RAD51 restricts DNA over-replication from re-activated origins.

Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation.

Elevated HIV Viral Load is Associated with Higher Recombination Rate In Vivo.

HIV's exceptionally high recombination rate drives its intrahost diversification, enabling immune escape and multidrug resistance within people living with HIV. While we know that HIV's recombination rate varies by genomic position, we have little understanding of how recombination varies throughout infection or between individuals as a function of the rate of cellular coinfection. We hypothesize that denser intrahost populations may have higher rates of coinfection and therefore recombination. To test this hypothesis, we develop a new approach (recombination analysis via time series linkage decay or RATS-LD) to quantify recombination using autocorrelation of linkage between mutations across time points. We validate RATS-LD on simulated data under short read sequencing conditions and then apply it to longitudinal, high-throughput intrahost viral sequencing data, stratifying populations by viral load (a proxy for density). Among sampled viral populations with the lowest viral loads (<26,800 copies/mL), we estimate a recombination rate of 1.5×10-5 events/bp/generation (95% CI: 7×10-6 to 2.9×10-5), similar to existing estimates. However, among samples with the highest viral loads (>82,000 copies/mL), our median estimate is approximately 6 times higher. In addition to co-varying across individuals, we also find that recombination rate and viral load are associated within single individuals across different time points. Our findings suggest that rather than acting as a constant, uniform force, recombination can vary dynamically and drastically across intrahost viral populations and within them over time. More broadly, we hypothesize that this phenomenon may affect other facultatively asexual populations where spatial co-localization varies.

PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks.

DNA interstrand crosslinks (ICLs) induced by endogenous aldehydes or chemotherapeutic agents interfere with essential processes such as replication and transcription. ICL recognition and repair by the Fanconi Anemia pathway require the formation of an X-shaped DNA structure that may arise from convergence of two replication forks at the crosslink or traversing of the lesion by a single replication fork. Here, we report that ICL traverse strictly requires DNA repriming events downstream of the lesion, which are carried out by PrimPol, the second primase-polymerase identified in mammalian cells after Polα/Primase. The recruitment of PrimPol to the vicinity of ICLs depends on its interaction with RPA, but not on FANCM translocase or the BLM/TOP3A/RMI1-2 (BTR) complex that also participate in ICL traverse. Genetic ablation of PRIMPOL makes cells more dependent on the fork convergence mechanism to initiate ICL repair, and PRIMPOL KO cells and mice display hypersensitivity to ICL-inducing drugs. These results open the possibility of targeting PrimPol activity to enhance the efficacy of chemotherapy based on DNA crosslinking agents.

Evaluation of usability, adherence, and clinical efficacy of therapeutic footwear in persons with diabetes at moderate to high risk of diabetic foot ulcers: A multicenter prospective study.

OBJECTIVE: To evaluate therapeutic footwear expectations and usability of individuals with diabetes and foot complications. DESIGN: A prospective multicenter study was conducted on participants with a high risk of developing a diabetic foot ulcer. SETTING: Participants were enrolled in 11 different specialized diabetic foot units in Spain between March 2022 and June 2023. SUBJECTS: Patients with diabetes at moderate to high risk of foot ulceration receiving first therapeutic footwear prescription. INTERVENTIONS: All the patients included in the research were prescribed with their first pair of therapeutic footwear. MAIN MEASURES: Primary outcome measures were MOS-pre and MOS-post questionnaires evaluating use and usability of prescribed therapeutic footwear. Secondary outcome measures aimed to evaluate footwear clinical efficacy as ulceration rate and self-reported perceived walking distance per day. RESULTS: The use of therapeutic footwear exceeded the patient's pre-provision prediction of their anticipated use in 94% of people (n = 126). Based on the visual analogic satisfaction scale, the median satisfaction of daily wearing their therapeutic footwear was 7 points, Interquartile Range (IQR) [5-8.25]. During the follow-up period, 39 participants (29.1%) experienced diabetic foot ulcer. Perceived walking distance participants reported an improvement in their perceived walking ability during various daily life activities. CONCLUSIONS: Diabetes patients at moderate to high risk of diabetic foot ulcer improved their perception of walking ability after therapeutic footwear prescription. Adherence to the therapeutic footwear prescription resulted in less ulcerations.

Prevalence of anterior uveitis in cases of systemic inflammatory response syndrome in dogs and cats.

