The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Management of pain in cancer patients- lessons from practices during the COVID-19: a qualitative study of cancer care providers' perspectives.

BACKGROUND: The ongoing COVID-19 pandemic has impacted health systems globally and affected managing many chronic conditions, including cancer. This study aimed to explore the perceptions of multi-disciplinary cancer care providers on how cancer pain management was affected by the COVID-19 pandemic. METHODS: Participants were eligible if they were cancer care providers of any specialty and discipline from two tertiary hospitals in Australia. Data were collected using semi-structured interviews to explore cancer care providers' perspectives on cancer pain management within COVID-19. Thematic analysis of interview transcripts used an integrated approach that started with inductive coding before coding deductively against a behaviour framework called the COM-B Model, which proposes that 'capability', 'motivation' and 'opportunity' are requisites for any behaviour. RESULTS: Twenty-three providers participated. Five themes were developed and interpreted from the analysis of data, namely: "Telehealth enables remote access to cancer pain management but also created a digital divide", "Access to cancer pain management in the community is compromised due to the pandemic", "COVID-19 negatively impacts hospital resource allocation", "Patients were required to trade off cancer pain management against other health priorities" and "Hospital restrictions result in decreased social and psychological support for patients with cancer pain". CONCLUSIONS: The landscape of cancer pain management in the Australian health system underwent substantial shifts during the COVID-19 pandemic, with lasting impacts. Cancer care providers perceived the pandemic to have significant adverse effects on pain management across multiple levels, with repercussions for patients experiencing cancer-related pain. A more adaptive health system model needs to be established in the future to accommodate vulnerable cancer patients.

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real-World Cohort.

OBJECTIVE: This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease. METHODS: Patients were ≥50 years and received neuroimaging for non-stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. RESULTS: 230,062 patients were included (median follow-up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time-to-event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 person-years), from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio = 1.05 [0.88, 1.24]). INTERPRETATION: Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620-630.

Stratifying Future Stroke Risk with Incidentally Discovered White Matter Disease Severity and Covert Brain Infarct Site.

BACKGROUND: Covert cerebrovascular disease (CCD) includes white matter disease (WMD) and covert brain infarction (CBI). Incidentally discovered CCD is associated with increased risk of subsequent symptomatic stroke. However, it is unknown whether the severity of WMD or the location of CBI predicts risk. OBJECTIVES: The aim of this study was to examine the association of incidentally discovered WMD severity and CBI location with risk of subsequent symptomatic stroke. METHOD: This retrospective cohort study includes patients aged ≥50 years old in the Kaiser Permanente Southern California health system who received neuroimaging for a nonstroke indication between 2009 and 2019. Incidental CBI and WMD were identified via natural language processing of the neuroimage report, and WMD severity was classified into grades. RESULTS: A total of 261,960 patients received neuroimaging; 78,555 patients (30.0%) were identified to have incidental WMD and 12,857 patients (4.9%) to have incidental CBI. Increasing WMD severity is associated with an increased incidence rate of future stroke. However, the stroke incidence rate in CT-identified WMD is higher at each level of severity compared to rates in MRI-identified WMD. Patients with mild WMD via CT have a stroke incidence rate of 24.9 per 1,000 person-years, similar to that of patients with severe WMD via MRI. Among incidentally discovered CBI patients with a determined CBI location, 97.9% are subcortical rather than cortical infarcts. CBI confers a similar risk of future stroke, whether cortical or subcortical or whether MRI- or CT-detected. CONCLUSIONS: Increasing severity of incidental WMD is associated with an increased risk of future symptomatic stroke, dependent on the imaging modality. Subcortical and cortical CBI conferred similar risks.

Stratifying future stroke risk with incidentally-discovered white matter disease severity and covert brain infarct site.

