bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging Myocardial Innervation by SPECT and PET
Authors: Travin Mark I.
Published: February 2024

Nuclear cardiology, able to directly assess underlying pathophysiology, is uniquely advantageous for assessing cardiac autonomic innervation that plays a crucial role in proper cardiovascular function. Cardiac disease disrupts this innervation, contributing to and being a marker for disease severity and worsened patient outcome. Sympathetic and parasympathetic components can be imaged with radiotracers, with current clinical applications limited to analogs of the sympathetic mediator norepinephrine, mostly with the adrenergic SPECT tracer iodine-123 metaiodobenzylguanidine (123I-mIBG) and the PET tracer 11C-hydroxyephedrine. Sympathetic innervation image analysis involves determining global cardiac radiotracer uptake and retention on planar displays, and regional uptake patterns on tomography. Image findings consistently demonstrate ability to risk stratify patients with advanced heart failure and associated potentially lethal ventricular arrhythmias independently of, and often better than, conventional clinical, ECG, serum, and imaging modalities, in particular able to identify extremely low short-term risk subgroups. Cardiac innervation imaging has potential to better guide use of invasive, costly electronic devices, especially improved selection of patients for an implantable cardioverter defibrillator. Such clinical implementation of innervation imaging has been hampered by lack of the randomized clinical trials required for acceptance. There are promising studies using innervation imaging to guide ventricular and atrial arrhythmia ablation. Given the ubiquitous role of innervation in cardiovascular processes, innervation imaging also shows promise for evaluating coronary disease risk, following heart transplant patients, detecting dangers from diabetes, and monitoring deleterious chemotherapy effect. The technique can be advanced through improved imaging hardware and analysis software, and development of new, especially PET, radiotracers.
Physician Certification and Laboratory Accreditation
Authors: Hendel Robert C. , Park Minnsun K. , Sidhu Gursukhmandeep S.
Published: February 2024

Physician certification and laboratory accreditation are two major components of quality assurance and the optimal performance of a nuclear cardiology program. Physician certification is a process by which a physician receives professional recognition for having achieved the necessary knowledge, skills, and experience in a specific field. Different pathways for certification are available, often based on prerequisites depending on the candidate’s training background, experience, and location of training. Laboratory accreditation is an analytical process that provides stringent national standards to ensure a high level of quality, hopefully with a direct impact on patient care. The process may usually be completed in 3 to 6 months and is valid for up to 3 years. Accreditation may be done via national CMS-certified agencies, each with individual established rigorous criteria. Accreditation is an independent peer-review process with the objective of overall improvement in the quality of the nuclear laboratory. Accreditation is an ongoing effort striving for uninterrupted value to confirm adherence to high-quality care.
Radiation Considerations in Imaging
Authors: Einstein Andrew J.
Published: February 2024

As a group of procedures involving exposure of patients and providers to ionizing radiation, nuclear cardiac imaging studies should adhere to the fundamental principles of radiological protection: justification, optimization, and dose limitation. Justification refers to ensuring that the right test is performed for the right patient at the right time, and is aided by Appropriate Use Criteria developed by professional societies. Optimization, often framed in terms of the as low as reasonably achievable (ALARA) principle, refers to ensuring that the test is performed in the right manner while ensuring diagnostic image quality. There are a variety of approaches to optimization in nuclear cardiac imaging, including utilizing stress-first/stress-only 99mTc protocols, selecting administered activities reflecting a patient’s habitus, avoiding protocols incorporating 201Tl as a perfusion tracer, and using technological advances in software and hardware instrumentation, such as positron emission tomography or solid-state cameras, which permit reduced radiation dose from radiopharmaceuticals without loss of image quality. Dose limitation is not applicable in the context of radiologic protection of patients, but dose limits for health care workers and the general public remain important aspects of radiological protection. This chapter addresses a variety of radiation-related considerations in nuclear cardiac imaging, reflecting each of these principles of protection.
Measurement of Myocardial Blood Flow by PET
Authors: Schelbert Heinrich R.
Published: February 2024

MBF measurements of MBF with PET have now become widely available for clinical use. Such measurements expand the scope of MPI for the detection of obstructive coronary artery disease; they offer noninvasive assessment of functional consequences of flow-limiting disease of the epicardial conduit vessels but also of functional or structural alterations of the microvascular circulation. Besides O-15 water and N-13 ammonia, Rb-82, supplied ready for use with a clinically practical generator system, has become the most widely used flow tracer. Fundamental to flow measurements is knowledge of the tissue tracer kinetics of the radiotracer and their description by a tracer compartment model, that, when applied to the arterial radiotracer input function and the myocardial radiotracer uptake response to it, both captured from serially acquired PET images, yield quantitative estimates of global and regional MBF. Noninvasive estimates of flow have been validated against microsphere-measured flows. Commercial software packages facilitated the clinical use of PET MBF measurements; they re-sort and process the dynamically acquired image data and report values of rest and hyperemic stress flows and of the myocardial flow reserves in quantitative units. Highly automated, they reduce intra- and inter-observer as well as test-retest variabilities. Yet, estimates of MBF and, of myocardial flow reserves differ between software packages, with additional variabilities imposed by type of radiotracer and the imaging device with specific image-reconstruction algorithms. Harmonization across imaging platforms will therefore be essential for flow estimates to become comparable across institutions and for widespread use and acceptance.
Myocardial Viability Assessment by Nuclear Techniques
Authors: Dilsizian Vasken , Valenta Ines , Schindler Thomas H.
Published: February 2024