OBJECTIVE: To determine the prevalence of anterior uveitis in dogs and cats hospitalized with a diagnosis of systemic inflammatory response syndrome (SIRS). ANIMALS STUDIED: Dogs and cats hospitalized between May 2020 and January 2021 were prospectively included. PROCEDURES: Patients were categorized into two different groups: The first group included patients diagnosed with SIRS, and the second group included patients hospitalized without SIRS as a control group. Daily physical and ophthalmological examinations were conducted during hospitalization. Diagnosis of anterior uveitis was made based on the presence of aqueous flare, low intraocular pressure, and other associated ocular signs such as episcleral injection and miosis. A multinomial logistic regression analysis was conducted to investigate factors associated with SIRS and anterior uveitis development. RESULTS: The study comprised 42 patients with SIRS and 26 patients without SIRS. Among those with SIRS, 38% developed anterior uveitis, whereas only 7.7% of patients without SIRS showed signs of anterior uveitis. The prevalence of uveitis was significantly higher in animals with SIRS compared to those without SIRS (p < .05). CONCLUSION: Anterior uveitis is more prevalent in patients with SIRS than patients without SIRS. Therefore, complete ophthalmic examination is recommended in all patients presenting with this syndrome.

Wireless EEG: A survey of systems and studies.

The popular brain monitoring method of electroencephalography (EEG) has seen a surge in commercial attention in recent years, focusing mostly on hardware miniaturization. This has led to a varied landscape of portable EEG devices with wireless capability, allowing them to be used by relatively unconstrained users in real-life conditions outside of the laboratory. The wide availability and relative affordability of these devices provide a low entry threshold for newcomers to the field of EEG research. The large device variety and the at times opaque communication from their manufacturers, however, can make it difficult to obtain an overview of this hardware landscape. Similarly, given the breadth of existing (wireless) EEG knowledge and research, it can be challenging to get started with novel ideas. Therefore, this paper first provides a list of 48 wireless EEG devices along with a number of important-sometimes difficult-to-obtain-features and characteristics to enable their side-by-side comparison, along with a brief introduction to each of these aspects and how they may influence one's decision. Secondly, we have surveyed previous literature and focused on 110 high-impact journal publications making use of wireless EEG, which we categorized by application and analyzed for device used, number of channels, sample size, and participant mobility. Together, these provide a basis for informed decision making with respect to hardware and experimental precedents when considering new, wireless EEG devices and research. At the same time, this paper provides background material and commentary about pitfalls and caveats regarding this increasingly accessible line of research.

Incidence and Prognosis of Colorectal Cancer After Heart Transplantation: Data From the Spanish Post-Heart Transplant Tumor Registry.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

A comprehensive assessment of long-term SARS-CoV-2-specific adaptive immune memory in convalescent COVID-19 Solid Organ Transplant recipients.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.

Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. METHODS: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). RESULTS: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. CONCLUSIONS: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults.

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 µg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 µg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

Results of Surgical Treatment for Popliteal Aneurysm.

BACKGROUND: Evaluate the results of open surgery treatment of popliteal artery aneurysms (PAAs), performed in our department for over 25 years, comparing those treated with a medial approach with those treated with a posterior approach. MATERIAL AND METHOD: A retrospective analysis of a total of 88 PAAs, performed between January 1994 and December 2018, with an average of 65 months follow-up, comparing the results of 59 patients operated by a medial approach (group 1) in which aneurysm exclusion and femoro-popliteal bypass below the knee was carried out, with 29 cases treated by a direct posterior approach (group 2) - aneurismectomy and graft interposition-. The postoperative complications, immediate and long term patency, limb salvage and mortality rate were studied. RESULTS: In group 1 the chosen material for the bypass was reversed greater saphenous vein (GSV) in 45 cases (76.3%), expanded polytetrafluoroethylene (ePTFE) grafts in 12 (20.3%) and Dacron grafts on 2 (3.4%), while in group 2, a 6 mm diameter ringed ePTFE graft was used in 27 cases (93.1%) and reversed GSV in 2 (6.9%). There were eight (13.6%) postoperative graft thrombosis in group 1, 5 (8.9%) of them needing amputation, and 1 (3.4%) graft thrombosis in group 2 (P = 0.077). During the follow up, major amputation was necessary in 2 cases (3.7%) in group 1, while there were no cases of major amputation in group 2. Mortality was 61% (36 patients) in group 1 and 27% (8 patients) in group 2 (p = 0.003), at the end of surveillance. CONCLUSION: In our experience, in the open surgical treatment of PAAs, the posterior approach could be considered as the first choice in selected cases.

SARS-CoV-2-specific serological and functional T cell immune responses during acute and early COVID-19 convalescence in solid organ transplant patients.

