bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Therapies for Extremity Sarcoma
Authors: Colombo Chiara , Pasquali Sandro
Published: January 2021

Several regional therapies are used for the local treatment of patients with soft tissue sarcomas (STS), especially for tumors at high risk for local recurrence. Surgery with negative tumor resection margins is the main treatment for primary STS. External-beam radiation therapy is considered for deeply seated, large, and high-grade disease to lower the risk of local recurrence. A combination of preoperative chemo-radiation is associated with improved local control. TNF-α-based isolated limb perfusion is another regional chemotherapy strategy available at specialized surgical oncology units for unresectable STS. Other strategies suitable for management of advanced STS include cryoablation and radiofrequency. This review discusses these and other current regional treatment strategies. 

This review contains 10 figures, 6 Tables and 64 references
Key words: cryoablation, extremity, hyperthermia, isolated limb perfusion, limb infusion, radiotherapy, regional therapy, sarcoma
Sarcomas of the Breast
Authors: Rayfield Corbin A , Bagaria Sanjay P , Wasif Nabil
Published: January 2021

Sarcomas of the breast can be sporadic (primary) or secondary (postradiation). In this review, we discuss clinical presentation, imaging characteristics, diagnostic evaluation, and histologic classification of these rare tumors. Evidence-based management of breast sarcoma with regard to surgery, neoadjuvant or adjuvant chemotherapy and radiation, nodal staging, and outcomes are also discussed. Finally, a clinical case with radiologic and pathologic correlates is presented.
This review contains 3 figures, 5 tables, and 44 references.
Key words: angiosarcoma, breast sarcoma, radiation-induced sarcoma
Sickle Cell Disease
Authors: Freiermuth Caroline , Cudykier Idan
Published: January 2021

Sickle cell disease affects between 70,000 and 90,000 individuals in the United States, the majority of whom are of African-American descent. The genetic basis of the disease is an abnormality in the β-globin gene, which causes the red blood cells to change to a “sickle” shape due to low oxygenation. The life span of patients with this disease has improved over the past few decades, although morbidity remains high. This review covers the pathophysiology of sickle cell disease and the stabilization and assessment, diagnosis and treatment, maintenance and preventive therapies, and cure of patients with sickle cell disease. Figures show hemoglobin electrophoresis; age at death for individuals with sickle cell disease in the years 1979, 1989, 1999, and 2006; sickled cells blocking blood flow; acute chest syndrome; dactylitis; and avascular necrosis. Tables list important trials, topics in need of further research, common complications, most common intravenous pain medications, and indications for transfusion.
This review contains 6 highly rendered figures, 5 tables, 97 references, and a list of educational resources.
Nondiabetic Endocrine Emergencies 1: Adrenal Crisis, Pheochromocytoma, And Hypopituitarism
Authors: Lewis Jason J , Wolfe Richard E
Published: January 2021

Nondiabetic endocrine emergencies are less frequent but equally concerning as diabetic emergencies. The diagnosis of adrenal crises, pheochromocytoma, or pituitary deficiencies can be difficult in the emergent setting given the nonspecific findings frequently confused with other presenting illnesses. Although the differential is broad for patients presenting with shock and hypotension, as seen in adrenal crises, hypertensive emergencies in pheochromocytoma, or a litany of potential symptoms in pituitary abnormalities, the diagnosis should be considered in a patient presenting to the emergency department with severe metabolic abnormalities, undifferentiated shock, or cardiovascular lability. This review demonstrates how to recognize and manage acute adrenal crisis, pheochromocytoma, and pituitary deficiencies in the acute care setting. Patients with nondiabetic endocrine emergencies may present in extremis, and immediate stabilization, typically without confirmatory testing, is necessary. Early intervention is key in treating such presentations.

This review contains 1 figure, 2 tables and 21 references
Key words: adrenal crisis, adrenal insufficiency, catecholamine surge, pheochromocytoma, pituitary deficiency
Approach to the Patient with Respiratory Symptoms
Authors: Silvestri David , Huang Calvin
Published: January 2021

Respiratory complaints are among the most common symptoms encountered by emergency physicians (EPs). Collectively, acute and chronic respiratory diseases account for 11.1% of all mortality and 8.8% of all disability-adjusted life-years lost worldwide. Acute respiratory infections are the single greatest contributor to the overall global burden of disease. Chronic respiratory conditions, including asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, and occupational lung disease, affect an estimated 1 billion people. Many of these chronic conditions present as acute and life-threatening exacerbations in emergency care settings. Respiratory complaints are not specific to pulmonary pathology. Indeed, cardiovascular, neurologic, musculoskeletal, and even gastrointestinal and endocrine diseases can all manifest principally with respiratory symptoms. Moreover, primary conditions of the lung need not present with respiratory symptoms and may instead be heralded only by nonspecific symptomatology, including weakness or confusion. The EP’s approach must be systematic, rooted in a firm grasp of relevant respiratory pathophysiology, with a rapid and yet comprehensive approach to stabilization, diagnosis, and treatment. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of respiratory diseases in the emergency department. Figures show an illustration of the respiratory system and the relation of oxygen saturation, partial pressure, and minute ventilation. The table lists clinical indications for microbiological testing in suspected community-acquired pneumonia. 
Key words: asthma, chronic obstructive pulmonary disease, dyspnea, expiratory wheeze, respiratory symptoms
This review contains 2 highly rendered figures, 1 table, and 98 references.
Pediatric Infectious Diarrhea and Dehydration
Authors: Martel John W. , McCorvey Scott
Published: January 2021

