bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV Coinfection
Authors: Chan Justin , Yu-Shin Kim Arthur
Published: January 2021

Improved screening of the blood supply and safer injection practice have led to a decreased prevalence of hepatitis C virus (HCV) worldwide over the past decade. However, those who are coinfected with HIV and HCV experience synergistic interaction between the viruses, leading to accelerated liver fibrosis and possibly increased HIV progression. Left untreated, these coinfected patients experience higher mortality compared with monoinfected individuals. The recent availability of highly efficacious direct-acting antivirals (DAAs) provides opportunity to prioritize coinfected patients for curing HCV, which can improve liver-related and overall mortality. This review summarizes the epidemiology, virology, and natural history of coinfection. Major clinical trials involving coinfected patients are summarized, and drug-drug interactions between HIV antiretroviral therapy and HCV DAA therapy are discussed. Given the numbers of people at risk for primary infection and reinfection after cure, we also discuss important strategies of harm reduction and treatment as prevention. The revolution in DAAs provides the prospect of reducing the burden of liver disease, which remains one of the leading causes of death in people living with HIV.
Key words: HIV-HCV coinfection; Epidemiology; Natural history; Viral interaction; Direct-acting antiviral; Drug-drug interaction
Extraintestinal Manifestations of Inflammatory Bowel Disease
Authors: Silva Punyanganie de , Patel Mital
Published: January 2021

The extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) can be classified as the following: (a) true EIMs due to reactive IBD affecting organ systems, (b) complications secondary to IBD activity, (c) non–IBD-specific autoimmune disease which occurs in increased frequency in individuals with IBD. Overlap is frequent between EIMs and extraintestinal complications, and it is increasingly evident that multiple organ systems may be involved. This review covers EIMs through their epidemiology, etiology/genetics/pathogenesis, prognosis, complications, and treatment. Also detailed are the organ systems involved with reactive IBD, including musculoskeletal, pulmonary, dermatological, ophthalmic, and hepatobiliary manifestations. Figures show the classification, etiology, and pathogenesis of EIMs of IBD, musculoskeletal and pulmonary manifestations of IBD, metastatic Crohn disease of the intergluteal cleft, pyoderma gangrenosum, oral apthous ulcers, Sweet syndrome, leucocytoclastic vasculitis, anti-tumor necrosis factor–induced psoriasis, uveitis, episcleritis, and primary sclerosing cholangitis. Tables list the modified New York criteria for ankylosing spondylitis, pulmonary manifestations of IBD and IBD-related treatment, diagnostic techniques in lung disorders associated with IBD, dermatologic manifestations of IBD based on classifications, specific cutaneous manifestations or granulomatous cutaneous lesions with the same histological features as the underlying bowel disease, reactive cutaneous manifestation of IBD with immunological mechanisms triggered by common antigens shared by gut bacteria and skin, cutaneous disorders or dermatosis associated with IBD, secondary cutaneous manifestations due to complications of IBD and adverse effects of IBD treatment, treatment of dermatological manifestations of IBD, diagnosis of ophthalmological manifestations of IBD, and other hepatobiliary manifestations of IBD. 
This review contains 13 highly rendered figures, 12 tables, and 79 references.
Pancreatitis in the Critical Care Setting
Authors: Kodadek Lisa M. , Lipsett Pamela A.
Published: January 2021

Pancreatitis is a complex spectrum of disease including chronic pancreatitis, acute pancreatitis, and manifestations of severe acute pancreatitis such as sterile and infected necrotizing pancreatitis. Acute pancreatitis is the leading cause of hospitalization for gastrointestinal disorders in the United States. Pancreatitis is a dynamic condition, and severity may change and evolve during the course of the disease. Although most patients with acute pancreatitis have mild disease, 10 to 15% will run a fulminant course, leading to severe acute pancreatitis, pancreatic necrosis, and multisystem organ injury. The mortality for severe acute pancreatitis is 15 to 30%; however, the overall mortality for all patients with acute pancreatitis is less than 5%. Early management of acute pancreatitis includes fluid resuscitation, pain control, and enteral nutrition. There are no specific directed therapies proven to be effective for the early treatment of acute necrotizing pancreatitis; therapy is entirely supportive. Chronic pancreatitis is a challenging disease often marked by chronic pain. Surgical intervention may help improve quality of life and relieve pain in selected patients. International consensus guidelines provide definitions and classifications to aid clinicians with diagnosis and management of pancreatitis. This review covers advances related to pancreatitis, including literature pertaining to the step-up approach for necrotizing pancreatitis first published in 2010, discussion of the revised Atlanta Classification System for severity of acute pancreatitis published in 2013, review of the current spectrum of microbial pathogens implicated in infected necrotizing pancreatitis, and the international draft consensus proposal for a new mechanistic definition for chronic pancreatitis published in 2016.
Key words: acute pancreatitis, antibiotic prophylaxis, Atlanta Classification System, biliary pancreatitis, chronic pancreatitis, necrosectomy, pancreatic necrosis, pancreatitis, step-up approach, video-assisted retroperitoneal drainage (VARD)
Metabolic Disorders: Inborn Errors of Carbohydrate Metabolism
Authors: Chopra Sameer S , Berry Gerald T
Published: January 2021

