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Chronic cough (CC) is associated with many conditions, so identifying contributing causes poses a diagnostic challenge. However, guidelines written for US physicians do not explicitly outline suggested roles for primary care providers (PCPs) in the approach to patients with CC, including refractory or unexplained CC. The objective of this review is to describe the role of PCPs in the diagnosis and treatment of CC in adults. This narrative review draws upon literature (identified via a PubMed search performed January 9, 2023, using primary care/disease state–related terms) and expertise from specialist physicians to provide recommendations for CC management in primary care. Cough is one of the top reasons patients seek care from PCPs; accordingly, PCPs are often the first physicians to conduct workup and initiate treatment. Patients with CC often experience a burdensome cough that lasts for years, have high healthcare resource utilization (HCRU), undergo multiple or failed treatment trials, and have limited success finding an etiology. Although specialist referral may be needed for many diagnostic tests, initial aspects of CC workup and management should be completed in primary care. Often more accessible than specialists, real-world evidence on HCRU suggests PCPs are important stakeholders in diagnosing and managing CC, including during initial workup and treatment for the most common causes of CC (i.e. upper-airway cough syndrome, asthma, noneosinophilic asthmatic bronchitis, and gastroesophageal reflux disease). Thorough workup at the primary care level may facilitate earlier identification of CC cause(s), improving patient journey to diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome.Methods: Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux?Results: We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely.Conclusions: The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing. [ABSTRACT FROM AUTHOR]

Background: In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected.Methods: MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel.Results: The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature.Conclusions: Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future. [ABSTRACT FROM AUTHOR]

Background: Several recent cough guidelines have advised consideration of occupational or environmental causes for chronic cough, but it is unclear how frequently this recommendation has been routinely applied. Therefore, we undertook a systematic review to address this aspect.Methods: Cough guidelines and protocols were reviewed to identify recommendations for assessment of occupational and environmental aspects of chronic cough. The systematic search previously used to identify intervention fidelity to the use of protocols for diagnosis and management of chronic cough in adults was used for this review after extension to June 2015. PubMed, Scopus, and the Cochrane Library were searched using the same search terms and inclusion criteria as previously. Papers that met our criteria were then reviewed to identify methods used to assess occupational and environmental aspects of chronic cough and the outcomes of these assessments.Results: Among the 10 general chronic cough guidelines and protocols identified, only the three published since 2006 included details advising detailed occupational and environmental assessments. One additional cough statement focused entirely on occupational cough. Of the 28 cohort studies of patients with chronic cough that specifically noted that they followed guidelines or protocols, none provided details of occupational and environmental assessments.Conclusions: Despite published recommendations, it is not apparent that occupational and environmental causes for chronic cough are addressed in detail during assessments of patients with chronic cough. This leaves open to speculation whether lack of recognition of an occupational cause may delay important preventive measures, put additional workers at risk, and/or be the reason why a chronic cough may remain unexplained. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett's esophagus (BE) is a known precursor of esophageal adenocarcinoma. This review aims to explore Barrett's esophagus, esophageal adenocarcinoma, and the progression from the former to the latter. An overview of the definition, diagnosis, epidemiology, and risk factors for both entities are presented, with special attention being given to the areas of debate in the literature. The progression from Barrett's esophagus to esophageal adenocarcinoma is reviewed and the relevant molecular pathways are discussed. The definition of Barrett's esophagus remains debated and without international consensus. This, alongside other factors, has made establishing the true prevalence of Barrett's esophagus challenging. The degree of dysplasia can be a histological challenge, but is necessary to guide clinical management. The progression of BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is maintained through serial endoscopic evaluation, with shorter intervals recommended for high-risk features. [ABSTRACT FROM AUTHOR]