Diarrhea is a common emergency department (ED) complaint, leading to more than 1.5 million outpatient visits and 200,000 hospital admissions in the United States alone. Although concomitant dehydration also exists in some cases, there are no standard clinical criteria to aid in identifying those children who merit intravenous resuscitation. Current pediatric volume repletion guidelines are based primarily on the estimated degree of volume depletion per the World Health Organization, Centers for Disease Control and Prevention, and American Academy of Pediatrics criteria. These practice guidelines stratify patients into mild (3 to 5% volume depletion), moderate (5 to 10% volume depletion), and severe (> 10% volume depletion). The vast majority of pediatric patients presenting with nausea, vomiting, and/or diarrhea suffer from virus-mediated enterocolitis and require no testing or intravenous fluid resuscitation due to the self-limiting nature of these syndromes; rotavirus and Norwalk virus are two of the most common causes of infectious diarrhea in both developing and developed countries. Although bacterial pathogens rarely cause infectious colitis, children who present with more severe symptoms, including fever, bloody stool, and significant abdominal discomfort, warrant additional diagnostic evaluation. Obtaining a careful history, including exposures to livestock, well water, travel, and antibiotic use, as well as recent intake of undercooked meat, is key to identifying patients who may be at higher risk for bacteria-mediated illnesses. Tables identify common diarrheal pathogens, diarrheal subtypes, and clinical abnormalities associated with volume depletion and more severe syndromes, such as hemolytic-uremic syndrome.
This review contains 5 figures, 10 tables, and 80 references.
Key words: Clostridium difficile, dehydration, diarrhea, gastroenteritis, hemolytic-uremic syndrome, pediatrics
Surgical Management of Benign and Malignant Colorectal Disease in the Immunocompromised Patient
Authors: Kin Cindy , Lightner Amy , Welton Mark
Published: January 2021

Patients who are immunosuppressed either due to an underlying disease process or medications to treat a disease require important perioperative considerations. Preoperative evaluation mandates a higher index of suspicion for pathology given that peritoneal and systemic markers of illness may be masked. Intraoperatively, consideration should be given for diversion more frequently than in a nonimmunosuppressed patient. Postoperatively, patients should be managed in a multidisciplinary fashion. This review largely focuses on the immunosuppressive mediations used for the treatment of inflammatory bowel disease, benign colorectal disease in an immunosuppressed patient, and colorectal malignancies in immunosuppressed patients to highlight important considerations for this patient population.
This review contains 4 figures, 5 tables, and 78 references.
Key words: anal squamous cell carcinoma, appendicitis versus typhlitis, biologic therapy, corticosteroids, human papillomavirus, immunosuppression, neutropenic enterocolitis
The Role of Enteral Nutritional Therapy in Inflammatory Bowel Disease
Authors: Albenberg Lindsey , Baldassano Robert
Published: January 2021

Enteral nutrition therapy is a dietary treatment regimen for inflammatory bowel disease that has the benefit of avoiding suppression of the immune system. Its mechanism of action has not been well characterized, but may be related to the elimination of dietary antigens or modulation of the gut microbiota. This treatment has shown success for induction of remission, and may also have a role in maintenance of remission. In the pediatric population, enteral nutrition therapy has the dual benefit of targeting both the inflammatory processes and the poor growth of these patients. This review details the administration and mechanism of action of enteral nutritional therapy, the induction and maintenance of remission, the impact of enteral nutritional therapy on growth and nutrition, and side effects and quality of life. A table summarizes studies investigating enteral nutritional therapy for induction of remission.
This review contains 1 table and 49 references.
Esophageal Cancer
Authors: Won Elizabeth S. , Ilson David H.
Published: January 2021

Esophageal cancers are malignancies that can arise along the entire length of the esophagus, from the cervical inlet to the gastroesophageal junction (GEJ). The most common histologic types are adenocarcinoma and squamous cell carcinoma, which account for almost 95% of esophageal cancers. The location of esophageal cancer varies by histology and strongly influences its behavior and treatment approach. The esophagus is divided into four distinct anatomic regions: the cervical, upper thoracic, midthoracic, and lower thoracic esophagus. Squamous cancers usually occur in the upper or middle esophagus. Adenocarcinomas are more commonly found in the lower third of the esophagus and in the GEJ of the stomach. This review of esophageal cancer addresses the epidemiology, etiology/genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, complications, and prognosis. Figures show Siewert classification, age-standardized esophageal cancer incidence rates by sex and world area, endoscopic images of esophageal tumors, chemotherapy for metastatic esophageal cancer, and a management algorithm for localized esophageal cancer. Tables list hereditary cancer syndromes associated with esophageal cancer, differential diagnosis of dysphagia, physical examination findings in esophageal cancer, differential diagnosis of esophageal lesions seen on endoscopy, and prognosis by stage at diagnosis.
This review contains 5 highly rendered figures, 5 tables, and 42 references.
Small Bowel Dysmotilities and Small Bowel Bacterial Overgrowth
Authors: Guay Laurence , Kuo Braden
Published: January 2021

