Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Immunotargeting and personalized therapies in genitourinary cancers.
Future Oncol. 2016 Apr 26;
Authors: Mazzucchelli R, Gasparrini S, Galosi AB, Massari F, Ciccarese C, Scarpelli M, Lopez-Beltran A, Cheng L, Montironi R
PMID: 27113700 [PubMed - as supplied by publisher]
Novel Technologies for Isolated Lung Perfusion: Beyond Lung Transplant.
Thorac Surg Clin. 2016 May;26(2):139-45
Authors: Cypel M, Keshavjee S
Abstract
Isolated lung perfusion (ILP) has been examined and developed in lung transplantation and thoracic oncology research. In lung transplantation, ILP has been used to assess physiologic integrity of donor lungs after removal from the donor, and it has also been proposed as a method for active treatment and repair of injured unsuitable donor organs ex vivo. ILP is attractive as a concept to deliver high-dose chemotherapy to treat pulmonary metastatic disease, referred to as in vivo lung perfusion. This article focuses on the rationale, technical aspects, and experimental and clinical experience of in vivo lung perfusion. A perspective on the future application of these techniques is described.
PMID: 27112253 [PubMed - in process]
Emerging Therapeutics in Refractory Renal Cell Carcinoma.
Expert Opin Pharmacother. 2016 Apr 26;
Authors: Koshkin VS, Rini BI
Abstract
INTRODUCTION: Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies ('refractory' mRCC). Recently approved agents in this space have shown great promise. Areas Covered: This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents. Expert Opinion: Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.
PMID: 27112171 [PubMed - as supplied by publisher]
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Preclinical Models Provide Scientific Justification and Translational Relevance for Moving Novel Therapeutics into Clinical Trials for Pediatric Cancer.
Cancer Res. 2015 Dec 15;75(24):5176-86
Authors: Langenau DM, Sweet-Cordero A, Wechsler-Reya RJ, Dyer MA
Abstract
Despite improvements in survival rates for children with cancer since the 1960s, progress for many pediatric malignancies has slowed over the past two decades. With the recent advances in our understanding of the genomic landscape of pediatric cancer, there is now enthusiasm for individualized cancer therapy based on genomic profiling of patients' tumors. However, several obstacles to effective personalized cancer therapy remain. For example, relatively little data from prospective clinical trials demonstrate the selective efficacy of molecular-targeted therapeutics based on somatic mutations in the patient's tumor. In this commentary, we discuss recent advances in preclinical testing for pediatric cancer and provide recommendations for providing scientific justification and translational relevance for novel therapeutic combinations for childhood cancer. Establishing rigorous criteria for defining and validating druggable mutations will be essential for the success of ongoing and future clinical genomic trials for pediatric malignancies.
PMID: 26627009 [PubMed - indexed for MEDLINE]
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Cervical cancer stem cells.
Cell Prolif. 2015 Dec;48(6):611-25
Authors: Yao T, Lu R, Zhang Y, Zhang Y, Zhao C, Lin R, Lin Z
Abstract
The concept of cancer stem cells (CSC) has been established over the past decade or so, and their role in carcinogenic processes has been confirmed. In this review, we focus on cervical CSCs, including (1) their purported origin, (2) markers used for cervical CSC identification, (3) alterations to signalling pathways in cervical cancer and (4) the cancer stem cell niche. Although cervical CSCs have not yet been definitively identified and characterized, future studies pursuing them as therapeutic targets may provide novel insights for treatment of cervical cancer.
PMID: 26597379 [PubMed - indexed for MEDLINE]
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Testicular orphan nuclear receptor 4 is associated with the radio-sensitivity of prostate cancer.
Prostate. 2015 Oct;75(14):1632-42
Authors: Yu S, Wang M, Ding X, Xia L, Chen B, Chen Y, Zhang Z, Niu Y, Li G, Chang C
Abstract
BACKGROUND: It is well known that a significant number of prostate cancers (PCa) showed different extents of radio-resistance and the tumor may recur after treatment. Recent studies demonstrated that Testicular orphan nuclear receptor 4 (TR4) could play a critical role in anti-oxidative stress responses and might modulate the DNA damage repair. The objective of this study is to investigate the role of TR4 in the radiotherapy for PCa.
METHODS: The TR4 expression in tissue samples from PCa patients treated with brachytherapy was measured by immunohistochemistry (IHC). Cell survival test and colony formation assay were applied to test the radio-sensitivity of PCa cells with modulated TR4 gene expression upon irradiation.
RESULTS: PCa patients with biochemical recurrence (BCR) after brachytherapy tend to have higher TR4 expression (80%, n = 30) as compared to those without BCR (36.67%, n = 30). Survival analysis demonstrated a significant higher BCR occurrence in patients with high level of TR4 expression (HR = 3.474, 95%CI 1.678-7.192, P = 0.0008). Multivariate analysis showed that the TR4 staining score on IHC was the only significant variable for predicting the PCa patients' clinical outcomes after radiotherapy (OR = 9.919, 95% CI 2.516-39.101, P = 0.001). Using cell survival test and colony forming assay, we found that the addition of functional TR4 in PC3 cells lead to elevated radio-resistance. In contrast, knocking-down TR4 in LNCaP cells resulted in increased radio-sensitivity. The γH2AX foci kinetic analysis suggested that knocking down TR4 might delay the PCa cell's DNA damage repair which would enhance the radio-sensitivity.