Following the World Trade Center (WTC) collapse on September 11, 2001, more than 40,000 people were exposed to a complex mixture of inhalable nanoparticles and toxic chemicals. While many developed chronic respiratory symptoms, to what degree olfaction was compromised is unclear. A previous WTC Medical Monitoring and Treatment Program study found that olfactory and nasal trigeminal thresholds were altered by the toxic exposure, but not scores on a 20-odor smell identification test. Objectives: To employ a well-validated 40-item smell identification test to definitively establish whether the ability to identify odors is compromised in a cohort of WTC-exposed individuals and, if so, whether the degree of compromise is associated with self-reported severity of rhinitic symptoms. Methods: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 99 WTC-exposed persons and 99 matched normal controls. The Sino-Nasal Outcomes Test (SNOT-20) was administered to the 99 WTC-exposed persons and compared to the UPSIT scores. Results: The mean (SD) UPSIT scores were lower in the WTC-exposed group than in age-, sex-, and smoking history-matched controls [respective scores: 30.05 (5.08) vs 35.94 (3.76); p = 0.003], an effect present in a subgroup of 19 subjects additionally matched on occupation ( p < 0.001). Fifteen percent of the exposed subjects had severe microsmia, but only 3% anosmia. SNOT-20 scores were unrelated to UPSIT scores ( r = 0.20; p = 0.11). Conclusion: Exposure to WTC air pollution was associated with a decrement in the ability to identify odors, implying that such exposure had a greater influence on smell function than previously realized. [ABSTRACT FROM AUTHOR]

Objectives: The H+/K+-ATPase proton pump has been demonstrated in human laryngeal submucosal glands, and is not solely present in the parietal cells of the stomach. Although proton secretion is present in the lung, a variety of mechanisms have been elucidated. The hypothesis of this study is that the H+/K+-ATPase proton pump is one additional path- way of proton secretion in the human lung. Methods: Fourteen surgical lung specimens from 10 subjects were retrospectively obtained after approval from our Human Subjects Committee. Banked human stomach tissue was used for comparative positive and negative controls. Sections were immunostained with 2 monoclonal antibodies selectively reactive with alpha or beta subunits of the H+/K+- ATPase proton pump. Results: In the human lung, consistent staining for both subunits was present in the mucous gland cells and ducts in all specimens in which mucous glands were present (6 specimens from 5 subjects). Overall, weak to strong staining was present in focal areas within the multicellular mucous glands. There was only scant focal staining in the respiratory epithelium in 4 specimens. Stomach parietal cells exhibited strongly positive staining for both subunits of the proton pump. There was no staining in stomach cells that were not morphologically consistent with parietal cells. Conclusions: The H+/K+-ATPase proton pump is present in mucous cells and ducts in the human lung, with some variable expression noted. Proton pump inhibitor pharmacotherapy may have a site of action in the human lung, explaining some of the controversies otherwise attributable to interrelatedness of aerodicestive tract disease. [ABSTRACT FROM AUTHOR]

The author discusses how physicians and surgeons can preserve their professional identity, meet challenges and emerge stronger. Topics discussed include the dependence on the profession's integrity on shared commitment to best practices, compassionate care of patients and upholding the standards and expectations of the community, the importance of a commitment to unity as a vital part of integrity and the need to work together to preserve common values and ideals despite outside pressures.

There is a high prevalence of dysphagia among patients with neuromuscular diseases and cerebrovascular diseases, and its consequences can be profound. However, the correlation between dysarthria and oral-oropharyngeal dysphagia remains unclear. We conducted a literature review to define the clinical presentation of both dysarthria and dysphagia in patients with neuromuscular and cerebrovascular diseases. We performed a systematic PubMed search of the English-language literature since 1995. Objective and subjective outcomes instruments were identified for both dysarthria and dysphagia. Studies that included the incidence of concomitant presentations were included. Inclusion and exclusion criteria were applied according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Of the 1,056 articles we reviewed, we selected 24 for analysis. We found that dysarthria and dysphagia were common among patients with neuromuscular and cerebrovascular diseases. Overall, there was a higher prevalence of dysarthria than dysphagia. Of those patients with dysphagia, some reports found that 76 to 90% of patients with neuromuscular disease also had dysarthria. Dysarthria is a strong clinical clue to the presence of dysphagia. Existing subjective questionnaires may not reveal the presence of oropharyngeal dysphagia; objective measures are obviously more revealing. Further studies to correlate the degree of dysarthria and the severity of oral-oropharyngeal dysphagia are warranted. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effect of Early vs. Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial" by D. Young and colleagues in a 2013 issue.