The main role of the small bowel is nutrient absorption; its mucosa lined with villi increases the contact surface between chyme and intestinal cells. Although the small bowel is the longest segment of the gastrointestinal (GI) tract, its transit takes between 2 and 5 hours and is the shortest of the whole gut. It is the most resilient segment of the GI tract and is thus rarely affected by motility disorders. Small bowel dysmotilities comprise a group of rare disorders affecting the function of any structure of the contractile apparatus from the muscular cells, the intrinsic neurons, or the extrinsic neurons. This review covers the epidemiology, etiology, differential diagnosis, clinical manifestations, physical examination, diagnosis, and treatment of small bowel dysmotilities and bacterial overgrowth. The figure shows GI tract innervations and related pharmacologic treatments. Tables list etiologies of small bowel dysmotilities categorized as primary or secondary causes, treatment strategies related to physiologic abnormalities, and pharmacologic treatments for GI dysmotilities.
Key words: chronic intestinal pseudo-obstruction, gastrointestinal dysmotility, motility disorder, small bowel dysmotility, small intestinal bacterial overgrowth
This review contains 1 highly rendered figure, 3 tables, and 51 references.
Colorectal Cancer Screening
Authors: Inra Jennifer A. , Perencevich Molly , Lim Ramona
Published: January 2021

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men and is the third leading cause of all cancer deaths in the United States. Due to screening examinations used to detect and remove premalignant colon polyps, as well as modification of risk factors and improvements in the treatment of CRC, the incidence and mortality due to CRC have declined over the last several decades. Regardless, CRC continues to account for about 9% of all cancer deaths in the United States. This review addresses CRC, including the epidemiology, pathophysiology and genetics, screening modalities, treatment, and complications associated with CRC screening. Figures show etiologies of CRC, multiple sessile adenomas, a pedunculated adenoma, a sessile polyp, a large polyp found on computed tomographic colonography, and a characteristic sessile serrated adenoma/polyp with a mucus cap in the proximal colon. Tables list oncogenes, tumor suppressor genes, and mismatch repair genes involved in CRC; surveillance recommendations based on a family history of CRC; CRC risk stratification; CRC screening recommendations by risk stratification; and CRC surveillance recommendations.
This review contains 6 highly rendered figures, 5 tables, and 82 references.
Portal Hypertension and Variceal Hemorrhage
Authors: Qamar Amir
Published: January 2021

Gastrointestinal bleeding in patients with cirrhosis can occur from a number of different causes, including portal hypertension, gastric antral vascular ectasia, and acute variceal hemorrhage. The management of these conditions involves a combined medical and endoscopic approach, with radiologic and surgical therapies restricted to refractory cases. This review covers the natural history of gastroesophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia; diagnostic principles; primary and secondary prophylaxis relating to esophageal variceal hemorrhage; and treatment overviews for gastric variceal hemorrhage, portal hypertensive gastropathy, and gastric antral vascular ectasia. Figures show the pathophysiology of complications of cirrhosis, esophageal varices as seen during an upper endoscopic procedure, natural history of esophageal varices in patients with cirrhosis, portal hypertensive gastropathy, gastric antral vascular ectasia, and management principles for acute variceal hemorrhage, esophageal variceal ligation, and gastric varices. Tables list the prevalence of various etiologies of hemorrhage in patients with cirrhosis, current recommendations for follow-up screening and surveillance of varices, sensitivities and specificities of some noninvasive markers, and principles of initial management of acute variceal hemorrhage.
This review contains 8 highly rendered figures, 4 tables, and 44 references.
Adrenal Neoplasia
Authors: Vaidya Anand
Published: January 2021

