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Background Postoperative dehiscence and surgical site infection after spinal surgery can carry serious morbidity. Multidisciplinary involvement of plastic surgery is essential to minimizing morbidity and achieving definitive closure. However, a standardized approach is lacking. The aim of this study was to identify effective reconstructive interventions for the basis of an evidence-based management protocol. Methods A retrospective review was performed at a single tertiary institution for 45 patients who required 53 reconstruction procedures with plastic surgery for wounds secondary to spinal surgery from 2010 to 2019. Statistical analysis was performed for demographics, comorbidities, and treatment methods. Primary outcomes were postoperative complications, including dehiscence, seroma, and infection. The secondary outcome was time to healing. Results The overall complication rate was 32%, with dehiscence occurring in 17%, seroma in 15% and infection in 11% of cases. Median follow-up was 10 months (interquartile range, 4–23). Use of antibiotic beads did not affect rate of infection occurrence after wound closure (P=0.146). Use of incisional negative pressure wound therapy (iNPWT) was significant for reduced time to healing (P=0.001). Patients treated without iNPWT healed at median of 67.5 days while the patients who received iNPWT healed in 33 days. Demographics and comorbidities between these two groups were similar. Conclusions This data provides groundwork for an evidence-based approach to soft tissue reconstruction and management of dehiscence after spinal surgery. Timely involvement of plastic surgery in high-risk patients and utilization of evidence-based interventions such as iNPWT are essential for improving outcomes in this population.

Using 2003–2018 National Ambulatory Medical Care Survey data for office-based visits and 2003–2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care settings. We included adult (≥18 years) patient visits with respiratory-infection-related or non-infection-related cough as reason-for-visit or diagnosis without malignant cancer or benign respiratory tumor diagnoses. Using multivariable logistic regressions, we examined opioid antitussive, benzonatate, dextromethorphan-containing antitussive, and gabapentinoid use trends. From 2003–2005 to 2015–2018, opioid antitussive use decreased in office-based visits (8.8% to 6.4%, Ptrend = 0.03) but remained stable in ED visits (6.3% to 5.9%, Ptrend = 0.99). In both settings, hydrocodone-containing antitussive use declined over 50%. Benzonatate use more than tripled (office-based:1.6% to 4.8%; ED:1.5% to 8.0%; both Ptrend < 0.001). Dextromethorphan-containing antitussive use increased in ED visits (1.8% to 2.6%, Ptrend = 0.003) but stayed unchanged in office-based visits (3.8% to 2.7%; Ptrend = 0.60). Gabapentinoid use doubled in office-based visits (1.1% in 2006–2008 to 2.4% in 2015–2018, Ptrend < 0.001) but was negligible in ED visits. In US office-based and ED ambulatory care settings, hydrocodone-containing antitussive use substantially declined from 2003 to 2018, while benzonatate use more than tripled, and dextromethorphan-containing antitussive and gabapentinoid use remained low (

Purpose This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. Methods Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics. Results Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). Conclusion Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. Trial registration: ClinicalTrials.gov, NCT02612610; registered November 20, 2015

Background: Eosinophilic esophagitis (EoE) is a Type-2 chronic inflammatory food antigen‐driven disease of the esophagus, characterized by eosinophilic predominant inflammation and a constellation of symptoms. The incidence and prevalence of EoE has increased over the past 2 decades. There is an unmet need for approved less burdensome treatment options. Objective: To describe the underlying pathophysiology and diagnosis of EoE and discuss the currently available treatment options. We also aim to review the new and emerging therapies for EoE. Methods: A search of a medical literature data base was performed for articles that discuss treatment for EoE. Results: A comparison of current therapies showed that dietary elimination, swallowed topical corticosteroids, and proton-pump inhibitor therapy are all effective for different populations. Emerging therapies that were reviewed include new topical corticosteroids and biologics directed against Type 2 inflammation. Conclusion: EoE is a chronic inflammatory disorder that can be debilitating, with long-term sequelae. There are no current approved therapies in the United States. Numerous new treatments are on the horizon. Increasing amounts of data are helping to tailor treatment for each patient. Ultimately, shared decision-making is the best approach to guide treatment choices with patients to manage the ever-increasing burden of this disease.