Viability assessment with cardiac FDG-PET/CT is commonly applied in ischemic cardiomyopathy patients with an LVEF of 35% or less and pronounced segmental wall-motion disturbances (severe hypokinesis to akinesis, or dyskinesis). The combined application of rest perfusion imaging and FDG-PET/CT may unmask “match” findings between perfusion and viability assessment, indicative of transmural necrosis or non-transmural necrosis and no ischemic component, and “mismatch” findings, denoting non-transmural necrosis with viable but ischemic, compromised myocardium, or completely viable and ischemic, and compromised myocardium. In about 20% to 40% of these patients, FDG-PET/CT is likely to detect a sufficient amount of viable myocardium, unmasking viable but ischemic, compromised myocardium. Cardiomyopathy patients with mismatch-defined hibernating-stunned myocardium in dysfunctional wall segments, if large enough (at least four segments), who undergo coronary revascularization are likely to benefit in terms of both recovery of LV function and clinical outcome. However, no such benefit is commonly observed for those with “match” findings, and optimized medical heart failure treatment may be preferred. Predominantly viable but ischemic, compromised myocardium may have a positive predictive value of up to 74% for functional recovery after coronary revascularization. Thus, in about 16% of patients with classical “mismatch” findings, the restoration of coronary flow may not translate into recovery of LV function due to an advanced remodeling process with interstitial fibrosis and structural disintegration of cardiomyocytes, whereas improvement in clinical outcome may still ensue.
Artificial Intelligence and Nuclear Imaging
Authors: Miller Robert J. H. , Slomka Piotr J.
Published: February 2024

Artificial intelligence (AI) has become an increasingly important tool, with rapidly expanding implications for use in the field of nuclear cardiology. In this chapter the authors first review common terminology used in AI, including the differences between deep learning and classical machine learning. The potential role for AI to improve image processing or image segmentation is discussed, followed by the potential clinical role for AI in assisting with image reporting and the evidence for the use of AI to improve the diagnosis of disease or to predict risk. The authors conclude the chapter by reviewing potential clinical applications of AI and methods to improve its implementation.
The Role of Nuclear Cardiology in the Management of Cardiovascular Diseases in Patients Living with HIV
Authors: Aljizeeri Ahmed , Al-Mallah Mouaz H.
Published: February 2024

The introduction of highly active retroviral therapy in the last decade of the 20th century has changed the natural history of HIV infection. HIV evolved from an acute infectious process to a chronic stable condition with improved survival. With near-normal life expectancy, people living with HIV have a higher risk of cardiovascular diseases due to aging and an increased prevalence of traditional risk factors in addition to other factors associated with HIV infection and antiretroviral therapy. Nuclear cardiology is one of the cornerstones of the evaluation and management of a broad spectrum of cardiovascular diseases. This chapter summarizes the role of nuclear cardiology in the initial evaluation and management of cardiovascular diseases in people living with HIV.
Nuclear Imaging in Cardio-Oncology
Authors: Harinstein Matthew E. , Russell Raymond
Published: February 2024

Chemotherapeutic agents can cause a variety of cardiovascular toxicities that are unique to the specific drug that is being used to treat a cancer. The field of cardio-oncology focuses on recognizing those toxicities and utilizing noninvasive imaging as well as biomarkers to predict the risk of cardiotoxicity and to prevent or mitigate that toxicity. Nuclear cardiac imaging plays an important role in the prevention and detection of cardiotoxicity, during, immediately after, and years after cancer treatment, not only for well-characterized agents such as anthracyclines and trastuzumab but also for the newer molecularly targeted chemotherapeutic agents. This chapter reviews the important role of nuclear cardiac imaging in the management of patients with cancer.
Radionuclide Imaging in Patients with Congenital Heart Diseases
Authors: Partington Sara L. , Dorbala Sharmila
Published: February 2024

Patients with congenital heart disease (CHD) are at risk for myocardial ischemia due to coronary abnormalities from their CHD, atherosclerotic coronary artery disease, and iatrogenic complications from procedures and surgeries. Radionuclide imaging with SPECT or PET has a key role in evaluating cardiovascular diseases in adults and is emerging as an invaluable tool in select patients with CHD to assess for ischemia. Appreciating the physiologic state, congenital heart anatomy, and proposed mechanism of ischemia prior to initiating a stress radionuclide study ensures that the stress component of the study can be performed safely and effectively with acquisition of appropriate physiologic information. Understanding the CHD anatomy ensures that there is accurate interpretation of the myocardial perfusion imaging, particularly that the perfusion of the appropriate ventricle is assessed and patch and prosthetic material are taken into account. Nuclear medicine can also assess for device infections and pulmonary artery flow, frequent concerns in CHD. Planning the study to allow for the lowest possible radiation dose enhances the safety of studies in patients with CHD and allows for radionuclide imaging to be a safe and effective tool in assessing patients with CHD.
Gastrointestinal Motility Disorders,
Authors: Wang Xiao Jing (Iris)
Published: February 2024