The adrenal glands are composed of two distinct tissue types: the cortex, which serves as a factory for adrenal steroidogenesis, and the medulla, which produces catecholamines as a neuroendocrine organ. Neoplasia of the adrenal is approached by considering both whether the tumor is benign or malignant and whether it may represent a hormonally active tumor that can contribute to cardiometabolic disease or a hormonally silent tumor. Adrenal neoplasia is rarely malignant. This module discusses the approach to an incidentally discovered adrenal mass, with emphasis on the clinical determination as to whether it is benign or malignant and hormonally functional or nonfunctional. The pathogenesis and genetics of hyperaldosteronism and pheochromocytoma-paraganglioma are reviewed, as are the pathogenesis and management of adrenocortical carcinoma. Tables describe the differential diagnosis and diagnostic approach for an incidentally discovered adrenal mass; suggested biochemical screening tests for incidentally discovered adrenal masses; radiographic features of adrenal masses to determine benign or malignant potential; and the genetics of primary hyperaldosteronism, pheochromocytoma, and paraganglioma syndromes. A drawing shows the genetic mechanisms of hyperaldosteronism in familial hyperaldosteronism type III. Algorithms outline the suggested management approach for the incidentally discovered adrenal mass, genetic counseling and testing for patients with pheochromocytoma or paraganglioma, testing for family members of patients with pheochromocytoma and positive genetic testing, patients with stage I–III adrenocortical carcinoma, and patients with advanced adrenocortical carcinoma.
This module contains 6 highly rendered figures, 6 tables, 55 references, and 5 MCQs.
Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, And Pathology
Authors: Maksymowych Walter P
Published: January 2021

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI.

This review contains 8 figures, 5 tables and 33 references
Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis
The Spleen
Authors: III Donald P. Lesslie , Kao Lillian S.
Published: January 2021

The structure of the spleen allows it to carry out its major functions, which can be categorized as hematologic and immunologic. The importance of the spleen in the immunologic response is evidenced by the increased risk of infection in patients with congenital absence of splenic dysfunction and in splenectomized patients. The presence of one or more accessory spleens is the most common congenital abnormality related to splenic development. This review covers the history, embryology, congenital anomalies, anatomy, and histology/pathophysiology of the spleen. It is important for the student and general surgeon to understand the anatomy and physiology of the spleen to perform operative procedures on the spleen, to avoid intraoperative complications during splenectomy as well as procedures such as mobilization of the splenic flexure and distal pancreatectomy, and to care for the postoperative splenectomized patient.
This review contains 7 highly rendered figures and 17 references.
Nutritional Considerations In The Management Of Dyslipidemia
Authors: Saleh Mohamad , Welty Francine K
Published: January 2021

Cardiovascular disease (CVD), the leading cause of death in industrialized countries, is a dietary disease. In this review, we summarize the evidence from prospective, observational studies and randomized primary and secondary prevention trials of various diets supporting a role of dietary components in the development of CVD and in lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. The role of saturated fat in raising cholesterol and triglyceride is discussed, as well as studies showing that elevated levels of both LDL-C and triglyceride increase the risk of atherosclerosis and that lowering of LDL-C lowers the risk of CVD and its clinical sequelae, including unstable angina, myocardial infarction, and death. Randomized trials of omega-3 fatty acids and the Mediterranean diet and CVD outcomes are reviewed. Classification and causes of various types of hypercholesterolemia and hypertriglyceridemia are summarized. Finally, guidelines for nutritional management and treatment of these lipid disorders to lower levels of LDL-C and triglyceride and prevent CVD are provided. 
This review contains 4 figures, 5 tables and 64 references
Key words: cardiovascular disease, coronary heart disease, lipids, low-density lipoprotein cholesterol, Mediterranean diet, nutrition, saturated fat, triglyceride
Paraproteinemia and Deposition Diseases
Authors: Sathick Insara Jaffer , Leung Nelson
Published: January 2021

The kidney is often involved in diseases associated with monoclonal proteins. In large part, this is due to the physiology and glomerular architecture leading to interactions between the monoclonal proteins and nephron. A variety of pathologic lesions have been described in the kidney as a result of monoclonal immunoglobulins. The spectrum of kidney diseases associated with plasma cell dyscrasias is quite broad and involves almost the entire nephron. This is due to the different types of monoclonal proteins (light chain, heavy chain, and entire immunoglobulin), the highly variable nature of immunoglobulins, and the diversity of paraproteinemias themselvesIt is important for the nephrologist to recognize these conditions because the treatment of plasma cell dyscrasias has vastly improved over the past decade. This chapter discusses myeloma cast nephropathy, amyloidosis, and other glomerulopathies. Figures show paraproteinemia-associated kidney disease, and an algorithm for the typing of amyloidosis. Tables list a classification of amyloidosis affecting the kidney, distinguishing features of diseases with organized deposits, and classification of cryoglobulinemia.
This review contains 2 figures, 3 tables, and 105 references.
Key words: myeloma cast nephropathy, amyloidosis, glomerulopathies, monoclonal immunoglobulins, monoclonal proteins, monoclonal gammopathy of undetermined significance, MGUS, monoclonal gammopathy of renal significance, MGRS
The Porphyrias
Authors: Anderson Karl E , Kappas Attallah
Published: January 2021