The aim of this study is to critically examine the multidisciplinary approach to abdominal wall reconstruction (AWR) in the solid organ transplant (SOT) population at our institution, MedStar Georgetown University Hospital, using a modified component separation technique (CST). A retrospective review of AWR utilizing modified open CST with biologic mesh in SOT patients was performed from January 2010 to June 2018. Patient demographics, comorbidities, operative details, complications, and outcomes were recorded. Descriptive statistics, logistic and linear regression analyses were performed to appraise outcomes. Thirty-five patients were included; mean age was 53 years. Patient demographics and comorbidities were: 82.9% male, 45.7% history of tobacco use, and 28.6% diabetes. Fifty-one percent had undergone prior hernia repair. Transplant types were: kidney (9), liver (16), liver/kidney (1), small bowel (7), multivisceral (2). All were on an immunosuppressive regimen at time of surgery; 22.9% included steroids. Average defect size was 361 cm2. Additional soft tissue procedures were performed in 65.7% (n = 23) of patients. Median time to healing was 29.0 days. Complication rate was 31.4% (n = 11); six patients required reoperation within 90 days. Recurrence rate was 5.7% (n = 2) at mean of follow up of 3.0 years. Additional soft tissue procedures were statistically significant for healing time (p = 0.037). Steroid use was statistically significant for reoperation within 90 days (OR = 12.500; 95% CI 1.694–92.250); however, steroid use was not significant after correction for confounders. Modified open CST with biologic mesh is a safe, efficacious approach to complex AWR in the SOT population with recurrence rates comparable to the general population.

BACKGROUND: Gefapixant is a P2X3 receptor antagonist that has shown promise for the treatment of refractory and unexplained chronic cough. The aim of this study was to evaluate the efficacy of gefapixant compared with placebo after 12 weeks of treatment for refractory chronic cough or unexplained chronic cough.METHODS: We did a 12-week, phase 2b, randomised, double-blind, placebo-controlled study in patients with refractory chronic cough or unexplained chronic cough aged 18-80 years who were recruited from 44 primarily outpatient pulmonologist or allergist sites in the UK and the USA. Eligible patients had refractory or unexplained chronic cough lasting 1 year or longer, no radiographic chest abnormality, and 40 mm or more on a 100-mm cough severity visual analogue scale at enrolment. Patients were randomly assigned to receive placebo or one of three doses (7·5 mg, 20 mg, or 50 mg) of oral gefapixant twice daily, every day, for 84 days; visits to investigative sites were on days 1, 28, 42, 56, 70, 84, and 85. The randomisation schedule was computer generated using a permuted block algorithm by Advance Research Associates (Santa Clara, CA, USA). Patients and all personnel involved in the conduct and interpretation of the study were masked to treatment assignment. The primary endpoint was placebo-adjusted change from baseline in awake cough frequency after 12 weeks, assessed in the full analysis set, which is a subset of the intention-to-treat population. Adverse events were monitored and safety was evaluated in all patients receiving one or more doses of study drug. This trial is registered with ClinicalTrials.gov, NCT02612610.FINDINGS: Between Dec 21, 2015, and July 26, 2016, 253 patients were randomly assigned to placebo (n=63), gefapixant 7·5 mg (n=64), gefapixant 20 mg (n=63), or gefapixant 50 mg (n=63) twice daily. The mean age of patients was 60·2 (SD 9·9) years and 193 (76%) were women. At 12 weeks, patients' geometric mean awake cough frequency was 18·2 coughs per h (geometric SD 3·1) with placebo, and 14·5 coughs per h (3·7) with 7·5 mg, 12·0 coughs per h (4·2) with 20 mg, and 11·3 coughs per h (2·8) with 50 mg gefapixant. Estimated percentage change relative to placebo was -22·0% (-41·8 to 4·6; p=0·097) with 7·5 mg, -22·2% (-42·0 to 4·3; p=0·093) with 20 mg, and -37·0% (95% CI -53·3 to -14·9; p=0·0027) with 50 mg gefapixant. Dysgeusia was the most common adverse event, occurring in three (5%) patients given placebo, six (10%) given 7·5 mg gefapixant, 21 (33%) given 20 mg gefapixant, and 30 (48%) given 50 mg gefapixant.INTERPRETATION: Targeting purinergic receptor P2X3 with gefapixant at a dose of 50 mg twice daily significantly reduced cough frequency in patients with refractory chronic cough or unexplained chronic cough after 12 weeks of treatment compared with placebo. Further development of gefapixant is warranted for the treatment of chronic cough.FUNDING: Afferent Pharmaceuticals (acquired by Merck & Co., Inc., Kenilworth, NJ, USA).

