bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic patterns of liver injury induced by anti-PD-1 therapy
Authors: Zhang Dongwei , Hart John , Ding Xianzhong , Zhang Xuchen , Feely Michael , Yassan Lindsay , Alpert Lindsay , Soldevila-Pico Consuelo , Zhang Xuefeng , Liu Xiuli , Lai Jinping
Published: August 2019

Background

Nivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1 (PD-1)—have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them.

Methods

Eight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients.

Results

Seven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy.

Conclusions

Our study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients.
Visual Impairment and Frailty: Examining an Understudied Relationship
Authors: Swenor Bonnielin K , Lee Moon J , Tian Jing , Varadaraj Varshini , Bandeen-Roche Karen
Published: August 2019

Background

Older adults with visual impairments are at increased risk of negative health outcomes. Here, we investigate the association between visual impairment and frailty.

Methods

Cross-sectional and longitudinal relationships between visual impairment (distance visual acuity) and frailty (frailty phenotype criteria) were examined using data from the National Health and Nutrition Examination Survey (NHANES, 1999–2002, ≥60 years) and the Women’s Health and Aging Studies (WHAS III). Imbalance of potential confounders, particularly age, was addressed using propensity score-based adjustment. Multinomial logistic regression determined the odds of prefrailty and frailty at baseline in NHANES and ordinal logistic regression examined the odds of baseline and incident frailty over 3 years in WHAS III after adjustment for confounders and probability weighting (survey weights × inverse propensity scores).

Results

In NHANES (n = 2,639, 9% vision impairment), participants with visual impairment were more likely to be prefrail (odds ratio [OR] = 3.2; 95% confidence interval [CI]: 1.9–5.3) and frail (OR = 3.7; 95% CI: 1.5–9.2) than those without visual impairment. In WHAS III (n = 796, 26% mild, 37% moderate/severe vision impairment), participants with mild and moderate/severe vision impairment were more likely to be frail (OR = 2.0; 95% CI: 1.5–2.5; OR = 5.5; 95% CI: 4.2–7.2, respectively). A one-line worse visual acuity (0.1 logMAR increase) was associated with greater odds of frailty (OR = 1.5; 95% CI: 1.4–1.7). Of those non-frail at baseline (n = 549), moderate/severe visual impairment and one-line worse visual acuity was associated with greater odds of incident frailty (OR = 3.5; 95% CI: 1.4–8.4; OR = 1.3; 95% CI: 1.1–1.5, respectively) over 3 years.

Conclusions

Visual impairment may be an important, yet understudied risk factor for frailty.
Movements of Atlantic halibut in the Gulf of Maine based on geolocation
Authors: Liu Chang , Bank Crista , Kersula Michael , Cowles Geoffrey W , Zemeckis Douglas R , Cadrin Steven X , McGuire Christopher
Published: August 2019

Atlantic halibut are a “Species of Concern” in US waters and little is known about their movements and stock structure. Recent stock assessments drew attention to the paucity of information for assessing and managing this stock. To investigate movement patterns and stock structure, halibut were tagged off Massachusetts and Maine within US waters of the Gulf of Maine region using pop-up satellite archival tags and data storage tags. A hidden Markov model (HMM) geolocation method previously developed for other groundfish species was adapted to estimate the movement tracks of the tagged halibut (n = 25) based on the tag-recorded depth and temperature. Total distance travelled based on geolocation ranged from 36 to 1701 km, whereas straight line distance between tagging and end locations ranged from 0.4 to 440.7 km. Estimated movement rates varied between 2.7 and 10 km day−1. Two tagged halibut made long-distance movements to putative spawning habitat in the Northeast Channel off Georges Bank. Thirteen (13) out of 25 geolocated individuals were estimated to have reached Canadian waters. Geolocation results revealed home range, return movement, and seasonal migration movement patterns exhibited by the tagged halibut. The HMM geolocation method could be a useful tool in providing information on halibut movements that can inform stock assessment and management decisions.
Pulmonary carcinosarcoma: analysis from the Surveillance, Epidemiology and End Results database
Authors: Sun Liangdong , Dai Jie , Wang Xujun , Jiang Gening , Gonzalez-Rivas Diego , Song Jiong , Zhang Peng
Published: August 2019

OBJECTIVES

Pulmonary carcinosarcoma (PCS) is a rare neoplasm. This study explored the clinicopathological characteristics and survival outcomes of PCS.

METHODS

The Surveillance, Epidemiology and End Results (SEER) database (1988–2014) was queried for PCS. Overall survival (OS) was evaluated by multivariable Cox regression and nomograms were constructed to predict 3-year OS for PCS. Prognostic performance was evaluated using concordance index and area under the curve analysis. In M0 surgically treated patients, interaction assessments were performed using likelihood ratio tests. Subgroup analysis was performed according to patient age. The clinical features of PCSs were further compared to other non-small-cell lung cancers (NSCLCs).

