Sex differences in transthyretin cardiac amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease characterized by the deposition of abnormal transthyretin protein fibrils in the heart, leading to cardiac dysfunction. Recent evidence suggests that sex differences may play a significant role in various steps of ATTR-CA, including clinical presentation, diagnostic challenges, disease progression, and treatment outcomes. ATTR-CA predominantly affects men, whereas women are older at presentation. Women generally present with a history of heart failure with preserved ejection fraction and/or carpal tunnel syndrome. When indexed, left ventricular (LV) wall thickness is equal, or even increased, than men. Women also have smaller LV cavities, more preserved ejection fractions, and apparently a slightly worse right ventricular and diastolic function. Given the under-representation on women in clinical trials, no data regarding sex influence on the treatment response are currently available. Finally, it seems there are no differences in overall prognosis, even if premenopausal women may have a certain level of myocardial protection. Genetic variations, environmental factors, and hormonal changes are considered as potential contributors to observed disparities. Understanding sex differences in ATTR-CA is vital for accurate diagnosis and management. By considering these differences, clinicians can improve diagnostic accuracy, tailor treatments, and optimize outcomes for both sexes with ATTR-CA.

Echocardiographic derived forward left ventricular output improves risk prediction in systolic heart failure.

BACKGROUND AND AIMS: Though widely used to classify heart failure (HF) patients, the prognostic role of left ventricular ejection fraction (LVEF) is debated. We hypothesized that the echocardiographic measures of forward LV output, being more representative of cardiac hemodynamics, may improve risk prediction in a large cohort of HF patients with systolic dysfunction. METHODS: Consecutive stable HF patients with LVEF <50% on guideline-recommended therapies undergoing an echocardiography including the evaluation of forward LV output (i.e., LV outflow tract velocity-time integral [LVOT-VTI], stroke volume index [SVi], and cardiac index [CI]) over a 6-year period, were selected and followed-up for the endpoint of cardiac and all-cause death. RESULTS: Among the 1,509 patients analyzed (71±12 years, 75% males, LVEF 35±9%), 328 (22%) died during a median 28-month (14-40) follow-up, 165 (11%) of which for cardiac causes. At multivariable regression analysis, LVOT-VTI (<0.001), SVi (p<0.001), and CI (p<0.001), but not LVEF (p>0.05), predicted cardiac and all-cause death. The optimal prognostic cut-offs for LVOT-VTI, SVi, and CI were 15 cm, 38 mL/m2, and 2 L/min/m2, respectively. Adding each of these measures to a multivariable risk model (including clinical, biohumoral, and echocardiographic markers) improved risk prediction (p<0.001). Among the different measures of forward LV output, CI was less accurate than LVOT-VTI and SVi. CONCLUSION: The echocardiographic evaluation of forward LV output improves risk prediction in HF patients across a wide LVEF spectrum over other well-established clinical, biohumoral, and echocardiographic prognostic markers.

Left ventricular outflow tract velocity-time integral improves outcome prediction in patients with secondary mitral regurgitation.

AIMS: Left ventricular outflow velocity-time integral (LVOT-VTI) has been shown to improve outcome prediction in different patients' subsets, with or without heart failure (HF). Nevertheless, the prognostic value of LVOT-VTI in patients with HF and secondary mitral regurgitation (MR) has never been investigated so far. Therefore, in the present study, we aimed to assess the prognostic value different metrics of LV forward output, including LVOT-VTI, in HF patients with secondary MR. METHODS AND RESULTS: Consecutive patients with HF and moderate-to-severe/severe secondary MR and systolic dysfunction (i.e., left ventricular ejection fraction [LVEF] <50%) were retrospectively selected and followed-up for the primary endpoint of cardiac death. Out of the 287 patients analyzed (aged 74 ± 11 years, 70% men, 46% ischemic etiology, mean LVEF 30 ± 9%, mean LVOT-VTI 20 ± 5 cm), 71 met the primary endpoint over a 33-month median follow-up (16-47 months). Patients with an LVOT-VTI ≤17 cm (n = 96, 32%) showed the greatest risk of cardiac death (Log Rank 44.3, p < 0.001) and all-cause mortality (Log rank 8.6, p = 0.003). At multivariable regression analysis, all the measures of LV forward volume (namely LVOT-VTI, stroke volume index, cardiac output, and cardiac index) were predictors of poor outcomes. Among these, LVOT-VTI was the most accurate in risk prediction (univariable C-statistics 0.70 [95%CI 0.64-0.77]). CONCLUSION: Left ventricular forward output, noninvasively estimated through LVOT-VTI, improves outcome prediction in HF patients with low LVEF and secondary MR.

