Richard A. Helmers

Influence of Individual Characteristics on Outcome of Glycemic Control in Intensive Care Unit Patients With or Without Diabetes Mellitus

OBJECTIVE To clarify the relationship of patient and critical illness characteristics (including any history of diabetes mellitus) to glycemic control with insulin and hospital mortality. PATIENTS AND METHODS A case-control descriptive study was performed of patients admitted to a tertiary-care center multidisciplinary closed intensive care unit (ICU) at Mayo Clinic Hospital in Phoenix, Ariz, between January 1, 1999, and December 31, 2003, after implementation of a glycemic management protocol. Hospital mortality, the primary outcome, was examined in nondiabetic and diabetic ICU patients receiving insulin and in patients not requiring insulin (control group). RESULTS Of 7285 patients, 2826 (39%) required insulin, 1083 of whom (15% of total) had a history of diabetes mellitus. The control group had a median (10th-90th percentile) glucose level of 118 mg/dL (range, 97-153 mg/dL) and a 5% mortality rate. The median glucose level was 134 mg/dL (range, 110-181 mg/dL) in nondiabetic patients and 170 mg/dL (121-238 mg/dL) in diabetic patients (P<.001), whereas mortality rates were 10% and 6%, respectively (P<.001). Compared with nondiabetic survivors, nondiabetic nonsurvivors had longer periods with glucose levels greater than 144 mg/dL. Diabetic nonsurvivors vs diabetic survivors had longer periods with glucose levels greater than 200 mg/dL. Poor glycemic control in nondiabetic patients was associated with increased insulin requirement and increased mortality. Critical illness characteristics that predicted poor glycemic control were advanced age, history of diabetes, cardiac surgery, postoperative complications, severity of illness, nosocomial infections, prolonged mechanical ventilation, or concurrent medications. CONCLUSIONS Critical illness characteristics determined glycemic control and clinical outcome in ICU patients. Acute insulin resistance was associated with worse outcomes in nondiabetic patients. Although critical illness characteristics influenced glycemic control, future evaluation of the effect of insulin administration and optimal glycemic control in ICU patients is necessary.

Diffuse Pulmonary Disease Caused by Nontuberculous Mycobacteria in Immunocompetent People (Hot Tub Lung)

The clinicopathologic spectrum of infections due to nontuberculous mycobacteria (NTM) includes cavitary disease, opportunistic infection, and nodular disease associated with bronchiectasis. We report a less well-described manifestation of NTM infection: 10 immunocompetent patients without preexisting bronchiectasis had radiographic evidence of diffuse infiltrative lung disease. The most common symptoms were dyspnea, cough, hypoxia, and fever. All 10 patients had used a hot tub. Histologic examination revealed exuberant nonnecrotizing, frequently bronchiolocentric, granulomatous inflammation in all cases. In 1 case, necrotizing granulomas were also noted. The inflammation often was associated with patchy chronic interstitial pneumonia and organization. Cultures revealed NTM in all cases (Mycobacterium avium complex in all but 1 case), but staining for acid-fast bacilli was positive in only 1 case. Four patients received corticosteroids alone for presumed hypersensitivity pneumonia, 4 were treated with antimycobacterial therapy, and 2 received both. All patients demonstrated significant improvement at the time of follow-up. These findings suggest that disease due to NTM may manifest as diffuse infiltrates in immunocompetent adults and that hot tub use may be an important risk factor for this disease pattern.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: A systematic overview

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is being recognized with increasing frequency. Diagnostic and treatment information is limited. A systematic review is presented, focusing on patient demographics, clinical presentation, diagnosis, treatment options, and outcomes. A systematic electronic literature search was conducted for adult DIPNECH cases reported in the English literature during the past 6 years. Twenty-four DIPNECH cases were identified. Another case from our institution is contributed. Women represent 92% (23 of 25). Mean age at diagnosis was 58 years (range, 36-76 yr). Most were nonsmokers (16 of 24). Symptoms included cough (71%), dyspnea (63%), and wheezing (25%) occurring days to years before diagnosis. Pulmonary function testing showed obstructive ventilatory disease in 54%. Lung nodules were seen in 15 patients (63%), ground-glass attenuation in 7 patients (29%), and bronchiectasis in 5 patients (21%). Histological confirmation required surgical lung biopsy for 88%; however, transbronchial biopsies alone were diagnostic in three patients. Treatments strategies included systemic and inhaled corticosteroids, bronchodilators, and lung resection. Available follow-up data in 17 patients showed 6 clinically improved, 7 who remained stable, and 4 clinically deteriorated. The majority of patients presenting with DIPNECH are middle-aged females with symptoms of cough and dyspnea; obstructive abnormalities on pulmonary function testing; and radiographic imaging showing pulmonary nodules, ground-glass attenuation, and bronchiectasis. In general, the clinical course remains stable; however, progression to respiratory failure does occur. Long-term follow-up and treatment remains incomplete. Establishment of a national multicenter DIPNECH registry would allow formulation of optimal evidence-based guidelines for management of these patients.

Thymic Hyperplasia Presenting as Anterior Mediastinal Mass in 2 Patients With Graves Disease

Graves disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. The autoantibodies mimic the effect of the hormone on thyroid cells, which stimulates autonomous production of thyroxine and triiodothyronine. It has been hypothesized that cross-reactivity of autoantibodies may result in Graves ophthalmopathy and dermopathy. A seldom-recognized feature of Graves disease is thymic hyperplasia. We report 2 patients with Graves disease and incidentally discovered anterior mediastinal masses presumed to be thymic hyperplasia. In both cases, these masses regressed spontaneously after treatment of hyperthyroidism.

