Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells.

Previous studies have shown that exposure to a hypoxic in vitro environment increases the secretion of pro-angiogenic growth factors by human adipose-derived stromal cells (hASCs) [Cao Y, et al., Biochem Biophys Res Commun 332: 370-379, 2005; Kokai LE, et al., Plast Reconstr Surg 116: 1453-1460, 2005; Park BS, et al., Biomed Res (Tokyo) 31: 27-34, 2010; Rasmussen JG, et al., Cytotherapy 13: 318-328, 2010; Rehman J, et al., Circulation 109: 1292-1298, 2004]. Previously, it has been demonstrated that hASCs can differentiate into pericytes and promote microvascular stability and maintenance during angiogenesis in vivo (Amos PJ, et al., Stem Cells 26: 2682-2690, 2008; Traktuev DO, et al., Circ Res 102: 77-85, 2008). In this study, we tested the hypotheses that angiogenic induction can be increased and pericyte differentiation decreased by pretreatment of hASCs with hypoxic culture and that hASCs are similar to human bone marrow-derived stromal cells (hBMSCs) in these regards. Our data confirms previous studies showing that hASCs: 1) secrete pro-angiogenic proteins, which are upregulated following culture in hypoxia, and 2) migrate up gradients of PDGF-BB in vitro, while showing for the first time that a rat mesenteric model of angiogenesis induced by 48/80 increases the propensity of both hASCs and hBMSCs to assume perivascular phenotypes following injection. Moreover, culture of both cell types in hypoxia before injection results in a biphasic vascular length density response in this model of inflammation-induced angiogenesis. The effects of hypoxia and inflammation on the phenotype of adult progenitor cells impacts both the therapeutic and the basic science applications of the cell types, as hypoxia and inflammation are common features of natural and pathological vascular compartments in vivo.

The Microbiology of Complicated Acute Sinusitis among Pediatric Patients: A Case Series.

OBJECTIVE: The microbiology of pediatric complicated acute rhinosinusitis (ARS) has evolved, and our current understanding of pathogenic organisms is limited. The objectives of this study are to describe the incidence of pathogens causing complicated ARS requiring surgical intervention at our institution over a 10-year period as well as their associated treatment outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: A single tertiary care children's hospital. SUBJECTS AND METHODS: Data were reviewed from all patients who underwent surgery for complicated ARS and had positive culture data from 2006 to 2016. Associations among pathogens, complications, and outcomes were analyzed with Pearson χ2 and Wilcoxon rank-sum tests. RESULTS: Eighty-nine patients met criteria. Complications included orbital infections (78%), intracranial infections (48%), Pott's puffy tumor (13%), and cavernous sinus thrombosis (9.0%). Bacterial isolates were majority polymicrobial (55%) and included Streptococcus species (58%), Staphylococcus species (49%; including methicillin-resistant S aureus [MRSA], 11%), and anaerobic bacteria (35%). S pneumoniae (9.0%), Haemophilus species (4.5%), and Moraxella catarrhalis (1.1%) were relatively uncommon. Bacterial isolates were similar among patients with all types of complications. CONCLUSION: Among a large cohort of pediatric patients with complicated ARS, most bacterial isolates were polymicrobial, with Streptococcus and Staphylococcus species contributing to the majority of cases. S aureus species, including MRSA and anaerobic pathogens, were common. The pattern of bacterial isolates was similar among patients with all types of complications of ARS. We suggest treatment for complicated ARS with broad-spectrum antibiotics with coverage for Streptococcus species, Staphylococcus species including MRSA, and anaerobic bacteria.

Predictive ability of bedside nasal endoscopy to diagnose invasive fungal sinusitis in a pediatric population.

INTRODUCTION: Invasive fungal sinusitis (IFS) is a rare but deadly clinical entity that occurs in immunocompromised patients. Diagnosis in children typically requires operative biopsies under general anesthesia, which has associated risks. Findings on bedside nasal endoscopy (BNE) can be used with history, exam, and imaging to determine the need for surgery, however, the accuracy of this tool has not been established among pediatric patients. METHODS: Patients who underwent BNE for evaluation of IFS from 2008 to 2016 at the Children's Hospital of Philadelphia were identified using Current Procedural Terminology (CPT) codes. Retrospective chart analysis was performed and included underlying diagnoses, presenting signs and symptoms, imaging findings, endoscopic findings and outcomes. RESULTS: Nineteen patients were identified who underwent evaluation for IFS using BNE during the period studied. Eight patients had exam findings that were concerning for IFS, including debris or crusting, darkened or pale mucosa, or copious, thick and/or purulent secretions. Immediate operative biopsies and debridement revealed IFS in six of eight patients. Eleven patients had exam findings deemed not concerning for IFS including mucosal edema, mucous without purulence, or normal findings. Six of eleven patients underwent operative biopsy despite negative endoscopy, and five were observed clinically. None of the 11 patients with negative bedside endoscopy developed IFS. CONCLUSIONS: All patients with IFS had concerning exam findings on endoscopy and were treated with immediate biopsies and debridement. No patient with normal or non-concerning findings on BNE progressed to have invasive fungal sinusitis. While suspicion for IFS in immunocompromised children must remain high, BNE is feasible and useful in its assessment.

