efforts regarding resources and key barriers to success around organizational-level supports and promotion of suitable EBP programs.

Botulinum Toxin Can Abolish and/or Quiet Tinnitus Associated with Chronic Migraine: Serendipidous Observations.

INTRODUCTION: It is well established that treatment of head and neck myofascial dysfunction can alleviate both tinnitus and chronic migraine (CM). Onabotulinumtoxin A (OnaA) has become a standard treatment for CM. In a recent systematic study a subject reported tinnitus improvement. This prompted a survey of the tinnitus in all study participants. METHODS: Fifty-seven patients with CM at a tertiary headache referral center received intramuscular Onabotulinumtoxin A (OnaA) injections into craniocervical muscles using the "follow-the-pain" protocol for headache. Effectiveness of OnaA was assessed by changes in (i) tinnitus loudness and (ii) number of headache days. RESULTS: Of the five patients with pre-existing tinnitus OnaA abolished the tinnitus in two, including one whose tinnitus of ten years' duration resolved permanently with one treatment. The tinnitus loudness of the other four was attenuated between 70 to 100 percent for about three months, which paralleled their headaches response. All were women who had (i) a significant improvement of their CM and (ii) headaches located fronto-temporally. None of the CM non-responders reported tinnitus. Analysis of injection sites revealed that the temporalis muscle injections were likely accounting for the tinnitus attenuation. CONCLUSION: Tinnitus associated with chronic migraine is abolished/quieted by intramuscular craniocervical Onabotulinumtoxin A injections. These results are consistent with the dorsal cochlear nucleus hypothesis for craniocervical somatic tinnitus, as well as the association between migraine and tinnitus. This serendipitous result warrants further study of botulinum toxin for tinnitus.

Impact of a collaborative childhood anaemia intervention programme in Peru.

OBJECTIVES: To evaluate the impact of a 12-month multi-modal public health intervention programme for treating and preventing anaemia among children aged 6 months to 4 years in an underserved community in Peru. METHODS: The intervention included nutritional education, use of a Lucky Iron Fish® cooking tool, and dietary supplementation. The primary outcome measure was anaemia resolution. Secondary outcomes included absolute changes in haemoglobin, change in knowledge survey scores and adherence to interventions. Chi-square test and Mann-Whitney U-test were employed to identify associations between anaemia and intervention-related measures. Variables found to be significantly associated in bivariate analysis or of clinical importance were included in a logistic regression model. RESULTS: Of the 406 children enrolled, 256 (63.1%) completed the programme. Of those, 34.0% had anaemia at baseline; this decreased to 13.0% over 12 months. The mean haemoglobin for all ages at baseline was 11.3 g/dL (SD 0.9). At 12 months, the mean was 11.9 g/dL (SD 0.8), with a mean increase of 0.5 g/dL (95% CI 0.4-0.6). Children with anaemia at baseline saw an increase of 1.19 g/dL at the 12-month follow-up (95% CI 1.12-1.37). Parents correctly answered 79.0% of knowledge assessment questions at baseline, which increased to 86.6% at 12 months. CONCLUSIONS: We observed a reduction in the prevalence of mild to moderate anaemia among study participants in this vulnerable population and conclude that multi-modal intervention programmes providing nutrition education in conjunction with low-cost iron supplementation and easy-to-use Lucky Iron Fish® cooking tools may reduce and prevent anaemia in children.

Mutations in DCHS1 cause mitral valve prolapse.

Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease.

Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction.

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

Prognostic importance of the transmitral pressure gradient in mitral annular calcification with associated mitral valve dysfunction.

AIMS: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR). METHODS AND RESULTS: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively). CONCLUSION: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity.

Somatosensory Pulsatile Tinnitus Syndrome (SSPT) Revisited.

INTRODUCTION: Our initial study reported consecutive patients with constant cardiac synchronous subjective tinnitus (pulsatile tinnitus without an identifiable acoustic source (P)) all of whom could suppress their pulsations with head and neck intense muscle contractions ("somatic testing" (ST)). The term somatosensory pulsatile tinnitus syndrome (SSPT) was coined to refer to this type of P. With now more than a decade of clinical experience with P, herein are reported (a) other ways P can present, beside SSPT, (b) how P is related to the somatosensory system and recumbency, and (c) what treatments have been effective. METHODS: Retrospective case series of 58 adults with P encountered in an outpatient clinic or through telemedicine. RESULTS: P could be constant or intermittent, with or without non-pulsatile tinnitus (nP). 90% of cases could suppress their pulsations with ST; 9% could not. In 7 of 11 cases that had no P at time of testing, ST elicited P. The most common type of P was SSPT (constant pulsatile tinnitus suppressible by ST) (60%). Treatment of head and neck muscle dysfunction (muscle dry needling and Botulinum toxin injection) has abolished P; auricular electrical stimulation was effective in 2 cases. CONCLUSION: Suppression of pulsations by ST, eliciting P by ST, and abolishment of P by head and neck muscle treatments all support a major role of the craniocervical somatosensory system in the etiology of most, if not all, cases of P. Three mechanisms are proposed: (A) somatosensory afferents causing dysfunction of the CNS mechanisms that normally suppress self-generated cardiac and vascular sounds, (B) cardiac synchronous disinhibition of the auditory CNS by somatosensory afferents and (C) some combination of A and B.

Novel noninvasive estimation of mixed venous oxygen saturation by echocardiography and expired gas analysis.

Mixed venous oxygen (O2) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O2 consumption (V̇o2), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O2 saturation). Because V̇o2, CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism.NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Identification of two novel trace impurities in mobile phases prepared with commercial formic acid.

While liquid chromatography/high-resolution mass spectrometry (LC/HRMS) is a versatile analytical technique, it is also sensitive to trace impurities. These impurities may come from a variety of sources, including reagents, solvents, and the sample matrix itself. Impurities in reagents may become concentrated and elute as peaks when a gradient method is used, and these peaks may cause suppression of peaks of interest both in the electrospray source, as well as in the C-trap in systems that contain one. METHODS: We observed a notable increase in the size of several impurity peaks in a reversed-phase gradient method upon switching suppliers of formic acid. We used LC/HRMS to separate and fragment these impurity compounds and assign probable formulae. RESULTS: The mass spectra were compared with those of compounds found in the literature with the same formulae, and the observed peaks were matched to two amine compounds not previously reported as impurities in LC/MS systems: trihexylamine and N-methyldihexylamine. The identities were confirmed by high-resolution accurate mass and retention time matching against commercially available standards of these compounds. CONCLUSIONS: To the best of our knowledge, this is the first time that trihexylamine and N-methyldihexylamine have been reported in such systems. We hypothesize that these are derived from the formic acid manufacturing process and recommend that users monitor purchased formic acid for the presence of impurities.