Physiological predictors of acute coronary syndromes: emerging insights from the plaque to the vulnerable patient

In this review, the authors explore the evolving evidence linking physiological assessment of coronary artery disease with plaque progression and vulnerability. Reducing adverse clinical events remains the ultimate goal for diagnostic tests, and this review highlights evidence supporting the prognostic value of physiological metrics in predicting outcomes. Historical and contemporary studies support synergy among lesion severity, ischemia, plaque vulnerability, and patient prognosis. Ischemia contributes to clinical events through association with plaque burden, but this review addresses the emerging concept that it associates with atherothrombosis via disturbed lesion hemodynamics. Biomechanical pathophysiological forces including endothelial shear stress-the frictional force generated by blood flow on the vessel wall-are increasingly linked with atherogenesis, vulnerable plaque morphology, and platelet and leukocyte activation. The authors conclude by transitioning from the model of the vulnerable plaque to the concept of the "vulnerable patient," looking more broadly at physiological contributors to Virchow's triad underpinning acute coronary syndrome

Risk factors, complications and survival after upper abdominal surgery:a prospective cohort study

Background: Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival. More recently, a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle, visceral and subcutaneous adipose tissue has been examined with conflicting results. We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery. Methods: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. Patients were now, six years later, analyzed as a single prospective cohort and overall survival was retrieved from the National Population Registry. Body composition indices were calculated from CT images taken within three months preoperatively. Results: Preoperative serum-albumin 5 % (HR = 1.38, p = 0.023) were independently associated with reduced survival. There was no association between any of the preoperative body composition indices and reduced survival. Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis. Conclusions: Our study has confirmed the robust significance of the traditional indicators, preoperative serum-albumin and weight loss. The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery. We found no association between non-fatal postoperative complications and long-term survival

A systematic approach to the evaluation of the coronary microcirculation using bolus thermodilution: CATH CMD

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The design, implementation, and performance of the LZ calibration systems

LUX-ZEPLIN (LZ) is a tonne-scale experiment searching for direct dark matter interactions and other rare events. It is located at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The core of the LZ detector is a dual-phase xenon time projection chamber (TPC), designed with the primary goal of detecting Weakly Interacting Massive Particles (WIMPs) via their induced low energy nuclear recoils. Surrounding the TPC, two veto detectors immersed in an ultra-pure water tank enable reducing background events to enhance the discovery potential. Intricate calibration systems are purposely designed to precisely understand the responses of these three detector volumes to various types of particle interactions and to demonstrate LZ's ability to discriminate between signals and backgrounds. In this paper, we present a comprehensive discussion of the key features, requirements, and performance of the LZ calibration systems, which play a crucial role in enabling LZ's WIMP-search and its broad science program. The thorough description of these calibration systems, with an emphasis on their novel aspects, is valuable for future calibration efforts in direct dark matter and other rare-event search experiments

New constraints on ultraheavy dark matter from the LZ experiment

Searches for dark matter with liquid xenon time projection chamber experiments have traditionally focused on the region of the parameter space that is characteristic of weakly interacting massive particles, ranging from a few GeV/c2 to a few TeV/c2. Models of dark matter with a mass much heavier than this are well motivated by early production mechanisms different from the standard thermal freeze-out, but they have generally been less explored experimentally. In this work, we present a reanalysis of the first science run of the LZ experiment, with an exposure of 0.9  tonne×yr, to search for ultraheavy particle dark matter. The signal topology consists of multiple energy deposits in the active region of the detector forming a straight line, from which the velocity of the incoming particle can be reconstructed on an event-by-event basis. Zero events with this topology were observed after applying the data selection calibrated on a simulated sample of signal-like events. New experimental constraints are derived, which rule out previously unexplored regions of the dark matter parameter space of spin-independent interactions beyond a mass of 1017  GeV/c2. Published by the American Physical Society 2024 </jats:sec

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism

The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined

The energy balance in cancer cachexia revisited

PURPOSE OF REVIEW: To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour treatment with potential systemic consequences, this article reviews recent data on energy requirements. Furthermore, we focus on new insights in brown adipose tissue (BAT) activity and reward processing in the brain in relation to the cachexia process. RECENT FINDINGS: Nearly no new data have been published on energy requirements of cancer patients in the light of comprehensive new therapies in oncology. New developments, such as the introduction of staging with 18F-fluorodeoxyglucose PET-computed tomography scanning, led to the observation that BAT activation may contribute to impaired energy balance in cancer cachexia. Animal and human data to date provide an indication that BAT activation indeed occurs, but its quantitative impact on the degree of cachexia is controversial. The peripheral and central nervous system is known to influence satiation, with a possible role for impaired food reward processing in the brain. To date, there are limited confirmatory data, but this is an interesting new area to explore for better understanding and treating cancer-induced anorexia. SUMMARY: The multimodal approach to counteract cancer cachexia should expand its targets to BAT and food reward processing in the brain