The porphyrias are uncommon disorders caused by deficiencies in the activities of the enzymes of the heme biosynthetic pathway. The enzymatic defects that cause porphyrias may be either inherited or acquired, and there is significant interplay between the genetic defect and acquired or environmental factors. Acute forms of the porphyrias may be life threatening and may be misdiagnosed because of the nonspecific nature of the clinical presentation (e.g., acute abdominal pain, psychiatric disturbances, and polyneuropathies). The course of the acute forms of disease is characterized by long latent periods interrupted by acute attacks, which are associated with substantial morbidity and mortality. Porphyrias may be classified as neurovisceral or photosensitive, depending on their prominent clinical characteristic, but in some cases of porphyria, both symptoms are present. Alternatively, the porphyrias can be classified as hepatic or erythropoietic, depending on the principal site of expression of the specific enzymatic defect involved, but the expressions overlap in some porphyrias. The neurovisceral porphyrias correspond with the hepatic porphyrias (ie, acute intermittent porphyria [AIP], variegate porphyria [VP], hereditary coproporphyria [HCP], and ALA deficiency porphyria [ADP]); and the photosensitive porphyrias correspond with the erythropoietic porphyrias (i.e., porphyria cutanea tarda [PCT], hepatoerythropoietic porphyria [HEP], erythropoietic protoporphyria [EPP], and congenital erythropoietic porphyria [CEP]). This chapter covers the classification and pathophysiology of porphyrias and the epidemiology, molecular defects and pathophysiology, diagnosis, and treatment of each of the clinical presentations of porphyria. A table lists the drugs that are safe and unsafe for patients with AIP, VP, HCP, and ADP. Figures illustrate the classification and major symptoms of the porphyrias and the corresponding defect in the biosynthesis of heme that causes the disease; the steps in the biosynthesis of heme; and the mechanisms that precipitate symptoms in AIP. This chapter contains 99 references.
Syphilis and the Nonvenereal Treponematoses
Authors: Augenbraun Michael
Published: January 2021

Syphilis is an infectious disease with complex acute and chronic manifestations that is transmitted primarily through sexual contact. The disease has been recognized for many centuries, although its origin remains unknown. This chapter’s discussion of the epidemiology of syphilis includes figures illustrating the rate of syphilis in the United States by state and county and the rate of syphilis in the United States from 1941 to 2009. The etiology, pathogenesis and disease course, diagnosis, differential diagnosis, treatment, and complications of syphilis are discussed. Special cases of syphilis—in pregnant women, in children, in HIV-infected patients, and congenital syphilis—are also considered. Illustrations include a dark-field microphotograph of treponemes and photographs of a syphilitic chancre, the classic aculopapular rash from spirochetemia, condylomata lata, and a gumma. Tables outline the clinical manifestations of syphilis in adults and the treatment of syphilis. The nonvenereal treponematoses—yaws, endemic syphilis, and pinta—are a group of infections distributed throughout tropical and semitropical areas of the world. They are primarily noted to cause a variety of skin and skeletal lesions. There is little biologic difference between the treponemes that cause these conditions. The epidemiology, pathogenesis, diagnosis, differential diagnosis, and treatment of the nonvenereal treponematoses are discussed.
This chapter contains 7 highly rendered figures, 2 tables, 60 references, 1 teaching slide set, and 5 MCQs.
Neurobiology of Anxiety Disorders
Authors: Hollander Eric , Palkar Pooja
Published: January 2021

In recent years, advances in the fields of neuroimaging and experimental psychology increased our understanding of the basic mechanisms of classical conditioning and learning, contributing to our knowledge of the neurobiology of anxiety disorders. Research has shown that the amygdala is the cornerstone of fear circuitry and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Activation of the amygdala in response to disorder-relevant stimuli has been observed in anxiety disorders. The roles of the hippocampus, nucleus accumbens, periaqueductal gray, and insular and medial prefrontal cortices in response to fear have been identified as well. Neurotransmitters such as serotonin, dopamine, γ-aminobutyric acid, glutamate, and some neurosteroids play an important part in the neurobiology of anxiety disorders. Neuropeptides such as oxytocin, neuropeptide Y, galanin, and cholecystokinin have been shown to modulate stress response. Drugs such as N-methyl-d-aspartate (NMDA) antagonists and blockers of voltage-gated calcium channels in the amygdala are anxiolytic. Fear extinction, which entails new learning of fear inhibition, is the mechanism of effective antianxiety treatments such as d-cycloserine, a partial NMDA agonist. Extinction is thought to occur by the medial prefrontal cortex, which inhibits the lateral amygdala under hippocampal modulation. Harnessing extinction to delink neutral stimuli from aversive responses is an important goal of the psychotherapy and pharmacotherapy of anxiety disorders. Discovery of the role of microRNAs in the etiology of anxiety disorders and their possible utility as targets to treat these disorders is fascinating. In this review, we discuss the neurobiology of anxiety disorders, which will help us better manage them clinically.
This review contains 5 figures, 6 tables, and 39 references.
Key words: Amygdala, anxiety disorders, neurobiology, fear conditioning, neurocircuitry, neurotransmitters, neuropeptides, neurosteroids, endogenous opioids.
Contemporary Evidence-Based Approach to the Couple Experiencing Recurrent Pregnancy Loss: Standardizing Terminology, Testing, and Treatment
Authors: Burks Channing , Stephenson Mary D , Schust Danny J
Published: January 2021