The small molecule diseases include the inborn errors of carbohydrate, ammonia, amino acid, organic acid, and fatty acid metabolism. They are central to the cohort of biochemical genetic diseases that are often associated with catastrophic presentations and life-threatening illness during infancy and childhood. Many of these entities are now routinely detected through newborn screening in the majority, if not all, of the states in the United States. Several of these diseases have effective therapies that largely eliminate the signs and symptoms of disease. In many, however, the disease process is without an effective treatment or may be brought under control but not corrected.
This review contains 1 figure, 6 tables, and 11 references.
Keywords: glycogen storage diseases, galactosemia, hyperbilirubinemia, hyperchloremic metabolic acidosis, hypofibrinogenemia, and thrombocytopenia, hypophosphatemia, fructose-1,6-bisphosphatase deficiency
Pathophysiology of Alzheimer Disease
Authors: Knopman David
Published: January 2021

Genetic discoveries coupled with neuropathologic investigations initially established the central role for β-amyloidosis in Alzheimer disease (AD). Three dominantly inherited genes (APP, PSEN1, and PSEN2) and one common allelic variant with lower penetrance (APOE) account for the majority of the genetic basis for AD. PET biomarkers for AD have been developed in the past decade and are fundamentally altering our view of the disease. The availability of PET tracers, first for amyloid and now for tau, has enabled researchers to develop a model of AD that begins long before people become symptomatic. In persons destined to develop dementia due to AD, brain β-amyloid levels begin to rise 10 to 20 years earlier. Other imaging changes that might precede symptomatic disease include (1) reductions in brain metabolic activity in a group of temporal and parietal cortical association areas that can be demonstrated by [18F]fluorodeoxyglucose-PET scanning; (2) losses of hippocampal volume as measured on structural magnetic resonance imaging; and (3) loss of cortical thickness or cortical volume in temporal and parietal cortical association areas. All of these changes are greatly accentuated once people become symptomatic. Although mild elevations in tau PET abnormalities can also be seen in presymptomatic individuals, it is only when persons become symptomatic that marked elevations in these abnormalities begin to occur in those same temporal and parietal cortical association areas. Cerebrospinal fluid (CSF) biomarkers provide a complementary view, with CSF β-amyloid levels falling (presumably due to aggregation within the cortex) even before amyloid PET abnormalities are visible. CSF total tau and phospho-tau levels begin to rise when persons are much closer to being symptomatic. The sum of these observations has allowed researchers to gain a far more insightful antemortem view of the pathophysiology of AD in humans than had previously been available from neuropathologic investigations. 
Keywords: β-amyloid, cerebrospinal fluid β-amyloid, cerebrospinal fluid phospho-tau, cortical thickness, [18F]fluorodeoxyglucose–positron emission tomography, hippocampal atrophy, preclinical Alzheimer disease, tau protein
Hemophilia
Authors: Parnes Aric , Rotenstein Lisa
Published: January 2021

Hemophilia is a family of rare bleeding disorders characterized by deﬁciency of clotting factors. Hemophilia A is an inherited deﬁciency of factor VIII, whereas hemophilia B (Christmas disease) represents a deﬁciency of factor IX. Both hemophilia A and B are X-linked diseases, with hemophilia A accounting for 80 to 85% of cases and hemophilia B 15 to 20%. Although hemophilia has historically referred to deﬁciencies of factors VIII and IX, it is important to recognize that similar bleeding disorders can occur with other missing clotting factors, although this is far more rare. This review covers the definition, history, epidemiology, biology/genetics, clinical manifestations, diagnosis, differential diagnosis, treatment, complications, measures of quality of care, and prognosis of hemophilia, as well as future directions. Figures show the clotting cascade, the genetic makeup of severe hemophilia A, an algorithm for diagnosing hemophilia, and hemophilic arthropathy in a patient’s knees. Tables list severity in hemophilia A and B, treatment of acute bleeding in hemophilia A and B, frequency of dosing in acute bleeding, and treatment of acute bleeding with inhibitors.
This review contains 4 highly rendered figures, 4 tables, and 59 references.
Rheumatoid Arthritis: Clinical Manifestations and Diagnosis
Authors: Firestein Gary S. , Ekwall Anna-Karin H.
Published: January 2021

The onset and course of rheumatoid arthritis (RA) can be highly variable, and the lack of a specific biologic marker can make diagnosis difficult in early disease. A careful history and physical examination and the integration of clinical and laboratory data are often required. The presence of anti-citrullinated peptide antibodies (ACPAs) is one of the best predictors of progression to establish RA. This review describes the clinical manifestations used to diagnose RA, such as physical examination of the hands and wrists, elbows and shoulders, hips, knees, ankles and feet, and cervical spine. Extra-articular manifestations related to rheumatoid nodules, eyes, lungs, heart, blood and blood vessels, and neuromuscular involvement are reviewed. Laboratory tests and differential diagnosis are also discussed. Figures show synovitis in the hand and wrist, rheumatoid nodules near the extensor surface of the elbow, a pelvic radiograph of a patient with classic seropositive RA, erosions in the metatarsal heads and phalanges of the foot of a patient with classic seropositive RA, the anterior edge of the odontoid process, and a typical rheumatoid nodule.
This review contains 6 highly rendered figures and 20 references.
Anatomy and Physiology of the Pancreas
Authors: Windsor John A.
Published: January 2021