The description of protective humoral and T cell immune responses specific against SARS-CoV-2 has been reported among immunocompetent (IC) individuals developing COVID-19 infection. However, its characterization and determinants of poorer outcomes among the at-risk solid organ transplant (SOT) patient population have not been thoroughly investigated. Cytokine-producing T cell responses, such as IFN-γ, IL-2, IFN-γ/IL-2, IL-6, IL-21, and IL-5, against main immunogenic SARS-CoV-2 antigens and IgM/IgG serological immunity were tracked in SOT (n = 28) during acute infection and at two consecutive time points over the following 40 days of convalescence and were compared to matched IC (n = 16) patients admitted with similar moderate/severe COVID-19. We describe the development of a robust serological and functional T cell immune responses against SARS-CoV-2 among SOT patients, similar to IC patients during early convalescence. However, at the infection onset, SOT displayed lower IgG seroconversion rates (77% vs. 100%; p = .044), despite no differences on IgG titers, and a trend toward decreased SARS-CoV-2-reactive T cell frequencies, especially against the membrane protein (7 [0-34] vs. 113 [15-245], p = .011, 2 [0-9] vs. 45 [5-74], p = .009, and 0 [0-2] vs. 13 [1-24], p = .020, IFN-γ, IL-2, and IFN-γ/IL-2 spots, respectively). In summary, our data suggest that despite a certain initial delay, SOT population achieve comparable functional immune responses than the general population after moderate/severe COVID-19.

Incidence of vasoplegic syndrome after cardiac transplantation in patients treated with sacubitril/valsartan.

Vasoplegic syndrome (VS) is associated with poor outcomes after heart transplantation (HT). Our aim was to determine whether SAC/VALS is associated with VS after HT. We retrospectively analyzed all consecutive HT performed in three centers between January 2017 and August 2018. VS was defined as vasopressor need (norepinephrine or epinephrine >.5 mcg/kg/min or vasopressin) for more than 24 hours to maintain a mean arterial pressure >70 mm Hg. Ninety-six recipients underwent HT in the study period: 60 elective HT with no LVAD, 5 elective HT on long term LVAD, and 31 emergent HT: 3 on long-term LVAD and 28 on temporary mechanical circulatory support. Fourteen patients were on SAC/VALS treatment at the time of transplant, and 82 were not. The global incidence of VS was 15.6%, with no significant differences between the groups (7.14% in with SAC/VALS vs 17.07% in no-SAC/VALS). In conclusion, in our small cohort SAC/VALS was not associated with VS development.

Outcome of phacoemulsification in 71 cats: A multicenter retrospective study (2006-2017).

PURPOSE: To assess outcome of phacoemulsification in cats. METHODS: Records of 71 cats (82 eyes) from five referral centers were reviewed. Groups were divided by cause of cataract (congenital/juvenile [n = 32], traumatic [n = 33], and secondary to uveitis [n = 6]), and group comparisons were performed for the most common complications: postoperative ocular hypertension (POH), uveitis, corneal ulceration, synechia/dyscoria, and posterior capsular opacity (PCO) in three different time periods: immediately postoperatively, at 1-90 days, and at >90 days. RESULTS: Median follow-up was 198 days (interquartile range 64-518 days). The overall visual success rate of the cats with a 12-month follow-up was 92.6% (25/27 eyes). POH occurred in 35/82 (42.6%) eyes. Immediately postoperatively, uveitis was the most common complication in 28/82 eyes (34.1%) followed by corneal ulceration in 22/82 eyes (26.8%). At 1-90 days, uveitis in 41/81 eyes (50.6%) remained the most common complication, followed by synechia/dyscoria in 21/81 eyes (25.9%), corneal ulceration in 16/81 eyes (19.7%), and PCO in 15/81 eyes (18.5%). At >90 days, PCO in 17/47 eyes (36.1%), followed by synechia/dyscoria in 16/47 eyes (34%), was the most common complications. The number of eyes with synechia/dyscoria in the trauma group was higher (13/33 [39.3%]) than in the congenital/juvenile group (5/31 [16.1%]) at 1-90 days (P = .039). No statistical difference was found for the other group comparisons. Three eyes in total were enucleated owing to endophthalmitis, post-traumatic ocular sarcoma, and secondary glaucoma. CONCLUSION: Uveitis in the short-term and PCO and synechia/dyscoria in the long-term were the most common complications following phacoemulsification in cats.

A review of phthalate pharmacokinetics in human and rat: what factors drive phthalate distribution and partitioning?