Objectives: The 585-nm pulsed dye laser (PDL) was recently deemed relatively safe and effective for treatment of laryn- geal papilloma, dysplasia, and granuloma. We report on in-office PDL treatment of laryngeal vascular polyps. Methods: Retrospective case results from 29 consecutive cases of laryngeal polyps were evaluated to determine the percent change in polyps after PDL treatment. Preoperative and postoperative measurements of polyp size, total power delivered to the site, and whether patients opted for postprocedure phonomicrosurgery were analyzed. Results: After PDL treatment, the results varied from complete to partial resolution of the polyp. Four patients requested conventional phonomicrosurgery, and the rest had enough improvement to defer surgery. Almost 40% of patients with larger polyps desired operative intervention after laser treatment, whereas only 13% of those with small polyps opted for phonomicrosurgery. Thirty-eight percent (II of 29) of the lesions had greater than 70% improvement after I or 2 laser treatments (average of 1.1 procedures). Smaller lesions responded better. Thirty-nine percent of small polyps resolved by greater than 70%, whereas only 20% of larger lesions improved by the same amount. There were no adverse events from the office procedure. Conclusions: In-office use of the PDL for treatment of vascular polyps may be a safe alternative to phonomicrosurgery. Small polyps seem to show a better response. [ABSTRACT FROM AUTHOR]

Chordomas are malignant, nonepithelial neoplasms derived from notochordal tissue. A primary chordoma of the nasal cavities and paranasal sinuses is extremely rare compared with clival chordomas, which often present as nasal masses after spreading anteriorly. Only a few cases of primary chordoma of the nasal cavities and paranasal sinuses have been reported in the literature. We report a case of a primary chordoma of the lateral nasal wall. Pathologic diagnosis was obtained using an intranasal endoscopic excision. As in our patient, a primary chordoma of the nasal cavity or paranasal sinuses may present with symptoms related to mechanical obstruction secondary to the tumor mass. We summarize our case in the context of the other reported cases, and we discuss treatment options, natural history, and prognosis. [ABSTRACT FROM AUTHOR]

Background: We performed systematic reviews using the population, intervention, comparison, outcome (PICO) format to answer the following key clinical question: Are the CHEST 2006 classifications of acute, subacute and chronic cough and associated management algorithms in adults that were based on durations of cough useful?Methods: We used the CHEST Expert Cough Panel's protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patient values and preferences and the clinical context were used to form recommendations or suggestions. Delphi methodology was used to obtain the final grading.Results: With respect to acute cough (< 3 weeks), only three studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 CHEST Cough Guidelines, the most common causes were respiratory infections, most likely of viral cause, followed by exacerbations of underlying diseases such as asthma and COPD and pneumonia. The subjects resided on three continents: North America, Europe, and Asia. With respect to subacute cough (duration, 3-8 weeks), only two studies met our criteria for quality assessment, and both had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were postinfectious cough and exacerbation of underlying diseases such as asthma, COPD, and upper airway cough syndrome (UACS). The subjects resided in countries in Asia. With respect to chronic cough (> 8 weeks), 11 studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were UACS from rhinosinus conditions, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, combinations of these four conditions, and, less commonly, a variety of miscellaneous conditions and atopic cough in Asian countries. The subjects resided on four continents: North America, South America, Europe, and Asia.Conclusions: Although the quality of evidence was low, the published literature since 2006 suggests that CHEST's 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017. [ABSTRACT FROM AUTHOR]

Objectives: The National Ambulatory Medical Care Survey (NAMCS) database was utilized to understand evolving national trends in diagnosis and management of reflux. Methods: The NAMCS database was queried for visits related to gastroesophageal reflux diagnosis and management. Analysis performed for time periods 1998-2001, 2002-2005, and 2006-2009 was weighted to provide national estimates of care. Results were compared to previously reported time periods from 1990 to 2001 to evaluate patterns in overall visits, age and ethnicity of patients, provider type, and prescriptions provided. Results: The number of ambulatory visits for reflux increased from 8 684 000 in 1998-2001 to 15 750 000 in 2006-2009. Visits increased across each time period for internal medicine, family, and gastroenterology physicians. Among otolaryngologists, absolute visits increased from 1998-2001 to 2002-2005 but decreased in 2006-2009; difference between these time periods did not reach statistical significance. From 1998-2001 to 2006-2009, reflux medication use increased 233%, with continuing trends toward increased proton pump inhibitor use. Conclusions: Reflux visits have increased across all demographic subgroups studied. Knowledge of these trends may inform further paradigm shifts in diagnosis and management of reflux. [ABSTRACT FROM AUTHOR]