The pancreas is the body’s largest digestive gland, situated in the center of the body, on either side of the transpyloric plane. It is notable for its complex anatomy and the co-location of exocrine and endocrine organs. Pancreatic surgery requires a detailed understanding of the anatomy of the pancreas and its relation to adjacent vital structures. This review describes the morphology of the pancreas, its ductal system, the major duodenal papilla, arterial anatomy, venous anatomy, lymphatic draining, and nerve supply. Because managing patients with pancreatic diseases requires a detailed understanding of the physiology of the exocrine and the endocrine pancreas, both are discussed here.
This review contains 16 highly rendered figures and 15 references.
Nutritional Support
Authors: Uhlich Rindi , Hu Parker , Bosarge Patrick L
Published: January 2021

Nutritional optimization of the critically ill patient remains a cornerstone of perioperative care. Significant effort and scrutiny are routinely directed to the field as it has the potential to improve outcomes, limit infectious complications, and decrease hospital length of stay and mortality. As such, previously identified cornerstones of care have been called into question. The timing, route, and intensity of nutritional supplementation remain the subject of controversy in an ever-evolving field. Previous methods of nutritional assessment, such as albumin and transthyretin, have proved unreliable, and their use is no longer recommended. In their place, new scoring systems are available to risk assess patients for malnutrition. We review the most pressing changes and assess the landscape of the field today.
Key words: critical illness, enteral, glutamine, malnutrition, nutrition, outcomes, parenteral, protein
The Renal System
Authors: Locke Jayme E. , Killian Jr John T
Published: January 2021

This updated review on the renal system provides a concise overview of the topics most important to the general surgeon. Anatomic topics have been expanded to also include variant anatomy and surgical approaches. There is a new focus on the accuracy and utility of equations for estimating the glomerular filtration rate, as well as supplementation and pharmacology for the general surgeon with discussions of vitamin D and erythropoietin. Acute kidney injury is defined; its pathophysiology is discussed; and its management is outlined, highlighting evidence-based practice. Finally, urologic surgery is addressed with a focus on donor nephrectomy and its consequences, as well as the management of iatrogenic ureteral injuries.
This review contains 6 highly rendered figures, 6 tables, and 68 references.
Key words: acute kidney injury; contrast nephropathy; erythropoiesis-stimulating agents; estimated glomerular filtration rate; iatrogenic ureteral injury; laparoscopic donor nephrectomy; renal surgical anatomy; vitamin D supplementation
Appendicitis
Authors: Creswell Simpson James , Sebbag Sarah
Published: January 2021

Appendicitis is defined as inflammation of the vermiform appendix. It is the most common abdominal surgical emergency and occurs at an annual rate of approximately one in 10,000 in the United States. The lifetime risk of appendicitis is about 9% for males and 7% for females; approximately 80% of cases occur before 45 years of age. Appendicitis rarely occurs in infants; it increases in frequency between 2 and 4 years of age and reaches a peak between the ages of 10 and 19 years. However, clinicians must maintain a high index of suspicion in patients of all age groups. This review covers the pathophysiology, stabilization and assessment, and diagnosis and treatment of complicated and uncomplicated appendicitis. The disposition and outcomes are also reviewed. Figures show an image of appendicitis on a bedside sonogram, and a computed tomographic image of appendicitis. Tables list likelihood ratios of signs and symptoms of appendicitis, the sonographic appearance of appendicitis, the Alvarado scoring system, and the differential diagnosis of appendicitis.

 This review contains 2 figures, 7 tables, and 36 references.
Key words: appendicitis, obstructed appendiceal lumen, rebound abdomen, right lower quadrant pain, ruptured appendix
Caustics
Authors: Babu Kavita , Farrugia Lynn A
Published: January 2021

A caustic is any substance capable of causing full-thickness damage on contact with healthy, intact tissue. Caustic agents are generally classified by pH as acids or bases. Irritants are those substances that do not produce true breakdown of tissue but cause discomfort and inflammation, such as vomiting, burning eyes, or coughing. This review covers caustic and irritant agents, dermal caustic exposure, caustic inhalation and pulmonary irritants, caustic ingestion, and ocular caustic exposure, along with special consideration of hydrofluoric acid, including hydrofluoric acid and dermal exposure, hydrofluoric acid ingestion, hydrofluoric acid inhalation, ocular hydrofluoric acid exposure, and systematic hydrofluoric acid toxicity. Figures show classification of burns; chemical burns; an autopsy specimen of the tongue, epiglottis, and esophagus after caustic ingestion; and an autopsy specimen of the stomach after caustic ingestion. Tables list common caustic and irritant agents, household products containing caustic and irritant agents, agents for which water or saline irrigation is not recommended, indications for endoscopy after caustic ingestion, ocular chemical burn management, and common chemicals and products containing fluoride.
Key words: caustic eye injury, caustic ingestion, caustic injury, chemical burn, hydrofluoric acid, pulmonary irritants 
This review contains 5 highly rendered figures, 6 tables, and 53 references.
Mesenteric Ischemia
Authors: Ezenkwele Ugo A.
Published: January 2021