RESULTS

Multivariable analysis identified age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01–1.04], surgery (HR 0.53, 95% CI 0.36–0.77) and chemotherapy (HR 0.51, 95% CI 0.36–0.73) as significantly associated with OS. The nomogram had a concordance index of 0.747 and an area under the curve of 0.803. The association between age and OS was stronger in those receiving pneumonectomy (P = 0.04 for interactions) compared to those that did not (HR 5.14, 95% CI 1.64–16.07), and was associated with a poorer outcome compared to lobectomy amongst the elderly (age ≥ 70 years). Patients with PCS were more likely to receive surgical treatment and had lower lymphatic metastasis compared to adenocarcinoma, squamous cell carcinoma and large cell carcinoma (all P < 0.05).

CONCLUSIONS

PCS had unique clinical features compared to common types of NSCLCs in terms of lymphatic invasion and surgical treatment. Pneumonectomy was associated with poorer survival in elderly patients.
The effects on nutrient utilization and stool quality of Beagle dogs fed diets with beet pulp, cellulose, and Miscanthus grass12
Authors: Donadelli Renan A , Aldrich Charles G
Published: August 2019

Dogs can benefit from dietary fibers. Traditionally, cellulose (CE) and beet pulp (BP) have been used by pet food companies as insoluble and soluble fiber sources. Miscanthus grass (MG) is a novel fiber ingredient made from Miscanthus giganteus, a C4 grass produced for its fiber content, but it has not been evaluated for dogs. The objectives of this study were to determine the effects of different fiber sources on nutrient utilization and stool consistency by dogs. Twelve Beagle dogs were fed 3 dietary treatments varying in their fiber sources (BP, CE, MG). Diets were fed for a 14-d period (9 d adaptation), fecal samples were collected (5 d total fecal collection) and scored. Nutrient digestibility was estimated using total fecal collection (TFC). Dogs fed BP diet had softer stools than dogs fed CE and MG (3.15 vs. 3.68 and 3.64, respectively). Wet fecal output was higher for dogs fed CE compared to MG, with dogs fed BP having the lowest values (254.3 g vs. 241.6 g vs. 208.5 g, respectively). Dogs fed CE and MG had lower DM digestibility than dogs fed BP (P < 0.05), dogs fed BP had lower CP digestibility compared with dogs fed MG and CE (81.4% vs. 85.5% and 85.8%, respectively). In conclusion, MG could be used as an alternative fiber source to CE.
First record of cuticle bands in the stomach ossicles of the red king crab Paralithodes camtschaticus (Tilesius, 1815) (Decapoda: Anomura: Lithodidae) from Norway
Authors: Bluhm Bodil A , Kilada Raouf , Ambrose William , Renaud Paul E , Sundet Jan H
Published: August 2019

The red king crab Paralithodes camtschaticus (Tilesius, 1815) is a large predator intentionally introduced to the Barents Sea and adjacent fjords in the 1960s. Its establishment has given rise to both a high-value fishery and destructive effects on seafloor habitats and communities. Given the need for accurate information on age, growth, and longevity that could improve management and mitigation strategies for red king crab, developing and testing new aging methods for this and other crustaceans has been an active field of research. We contribute to this test bed by investigating cuticle bands in gastric mill ossicles of male and female red king crabs. Cuticle bands were detectable in most individuals studied and maximum cuticle band count was 13 for males (N = 62, 38–180 mm carapace length (CL)) and 9 for females (N = 34, size range 80–147 mm CL). There was large variation of size-at-band count and band count-at-size data. The number of cuticle bands generally increased with CL in male red king crabs; low sample size and small size range in females prevented seeing any trend. Exploring calcein staining in a sub-sample of the crabs suggested uptake of the stain, yet without a clearly defined mark, and showed deposition of ossicular material beyond the calcein stain in the subsequent year. We recommend research on the mechanism generating band deposition to shed light on how and when bands are formed as the basis for testing whether the cuticle bands may reflect chronological (specifically annual) age. Specifically, we recommend long-term maintenance of crabs, study of both moults and newly formed ossicle structures, as well as stringent testing of band periodicity with known-age crabs, including all size classes and both sexes.
NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain
Authors: Luo Zhiyuan , Mu Lili , Zheng Yue , Shen Wenchen , Li Jiali , Xu Lichao , Zhong Bo , Liu Ying , Zhou Yan
Published: August 2019

The release and nuclear translocation of the intracellular domain of Notch receptor (NICD) is the prerequisite for Notch signaling-mediated transcriptional activation. NICD is subjected to various posttranslational modifications including ubiquitination. Here, we surprisingly found that NUMB proteins stabilize the intracellular domain of NOTCH1 receptor (N1ICD) by regulating the ubiquitin–proteasome machinery, which is independent of NUMB’s role in modulating endocytosis. BAP1, a deubiquitinating enzyme (DUB), was further identified as a positive N1ICD regulator, and NUMB facilitates the association between N1ICD and BAP1 to stabilize N1ICD. Intriguingly, BAP1 stabilizes N1ICD independent of its DUB activity but relying on the BRCA1-inhibiting function. BAP1 strengthens Notch signaling and maintains stem-like properties of cortical neural progenitor cells. Thus, NUMB enhances Notch signaling by regulating the ubiquitinating activity of the BAP1–BRCA1 complex.
Clinical Development of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Gougis Paul , Moreau Bachelard Camille , Kamal Maud , Gan Hui K , Borcoman Edith , Torossian Nouritza , Bièche Ivan , Le Tourneau Christophe
Published: August 2019

