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The main objective of this study was to examine the explanatory models of secondary school students, about the structure of the animal eukaryotic cells before and after an didactic intervention, based from the cognitive model of science (Giere, 1992) and the constructivist learning cycle (Sanmartí, 2000). The research took place in two stages: a. Descriptive and interpretative stage, we categorized the explanatory models identified in 18 families of models and b. The pre-experimental stage, it identifies whether there were significant differences between the models before and after the educational intervention by Wilcoxon test and data randomization, ANOVA. The main findings showed that didactic intervention encourages the building of explanatory models, which are characterized by more specialized language, new relationships between the organelles and cellular functions and the ability to incorporate new elements to enrich the school cell model, demonstrating that these models evolve progressively (RodrÍguez and Moreira, 1999; Justi, 2006).

Background: Surgeons are often asked to provide a diverting colostomy to enable healing or simplify management of sacral pressure ulcers. However, little evidence exists regarding the safety of a diversion in this often compromised patient population. We hypothesized that malnourished patients with sacral pressure ulcers have poor outcomes with fecal diversion., Methods: ACS-NSQIP (2012-2018) was used to identify patients who underwent elective diverting colostomy for sacral pressure ulcers. Demographics, comorbidities, and perioperative details were recorded. Postoperative complications and 30-day mortality were compared between patients with moderate/severe hypoalbuminemia (< 2.5 g/dL) vs those with albumin > 2.5 g/dL., Results: We identified a total of 863 patients who underwent elective diverting colostomy for sacral pressure ulcer. Mean age was 57.5 years old. Rate of associated comorbidities was high, with most patients classified as ASA class 3 or 4. Over 40% of patients had a preoperative albumin level < 2.5 g/dL. Thirty-day overall postoperative mortality was 6.7%. This was significantly higher in patients with hypoalbuminemia (11.4% vs. 3.5%, p < 0.001). On multivariable regression analysis, preoperative albumin < 2.5 g/dL was independently associated with mortality (OR 1.92, p = 0.039). Other factors associated with mortality included increased age (OR 1.04 per year, p < 0.001), preoperative sepsis (OR 1.66, p = 0.003), and Black race (OR 2.2, p = 0.01)., Conclusions: Diverting colostomy performed for patients with sacral pressure ulcers is associated with a substantial risk of postoperative death. Surgeons should carefully consider risks of diversion in this patient population, especially in malnourished patients with hypoalbuminemia., (© 2022. The Society for Surgery of the Alimentary Tract.)

Roughness-tactile perception is part of activity assessment in initial-caries-lesions. Hypothesizing that a probe's design influences this examiner's assessment, four probes were designed. The aims of this study were to select the probe with highest inter-/intra-examiners' roughness-assessment agreement and to determine its diagnostic accuracy on artificial initial-caries lesions. A pilot study was conducted with trained dentists to select one controlled-pressure probe design (n = 4) by assessing roughness on known-roughness metal plaques with 5-point Likert scale. Diagnostic accuracy of roughness assessment was conducted with the selected controlled-pressure probe and the WHO-probe on sound and artificial initial-caries-lesion (n = 20) human enamel blocks. Intra-class correlation coefficients (ICCs) and quadratic weighted-Kappa scores were used to assess examiners' reproducibility and Multilevel Poisson models to determine diagnostic accuracy between both probes controlling for confounding variables. The probe design with the highest inter/intra-examiner's agreement (ICC = 0.96) was selected for subsequent analyses. Unadjusted sensitivity, specificity and accuracy values were for the controlled-pressure and the WHO probes: 71.1%,90.6%,81.2%, and 67.4%,84.6%,75.8%, respectively (p > 0.05). Examiner remained the most important factor influencing diagnostic accuracy. While this study did not show significantly higher diagnostic accuracy of the designed controlled-pressure vs. the WHO-probe when used by trained dentists, all over roughness-assessment accuracy and reproducibility were high.