CONCLUSION: TR4 could mediate the PCa cells' radio-sensitivity and might become a prognostic indicator for PCa patients received radiotherapy. This study provides a novel approach to manipulate radio-sensitivity of PCa cells, and may bring a promoted therapeutic outcome of radiotherapy to battle PCa in future.
PMID: 26178291 [PubMed - indexed for MEDLINE]
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Current and future strategies in nonclear-cell metastatic renal cell carcinoma.
Curr Opin Urol. 2015 Sep;25(5):367-73
Authors: Albiges L, Escudier B
Abstract
PURPOSE OF REVIEW: Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC.
RECENT FINDINGS: The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib-gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes.
SUMMARY: Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto-oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design.
PMID: 26153638 [PubMed - indexed for MEDLINE]
Amputation Versus Limb-Salvage Surgery in Patients with Osteosarcoma: A Meta-analysis.
World J Surg. 2016 Apr 26;
Authors: Han G, Bi WZ, Xu M, Jia JP, Wang Y
Abstract
BACKGROUND: This meta-analysis compared survival and function in patients with limb osteosarcoma treated with limb-salvage surgery (LSS) versus amputation or rotationplasty.
METHODS: Medline, Cochrane, EMBASE, and Google Scholar were searched until November 30, 2015 for studies reporting Musculoskeletal Tumor Society (MSTS) scores and survival rates in osteosarcoma patients. Differences between patients undergoing LSS versus ablative surgery were analyzed based on MSTS scores and postoperative survival rates.
RESULTS: Of 1330 patients in the studies analyzed, 934 underwent LSS, and 662 were treated with amputation. A random-effects model was applied due to heterogeneity among studies (Q statistic = 1.829, I (2) = 0 %, p = 0.767). No difference was found in post-operative local recurrence rate between amputees and patients receiving LSS. The 5-year survival rate was significantly lower with amputation compared with LSS (OR 0.628; 95 % CI 0.431-0.913, p = 0.015). The 2-year survival rate was not different between amputation and LSS. In addition, amputees had lower MSTS scores than those undergoing LSS (difference in means = -4.46 %, 95 % CI 6.49-2.45 %, p < 0.001).
CONCLUSIONS: LSS results in higher 5-year survival rates and better functional outcomes as indicated by MSTS scores in patients with limb osteosarcomas.
PMID: 27116252 [PubMed - as supplied by publisher]
Corrigendum to "Endoscopic closure of persistent gastric leak and fistula following laparoscopic sleeve gastrectomy" [Int. J. Surg. Case Rep. 6 (2015) 186-187].
Int J Surg Case Rep. 2016;22:39
Authors: Luthra AK, Fernandez AZ, Evans JA
PMID: 27112288 [PubMed - as supplied by publisher]
The ADAMs Family of Proteases as Targets for the Treatment of Cancer.
Cancer Biol Ther. 2016 Apr 26;:0
Authors: Mullooly M, McGowan P, Crown J, Duffy MJ
Abstract
The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this causative role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.
PMID: 27115328 [PubMed - as supplied by publisher]
Vitamin D-fortified bread is as effective as supplement in improving vitamin D status: a randomized clinical trial.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161631
Authors: Nikooyeh B, Neyestani TR, Zahedirad M, Mohammadi M, Hedayat Hosseini S, Abdollahi Z, Salehi F, Mirzay Razaz J, Shariatzadeh N, Kalayi A, Lotfollahi N, Maleki MR
Abstract
CONTEXT: Bread can potentially be a suitable vehicle for fortification with vitamin D.
OBJECTIVE: This study was undertaken to evaluate (1) bioavailability of vitamin D from the fortified Iranian bread, and (2) the possible effects of daily consumption of the fortified bread on certain health aspects.
DESIGN, SETTING, AND PARTICIPANTS: This was a randomized double blind placebo-controlled trial conducted over 8 weeks in 90 healthy subjects aged 20-60 yr.
INTERVENTION: Subjects were randomly allocated to 1 of 3 groups: (a) fortified bread (FP; 50 g bread fortified with 25μg vitamin D3 plus placebo daily; n1 = 30); (b) supplement (SP; 50 g plain bread plus 25μg vitamin D supplement daily; n2 = 30); and (c) control (CP; 50 g plain bread plus placebo daily; n3 =30).
OUTCOME: Measures: Initial and final anthropometric and biochemical assessments were performed.
RESULTS: The within-group changes of serum 25(OH)D concentrations were 39.0±22.6 (p<0.001), 28.9±31.2 (p<0.001) and -9.2±12.3 nmol/L in the FP, SP and CP groups, respectively. Only in FP and SP groups, serum iPTH concentrations decreased approximately 13.5% and 14.5%, respectively. Visceral fat also showed a significant decrement in FP (-1.05±1.4%; p=<0.001) and SP (-0.96±1.7%; p=0.006). Serum LDL-C concentration showed a within-group reduction in FP (-10.4±11.2 mg/dL; p <0.001) and an insignificant decrement in SP (-6.6±20.2 mg/dL; p=0.083). Serum HDL increased in both vitamin D supplemented groups (FP: 9.7±7.6 vs. SP: 5.7±6.7 mg/dL; p<0.001).
CONCLUSION: Vitamin D-fortified bread could be a potentially effective in raising circulating 25(OH)D of the population to nearly adequate levels.