A better understanding of cancer biology has led to the development of molecular targeted therapy, which has dramatically improved the outcome of some cancer patients, especially when a biomarker of efficacy has been used for patients’ selection. In head and neck oncology, cetuximab that targets epidermal growth factor receptor is the only targeted therapy that demonstrated a survival benefit, both in the recurrent and in the locally advanced settings, yet without prior patients’ selection. We herein review the clinical development of targeted therapy in head and neck squamous cell carcinoma in light of the molecular landscape and give insights in on how innovative clinical trial designs may speed up biomarker discovery and deployment of new molecular targeted therapies. Given the recent approval of immune checkpoint inhibitors targeting programmed cell death-1 in head and neck squamous cell carcinoma, it remains to be determined how targeted therapy will be incorporated into a global drug development strategy that will inevitably incorporate immunotherapy.
An urban wildlife habitat experiment: conservation implications of altering management regimes on animals and plants along urban and rural rights-of-way
Authors: Leston Lionel , Koper Nicola
Published: August 2019

Biodiversity along rights-of-way (ROWs) can decline due to local-scale management, including frequent urban mowing and spraying, or with increasing amount of urban infrastructure surrounding those grassy spaces. Distinguishing effects of mowing regime from effects of surrounding urban land are necessary to determine what management strategies effectively conserve wildlife in different landscapes, and to justify changes in management that could increase populations of weeds. We used a manipulative Before/After-Control/Impact (BACI) experiment in 17 transmission line ROWs during 2007–2009, along an urbanization gradient, to disentangle effects of mowing frequency and the amount of urban land (buildings, hard surfaces like concrete, asphalt) surrounding ROWs. In the BACI study, we halted mowing and spraying for 1 year in five urban ROWs, introduced two rounds of mowing per year in three rural ROWs, and compared vegetation and arthropods found within these manipulated ROWs and within three urban and six rural control ROWs. European skipper butterflies Thymelicus lineola, lepidopteran biomass in herbaceous vegetation, milkweeds (Asclepias spp.) and Canada thistle Cirsium arvense increased when mowing and spraying were halted for one year. Conversely, monarch butterflies Danaus plexippus, legume cover and dandelion Taraxacum officinale increased when mowing was introduced to rural ROWs. To increase taller butterfly resource plants while still controlling weeds within urban ROWs, we recommend reducing management frequency within the interior of ROWs while maintaining frequent management along ROW borders that are adjacent to infrastructure.
Part III Section 4 in “Practice”, 8 Section 4’s Simple Core
Authors: Brian C Kalt
Published: August 2019

Since Section 4 of the Twenty-Fifth Amendment is untested outside the bounds of fiction, the best way to examine its “case history” is through hypothetical situations that tee up issues that might arise. The scenarios in this first chapter are simple: clear, total inability. When a president is unconscious for an indefinite period, when he is unable to communicate due to a stroke, when he is clearly delusional—these are the easy cases that showcase why the amendment was created. Stripping the President of power and restoring it once he has recovered are simple and non-controversial in these situations. These scenarios share an instant revocation followed by a careful and deliberate restoration. The President does not dispute his inability. Medical advice supports the opinion that the President is unable, and consensus exists to say he has regained his capacity. The entire process would be open to public scrutiny.
Part III Section 4 in “Practice”, 10 The Four-Day Wait
Authors: Brian C Kalt
Published: August 2019

When a President responds to a Section 4 action by declaring that she is not disabled, she does not take power back immediately—the Vice President and Cabinet are given four days in which to challenge her, during which time the Vice President remains in charge. But many people have misread this provision and think that the President retakes power immediately upon declaring she has recovered. Though the odds of a President following this misinterpretation may be small, the stakes are potentially enormous. A president who immediately regained control could purport to fire the Cabinet members who voted against her, which (according to her side) would prevent the remaining procedures in Section 4 from taking place. In that situation, the country could have two presidents leading two cabinets unless the correct understanding of Section 4 is widely known among the administration and by the public.

This chapter offers proof of the correct interpretation of the four-day waiting period. It is clear from Section 4’s plain text, its legislative history, and its basic structure.
A Muslim Neonatologist in a Canadian NICU
Authors: Tyebkhan Juzer M.
Published: August 2019

What is the impact on a Muslim family of having a baby in the neonatal intensive care unit (NICU)? This chapter is written by a Muslim neonatologist, trained in the United Kingdom and Canada, who now works in a level III NICU in Edmonton, Canada. In addition to describing religious requirements and community traditions, the author suggests ways that these can be incorporated into the care of Muslim babies and families in our high-stress, technology-based NICUs. As a member of the Dawoodi Bohra sect (a subset of the Shi’a Muslim community), the author provides a brief background of the community’s spiritual heritage and their viewpoint on modern medical treatment. The living spiritual leader of the Dawoodi Bohras, the Da’i, is their source of authoritative decision making. The author explains how and why decision making in situations of critical illness is referred to the Da’i for His trusted advice.
Introduction to Pediatric Sleep Clinic and Sleep Testing
Authors: Grigg-Damberger Madeleine , Wolfe Kathy M.
Published: August 2019

