Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis.

γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ-/- mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis.

Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study.

BACKGROUND: Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. METHODS: We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. RESULTS: We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2-4) and 6 days (stool; IQR 4.25-6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = - 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). CONCLUSIONS: The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.

Surgical Management of Hidradenitis Suppurativa: Outcomes of 590 Consecutive Patients.

BACKGROUND: Hidradenitis suppurativa is a progressive, recurrent inflammatory disease. Surgical management is potentially curative with limited efficacy data. OBJECTIVE: To evaluate hidradenitis surgical patients. METHODS: Retrospective review of outcomes of 590 consecutive surgically treated patients. RESULTS: Most patients were white (91.0% [435/478]), men (337 [57.1%]), smokers (57.7% [297/515]) with Hurley Stage III disease (476 [80.7%]). Procedure types were excision (405 [68.6%]), unroofing (168 [28.5%]), and drainage (17 [2.9%]) treating disease of perianal/perineum (294 [49.8%]), axilla (124 [21.0%]), gluteal cleft (76 [12.9%]), inframammary (12 [2.0%]), and multiple surgical sites (84 [14.2%]). Postoperative complications occurred in 15 patients (2.5%) and one-fourth (144 [24.4%]) suffered postoperative recurrence, which necessitated reoperation in one-tenth (69 [11.7%]) of patients. Recurrence risk was increased by younger age (hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.7-0.9), multiple surgical sites (HR, 1.6; 95% CI, 1.1-2.5), and drainage-type procedures (HR, 3.5; 95% CI, 1.2-10.7). Operative location, disease severity, gender, and operative extent did not influence recurrence rate. CONCLUSION: Excision and unroofing procedures were effective treatments with infrequent complications and low recurrence rates. Well-planned surgical treatment aiming to remove or unroof the area of intractable hidradenitis suppurativa was highly effective in the management of this challenging disease.

Association of Extubation Failure and Functional Outcomes in Patients with Acute Neurologic Illness.

BACKGROUND: An association between extubation failure and neurologic and functional outcomes in patients with primary neurologic illness has not been investigated rigorously. We plan to conduct a retrospective chart review to study this association. METHODS: A total of 949 unique patients intubated and ventilated for at least 48 h in Neuro ICU (NICU) were obtained. Extubation failure was defined as need for reintubation within 48 h of initial extubation. Independent and dependent association between extubation failure and clinical parameters was assessed. RESULTS: The patients had a median age [interquartile range (IQR)] of 58.5 (23.0) years. 60.5% were male and 81.9% were Caucasian. Extubation failure occurred in 108 (12.8%) patients. There was no difference in age, APACHE 3 score, FOUR score, or GCS score of patients at ICU admission between those who experienced extubation failure and those who did not. Extubation failure was associated with longer NICU and hospital LOS [median (IQR); 13.7 (11.3) vs. 9.1(8.2) days, P < 0.01 and 24.5 (20.0) vs. 16.8 (16.7) days, P < 0.01]. Patients with extubation failure had worse functional outcomes at 6 months as measured by the modified Rankin score [MRS; median (IQR), 5.0 (2.0) vs. 4.0 (3.0), P < 0.01]. After adjusting for confounders, extubation failure was associated with longer hospital and ICU LOS and worse functional outcomes. CONCLUSIONS: In patients with acute neurological illness, extubation failure is associated with longer ICU and hospital stays but does not impact hospital mortality. Patients with extubation failure may experience a worsening of their functional status over time.

Predicting renal cryoablation complications: new risk score based on tumor size and location and patient history.