PMID: 27115063 [PubMed - as supplied by publisher]
Secular changes in post-fracture outcomes over 2 decades in Australia: A time-trend comparison of excess post-fracture mortality in two birth controls over two decades.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161514
Authors: Bliuc D, Tran T, Alarkawi D, Nguyen TV, Eisman JA, Center JR
Abstract
CONTEXT: Hip fracture incidence has been declining and life expectancy improving. However, trends of post-fracture outcomes are unknown.
OBJECTIVES: To compare re-fracture risk and excess mortality following osteoporotic fracture between two birth cohorts, over two decades.
DESIGN: Prospective birth-cohorts followed over two decades (1989-2004 and 2000-2014) Setting: Community-dwelling participants in Dubbo, Australia.
PARTICIPANTS: Women and men aged 60-80, participating in DOES1 (born before 1930) and DOES2 (born after 1930).
MAIN OUTCOME MEASURE: Age-standardised fracture and mortality over two time intervals: 1989-2004 (DOES1) and 2000-2014 (DOES2).
RESULTS: DOES 2 cohort had higher BMI and BMD and lower initial fracture rate than DOES 1, but similar re-fracture rates [age-standardized re-fracture rates /1000 person-years: women: 53 (42-63) and 51 (95% CI, 41-60) and men: 53 (38-69) and 55 (40-71), for DOES 2 and DOES 1, respectively)]. Absolute post: fracture mortality rates declined in DOES 2 compared to DOES 1, mirroring the improvement in general-population life expectancy. However, when compared to period-specific general-population mortality, there was a similar 2.1-2.6 fold increased mortality risk post-fracture in both cohorts [age-adjusted SMR, women: 2.05 (1.43-2.83) and 2.43 (1.95-2.99) and men: 2.56 (1.78- 3.58) and 2.48 (1.87- 3.22), for DOES 2 and DOES 1, respectively].
CONCLUSION: Over the two decades, despite the decline in the prevalence of fracture risk factors, general-population mortality and initial fracture incidence, there was no improvement in post-fracture outcomes. Re-fracture rates were similar and fracture-associated mortality was 2-fold higher than expected. These data indicate that the low post-fracture treatment rates are still a major problem.
PMID: 27115062 [PubMed - as supplied by publisher]
Different effects of intraperitoneal and subcutaneous insulin administration on the GH-IGF-1 axis in type 1 diabetes.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161473
Authors: van Dijk PR, Logtenberg SJ, Chisalita SI, Hedman CA, Groenier KH, Gans RO, Kleefstra N, Arnqvist HJ, Bilo HJ
Abstract
CONTEXT: In type 1 diabetes mellitus (T1DM), low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of growth hormone (GH) and IGFBP-1 are present, probably due to portal vein insulinopenia.
OBJECTIVE: To test the hypothesis that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than subcutaneous (SC) insulin therapy on regulation of the GH-IGF-1 axis.
DESIGN: Prospective, observational case-control study. Measurements were performed twice at a 26-week interval.
SETTING: Two secondary care hospitals in the Netherlands.
PATIENTS: A total of 184 patients, age and gender matched, of which 39 used CIPII and 145 SC insulin therapy for the past 4 years.
OUTCOMES: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1 and IGFBP-3.
RESULTS: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/l (95% CI 111, 138) versus 108 μg/l (95% CI 102, 115) (p=0.035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/l (95% CI 3.49, 4.10) versus 3.31 mg/l (95% CI 3.17, 3.47) for IGFBP-3, 50.9 μg/l (95% CI 37.9, 68.2) versus 102.6 μg/l (95% CI 87.8, 119.8) for IGFBP-1 and 0.68 μg/l (95% CI 0.44, 1.06) versus 1.21 μg/l (95% CI 0.95, 1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c.
CONCLUSIONS: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during SC insulin therapy.
PMID: 27115061 [PubMed - as supplied by publisher]
Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161437
Authors: Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR
Abstract
CONTEXT: Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D have not been clearly established.
OBJECTIVE: To determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D.
DESIGN: Cross-sectional study.
SETTING: Tertiary medical center.
PATIENTS: Sixteen postmenopausal women with T2D and 19 matched controls.
MAIN OUTCOME MEASURES: Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF and circulating bone turnover markers.
RESULTS: BMSi was reduced by 9.2% in T2D (p=0.02) and was inversely associated with duration of T2D (r= -0.68, p= 0.004). Increased SAF was associated with reduced BMSi (r= -0.65, p=0.006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r= -0.63, p=0.01) in T2D, while no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (p=0.03).
CONCLUSIONS: Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.
PMID: 27115060 [PubMed - as supplied by publisher]
Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy. A Study within the Danish National Birth Cohort.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161387
Authors: Laurberg P, Andersenet SL, Hindersson P, Nohr EA, Olsen J
Abstract
CONTEXT: Thyroid hormones are important developmental factors and levels should be adequate both in the pregnant woman and in the fetus. However, there is no consensus on maternal thyroid test reference limits in early pregnancy.
OBJECTIVE: Estimation of week-to-week changes in and predictors of TSH and fT4 reference limits in the first trimester of pregnancy.
DESIGN: Measurement of TSH and fT4 in biobank sera collected in pregnancy weeks 5-19 from a random sample of the Danish National Birth Cohort (DNBC) that enrolled 101,032 pregnant in 1996-2002.