The objective of this review is to highlight central issues relating to recurrent pregnancy loss (RPL), including use of updated terminologies, updated criteria for initiating an RPL evaluation, and an evidence-based standard diagnostic evaluation. RPL is a condition characterized by repeated spontaneous demise of pregnancy. It is a multifactorial disorder that affects approximately 5% of couples in the general population who are trying to have a child. RPL should be defined as two or more pregnancy losses at any gestational age; these do not necessarily need to be consecutive. As 50 to 70% of pregnancy losses of less than 10 weeks gestational age are due to random numeric chromosome errors, we recommend chromosome testing of miscarriage tissues with the second and all subsequent miscarriages less than 10 weeks gestational age. If the second pregnancy loss is “unexplained,” meaning that the chromosome content is euploid (46,XX of pregnancy origin, 46,XY, or a balanced structural chromosomal rearrangement), then an RPL diagnostic evaluation is indicated. Despite a comprehensive evaluation, approximately 40% of couples with RPL will not have a specific etiologic factor identified. In these couples, as with all couples experiencing RPL, empirical management with close monitoring and supportive care during the first trimester is associated with encouraging subsequent live birth rates.
 
This review contains 10 figures, 5 tables and 57 references
Key words: factors associated with recurrent pregnancy loss, idiopathic recurrent pregnancy loss, miscarriage chromosome testing, nonvisualized pregnancy loss, pregnancy of unknown location, recurrent miscarriage, recurrent pregnancy loss
Neuropathic Pain
Authors: Zinboonyahgoon Nantthasorn , Al-Hawarey Sherif , Chen Grace
Published: January 2021

Neuropathic pain is a common but complex condition. The pathophysiology and mechanisms are not fully understood. The evaluation should incorporate a detailed history and physical examination with the selective investigations. There is still no standard classification of neuropathic pain; however, it may be classified as central or peripheral or by location and etiology. The common etiologies of neuropathic pain include diabetes mellitus, chemotherapy, alcohol, inflammation, and HIV. Since neuropathic pain is a chronic condition and unlikely to be cured or to disappear, the goal of treatment includes pain control as well as improved physical functions, attenuated psychological distress, and improved quality of life. The team approach by integrating pharmacologic treatment, physical therapy, pain psychology, and complementary medicine would improve the patient’s quality of life and outcome.
Key words: classification, diagnosis, etiology, neuropathic pain, treatment
Patients with Pain During Pregnancy
Authors: Fox Charles J. , Kaye Alan D. , Cornett Elyse , Stammen Katherine , Franklin Michael
Published: January 2021

Most women experience some degree of pain during pregnancy. Back pain occurs in about half of all pregnant women, with pain typically in the low back due to the physiologic changes in the body that occur with pregnancy, such as weight gain, changed center of gravity, increased ligament and joint laxity, and altered posture. Pelvic pain, leg cramps, and abdominal pain are all common among pregnant women. Many women who have pain during pregnancy are reluctant to use analgesics due to concerns about what the medications may do to their unborn child. Because of this, it is hypothesized that many women are either undertreated for pain or do not receive any treatment. Chronic, severe pain that is ineffectively treated is associated with hypertension, anxiety, and depression, all of which do not lead to a healthy pregnancy. A variety of interventional procedures are commonly performed during pregnancy that can safely alleviate pain. This review goes into detail about the types of pain treatments that are available to pregnant women and are safe and effective in alleviating pregnancy-related pain.
Keywords: Pelvic pain, leg cramps, abdominal pain, hypertension, anxiety, depression, joint laxity, ligament laxity, back pain, analgesics, pregnancy
Vascular Disorders of the Hand
Authors: Treiser Matthew , Sampson Christian E
Published: January 2021

Vascular disorders of the hand and upper extremity encompass a wide range of conditions that can cause peripheral ischemia. These can be purely mechanical in nature, secondary to trauma. They can also be the culmination of multiple systemic diseases, including peripheral arterial disease, end-stage renal disease, and a variety of connective tissue disorders. Key to the successful management of ischemia of the hand and upper extremity is a clear diagnosis. It is only then that the appropriate treatment algorithm can be employed. This review provides an overview of the relevant anatomy and key aspects of the hand and upper extremity physical examination as they pertain to identifying vascular pathology, as well as current state of the art diagnostic modalities. Finally, we discuss some of the more common conditions that affect the hand and upper extremity leading to upper extremity ischemia. The reader should come away with a clear understanding of hand and upper extremity vascular anatomy, how to perform a focused physical examination to identify relevant pathology, and which diagnostic modalities will be most appropriate to make a diagnosis.
This review contains 9 figures and 52 references.
Key words: Allen test, aneurysm, arteriography, botulinum toxin, Buerger disease, CT angiography, hypothenar hammer syndrome, ischemia, magnetic resonance angiography, Raynaud phenomenon, sympathectomy vascular anatomy, vascular pathology
Common Congenital Hand Differences
Authors: Soldado Francisco , Kozin Scott
Published: January 2021