Acute mesenteric ischemia is interruption of intestinal blood flow by embolism, thrombosis, or a low-flow state. Bowel infarction is the end result of a process initiated by mediator release and inflammation. On clinical assessment, the early hallmark is severe abdominal pain but minimal physical findings. The abdomen remains soft, with little or no tenderness. Mild tachycardia may be present. Early diagnosis is difficult, but selective mesenteric angiography and computed tomographic angiography have the most sensitivity; other imaging studies and serum markers can show abnormalities but lack sensitivity and specificity early in the course of the disease, when diagnosis is most critical. Treatment is by embolectomy, anticoagulation, revascularization of viable segments, or resection; sometimes vasodilator therapy is successful. If diagnosis and treatment take place before infarction occurs, mortality is low; after intestinal infarction, mortality approaches 30 to 70%. For this reason, in the emergency department, clinical diagnosis should supersede diagnostic tests, which may delay treatment.
This review contains 6 highly rendered figures, 4 tables, and 33 references.
Key words: acute mesenteric ischemia; bowel necrosis; chronic mesenteric ischemia; mesenteric occlusive disease; mesenteric venous thrombosis; nonocclusive mesenteric ischemia; postprandial abdominal pain; superior mesenteric artery thromboembolism
Metabolic Acidosis
Authors: Cohen Lisa , Savla Dipal , Anand Shuchi
Published: January 2021

Metabolic acidosis is a common clinical entity that can arise from a variety of disease states, medications, and toxic ingestions. This review covers the pathophysiology, diagnosis, and management of common presentations of metabolic acidosis. We have differentiated various causes of metabolic acidosis based on the presence of a normal or elevated anion gap (AG), the sum of serum anions unaccounted for by the measurement of plasma sodium, bicarbonate, and chloride levels. Normal AG metabolic acidosis, or non-AG metabolic acidosis, arises when there is excessive loss of bicarbonate from the gastrointestinal tract or in the urine. This review covers the development and diagnosis of non-AG metabolic acidosis, including a discussion of the spectrum of renal tubular acidosis subtypes. The treatment of non-AG metabolic acidosis is reviewed. Metabolic acidosis with an elevated AG, also called AG metabolic acidosis, develops when exogenous or endogenous nonchloride acid accumulates in the body. The most common causes of AG metabolic acidosis are lactic acidosis and ketoacidosis from starvation, heavy alcohol intake, or diabetes with total body insulin depletion. Medications, toxic substances, and uremia can also lead to AG acidosis. The mechanisms and management of these causes of metabolic acidosis with high AG are covered in detail.
Key words: anion-gap acidosis, diabetic ketoacidosis, lactic acidosis, non–anion gap acidosis
The Primary Glomerular Diseases
Authors: Glassock Richard J. , Sethi Sanjeev , Fervenza Fernando C.
Published: January 2021

Glomerular disorders in which the manifestations of disease are primarily confined to the kidneys, without multisystem involvement, are not only common but very heterogeneous in terms of pathogenesis and clinical features. Typically, these primary glomerular diseases are characterized according to the findings on renal biopsy, as studied by light, immunofluorescence, and electron microscopy. The principal primary glomerular diseases are minimal change disease, focal and segmental glomerulosclerosis, membranous nephropathy, C3 glomerulonephritis and dense deposit disease, IgA nephropathy, and renal-limited crescentic glomerulonephritis. These clinicopathologic entities are discussed according to epidemiology, clinical features, pathology, pathogenesis (and genetics if appropriate), prognosis, and treatment, emphasizing recent findings. 
Key words: C3 glomerulonephritis, dense deposit disease, focal and segmental glomerulosclerosis, glomerulonephritis, IgA nephropathy, membranous nephropathy, minimal change disease, renal biopsy, renal-limited crescentic glomerulonephritis
Cystic Diseases of the Kidney
Authors: Riella Christian , Czarnecki Peter G , Steinman Theodor I
Published: January 2021

The spectrum of cystic kidney diseases encompasses a wide range of genetic syndromes with different identified disease genes, modes of inheritance, extrarenal organ manifestations, and clinical progression. Depending on the given disease gene and type of mutation in a respective cystic kidney disease, the age of onset, pathologic characteristics, and rate of progression to end-stage kidney disease vary considerably. This review covers disease definitions, etiology and genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of cystic kidney disease. Additionally, simple and complex renal cysts in adults are discussed. Tables list the epidemiology of polycystic kidney disease, gene locus, and encoded protein, unified criteria for ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (APDKD), risk factors for progressive kidney disease in APDKD, differential diagnosis of cystic diseases of the kidney, Halt Progression of Polycystic Kidney Disease trial summary, and other extrarenal manifestations of ADPDK.
Key Words: Cystic kidney disease; Autosomal dominant polycystic kidney disease; APDKD; Polycystic kidney disease; PKD; End-stage renal disease; Renal cysts; Progressive kidney disease
Pharmacologic Approach to Renal Insufficiency
Authors: Olyaei Ali J. , Bennett William M.
Published: January 2021