This chapter covers the diagnostic evaluation of children and adolescents referred to sleep centers. Diagnosis of sleep disorders in children begins with a structured history. Pediatric sleep questionnaires can be useful. Polysomnography can be frightening for children, and child-friendly polysomnography techniques are discussed. The authors outline how sleep studies are scored in children. The use of actigraphy, nocturnal home oximetry, and multiple sleep latency testing is reviewed. Smartphone apps for monitoring sleep/wake are summarized. The authors believe that more evidence of the validity of smartphone apps is needed before we accept data from them and integrate this information into decision making and the electronic medical records.
LA Night Moves
Authors: Avidan Alon Y. , Grigg-Damberger Madeleine
Published: August 2019

Two cases of non–rapid-eye-movement (NREM) arousal parasomnias in adults are discussed in this chapter. NREM arousal parasomnias occur in 2% of adults and are often triggered by sleep deprivation, emotional stress, circadian rhythm disorders, and sleep fragmentation. Disorders of arousal include confusional arousal, sleepwalking, and sleep terrors. Research into the pathogenesis of arousal disorders in adults suggests that they reflect aberrant slow-wave sleep regulation, impaired arousal specifically from NREM 3 sleep, and/or sleep/wake state dissociations. Treatment of DoA includes avoidance of sleep deprivation/restriction, irregular sleep/wake schedules, and predisposing/precipitating factors. Pharmacotherapy can be considered when events pose a danger and/or sleep disturbance to the patient and/or others; involve potentially violent, dangerous, or sexual behavior; are frequent, chronic, and refractory to initial therapies; and/or have secondary consequences such as excessive daytime sleepiness, impaired quality of life, excessive weight gain, and injuries.
Is Resistance Futile?
Authors: Walia Harneet K. , Mansukhani Meghna P.
Published: August 2019

Obstructive sleep apnea (OSA) is highly prevalent in patients with hypertension, particularly in the resistant hypertension population. A large body of evidence supports the association between OSA and incident hypertension independent of confounding risk factors. This chapter discusses the relationship between OSA and hypertension and resistant hypertension, including the prevalence, epidemiology, and pathophysiologic mechanisms linking these conditions. Treatment of OSA has been shown to reduce blood pressure in patients with hypertension, and the reduction is more marked in those with resistant hypertension. Given the high prevalence of OSA in patients with resistant hypertension, clinicians should be cognizant about screening and evaluating for OSA in patients with resistant hypertension, as treatment of OSA can improve blood-pressure control.
Rewriting One Patient’s Story of Disrupted Sleep
Authors: Domingo Samantha , Drerup Michelle L.
Published: August 2019

This chapter covers treatment options for individuals with chronic insomnia disorder. We describe the effectiveness of cognitive behavioral therapy for insomnia (CBT-i) and various modalities of delivery of the treatment. CBT-i is an alternative treatment for insomnia that has been demonstrated to be as successful as pharmacological therapies in the short term, and more effective in the long term. CBT-i comprises sleep restriction, stimulus control, relaxation training, sleep hygiene, and cognitive restructuring. The authors examine group CBT-i as a way to increase social support and enhance treatment adherence. Computerized CBT-i is a newer option to provide increased access to this treatment.
Too Much of a Good Thing
Authors: Bae Charles , Roy Asim , Ling Lim Li
Published: August 2019

This chapter covers the diagnostic criteria and epidemiology of restless legs syndrome (RLS) and pharmacotherapy for this highly prevalent disorder. Specifically, the case illustrates a patient with RLS treated with dopaminergic medication and the phenomenon of augmentation. The diagnosis of RLS with augmentation due to dopaminergic medication was based on the history of worsening symptoms in relation to upward titration of a dopaminergic agent that was initially effective, with symptom improvement after the agent was discontinued. The differentiation of augmentation and rebound is discussed. Familial and secondary forms of RLS are viewed. Pharmacotherapy for RLS includes dopaminergic agents, alpha-2-delta ligands, benzodiazepines, and opioids; these are detailed and indications, approval by the U.S. Food and Drug Administration, dosing, and adverse effects are discussed.
CPAP, What’s Not to Love?
Authors: Polk Edwina , Chakrabarti Subhra , Mehra Reena , Cerejo Sushruta
Published: August 2019

Obstructive sleep apnea (OSA) has been associated with significant decrements in quality of life, including daytime sleepiness, drowsy driving, and adverse health effects. Treatment of OSA with continuous positive airway pressure (CPAP) improves sleepiness symptoms, and some data support improvement in cardiometabolic outcomes. CPAP adherence, however, remains suboptimal, thereby hampering the symptom-based and health benefits that could be fully realized. Many strategies have been developed to increase PAP adherence, including behavioral interventions and an approach known as the PAP-NAP study, an intervention that focuses on improving the patient’s acceptance of PAP therapy by using regimented acclimation and desensitization techniques.
Lost in a Dream
Authors: Rodriguez Carlos L. , Tousi Babak
Published: August 2019