Congenital differences of the hand are common in a pediatric hand surgery practice. The child’s global health and genetic counseling should be addressed before focusing on the upper limb disorder. Appropriate referral is necessary to facilitate education about the congenital difference and its effect on subsequent generations. The physician must be comfortable and have a sound understanding of the diagnosis and treatment algorithm. Reoperation rates are high for even the most common congenital hand defects treated by experienced surgeons. Syndactyly, polydactyly, thumb hypoplasia, and symbrachydactyly are particularly commonplace and are discussed in this review. The main aim when treating these disorders is improving hand function; however, aesthetics must also be considered when planning surgery.

This review contains 36 figures, 3 tables and 50 references
 Key words: congenital hand differences, pediatric hand, symbrachydactyly, syndactyly, thumb duplication, thumb hypoplasia
Vascular Anomalies
Authors: Couto Javier A , Greene Arin K
Published: January 2021

Vascular anomalies are common pediatric lesions affecting approximately 5% of the population. Lesions are broadly classified into tumors and malformations. The most common tumors are infantile hemangioma, congenital hemangioma, pyogenic granuloma, and kaposiform hemangioendothelioma. The major malformations are capillary, lymphatic, venous, and arteriovenous. Almost all lesions can be diagnosed by the history and physical examination. Ultrasonography is usually the first-line imaging study to confirm a diagnosis. Management of vascular anomalies is based on the type of lesion. Treatments include resection, systemic pharmacotherapy, intralesional drugs, laser, sclerotherapy, and/or embolization. Most patients are best managed in an interdisciplinary vascular anomalies center.
This review contains 9 figures, 2 tables and 29 references
Key words: arteriovenous, capillary, congenital, hemangioma, kaposiform, lymphatic, malformation, pyogenic, vascular, venous
Interpersonal Psychotherapy
Authors: Ashen Ceth , Back-Price Ann , Belik-Tuller Olga , Brandon Anna , Fairhurst Scott , Grause Aimee , Schultz Jessica , Stuart Scott , Stuart-Parrigon Kaela
Published: January 2021

Interpersonal psychotherapy (IPT) is an empirically validated treatment for affective, anxiety, and eating disorders. IPT rests on attachment theory and posits that individuals become distressed when they have interpersonal problems, conceptualized in IPT as transitions, interpersonal disputes, or grief and loss issues. IPT is short term, with a typical dosing range of six to 20 sessions followed by maintenance treatment to reduce the risk of relapse. Dissemination of IPT has greatly increased over the last decade, with several large-scale efforts in public health settings in the United States and abroad. We review the basics of IPT for depression and anxiety. We also describe its application to groups and adolescents. Recently developed clinical tools that have enhanced the delivery of IPT and have increased fidelity are described. Opportunities for training in IPT are also reviewed.
This review contains 10 figures, 1 table, and 71 references.
Key words: adolescents, anxiety, depression, grief and loss, group therapy, interpersonal inventory, interpersonal psychotherapy, interpersonal summary, maintenance psychotherapy, posttraumatic stress disorder
Couple and Family Therapy
Authors: ChenFeng Jessica , Gehart Diane
Published: January 2021

Evidence-based couple and family therapies have a robust and well-established evidence base as a cost-effective treatment for numerous conditions and are the treatment of choice for several childhood and adult mental health issues. This review provides a brief overview of systemic couple and family therapy principles and then reviews the evidence base for using these methods with specific disorders. Family therapy treatments have been identified as a primary intervention for several childhood and adolescent disorders, including conduct, alcohol and substance use, attention-deficit, autism, psychotic, mood, anxiety, and eating disorders, as well as certain physical disorders, including diabetes, enuresis, and asthma. For adults, the current evidence base supports couples therapy for major depressive disorder with couple distress, alcohol and substance use disorders, anxiety disorders, distressed couples, and interpersonal violence with certain batterers. In addition, couple and family therapy is indicated for certain adult chronic health conditions, including stroke, traumatic brain injury, spinal cord injury, cardiovascular diseases, cancer, dementia, and diabetes. The review concludes with a discussion of effective referral for and training in evidence-based family therapy approaches.
This review contains 6 figures, 5 tables, and 53 references.
Key words: ADD/ADHD, adolescent, childhood trauma, conduct disorder, couples therapy, depression, eating disorders, family therapy,  marital therapy, mood disorder
Anxiolytics
Authors: Doroudgar Shadi , Bains Gurjit
Published: January 2021

The underlying pathophysiology of anxiety disorders revolve around neurotransmitter transmission, the pharmacologic target of common medication treatments. Pharmacologic treatment of anxiety disorders generally consists of benzodiazepines for short-term relief of anxiety symptoms and antidepressants as a long-term therapy. Benzodiazepines use should be limited because of habit-forming properties, dependence, and risk of adverse effects. Antidepressants are the typically preferred initial agents for long-term use due to efficacy and lack of dependence. Anxiety disorders may occur as comorbidities with other psychiatric disorders. Other pharmacologic agents are utilized as alternative therapy for patients who do not respond to mainstay therapy or are not candidates for the treatment with antidepressants.