Background Incisional hernia is a common complication following visceral organ transplantation. Transplant patients are at increased risk of primary and recurrent hernias due to chronic immune suppression and large incisions. We conducted a retrospective review of patients with a history of liver or kidney transplantation who underwent hernia repair to analyze outcomes and hernia recurrence. Methods This is a single center, retrospective review of 19 patients who received kidney and/or liver transplantation prior to presenting with an incisional hernia from 2011 to 2017. All hernias were repaired with open component separation technique (CST) with biologic mesh underlay. Results The mean age of patients was 61.0±8.3 years old, with a mean body mass index of 28.4±4.8 kg/m2, 15 males (78.9%), and four females (21.1%). There were seven kidney, 11 liver, and one combined liver and kidney transplant patients. The most common comorbidities were hypertension (16 patients, 84.2%), diabetes (9 patients, 47.4%), and tobacco use (8 patients, 42.1%). Complications occurred in six patients (31.6%) including hematoma (1/19), abscess (1/19), seroma (2/19), and hernia recurrence (3/19) at mean follow-up of 28.7±22.8 months. With the exception of two patients with incomplete follow-up, all patients healed at a median time of 27 days. Conclusions This small, retrospective series of complex open CST in transplant patients shows acceptable rates of long-term hernia recurrence and healing. By using a multidisciplinary approach for abdominal wall reconstruction, we believe that modified open CST with biologic mesh is a safe and effective technique in the transplant population with complex abdominal hernias.

Summary:. Chlorhexidine is a topical antiseptic that is generally well tolerated in patients, making it a common preparatory substance in various surgical settings. Sparse case reports have identified immediate hypersensitivity reactions after exposure to this substance, especially in patients with a history of atopy. The purpose of this case report is to describe 3 unique presentations of delayed hypersensitivity to epidermal chlorhexidine preparation. Patients undergoing breast surgery by a single surgeon between December 2018 and January 2019 were retrospectively reviewed for incidence of dermatologic complications. Medical and surgical history of patients as well as dermatologic hypersensitivity course were collected. Three patients presented with a delayed hypersensitivity to the epidermal chlorhexidine surgical preparation, ChloraPrep. Each patient developed an erythematous, pruritic maculopapular rash in the distribution of the chlorhexidine application. This occurred beyond the immediate postoperative period—ranging from postoperative days 5 to 35. Initial treatment included the use of 1% hydrocortisone along with a systemic antihistamine. If there was no improvement in symptoms after 3 days, we transitioned patients to 0.5% triamcinolone ointment. If there was no improvement after 5 days on triamcinolone, the patient was reexamined and systemic steroids were prescribed. In each of our cases, all skin changes had resolved within 7–10 days of initial symptoms. Our findings highlight a series of delayed adverse reactions to epidermal chlorhexidine occurring beyond the intraoperative and immediate postoperative period. This case report serves to recognize a unique presentation pattern to ensure that all patients are accurately diagnosed and promptly treated via a systematic treatment algorithm.

Introduction Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools. Methods We tested the efficiency and sensitivity of pooling strategies for RNA extraction and RT-PCR detection of SARS-CoV-2. We tested 184 samples both individually and in pools to estimate the effects of pooling. We further implemented Dorfman pooling with a pool size of eight samples in large-scale clinical tests. Results We demonstrated pooling strategies that increase testing throughput while maintaining high sensitivity. A comparison of 184 samples tested individually and in pools of eight samples showed that test results were not significantly affected. Implementing the eight-sample Dorfman pooling to test 26 576 samples from asymptomatic individuals, we identified 31 (0.12%) SARS-CoV-2 positive samples, achieving a 7.3-fold increase in throughput. Discussion Pooling approaches for SARS-CoV-2 testing allow a drastic increase in throughput while maintaining clinical sensitivity. We report the successful large-scale pooled screening of asymptomatic populations.

Background and objectivesGefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.Materials and methodsTwo randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.ResultsIn clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (pConclusionsP2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.