Motility disorders result from impaired control of the neuromuscular apparatus of the gut. Symptoms vary according to which portion of the gastrointestinal tract is affected. Motility disorders specifically affecting the esophagus and colon are addressed in other chapters of this book and can lead to symptoms such as dysphagia (ineffective esophageal peristalsis, achalasia) or constipation (slow transit constipation). Gastroparesis, which affects the stomach, and intestinal pseudo-obstruction, which affects the small intestine and colon, are motility disorders that can cause symptoms of recurrent or chronic nausea, vomiting, bloating and abdominal discomfort, constipation, or diarrhea, all of which occur in the absence of a structural lesion.
Clinical Features of Malabsorptive Disorders, Small-Bowel Diseases, and Bacterial Overgrowth Syndromes
Authors: Oxentenko Amy S.
Published: February 2024

Both malabsorption (a defect in the mucosal absorption of nutrients) and maldigestion (a defect in the hydrolysis of nutrients) imply disordered physiologic mechanisms in the gastrointestinal system. Malabsorption and maldigestion of nutritional substrates can occur in multiple phases: 1) the luminal phase, in which there is contact between ingested food and various digestive enzymes; 2) the mucosal phase, in which substances are assimilated and absorbed in the required constituent form; and 3) the delivery phase, in which nutrients are taken up into the cytoplasm and transported to the lymphatics or portal venous system.
Nutritional Disorders: Vitamins and Minerals
Authors: Arora Amindra S.
Published: February 2024

Vitamins and minerals are critical for normal health because they are essential in a vast assortment of metabolic functions. This chapter focuses on selected important vitamins and minerals and their relationships with gastrointestinal tract disorders. Iron deficiency can result in microcytic hypochromic anemia, altered immune function, angular stomatitis, koilonychia, and atrophic lingual papillae. Causes of iron deficiency include lack of dietary iron, increased gastrointestinal loss of iron (bleeding), poor absorption of iron (celiac disease), surgical procedures that bypass the duodenum, achlorhydria, and Helicobacter pylori infection.
Vascular Disorders of the Gastrointestinal Tract
Authors: Sweetser Seth R.
Published: February 2024

Mesenteric ischemia (MI) includes several clinical conditions that occur when splanchnic blood flow is inadequate and thus fails to meet the metabolic demands of the intestines. The condition can result in symptomatic and life-threatening clinical presentations. The incidence of MI is increasing because of the aging population, increasing number of critically ill patients, and heightened clinical awareness. MI produces a spectrum of disorders that depend on many factors, including the acuity of the event, the vessel involved, and the length of bowel affected. In general, MI can be divided into 4 clinical syndromes: acute mesenteric ischemia, chronic mesenteric ischemia, colonic ischemia, and focal segmental ischemia. These 4 syndromes account for most manifestations of ischemic injury to the gut. This chapter reviews the epidemiology, pathophysiology, clinical presentation, and management of these conditions and discusses other vascular syndromes of the gastrointestinal tract.
Irritable Bowel Syndrome
Authors: Vijayvargiya Priya , Prichard David O.
Published: February 2024

Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits in the absence of detectable biochemical or structural abnormalities. The goal of therapy is to improve the patient’s symptoms, prevent suffering, and improve quality of life. Altered bowel habits and abdominal pain may need to be treated independently. The bidirectional relationship between gastrointestinal symptoms and psychological issues is well established, and behavioral therapies are effective. The diagnosis of IBS is symptom based. Routine serologic screening for celiac disease in patients with IBS is recommended. Initial treatment involves lifestyle and dietary modifications with symptomatic remedies. Patients with persistent gastrointestinal symptoms despite these initial measures should undergo tests to identify causative factors.
Viral Hepatitis,
Authors: Leise Michael D.
Published: February 2024

Viral infections are important causes of liver disease worldwide. The 5 primary hepatitis viruses that have been identified are A, B, C, D (or delta), and E. Other viruses, such as cytomegalovirus and Epstein-Barr virus, also can result in hepatitis as part of a systemic infection. In addition, medications, toxins, autoimmune hepatitis, or Wilson disease may cause acute or chronic hepatitis. It is useful to divide hepatitis syndromes into acute and chronic forms. Acute hepatitis can last from a few weeks to 6 months and is often accompanied by jaundice. Symptoms of acute hepatitis tend to be similar regardless of cause and include anorexia, malaise, dark urine, fever, and mild abdominal pain. In chronic hepatitis, patients are often asymptomatic but may complain of fatigue.
Alcohol-Related Liver Disease
Authors: Huebert Robert C. , Shah Vijay H.
Published: February 2024

Alcoholic liver disease is a major cause of morbidity and mortality worldwide. Globally, approximately 2 billion people consume alcohol, and alcohol use disorder is diagnosed in more than 75 million people—and these numbers are probably underestimates. In the US, chronic liver disease is the 12th leading cause of death, and alcohol is implicated in approximately 50% of these deaths. Also, alcoholic liver disease is a major source of health care expenditures, accounting for nearly $5 billion annually. Alcohol-related liver disease is the leading indication for liver transplant in the US. Recent increases in deaths due to alcohol-related liver disease are skewed toward younger age groups (25-34 years), and deaths due to alcohol-related liver disease are projected to increase in the coming years, particularly among women.
Vascular Diseases of the Liver
Authors: Kulai Tasha B. , Sanchez William
Published: February 2024