Rapid-eye-movement sleep behavior disorder (RBD) is a parasomnia that is closely associated with neurodegenerative disorders. RBD is usually caused by neurodegeneration within the brainstem that disables the system responsible for immobilizing skeletal muscles during REM sleep and thus permits motor neurons to activate these muscles during dreaming. The underlying source of the brainstem neurodegeneration spreads over time to other central nervous system regions until it has sufficiently evolved to permit clinical recognition of the underlying neurodegenerative disorder. Longitudinal follow-up of patients with RBD has demonstrated that most patients subsequently develop some neurodegenerative disorder years later, particularly the synucleinopathies. We review the relationship between RBD and dementia with Lewy bodies, which is one of the synucleinopathies. The management of RBD is reviewed with discussion of the relevant considerations in patients with dementia with Lewy bodies.
Napping the Day Away
Authors: Golden Erin , Tippmann-Peikert Maja
Published: August 2019

This chapter describes a patient with narcolepsy type 1, a disorder of central hypersomnolence. His history, clinical evaluation, study results, treatment, and clinical course are detailed. The disorder is then reviewed, highlighting its classic clinical features—hypersomnia, cataplexy, sleep paralysis, hypnagogic and hypnopompic hallucinations, and disturbed sleep—and its underlying pathophysiology. The differential diagnosis is discussed, and recommendations for clinical evaluation are provided with official diagnostic criteria from the International Classification of Sleep Disorders, 3rd edition. Pharmacologic and nonpharmacologic treatment options are then addressed, along with their respective benefits and side-effect profiles.
Oh My, Wet Bed and Dry Mouth Lead to Wet Eyes
Authors: Krishna Jyoti , Grigg-Damberger Madeleine
Published: August 2019

The association between childhood obstructive sleep apnea (OSA) and sleep enuresis has been known for some time. This case discusses current understanding of the pathophysiologic relationship between the two. The authors also discuss the current diagnostic criteria and standardized terminology of enuresis as developed by the International Children’s Continence Society and the American Academy of Sleep Medicine. Components of a sleep history and physical examination that are key to establishing the complex relationships between enuresis and OSA are reviewed. Hypotheses for the higher prevalence of sleep enuresis in patients with OSA are summarized. Although the treatment of OSA often results in reversal of enuresis, and the mechanistic pathways appear plausible, the strength of evidence in the literature that OSA causes enuresis in children is not very strong, and further research is warranted.
What a Pain! My Childhood Leg Cramps Are Back
Authors: Lim Li Ling
Published: August 2019

This case report illustrates an example of restless legs syndrome (RLS) with a positive family history and several secondary and exacerbating factors (including iron and vitamin B12 deficiency). RLS is a common yet often overlooked condition for which effective treatment is available. Symptoms can be triggered or exacerbated by common medications such as over-the-counter antihistamines, caffeine, and antidepressant medication. Secondary causes for RLS, including iron deficiency, should be excluded and treated. RLS can be inheritable. Childhood-onset symptoms and the presence of a first-degree relative with symptoms of RLS are suggestive of familial RLS. Symptoms of RLS are effectively managed by correction of secondary causes and medications, including dopamine agonists and certain anticonvulsants.
Bonnie and Clyde, the Overlap Syndrome
Authors: Mar Hugo Paz y , Mehra Reena
Published: August 2019

This chapter reviews the “overlap syndrome” between obstructive sleep apnea and chronic obstructive pulmonary disease. The authors discuss the potential mechanisms implicated in these interactions and the bidirectional influences that the entities exert on one another. Overlap syndrome is a highly prevalent condition associated with increased morbidity and mortality. It has been associated with a high recurrence of acute exacerbations of COPD compared to isolated COPD. The chapter also reviews the interactions of overlap syndrome during sleep and the clinical consequences of untreated overlap syndrome. Therapeutic options and the benefits of continuous positive airway pressure are also reviewed. The mortality benefits of treating overlap syndrome with CPAP have been extensively demonstrated but the role of noninvasive positive-pressure ventilation in the treatment of overlap syndrome remains poorly established.
Help, I Can’t Breathe!
Authors: Chua Ai Ping , Aboussouan Loutfi S.
Published: August 2019

This chapter presents a case of treatment-emergent central sleep apnea (TECSA), which is also known as complex sleep apnea syndrome or continuous positive airway pressure (CPAP)–emergent central sleep apnea. In this disorder, central apnea events emerge in patients with obstructive sleep apnea (OSA) after initiation of CPAP treatment. This phenomenon has been identified in up to 20% of patients with OSA who undergo CPAP titration. Polysomnography in those with TECSA usually shows an elevated residual Apnea–Hypopnea Index and arousal index after PAP initiation and occurs primarily during non–rapid-eye-movement sleep. Several mechanisms that have been postulated will be reviewed. The phenomenon is usually self-limiting, and recommended management includes applying the lowest PAP pressure needed to achieve reasonable control and avoiding modalities that exacerbate hypocapnia.
Midnight Mystery
Authors: Lavery Megan E. , White Emily K.
Published: August 2019