Prescribing drugs in patients with kidney disease is complex: drug dosing needs to be adjusted by the stage of kidney disease (whether chronic kidney disease [CKD] stages 1 through 5 or acute kidney injury [AKI] stages 1 through 3); because potential interactions with other agents that are being used need to be considered; and because of the possibility of extracorporeal treatment that might need to be used (e.g., continuous renal replacement therapy [CRRT], peritoneal dialysis [PD], or hemodialysis [HD]). Besides this complexity, there has been an explosion in the classes of new agents and the routes of delivery of these agents. The purpose of this chapter is to review the basic pharmacokinetic and pharmacologic principles that should guide therapy and to summarize basic recommendations for patients with CKD and AKI. The general principles for drug dosing in CKD and AKI include pharmacokinetics in renal failure; bioavailability; volume of distribution; protein binding; and biotransformation. A stepwise approach to dosage adjustment is described and created as an algorithmic approach. Drug dosing considerations in dialysis patients and in AKI patients are covered as well. This chapter contains 2 algorithms, 7 tables, 25 references, 5 Board-styled MCQs, and 1 Teaching Slide Set.
Cardiac Resuscitation
Authors: Pozner Charles N. , Martindale Jennifer L , Geyer Brian C.
Published: January 2021

Over 1,000 people suffer sudden cardiac death every day in the United States. About half occur in the hospital, the remainder occurring in the home, outpatient medical environments, or public spaces. The ultimate goal of cardiac resuscitation is survival with full neurologic recovery. Interventions that have the greatest potential to provide this outcome are often those interventions that can be performed by trained laypersons. Delay in the initiation of compressions in a cardiac arrest is one of the leading predictors of mortality. This chapter deliberately opens with a discussion of one of the most vital, yet relatively under-appreciated aspects of cardiac resuscitation—teamwork. Following an overview of cardiac arrest, the chapter covers epidemiology and recognition of cardiac arrest, then activation of the emergency response system. Chest compressions, defibrillation and airway management are discussed, then end-tidal CO2, vascular access, rhythm analysis during cardiac arrest, and drugs used during cardiac resuscitation. The chapter concludes with a look at postresuscitation care, special considerations in cardiac arrest, and future directions. Figures include the foundations of cardiac resuscitation, a management algorithm for the initial treatment of cardiac arrest, coronary perfusion pressure as a function of time, an impedance threshold device incorporated into a bag-valve mask, a colorimetric CO2 detector, four basic phases of a capnogram, sample capnographs, a battery-powered intraosseous drill, electrocardiogram readouts of ventricular arrhythmias, a sonogram of large pericardial effusion, and electrocardiographic appearance of varying degrees of hyperkalemia. Tables summarize recommendations from the American Heart Association, the components of optimal and suboptimal chest compressions, and underlying causes of nonshockable rhythms and their management.
This chapter contains 11 highly rendered figures, 3 tables, 138 references, 5 MCQs.
Chronic Pelvic Pain: The Neuropathic Pain Basis
Authors: Antolak Jr Stanley J.
Published: January 2021

Chronic pelvic pain (CPP) in both genders has been chiefly the province of surgical subspecialists. Morphologic end-organ processes have been studied for decades without significant advances in understanding the etiology of CPP or developing adequate therapeutic outcomes. The neurogenic basis of CPP has received little attention. Several peripheral nerves may be the source. The largest of these is a pudendal nerve and is the most important because it is a mixed nerve and affects sensory and motor symptoms in both the somatic and autonomic nervous systems. Nerve compression and stretch are the two most important etiologic factors.
Practitioners can diagnose these painful neuropathies by a careful symptom history and physical examination. The most important diagnostic tool is sensory examination of the pudendal territory using pinprick. Various neurophysiologic tests can confirm pudendal neuropathy. The smaller peripheral nerves affect CPP.
Because pudendal neuropathy is a tunnel syndrome related to cumulative, repetitive microtrauma, it can be treated accordingly. Treatment options include nerve protection, medications (analeptics, tricyclic amines), perineural infiltrations of local anesthetics with or without corticosteroids, and, in a significant minority, decompression of the pudendal nerves. The smaller nerves often respond to a program of postural correction and perineural anesthetic blockades. All patients require attention to central sensitization. Treatment success depends on the duration of symptoms, etiology, and severity of nerve damage. The last item can only be evaluated at surgery. Complete cures of CPP, treated using each modality, can be measured by validated symptom scores for as long as 13 years.
To progress in the diagnosis and treatment of CPP, interspecialty studies are needed that distinctly separate neurogenic from nonneurogenic CPP. To date, this has not been done. Thus, diagnostic, etiologic, and treatment conclusions are quite limited. CPP provides a rich foundation for clinical research for neurologists.
Key Words: abdominal cutaneous neuropathy, chronic pelvic pain, interstitial cystitis, irritable bowel syndrome, middle cluneal neuropathy, neurogenic pelvic pain, pudendal neuropathy, sexual dysfunction, thoracolumbar junction syndrome
Parkinson Disease: Treatment
Authors: Martinez-Ramirez Daniel , Okun Michael S.
Published: January 2021