Phthalates are a class of compounds that have been extensively used as plasticizers in different applications. Several phthalates have been recognized as substances of very high concern (SVHCs) in the EU, because of their toxicity for reproduction. However, high amounts of other phthalates are still produced and imported in the European Economic Area. In China and the US, recent studies show increasing concentrations of several phthalates in the air and in human urine, respectively. The understanding of phthalate absorption, distribution, metabolism, and elimination ('pharmacokinetics') in the organism is still limited. Specifically, phthalate partitioning among tissues is insufficiently understood. Here, we estimate partition coefficient (PC) values for different phthalates by using five algorithms and compare them to experimental (in-vivo and in-vitro) PC values. In addition, we review all pharmacokinetic steps for phthalates in human and rat, based on data from 133 peer-reviewed publications. We analyze the factors that determine phthalate partitioning and pharmacokinetics. Four processes are particularly relevant to phthalate distribution: protein binding, ionization, passive partitioning, and metabolism in different tissues. The interplay of these processes needs to be better represented in methods for determining the PC values of phthalates. The hydrophobicity of phthalates affects all pharmacokinetic steps. The exposure route has an influence on specific steps of phthalate pharmacokinetics but generally does not affect the pattern of metabolites in urine. The age of the organism has an influence on phthalate metabolism. More studies on the protein-bound fraction of phthalates in plasma and pharmacokinetic studies following inhalation and dermal exposure are desirable.

Physiology-based toxicokinetic modelling in the frame of the European Human Biomonitoring Initiative.

Given the opportunities provided by internal dosimetry modelling in the interpretation of human biomonitoring (HBM) data, the assessment of the links between exposure to chemicals and observed HBM data can be effectively supported by PBTK modelling. This paper gives a comprehensive review of available human PBTK models for compounds selected as a priority by the European Human Biomonitoring Initiative (HBM4EU). We highlight their advantages and deficiencies and suggest steps for advanced internal dose modelling. The review of the available PBTK models highlighted the conceptual differences between older models compared to the ones developed recently, reflecting commensurate differences in research questions. Due to the lack of coordinated strategies for deriving useful biomonitoring data for toxicokinetic properties, significant problems in model parameterisation still remain; these are further increased by the lack of human toxicokinetic data due to ethics issues. Finally, questions arise as well as to the extent they are really representative of interindividual variability. QSARs for toxicokinetic properties is a complementary approach for PBTK model parameterisation, especially for data poor chemicals. This approach could be expanded to model chemico-biological interactions such as intestinal absorption and renal clearance; this could serve the development of more complex generic PBTK models that could be applied to newly derived chemicals. Another gap identified is the framework for mixture interaction terms among compounds that could eventually interact in metabolism. From the review it was concluded that efforts should be shifted toward the development of generic multi-compartmental and multi-route models, supported by targeted biomonitoring coupled with parameterisation by both QSAR approach and experimental (in-vivo and in-vitro) data for newly developed and data poor compounds.

Visual outcome following phacoemulsification in English Cocker Spaniels with suspected progressive retinal atrophy: A retrospective multicenter study of 54 cases (2002-2017).

OBJECTIVE: To describe the visual outcome following phacoemulsification in English Cocker Spaniels (ECS) affected by cataracts and suspected progressive retinal atrophy (PRA). ANIMALS STUDIED: Fifty-four client-owned dogs. PROCEDURES: A multicenter, retrospective study was performed including ECS with suspected PRA which underwent phacoemulsification. PRA was suspected on ophthalmic examination before and after surgery, and/or after electroretinography (ERG) was performed. Visual outcome was assessed by menace response per eye at seven time periods post-surgery (P1= 25-90 days, P2 = 91-180 days, P3 = 181-364 days, P4 = 365-549 days, P5 = 550-729 days, P6 = 730-1094 days, and P7 ≥ 1095 days). Descriptive statistics were performed. Generalized estimating equations were used to identify predictors associated with vision after surgery. Odds ratio and confidence intervals were reported. Significance was set at P < 0.05. Owners were invited to participate in a questionnaire. RESULTS: Phacoemulsification was performed in 85 eyes. Median age at surgery was 9.09 years (min. 2.17 years, max. 13.49 years). At all re-examinations, up to and including P5, significantly more eyes were visual than before surgery (P ≤ 0.003). Odds for vision were significantly increased for eyes that underwent surgery. Electroretinograms were performed in 75/85 eyes that underwent surgery, demonstrating low b-wave amplitudes. There was no significant effect of the age, gender, vision before surgery, presence of dazzle reflex, cataract stage or abnormality on gonioscopy on visual outcome. The questionnaire response rate was 48.2%. Most participants (92.5%) felt that cataract surgery led to improvement of the dog's quality of life. CONCLUSIONS: English Cocker Spaniels with suspected PRA may benefit from phacoemulsification with vision up to 2 years following surgery.