This chapter discusses the treatment of night eating syndrome (NES) in an obese man seeking bariatric surgery. There is some evidence to suggest that the prevalence of NES increases with higher body mass and is relatively common in the bariatric surgery population. NES is considered to be a contraindication for surgery by many bariatric surgery programs. Therefore, targeted treatment is often necessary prior to approval for surgery. Although research is still emerging in regards to treatment of NES, current approaches include pharmacologic, biologic, and behavioral or cognitive-behavioral interventions. The authors describe the application of key treatment approaches in the current case and differentiate NES, sleep-related eating disorder, and binge eating disorder.
Mechanical Ventilation: Advanced Modes
Authors: Lowell Amelia A. , Patel Bhavesh M.
Published: August 2019

The primary purpose of mechanical ventilation is to support the physiologic processes of oxygenation and ventilation and to reduce the work of breathing. The present chapter focuses on advanced modes and modalities of therapy for patients receiving mechanical ventilation. The term advanced must be interpreted with caution because the use of many of the newer modes of ventilation is not supported with substantial evidence of superiority to the basic modes of ventilation for patient outcomes. Rather, advanced refers to the engineering controls and the proposed patient benefits.
Cardiogenic Shock
Authors: Ratzlaff Robert A. , Siegel Jason L.
Published: August 2019

Like all forms of shock, cardiogenic shock (CS) is a life-threatening condition of decreased blood circulation that ultimately causes systemic hypoperfusion and end-organ failure. Unlike other forms of shock, however, CS is characterized by failure of the heart itself. This chapter describes CS, including its causes and diagnosis, and provides a brief overview of management.
Acute Perforations of the Gastrointestinal Tract
Authors: Tsamalaidze Levan , Stauffer John A.
Published: August 2019

Acute perforations of the gastrointestinal tract (GI) with subsequent release of gastric or intestinal contents into the peritoneal space have multiple causes and portend a high mortality depending on the cause. The key symptom is a sudden appearance of abdominal pain followed by signs of peritoneal irritation, severe sepsis, or shock. A proper imaging evaluation should lead to surgical intervention and aggressive supportive management.
Drug Dosing in Renal Failure
Authors: Jackson Daniel A.
Published: August 2019

Optimal dosing of medications can be influenced by many factors. These factors are important to consider because the therapeutic effects of drugs are frequently concentration dependent and can even result in toxicity. One factor of great importance is the pharmacokinetics of a medication. Pharmacokinetics is the way in which medications move through the body during absorption, distribution, metabolism, and excretion. This chapter focuses on the excretion of medications as it relates to renal function.
Principles of Renal Replacement Therapies
Authors: Fitzpatrick Peter M.
Published: August 2019

Renal replacement therapy is frequently used in the intensive care unit, primarily for the management of acute kidney injury, but it is also indicated for removal of some toxins and medications. Additionally, patients with dialysis-dependent chronic kidney failure who are admitted to the intensive care unit require their therapy to be continued. This chapter reviews the mechanisms by which renal replacement therapy operates and the types of replacement therapies that are available. Access for renal replacement and anticoagulation are also discussed.
Antibiotics in the Intensive Care Unit
Authors: Aviles David A. Sotello , Hellinger Walter C.
Published: August 2019

Antimicrobial therapy is a critical component in the management of many infections. Antimicrobial therapy should not be initiated before infection with a susceptible pathogen is suspected or confirmed or before appropriate diagnostic specimens, including those for cultures, are collected. Recognizing indications for antibiotic administration and appropriately selecting antimicrobial agents based on clinical and microbiologic findings are required. Distinguishing between empiric prescribing, when infection syndromes and pathogens are suspected, and therapeutic prescribing, when infection syndromes are confirmed and pathogens identified, is critically important.
Dermatologic Emergencies in the Intensive Care Unit
Authors: Hall Matthew R.
Published: August 2019

Rashes are relatively common in hospitalized patients, but only rarely are they life threatening. Emergent skin conditions in these patients are usually sequelae of medication reactions (drug eruptions) or complications from sepsis. Most drug eruptions are benign and resolve if the offending medication is discontinued. However, the drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are urgent conditions that require prompt diagnosis and management. Purpura fulminans can develop in patients with sepsis and disseminated intravascular coagulation.
Extracorporeal Membrane Oxygenation
Authors: Bohman J. Kyle , Schears Gregory J.
Published: August 2019

Extracorporeal membrane oxygenation (ECMO) is a general term describing an extracorporeal circuit with a pump and a gas exchange membrane that can be used for cardiac support or respiratory support (or both) depending on its configuration. The 2 basic configurations of ECMO are venoarterial (VA) and venovenous (VV). VA ECMO removes blood from the venous circulation and pumps it through the oxygenator and back into the patient’s arterial circulation. VV ECMO removes blood from the venous circulation and pumps it through the oxygenator and back into the patient’s venous circulation. Common indications for VA ECMO include postcardiotomy, malignant ventricular arrhythmias, cardiogenic shock, and extracorporeal cardiopulmonary resuscitation.
Basilar Artery Occlusion
Authors: Pichler Michael R. , Fugate Jennifer E.
Published: August 2019