Parkinson disease (PD) is a chronic neurodegenerative disorder affecting more than 4 million people worldwide. It is expected that this number will potentially double by 2030 due to the aging population, thus transforming PD into an even bigger worldwide health concern. As PD knowledge has expanded over the past three decades, it is now recognized that multiple brain neurotransmitters and circuits are altered and collectively contribute to a constellation of motor and nonmotor symptoms. The classic symptoms required for the clinical diagnosis of PD are bradykinesia, resting tremor, rigidity, and/or loss of postural reflexes. Due to the multiple brain circuits affected as the disease advances, the nonmotor manifestations become equally, or even potentially, more troublesome for patients and caregivers. This review covers general considerations and aspects of treatment of PD. Figures show expected phases of PD, how to start therapy, and the approach to levodopa-induced complications. Tables list suggested dosages of available medications for the treatment of motor symptoms in PD, classification of levodopa-induced complications, suggested dosages of available medications for the treatment of neuropsychiatric symptoms, and suggested dosages of available medications for the treatment of autonomic symptoms and sleep disorders.
Key words: levodopa, levodopa-induced complications, movement disorders, neurodegenerative disorders, Parkinson disease
 
This review contains 3 highly rendered figures, 4 tables, and 226 references.
Acquired Demyelinating Syndromes in Children
Authors: Adang Laura , Banwell Brenda
Published: January 2021

Collectively, pediatric acquired demyelinating syndromes encompass a diverse clinical spectrum and include disorders such as multiple sclerosis (MS), acute disseminated encephalomyelitis, acute transverse myelitis, optic neuritis, and neuromyelitis optica spectrum disorders (NMOSDs). Acquired demyelination may occur as a monophasic illness or represent chronic demyelinating disease (such as MS or NMOSD) and thus prompt identification and classification is essential for proper treatment and guidance. As such, approximately 3% of all patients affected by MS experience their first attack during childhood. In general, one quarter of children diagnosed with an acute demyelinating syndrome will be ultimately confirmed to have MS. The likelihood that an incident demyelinating attack represents the first attack of MS is increased in adolescents, females, patients with positive cerebrospinal fluid oligoclonal bands, and those with clinically silent T2 bright and T1 hypointense lesions on brain magnetic resonance imaging at onset. Early therapeutic intervention for MS and NMOSD is recommended to reduce relapses, modify relapse severity, and, it is hoped, limit future disability and reduce demyelination-related central nervous system injury. Of particular clinical relevance in children, there are many mimics of demyelinating disease that must be considered.
Amniotic Fluid Embolism
Authors: Quiner Trevor E , Foley Michael R
Published: January 2021

Amniotic fluid embolism remains a devastating and incompletely understood phenomenon of acute cardiopulmonary collapse and coagulopathy in labor and immediate postpartum period not explained by other diagnoses. It is rare in the general population but is a relatively frequent cause of maternal death and long-term neurologic deficit. Diagnosis should rely on the presence of classic clinical findings and not histopathologic findings of squamous cells in the vasculature of the deceased. Management relies on quick and aggressive support measures and advanced cardiac life support in cases of cardiac arrest. Coagulopathy and hemorrhage is best managed with massive transfusion protocols.
 
This review contains 6 figures, 5 tables and 65 references
Key Words: amniotic fluid, amniotic fluid embolism, anaphylactoid syndrome of pregnancy, disseminated intravascular coagulopathy; massive transfusion, maternal cardiac arrest, obstetric hemorrhage, pregnancy, pulmonary embolism, respiratory distress
Common Maternal Genetic Syndromes II: Marfan Syndrome
Authors: Al-Beshri Ali Said , Robin Nathaniel H.
Published: January 2021

Marfan syndrome is an autosomal dominant syndrome that affects various connective tissues including the aorta and skeletal system. It represent a major cause of aortic dissection in individuals with seemingly unremarkable past medical history, and is the most common cause of aortic dissection in pregnancy. Prompt and accurate diagnosis can be lifesaving. Careful physical examination and detailed personal and family history is vital for clinical evaluation. Genetic testing is often needed for accurate diagnosis but result interpretation might be challenging and genetic counseling is always required. Established guidelines can help navigate the challenges in obstetric management, which may include major surgical interventions during or after pregnancy.
This review contains 6 figures, 4 tables, and 40 references.
Keywords: Marfan syndrome, FBN1, aortic dissection, dilatation, connective tissue, ectopia lentis, pectus, systemic score, Ghent diagnostic criteria, genetic testing.
Connective Tissue Disorders: Ehlers-Danlos Syndrome
Authors: Chopra Pradeep
Published: January 2021