Epidemiological studies use biomarkers of fluoride exposure in pregnant women as surrogate measures of fetal fluoride exposure; however, there is little understanding of how pregnancy affects fluoride metabolism and its biomarkers. This narrative review summarizes the changes of pregnancy that have the potential to impact fluoride's absorption, distribution and excretion, and highlights the limited body of evidence on the topic. The physiologic systems that experience pregnancy-associated changes relevant to fluoride's metabolism are the cardiovascular, renal, metabolic and gastrointestinal, as well bone and calcium metabolism and the body's acid-base balance. The available evidence indicates that fluoride is found in the maternal plasma and urine, placenta, amniotic fluid and fetus. Although plasma and urinary fluoride vary across gestation, there is insufficient quality evidence to determine the direction or extent of such variation. Furthermore, there is no doubt that fluoride from maternal blood crosses the placenta and is absorbed and excreted by the fetus; however, the biological mechanisms behind this placental passage are unknown. Research on maternal and prenatal biomarkers of fluoride exposure would benefit from studies on how pregnancy-associated changes affect the metabolism of fluoride across gestation, the mechanisms for the intestinal absorption of fluoride in pregnant women, and the placental passage of fluoride.

Dietary factors are known to influence urinary fluoride (UF) levels in nonpregnant people. Maternal UF is used as a biomarker of fluoride exposure; however, dietary influences on UF during pregnancy are unknown. We compared UF levels and assessed the associations between UF and five select dietary influences in pregnancy vs. one-year postpartum: dietary fluoride (F), calcium intake from diet (Ca-diet), calcium intake from supplements (Ca-sup), dietary acid load (AL), and table salt use (TS) in 421 women exposed to fluoridated salt in the Mexican diet. Spot UF (mg/L) was measured by microdiffusion/fluoride-specific electrode and dilution-corrected with specific gravity (SG). Dietary variables were estimated from a validated Food Frequency Questionnaire. Comparisons among UF in pregnancy vs. one-year postpartum were performed with non-parametric tests. Associations between dietary variables and UF were assessed using random effect models (for pregnancy) and linear regression (for one-year postpartum). SG-corrected UF (median, range) during pregnancy (0.77, 0.01-4.73 mg/L) did not significantly differ from one-year postpartum (0.75, 0.15-2.62 mg/L) but did increase every 10 gestational weeks, β = 0.05 (CI: 0.00-0.10). Different dietary influences on UF were identified at each state. Although Ca-diet and AL were not associated with UF in either state, Ca-sup decreased UF only during pregnancy, β =  - 0.012 mg/L (CI: - 0.023-0.00). Reporting TS use was associated with 12% increase in UF only at one-year postpartum (p = 0.026). These results suggest different dietary influences on UF in the pregnant state, which need consideration when using UF as a biomarker of fluoride exposure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To estimate dietary fluoride intake (F) over the course of pregnancy and the overall adjusted difference in dietary F intake by pregnancy stages and levels of compliance with dietary recommendations., Design: Secondary data analysis from a longitudinal pregnancy cohort study in a population exposed to fluoridated salt. Women were followed during the early, middle and late stages of their pregnancy (n 568). The dietary intake of recommended prenatal nutrients according to Mexican dietary guidelines and F intake (mg/d) was estimated with a validated FFQ. Data were summarised with descriptive statistics. Levels of F intake were compared with the USA's Institute of Medicine adequate intake (AI) of 3 mg/d for pregnancy. Adjusted differences in F intake by pregnancy stages and levels of compliance with recommendations were estimated using random effects models., Setting: Mexico City., Participants: Women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, from 2001 to 2003., Results: Median dietary F intake throughout pregnancy ranged from 0·64 (interquartile range (IQR) 0·38) in the early to 0·70 (IQR 0·42) in the middle, and 0·72 (IQR 0·44) mg/d in the late stage (0·01 mg F/kg per d). Corresponding adjusted intakes of F were 0·72 (95 % CI 0·70, 0·74), 0·76 (95 % CI 0·74, 0·77) and 0·80 (95 % CI 0·78, 0·82) mg/d. Women who were moderately and highly compliant with Mexican dietary recommendations ingested, on average, 0·04 and 0·14 mg F/d more than non-compliant women (P < 0·005)., Conclusions: Dietary F intake was below current AI, was greater with the progression of pregnancy and in women who were moderately and highly compliant with dietary recommendations.

