John G. Park

Updates on Definition, Consequences, and Management of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a breathing disorder during sleep that has implications beyond disrupted sleep. It is increasingly recognized as an independent risk factor for cardiac, neurologic, and perioperative morbidities. Yet this disorder remains undiagnosed in a substantial portion of our population. It is imperative for all physicians to remain vigilant in identifying patients with signs and symptoms consistent with OSA. This review focuses on updates in the areas of terminology and testing, complications of untreated OSA, perioperative considerations, treatment options, and new developments in this field.

Mediastinal Lymphangioma: Mayo Clinic Experience of 25 Cases

OBJECTIVE To describe the clinical findings, treatment outcomes, disease recurrence rates, and survival of patients with pathologically confirmed mediastinal and cervicomediastinal lymphangioma. PATIENTS AND METHODS There are 2 patient cohorts. Cohort A consisted of 12 Mayo Clinic patients with pathologically confirmed medilastinal or cervicomediastinal lymphangioma identified from 1986 to 1999. Cohort B consisted of 13 additional patients with mediastinal lymphangioma who had been previously reported from the Mayo Clinic (from 1976 to 1986). All patients were retrospectively identified, and follow-up was performed by either telephone or medical record review. RESULTS The mean age at the time of diagnosis was 36.5 years, with a male-female ratio of 1:3. All but 3 patients were symptomatic at presentation, with dyspnea being the most common symptom. Computed tomographic scans commonly revealed a homogeneous, low-attenuation mass that often Involved vascular or airway structures. Although 3 patients were initially observed, all patients had surgical intervention because of symptoms or enlargement of the mass. Thoracotomy with resection was the most common surgical intervention. Five recurrences were noted. Recurrence was minimized by complete excision of the lymphangioma. On follow-up that spanned 23 years, 75% of patients were alive. These survival rates were not statistically different from the expected survival rates of the same age- and sex-matched controls. Only 1 death was attributed to complication from lymphangioma. CONCLUSION Mediastinal and cervicomediastinal lymphangioma are rare lesions that can be treated successfully with surgical excision. Prognosis appears to be excellent because no difference in survival was found between patients and age- and sex-matched controls.

Increased fluid administration in the first three hours of sepsis resuscitation is associated with reduced mortality: a retrospective cohort study.

BACKGROUND The surviving sepsis guidelines recommend early aggressive fluid resuscitation within 6 h of sepsis onset. Although rapid fluid administration may offer benefit, studies on the timing of resuscitation are lacking. We hypothesized that there is an association between quicker, adequate fluid resuscitation and patient outcome from sepsis onset time. METHODS This is a retrospective cohort study of consecutive adults with severe sepsis and septic shock admitted to a quaternary care medical ICU between January 2007 and December 2009. Data were collected from a previously validated electronic medical database. Multivariate regression modeling was performed, adjusting for age, admission weight, Sequential Organ Failure Assessment score, APACHE (Acute Physiology and Chronic Health Examination) III score, and total fluid administration within the first 6 h of sepsis onset time. RESULTS Of 651 patients with severe sepsis and septic shock screened, 594 had detailed fluid data. In a univariate analysis, the median amount of fluid within the first 3 h for survivors at discharge was 2,085 mL (940-4,080 mL) and for nonsurvivors, 1,600 mL (600-3,010 mL; P = .007). In comparison, during the latter 3 h, the median amount was 660 mL (290-1,485 mL) vs 800 mL (360-1,680 mL; P = .09), respectively. After adjusting for confounders, the higher proportion of total fluid received within the first 3 h was associated with decreased hospital mortality (OR, 0.34; 95% CI, 0.15-0.75; P = .008). CONCLUSIONS Earlier fluid resuscitation (within the first 3 h) is associated with a greater number of survivors with severe sepsis and septic shock.