BACKGROUND: Covert cerebrovascular disease (CCD) includes white matter disease (WMD) and covert brain infarction (CBI). Incidentally-discovered CCD is associated with increased risk of subsequent symptomatic stroke. However, it is unknown whether the severity of WMD or the location of CBI predicts risk. OBJECTIVES: To examine the association of incidentally-discovered WMD severity and CBI location with risk of subsequent symptomatic stroke. METHOD: This retrospective cohort study includes patients 50 years old in the Kaiser Permanente Southern California health system who received neuroimaging for a non-stroke indication between 2009-2019. Incidental CBI and WMD were identified via natural language processing of the neuroimage report, and WMD severity was classified into grades. RESULTS: 261,960 patients received neuroimaging; 78,555 (30.0%) were identified to have incidental WMD, and 12,857 (4.9%) to have incidental CBI. Increasing WMD severity is associated with increased incidence rate of future stroke. However, the stroke incidence rate in CT-identified WMD is higher at each level of severity compared to rates in MRI-identified WMD. Patients with mild WMD via CT have a stroke incidence rate of 24.9 per 1,000 person-years, similar to that of patients with severe WMD via MRI. Among incidentally-discovered CBI patients with a determined CBI location, 97.9% are subcortical rather than cortical infarcts. CBI confers a similar risk of future stroke, whether cortical or subcortical, or whether MRI- or CT-detected. CONCLUSIONS: Increasing severity of incidental WMD is associated with an increased risk of future symptomatic stroke, dependent on the imaging modality. Subcortical and cortical CBI conferred similar risks.

A case of disappearing amyloid on technetium pyrophosphate scan.

Technetium-99mm pyrophosphate (Tc-PYP) scintigraphy is a highly accurate non-invasive method for the diagnosis of transthyretin (ATTR) cardiac amyloidosis. Prognosis for this disease is improved following treatment with the transthyretin (TTR) stabilizer tafamidis. Although tafamidis slows disease progression, its effects on myocardial amyloid and Tc-PYP uptake remain unclear. We present a patient with ATTR cardiac amyloidosis who had a strongly positive initial Tc-PYP scan, with a dramatic decrease in Tc-PYP uptake on repeat scan after 3 years of tafamidis treatment. However, myocardial biopsy showed persistent diffuse amyloid deposits. This case highlights the need for further studies regarding the utility of serial Tc-PYP scans in monitoring the progress of ATTR cardiomyopathy.

Depth of anaesthesia and mortality after cardiac or noncardiac surgery: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Recent randomised controlled trials have failed to show a benefit in mortality by using processed electroencephalography (pEEG) to guide lighter anaesthesia. We performed a meta-analysis of mortality data from randomised trials of pEEG monitoring to assess the evidence of any protective effect of pEEG-guided light anaesthesia compared with deep anaesthesia in adults aged ≥18 yr. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In February 2022, we searched three databases (Cochrane CENTRAL, OVID Medline, EMBASE) for RCTs of pEEG monitoring that provided mortality data at 30 days, 90 days, and/or 1 yr or longer. RESULTS: We included 16 articles from 12 RCTs with 48 827 total participants. We observed no statistically significant mortality reduction with light anaesthesia compared with deep anaesthesia in patients aged ≥18 yr when all studies were pooled (odds ratio [OR]=0.99; 95% confidence interval (CI), 0.92-1.08). This result did not change significantly when analysing mortality at 30 days, 90 days, 1 yr or longer. We observed no mortality benefit for pEEG monitoring compared with usual care (OR=1.02; 95% CI, 0.89-1.18), targeting higher pEEG index values compared with lower values (OR=0.89; 95% CI, 0.60-1.32), or low pEEG index value alerts compared with no alerts (OR=1.02; 95% CI, 0.41-2.52). CONCLUSIONS: pEEG-guided lighter anaesthesia does not appear to reduce the risk of postoperative mortality. The absence of a plausible rationale for why deeper anaesthesia should increase mortality has hampered appropriate design of definitive clinical trials. CLINICAL TRIAL REGISTRATION: CRD42022285195 (PROSPERO).

Giant cystic hypothalamic hamartoma in an infant associated with persistent syndrome of inappropriate antidiuretic hormone secretion.