Background Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). Methods Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). Results 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Background Omalizumab was approved for the treatment of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March 2014. Objective This study sought to describe real-world omalizumab use, in the United States, in a large cohort of patients with CIU/CSU. Methods Patients with CIU/CSU (ages ≥12 years) initiated on omalizumab (index date) with ≥12 months of pre- and postindex data were identified in the an insurance claims data base (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing regimen and continuous use of omalizumab (no gaps for ≥60 days), were described during the 12-month postindex follow-up period. Results A total of 1546 patients (mean ± standard deviation [SD] ages, 44 ± 14.5 years; 73.1% women) were identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a dose decrease. The mean ± SD omalizumab treatment duration was 9.1 ± 3.8 months, the mean ± SD number of omalizumab administrations was 8.3 ± 4.8, and the mean ± SD administration frequency was 44 ± 29 days. A proportion of the patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3, 54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for ≥3 months (39.8%), 21% restarted the treatment after a mean ± SD of 4.4 ± 1.3 months. The proportion of patients who used other CIU/CSU-related medications decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed in oral corticosteroids (75.7 to 49.9%). Conclusion In this large real-world study, the majority of the patients with CIU/CSU were initiated on a 300-mg omalizumab dose and treated without titration up or down for 9 months on average. Most of the patients were continuously treated with omalizumab for ≥6 months, and one-fourth of the patients who discontinued treatment resumed it. Moreover, compared with baseline levels, the use of other CIU/CSU-related medications was lower after omalizumab initiation, with the most prominent decrease observed in oral corticosteroids.

The safety of a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) has been established in adults and adolescents with allergic rhinitis but not in children12 years old.To evaluate the safety and tolerability of an intranasal formulation of AZE and FP in children ages 4-11 years with allergic rhinitis.The study was a randomized, 3-month, parallel-group, open-label design. Qualified patients were randomized in a 3:1 ratio to AZE/FP (n = 304) or fluticasone propionate (FP) (n = 101), one spray per nostril twice daily, and to one of three age groups: ≥4 to6 years, ≥6 to9 years, and ≥9 to12 years. Safety was assessed by child- or caregiver-reported adverse events, nasal examinations, vital signs, and laboratory assessments.The incidence of treatment-related adverse events (TRAEs) was low in both the AZE/FP (16%) and FP-only (12%) groups after 90 days' continuous use. Epistaxis was the most frequently reported TRAE in both groups (AZE/FP, 9%; FP, 9%), followed by headache (AZE/FP, 3%; FP, 1%). All other TRAEs in the AZE/FP group were reported by ≤1% of the children. The majority of TRAEs were of mild intensity and resolved spontaneously. Results of nasal examinations showed an improvement over time in both groups, with no cases of mucosal ulceration or nasal septal perforation. There were no unusual or unexpected changes in laboratory parameters or vital signs.The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered onext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov"ClinicalTrials.gov/ext-link(NCT01794741).

Conjoined twinning is a rare anomaly, with an incidence of approximately 1 in 100,000 live births. There is a high perinatal mortality rate, but twins who survive pose reconstructive challenges that require meticulous preoperative planning. The authors describe the senior surgeon's career experience with conjoined twin separation, and the evolution of medical modeling and 3-dimensional imaging as a critical component in presurgical planning.The authors performed a retrospective review of all consecutive patients of conjoined twin separation at a single institution from January 2004 to December 2013. Data were collected related to patient demographics, comorbidities, operative technique, perioperative complications, survival, long-term outcomes, and the type of medical modeling system used for preoperative planning.Five sets of conjoined twins underwent separation during the 10-year study period. There were 3 sets of thoraco-omphalopagus twins, 1 set of pyopagus twins, and 1 set of ischiopagus tetrapus twins. The mean age at separation was 70 days, with a mean of 3.5 surgical procedures performed per patient during the first year of life. One set of twins experienced postseparation complications that warranted immediate return to the operating room. The overall survival rate after separation was 70%. The imaging methods used were computed tomography scan with 3-dimensional reconstruction, plaster molds, medical modeling with composite printing, and virtual surgical planning.The use of imaging and medical modeling in presurgical planning has proven to be an important element in optimizing the outcomes for patients with this rare anomaly.