Vascular diseases of the liver can be divided into disorders of hepatic inflow (ie, disorders of portal venous inflow and disorders of hepatic arterial inflow) and disorders of hepatic venous outflow. For a better understanding of the vascular diseases of the liver, a concise review of the vascular anatomy of the liver is important. The splanchnic circulation comprises the arterial blood supply and venous drainage of the entire gastrointestinal tract from the distal esophagus to the midrectum and includes the spleen (which is why splenomegaly and thrombocytopenia develop in the presence of portal hypertension), pancreas, gallbladder, and liver.
Acute Pancreatitis
Authors: Maselli Daniel B. , Chandrasekhara Vinay
Published: February 2024

Acute pancreatitis is an inflammatory condition characterized by severe abdominal pain and both locoregional and systemic inflammatory complications. More than 200,000 new cases of acute pancreatitis occur in the US each year, and the incidence is increasing. The disease is severe in 20% of patients with acute pancreatitis, and approximately 5% of all patients with pancreatitis die of the disease. Hence, key management principles include prompt diagnosis, triage of patients with severe pancreatitis to aggressive care, and identification of the underlying cause to prevent recurrence. Necrotizing pancreatitis accounts for most of the morbidity and nearly all the mortality associated with acute pancreatitis.
Chronic Pancreatitis
Authors: Janssens Laurens P. , Majumder Shounak
Published: February 2024

Chronic pancreatitis is an inflammatory condition of the pancreas characterized by progressive fibrosis that leads to irreversible destruction of exocrine and endocrine tissue, resulting eventually in exocrine and endocrine insufficiency. There is considerable heterogeneity in the manifestation and natural history of the condition. Chronic pancreatitis is classified broadly into chronic calcifying pancreatitis, chronic obstructive pancreatitis, and chronic autoimmune pancreatitis. Chronic calcifying pancreatitis is usually characterized by recurrent bouts of clinically acute pancreatitis early in the course of the disease and development of intraductal stones later in the disease course. Steatorrhea and diabetes mellitus eventually develop in most patients. This is the clinical profile of the disease that readily comes to mind when the term chronic pancreatitis is used in clinical practice.
Pancreatic Neoplasms
Authors: De La Fuente Jaime , Majumder Shounak
Published: February 2024

Pancreatic ductal adenocarcinoma (PDAC), sometimes referred to as pancreatic cancer, is a leading cause of cancer death in the US. In 2021 in the US, an estimated 60,430 new cases of PDAC occurred, and 48,220 people died of the disease. Although only 3.2% of new cancer diagnoses in the US were PDAC, it accounts for 7.9% of all cancer deaths. The worldwide trend shows increasing PDAC incidence and mortality. Survival has improved in recent years, but the overall 5-year survival is only about 11%; it is nearly 50% among persons with a diagnosis of localized disease. Less than 20% of patients are candidates for surgical resection, and more than 50% have metastatic disease at the time of diagnosis. In the US, the lifetime risk for PDAC is approximately 1.6%, and the risk increases with age.
An 84-Year-Old Man With Chronic Obstructive Pulmonary Disease and Cirrhosis
Authors: Vashistha Kirtivardhan , Kashyap Rahul , Patel Ashokakumar M.
Published: February 2024

α1-Antitrypsin deficiency is an underdiagnosed, widely prevalent systemic disease, and clinicians should maintain a high degree of awareness during evaluation of patients with chronic obstructive pulmonary disease, unexplained liver disease, or specific skin manifestations. Early identification helps provide specific therapy for patients, improve prognosis, and decrease associated morbidity and mortality. Therapy should be based on the patient’s candidacy and comorbidities and on the risks, benefits, and cost of treatment.
A 66-Year-Old Man With Fatigue, Dyspnea, and Hypoxemia
Authors: Bourne Michael , Diedrich Daniel A.
Published: February 2024

Methemoglobinemia can be congenital or acquired. Congenital methemoglobinemia is secondary to enzymatic deficiencies that result in decreased reduction of methemoglobin. Acquired methemoglobinemia is most commonly caused by drugs, but other sources of oxidative stress, such as surgical procedures, have been implicated. The diagnosis of methemoglobinemia requires a high degree of clinical awareness and corresponding ABG and co-oximetry results.
A 45-Year-Old Man With Worsening Dyspnea and Hypoxemia
Authors: Myers Melissa K. , Wylam Mark E. , Rishi Muhammad A.
Published: February 2024

Pulmonary alveolar proteinosis is caused by excess accumulation of surfactant within alveoli and results in a crazy-paving pattern on computed tomography. Pulmonary alveolar proteinosis may be categorized as congenital, autoimmune (most commonly), or secondary. Diagnosis is made with positive periodic acid–Schiff staining of bronchoalveolar lavage fluid, transbronchial biopsy, or surgical lung biopsy. Whole-lung lavage improves gas exchange immediately. Established alternatives are granulocyte-macrophage colony-stimulating factor supplementation or granulocyte-macrophage colony-stimulating factor antibody depletion.
A 59-Year-Old Woman With Progressive Dyspnea Undergoing Evaluation for Lung Transplant
Authors: Zhang Zhenmei , Peters Steve G.
Published: February 2024