BACKGROUND: A giant hypothalamic hamartoma (GHH) is a rare congenital malformation only reported in a few cases in the literature and is often associated with precocious puberty, gelastic seizures, or less commonly, Pallister-Hall syndrome. Persistent syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare in infancy, and most patients with GHH do not develop persistent SIADH, usually only transient electrolyte disturbances postoperatively. Previous cases of GHH have not been associated with persistent derangements in antidiuretic hormone levels. CASE DESCRIPTION: A 7-month-old male infant presented to our hospital with a history of an intracranial cystic lesion diagnosed at 23 weeks gestational age (GA), later impressed as a solid-cystic mass at 37 weeks GA by ultrasound prenatally. Postnatal MRI after birth showed a large mass with a dorsal cyst occupying the hypothalamus, causing hydrocephalus and brainstem compression. The patient started to have subtle seizures on the seventh day after birth and eventually developed dacrystic seizures. Hyponatremia with persistent SIADH was observed at 3 months of age before surgery. He received long-term oral sodium supplementation, polytherapy of anti-epileptic medications, ventriculocystostomy for progressive enlargement of the cystic cavity, and later surgical treatment for disconnection and partial resection which confirmed a histological diagnosis of hypothalamic hamartoma. CONCLUSION: In this case study, we present a novel association of GHH with persistent SIADH and a rare presentation of a cystic component at the dorsal part of the tumor. Clinicians should be aware of this potential endocrine derangement and provide emergent treatment.

Arnold Max Meirowsky: champion of the American mobile neurosurgical unit during the Korean War.

Dr. Arnold Max Meirowsky (1910-1984) was enormously influential to military neurosurgery during the Korean War, introducing to the American military the concept of the mobile neurosurgical unit. After implementation of the neurosurgical detachment, meningocerebral infections saw a decrease from 41% to less than 1%, with similar improvements in mortality and complication rates. Additionally, Meirowsky developed many techniques and improvements in neurosurgery, specifically in the field of neurosurgical trauma, which he dedicated himself to even after reentering civilian practice. Furthermore, his mentorship of Korean surgeons and the influence of his mobile neurosurgical unit were major influences cited to be pivotal to the founding of neurosurgery as a specialty in South Korea. As he is underrecognized for these accomplishments in the neurosurgical literature, the authors seek to review his wartime and career contributions. They also specifically present details of his standardization of the mobile neurosurgical unit and showcase several of his other advancements in the treatment of neurosurgical trauma.

Radiographic risk factors for intracranial hemorrhage in patients with left ventricular assist devices.

OBJECTIVE: Intracranial hemorrhage (ICH) in patients with left ventricular assist devices (LVAD) is a devastating complication. Demographic risk factors for ICH in LVAD patients are defined, however anatomic predispositions to ICH are unknown. We sought to interrogate intracranial radiographic risk factors for ICH in LVAD patients. METHODS: We reviewed 440 patients who received an LVAD from 2008-2021. We selected patients with CT scans of the head either before or after LVAD placement, but typically within 5 years. 288 patients (21 ICH, 267 Control) with imaging were included. A detailed chart review was performed on demographics, radiographic features, and management. RESULTS: The incidence of ICH in our total cohort was 8.6% (38/440). The presence of pump thrombosis (p=0.001), driveline infection (p=0.034), other hemorrhage (p=0.001), or previous placement of a cardio-defibrillator (p=.003) was associated with increased risk for ICH. An analysis of imaging revealed that the presence of a mass (p=0.006), vascular pathology (p=0.001), and microangiopathy (p=0.04) was significantly associated with ICH in LVAD patients. These radiographic features were validated with a multivariate logistic regression which confirmed presence of a mass (aOR 332.1, 95% CI: 14.7-7485.1, p<0.001), vascular pathology (aOR 69.7, 95% CI: 1.8-2658.8, p=0.022), and microangiopathy (aOR 6.5, 95% CI: 1.1-37.6, p=0.035) were independently associated with ICH. CONCLUSION: Radiographic evidence of microangiopathy, intracranial mass, and vascular pathology are independent risk factors for ICH which are readily identified by imaging. We advocate that CT imaging be used to further stratify patients at highest risk of ICH during treatment with an LVAD.

Impact of similarity metrics on single-cell RNA-seq data clustering.