SETTING: National cohort of pregnant women.
PARTICIPANTS: Healthy participants (n=6,671) were identified and individual characteristics retrieved using interview data and data from Danish national health registers.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Reference limits for TSH and fT4 in each first trimester pregnancy week and predictors of these reference limits.
RESULTS: TSH reference limits were very variable. Up to and including week 6, non-pregnancy reference limits could be used. In weeks 9-12, TSH upper reference limit was ∼0.4 mU/l lower than the non-pregnancy upper limit. The TSH lower reference limit was ∼0.1 mU/l. fT4 variations were reverse to those of TSH, but changes were small with ∼4% higher reference limits during the weeks 9-12. TSH upper reference limit was lower in multiparous women and women with lower iodine intake, but higher in obese women. fT4 was lower in smokers.
CONCLUSIONS: TSH reference limits differ widely in the first trimester of pregnancy. The use of a uniform set of reference limits is an inordinate simplification that will lead to frequent misclassification and possibly to incorrect choice of therapy.
PMID: 27115059 [PubMed - as supplied by publisher]
Calcium sensing receptor tumor expression and lethal prostate cancer progression.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161082
Authors: Ahearn TU, Tchrakian N, Wilson KM, Lis R, Nuttall E, Sesso HD, Loda M, Giovannucci E, Mucci LA, Finn S, Shui IM
Abstract
CONTEXT: Prostate cancer metastases preferentially target bone and the calcium sensing receptor (CaSR) may play a role in promoting this metastatic progression.
OBJECTIVE: We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer.
DESIGN: A validated CaSR immunohistochemistry (IHC) assay was performed on tumor tissue microarrays (TMA). Vitamin D receptor expression and PTEN loss were previously assessed in a subset of cases by IHC. Cox proportional hazards models adjusting for age and BMI at diagnosis, Gleason grade, and pathologic TNM stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer.
SETTING: The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study.
PARTICIPANTS: We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009.
MAIN OUTCOME: Participants were followed for cancer-specific mortality or development of metastatic disease.
RESULTS: On average men were followed 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathologic variables (HR=2.0; 95% CI=1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR=3.2; 95% CI=1.4-7.3), but not in cases with high tumor VDR expression (HR=0.8; 95% CI=0.2-3.0).
CONCLUSIONS: Tumor CaSR expression is associated with increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.
PMID: 27115058 [PubMed - as supplied by publisher]
Spontaneous Acute Mesenteroaxial Gastric Volvulus Diagnosed by Computed Tomography Scan in a Young Man.
Am J Case Rep. 2016;17:283-8
Authors: Jabbour G, Afifi I, Ellabib M, El-Menyar A, Al-Thani H
Abstract
BACKGROUND Acute gastric volvulus is a surgical emergency that requires early recognition and treatment. Acute idiopathic mesenteroaxial gastric volvulus is a rare sub-type and there are few cases reported in children and there are even fewer reports in adults. CASE REPORT We report a rare case of a 23-year-old man who presented with a 1-day history of vomiting, epigastric pain, distention, and constipation. The diagnosis for mesenteroaxial type gastric volvulus was confirmed by abdominal radiography and computed tomography. The patient was successfully treated by laparotomy with resection of the ischemic stomach wall and anastomosis. Acute spontaneous mesenteroaxial gastric volvulus is rare in adults and early diagnosis is challenging due to non-specific symptoms. A missed or delayed diagnosis may result in serious complications due to gastric obstruction. CONCLUSIONS A patient presenting with severe epigastric pain and clinical evidence of gastric outlet obstruction should be considered as a surgical emergency to rule out gastric volvulus. High index of suspicion, early diagnosis and prompt surgical management are important for favorable outcome in patients with acute spontaneous gastric volvulus.
PMID: 27112797 [PubMed - in process]
The presentation and management of granulomatosis with polyangiitis (Wegener's Granulomatosis) in the pediatric airway.
Laryngoscope. 2016 Apr 26;
Authors: Lee PY, Adil EA, Irace AL, Neff L, Son MB, Lee EY, Perez-Atayde A, Rahbar R
Abstract
OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a necrotizing inflammatory disease that can affect the airway. The purpose of this study was to present a case of pediatric laryngotracheal GPA and provide management recommendations based on a thorough review of the literature.
DATA SOURCES: Retrospective chart and literature review REVIEW METHODS: A pediatric patient with laryngotracheal and pulmonary manifestations of GPA who underwent chemotherapy and intralesional corticosteroid injection is described. An extensive literature review of pediatric GPA affecting the larynx/trachea was also performed.
RESULTS: A pediatric patient presented with acute respiratory distress. Flexible laryngoscopy revealed a laryngeal mass. Magnetic resonance imaging showed circumferential subglottic stenosis, and chest computed tomography demonstrated multiple pulmonary nodules. Laryngeal and tracheal biopsy revealed granulation tissue and primary vasculitis. Labs demonstrated positive cytoplasmic antineutrophil cytoplasmic antibody, consistent with GPA. Methylprednisone, rituximab, cyclophosphamide, and intralesional steroid injection resulted in remission after 12 weeks. Review of the literature revealed two pediatric cases series and 10 case reports of GPA affecting the larynx or trachea.
CONCLUSIONS: There is a higher prevalence of GPA of the airway in children when compared to adults. Biopsy of the airway lesion may not be necessary and has lower diagnostic yield compared to other GPA subsites. Medical management includes induction therapy followed by maintenance therapy once the disease is in remission. Most patients will require a surgical intervention to maintain the airway.