Applications of Mendelian randomization in psychiatry: a comprehensive systematic review.

Psychiatric diseases exact a heavy socioeconomic toll, and it is particularly difficult to identify their risk factors and causative mechanisms due to their multifactorial nature, the limited physiopathological insight, the many confounding factors, and the potential reverse causality between the risk factors and psychiatric diseases. These characteristics make Mendelian randomization (MR) a precious tool for studying these disorders. MR is an analytical method that employs genetic variants linked to a certain risk factor, to assess if an observational association between that risk factor and a health outcome is compatible with a causal relationship. We report the first systematic review of all existing applications and findings of MR in psychiatric disorders, aiming at facilitating the identification of risk factors that may be common to different psychiatric diseases, and paving the way to transdiagnostic MR studies in psychiatry, which are currently lacking. We searched Web of Knowledge, Scopus, and Pubmed databases (until 3 May 2022) for articles on MR in psychiatry. The protocol was preregistered in PROSPERO (CRD42021285647). We included methodological details and results from 50 articles, mainly on schizophrenia, major depression, autism spectrum disorders, and bipolar disorder. While this review shows how MR can offer unique opportunities for unraveling causal links in risk factors and etiological elements of specific psychiatric diseases and transdiagnostically, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

Detecting the occluding contours of the uterus to automatise augmented laparoscopy: score, loss, dataset, evaluation and user study.

PURPOSE: The registration of a preoperative 3D model, reconstructed, for example, from MRI, to intraoperative laparoscopy 2D images, is the main challenge to achieve augmented reality in laparoscopy. The current systems have a major limitation: they require that the surgeon manually marks the occluding contours during surgery. This requires the surgeon to fully comprehend the non-trivial concept of occluding contours and surgeon time, directly impacting acceptance and usability. To overcome this limitation, we propose a complete framework for object-class occluding contour detection (OC2D), with application to uterus surgery. METHODS: Our first contribution is a new distance-based evaluation score complying with all the relevant performance criteria. Our second contribution is a loss function combining cross-entropy and two new penalties designed to boost 1-pixel thickness responses. This allows us to train a U-Net end to end, outperforming all competing methods, which tends to produce thick responses. Our third contribution is a dataset of 3818 carefully labelled laparoscopy images of the uterus, which was used to train and evaluate our detector. RESULTS: Evaluation shows that the proposed detector has a similar false false-negative rate to existing methods but substantially reduces both false-positive rate and response thickness. Finally, we ran a user study to evaluate the impact of OC2D against manually marked occluding contours in augmented laparoscopy. We used 10 recorded gynecologic laparoscopies and involved 5 surgeons. Using OC2D led to a reduction of 3 min and 53 s in surgeon time without sacrificing registration accuracy. CONCLUSIONS: We provide a new set of criteria and a distance-based measure to evaluate an OC2D method. We propose an OC2D method which outperforms the state-of-the-art methods. The results obtained from the user study indicate that fully automatic augmented laparoscopy is feasible.