Almost every physician is bound to come across patients with connective tissue disorders, especially Ehlers-Danlos syndrome (EDS). These patients present with a cluster of conditions, including chronic joint, muscle, and neuropathic pain; easy fractures; gastrointestinal symptoms; orthostatic intolerance; headaches; spinal pain; urinary symptoms; recurrent joint subluxations and dislocations; and aneurysm. The incidence of EDS is 10 in 100,000. These patients have a genetic defect in their collagen. A weak connective tissue makes the joints hypermobile, causes muscle fatigue,  easy bruising, fragile skin, spinal pain, and headaches. The diagnosis is made clinically based on a medical history and clinical examination. It does not depend on genetic testing. The Beighton score has been the most widely accepted for diagnosing EDS. It has proven to be a very consistent screening tool. The most common symptom patients present with is pain. They have increased pain at different stages of their life; as adolescents, they have growing pains. These pains are usually worse during periods of growth spurt. The pain is intense and usually in the lower extremity around the knees, and they have leg cramps, especially at night. Concerned parents are told to ignore it, and no specific treatment is offered to these children. As adults, patients present with a more specific pain to either a region or the spine. Musculoskeletal pain is most commonly around the neck, upper back, hips, legs, and forearms. In most cases, the pain is around the weight-bearing muscles, such as the legs and spine. Patients with EDS present with both nociceptive (structural) and neuropathic pain; in some cases, the neuropathic pain component may be more prominent than the nociceptive component and vice versa. One of the major issues in EDS is a loss of proprioception, also known as joint position sense. Proprioception is the ability of a joint to determine its position, detect movement, and sense resistance to force. EDS is associated with other coexisting conditions, such as postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), Chiari malformation, and tethered cord syndrome. Significant fatigue is a common feature in EDS. The reason for fatigue may be an abnormality of the muscle structure, POTS, MCAS, and excessive dependence on muscles to maintain posture in light of ligamentous laxity.
Pain and Chemical Dependency
Authors: Silverman Sanford M
Published: January 2021

Pain can mean different things to different people. At the same time, it is a subjective and objective sensation. For the patient experiencing pain, it is an unpleasant sensation that causes undue suffering. Chemical dependency or addiction is characterized by inability to consistently abstain, impairment in behavioral control, and craving; diminished recognition of significant problems with one’s behaviors and interpersonal relationships; and a dysfunctional emotional response. It is a complex chronic disease of brain reward, motivation, memory, and related circuitry. The prevailing view of opioid therapy for chronic pain is a pendulum swinging between opiophobia and opiophilia. The intersection between pain and addiction is also a moving target. Various stakeholders have attempted to find a balance between addressing the crisis of chronic pain in society and not exacerbating the problem of substance abuse. The pain practitioner must recognize the duality that exists between chronic and chemical dependency and must assess risk prior to using controlled substances to manage that pain, and if things go awry, the physician must have an exit strategy. Discharging problem patients merely transfers the problem elsewhere. Offering patients a solution to iatrogenic dependence on controlled substances is a viable and compassionate path for both the patient and the practitioner.
This review contains 2 figures, 2 tables, and 20 references.
Key Words: pain, opioids, opiophobia, opiophilia, substance abuse, chemical dependency, addiction, chronic pain
Lumbar Spinal Stenosis and Neurogenic Claudication
Authors: Manchikanti Laxmaiah , Albers Sheri L , Latchaw Richard
Published: January 2021

Lumbar spinal stenosis is a degenerative condition that develops and progresses slowly over time. Lumbar spinal stenosis may be local, segmental, or generalized. The majority of lumbar spinal stenosis cases are acquired, degenerative stenosis, resulting from aging of the spine or following surgery or infection. Management of lumbar spinal stenosis is challenging and requires the integration of the history, clinical findings, and results of diagnostic imaging. Magnetic resonance imaging is the most commonly used imaging modality in diagnosing lumbar spinal stenosis. Typical features of spinal stenosis with neurogenic claudication include an increase in symptoms with extension and a decrease with flexion. With lateral recess stenosis or foraminal stenosis, isolated radiculopathy can occur. Spinal stenosis is classified as mild, moderate, and severe, ranging from one third to two thirds of the canal, and grade I to grade III classification of neurogenic intermittent claudication. Management of lumbar spinal stenosis is largely conservative except in cases of severe spinal stenosis and neurogenic claudication with or without paresis and other symptoms. Nonsurgical management of lumbar spinal stenosis includes drugs, physiotherapy, epidural injections, multidisciplinary rehabilitation, and spinal cord stimulation. Minimally invasive techniques include minimally invasive lumbar spinal decompression, interspinous spacers, and endoscopic surgical decompression. The final treatments include open surgery with decompression with or without fusion and spinal cord stimulation.
Key words: acquired stenosis, central spinal stenosis, congenital stenosis, decompression with fusion, decompression without fusion, endoscopic spinal decompression, epidural injections, foraminal spinal stenosis, interspinous spacers, lateral spinal stenosis, lumbar spinal stenosis, minimally invasive lumbar decompression, neurogenic claudication, percutaneous adhesiolysis, shopping cart syndrome, spondylolisthesis, vascular claudication
Continuous Peripheral Catheters/Regional Anesthesia in Postoperative Pain Management
Authors: Hirsch David E. , Solanki Daneshvari R.
Published: January 2021