LEVEL OF EVIDENCE: NA Laryngoscope, 2016.
PMID: 27113905 [PubMed - as supplied by publisher]
Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.
Laryngoscope. 2016 Apr 26;
Authors: Puram SV, Chow H, Wu CW, Heaton JT, Kamani D, Gorti G, Chiang FY, Dionigi G, Barczynski M, Schneider R, Dralle H, Lorenz K, Randolph GW
Abstract
OBJECTIVES/HYPOTHESIS: Injury to the recurrent laryngeal nerve (RLN) is a dreaded complication of endocrine surgery. Intraoperative neural monitoring (IONM) has been increasingly utilized to assess the functional status of the RLN. Although the posterior cricoarytenoid muscle (PCA) is innervated by the RLN as the abductor of the larynx, PCA electromyography (EMG) is infrequently recorded during IONM and PCA activity after RLN compressive injury remains poorly characterized.
STUDY DESIGN: Single-subject prospective animal study.
METHODS: We employed a canine model to identify postcricoid EMG correlates of postoperative vocal cord paralysis (VCP). Postcricoid electrode recordings were obtained before and after compressive RLN injury associated with VCP.
RESULTS: Normative postcricoid recordings revealed mean amplitude of 1288 microvolt (μV) and latency of 8.2 millisecond (ms) with maximum (1 milliamp [mA]) vagal stimulation, and mean amplitude of 1807 μV and latency of 3.5 ms with maximum (1 mA) RLN stimulation. Following injury that was associated with VCP, there was 62.1% decrement in postcricoid EMG amplitude with maximum vagal stimulation and 80% decrement with maximum RLN stimulation. Threshold stimulation of the vagus increased by 23%, and there was a corresponding 42% decrease in amplitude. For RLN stimulation, latency increased by 17.3% following injury, whereas threshold stimulation increased by 61% with 35.5% decrement in EMG amplitude. Thus, if RLN amplitude decreases by ≥ 80%, with absolute amplitude of ≤ 300 μV or less and latency increase of ≥ 10%, RLN injury is likely associated with VCP.
CONCLUSION: Our results predict postoperative VCP based on postcricoid electromyographic IONM and may guide surgical decision making.
LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.
PMID: 27113438 [PubMed - as supplied by publisher]
Office-based biopsies for laryngeal lesions: Analysis of consecutive 581 cases.
Laryngoscope. 2016 Apr 26;
Authors: Cha W, Yoon BW, Jang JY, Lee JC, Lee BJ, Wang SG, Cho JK, Cho I
Abstract
OBJECTIVES/HYPOTHESIS: Office-based biopsy (OBB) is widely used to diagnose suspicious laryngeal lesions. However, its routine use is still controversial and the algorithm for clinical strategy is not concrete. We tried to evaluate the accuracy of OBB as a diagnostic tool for laryngeal malignancy.
METHODS: Medical data of 581 patients undergoing OBB were reviewed. Diagnostic values of OBB were analyzed for malignancy and malignancy/premalignancy. False negative rates (FNRs) were analyzed according to subsites, lesion sizes, and morphology.
RESULTS: The collection rate of adequate specimens was 99.1%, and there were no complications during OBB. The false omission rates for malignancy of benign lesion; mild, moderate, and severe dysplasia; and carcinoma in situ (CIS) were 5.1%, 11.9%, 14.3%, 50.0%, and 100.0%, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy in OBB were 78.2%, 100.0%, 100.0%, and 87.3%, respectively. Those for malignancy/premalignancy in OBB were 88.2%, 86.7%, 85.7%, and 89.1%, respectively. The high FNRs were reported in glottis lesions (27.0%) and small lesions below 1 cm (27.5%). Morphologically fungating lesions showed low FNR (9.1%) compared to nonfungating ones.
CONCLUSION: Office-based biopsy could be used as an initial diagnostic tool for laryngeal malignancy for early detection and avoidance of general anesthesia. However, operative re-biopsy should be considered when severe dysplasia or CIS were reported in OBB, or when the lesions are clinically suspicious for malignancy.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2016.
PMID: 27113333 [PubMed - as supplied by publisher]
Thyroid carcinoma with rhabdoid phenotype: Case report with review of the literature.
Auris Nasus Larynx. 2016 Apr 21;
Authors: Lu YT, Huang HI, Yang AH, Tai SK
Abstract
OBJECTIVE: This paper aims to comprehensively document a rare case of thyroid carcinoma with rhabdoid phenotype and literature review of this disease.
METHODS: A 59-year-old man presented with a rapidly enlarging, painful left lateral cervical mass. CT scan revealed a tumor over the left the thyroid gland with multiple left cervical lymphadenopathy over left level II-IV and level VI. Fine-needle aspiration cytology reported carcinoma, type undetermined. Total thyroidectomy with central compartment and left neck dissection was performed.
RESULTS: Pathology report showed rhabdoid phenotype of thyroid carcinoma. Final staging was pT4N1M1.
CONCLUSIONS: Although WHO classification of thyroid tumor histology does not define this disease entity, few cases were reported. In the last 20 years, English literature review revealed only 12 cases about thyroid carcinoma with rhabdoid phenotype. Major treatment of thyroid carcinoma with rhabdoid phenotype is surgery, and the benefit of adjuvant therapies as radiotherapy or systemic chemotherapy is not clear. The prognosis of thyroid carcinoma with rhabdoid phenotype is extremely poor, with mean survival of only 6 months.