PURPOSE: To identify tumor and patient-related risk factors for major complications following renal cryoablation and to develop a model for predicting these adverse events. MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained for this HIPAA-compliant retrospective study. All 398 renal cryoablation procedures performed from 2003 through 2011 were reviewed to identify tumor and patient-related risk factors associated with major complications (Clavien-Dindo classification, ≥ grade III). A scoring system for predicting these adverse events was then developed using risk factor weighting obtained from a multivariate logistic regression model. To internally validate this model, the scoring system was then applied to all 73 renal cryoablation procedures performed during 2012. RESULTS: Among tumor-related factors evaluated, Maximal tumor diameter (P = .0006) and Central tumor location (P = .02) were significantly associated with major complications. Among patient-related factors evaluated, prior Myocardial infarction (MI) (P = .002) and Complicated diabetes mellitus (P = .01) were significantly associated with major complications. This resulted in the (MC)2 risk scoring system, with (MC)2 risk score = 2.5 points (for tumors ≤ 2.5 cm in maximal diameter) or 0.1 points for each millimeter of maximal tumor diameter (for tumors > 2.5 cm) + 1.5 points (if central tumor location) + 2.5 points (if patient history of prior MI) + 3.0 points (if patient history of complicated diabetes). Mean (MC)2 risk score for all renal cryoablations was 4.7 (standard deviation, 1.9; range, 2.5-15.3). The observed major complication rates were 2.0% (95% confidence interval [CI]: 0.6%, 4.6%) in the low-risk group (score < 5.0), 12.8% (95% CI: 7.5%, 19.9%) in the moderate-risk group (score of 5.0-8.0), and 39.1% (95% CI: 19.7%, 61.5%) in the high-risk group (score > 8.0). Application of the (MC)2 scoring system to the validation group yielded a concordance index of 0.82 (95% CI: 0.62, 1.00). CONCLUSION: The results of this study suggest that the (MC)2 risk score is a valuable tool for predicting major complications in patients undergoing renal cryoablation. However, external validation is warranted.

The impact of respiratory infections and probiotic use on the nasal microbiota of frail residents in long-term care homes.

Background: Residents in long-term care homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrolment in a placebo-controlled trial testing the feasibility of administering a Lactobacillus rhamnosus GG probiotic to prevent respiratory infection (2014-2017). Methods: The microbiome of the nasal (mid-turbinate) of 150 residents of long-term care homes was interrogated using 16S rRNA gene sequencing. Results: We identified a diverse and individualised microbiota which could be separated into nine distinct clusters based on Bray-Curtis distances. Samples collected during symptoms of ILI differed statistically from those collected pre- and post-cold and influenza season, and we observed decreased temporal stability (as measured by movement between clusters) in individuals who experienced ILI compared to those who did not. Conclusions: The use of probiotics decreased ILI-induced changes to the microbiota; however, it is not clear whether this decrease is sufficient to prevent respiratory illness.

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction.

Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity. Co-housing germ-free mice with old, but not young, conventionally raised mice increases pro-inflammatory cytokines in the blood. In tumor necrosis factor (TNF)-deficient mice, which are protected from age-associated inflammation, age-related microbiota changes are not observed. Furthermore, age-associated microbiota changes can be reversed by reducing TNF using anti-TNF therapy. These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.

Composition and immunological significance of the upper respiratory tract microbiota.

The intestinal microbiota is essential for nutrient acquisition, immune development, and exclusion of invading pathogens. The upper respiratory tract (URT) microbiota is less well studied and does not appear to abide by many of the paradigms of the gastrointestinal tract. Decades of carriage studies in children have demonstrated that microbe-microbe competition and collusion occurs in the URT. Whether colonization with common pathogens (e.g., Staphylococcus aureus and Streptococcus pneumoniae) alters immune development or susceptibility to respiratory conditions is just beginning to be understood. Herein, we discuss the biogeography of the URT microbiota, the succession and evolution of the microbiota through the life course, and discuss the evidence for microbe-microbe interactions in colonization and infection.

Impact of Long-Term Poor and Good Glycemic Control on Metabolomics Alterations in Type 1 Diabetic People.