Pulmonary alveolar microlithiasis is a rare autosomal recessive disorder that is characterized by intra-alveolar accumulation of microliths and a sandstorm appearance on chest radiography. The only currently available and effective therapy for pulmonary alveolar microlithiasis is lung transplant. Appropriate patients with progressive, chronic lung disease should be referred to transplant centers in a timely manner to complete the comprehensive multidisciplinary evaluation.
A 52-Year-Old Woman With Arthralgias, Hair Loss, and Skin Ulcers
Authors: Varghese Cyril , Ryu Jay H.
Published: February 2024

Pulmonary Langerhans cell histiocytosis (PLCH) is a diffuse cystic lung disease related to smoking in adults. The disease may coexist with other smoking-related conditions, including respiratory bronchiolitis, DIP, and emphysema. Decreased Dlco is the most common finding on pulmonary function testing. Extrapulmonary involvement, mainly with bone and pituitary involvement, occurs in 10% to 15% of adults with smoking-related PLCH. Treatment of PLCH is mainly smoking cessation; rarely, corticosteroids and cladribine are used if the disease continues to progress despite smoking cessation. Complications of PLCH include spontaneous pneumothorax, pulmonary hypertension, and increased risk of malignancies.
A 68-Year-Old Man With Dyspnea and Multiple Pulmonary Nodules
Authors: Canepa Scott M. , Stroh Gregory R. , Ryu Jay H.
Published: February 2024

The differential diagnosis of pulmonary nodules is broad and encompasses various systemic and lung-limited diseases. An organized and algorithmic diagnostic approach is necessary to formulate and narrow an accurate differential diagnosis. The present case demonstrates how the use of such an approach with key features of the clinical history can direct a focused and successful diagnostic investigation.
A 71-Year-Old Woman With a Nodule in the Right Lung
Authors: Veerabattini Naresh K. , Aragon Pinto Catarina N. , Hoskote Sumedh S.
Published: February 2024

Oligometastatic adenocarcinoma of the lung is a distinct subset of stage IV oligometastatic non–small cell lung cancer that potentially carries a better prognosis. In the early course of the disease, surgery or radiotherapy for local control therapy should be considered before systemic therapy. Guidelines recommend performing molecular testing and PD-L1 testing for all patients with metastatic adenocarcinomas.
A 60-Year-Old Man With Fever, Cough, and Fatigue 2 Months After Bilateral Lung Transplant
Authors: Cecchini Matthew J. , Roden Anja C.
Published: February 2024

Acute cellular rejection is a common and important cause of graft dysfunction and failure after lung transplant. It is graded histologically according to the degree of inflammation surrounding the vessels and small airways. Patients with high-grade A4 rejection also have features of acute lung injury. Even mild rejection is often treated with increased immunosuppression. Infectious causes and other mimics of rejection should always be considered.
A 57-Year-Old Man With a History of Recurrent Epistaxis and Arteriovenous Malformations
Authors: Iyer Vivek N. , Ahluwalia Vaibhav
Published: February 2024

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. Spontaneous and recurrent epistaxis is a cardinal symptom of HHT, and its presence should alert the clinician to the possibility of HHT. Antiangiogenic therapies have been very effective for the management of HHT-related epistaxis and gastrointestinal tract bleeding. Patients and their family members with HHT should seek care at an accredited HHT Center of Excellence, where a comprehensive plan for screening diagnostic tests and discussions about therapeutic options can be undertaken without delay.
Early Versus Late Antipseudomonal β-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study
Authors: Aldardeer Namareq F , Alshreef Maram M , Alharbi Emad A , Aljabri Ahmad K , Aljawadi Mohammad H , Almangour Thamer A , Alobaili Saad , Alarifi Mohammed I , Alomari Awad , Alhammad Abdullah M
Published: February 2024

Background

Acute kidney injury (AKI) is a common complication of sepsis, contributing to an increased mortality rate. However, some studies have demonstrated that renal function improves in sepsis patients with AKI within 48 hours, raising questions about the necessity for early antibiotic adjustment. This study evaluates the association between the timing of antipseudomonal β-lactam dose adjustment and the outcomes of critically ill sepsis patients with AKI.

Methods

A prospective, multicenter observational study of critically ill patients aged ≥18 years admitted to the intensive care unit with sepsis and AKI and started on antipseudomonal β-lactam therapy. After the initial dose, eligible patients were grouped as early β-lactam antibiotic (E-BLA) or late β-lactam antibiotic (L-BLA) dose adjustments based on the administration of subsequent renally adjusted doses within 24 hours and after 24 hours of sepsis recognition, respectively. The main outcome of interest was in-hospital mortality.

Results

Among 1185 patients screened, 224 (mean age, 62.7 ± 16.8 years; 62% were male) met inclusion criteria. Eighty-four and 140 patients were included in the E-BLA and L-BLA groups, respectively. Approximately half of the cohort presented with AKI stage II, and piperacillin-tazobactam was prescribed as initial empirical therapy in more than 50% of the cohort. In the multivariable Cox proportional hazards model, L-BLA was associated with a significant reduction in in-hospital mortality compared to E-BLA (hazard ratio, 0.588 [95% confidence interval, .355–.974]).