Advances in high-throughput sequencing on single-cell gene expressions [single-cell RNA sequencing (scRNA-seq)] have enabled transcriptome profiling on individual cells from complex samples. A common goal in scRNA-seq data analysis is to discover and characterise cell types, typically through clustering methods. The quality of the clustering therefore plays a critical role in biological discovery. While numerous clustering algorithms have been proposed for scRNA-seq data, fundamentally they all rely on a similarity metric for categorising individual cells. Although several studies have compared the performance of various clustering algorithms for scRNA-seq data, currently there is no benchmark of different similarity metrics and their influence on scRNA-seq data clustering. Here, we compared a panel of similarity metrics on clustering a collection of annotated scRNA-seq datasets. Within each dataset, a stratified subsampling procedure was applied and an array of evaluation measures was employed to assess the similarity metrics. This produced a highly reliable and reproducible consensus on their performance assessment. Overall, we found that correlation-based metrics (e.g. Pearson's correlation) outperformed distance-based metrics (e.g. Euclidean distance). To test if the use of correlation-based metrics can benefit the recently published clustering techniques for scRNA-seq data, we modified a state-of-the-art kernel-based clustering algorithm (SIMLR) using Pearson's correlation as a similarity measure and found significant performance improvement over Euclidean distance on scRNA-seq data clustering. These findings demonstrate the importance of similarity metrics in clustering scRNA-seq data and highlight Pearson's correlation as a favourable choice. Further comparison on different scRNA-seq library preparation protocols suggests that they may also affect clustering performance. Finally, the benchmarking framework is available at http://www.maths.usyd.edu.au/u/SMS/bioinformatics/software.html.

Psychosocial stratification of antenatal indicators to guide population-based programs in perinatal depression.

BACKGROUND: There is increasing awareness that perinatal psychosocial adversity experienced by mothers, children, and their families, may influence health and well-being across the life course. To maximise the impact of population-based interventions for optimising perinatal wellbeing, health services can utilise empirical methods to identify subgroups at highest risk of poor outcomes relative to the overall population. METHODS: This study sought to identify sub-groups using latent class analysis within a population of mothers in Sydney, Australia, based on their differing experience of self-reported indicators of psychosocial adversity. This study sought to identify sub-groups using latent class analysis within a population of mothers in Sydney, Australia, based on their differing experience of self-reported indicators of psychosocial adversity. Subgroup differences in antenatal and postnatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. RESULTS: Latent class analysis identified four distinct subgroups within the cohort, who were distinguished empirically on the basis of their native language, current smoking status, previous involvement with Family-and-Community Services (FaCS), history of child abuse, presence of a supportive partner, and a history of intimate partner psychological violence. One group consisted of socially supported 'local' women who speak English as their primary language (Group L), another of socially supported 'migrant' women who speak a language other than English as their primary language (Group M), another of socially stressed 'local' women who speak English as their primary language (Group Ls), and socially stressed 'migrant' women who speak a language other than English as their primary language (Group Ms.). Compared to local and not socially stressed residents (L group), the odds of antenatal depression were nearly three times higher for the socially stressed groups (Ls OR: 2.87 95%CI 2.10-3.94) and nearly nine times more in the Ms. group (Ms OR: 8.78, 95%CI 5.13-15.03). Antenatal symptoms of depression were also higher in the not socially stressed migrant group (M OR: 1.70 95%CI 1.47-1.97) compared to non-migrants. In the postnatal period, Group M was 1.5 times more likely, while the Ms. group was over five times more likely to experience suboptimal mental health compared to Group L (OR 1.50, 95%CI 1.22-1.84; and OR 5.28, 95%CI 2.63-10.63, for M and Ms. respectively). CONCLUSIONS: The application of empirical subgrouping analysis permits an informed approach to targeted interventions and resource allocation for optimising perinatal maternal wellbeing.

Metabolites downstream of predicted loss-of-function variants inform relationship to disease.