CONTEXT: Poor glycemic control in individuals with type 1 diabetes (T1D) is associated with both micro- and macrovascular complications, but good glycemic control does not fully prevent the risk of these complications. OBJECTIVE: The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control. DESIGN: We compared plasma metabolites in T1D with poor (glycated hemoglobin ≥ 8.5%, T1D[-] and good (glycated hemoglobin < 6.5%, T1D[+]) glycemic control with nondiabetic controls (ND). SETTING: The study was conducted at the clinical research unit. PATIENTS OR OTHER PARTICIPANTS: T1D with poor (n = 14), T1D(-) and good, T1D(+) (n = 15) glycemic control and matched (for age, sex, and body mass index) ND participants were included in the study. INTERVENTION(S): There were no intervention. MAIN OUTCOME MEASURE(S): Comparison of qualitative and quantitative profiling of metabolome was performed. RESULTS: In T1D(-), 347 known metabolites belonging to 38 metabolic pathways involved in cholesterol, vitamin D, tRNA, amino acids (AAs), bile acids, urea, tricarboxylic acid cycle, immune response, and eicosanoids were different from ND. In T1D(+),154 known metabolites belonging to 26 pathways including glycolysis, gluconeogenesis, bile acids, tRNA biosynthesis, AAs, branch-chain AAs, retinol, and vitamin D metabolism remained altered from ND. Targeted measurements of AA metabolites, trichloroacetic acid, and free fatty acids showed directional changes similar to the untargeted metabolomics approach. CONCLUSIONS: Comprehensive metabolomic profiling identified extensive metabolomic abnormalities in T1D with poor glycemic control. Chronic good glycemic control failed to normalize many of these perturbations, suggesting a potential role for these persistent abnormalities in many complications in T1D.

Early prediction of extracorporeal membrane oxygenation eligibility for severe acute respiratory distress syndrome in adults.

PURPOSE: Appropriately identifying and triaging patients with newly diagnosed acute respiratory distress syndrome (ARDS) who may progress to severe ARDS is a common clinical challenge without any existing tools for assistance. MATERIALS AND METHODS: Using a retrospective cohort, a simple prediction score was developed to improve early identification of ARDS patients who were likely to progress to severe ARDS within 7 days. A broad array of comorbidities and physiologic variables were collected for the 12-hour period starting from intubation for ARDS. Extracorporeal membrane oxygenation (ECMO) eligibility was determined based on published criteria from recent ECMO guidelines and clinical trials. Separate data-driven and expert opinion approaches to prediction score creation were completed. RESULTS: The study included 767 patients with moderate or severe ARDS who were admitted to the intensive care unit between January 1, 2005, and December 31, 2010. In the data-driven approach, incorporating the ARDS index (a novel variable incorporating oxygenation index and estimated dead space), aspiration, and change of Pao2/fraction of inspired oxygen ratio into a simple prediction model yielded a c-statistic (area under the receiver operating characteristic curve) of 0.71 in the validation cohort. The expert opinion-based prediction score (including oxygenation index, change of Pao2/fraction of inspired oxygen ratio, obesity, aspiration, and immunocompromised state) yielded a c-statistic of 0.61 in the validation cohort. CONCLUSIONS: The data-driven early prediction ECMO eligibility for severe ARDS score uses commonly measured variables of ARDS patients within 12 hours of intubation and could be used to identify those patients who may merit early transfer to an ECMO-capable medical center.

"Bundle" Practices and Ventilator-Associated Events: Not Enough.

OBJECTIVE Ventilator-associated events (VAEs) are nosocomial events correlated with length of stay, costs, and mortality. Current ventilator bundle practices target the older definition of ventilator-associated pneumonia and have not been systematically evaluated for their impact on VAEs. DESIGN Retrospective cohort study. SETTING Tertiary medical center between January 2012 and August 2014. PARTICIPANTS All adult patients ventilated for at least 24 hours at our institution. INTERVENTIONS We conducted univariate analyses for compliance with each element; we focused on VAEs occurring within a 2-day window of failure to meet any ventilator bundle element. We used Cox proportional hazard models to assess the effect of stress ulcer prophylaxis, deep vein thrombosis (DVT) prophylaxis, oral care, and sedation breaks on VAEs. We adjusted models for gender, age, and Acute Physiology and Chronic Health Evaluation (APACHE) III scores. RESULTS Our cohort comprised 2,660 patients with 16,858 ventilator days and 77 VAEs. Adjusting for APACHE score and gender, only oral care was associated with a reduction in the risk of VAE (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.26-0.77). The DVT prophylaxis and sedation breaks did not show any significant impact on VAEs. Stress ulcer prophylaxis trended toward an increased risk of VAE (HR, 1.59; 95% CI, 1.00-2.56). CONCLUSION Although limited by a low baseline rate of VAEs, existing ventilator bundle practices do not appear to target VAEs well. Oral care is clearly important, but the impact of DVT prophylaxis, sedation breaks, and especially stress ulcer prophylaxis are questionable at best. Infect Control Hosp Epidemiol 2016;1453-1457.