Comprehensive assessment of left ventricular myocardial function by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Left ventricular ejection fraction (LVEF) results from the combined action of longitudinal and circumferential contraction, radial thickening, and basal and apical rotation. The study of these parameters together may lead to an accurate assessment of the cardiac function. METHODS: Ninety healthy volunteers, categorized by gender and age (≤ 55 and >  55 years), were evaluated using two-dimensional speckle tracking echocardiography. Transversal views of the left ventricle (LV) were obtained to calculate circumferential strain and left ventricular twist, while three apical views were obtained to determine longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We established the integral myocardial function of the LV according to: 1. The Combined Deformation Parameter (CDP), which includes Deformation Product (DP) - Twist x LS (° x %) - and Deformation Index (DefI) -Twist / LS (° / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE (° / cm). RESULTS: The mean age of our patients was 50.3 ± 11.1 years. CDP did not vary with gender or age. The average DP was - 432 ± 172 ° x %, and the average DefI was - 0.96 ± 0.36 ° / %. DP provides information about myocardial function (normal, pseudonormal, depressed), and the DefI quotient indicates which component (s) is/are affected in cases of abnormality. TorI was higher in volunteers over 55 years (16.5 ± 15.2 vs 13.1 ± 5.0 °/cm, p = 0.003), but did not vary with gender. CONCLUSIONS: The proposed parameters integrate values of twisting and longitudinal shortening. They allow a complete physiological assessment of cardiac systolic function, and could be used for the early detection and characterization of its alteration.

Chronic total occlusion in an infarct-related coronary artery and the risk of appropriate ICD therapies.

INTRODUCTION: Risk stratification for ventricular arrhythmias in patients with ischemic cardiomyopathy needs to be improved. Coronary chronic total occlusions in an infarct-related artery (IRA-CTOs) have been associated with an increased arrhythmic risk. This study aimed to evaluate the association between IRA-CTOs and appropriate implantable cardioverter-defibrillator (ICD) therapies. METHODS AND RESULTS: Observational cohort study that included 342 patients with ischemic cardiomyopathy, an ICD implanted for primary or secondary prevention, and a coronary angiography performed shortly before ICD implantation. The ICD was implanted for primary prevention in 163 patients (48%). IRA-CTO was found in 161 patients (47%). During a median follow-up of 33 months, 41% of patients experienced at least one appropriate ICD therapy. Patients with IRA-CTO had higher proportions of appropriate ICD therapies (57% vs. 26%, P < 0.001) and appropriate ICD shocks (40% vs. 17%, P < 0.001). At multivariate Cox regression, IRA-CTO was the only variable that consistently resulted as independent predictor of appropriate ICD therapies and shocks both in the global population of the study (HR 2.3, P < 0.001 and HR 3, P < 0.001, respectively) and when analyzing separately patients with primary or secondary prevention ICD. CONCLUSIONS: IRA-CTO is an independent predictor of appropriate ICD therapies, including appropriate ICD shocks. This association is consistent across all the subgroups analyzed. Patients with IRA-CTO have a very high risk of appropriate ICD therapies. These findings may help improving risk stratification as well as the management of ventricular arrhythmias in patients with ischemic cardiomyopathy.

Delayed surgery in hip fracture patients. Can we afford it?

The aim is to analyze whether time to surgery (TtoS) in hip fracture patients is associated with longer than expected length of stay (LofS) and whether there is any particular group in which this is especially relevant. We developed an observational study in Madrid, Spain. From 771 patients admitted to the orthopedic ward, we selected 723 with surgical delay ≤7 days. Age was characterized as younger (<81), elderly (81-90), very elderly (>90). Modified Barthel Index was classified as very dependent (<41), moderately dependent (41-80), independent (>80). RESULTS: Median (IQR) TtoS was 3 (1-4) days; LofS 12 (7-15). Mean age was 84.3 years, 78.4% were women. TtoS was associated with LofS, which increased by 1.80 days (95% CI, 1.50-2.10) per delayed day (p<0.001). After adjustment for age, sex, functional status, we found an increase of 1.75 days (1.46-2.04) per day (p<0.001). We did not find effect of age or sex. Functional status had a higher effect in moderately dependent patients 2.25 days (1.78-2.72) than in very dependent or independent patients, 1.33 (0.37-2.30) and 1.50 days (1.09-1.91) respectively (p 0.012). As conclusion we could affirm that increasing TtoS leads to longer than expected LofS in hip fracture patients, particularly moderately dependent patients. Copyright © 2016 John Wiley & Sons, Ltd.