Anestesia intravenosa total utilizando propofol ou propofol/cetamina em cadelas submetidas à ovariossalpingohisterectomia / Total intravenous anesthesia using propofol or propofol/ketamine in bitches undergoing ovariohysterectomy

Objetivou-se avaliar os efeitos cardiorrespiratório e analgésico da infusão contínua com propofol e propofol/cetamina em cadelas pré-medicadas com atropina e xilazina, submetidas a ovariossalpingohisterectomia (OSH). Em seis cadelas (GP) a indução anestésica foi realizada com propofol (5mg kg-1 iv), seguido da manutenção anestésica com o mesmo fármaco em infusão contínua intravenosa na taxa inicial de 0,4mg kg-1.min-1. Outras seis cadelas (GPC) receberam a associação de propofol (3,5mg kg-1 iv) e cetamina (1mg kg-1 iv) como indução anestésica. Depois, foi feita manutenção anestésica em infusão contínua intravenosa inicial com 0,28mg kg-1.min-1 e 0,06mg kg-1.min-1 de propofol e cetamina, respectivamente. Os seguintes parâmetros foram mensurados durante a anestesia a cada 10 minutos: freqüências cardíaca (FC) e respiratória (f), pressão arterial sistólica, média e diastólica (PA), concentração final expirada de CO2 (EtCO2), volume minuto (VM), pressão parcial de gás carbônico (PaCO2), pressão parcial de oxigênio (PaO2), saturação de oxigênio na hemoglobina (SatO2), pH, bicarbonato, glicemia e temperatura retal (T). Observou-se redução da pressão arterial média entre 20 e 40 minutos de anestesia no GP. Ocorreu redução da temperatura, hipercapnia e acidose respiratória em ambos os grupos durante a anestesia. A PaO2, o bicarbonato e a glicose aumentaram de forma significativa apenas no GPC durante a anestesia. Houve necessidade de aumentar em 50 e 20 por cento a taxa de infusão de propofol no GP e GPC respectivamente para anestesia cirúrgica satisfatória. Dessa forma, ambos os protocolos mostraram-se seguros e suficientes do ponto de vista de anestesia cirúrgica para realização da OSH em cadelas, desde que a ventilação assistida ou controlada seja instituída quando necessária e a velocidade de infusão do propofol seja 0,6 e 0,34mg kg-1.min-1 nos grupos GP e GPC, respectivamente.

This study aimed to investigate the cardiopulmonary and analgesic effects of propofol and propofol/ketamine infusion in bitches premedicated with atropine and xylazine and submitted to ovariohisterectomy. In six bitches, anesthesia was induced by 5mg kg-1of propofol and maintained initially with 0.4mg kg-1.min-1 of propofol (GP). In the other six bitches, anesthesia was induced with a combination of 3.5mg kg-1 propofol and 1mg kg-1 of ketamine and maintained initially with 0.28mg kg-1.min-1 propofol and 0.06mg kg-1.min-1 of ketamine (GPK). Heart and respiratory rates, arterial blood pressure, minute ventilation, end tidal CO2, pulse hemoglobin O2 saturation, blood gas analysis, plasma glucose concentration and temperature were measured before and every 10 minutes during anesthesia. Mean arterial blood pressure reduced from 20 to 40 minutes of propofol anesthesia. Temperature reduction and hypercapnia with respiratory acidosis occurred in both groups during anesthesia. PaO2, bicarbonate and glucose increased only during propofol/ketamine anesthesia. Propofol infusion rate was increased by 50 and 20 percent during anesthesia in GP and GPK respectively to allow satisfactory surgical anesthesia. Both anesthetic protocols were safe and adequate for ovariohysterectomy in bitches, considering that controlled ventilation is performed when necessary and propofol infusion rate is adjusted to 0,.6 and 0.34mg kg-1.min-1 in GP and GPK according to the surgical stimulus.

Evaluation of laryngeal mask as an alternative to endotracheal intubation in cats anesthetized under spontaneous or controlled ventilation.