Complications Associated with Mortality after Head and Neck Surgery.

Objective To determine which complications, as defined by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, correlate with 30-day mortality in surgery for malignancies of the head and neck. Study Design Retrospective review of prospectively collected national database. Setting NSQIP. Subjects and Methods NSQIP data from 2005 to 2014 were queried for ICD-9 codes head and neck malignancies. Multivariate logistic regression was used to examine the correlation of individual complications with 30-day mortality. Results In total, 15,410 cases met criteria with 3499 complications in 2235 cases. After controlling for patient and surgical variables, postoperative pneumonia ( P = .02; odds ratio [OR], 2.39; 95% confidence interval [CI], 1.15-4.72), progressive renal insufficiency ( P < .001; OR, 21.28; 95% CI, 4.22-87.94), bleeding requiring transfusion ( P = .02; OR, 2.10; 95% CI, 1.12-3.84), sepsis ( P = .02; OR, 2.86; 95% CI, 1.15-6.46), septic shock ( P = .045; OR, 2.87; 95% CI, 0.98-7.81), stroke ( P < .001; OR, 19.81; 95% CI, 6.23-56.03), and cardiac arrest ( P < .001; OR, 135.59; 95% CI, 65.00-286.48) were independently associated with increased odds of 30-day mortality. Conclusion The NSQIP database has been extensively validated and used to examine surgical complications, yet there is little analysis on which complications are associated with death. This study identified complications associated with increased risk of 30-day mortality following head and neck cancer surgery. These associations may be used as a measure of complication severity and should be considered when using the NSQIP database to evaluate outcomes in head and neck surgery.

Use of inpatient palliative care services in patients with metastatic incurable head and neck cancer.

BACKGROUND: Substantial health care resources are used on aggressive end-of-life care, despite an increasing recognition that palliative care improves quality of life and reduces health care costs. We examined the incidence of palliative care encounters in in-patients with incurable head and neck cancer and associations with in-hospital mortality, length of hospitalization, and costs. METHODS: Data from the Nationwide Inpatient Sample (NIS) for 80,514 head and neck cancer patients with distant metastatic disease in 2001 to 2010 was analyzed using cross-tabulations and multivariate regressions. RESULTS: Palliative care encounters occurred in 4029 cases (5%) and were significantly associated with age ≥80 years, female sex, self-pay payor status, and prior radiation. Palliative care was significantly associated with increased in-hospital mortality and reduced hospital-related costs. CONCLUSION: Inpatient palliative care consultation in terminal head and neck cancer is associated with reduced hospital-related costs, but appears to be underutilized and restricted to the elderly, uninsured, and patients with an increased risk of mortality.

Association of Clinical Risk Factors and Postoperative Complications With Unplanned Hospital Readmission After Head and Neck Cancer Surgery.

Importance: Unplanned hospital readmission is costly and in recent years has become a focus of health care legislation intended to reduce health care expenditures. Greater understanding of which perioperative complications are associated with hospital readmission after surgery for head and neck cancer is needed to reduce unplanned readmissions. Objective: To determine which clinical risk factors and complications are associated with 30-day unplanned readmission after surgery for malignant neoplasms of the head and neck. Design, Setting, and Participants: This retrospective longitudinal claims analysis included data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from January 1, 2012, to December 31, 2014. Patients undergoing surgery for malignant tumors of the head and neck were included; those with a primary diagnosis of thyroid malignant disease and those undergoing free autologous tissue transfer were excluded. Main Outcomes and Measures: Clinical risk factors and complications were analyzed for association with unplanned hospital readmission using multivariable regression analysis. Statistical significance was determined using P < .05. Results: A total of 7605 patients (5007 men [65.8%]; mean [SD] age, 64.2 [0.2] years) were identified and included for analysis. Overall, 1472 complications occurred in 912 cases. Three hundred eighty-eight patients (5.1%) had an unplanned readmission, which was lower than the previously published overall readmission rate for noncardiac surgical procedures in the NSQIP (6.8%). Clinical factors that were independently associated with unplanned readmission were age (adjusted odds ratio [AOR], 1.12; 95% CI, 1.03-1.22), diabetes (AOR, 1.60; 95% CI, 1.01-2.43), preoperative dyspnea at rest (AOR, 2.89; 95% CI, 1.40-5.55) and with moderate exertion (AOR, 1.48; 95% CI, 1.01-2.11), long-term use of corticosteroids (AOR, 2.45; 95% CI, 1.63-3.58), disseminated cancer (AOR, 1.57; 95% CI, 1.14-2.20), and a contaminated wound (AOR, 2.05; 95% CI, 1.05-3.7). When specific complications were examined, superficial incisional surgical site infection (SSI) (AOR, 2.02; 95% CI, 1.14-3.40), deep incisional SSI (AOR, 2.57; 95% CI, 1.26-5.03), organ or space SSI (AOR, 13.27; 95% CI, 6.57-26.61), wound disruption (AOR, 3.58; 95% CI, 1.95-6.31), pneumonia (AOR, 3.39; 95% CI, 1.88-5.96), deep vein thrombosis (AOR, 5.60; 95% CI, 1.90-15.25), pulmonary embolism (AOR, 20.72; 95% CI, 7.86-55.68), urinary tract infection (AOR, 2.66; 95% CI, 1.00-6.34), stroke (AOR, 12.42; 95% CI, 3.99-36.50), sepsis (AOR, 2.64; 95% CI, 1.27-5.30), and septic shock (AOR, 4.12; 95% CI, 1.10-15.81) were all associated with 30-day unplanned hospital readmission. Conclusions and Relevance: This study evaluated clinical factors and postoperative complications to determine which ones were associated with 30-day unplanned hospital readmission among patients undergoing surgery for malignant tumors of the head and neck. Further understanding of which complications are associated with unplanned readmission after head and neck surgery will allow for improved risk stratification and development of postoperative care protocols to reduce unplanned hospital readmission.