This review contains 1 figure, 6 table and 77 references
Key Points: anxiety disorders, benzodiazepines, generalized anxiety disorder, norepinephrine, panic disorder, social anxiety disorder, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors
Pathophysiology and Treatment of Uric Acid Stones
Authors: Whitaker Dustin , Saidian Ava , Britt Jacob , Boyd Carter , Wood Kyle , Assimos Dean G
Published: January 2021

Uric acid is the third most common stone composition and comprises 7 to 10% of all kidney stones sent for analysis. These stones are more common with increasing age and in men. Uric acid stone disease is associated with conditions such as the metabolic syndrome and type 2 diabetes mellitus. Uric acid is produced by the enzyme, xanthine oxidase and is the final product of purine metabolism in humans. Three main factors contribute to the formation of uric acid stones: low urine pH (the most important), hyperuricosuria (rare, includes conditions such as myeloproliferative disorders and Lesch-Nyhan syndrome), and low urine volume. Uric acid stones appear radiolucent on plain radiographs and are ultimately diagnosed via stone analysis. These stones may be treated with medical expulsive therapy, dissolution therapy, or surgical intervention depending on the size, location, and clinical presentation. Urine pH manipulation therapy with potassium citrate is the first-line treatment for the prevention of uric acid stones and attempts at dissolution. Allopurinol should not be offered as the first-line therapy for uric acid stones.
 This review contains 3 figures, 1 table and 38 references
Key Words: ammonium, diabetes mellitus, epidemiology, management, metabolic syndrome, nephrolithiasis, pathophysiology, potassium citrate, uric acid, urine pH
Orthopedic outcomes of hybrid and conventional Hyrax expanders:
Authors: Garib Daniela , Miranda Felicia , Palomo Juan Martin , Pugliese Fernando , da Cunha Bastos José Carlos , dos Santos Alexandre Magno , Janson Guilherme
Published: January 2021

Objectives

To compare the effects of a hybrid miniscrew-supported expander versus a conventional Hyrax (CH) expander in growing patients.

Materials and Methods

Forty patients were randomized into two groups: a hybrid Hyrax (HH) expander group using a Hyrax expander with two miniscrews and a CH expander group. The final sample had 18 subjects (8 female, 10 male; initial age of 10.8 years) in the HH group and 14 subjects (6 female, 8 male; initial age of 11.4 years) in the CH group. Cone-beam computed tomography examinations and digital dental models were obtained before expansion and 11 months postexpansion. The primary outcomes included the orthopedic transverse effects of expansion. Intergroup comparison was performed using analysis of covariance (P < .05).

Results

Significantly greater increases in the nasal cavity width, maxillary width, and buccal alveolar crest width were found for the HH group. No intergroup differences were observed for dental arch width or shape changes.

Conclusions

The HH group showed greater increases in the nasal cavity width, maxillary width, and buccal alveolar crest width. No differences were observed for intermolar, interpremolar, or intercanine widths; arch length; or arch perimeter. Arch size and shape showed similar changes in both groups.
Parameters of macrophage reaction and humoral immunity in patients with implant-associated in-flammation after primary endoprosthetics of knee joint
Authors: Galashina Elena A. , Gladkova Ekaterina V. , Blinnikova Veronika , Shpinyak Sergey P. , Ulyanov Vladimir
Published: January 2021

Aim. To study peculiarities of macrophage reaction and humoral immunity in patients with signs of implant-associated inflammation after the primary endoprosthetics of the knee joint.
Materials and Methods. Examination of 48 patients with signs of implant-associated inflammation after the primary endoprosthetics of the knee joints (the main group) and of 44 patients without signs of inflammatory reactions (comparison group) was carried out. Control group involved 30 healthy donors without diseases of the musculoskeletal system.
Results. In 1 and 12 months after the surgery, patients of the main group showed elevated levels of the factor inhibiting migration of macrophages (MIF), of macrophage stimulating protein (MSP), class A immunoglobulins (IgA), С3 and С4 complement components as compared to control, and also to each previous period. In 1 month after the surgery, the content of class M and G immunoglobulins (IgM and IgG) decreased relative to control; in 12 months after the surgery a more pronounced reduction was noted. Increase in serum concentrations of MIF, MSP, IgA, С3 and С4-complement components was noted in the comparison group in 1 and 12 months and also in comparison with the previous period. Reduction of the levels of IgM, IgG in 1 and 12 months after the operation was noted in comparison with control and with the previous period.
Conclusion. A study of parameters of macrophage reaction, proteins of complement system and the main classes of immunoglobulins permits to identify signs of implant-associated inflammation in 1 and 12 months after surgery, and, consequently, to determine patients of risk groups that require additional diagnostics measures.