Background The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. Objective ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Methods Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non–daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Results Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non–daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non–daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Conclusions Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Summary. This case describes a healthy 37-year-old woman who presented with bilateral breast pain and nodules years after receiving free silicone injections to her breasts. Mammogram revealed extremely dense breasts with innumerable bilateral masses of various sizes. Ultrasound was non-diagnostic due to poor penetration and artifact from silicone. Histologic examination revealed vacuolated histiocytes and innumerable cystic spaces containing material consistent with silicone. Patient underwent bilateral nipple-sparing mastectomy with immediate reconstruction using tissue expanders. This case highlights the potential for serious complications developing years after free silicone injections as well as our team’s surgical management of these complications.

Background Asthma exacerbation risk increases with worsening asthma control. Prevailing numerical control tools evaluate only current symptom impairment despite the importance of also assessing risk based on exacerbation history. An easy-to-use questionnaire addressing impairment and risk domains of control is needed. Objective To validate a composite asthma control tool that includes impairment and risk assessments (Asthma Impairment and Risk Questionnaire [AIRQ]). Methods Four-hundred forty-two patients aged ≥12 years with physician-diagnosed asthma who were followed in specialty practices completed 15 impairment and risk questions with dichotomized yes/no responses. Patients spanned all Global Initiative for Asthma severities and were classified as well-controlled, not well-controlled, or very poorly controlled according to a standard of Asthma Control Test (ACT) score plus prior-year exacerbations. Logistic regression analyses identified questions with the greatest predictive validity to discriminate among patients and determine cut points for these 3 classifications. Results The final AIRQ comprises 10 equally weighted yes/no impairment and risk questions. The final 10-item models yielded receiver operating characteristic curves of 0.94 to identify well-controlled versus not well-/very poorly controlled and 0.93 to identify well-/not well-controlled versus very poorly controlled asthma, as reflected by the ACT plus prior-year exacerbations standard. Cut points of 0-1, 2-4, and 5-10 best represented well-, not well-, and very poorly controlled asthma. Conclusions AIRQ is a rigorously validated composite measure designed to identify adults and adolescents with varying degrees of asthma control. Ongoing investigations will determine test-retest reliability, responsiveness to change, and predictive ability for future exacerbations.

Objectives: We evaluated demographic and baseline characteristics associated with efficacy response with MK-7264, a P2X3 antagonist, in refractory chronic cough patients. Methods: Patients with chronic cough (duration of ≥1 year) refractory to treatment enrolled in a double-blind, parallel group study (NCT02612610) conducted in the US and UK and were randomized to placebo or MK-7264 (7.5 mg BID, 20 mg BID, or 50 mg BID). Awake Cough Frequency (ACF; coughs/hr) after 12 weeks was the primary endpoint; treatment effect was evaluated using a mixed model repeated measures analysis of log-transformed change from baseline adjusting for log-transformed baseline cough count, duration of cough, country, age, sex, visit, and treatment-by-visit interaction. Results: 253 patients (mean age 60 years; 76% female) were randomized. Adjusted to placebo, ACF was significantly reduced by MK-7264 50 mg (p=0.0027) (1); we observed a statistically significant country effect with a larger reduction in ACF in the US vs. the UK. Demographic and baseline cough characteristics between the two countries were comparable. Conclusions: This analysis suggests consistent treatment effect with MK-7264 across a range of factors (e.g. baseline cough count, duration of cough, age, sex, visit, and treatment-by-visit interaction), though some difference in response by region was observed. Further assessment across a broader range of subjects and regions would be informative. Reference: (1) Smith JA et al. American Thoracic Society 2017.

Radiation arteritis is a rare but serious complication following radiation therapy for the treatment of breast cancer. We present the case of a 53-year-old female presenting with right upper extremity claudication 4 months following radiation therapy for the treatment of right breast cancer, stage 3b invasive ductal carcinoma. She was referred to vascular surgery and initial imaging with computed tomography angiography (CTA) revealed occlusion from the origin of the subclavian to axillary artery. We discuss the implications that these vascular findings have on potential breast reconstruction options.

Supplemental Digital Content is available in the text., Summary: Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.