Comparison of facet joint activity on 99mTc-MDP SPECT/CT with facet joint signal change on MRI with fat suppression.

PURPOSE: We compared signal change on magnetic resonance imaging (MRI) with fat suppression and bone scan activity of lumbar facet joints to determine if these two imaging findings are correlated. METHODS: We retrospectively identified all patients who underwent imaging of the lumbar spine for pain evaluation using both technetium-99m methylene disphosphonate single-photon emission computed tomography/computed tomography (99mTc-MDP SPECT/CT) and MRI with at least one fat-suppressed T2- or T1-weighted sequence with gadolinium enhancement within a 180-day interval, at our institution between 1 January 2008 and 19 February 2013. Facet joint activity on 99mTc-MDP SPECT/CT and peri-facet signal change on MRI were rated as normal or increased. Agreement between the two examination types were determined with the κ and prevalence-adjusted bias-adjusted κ (PABAK) statistics. RESULTS: This study included 60 patients (28 male, 47%), with a mean age of 49±19.7 years (range, 12-93 years). The κ value indicated no agreement between 99mTc-MDP SPECT/CT and MRI (κ=-0.026; 95% confidence interval: -0.051, 0.000). The PABAK values were fair to high at each spinal level, which suggests that relatively low disease prevalence lowered the κ values. Together, the κ and PABAK values indicate that there is some degree of intermodality agreement, but that it is not consistent. CONCLUSION: Overall, facet joint signal change on fat-suppressed MRI did not always correlate with increased 99mTc-MDP SPECT/CT activity. MRI and 99mTc-MDP SPECT/CT for facet joint evaluation should not be considered interchangeable examinations in clinical practice or research.

Long-term risk of myocardial infarction and stroke in bipolar I disorder: A population-based Cohort Study.

OBJECTIVES: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder. METHOD: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders. RESULTS: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46). LIMITATIONS: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses. CONCLUSION: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors.

Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death.

Early goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients' outcomes. Our hypothesis was that patients with sepsis treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted, and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload, and in 48%, fluid overload persisted to day 3. Interrater agreement for presence of fluid overload was substantial (κ = 0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (odds ratio, 1.92; confidence interval, 1.16-3.22). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality.

Critical care ultrasonography differentiates ARDS, pulmonary edema, and other causes in the early course of acute hypoxemic respiratory failure.

BACKGROUND: Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS). METHODS: Adult patients in the ICU were prospectively enrolled from January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous causes after reviewing the hospitalization course in electronic medical records. RESULTS: One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio, 191; interquartile range, 122-253). Fifty-nine patients (44%) received a diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines relative to all zones examined) was predictive of miscellaneous cause vs CPE or ARDS (receiver operating characteristic area under the curve [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left-sided pleural effusion (> 20 mm), moderately or severely decreased left ventricular function, and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87). CONCLUSIONS: Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

Adverse in-hospital events are associated with increased in-hospital mortality and length of stay in patients with or at risk of acute respiratory distress syndrome.