Basilar artery occlusion (BAO), a type of posterior circulation stroke, refers to occlusion of the basilar artery at any point along its course. Patients with BAO can present in many ways, depending on the location of the occlusion and the collateral blood supply. Timely recognition of BAO is essential given the potential for effective therapeutic interventions shown to improve outcome.
Intracerebral and Intraventricular Hemorrhage
Authors: Dumitrascu Oana , Aguilar Maria I.
Published: August 2019

Intraparenchymal cerebral hemorrhage and intraventricular hemorrhage are common cerebrovascular emergencies with various causes and prognoses. Rapid triage and individualized management are required because appropriate critical care management improves morbidity and mortality. A multidisciplinary approach for diagnosis and treatment is recommended.
Amyotrophic Lateral Sclerosis
Authors: Martinez-Thompson Jennifer M. , Staff Nathan P.
Published: August 2019

Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disorder with both upper and lower motor neuron involvement. It presents with weakness, muscle wasting, spasticity involving the limbs, bulbar dysfunction, and, typically later in the disease, respiratory involvement. Up to 20% of patients may also have a frontotemporal-type dementia. Average duration of survival is 2 to 4 years from symptom onset, and the peak incidence is between the ages of 50 and 75 years. Only 10% of patients have familial forms, and the remainder have sporadic ALS.
Posterior Reversible Encephalopathy Syndrome
Authors: Datar Sudhir V. , Fugate Jennifer E.
Published: August 2019

Posterior reversible encephalopathy syndrome (PRES), previously known as hypertensive encephalopathy, is a clinicoradiologic entity manifesting as acute onset of headache, encephalopathy, seizures, and vision abnormalities. The characteristic clinical features and predominantly posterior cerebral edema were first described by Hinchey and colleagues in 1996. Since then, many conditions have been associated with PRES.
Rapidly Progressive Dementia and Coma
Authors: Kamireddi Prasuna , Siegel Jason L. , Dickson Dennis W.
Published: August 2019

In most patients with dementia, the clinical signs and symptoms progress gradually over many years. However, neurointensivists may encounter patients who have rapidly progressive dementia (RPD). Often these patients need to be admitted to the intensive care unit for management of status epilepticus, agitation, or ventilation in coma. Although the prototype of RPD is Creutzfeldt-Jakob disease, this chapter reviews other common causes of RPD. An established definition of RPD does not exist, but in this chapter RPD refers to the loss of more than 1 cognitive domain and functional ability, usually occurring over a few months.
Intensive Care After Neuroendovascular Procedures
Authors: Sattur Mithun , Krishna Chandan , Bendok Bernard R. , Chong Brian W.
Published: August 2019

Endovascular therapy for cerebrovascular disease is widespread. Patients with brain aneurysms, acute stroke, brain vascular malformations, and tumors are treated with endovascular techniques primarily or in conjunction with other traditional surgical and medical approaches. Postprocedural concerns unique to endovascular treatment include complications related to access or arterial puncture, contrast nephrotoxicity, and radiation dose complications (eg, alopecia and skin burns). Other complications, such as stroke and hemorrhage, that are not unique are discussed below.
Radiography and Computed Tomography of the Chest
Authors: McComb Barbara L.
Published: August 2019

A portable chest radiograph frequently complements the clinical evaluation of a patient in the intensive care unit (ICU). Standard posteroanterior (PA) chest radiographs are obtained from a distance of 72 inches with the patient erect and facing the detector. The x-ray tube is behind the patient, and the beam passes from posterior to anterior. In the ICU, the PA radiograph is replaced by the portable anteroposterior radiograph, which is obtained from a 40-inch distance with the tube in front of the patient and the patient supine or semierect.
Abdominal Radiography
Authors: Cernigliaro Joseph G. , DiSantis David J.
Published: August 2019

Hospitalized patients in a critical care environment are at risk for adverse intra-abdominal events involving bowel, solid organs, and vasculature. For assessment of hospitalized patients with abdominal pain, a thorough history and physical examination should precede indicated laboratory testing and imaging studies. One expedient means of evaluation is abdominal radiography. In very ill patients, it can be performed at the bedside. Because of its ready availability and occasional definitive diagnostic information, however, abdominal radiography often is the first imaging study performed. Ideally, a supine frontal image is supplemented with an upright or left lateral decubitus (left-side down) frontal view.
Endotracheal Intubation Procedures
Authors: Ritter Matthew J.
Published: August 2019

Endotracheal intubation (ETI) is one of the most common procedures performed in the intensive care unit (ICU). It is also associated with a high incidence of complications. Indications for ETI include acute hypoxemic or hypercapnic respiratory failure, loss of protective reflexes, and inability to manage secretions. Additionally, in the neurosciences ICU, intubation may be necessary for transient hyperventilation in patients with elevated intracranial pressure.
Intracranial Pressure Monitoring and External Ventricular Drainage
Authors: Babu Maya A. , Atkinson John L. D.
Published: August 2019

Several studies have shown that increased ICP has been associated with poor neurologic outcomes. Management of elevated ICP can improve neurologic outcomes and influence medical and surgical therapy, and accurate recording of ICP is helpful in assessing a patient’s clinical status. Currently, the 2 most common forms of monitoring ICP involve 1) placement of a fiberoptic or strain gauge intraparenchymal monitor or 2) placement of a ventricular drain.
Transcranial Doppler Ultrasonography
Authors: Rubin Mark N.
Published: August 2019