Background: There is a paucity of literature on treatment of melanoma in children with surgical management extrapolated from adult experience. The incidence and clinical outcomes of pediatric extremity melanoma were studied., Methods: SEER registry was analyzed between 1973 and 2010 for patients <20years old with extremity melanoma. Multivariate and propensity-score matched analyses were performed to identify independent predictors of survival., Results: Overall, 917 patients were identified with an age-adjusted incidence of 0.2/100,000 persons, annual percent change 0.96. Most had localized disease (77%), histology revealing melanoma-not otherwise specified (52%). Surgical procedures performed included wide local excision (50%), excisional biopsy (32%), lymphadenectomy (LA) (28%), and sentinel lymph node biopsy (SLNB) (15%). Overall, 30-year disease specific mortality was 7% with lower survival for extremity melanoma (90%), males (89%), nodular histology (69%), and distant disease (36%) (all P<0.05). Post-treatment multivariate analysis revealed localized disease (HR 9.76; P=0.006) as an independent prognosticator of survival; earlier diagnostic years 1988-1999 (HR 2.606; P=0.017) were a negative prognosticator of survival. Propensity-score matched analysis found no difference in survival between SLNB/LA vs no sampling for regional/distant disease., Conclusions: Pediatric extremity melanoma in SEER demonstrate no survival advantage between children undergoing sampling procedures vs no sampling for regional/distant disease., Type of Study: Retrospective, prognostic study., Level of Evidence: III., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fibrosis can develop in nearly any tissue leading to a wide range of chronic fibrotic diseases. However, current treatment options are limited. In this study, we utilized an established aged mouse model of bleomycin-induced lung fibrosis (BLM) to test our hypothesis that fibrosis may develop simultaneously in multiple organs by evaluating skin fibrosis and wound healing. Fibrosis was induced in lung in aged (18-22-month-old) C57BL/6 male mice by intratracheal BLM administration. Allogeneic adipose-derived mesenchymal stromal cells (ASCs) or saline were injected intravenously 24 hr after BLM administration. Full thickness 8-mm punch wounds were performed 7 days later to study potential systemic anti-fibrotic and wound healing effects of intravenously delivered ASCs. Mice developed lung and skin fibrosis as well as delayed wound closure. Moreover, we observed similar changes in the expression of known pro-fibrotic factors in both lung and skin wound tissue, including miR-199 and protein expression of its corresponding target, caveolin-1, as well as phosphorylation of protein kinase B. Importantly, ASC-treated mice exhibited attenuation of BLM-induced lung and skin fibrosis and accelerated wound healing, suggesting that ASCs may prime injured tissues and prevent end-organ fibrosis., (© 2017 Wiley Periodicals, Inc.)

Background: Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC., Methods: A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression., Results: Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6)., Conclusion: Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: End-stage renal disease (ESRD) is associated with increased cardiovascular risk factors, electrolyte imbalances, and iron deficiency anemia. These factors may increase the risk of adverse outcomes in patients undergoing panniculectomy. There is a paucity of data regarding outcomes in patients with ESRD undergoing panniculectomy. The purpose of this study is to investigate whether ESRD is associated with increased rate of complications following a panniculectomy., Method: The Nationwide Inpatient Sample database (2006-2011) was used to identify patients who underwent a panniculectomy. Among this cohort, patients diagnosed with end-stage renal disease were identified. Patients excluded from the study were emergency admissions, pregnant women, patients less than 18 years old, and patients with concurrent nephrectomy or kidney transplants. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-squared and risk-adjusted multivariate logistic regression analyses were performed to determine whether end-stage renal disease was associated with increased rate of postoperative complications., Results: A total of 34,779 panniculectomies were performed during the study period. Of these, 613 (1.8%) were diagnosed with ESRD. Patients with ESRD were older (mean age 58.9 vs. 49.3, p < 0.01) and more likely to have Medicare (63.5 vs. 18.4%, p < 0.01). They had higher rates of comorbidities, including diabetes, hypertension, congestive heart failure, chronic lung disease, chronic anemia, liver disease, peripheral artery disease, obesity, and coagulopathies (p < 0.01). The procedure was more likely to occur at a large, teaching hospital (p < 0.01). Postoperatively, patients with ESRD had a higher rate of death (3.3 vs. 0.2%, p < 0.01), wound complications (10.6 vs. 6.2%, p < 0.01), venous thromboembolism (4.9 vs. 0.8%, p < 0.01), blood transfusions (25.3% vs. 7.0%, p < 0.01), non-renal major medical complications (40.0% vs. 8.4%), and longer hospital stay (9.2 vs. 3.8 days, p < 0.01). Multivariate logistic regression analysis controlling for age, race, sex, hospital location/teaching hospital, payer, and all comorbidities demonstrated that ESRD was independently associated with increased venous thromboembolisms (OR 2.38, 95% CI 1.48-3.83) and non-renal major medical complications (OR 1.51, 