A small minority (< 3%) of protein-coding genetic variants are predicted to lead to loss of protein function. However, these predicted loss-of-function (pLOF) variants can provide insight into mode of transcriptional effect. To examine how these changes are propagated to phenotype, we determined associations with downstream metabolites. We performed association analyses of 37 pLOF variants - previously reported to be significantly associated with disease in >400,000 subjects in UK Biobank - with metabolites. We conducted these analyses in three community-based cohorts: the Framingham Heart Study (FHS) Offspring Cohort, FHS Generation 3, and the KORA F4 cohort. We identified 19 new low-frequency or rare (minor allele frequency (MAF) <5%) pLOF variant-metabolite associations, and 12 new common (MAF > 5%) pLOF variant-metabolite associations. Rare pLOF variants in the genes BTN3A2, ENPEP, and GEM that have been associated with blood pressure in UK Biobank, were associated with vasoactive metabolites indoxyl sulfate, asymmetric dimethylarginine (ADMA), and with niacinamide, respectively. A common pLOF variant in gene CCHCR1, associated with asthma in UK Biobank, was associated with histamine and niacinamide in FHS Generation 3, both reported to play a role in this disease. Common variants in olfactory receptor gene OX4C11 that associated with blood pressure in UK Biobank were associated with the nicotine metabolite cotinine, suggesting an interaction between altered olfaction, smoking behaviour, and blood pressure. These findings provide biological validity for pLOF variant-disease associations, and point to the effector roles of common metabolites. Such an approach may provide novel disease markers and therapeutic targets.

Gram Scale Conversion of R-BINAM to R-NOBIN.

A mild, operationally simple, and single-step transition-metal-free protocol for the synthesis of enantiomerically pure (R)-(+)-2'-amino-1,1'-binaphthalen-2-ol (R-NOBIN) from (R)-(+)-1,1'-binaphthyl-2,2'-diamine (R-BINAM) is reported. The one-pot conversion proceeds with good yield and shows no racemization. The hydroxyl on the R-NOBIN product was shown to have come from water in the reaction medium via an H2(18)O study. The correct value of the specific rotation of R-NOBIN was reported.

Fine-tuning Large Language Models for Rare Disease Concept Normalization.

Objective: We aim to develop a novel method for rare disease concept normalization by fine-tuning Llama 2, an open-source large language model (LLM), using a domain-specific corpus sourced from the Human Phenotype Ontology (HPO). Methods: We developed an in-house template-based script to generate two corpora for fine-tuning. The first (NAME) contains standardized HPO names, sourced from the HPO vocabularies, along with their corresponding identifiers. The second (NAME+SYN) includes HPO names and half of the concept's synonyms as well as identifiers. Subsequently, we fine-tuned Llama2 (Llama2-7B) for each sentence set and conducted an evaluation using a range of sentence prompts and various phenotype terms. Results: When the phenotype terms for normalization were included in the fine-tuning corpora, both models demonstrated nearly perfect performance, averaging over 99% accuracy. In comparison, ChatGPT-3.5 has only ~20% accuracy in identifying HPO IDs for phenotype terms. When single-character typos were introduced in the phenotype terms, the accuracy of NAME and NAME+SYN is 10.2% and 36.1%, respectively, but increases to 61.8% (NAME+SYN) with additional typo-specific fine-tuning. For terms sourced from HPO vocabularies as unseen synonyms, the NAME model achieved 11.2% accuracy, while the NAME+SYN model achieved 92.7% accuracy. Conclusion: Our fine-tuned models demonstrate ability to normalize phenotype terms unseen in the fine-tuning corpus, including misspellings, synonyms, terms from other ontologies, and laymen's terms. Our approach provides a solution for the use of LLM to identify named medical entities from the clinical narratives, while successfully normalizing them to standard concepts in a controlled vocabulary.

Fine-tuning large language models for rare disease concept normalization.