OBJECTIVE: To explore the effect of various adverse hospital events on short- and long-term outcomes in a cohort of acutely ill hospitalized patients. PATIENTS AND METHODS: In a secondary analysis of a retrospective cohort of acutely ill hospitalized patients with sepsis, shock, or pneumonia or undergoing high-risk surgery who were at risk for or had developed acute respiratory distress syndrome between 2001 and 2010, the effects of potentially preventable hospital exposures and adverse events (AEs) on in-hospital and intensive care unit (ICU) mortality, length of stay, and long-term survival were analyzed. Adverse effects chosen for inclusion were inadequate empiric antimicrobial coverage, hospital-acquired aspiration, medical or surgical misadventure, inappropriate blood product transfusion, and injurious tidal volume while on mechanical ventilation. RESULTS: In 828 patients analyzed, the distribution of 0, 1, 2, and 3 or more cumulative AEs was 521 (63%), 126 (15%), 135 (16%), and 46 (6%) patients, respectively. The adjusted odds ratios (95% CI) for in-hospital mortality in patients who had 1, 2, and 3 or more AEs were 0.9 (0.5-1.7), 0.9 (0.5-1.6), and 1.4 (0.6-3.3), respectively. One AE increased the length of stay, difference between means (95% CI), in the hospital by 8.7 (3.8-13.7) days and in the ICU by 2.4 (0.6-4.2) days. CONCLUSION: Potentially preventable hospital exposure to AEs is associated with prolonged ICU and hospital lengths of stay. Implementation of effective patient safety interventions is of utmost priority in acute care hospitals.

Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

PURPOSE: Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. PATIENTS AND METHODS: Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. RESULTS: ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). CONCLUSION: The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

A population-based study of the incidence of burning mouth syndrome.

OBJECTIVE: To calculate the incidence of burning mouth syndrome (BMS) in Olmsted County, Minnesota, from 2000 through 2010. PATIENTS AND METHODS: By using the medical record linkage system of the Rochester Epidemiology Project, we identified newly diagnosed cases of BMS from January 1, 2000, through December 31, 2010. Diagnoses were confirmed through the presence of burning pain symptoms of the oral mucosa with normal oral examination findings and no associated clinical signs. Incidence was estimated using decennial census data for Olmsted County. RESULTS: In total, 169 incident cases were identified, representing an annual age- and sex-adjusted incidence of BMS of 11.4 per 100,000 person-years. Age-adjusted incidence was significantly higher in women than in men (18.8 [95% CI, 16.4-22.9] per 100,000 person-years vs 3.7 [95% CI, 2.6-5.7] per 100,000 person-years; P<.001). Postmenopausal women aged 50 to 89 years had the highest incidence of the disease, with the maximal rate observed in women aged 70 to 79 years (70.3 per 100,000 person-years). After the age of 50 years, the incidence of BMS in men and women significantly increased across age groups (P=.02). Study participants residing in Olmsted County, Minnesota, were predominantly white, which is a study limitation. In addition, diagnostic criteria for identifying BMS in the present study may not apply for all situations because no diagnostic criteria are universally recognized for identifying BMS. CONCLUSION: To our knowledge, this is the first population-based incidence study of BMS reported to date. The data reveal that BMS is an uncommon disease highly associated with female sex and advancing age.

Thin endometrial stripe does not affect likelihood of achieving pregnancy in clomiphene citrate/intrauterine insemination cycles.

OBJECTIVE: To determine whether there is a correlation between preovulatory endometrial stripe thickness (EST) and pregnancy rates in clomiphene citrate (CC)/IUI cycles. DESIGN: Retrospective cohort. SETTING: Infertility clinic of an academic medical center. PATIENT(S): A total of 262 patients completed 562 transvaginal ultrasound-monitored CC/IUI cycles from January 2005 through December 2012. INTERVENTION(S): All patients received oral CC. In 362 of the cycles, a single dose of gonadotropin was administered on cycle day 9 (MinStim). A transvaginal ultrasound was performed on cycle day 10, 11, or 12. MAIN OUTCOME MEASURE(S): Pregnancy rate per initiated cycle. RESULT(S): A total of 91 pregnancies ensued, yielding a pregnancy rate of 16.2% per initiated cycle. Pregnancy rates did not vary with EST <6 mm, 6-9 mm, and >9 mm (14.8%, 16.3%, and 19.0%, respectively). There was no significant difference in mean EST between stimulation types (6.8 mm for CC vs. 6.7 mm for MinStim). When conception and nonconception cycles were compared, no difference in mean EST (6.9 mm vs. 6.8 mm, respectively) was observed. Area under the receiver operating characteristic curve for the probability of pregnancy based on EST was 0.51. CONCLUSION(S): Preovulatory EST had no significant correlation with pregnancy rates in CC/IUI cycles. The decision to switch from CC to another treatment strategy should be influenced by factors other than thin endometrial stripe.