95% CI 1.19-1.91). ESRD was not independently associated with increased rate of wound complications or transfusions., Conclusion: Patients with ESRD are at increased risk of VTE and non-renal major medical complications following panniculectomy. Moreover, patients with ESRD have longer hospital stays and higher rates of mortality., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Obesity may increase the risk of complications following abdominal contouring. The aim of this study is to evaluate panniculectomy outcomes in patients with class III obesity (BMI > 40 kg/m 2 )., Methods: The American College of Surgeon's National Surgical Quality Improvement Program ACS-NSQIP (2010-2014) was used to identify patients who underwent panniculectomy. Class III obesity patients were identified. Demographics, comorbidities and postoperative outcomes were evaluated. Risk-adjusted multivariate logistic regression analyses were performed to assess impact of class III obesity on panniculectomy outcomes., Results: A total of 4497 panniculectomies were identified. Of these, 545 (12.1%) were performed in patients with class III obesity. This group was older (mean age 50.3 vs. 45.9, p < 0.01) with a higher proportion of men (23.4 vs. 12.4%, p < 0.01). Class III obesity group also had higher rates of comorbidities (p < 0.01). Postoperatively, class III obesity patients experienced much higher rates of wound complications (17.8 vs. 6.8%), sepsis (3.3 vs. 0.8%), venous thromboembolism (1.5 vs. 0.7%) and medical complications (6.4 vs. 1.8%), p < 0.05. Additionally, this group had higher rates of unplanned reoperation (9.2 vs. 3.7%) and 30-day readmissions (3.5 vs. 1.0%), p < 0.01. On risk-adjusted multivariate regression analyses, class III obesity was independently associated with increased risk of wound complications (OR 2.22, p < 0.01), sepsis (OR 3.53, p < 0.01), medical adverse events (OR 1.98, p < 0.05), unplanned reoperation (OR 1.62, p < 0.05) and 30-day readmission (OR 2.30, p < 0.05)., Conclusion: Class III obesity patients are at significantly increased risk of adverse outcomes following abdominal contouring. Plastic surgeons should consider these risks for counseling and preoperative risk optimization., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: This study evaluates differences in wound complication rate when transverse versus longitudinal incision is utilized to expose femoral vessels in managing patients with peripheral vascular disease., Methods: A retrospective review from 2013 to 2015 was conducted of 150 patients undergoing 156 lower extremity revascularizations with femoral artery exposure through a groin incision. Patients were stratified into 2 groups, transverse versus longitudinal groin incision. Data were reviewed for 3 surgeons that utilize either transverse or longitudinal groin incision in patients undergoing common or iliofemoral endarterectomies, or where femoral artery was used as inflow and/or outflow vessel for limb revascularization. Each group had a comparative outcomes analysis based on incision type. The primary outcome was wound complication, defined as any wound infection, lymphocele, hematoma, dehiscence, pseudoaneurysm, or necrosis. Other outcomes studied included unplanned return to operating room for wound complication, wound vacuum therapy, and soft-tissue flap closure. Data were analyzed using 2-tailed chi-squared test and Student's t-test., Results: Patients in the transverse (n = 85 cases) versus longitudinal (n = 71 cases) cohorts were similar in relation to demographics and comorbidities. Overall mean follow-up was 220 days. Patients with a transverse as compared to longitudinal incision had a significantly lower overall wound complication rate, 7% vs. 42%, respectively (P < 0.001). Furthermore, transverse incisions were associated with lower incidence of unplanned return to the operating room to manage wound complications than patients with a longitudinal incision (5% vs. 23%, respectively; P < 0.001). Transverse versus longitudinal incisions were also associated with significantly lower need for wound vacuum therapy (6% vs. 15%, respectively; P < 0.05) and muscle flap closure (0% vs. 13%, respectively; P < 0.001) for wound complications., Conclusions: Transverse groin incisions for femoral artery exposure may offer a lower risk of wound complications for open procedures as compared to a longitudinal incision. While longitudinal incisions may have higher wound complication rates, incisional approach is contingent on anatomical circumstance and treated disease pattern. Patients should undergo appropriate preoperative counseling regarding wound healing in preparation for limb revascularization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Estrogen receptors can regulate growth in papillary thyroid cancer and may affect prognosis after menopause. This study examines changes of estrogen receptor subtype ratio expression in papillary thyroid cancer cell lines derived from pre- and postmenopausal women., Methods: Cells were harvested from papillary thyroid cancer and non-papillary thyroid cancer thyroid tissue (control) from pre- (n = 9) and postmenopausal women (n = 11). Protein expression of estrogen receptor α, estrogen receptor β, and phosphorylated extracellular signal-regulated kinase and protein kinase B were analyzed. Matrix metalloproteinase-2 activity was determined as a measure of tumor invasiveness. Mitochondrial retrograde signaling was altered with ethidium bromide to determine its effect on estrogen receptor α protein expression., Results: Estrogen receptor α expression was increased in postmenopausal papillary thyroid cancer cells compared with controls but was unchanged in premenopausal papillary thyroid cancer. Estrogen receptor β expression did not change in either group. Increased matrix metalloproteinase-2 activity was observed only in postmenopausal papillary thyroid cancer. Premenopausal papillary thyroid cancer cells demonstrated increased extracellular signal-regulated kinase and unchanged protein kinase B activation. Conversely, postmenopausal papillary thyroid cancer cells had decreased extracellular signal-regulated kinase and increased protein kinase B activation. Ethidium bromide treatment resulted in increased estrogen receptor α protein expression only in premenopausal papillary thyroid cancer cells., Conclusion: Increased estrogen receptor α expression may be involved in papillary thyroid cancer aggressiveness after menopause. This process may be regulated by differential activation of intracellular pathways and differing sensitivities to mitochondrial signaling regulation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Natural lung aging is characterized by molecular and cellular changes in multiple lung cell populations. These changes include shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, apoptosis, and stem cell exhaustion. Aging, combined with the loss of protective repair processes, correlates with the development and incidence of chronic respiratory diseases, including idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Ultimately, it is the interplay of age-related changes in biology and the subsequent responses to environmental exposures that largely define the physiology and clinical course of the aging lung., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The risk of venous thromboembolism (VTE) in patients undergoing bilateral breast reduction surgery remains unknown. This study aimed to determine VTE incidence and risk factors in this patient cohort., Methods: American College of Surgeons National Surgical Quality Improvement Program (2010-2014) was used to identify women undergoing bilateral breast reduction. Demographic factors, comorbidities, and incidence of postoperative VTE were evaluated. Bivariate and risk-adjusted multivariate logistic regressions were performed to determine factors associated with the development of postoperative VTE., Results: A total of 5371 cases were identified. The mean age was 43.7 years (SD ± 13.9 years). The rate of VTE was 0.22%, with 0.17% rate of pulmonary embolism and 0.07% rate of deep venous thrombosis requiring treatment. Patients who suffered VTE were older (52.4 ± 12.8 vs. 43.7 ± 13.9 years, p < 0.05), had longer length of stay (1.7 ± 2.9 vs. 0.4 ± 2.1 days, p < 0.05), and had higher rates of blood transfusion (8.3% vs. 0.4%, p < 0.01) and reoperation (16.7% vs. 2.0%, p < 0.01). Risk-adjusted multivariate analysis demonstrated that older age (OR 1.05, 95% CI 1.01-1.10), postoperative blood transfusion (OR 12.1, 95% CI 1.3-112.0) and unplanned return to the operating room (OR 6.7, 95% CI 1.3-34.8) were independent risk factors for developing postoperative VTE., Conclusion: In bilateral breast reduction surgery, older patients, patients requiring blood transfusion, and patients who have unplanned return to the operating room are at an increased risk of developing postoperative VTE. These factors can be considered for patient risk-stratification and perioperative decision-making regarding VTE prevention., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Both functional (hormone hypersecreting) and nonfunctional (nonhypersecreting) adrenal tumors can have benign or malignant pathology. This study compares perioperative in-hospital outcomes after adrenalectomy in patients with benign versus malignant nonfunctional primary adrenal tumors., Methods: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database (2006-2011) to identify patients who underwent unilateral open or laparoscopic adrenalectomy for nonfunctional primary adrenal tumors. Patients were subdivided by benign and malignant final pathology. Demographics, comorbidities, and perioperative complications were compared between groups using bivariate and multivariate logistic regression., Results: Of 23,297 patients, 89.7% (n = 20,897) had benign tumors, whereas 10.3% (n = 2400) had malignant tumors. Those with malignant tumors had higher Charlson Comorbidity Index scores and were more likely to undergo adrenalectomy at high volume centers. For both laparoscopic and open approach, patients with malignant nonfunctional tumors had higher rates of intraoperative complications including vascular and splenic injury (P < 0.01), as well as postoperative complications including hematoma, shock, acute kidney injury, venous thromboembolism, and pneumothorax (P < 0.01). In addition, the malignant group had higher rates of blood transfusions, longer hospital stay, and higher in-hospital mortality (P < 0.05) than benign counterparts. On risk-adjusted multivariate analysis, malignant nonfunctional primary adrenal tumors were independently associated with increased risk of complications following adrenalectomy., Conclusions: Patients with malignant nonfunctional primary adrenal tumors have higher perioperative morbidity and mortality compared to patients with benign nonfunctional adrenal tumors. Such patients should be medically optimized before adrenalectomy, and surgeons must remain vigilant in preventing perioperative complications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans.