As the number of surgical procedures has increased worldwide, so has the need for safe and effective postoperative pain control. Regional anesthesia, in which a provider uses local anesthesia and potentially other medications to provide anesthesia by focusing on blocking sensation at the surgical site, has become an important part of the postoperative pain regimen, thereby improving outcomes and comfort. Regional anesthesia plays a critical and significant role with regard to preemptive analgesia and multimodal anesthetic techniques. With the widespread use of ultrasonography and the introduction of peripheral nerve catheters, regional anesthesia has grown in its ability to provide longer-lasting, safe, and targeted pain control. Extended-relief lipid emulsion bupivacaine is another example of recent developments in drug technology that will further aid regional anesthesia delivery in the future.
This review contains 5 figures, 4 tables, and 23 references.
Flexor Tendon Injuries
Authors: Long Chao , Moody Lisa C , Fox Paige M , Chang James
Published: January 2021

Flexor tendon injuries are common hand injuries that can significantly affect hand function. Treatment of these injuries requires a thorough understanding of the intricate anatomy and biomechanics of flexor tendons. The goals of reconstruction include restoration of tendon continuity, preservation and reconstruction of the pulley system, maximizing tendon gliding, and minimizing adhesion formation. Surgical treatment, in conjunction with postoperative hand therapy, provides enhanced function. This review provides the surgeon with the relevant anatomy, pearls of clinical evaluation, necessary investigative studies, management algorithms, surgical techniques, rehabilitation protocols, and approaches to common complications. It ends with a discussion of basic and translational research currently being undertaken to address the challenges posed by flexor tendon injuries and how this research can potentially advance patient care.
 
This review contains 16 figures, 5 tables and 55 references
Key words: flexor tendon, flexor tendon injuries, flexor tendon reconstruction, flexor tendon repair, hand, hand surgery, injury, surgical technique, tendons
Male-to-Female Gender-Confirming Surgery
Authors: Morrison Shane D , Wilson Stelios C , Perez Marcelina G , Satterwhite Thomas
Published: January 2021

Advances in male-to-female gender-confirming surgery enable acquisition of female secondary sexual characteristics for gender dysphoric patients desiring surgical transition. It is imperative for medical professionals caring for transgender patients to be informed of the current standards of care and the available surgical options. This review discusses male-to-female chest and genital reconstructive surgical approaches.

This review contains 27 figures, 5 tables and 52 references
 Key words: augmentation mammoplasty, gender-confirming surgery, genital reconstruction, male to female, transgender, vaginoplasty
Neurobiology of Trauma and Stressor-Related Disorders
Authors: Maheu Marissa Elizabeth , Howie Joseph Hunter , Ressler Kerry James
Published: January 2021

Posttraumatic stress disorder (PTSD) and acute stress disorder are precipitated by exposure to one or more traumatic events, and result in debilitating fear-related symptoms. Advances made over the past several years have greatly improved our understanding of these disorders, as well as the neurobiological and genetic factors that contribute to their emergence and progression. In this review, we provide an overview of this research, with a particular focus on recent developments in understanding the neurocircuitry underlying relevant aspects of fear learning, including acquisition, generalization, and the extinction of fear. Molecular regulators of stress response and candidate genes implicated in PTSD are also discussed. Although there remains a great deal to learn about these disorders, novel approaches, large-scale genomic studies, and new molecular techniques promise to help untangle the neurobiology of trauma- and stressor-related illness over the coming years.

This review contains 3 figures, 3 tables and 56 references
Key words: Posttraumatic stress disorder, fear, genetics, GWAS, HPA stress response, neurocircuitry models of trauma, generalization, extinction learning.
Gambling Disorder and Related Behavioural Addictions
Authors: Grant Jon E , Leppink Eric W
Published: January 2021

Behavioral addictions are defined as behaviors characterized by the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others. These disorders share many similarities with substance addictions but may have unique treatment considerations. This category of disorders includes many separate behaviors, but some of the most common are gambling disorder, Internet addiction, compulsive buying, and compulsive sexual behavior. Although research remains limited on the neurobiology and treatment of these disorders, some limited evidence to date can help guide initial treatment recommendations. Additional research will be necessary to clarify the optimal treatment approach for these disorders, however. This review provides a general discussion of available research related to these four disorders, including neurobiological, epidemiologic, and treatment considerations.
Key words: behavioral addiction, gambling, Internet, neurobiology, phenomenology, sex, shopping, treatment
Psychodynamic Psychotherapy
Authors: Brenner Adam , Laney Michael
Published: January 2021

Psychodynamic psychotherapy is an evidence-based treatment that historically had its origins in psychoanalysis. It is based on an appreciation that the past continues to interfere with the present through the persisting existence of relationship templates generated during development. These developmental experiences include ideas, wishes, and fears that are too disturbing for the patient to allow awareness but continue to exert their effects outside of conscious awareness. The psychodynamic therapist fosters an experience that allows for unconscious material to become more available, through free association, examination of resistance, and exploration of transference. As therapy progresses, the growth of the patient’s insight and the resumption of stalled developmental opportunities result in symptomatic improvement and an enhanced quality of life. Psychodynamic psychotherapy has both a long history and an expanding literature that will both reward further study and assist in the care and understanding of those sufferers who are seen by clinicians every day.
This review contains 5 tables, and 60 references.
Key words: attachment, autonomy, free association, identity, resistance, separation, therapeutic attitude, transference, triangular relationships, unconscious motivation