Corticosteroids influence the mortality and morbidity of acute critical illness

IntroductionUse of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness.MethodsThis case–control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge.ResultsCorticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics.ConclusionCorticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.

A sensitive high throughput ELISA for human eosinophil peroxidase: A specific assay to quantify eosinophil degranulation from patient-derived sources

Quantitative high throughput assays of eosinophil-mediated activities in fluid samples from patients in a clinical setting have been limited to ELISA assessments for the presence of the prominent granule ribonucleases, ECP and EDN. However, the demonstration that these ribonucleases are expressed by leukocytes other than eosinophils, as well as cells of non-hematopoietic origin, limits the usefulness of these assays. Two novel monoclonal antibodies recognizing eosinophil peroxidase (EPX) were used to develop an eosinophil-specific and sensitive sandwich ELISA. The sensitivity of this EPX-based ELISA was shown to be similar to that of the commercially available ELISA kits for ECP and EDN. More importantly, evidence is also presented confirming that among these granule protein detection options, EPX-based ELISA is the only eosinophil-specific assay. The utility of this high throughput assay to detect released EPX was shown in ex vivo degranulation studies with isolated human eosinophils. In addition, EPX-based ELISA was used to detect and quantify eosinophil degranulation in several in vivo patient settings, including bronchoalveolar lavage fluid obtained following segmental allergen challenge of subjects with allergic asthma, induced sputum derived from respiratory subjects following hypotonic saline inhalation, and nasal lavage of chronic rhinosinusitis patients. This unique EPX-based ELISA thus provides an eosinophil-specific assay that is sensitive, reproducible, and quantitative. In addition, this assay is adaptable to high throughput formats (e.g., automated assays utilizing microtiter plates) using the diverse patient fluid samples typically available in research and clinical settings.

Nasal and pharyngeal eosinophil peroxidase levels in adults with poorly controlled asthma correlate with sputum eosinophilia

The objective of the study was to compare nasal, pharyngeal, and sputum eosinophil peroxidase (EPX) levels with induced sputum eosinophil percentage in 10 adults with poorly controlled asthma and 10 normal controls. EPX was measured using an ELISA and normalized for grams of protein for nasal and pharynx specimens and for mL‐gram of protein for sputum. Sputum EPX levels were statistically different between asthma and control subjects (P = 0.024). EPX levels measured in the nasal and pharyngeal swab samples derived from the same patients were also different between asthma and control subjects, each displaying a high degree of significance (P = 0.002). Spearmans correlation coefficients for nasal EPX and pharyngeal EPX levels compared to induced sputum eosinophil percentage were 0.81 (P = 0.0007) and 0.78 (P = 0.0017), respectively. Thus, there is a strong association in a given patient between both nasal and pharyngeal EPX levels and the eosinophil percentage of induced sputum.

Serious Pulmonary Toxicity Secondary to Novel Hepatitis C Antiviral Therapy in a Liver Transplant Recipient

Historically, the treatment of hepatitis C virus infection has been difficult, but therapeutic options have improved markedly recently because of the development of novel antiviral therapies. These therapies have been well tolerated. We describe a patient who was receiving such therapy and had development of temporally related and histologically confirmed severe pulmonary toxicity. Pulmonary toxicity should be considered a potential serious complication of novel antiviral therapy for hepatitis C virus infection.

Nitrofurantoin-Induced Granulomatous Interstitial Pneumonia

Nitrofurantoin-induced lung toxicity is relatively common, but rare histologic patterns sometimes occur that may make diagnosis difficult. We present the case of a 69-year-old woman taking prophylactic nitrofurantoin for urinary tract infections, who developed granulomatous interstitial pneumonia. She improved with cessation of nitrofurantoin, without other therapy. To our knowledge, this is the fourth reported case of granulomatous interstitial pneumonia associated with nitrofurantoin, and the first to show complete resolution with cessation of the drug alone, without steroids. It is important to recognize that idiosyncratic reactions to nitrofurantoin can produce a wide spectrum of histologic patterns. Of these patterns, granulomatous interstitial pneumonia is a rarely evidenced manifestation (possibly because few cases undergo a confirmatory lung biopsy). Recognition of granulomatous interstitial pneumonia as a manifestation of nitrofurantoin toxicity can aid in early identification of the reaction and prompt withdrawal of the drug, both of which are essential to prevent long-term complications.

Nitric oxide therapy for post-laparoscopic surgery associated patent foramen ovale: Incidence, mechanisms, diagnosis and therapy

OBJECTIVE Postoperative hypoxemia is a common clinical challenge. The diagnosis of an underlying cause of hypoxemia may not immediately be apparent. Clinically silent and non-functional intracardiac shunt may become apparent and pose significant management problems in the postoperative period. DATA SOURCE We describe a case where clinically significant hypoxemia resulted from a patent foramen ovale (PFO) after laparoscopic surgery due to changes in the intra-abdominal and intrathoracic pressures. CONCLUSION This condition was effectively diagnosed by bedside echocardiography, and was effectively treated with nitric oxide.