Conclusions

In sepsis patients with AKI, L-BLA was associated with in-hospital mortality benefits.
Landscape and Saturation Analysis of Mutations Associated With Race in Cancer Genomes by Clinical Sequencing
Authors: Muquith Maishara , Hsiehchen David
Published: February 2024

Differences in cancer genomes between racial groups may impact tumor biology and health disparities. However, the discovery of race-associated mutations is constrained by the limited representation and sample size of different racial groups in prior genomic studies. We evaluated the influence of race on the frequency of gene mutations using the Genomics, Evidence, Neoplasia, Information, Exchange database, a large genomic dataset aggregated from clinical sequencing. Matched cohort analyses were used to identify histology-specific race-associated mutations including increased TERT promoter mutations in Black and Asian patients with gliomas and bladder cancers, and a decreased frequency of mutations in DNA repair pathway genes and subunits of the SWI/SNF chromatin complex in Asian and Black patients across multiple cancer types. The distribution of actionable mutations in oncogenes was also race-specific, demonstrating how targeted therapies may have a disparate impact on racial groups. Down-sampling analyses indicate that larger sample sizes are likely to discover more race-associated mutations. These results provide a resource to understand differences in cancer genomes between racial groups which may inform the design of clinical studies and patient recruitment strategies in biomarker trials.
Endocrinology’s early historians (1889-1914) and the forgotten prehistory of testosterone
Authors: Janssen Diederik F
Published: February 2024

Introduction

An often-retold historical outline of endocrinology was established over a century ago. An exhaustive history of sexual physiology remains forthcoming, however.

Objectives

To explore and contextualize the remarkable medical-historical and medical-anthropologic frenzy triggered by Brown-Séquard’s 1889 self-injections with testicular juice, which ultimately settled down into an early history of endocrinology.

Methods

Pertinent primary sources were selected from a broader study, primarily between 1889 and 1914, as well as selected older texts identified and unidentified by these sources.

Results

Endocrinology’s early historians in a short space of time moved from the history of testicular opotherapy to that of glandular typology and physiology and to increasingly encompassing medical-historical accounts of internal secretion as an epochal idea. Early historians nominated “precursors” to Brown-Séquard but underestimated physiologic continuities—specifically, early modern protoendocrinologic notions concerning semen as a “recrement,” notions still recited by Brown-Séquard and early Brown-Séquardists as well their detractors. Brown-Séquard himself worked through this old (recremental) concept of semen between 1889 and 1892 but was later identified with it, by among others Ancel and Bouin.

Conclusion

Western sexual physiology is a medical palimpsest, the undertexts of which remain to be studied in detail.
Aphelenchoides besseyi Parasitizing Tobacco Cultivars in Brazil
Authors: Favoreto Luciany , Meyer Maurício Conrado , Loreto Rafaela Bueno , Calandrelli Angélica , França Patricia Pricilla , Aleandro da Silva Santino , Zamboni Machado Andressa Cristina
Published: February 2024

Foliar nematodes (Aphelenchoides spp.) are known to be parasites of tobacco in restricted areas, but symptoms caused by A. besseyi in tobacco are not well characterized, despite the great importance of this nematode worldwide. This study aimed to evaluate the host reaction of four Nicotiana tabacum cultivars (Comum, Xanthi, Samsun, and TNN) and N. benthamiana cultivar Comum to A. besseyi and to characterize the symptoms and the parasitism of this nematode. Two experiments were conducted under greenhouse conditions with controlled humidity and temperature, in which the plants were inoculated with 600 A. besseyi. At 30 days after inoculation (DAI), nematodes present in the soil, roots, and shoot parts were extracted, and roots and shoot tissues were stained with acid fuchsin. A high number of A. besseyi was obtained per gram of shoot tissues (125 to 2,169 nematodes), and severe symptoms were observed in leaves and inflorescences of all cultivars. The symptoms included foliar distortion and deformation, necrotic spots delimited by the veins, flower abortion, and poor development of plants. In addition, A. besseyi was observed to penetrate tobacco roots at 30 DAI, and nematodes were also observed in the foliar mesophyll, inflorescences, and stems, a parasitism that has not been previously reported in tobacco plants. The disease caused by A. besseyi in tobacco could be a concern for growers in southern and northeastern Brazil because this nematode can cause severe damage to the marketable leaves of tobacco, reducing its commercial value.
Lavender Harbors More Viruses than Previously Thought: First Report of Raspberry Ringspot Virus and Phlox Virus M in Lavandula × intermedia
Authors: Tang Joe , Lilly Sonia , Liefting Lia , Veerakone Stella , Ward Lisa , Thompson Jeremy R.
Published: February 2024