Pneumocystis carinii BCK1 functions in a mitogen-activated protein kinase cascade regulating fungal cell-wall assembly

Pneumocystis pneumonia remains the most common AIDS‐defining opportunistic infection in people with HIV. The process by which Pneumocystis carinii constructs its cell wall is not well known, although recent studies reveal that molecules such as β‐1‐3‐glucan synthetase (GSC1) and environmental pH‐responsive genes such as PHR1 are important for cell‐wall integrity. In closely related fungi, a specific mitogen‐activated protein kinase (MAPK) cascade regulates cell‐wall assembly in response to elevated temperature. The upstream mitogen‐activated protein kinase kinase kinase (MAPKKK, or MEKK), BCK1, is an essential component in this pathway for maintaining cell‐wall integrity and preventing fungal cell lysis. We have identified a P. carinii MEKK gene and have expressed it in Saccharomyces cerevisiae to gain insights into its function. The P. carinii MEKK, PCBCK1, corrects the temperature‐sensitive cell lysis defect of bck1Δ yeast. Further, at elevated temperature PCBCK1 restored the signaling defect in bck1Δ yeast to maintain expression of the temperature‐inducible β‐1‐3‐glucan synthetase gene, FKS2. PCBCK1, as a functional kinase, is capable of autophosphorylation and substrate phosphorylation. Since glucan machinery is not present in mammals, a better understanding of this pathway in P. carinii might aid in the development of novel medications which interfere with the integrity of the Pneumocystis cell wall.

Clinical Practice Guideline: Improving Nasal Form and Function after Rhinoplasty.

Objective Rhinoplasty, a surgical procedure that alters the shape or appearance of the nose while preserving or enhancing the nasal airway, ranks among the most commonly performed cosmetic procedures in the United States, with >200,000 procedures reported in 2014. While it is difficult to calculate the exact economic burden incurred by rhinoplasty patients following surgery with or without complications, the average rhinoplasty procedure typically exceeds

The Use of ECMO in HIV/AIDS with Pneumocystis jirovecii Pneumonia: A Case Report and Review of the Literature

4000. The costs incurred due to complications, infections, or revision surgery may include the cost of long-term antibiotics, hospitalization, or lost revenue from hours/days of missed work. The resultant psychological impact of rhinoplasty can also be significant. Furthermore, the health care burden from psychological pressures of nasal deformities/aesthetic shortcomings, surgical infections, surgical pain, side effects from antibiotics, and nasal packing materials must also be considered for these patients. Prior to this guideline, limited literature existed on standard care considerations for pre- and postsurgical management and for standard surgical practice to ensure optimal outcomes for patients undergoing rhinoplasty. The impetus for this guideline is to utilize current evidence-based medicine practices and data to build unanimity regarding the peri- and postoperative strategies to maximize patient safety and to optimize surgical results for patients. Purpose The primary purpose of this guideline is to provide evidence-based recommendations for clinicians who either perform rhinoplasty or are involved in the care of a rhinoplasty candidate, as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The target audience is any clinician or individual, in any setting, involved in the management of these patients. The target patient population is all patients aged ≥15 years. The guideline is intended to focus on knowledge gaps, practice variations, and clinical concerns associated with this surgical procedure; it is not intended to be a comprehensive reference for improving nasal form and function after rhinoplasty. Recommendations in this guideline concerning education and counseling to the patient are also intended to include the caregiver if the patient is <18 years of age. Action Statements The Guideline Development Group made the following recommendations: (1) Clinicians should ask all patients seeking rhinoplasty about their motivations for surgery and their expectations for outcomes, should provide feedback on whether those expectations are a realistic goal of surgery, and should document this discussion in the medical record. (2) Clinicians should assess rhinoplasty candidates for comorbid conditions that could modify or contraindicate surgery, including obstructive sleep apnea, body dysmorphic disorder, bleeding disorders, or chronic use of topical vasoconstrictive intranasal drugs. (3) The surgeon, or the surgeon’s designee, should evaluate the rhinoplasty candidate for nasal airway obstruction during the preoperative assessment. (4) The surgeon, or the surgeon’s designee, should educate rhinoplasty candidates regarding what to expect after surgery, how surgery might affect the ability to breathe through the nose, potential complications of surgery, and the possible need for future nasal surgery. (5) The clinician, or the clinician’s designee, should counsel rhinoplasty candidates with documented obstructive sleep apnea about the impact of surgery on nasal airway obstruction and how obstructive sleep apnea might affect perioperative management. (6) The surgeon, or the surgeon’s designee, should educate rhinoplasty patients before surgery about strategies to manage discomfort after surgery. (7) Clinicians should document patients’ satisfaction with their nasal appearance and with their nasal function at a minimum of 12 months after rhinoplasty. The Guideline Development Group made recommendations against certain actions: (1) When a surgeon, or the surgeon’s designee, chooses to administer perioperative antibiotics for rhinoplasty, he or she should not routinely prescribe antibiotic therapy for a duration >24 hours after surgery. (2) Surgeons should not routinely place packing in the nasal cavity of rhinoplasty patients (with or without septoplasty) at the conclusion of surgery. The panel group made the following statement an option: (1) The surgeon, or the surgeon’s designee, may administer perioperative systemic steroids to the rhinoplasty patient.