PMID: 27112272 [PubMed - as supplied by publisher]
| Related Articles |
[The follow up observation of an 11 year exploitation of the domestically produced voice prosthesis in the patient who underwent laryngectomy with the use of the tracheoesophageal shunt and the endoprosthetic correction].
Vestn Otorinolaringol. 2015;80(6):55-6
Authors: Kozhanov LG, Kryukov AI, Kozhanov AL
PMID: 26978754 [PubMed - indexed for MEDLINE]
Vitamin D-fortified bread is as effective as supplement in improving vitamin D status: a randomized clinical trial.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161631
Authors: Nikooyeh B, Neyestani TR, Zahedirad M, Mohammadi M, Hedayat Hosseini S, Abdollahi Z, Salehi F, Mirzay Razaz J, Shariatzadeh N, Kalayi A, Lotfollahi N, Maleki MR
Abstract
CONTEXT: Bread can potentially be a suitable vehicle for fortification with vitamin D.
OBJECTIVE: This study was undertaken to evaluate (1) bioavailability of vitamin D from the fortified Iranian bread, and (2) the possible effects of daily consumption of the fortified bread on certain health aspects.
DESIGN, SETTING, AND PARTICIPANTS: This was a randomized double blind placebo-controlled trial conducted over 8 weeks in 90 healthy subjects aged 20-60 yr.
INTERVENTION: Subjects were randomly allocated to 1 of 3 groups: (a) fortified bread (FP; 50 g bread fortified with 25μg vitamin D3 plus placebo daily; n1 = 30); (b) supplement (SP; 50 g plain bread plus 25μg vitamin D supplement daily; n2 = 30); and (c) control (CP; 50 g plain bread plus placebo daily; n3 =30).
OUTCOME: Measures: Initial and final anthropometric and biochemical assessments were performed.
RESULTS: The within-group changes of serum 25(OH)D concentrations were 39.0±22.6 (p<0.001), 28.9±31.2 (p<0.001) and -9.2±12.3 nmol/L in the FP, SP and CP groups, respectively. Only in FP and SP groups, serum iPTH concentrations decreased approximately 13.5% and 14.5%, respectively. Visceral fat also showed a significant decrement in FP (-1.05±1.4%; p=<0.001) and SP (-0.96±1.7%; p=0.006). Serum LDL-C concentration showed a within-group reduction in FP (-10.4±11.2 mg/dL; p <0.001) and an insignificant decrement in SP (-6.6±20.2 mg/dL; p=0.083). Serum HDL increased in both vitamin D supplemented groups (FP: 9.7±7.6 vs. SP: 5.7±6.7 mg/dL; p<0.001).
CONCLUSION: Vitamin D-fortified bread could be a potentially effective in raising circulating 25(OH)D of the population to nearly adequate levels.
PMID: 27115063 [PubMed - as supplied by publisher]
Secular changes in post-fracture outcomes over 2 decades in Australia: A time-trend comparison of excess post-fracture mortality in two birth controls over two decades.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161514
Authors: Bliuc D, Tran T, Alarkawi D, Nguyen TV, Eisman JA, Center JR
Abstract
CONTEXT: Hip fracture incidence has been declining and life expectancy improving. However, trends of post-fracture outcomes are unknown.
OBJECTIVES: To compare re-fracture risk and excess mortality following osteoporotic fracture between two birth cohorts, over two decades.
DESIGN: Prospective birth-cohorts followed over two decades (1989-2004 and 2000-2014) Setting: Community-dwelling participants in Dubbo, Australia.
PARTICIPANTS: Women and men aged 60-80, participating in DOES1 (born before 1930) and DOES2 (born after 1930).
MAIN OUTCOME MEASURE: Age-standardised fracture and mortality over two time intervals: 1989-2004 (DOES1) and 2000-2014 (DOES2).
RESULTS: DOES 2 cohort had higher BMI and BMD and lower initial fracture rate than DOES 1, but similar re-fracture rates [age-standardized re-fracture rates /1000 person-years: women: 53 (42-63) and 51 (95% CI, 41-60) and men: 53 (38-69) and 55 (40-71), for DOES 2 and DOES 1, respectively)]. Absolute post: fracture mortality rates declined in DOES 2 compared to DOES 1, mirroring the improvement in general-population life expectancy. However, when compared to period-specific general-population mortality, there was a similar 2.1-2.6 fold increased mortality risk post-fracture in both cohorts [age-adjusted SMR, women: 2.05 (1.43-2.83) and 2.43 (1.95-2.99) and men: 2.56 (1.78- 3.58) and 2.48 (1.87- 3.22), for DOES 2 and DOES 1, respectively].
CONCLUSION: Over the two decades, despite the decline in the prevalence of fracture risk factors, general-population mortality and initial fracture incidence, there was no improvement in post-fracture outcomes. Re-fracture rates were similar and fracture-associated mortality was 2-fold higher than expected. These data indicate that the low post-fracture treatment rates are still a major problem.