Plants of the genus Lavandula are thought to be rarely infected by viruses. To date, only alfalfa mosaic virus, cucumber mosaic virus, tobacco mosaic virus, and tomato spotted wilt virus have been reported in this host. In this study, we identified for the first time raspberry ringspot virus (RpRSV) and phlox virus M (PhlVM) in lavender using herbaceous indexing, enzyme-linked immunosorbent assay, and high-throughput sequencing. Nearly complete genome sequences for both viruses were determined. Phylogenetic and serological characterizations suggest that the obtained RpRSV isolate is a raspberry strain. A preliminary survey of 166 samples indicated RpRSV was spread only in the lavender cultivar ‘Grosso’, while PhlVM was detected in multiple lavender cultivars. Although RpRSV raspberry strain may have spread throughout Auckland and nearby areas in New Zealand, it is very likely restricted to the genus Lavandula or even to the cultivar ‘Grosso’ due to the absence or limited occurrence of the nematode vector. Interestingly, all infected lavender plants, regardless of their infection status (by RpRSV, PhlVM, or both) were asymptomatic. RpRSV is an important virus that infects horticultural crops including grapevine, cherry, berry fruits, and rose. It remains on the list of regulated pests in New Zealand. RpRSV testing is mandatory for imported Fragaria, Prunus, Ribes, Rosa, Rubus, and Vitis nursery stock and seeds for sowing, while this is not required for Lavandula importation. Our study revealed that lavender could play a role not only as a reservoir but also as an uncontrolled import pathway of viruses that pose a threat to New Zealand’s primary industries.
Kinesin light chain 1 stabilizes insulin receptor substrate 1 to regulate the IGF‐1‐AKT signaling pathway during myoblast differentiation
Authors: Qu Zihao , Shi Linjing , Wu Zhen , Lin Peng , Zhang Guangan , Cong Xiaoxia , Zhao Xiang , Ge Huiqing , Yan Shigui , Jiang Liangjun , Wu Haobo
Published: February 2024

The IGF signaling pathway plays critical role in regulating skeletal myogenesis. We have demonstrated that KIF5B, the heavy chain of kinesin‐1 motor, promotes myoblast differentiation through regulating IGF‐p38MAPK activation. However, the roles of the kinesin light chain (Klc) in IGF pathway and myoblast differentiation remain elusive. In this study, we found that Klc1 was upregulated during muscle regeneration and downregulated in senescence mouse muscles and dystrophic muscles from mdx (X‐linked muscular dystrophic) mice. Gain‐ and loss‐of‐function experiments further displayed that Klc1 promotes AKT–mTOR activity and positively regulates myogenic differentiation. We further identified that the expression levels of IRS1, the critical node of IGF‐1 signaling, are downregulated in Klc1‐depleted myoblasts. Coimmunoprecipitation study revealed that IRS1 interacted with the 88‐154 amino acid sequence of Klc1 via its PTB domain. Notably, the reduced Klc1 levels were found in senescence and osteoporosis skeletal muscle samples from both mice and human. Taken together, our findings suggested a crucial role of Klc1 in the regulation of IGF‐AKT pathway during myogenesis through stabilizing IRS1, which might ultimately influence the development of muscle‐related disorders.
Structural Racism and Use of Labor Neuraxial Analgesia Among Non-Hispanic Black Birthing People
Authors: Guglielminotti Jean , Lee Allison , Landau Ruth , Samari Goleen , Li Guohua
Published: February 2024

OBJECTIVE:

To assess the association between structural racism and labor neuraxial analgesia use.

METHODS:

This cross-sectional study analyzed 2017 U.S. natality data for non-Hispanic Black and White birthing people. The exposure was a multidimensional structural racism index measured in the county of the delivery hospital. It was calculated as the mean of three Black–White inequity ratios (ratios for lower education, unemployment, and incarceration in jails) and categorized into terciles, with the third tercile corresponding to high structural racism. The outcome was the labor neuraxial analgesia rate. Adjusted odds ratios and 95% CIs of neuraxial analgesia associated with terciles of the index were estimated with multivariate logistic regression models. Black and White people were compared with the use of an interaction term between race and ethnicity and the racism index.

RESULTS:

Of the 1,740,716 birth certificates analyzed, 396,303 (22.8%) were for Black people. The labor neuraxial analgesia rate was 77.2% for Black people in the first tercile of the racism index, 74.7% in the second tercile, and 72.4% in the third tercile. For White people, the rates were 80.4%, 78.2%, and 78.2%, respectively. For Black people, compared with the first tercile of the racism index, the second tercile was associated with 18.4% (95% CI, 16.9–19.9%) decreased adjusted odds of receiving neuraxial analgesia and the third tercile with 28.3% (95% CI, 26.9–29.6%) decreased adjusted odds. For White people, the decreases were 13.4% (95% CI, 12.5–14.4%) in the second tercile and 15.6% (95% CI, 14.7–16.5%) in the third tercile. A significant difference in the odds of neuraxial analgesia was observed between Black and White people for the second and third terciles.

CONCLUSION:

A multidimensional index of structural racism is associated with significantly reduced odds of receiving labor neuraxial analgesia among Black people and, to a lesser extent, White people.
Effect of Increasing Blood Pressure on Brain Tissue Oxygenation in Adults After Severe Traumatic Brain Injury*
Authors: Kunapaisal Thitikan , Lele Abhijit V. , Gomez Courtney , Moore Anne , Theard Marie Angele , Vavilala Monica S.
Published: February 2024

OBJECTIVES:

To examine if increasing blood pressure improves brain tissue oxygenation (PbtO2) in adults with severe traumatic brain injury (TBI).

DESIGN:

Retrospective review of prospectively collected data.

SETTING:

Level-I trauma center teaching hospital.

PATIENTS:

Included patients greater than or equal to 18 years of age and with severe (admission Glasgow Coma Scale [GCS] score < 9) TBI who had advanced neuromonitoring (intracranial blood pressure [ICP], PbtO2, and cerebral autoregulation testing).