Impact of Zaleplon on Continuous Positive Airway Pressure Therapy Compliance

There are few reports of extracorporeal membrane oxygenation (ECMO) therapy for respiratory failure because of Pneumocystis jirovecii pneumonia (PJP) in patients with acquired immunodeficiency syndrome (AIDS). None of the cases reported involvement of immune reconstitution inflammatory syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients because of an exaggerated systemic inflammation with cell count recovery. We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous ECMO was initiated. He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in human immunodeficiency virus patients secondary to PJP treated with ECMO, three of the five patients survived to ECMO decannulation. Extracorporeal membrane oxygenation is considered an accepted modality for adult patients with respiratory and/or cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research.

Novel and Emerging Nonpositive Airway Pressure Therapies for Sleep Apnea

STUDY OBJECTIVE To determine whether pretreatment with zaleplon immediately before CPAP titration improves 1-month CPAP adherence in subjects newly diagnosed with OSA. METHODS Prospective, randomized, double-blinded, placebo-controlled trial of a single dose of zaleplon 10 mg or matching placebo at the start of CPAP titration during laboratory-based, split-night polysomnography (PSG). Baseline sleep symptoms were assessed with the Functional Outcomes of Sleep Questionnaire (FOSQ) and Epworth Sleepiness Scale (ESS). CPAP usage and change in symptom questionnaire responses were assessed at 1-month follow-up. RESULTS One hundred thirty-four newly diagnosed OSA patients undergoing their initial split-night PSG (49.8 ± 11.3 years old with an apnea-hypopnea index of 16.5 (7, 32) [median (interquartile range)] were randomized to zaleplon (n = 73) or placebo (n = 63). Complete follow-up data were available in 83 subjects (44 zaleplon group; 39 placebo group). CPAP was used for 6.5 (5, 7) h/day with zaleplon versus 6.5 (5, 8) h/ day with placebo (p = 0.64). Improvements in FOSQ and ESS scores did not differ between the two groups. CONCLUSION A single dose of zaleplon at the start of a split-night CPAP titration does not result in superior CPAP adherence or improvement in symptoms at 1-month compared to placebo. Our data show that zaleplon is safe and is associated with shorter sleep latency during CPAP titration, but it does not translate into improved short-term CPAP adherence.

Sleep-Disordered Breathing and Stroke: Therapeutic Approaches

CPAP therapy has remained the standard of care for the treatment of sleep apnea for nearly 4 decades. Its overall effectiveness, however, has been limited by incomplete adherence despite many efforts to improve comfort. Conventional alternative therapies include oral appliances and upper airway surgeries. Recently, several innovative alternatives to CPAP have been developed. These novel approaches include means to increase arousal thresholds, electrical nerve stimulation, oral vacuum devices, and nasal expiratory resistive devices. We will review the physiologic mechanisms and the current evidence for these novel treatments.

Clinical Practice Guideline: Improving Nasal Form and Function after Rhinoplasty Executive Summary

The majority of stroke patients have clinically significant obstructive sleep apnea (OSA). Also, recent evidence demonstrates that OSA serves as an independent risk factor for stroke. Treatment of OSA following stroke is associated with neurologic and functional improvements, as well as long-term reduced risk of cardiovascular events. Identification of stroke patients at risk of OSA and subsequent diagnosis and treatment is essential in stroke recovery and reducing recurrent stroke risk. Continuous positive airway pressure (CPAP), the standard modality of treating OSA, is highly effective, but is often inadequately tolerated by stroke patients. Education and medical provider support are essential in establishing CPAP use in this population. However, in cases where CPAP therapy is not feasible, it is important for clinicians to be familiar with alternative modalities in treating OSA.