Transcranial Doppler (TCD) ultrasonography is a diagnostic technology for ascertaining numerous physiologic and pathologic phenomena by monitoring the direction and velocity of blood flow in intracranial vasculature. It is a noninvasive, point-of-care diagnostic tool that provides continuous and reproducible bedside data without the use of ionizing radiation.
Anticonvulsant Drugs
Authors: Feyissa Anteneh M. , Britton Jeffrey W.
Published: August 2019

Seizures are a common occurrence in intensive care units harboring patients with acute brain injury. The increased use of continuous electroencephalographic (EEG) monitoring has led to an increase in seizure detection in this setting. Independent variables predicting seizure detection in this setting are age, cardiopulmonary arrest, and use of continuous EEG.
Inotropes, Vasopressors, and Antihypertensive Agents
Authors: Pulido Juan N.
Published: August 2019

Pharmacologic manipulation of the cardiovascular system is considered one of the cornerstones of day-to-day management of critically ill patients. For formulation of an adequate hemodynamic plan, it is crucial 1) to have a thorough understanding of cardiovascular physiology and its intricate relationship with the autonomic nervous system and 2) to identify a clear hemodynamic goal, such as maintenance of oxygen delivery and perfusion in shock, permissive hypertension in acute stroke, or blood pressure control in hypertensive emergencies.
Minimally Conscious State and Persistent Vegetative State
Authors: Jones David T.
Published: August 2019

Advances in critical care medicine have allowed for more patients to survive catastrophic brain injuries. However, the degree of recovery from serious neurologic injury is highly variable. An acute, severe neurologic insult can cause a state of pathologic unconsciousness referred to as a coma. Common causes of brain injuries leading to a comatose state include cardiac arrest, a severe vascular event, a profound metabolic disturbance (eg, hypoglycemia), carbon monoxide or other poisoning, intoxications, or overdoses. The duration of a comatose state is rarely longer than days to weeks.
Acute Spinal Cord Injury
Authors: Stricsek Geoffrey , Khanna Omaditya , Emes Alexandra , Harrop James
Published: August 2019

Spinal cord injury (SCI) can be a complex injury pathology with high rates of morbidity and mortality. Care for the patient with spinal cord injury is dictated by their neurological status and the structural morphology of their injury and begins with prehospital management, thorough neurological assessment, and advanced imaging. Often surgical intervention is required for fracture stabilization and decompression of spinal cord pressure. Vigilance needs to remain high after surgery as SCI patients are at increased risk for multiple medical complications as a result of their injuries. Focused, comprehensive care delivered by the hospitalist and care team can facilitate improved outcomes.
Critical Approaches to Life-Writing
Authors: Crawford Allison
Published: August 2019

This chapter describes some of the tools and methods for critically reading life-writing texts, including memoirs and autobiography, with an emphasis on life-writing by health professionals and/or in the context of healthcare. Life-writing texts allow research into the internal and lived experiences of those who provide healthcare, such as physicians and nurses, and those who receive healthcare. Texts by life-writing subjects from different historical periods, geographic locations, genders, diagnoses, and stages and contexts of training can offer shifting perspectives on a range of topics from the development of health professional identity, what it means to be sick, and about how these experiences relate to the practices and institutions of healthcare. Steps in the research process and methods for analyzing life-writing texts are outlined, along with relevant resources. The field of life-writing offers many possibilities for health humanities researchers and can be enriched by bringing interdisciplinary theories to the analysis of life-writing texts.
Comics
Authors: Al-Jawad Muna , Czerwiec MK
Published: August 2019

Comics can be used to research healthcare practice and experiences with illness and caregiving. Comics can also be sources of data themselves: professional healthcare providers engaged in research use comics to understand their practice in order to improve it and to promote humanism in healthcare. Patients and caregivers create comics to share their personal accounts of illness and caregiving. Comics can also be a means for collecting data: asking research participants to draw comics of themselves and their experiences can offer data otherwise difficult to elicit. Comics are constructed narratives that can be analyzed for visual, textual, and narrative elements; gutters; style; influences; external references; and use of humor, as well as for what is present in a panel and what is absent. Using comics as a research tool allows access to autobiographical and emotional aspects of healthcare, enabling health humanities researchers to reconceptualize both practice and illness.
Health and Social Justice Studies
Authors: Berry Sarah L.
Published: August 2019

Health and social justice studies (HSJS) builds on close reading and archival research methods to examine the ways in which diverse people experience health and healthcare at the often highly charged intersection of culture, law, economics, and biomedical systems. This scholarly method focuses on socioeconomic disparities among groups in a society and examines how ordinary people experience health and care in everyday social environments. Health and social justice studies research with a history focus reconstructs particular health and healthcare disparities at particular times and examines reform movements aimed at reducing these disparities, with the objective of suggesting ways to reduce disparities in the future. By privileging marginalized people, this research method advances the goals of person-centered care and population health equity in health humanities.