Introduction: MK-7264 (formerly AF-219) is a P2X3 receptor antagonist that has been shown to reduce cough frequency in patients with chronic cough. Methods: This 12-week, double-blind, parallel group study conducted at 46 sites in the US and UK randomized patients with refractory chronic cough (≥1 year) to placebo or MK-7264 at doses of 7.5 mg BID, 20 mg BID, or 50 mg BID. Awake Cough Frequency (coughs/hr) was the primary endpoint (1); 24-hour Cough Frequency was a key secondary endpoint. Responder analyses assessed the % of patients with 30%, 50%, and 70% reduction of cough frequency from baseline. Results: 253 patients (mean age 60 years; 76% female) were randomized to placebo (n=63), and the 7.5 mg (n=64), 20 mg (n=63), and 50 mg (n=63) doses of MK-7264. Awake Cough Frequency was significantly reduced by MK-7264 50 mg vs. placebo (p=0.003) (1). 24-hour Cough frequency was significantly reduced with the 50 mg dose vs. placebo (p=0.001); additionally, the 50 mg group had the highest % of patients with at least a 70% reduction in 24-hr cough frequency (table). Overall, MK-7264 was well tolerated with dysgeusia the most common AE (48% for MK-7264 50 mg) Conclusions: MK-7264 significantly reduced the 24 hour cough frequency in patients with refractory chronic cough after 12 weeks of treatment compared with placebo. Reference: (1) Smith JA et al. American Thoracic Society 2017

Allergic rhinitis (AR) is a disease with a significant global burden, associated with many comorbidities and quality-of-life issues. Overwhelming evidence shows that intranasal corticosteroids are the most effective treatment for AR to control the disease, decrease comorbidities, and decrease costs. Poor adherence is a major barrier to achieving control of AR. This article addresses patient preferences and satisfaction regarding intranasal corticosteroids and factors leading to better adherence. We review and summarize the published literature. Factors affecting patient preference and, ultimately, adherence include a variety of sensory components such as odor, taste, comfort of delivery, delivery devices (aerosol versus aqueous) and patient cost. The intensity of adverse sensory attributes is negatively correlated with patient preference and the likelihood of adherence. Selection of an intranasal steroid (INS) with patient preference and satisfaction in mind can influence patient outcomes and cost. Providers need to assess each patient to determine which inhaled INS will lead to the best adherence, thereby improving outcomes in our patients and ultimately reducing the overall global burden of this disease.

Background:Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia.Methods:One hundred thirty-five revision breast r

Introduction: Chronic cough is a challenging problem as available medications lack proven efficacy. AF-219, a P2X3 antagonist, effectively reduced cough frequency in 2 previous phase 2 trials at doses 50-600mg BID1. The present study explored the dose response relationship below 50mg BID. Methods: A randomized, double-blind, placebo-controlled, crossover, dose escalation study of AF-219 recruited patients with chronic cough ≥1 year and cough severity VAS≥40mm. Patients received 16 days of AF-219 or placebo, dose escalated every 4 days (7.5mg, 15mg, 30mg, 50mg BID consecutively); after ≥15days washout patients crossed over. Awake cough frequency was measured with an ambulatory cough monitor (VitaloJak). Results: 30 patients (12 naive, 18 previously treated at higher doses) at 10 US sites were randomized; mean age 60yrs, median cough duration 13yrs, 80% female. AF-219 30 and 50mg BID produced equivalent, marked reductions in awake cough vs. placebo (p 0.05). Patient perception of improvements in cough severity lagged the objective measure. Separation between efficacy and tolerability was seen, with few patients reporting taste AEs at 7.5 and 15mg (none in naive group). Conclusion: Lower doses of AF-219 produced marked reductions in cough frequency; fewer patients noted reduced taste, portending promising efficacy and tolerability in studies of longer duration. 1Lancet 2015;385:1198.

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a nu(mu)-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56 x 10(20) protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters theta(24) and Delta m(41)(2) and set limits on parameters of the four-dimensional Pontecorvo-Maki-Nakagawa-Sakata matrix, vertical bar U-mu 4 vertical bar(2) and vertical bar U-tau 4 vertical bar(2), under the assumption that mixing between nu(e) and nu(s) is negligible (vertical bar U-e4 vertical bar(2) = 0). No evidence for nu(mu) -> nu(s) transitions is found and we set a world-leading limit on theta(24) for values of Delta m(41)(2) less than or similar to 1 eV(2).