Hospital volume and failure to rescue after head and neck cancer surgery.

OBJECTIVE: To investigate the relationship between hospital volume and mortality, complications, and failure-to-rescue rates among patients undergoing head and neck cancer (HNCA) surgery. STUDY DESIGN: Cross-sectional analysis. SETTING: Nationwide Inpatient Sample. SUBJECTS AND METHODS: Discharge data for 159,301 patients who underwent an ablative procedure for a malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm from 2001 to 2010 were analyzed using cross-tabulations and multivariate regression modeling. Failure to rescue was defined as death after a major complication, including acute myocardial infarction, acute renal failure, venous thromboembolism, pneumonia, gastrointestinal bleed, pulmonary failure, hemorrhage, or surgical site infection. We compared the incidence of mortality, major complications, and failure-to-rescue rates across hospital volume tertiles. RESULTS: The majority of hospitals performing HNCA surgery were low-volume hospitals, which performed a mean of 6 HNCA cases per year (n = 7635). Intermediate-volume hospitals performed a mean of 37 cases per year (n = 729), and high-volume hospitals performed a mean of 131 cases (n = 207). High-volume hospital care was associated with significantly decreased odds of death (odds ratio, 0.56; 95% confidence interval, 0.46-0.86) and failure to rescue (odds ratio, 0.56; 95% confidence interval, 0.33-0.97) compared to low-volume hospital care. However, there was no significant difference in major complication rates between patients undergoing HNCA surgery at high-volume hospitals and those at low-volume hospitals. CONCLUSION: Patients with HNCA who receive care at high-volume hospitals compared with low-volume hospitals have a 44% lower odds of mortality, which appears to be associated with differences in the response to and management of complications rather than differences in complication rates.

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas.

To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.

Increased Flap Weight and Decreased Perforator Number Predict Fat Necrosis in DIEP Breast Reconstruction.

BACKGROUND: Compromised perfusion in autologous breast reconstruction results in fat necrosis and flap loss. Increased flap weight with fewer perforator vessels may exacerbate imbalances in flap perfusion. We studied deep inferior epigastric perforator (DIEP) and muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps to assess this concept. METHODS: Data from patients who underwent reconstruction with DIEP and/or MS-TRAM flaps between January 1, 2010 and December 31, 2011 (n = 123) were retrospectively reviewed. Patient demographics, comorbidities, intraoperative parameters, and postoperative outcomes were collected, including flap fat necrosis and donor/recipient site complications. Logistic regression analysis was used to examine effects of flap weight and perforator number on breast flap fat necrosis. RESULTS: One hundred twenty-three patients who underwent 179 total flap reconstructions (166 DIEP, 13 MS-TRAM) were included. Mean flap weight was 658 ± 289 g; 132 (73.7%) were single perforator flaps. Thirteen flaps (7.5%) developed fat necrosis. African American patients had increased odds of fat necrosis (odds ratio, 11.58; P < 0.001). Odds of developing fat necrosis significantly increased with flap weight (odds ratio, 1.5 per 100 g increase; P < 0.001). In single perforator flaps weighing more than 1000 g, six (42.9%) developed fat necrosis, compared to 14.3% of large multiple perforator flaps. CONCLUSIONS: Flaps with increasing weight have increased risk of fat necrosis. These data suggest that inclusion of more than 1 perforator may decrease odds of fat necrosis in large flaps. Perforator flap breast reconstruction can be performed safely; however, considerations concerning race, body mass index, staging with tissue expanders, perforator number, and flap weight may optimize outcomes.