Background: Management of velopharyngeal insufficiency (VPI) has traditionally involved surgical repair to improve speech. Posterior pharyngeal augmentation using injectable synthetic materials has been advocated. However, outcomes have been equivocal. More recently, autologous fat injection (AFI) has been advocated for correction of mild to moderate VPI. However, long-term efficacy and safety of this procedure remain unsettled., Methods: A systematic review of the literature was performed. Available studies that reported outcomes of autologous fat velopharyngeal injection for treatment of documented VPI were included. Preclinical animal studies were excluded. Study characteristics, patient demographics, treatment details including fat harvest site, volume injected, and outcome measures were evaluated., Results: Fifteen studies met inclusion criteria, yielding 251 patients who underwent AFI. There was high variability in terms of indications for procedure and reporting of outcomes. Majority of studies required velopharyngeal gap closure of at least 50% in order to undergo AFI. Most common etiology of VPI was secondary to cleft palate. Some studies included patients with velocardiofacial syndromes. Improvements in speech and nasalance were reported in a majority of patients. Major complications were rare. Only 1 patient with graft hypertrophy resulting in obstructive sleep apnea was reported., Conclusion: Autologous fat injection offers a minimally invasive approach to the treatment of VPI. Current literature is limited to small noncomparative studies. These appear to suggest efficacy and safety in mild to moderate patients with VPI. Future prospective studies with standardized technique and objective outcomes are required to definitively establish its safety and efficacy, as well as define patient selection criteria.

Background: Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors., Methods: A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors were excluded. Demographics, comorbidities, and postoperative complications were evaluated by univariate analysis, using two-tailed Chi-square and t-tests and multivariate logistic regression., Results: Of 27,312 patients who underwent adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism (Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with pheochromocytoma had higher rate of comorbidities including congestive heart failure, chronic lung disease, and malignant hypertension compared with remaining hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01). For patients with pheochromocytoma versus other hormonally active tumors, mean length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus $41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an independently higher risk for intraoperative blood transfusion (4.2, 95% confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2), and respiratory (1.9, 95% CI 1.0-3.3) complications., Conclusions: Patients with pheochromocytoma have high rates of preoperative comorbidities, postoperative cardiopulmonary complications, and longer and more costly hospitalizations. Such high-risk patients should undergo appropriate preoperative medical optimization in preparation for adrenalectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Current surgical indications for Graves' disease include intractability to medical and/or radioablative therapy, compressive symptoms, and worsening ophthalmopathy. Total thyroidectomy for Graves' disease may be technically challenging and lead to untoward perioperative outcomes. This study examines outcomes in patients with Graves' disease who underwent total thyroidectomy and assesses its safety for this patient population., Methods: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database from 2006 to 2011. Total thyroidectomy performed in patients with Graves' disease, benign multinodular goiter (MNG), and thyroid cancer was identified. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-square, one-way analysis of variance, and risk-adjusted multivariable logistic regression were performed., Results: Of 215,068 patients who underwent total thyroidectomy during the study period, 11,205 (5.2%) had Graves' disease, 110,124 (51.2%) MNG, and 93,739 (43.6%) thyroid malignancy. Patients with Graves' disease were younger than MNG and thyroid cancer patients (M age  = 42.8 years vs. 55.5 and 51.0 years; p < 0.01). The Graves' disease group included a higher proportion of women (p < 0.01) and nonwhites (p < 0.01). Postoperatively, Graves' patients had significantly higher rates of hypocalcemia (12.4% vs. 7.3% and 10.3%; p < 0.01), hematomas requiring reoperation (0.7% vs. 0.4% and 0.4%; p < 0.01), and longer mean hospital stay (2.7 days vs. 2.4 and 2.2 days; p < 0.01) compared to MNG and thyroid cancer patients, respectively. On risk-adjusted multivariate logistic regression, Graves' disease was independently associated with a higher risk of vocal-cord paralysis (odds ratio [OR] = 1.36 [confidence interval (CI) 1.08-1.69]), tracheostomy (OR = 1.35 [CI 1.1-1.67]), postoperative hypocalcemia (OR = 1.65 [CI 1.54-1.77]), and hematoma requiring reoperation (OR = 2.79 [CI 2.16-3.62]) compared to MNG patients. High-volume centers for total thyroidectomy were independently associated with lower risk of postoperative complications, including in patients with Graves' disease., Conclusions: Despite low overall morbidity following total thyroidectomy, Graves' disease patients are at increased risk of postoperative complications, including bleeding, vocal-cord paralysis, tracheostomy, and hypocalcemia. These risks appear to be lower when performed at high-volume centers, and thus referral to these centers should be considered. Total thyroidectomy may therefore be a safe treatment option for appropriately selected patients with Graves' disease when performed by experienced surgeons.