PMID: 27115062 [PubMed - as supplied by publisher]
Different effects of intraperitoneal and subcutaneous insulin administration on the GH-IGF-1 axis in type 1 diabetes.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161473
Authors: van Dijk PR, Logtenberg SJ, Chisalita SI, Hedman CA, Groenier KH, Gans RO, Kleefstra N, Arnqvist HJ, Bilo HJ
Abstract
CONTEXT: In type 1 diabetes mellitus (T1DM), low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of growth hormone (GH) and IGFBP-1 are present, probably due to portal vein insulinopenia.
OBJECTIVE: To test the hypothesis that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than subcutaneous (SC) insulin therapy on regulation of the GH-IGF-1 axis.
DESIGN: Prospective, observational case-control study. Measurements were performed twice at a 26-week interval.
SETTING: Two secondary care hospitals in the Netherlands.
PATIENTS: A total of 184 patients, age and gender matched, of which 39 used CIPII and 145 SC insulin therapy for the past 4 years.
OUTCOMES: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1 and IGFBP-3.
RESULTS: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/l (95% CI 111, 138) versus 108 μg/l (95% CI 102, 115) (p=0.035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/l (95% CI 3.49, 4.10) versus 3.31 mg/l (95% CI 3.17, 3.47) for IGFBP-3, 50.9 μg/l (95% CI 37.9, 68.2) versus 102.6 μg/l (95% CI 87.8, 119.8) for IGFBP-1 and 0.68 μg/l (95% CI 0.44, 1.06) versus 1.21 μg/l (95% CI 0.95, 1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c.
CONCLUSIONS: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during SC insulin therapy.
PMID: 27115061 [PubMed - as supplied by publisher]
Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161437
Authors: Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR
Abstract
CONTEXT: Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D have not been clearly established.
OBJECTIVE: To determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D.
DESIGN: Cross-sectional study.
SETTING: Tertiary medical center.
PATIENTS: Sixteen postmenopausal women with T2D and 19 matched controls.
MAIN OUTCOME MEASURES: Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF and circulating bone turnover markers.
RESULTS: BMSi was reduced by 9.2% in T2D (p=0.02) and was inversely associated with duration of T2D (r= -0.68, p= 0.004). Increased SAF was associated with reduced BMSi (r= -0.65, p=0.006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r= -0.63, p=0.01) in T2D, while no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (p=0.03).
CONCLUSIONS: Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.
PMID: 27115060 [PubMed - as supplied by publisher]
Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy. A Study within the Danish National Birth Cohort.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161387
Authors: Laurberg P, Andersenet SL, Hindersson P, Nohr EA, Olsen J
Abstract
CONTEXT: Thyroid hormones are important developmental factors and levels should be adequate both in the pregnant woman and in the fetus. However, there is no consensus on maternal thyroid test reference limits in early pregnancy.
OBJECTIVE: Estimation of week-to-week changes in and predictors of TSH and fT4 reference limits in the first trimester of pregnancy.
DESIGN: Measurement of TSH and fT4 in biobank sera collected in pregnancy weeks 5-19 from a random sample of the Danish National Birth Cohort (DNBC) that enrolled 101,032 pregnant in 1996-2002.
SETTING: National cohort of pregnant women.
PARTICIPANTS: Healthy participants (n=6,671) were identified and individual characteristics retrieved using interview data and data from Danish national health registers.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Reference limits for TSH and fT4 in each first trimester pregnancy week and predictors of these reference limits.
RESULTS: TSH reference limits were very variable. Up to and including week 6, non-pregnancy reference limits could be used. In weeks 9-12, TSH upper reference limit was ∼0.4 mU/l lower than the non-pregnancy upper limit. The TSH lower reference limit was ∼0.1 mU/l. fT4 variations were reverse to those of TSH, but changes were small with ∼4% higher reference limits during the weeks 9-12. TSH upper reference limit was lower in multiparous women and women with lower iodine intake, but higher in obese women. fT4 was lower in smokers.
CONCLUSIONS: TSH reference limits differ widely in the first trimester of pregnancy. The use of a uniform set of reference limits is an inordinate simplification that will lead to frequent misclassification and possibly to incorrect choice of therapy.
PMID: 27115059 [PubMed - as supplied by publisher]
Calcium sensing receptor tumor expression and lethal prostate cancer progression.
J Clin Endocrinol Metab. 2016 Apr 26;:jc20161082
Authors: Ahearn TU, Tchrakian N, Wilson KM, Lis R, Nuttall E, Sesso HD, Loda M, Giovannucci E, Mucci LA, Finn S, Shui IM
Abstract
CONTEXT: Prostate cancer metastases preferentially target bone and the calcium sensing receptor (CaSR) may play a role in promoting this metastatic progression.
OBJECTIVE: We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer.
DESIGN: A validated CaSR immunohistochemistry (IHC) assay was performed on tumor tissue microarrays (TMA). Vitamin D receptor expression and PTEN loss were previously assessed in a subset of cases by IHC. Cox proportional hazards models adjusting for age and BMI at diagnosis, Gleason grade, and pathologic TNM stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer.
SETTING: The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study.
PARTICIPANTS: We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009.
MAIN OUTCOME: Participants were followed for cancer-specific mortality or development of metastatic disease.
RESULTS: On average men were followed 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathologic variables (HR=2.0; 95% CI=1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR=3.2; 95% CI=1.4-7.3), but not in cases with high tumor VDR expression (HR=0.8; 95% CI=0.2-3.0).
CONCLUSIONS: Tumor CaSR expression is associated with increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.