OBJECTIVE: To compare the cardiorespiratory effects and incidence of gastroesophageal reflux with the use of a laryngeal mask airway (LMA) or endotracheal tube (ET) in anesthetized cats during spontaneous (SV) or controlled ventilation (CV). STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: Thirty-two adult crossbred cats, weighing 2.7 +/- 0.4 kg. METHODS: The cats were sedated with intramuscular (IM) methotrimeprazine (0.5 mg kg(-1)) and buprenorphine (0.005 mg kg(-1)), followed 30 minutes later by induction of anesthesia with intravenous (IV) thiopental (12.5-20 mg kg(-1)). An ET was used in 16 cats and an LMA in the remaining 16 animals. Anesthesia was maintained with 0.5 minimum alveolar concentration (0.6%) of halothane in oxygen using a Mapleson D breathing system. Cats in both groups were further divided into two equal groups (n = 8), undergoing either SV or CV. Neuromuscular blockade with pancuronium (0.06 mg kg(-1)) was used to facilitate CV. Heart and respiratory rates, direct arterial blood pressure, capnometry (PE'CO2) and arterial blood gases were measured. Gastric reflux and possible aspiration was investigated by intragastric administration of 5 mL of radiographic contrast immediately after induction of anesthesia. Cervical and thoracic radiographs were taken at the end of anesthesia. Data were analyzed using anova followed by Student-Newman-Keuls, Kruskal-Wallis or Friedman test where appropriate. RESULTS: Values for PaCO2 and PE'CO2 were higher in spontaneously breathing cats with the LMA when compared with other groups. Values of PaO2 and hemoglobin oxygen saturation did not differ between groups. Gastroesophageal reflux occurred in four of eight and two of eight cats undergoing CV with ET or LMA, respectively. There was no tracheal or pulmonary aspiration in any cases. CONCLUSIONS AND CLINICAL RELEVANCE: The use of an LMA may be used as an alternative to endotracheal intubation in anesthetized cats. Although aspiration was not observed, gastric reflux may occur in mechanically ventilated animals.

Anestesia epidural com ropivacaína, lidocaína ou associação de lidocaína e xilazina em cães: efeitos cardiorrespiratório e analgésico / Epidural anaesthesia using ropivacaine, lidocaine or the combination of lidocaine and xylazine in dogs: cardiorespiratory and analgesic effects

Este estudo investigou o efeito da ropivacaína, da lidocaína e da associação de lidocaína e xilazina na anestesia epidural de cães. Trinta cães foram tranqüilizados com acepromazina intravenosa, distribuídos em três grupos e submetidos à anestesia epidural no espaço lombo-sacro, com lidocaína 2 por cento com vasoconstrictor (GL), ropivacaína 1 por cento (GR) ou com xilazina associada à lidocaína (GXL). Mensuraram-se as freqüências cardíaca (FC) e respiratória (f), a pressão arterial sistólica (PAS), a concentração final expirada de CO2 (EtCO2), o volume minuto (VM) e a temperatura retal (T). Para avaliação da analgesia somática, utilizou-se o teste do panículo e o teste térmico a 55°C. Os protocolos produziram anestesia da região retro-umbilical, sendo que a associação XL produziu bloqueio anestésico mais cranial, porém causou bradicardia moderada. A duração da anestesia foi mais prolongada nos animais dos grupos GXL (240 min) e GR (250 min), quando comparada as do grupo GL (120 min).

This study was aimed at investigating the effects of ropivacaine, lidocaine or lidocaine combined with xylazine for epidural anaesthesia in dogs. Thirty dogs were sedated with acepromazine IV, divided in to three groups and submitted to lumbosacral epidural anaesthesia using 2 percent lidocaine with adrenaline (L) or 1 percent ropivacaine (R) or xylazine combined with lidocaine (XL). Heart and respiratory rates, systolic arterial blood pressure, EtCO2, minute volume and temperature were measured. Cutaneous anaesthesia was investigated using a forceps and thermic stimulus. All protocols produced retroumbilical anaesthesia. The combination of XL produced a more cranial anaesthetic block, with moderate bradycardia. The duration of the anaesthesia was more prolonged in animals treated with XL (240min) and R (250min), when compared to L alone (120min).