This is an overview of general wound healing and how this applies to abdominal wounds. We introduce the difference between acute and chronic wounds of the abdominal wall, and how management of each type varies. We then introduce our approach and timing for safe surgical debridement paired with negative pressure wound therapy. We then discuss the local wound care options that are used commonly in our practice. We have included several images to guide surgical debridement, followed by case examples of wounds treated in our practice.

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti) neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin(2) 2 theta(mu e) are set over 6 orders of magnitude in the sterile mass-squared splitting Delta m(41)(2). The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Delta m(41)(2) < 0.8 eV(2) at 95% CLs.

The charge ratio, R-mu = N mu+/N mu-, for cosmogenic multiple-muon events observed at an underground depth of 2070 mwe has been measured using the magnetized MINOS Far Detector. The multiple-muon events, recorded nearly continuously from August 2003 until April 2012, comprise two independent data sets imaged with opposite magnetic field polarities, the comparison of which allows the systematic uncertainties of the measurement to be minimized. The multiple-muon charge ratio is determined to be R mu = 1.104 +/- 0.006(stat)(-0.010)(+0.009) (syst). This measurement complements previous determinations of single-muon and multiple-muon charge ratios at underground sites and serves to constrain models of cosmic-ray interactions at TeV energies.

Patient satisfaction with appearance and improved quality of life are primary outcomes in cosmetic surgery. The purpose of this study was to assess changes in patient satisfaction with facial and nose appearance, and quality of life following rhinoplasty.Patients presenting for rhinoplasty completed the FACE-Q, a new patient-reported outcome instrument composed of scales that measure outcomes in patients undergoing facial cosmetic procedures. The following FACE-Q scales were used: satisfaction with facial appearance overall, satisfaction with nose, psychological well-being, and social function.Fifty-six patients completed the FACE-Q at the time of their preoperative consultation and/or at postoperative follow-up visits. Among all patients presenting for rhinoplasty, FACE-Q scores (range, 0 to 100) increased following the procedure in satisfaction with facial appearance (+26.5; p0.01), psychological well-being (+15.7; p0.01), and social function (+13.7; p = 0.03). Satisfaction with nose item scores (range, 1 to 4) all increased significantly from before to after rhinoplasty, including in satisfaction with nose appearance in the mirror (+1.4; p0.01), size (+1.1; p0.01), shape (+1.5; p0.01), profile (+1.6; p0.01), and in photographs (+1.6; p0.01). Similar results were seen among a subgroup of patients who completed the FACE-Q scales both before and after rhinoplasty.In an objective study using a validated patient-reported outcome instrument, improvements in satisfaction with facial and nose appearance and quality of life were demonstrated among rhinoplasty patients. This model supports the successful outcomes possible in rhinoplasty.Therapeutic, IV.

Metabolism initiated SAR studies led to the discovery of a new class of potent 2-azetidinone cholesterol absorption inhibitors. These studies found that a heteroatom at the para position of the C-4 phenyl ring is not a requirement for cholesterol absorption inhibition as was suggested by earlier findings. Substitution of Ph-linker-COOR for PhOMe at the C-4 position enhanced cholesterol absorption inhibition.

We report measurements of oscillation parameters from v(mu) and (v) over bar (mu) disappearance using beam and atmospheric data from MINOS. The data comprise exposures of 10.71 X 10(20) protons on target in the v(mu)-dominated beam, 3.36 X 10(20) protons on target in the (v) over bar (mu)-enhanced beam, and 37.88 kton yr of atmospheric neutrinos. Assuming identical v and (v) over bar oscillation parameters, we measure vertical bar Delta m(2)vertical bar = (2.41(-0.10)(+0.09)) X 10(-3) eV(2) and sin(2)(2 theta) = 0.950(-0.036)(+0.035). Allowing independent v and (v) over bar oscillations, we measure antineutrino parameters of vertical bar(m) over bar (2)vertical bar = (2.50(-0.250)(+0.23)) X 10(-3) eV(2) and sin(2)(2 (theta) over bar) = 0.97(-0.08)(+0.03), with minimal change to the neutrino parameters.