INTERVENTIONS:

The exposure was mean arterial pressure (MAP) augmentation with a vasopressor, and the primary outcome was a PbtO2 response. Cerebral hypoxia was defined as PbtO2 less than 20 mm Hg (low).

MAIN RESULTS:

MAP challenge test results conducted between ICU admission days 1–3 from 93 patients (median age 31; interquartile range [IQR], 24–44 yr), 69.9% male, White (n = 69, 74.2%), median head abbreviated injury score 5 (IQR 4–5), and median admission GCS 3 (IQR 3–5) were examined. Across all 93 tests, a MAP increase of 25.7% resulted in a 34.2% cerebral perfusion pressure (CPP) increase and 16.3% PbtO2 increase (no MAP or CPP correlation with PbtO2 [both R
2 = 0.00]). MAP augmentation increased ICP when cerebral autoregulation was impaired (8.9% vs. 3.8%, p = 0.06). MAP augmentation resulted in four PbtO2 responses (normal and maintained [group 1: 58.5%], normal and deteriorated [group 2: 2.2%; average 45.2% PbtO2 decrease], low and improved [group 3: 12.8%; average 44% PbtO2 increase], and low and not improved [group 4: 25.8%]). The average end-tidal carbon dioxide (ETCO2) increase of 5.9% was associated with group 2 when cerebral autoregulation was impaired (p = 0.02).

CONCLUSIONS:

MAP augmentation after severe TBI resulted in four distinct PbtO2 response patterns, including PbtO2 improvement and cerebral hypoxia. Traditionally considered clinical factors were not significant, but cerebral autoregulation status and ICP responses may have moderated MAP and ETCO2 effects on PbtO2 response. Further study is needed to examine the role of MAP augmentation as a strategy to improve PbtO2 in some patients.
Ustekinumab Drug Levels and Outcomes in Inflammatory Bowel Disease
Authors: Petrov Jessica , Fine Sean , Alzahrani Raneem , Mohamed Gamal , Al-Bawardy Badr
Published: February 2024

Background:

Data regarding the utility of therapeutic drug monitoring with ustekinumab (UST) are sparse. Our aim was to determine the correlation of UST levels with outcomes in a cohort of patients with inflammatory bowel disease (IBD).

Methods:

This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing [the absence of ulcers/erosions in Crohn’s disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)], and normal serum C-reactive protein (CRP) (≤5 mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes.

Results:

A total of 71 patients (74.6% with CD; 57.7% female) were included. The median age was 39.5 years [interquartile range (IQR): 26 to 52] and 12.6% were on combination therapy with immunomodulators. Median UST trough levels were significantly higher in patients who achieved endoscopic healing at 5.4 µg/mL versus 3.5 µg/mL (P=0.035) and normal CRP at 5.5 µg/mL versus. 3.1 µg/mL (P=0.002). A cutoff UST level of 4.8 µg/mL yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a cutoff of 3.5 µg/mL which yielded an AUC of 0.66 (95% CI: 0.52-0.81) to predict endoscopic healing.

Conclusions:

UST trough levels were significantly higher in patients who achieved a normal CRP and endoscopic healing. A cutoff UST level of 4.8 µg/mL reliably predicted CRP normalization.
Bibliometric and visual analysis of intestinal flora and immunity
Authors: Nie Kaidi , Deng Tingting , Wang Jie , Qi Luming , Liu Nannan , Chen Zhixuan , Xia Lina
Published: February 2024

Background:

The gut microbiota and its stability have important relationships with immunity. However, bibliometric analysis in this field is underdeveloped. This study aims to visualize publications related to the gut microbiota and immunity to identify research frontiers and hotspots, providing references and guidance for further research.

Methods:

Gut microbiota and immunity data were retrieved from the Web of Science Core Collection database, and Microsoft Excel, Scimago Graphica and VOSviewer software were used to analyze publication output trends, the most productive countries/regions, journals, authors, co-cited references, and keywords.

Results:

This study analyzed 16,611 publications, including 10,865 articles and 5746 reviews, and found a continuous increase in publications related to gut microbiota and immunity since 2013. We identified 62,872 authors contributing to this field from 2144 journals and 9965 organizations/institutions in 145 countries/regions. The top publisher with the highest output is University of California System with 525 papers. Among these journals, the top 3 most prolific journals are Frontiers in Immunology, Frontiers in Microbiology, and PLOS ONE. The literature with the highest citation frequency is published in Science and has been cited 3006 times by Patrick M. Smith and others.

Gut microbiota research hotspots include gut microbiota inflammation, immune response, inflammatory bowel diseases (IBDs), and microbiota tumors. The gut microbiota and its microbial homeostasis play critical roles in immune reactions, inflammation, and even tumors and IBDs.

Current research on gut microbiota and immunity is a popular field. Previous studies have shown that the gut microbiota and its microbial species have important effects on maintaining human health, immune function, inflammation, tumorigenesis, and IBDs. Understanding the roles of microbial communities and specific bacterial species as well as their interactions with humans has led to numerous discoveries that provide unique opportunities for exploring human health and future research.

Conclusion:

This study used bibliometric and visualization analysis to identify the development trends and hotspots of publications related to the gut microbiota and immunity. The findings of this study provide valuable insights into the emerging trends and future directions in this field.