An ever-increasing number of adult and pediatric disorders have been shown to be influenced or caused by airway reflux. This has become a controversial and complicated aspect of medicine that requires a multidisciplinary approach. Evidence indicates that it is not only the acidic components of gastric refluxate that injure extraesophageal tissues but also the nonacidic components, such as pepsin and bile. There is a realization that proton pump inhibitors will not be effective when nonacidic components of refluxate are causing the problem. New in vitro and in vivo models for the study of airway reflux and new therapeutic and surgical approaches are discussed in this review article. [ABSTRACT FROM AUTHOR]

Background: Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC.Methods: This systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology.Results: Eleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity.Conclusions: The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge as well as areas for future research. [ABSTRACT FROM AUTHOR]

Background: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.Methods: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.Results: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.Conclusions: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality. [ABSTRACT FROM AUTHOR]

Background: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.Methods: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.Results: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).Conclusions: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a systematic review conducted to update the recommendations and suggestions of the 2006 guidelines of the American College of Chest Physicians (CHEST) for managing psychogenic cough, habit cough, and tic cough. Topics covered include the summary of the recommendations and suggestions indicated in the "2006 CHEST Cough Guidelines", the interpretation of the CHEST Expert Panel who reviewed the 2006 cough guidelines, and the areas proposed for future research.

Background: Several pharmacologic and nonpharmacologic therapeutic options have been used to treat cough that is not associated with a pulmonary or extrapulmonary etiology.Methods: We conducted a systematic review to summarize the evidence supporting different cough management options in adults and children with psychogenic, tic, and habit cough. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched from the earliest inception of each database to September 2013. Content experts were contacted, and we searched bibliographies of included studies to identify additional references.Results: A total of 18 uncontrolled studies were identified, enrolling 223 patients (46% male subjects, 96% children and adolescents). Psychogenic cough was the most common descriptive term used (90% of the studies). Most of the patients (95%) had no cough during sleep; barking or honking quality of cough was described in only eight studies. Hypnosis (three studies), suggestion therapy (four studies), and counseling and reassurance (seven studies) were the most commonly used interventions. Hypnosis was effective in resolving cough in 78% of the patients and improving it in another 5%. Suggestion therapy resolved cough successfully in 96% of the patients. The greatest majority of improvements noted with these forms of therapy occurred in the pediatric age group. The quality of evidence is low due to the lack of control groups, the retrospective nature of all the studies, heterogeneity of definitions and diagnostic criteria, and the high likelihood of reporting bias.Conclusions: Only low-quality evidence exists to support a particular strategy to define and treat psychogenic, habit, and tic cough. Patient values, preferences, and availability of potential therapies should guide treatment choice. [ABSTRACT FROM AUTHOR]

The article presents a systematic review of different cough management techniques in adults and children with psychogenic, tic, and habit cough. Topics include the effects of chronic cough not associated with a pulmonary or extrapulmonary causes, the sources of information including the Cochrane Central Register of Controlled Trials and Medline, and the identification of psychogenic cough as the most descriptive term used. Interventions included hypnosis, suggestion therapy and counseling.

The free radical nitric oxide (NO•) is known to play a dual role in human physiology and pathophysiology. At low levels, NO• can protect cells; however, at higher levels, NO• is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO• in cancer has to date been tissue-specific, we herein review underlying commonalities of NO• which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO• in human physiology and pathophysiology, including the very important relationship between NO• and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO• in three main areas of epigenetics-DNA methylation, microRNAs, and histone modifications-is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO• (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO• in cancer. [ABSTRACT FROM AUTHOR]

Lingual hematoma is a rare but potentially fatal cause of upper airway obstruction. Patients receiving anticoagulants such as heparin can suffer from significant complications of these medications. Not only does heparin exert effects directly on the coagulation cascade, but it has the potential to cause thrombocytopenia by stimulating formation of antibodies against platelets. We present the case of a patient being treated with heparin for a deep-vein thrombosis, who subsequently developed heparin-induced thrombocytopenia and lingual hematoma, necessitating tracheotomy. [ABSTRACT FROM AUTHOR]