OBJECTIVE: We aim to develop a novel method for rare disease concept normalization by fine-tuning Llama 2, an open-source large language model (LLM), using a domain-specific corpus sourced from the Human Phenotype Ontology (HPO). METHODS: We developed an in-house template-based script to generate two corpora for fine-tuning. The first (NAME) contains standardized HPO names, sourced from the HPO vocabularies, along with their corresponding identifiers. The second (NAME+SYN) includes HPO names and half of the concept's synonyms as well as identifiers. Subsequently, we fine-tuned Llama 2 (Llama2-7B) for each sentence set and conducted an evaluation using a range of sentence prompts and various phenotype terms. RESULTS: When the phenotype terms for normalization were included in the fine-tuning corpora, both models demonstrated nearly perfect performance, averaging over 99% accuracy. In comparison, ChatGPT-3.5 has only ∼20% accuracy in identifying HPO IDs for phenotype terms. When single-character typos were introduced in the phenotype terms, the accuracy of NAME and NAME+SYN is 10.2% and 36.1%, respectively, but increases to 61.8% (NAME+SYN) with additional typo-specific fine-tuning. For terms sourced from HPO vocabularies as unseen synonyms, the NAME model achieved 11.2% accuracy, while the NAME+SYN model achieved 92.7% accuracy. CONCLUSION: Our fine-tuned models demonstrate ability to normalize phenotype terms unseen in the fine-tuning corpus, including misspellings, synonyms, terms from other ontologies, and laymen's terms. Our approach provides a solution for the use of LLMs to identify named medical entities from clinical narratives, while successfully normalizing them to standard concepts in a controlled vocabulary.

Validation of the American College of Surgeons National Surgical Quality Improvement Program risk predictor in an Australian general surgical cohort.

BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator from the American College of Surgeons is a widely available tool for peri-operative risk prediction. This study investigates its predictive performance in an Australian setting. METHODS: A single-centre retrospective external validation study was conducted at a tertiary referral centre in New South Wales, Australia. Data from a general surgical cohort in a 2-year period from 2020 to 2021 was collected from the NSQIP database and entered into the NSQIP calculator. The predictive performance of the calculator was analysed across the standard 14 NSQIP postoperative outcome measures at 30 days. RESULTS: There were 2121 patient records analysed using tests of accuracy and in the discrimination and calibration domains. The overall predictive performance of the NSQIP calculator was reasonable. There was greater accuracy at lower-risk predictions. At higher-risk predictions, Readmission, Death, and Discharge to Nursing or Rehab Facility, and Length of Stay were overestimated, whilst other outcomes were underestimated. CONCLUSION: This study demonstrates reasonable overall performance of the NSQIP calculator in the context of this cohort and provides data to support the need for locally adapted and validated risk prediction tools for use by Australian perioperative physicians.

Finerenone: Efficacy of a New Nonsteroidal Mineralocorticoid Receptor Antagonist in Treatment of Patients With Chronic Kidney Disease and Type 2 Diabetes.

Mineralocorticoid receptor stimulation by aldosterone can cause various cardiovascular and renal disease complications. Finerenone is a new oral nonsteroidal mineralocorticoid receptor antagonist that has been approved for clinical use by the Federal Drug Aministration, and has been shown in clinical trials to reduce the risk of sustained estimated glomerular filtration rate decline, end-stage renal disease, nonfatal myocardial infarction, hospitalization for heart failure and cardiovascular death in adult patients with chronic kidney disease associated with type 2 diabetes. The drug has also been shown to have fewer side effects than the steroidal mineralocorticoid receptor antagonists like spironolactone and eplerenone. In this review article, the authors will discuss the clinical pharmacology of finerenone, its clinical application and the additional studies that are now underway to further assess the efficacy of the drug in diabetic patients having cardiac and renal disease.

Diastolic Dysfunction and Atrial Fibrillation: Recognition, Interplay, and Management.

Diastolic dysfunction occurs when the left ventricle loses its ability to relax normally, impairing ventricular filling during diastole. This most commonly occurs as a pathological sequela of left ventricular hypertrophy and remodeling due to chronic hypertension and/or age-related sclerotic changes of the aortic valve. This can subsequently deteriorate to diastolic heart failure or heart failure with preserved ejection fraction. There is a substantive interplay between atrial fibrillation and diastolic dysfunction, as atrial fibrillation can cause, exacerbate, or be a direct result of diastolic dysfunction and vice versa. In this review, we first independently define diastolic heart failure and atrial fibrillation while discussing the diagnostic guidelines, which encompass various modalities such as medical history, electrocardiography, echocardiography, and laboratory tests. We subsequently examine their interplay and pathophysiological links drawing on recent evidence in the literature. Finally, we discuss management approaches, including pharmacological interventions targeting rate and rhythm control, diuretics, and addressing comorbidities.

The Impact of Long COVID-19 on the Cardiovascular System.

Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.