Background: Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis., Methods: Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 10 6 human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression., Results: No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide., Conclusions: Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF., Trial Registry: ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Primary hyperparathyroidism (pHPT) is commonly treated with targeted parathyroidectomy (PTX) guided by preoperative imaging and intraoperative parathormone monitoring. Despite advanced imaging techniques, failure of parathyroid localization still occurs. This study determines the anatomical distribution of single abnormal parathyroid glands, which may help direct the surgeon in PTX when preoperative localization is unsuccessful., Methods: A retrospective review of prospectively collected data of 810 patients with pHPT who underwent initial PTX at a tertiary medical center was performed. All patients had biochemically confirmed pHPT and single-gland disease. Abnormal parathyroid gland localization was determined at time of operation, correlated with operative and pathology reports, and confirmed by operative success defined as eucalcemia for ≥6 mo after PTX. Patients with multiple endocrine neoplasia, secondary, tertiary, or familial hyperparathyroidism, multiglandular disease, parathyroid cancer, and ectopic glands were excluded. Data were analyzed by chi-square and Z-test analyses., Results: Among 810 patients who underwent PTX for pHPT, single abnormal parathyroid glands were unequally distributed among the four eutopic locations (left superior, 15.7%; left inferior, 31.3%; right superior, 15.8%; right inferior, 37.2%; P < 0.01). Abnormal inferior parathyroid glands (68.5%) were significantly more common than abnormal superior glands (31.5%), respectively (P < 0.01). In men, the most common location for single abnormal parathyroid glands was the right inferior position (43.4%, P < 0.01). Overall, there was no significant difference in laterality., Conclusions: This large series of patients suggests that single eutopic abnormal parathyroid glands are more likely to be inferior. In men, moreover, if an abnormal parathyroid gland is not localized preoperatively, the right inferior location should be explored first. Nevertheless, successful PTX remains predicated on knowledge of parathyroid anatomy, experience, and judgment of the surgeon., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Dermatofibrosarcoma protuberans (DFSP) is a low-grade soft tissue sarcoma. In the pediatric population, DFSP is exceedingly rare. Aim of this study was to describe the epidemiology and clinical outcomes in a large pediatric cohort., Methods: Surveillance, Epidemiology, and End Results (SEER) database (1973-2010) was analyzed for all patients with dermatofibrosarcoma occurring in patients <20 years of age. Data were extracted based on age, gender, race, anatomic site, histology, stage, treatment modalities, and survival. Incidence rates were standardized to the 2000 US population., Results: A total of 451 patients were identified. Overall annual incidence was 0.10 per 100,000. Incidence was highest among black children and adolescents (ages 15 to 19 years). Trunk was most common site, followed by extremities. Head and neck region was least common site (P < 0.05). Majority (54%) of patients presented with localized disease. Overall, 95% underwent surgery. Only 2.2% were treated with perioperative radiation therapy. Overall prognosis was favorable with 5-year overall survival (OS) of 100%, 15-year OS of 98%, and 30-year OS of 97%. Median survival was 117 months. Male patients had lower 15- and 30-year OS compared with females (P < 0.05)., Conclusion: Pediatric DFSP has lower incidence but similar clinical characteristics to adults. Incidence is higher in black children and in the trunk region. While prognosis is favorable, male sex is associated with decreased OS.

Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease. In this study, 15-month-old female C57BL/6J mice were ovariectomized and administered either placebo (pla) or 17β-estradiol (E 2 , 0.025 mg) 2 weeks after ovariectomy. They were further divided into those that were exposed to CS and no-smoke controls (NSC). Mice were exposed to CS in stainless steel inhalation chambers 3 hours a day, 5 days a week for 6 months, and sacrificed after 24 weeks of CS exposure. Blood and urine were collected at sacrifice to measure estrogen and cotinine levels, a metabolite of nicotine. Uterine weight was recorded as an indicator of estrogen status. Results showed that CS in the absence of E 2 induced a decrease in hydroxyproline content, macrophage number, and respiratory chain complex-1 protein. CS without E 2 also resulted in an increase in matrix metalloproteinase-2 activity and apoptosis and a change in the ratio of estrogen receptor subtype. These findings were abrogated with administration of E 2, suggesting that estrogen deficiency increases susceptibility to CS-induced lung disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Age-related increases in oxidant stress (OS) play a role in regulation of estrogen receptor (ER) expression in the kidneys. In this study, we establish that in vivo 17β-estradiol (E2) replacement can no longer upregulate glomerular ER expression by 21 months of age in female mice (anestrous). We hypothesized that advanced glycation end product (AGE) accumulation, an important source of oxidant stress, contributes to these glomerular ER expression alterations. We treated 19-month old ovariectomized female mice with pyridoxamine (Pyr), a potent AGE inhibitor, in the presence or absence of E2 replacement. Glomerular ERα mRNA expression was upregulated in mice treated with both Pyr and E2 replacement and TGFβ mRNA expression decreased compared to controls. Histological sections of kidneys demonstrated decreased type IV collagen deposition in mice receiving Pyr and E2 compared to placebo control mice. In addition, anti-AGE defenses Sirtuin1 (SIRT1) and advanced glycation receptor 1 (AGER1) were also upregulated in glomeruli following treatment with Pyr and E2. Mesangial cells isolated from all groups of mice demonstrated similar ERα, SIRT1, and AGER1 expression changes to those of whole glomeruli. To demonstrate that AGE accumulation contributes to the observed age-related changes in the glomeruli of aged female mice, we treated mesangial cells from young female mice with AGE-BSA and found similar downregulation of ERα, SIRT1, and AGER1 expression. These results suggest that inhibition of intracellular AGE accumulation with pyridoxamine may protect glomeruli against age-related oxidant stress by preventing an increase of TGFβ production and by regulation of the estrogen receptor.

Background: Increasing utilization of genetic expression profiling (GEP) for thyroid nodules with indeterminate fine needle aspiration (FNA) results will potentially decrease the number of patients requiring diagnostic thyroidectomy. This study sought to determine the potential effects of GEP for indeterminate thyroid FNA results on thyroidectomy volume., Methods: A retrospective review of thyroidectomy procedures performed over 1 year at the University of Michigan in the endocrine surgery division evaluated the indications for thyroidectomy, FNA Bethesda classification, and final surgical pathology to determine how application of GEP on indeterminate FNA results would affect decision for surgery and subsequent thyroidectomy volume., Results: During the study period, 358 thyroidectomies were performed. The indication for procedure included: FNA findings, n = 122; symptomatic multinodular goiter, n = 85; nodule >4 cm, n = 30; Graves', n = 26; other, n = 95. FNA was performed in 231 patients. Bethesda classification included: benign, n = 69; malignant, n = 55; follicular lesion of undetermined significance, n = 59; follicular neoplasm, n = 20; suspicious for malignancy, n = 16; nondiagnostic, n = 12. If standard GEP was performed for all indeterminate FNA results, it would have influenced the decision for surgery in 68 (19 %) patients. Assuming 38 % of indeterminate FNA specimens will have benign results on genetic profiling, 27 patients would not have undergone thyroidectomy, translating into a 7.2 % decrease in overall thyroidectomy volume over a year., Conclusions: In an academic endocrine surgery program, the most common indication for thyroidectomy is an FNA result; however, standard application of GEP for all indeterminate thyroid FNAs would result in a minimal reduction in overall thyroidectomy volume.