The CoGeNT Collaboration has recently published results from a fifteen month data set which indicate an annual modulation in the event rate similar to what is expected from weakly interacting massive particle interactions. It has been suggested that the CoGeNT modulation may actually be caused by other annually modulating phenomena, specifically the flux of atmospheric muons underground or the radon level in the laboratory. We have compared the phase of the CoGeNT data modulation to that of the concurrent atmospheric muon and radon data collected by the MINOS experiment which occupies an adjacent experimental hall in the Soudan Underground Laboratory. The results presented are obtained by performing a shape-free chi(2) data-to-data comparison and from a simultaneous fit of the MINOS and CoGeNT data to phase-shifted sinusoidal functions. Both tests indicate that the phase of the CoGeNT modulation is inconsistent with the phases of the MINOS muon and radon modulations at the 3.0 sigma level. DOI: 10.1103/PhysRevD.87.032005

In steroid-resistant (SR) asthma, there is a lack of clinical responsiveness to oral prednisone. Previous studies indicate that this may be explained by the effect of the combination of interleukin 2 (IL-2) and IL-4 on glucocorticoid receptor binding affinity. By contrast, steroid-sensitive (SS) asthmatics respond well to glucocorticoids, and this is accompanied by a decrease in the numbers of bronchoalveolar lavage (BAL) messenger RNA+ (mRNA+) cells expressing IL-4 and IL-5, and an increase in interferon gamma (IFN-gamma) transcripts. In the present study, we hypothesized that SR asthma is associated with alterations in T helper types 1/2 (Th2/Th1)-type cytokine gene expression. BAL was performed in six SR asthmatics and six SS asthmatics, before and after a 1-wk course of 40 mg daily prednisone. mRNA+ cells for IL-2, IL-4, IL-5, and IFN-gamma was measured by in situ hybridization using 35S-labeled RNA probes. Before prednisone therapy, there were significantly greater numbers of BAL cells (per 1,000) expressing IL-2 mRNA (p < 0.01) and IL-4 mRNA (p < 0.05) in SR asthmatics as compared with SS asthmatics, but no differences between the two groups in the numbers of BAL cells expressing IFN-gamma or IL-5 mRNA expression were observed. After a 1-wk course of prednisone, IL-2 expression was not altered in either group. However, SS asthmatics had a significant decrease in the numbers of BAL cells expressing mRNA for IL-4 (p < 0.01) and IL-5 (p < 0.001), and a rise in the numbers of IFN-gamma mRNA+ cells (p < 0.01). In contrast, after prednisone treatment, SR asthmatics had no significant change in either the number of BAL cells expressing mRNA for IL-4 or IL-5. Of note, there was an unexpected decrease in the numbers of IFN-gamma mRNA+ cells (p = 0.05). Our current findings indicate that SR asthma is associated with a dysregulation of the expression of the genes encoding for Th2/Th1 cytokines in airway cells and is compatible with the concept that a combination of IL-2 and IL-4 induce glucocorticoid (GR) binding affinity and T cell responsiveness to glucocorticoids.

Prosthetic-based breast reconstruction commonly involves device placement in either a total submuscular pocket or a partial subpectoral position for just superior pole coverage, with various possible strategies for inferior pole coverage. Historically, the pectoralis major muscle is managed either by suturing the muscle to the inferior flap or with marionette sutures; alternatively, the device is placed under total muscle/fascia coverage (under the pectoralis major, plus the serratus anterior and rectus abdominis muscles or fascia). For many plastic surgeons, acellular dermal matrix is now used instead to function as a sling or "hammock" supporting the periprosthetic pocket and thus covering the inferior pole of the device, attached to the pectoralis major muscle above and to the inframammary fold below. In addition to its added soft-tissue support in the inferior pole, acellular dermal matrix may help to stabilize the pectoralis major muscle along its inferolateral margin, create a well-defined inframammary fold, provide the opportunity to significantly increase intraoperative fill volume of the tissue expander, and reduce the incidence or severity of significant or symptomatic capsular contracture, particularly in a patient whose breast has been treated with radiation. In addition to its indications in primary breast reconstruction, acellular dermal matrix has been increasingly used in secondary revision reconstruction cases. It can be used to buttress capsulorrhapy and capsulotomy sites and it can be used to replace periprosthetic capsule following capsulectomy. While clinical experience is accruing for these indications, acellular dermal matrix continues to be used in primary and secondary breast reconstruction.