PMID: 27115058 [PubMed - as supplied by publisher]
Emergency presentations of head and neck cancer: a modern perspective.
J Laryngol Otol. 2016 Apr 26;:1-4
Authors: Bannister M, Vallamkondu V, Ah-See KW
Abstract
BACKGROUND: Head and neck cancer emergency presentations are uncommon but persistent. However, there is little published literature on this aspect of cancer and patient demographics. This study aimed to assess the incidence, patient profile, tumour site and stage of emergency cancer presentations in our region.
METHOD: Retrospective review of regional cancer database over a five-year period.
RESULTS: Emergency presentations accounted for 7 per cent of all cases. There was no difference in patient age and risk factors between the emergency and non-emergency presentations. The emergency presentation group showed a greater proportion of female patients compared to the non-emergency presentation group (30 vs 15 per cent). In all emergency presentations, the cancer was at advanced stages. Oropharyngeal cancer was the commonest emergency presentation of cancer, but the third commonest in the non-emergency group.
CONCLUSION: Emergency presentations are increasing annually. Female patients and oropharyngeal cancer showed greater representation compared to male patients and laryngeal cancer.
PMID: 27112730 [PubMed - as supplied by publisher]
Perilymph fistula: the patients' experience.
J Laryngol Otol. 2016 Apr 26;:1-6
Authors: Meldrum JA, Prinsley PR
Abstract
OBJECTIVE: This study aimed to assess the experiences and outcomes of patients who underwent surgical repair of a perilymph fistula in Norfolk, UK.
METHODS: The study involved a retrospective questionnaire-based patient survey and case note review of patients who had undergone tympanotomy and perilymph fistula repair between 1998 and 2012 in two district general hospitals.
RESULTS: Fourteen patients underwent 20 procedures, of whom 7 completed the pre- and post-operative Vertigo Symptom Scale. In five patients, there was no obvious precipitating cause. Perilymph fistula was precipitated by noise in one patient, by a pressure-increasing event in six patients and by trauma in two patients. The Vertigo Symptom Scale scores showed a statistically significant improvement following surgical repair, from a median of 67 (out of 175) pre-operatively to 19 post-operatively.
CONCLUSION: In selected patients with vertigo, perilymph fistula should be considered; surgical repair can significantly improve symptoms.
PMID: 27112544 [PubMed - as supplied by publisher]
Decision making, reasoning, and analysis in real-world problems are complicated by imperfect information. Real-world imperfect information is mainly characterized by two features. In view of this, Professor Zadeh suggested the concept of a -number as an ordered pair of fuzzy numbers and , the first of which is a linguistic value of a variable of interest, and the second one is a linguistic value of probability measure of the first one, playing a role of its reliability. The concept of distance is one of the important concepts for handling imperfect information in decision making and reasoning. In this paper, we, for the first time, apply the concept of distance of -numbers to the approximate reasoning with -number based IF-THEN rules. We provide an example on solving problem related to psychological issues naturally characterized by imperfect information, which shows applicability and validity of the suggested approach.
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The Value of Vocal Extent Measure (VEM) Assessing Phonomicrosurgical Outcomes in Vocal Fold Polyps.
J Voice. 2016 Apr 21;
Authors: Salmen T, Ermakova T, Möller A, Seipelt M, Weikert S, Rummich J, Gross M, Nawka T, Caffier PP
Abstract
OBJECTIVE: This study aimed to present vocal extent measure (VEM), demonstrate its changes with phonomicrosurgical treatment in patients with vocal fold polyps (VFPs), and to compare its performance to that of established vocal parameters.
STUDY DESIGN: This is an individual cohort study.
METHODS: Microlaryngoscopic ablation was executed in 61 patients with manifestation of VFP (28 male, 33 female; 45 ± 13 years [mean ± SD]). Analysis of treatment outcome was based on pre- and postoperative voice function diagnostics and videolaryngostroboscopy. Examination instruments were: auditory-perceptual voice assessment (roughness, breathiness, and overall hoarseness [RBH]-status), voice range profile (VRP), acoustic-aerodynamic analysis, and patients' self-assessment of voice using the voice handicap index. The VEM, a parameter not yet commonly established in phoniatric diagnostics, was calculated from area and shape of the VRP to be compared with the dysphonia severity index (DSI) concerning diagnostic suitability.
RESULTS: All polyps were completely excised. Three months postoperatively, mucosal wave propagation had recovered. All subjective and most objective acoustic and aerodynamic parameters showed highly significant improvement. The VHI-9i-score decreased from 15 ± 8 to 6 ± 7 points. The average total vocal range extended by 4 ± 5 semitones, the mean speaking pitch decreased by 1 ± 2 semitones. The DSI increased on average from 2.6 ± 2.1 to 4.0 ± 2.2, VEM from 83 ± 28 to 107 ± 21 (P < 0.01). VEM and DSI correlated significantly with each other (rs = 0.65; P < 0.01).
CONCLUSION: Phonomicrosurgery of VFP is an objectively and subjectively satisfactory therapy for voice improvement. The VEM represents a comprehensible and easy-to-use unidimensional measure for objective VRP evaluation. This positive measure of vocal function seems to be a compelling diagnostic addition for objective quantification of vocal performance.
PMID: 27112100 [PubMed - as supplied by publisher]
Colorectal cancer (CRC) is one of the most common cancers all over the world. It is essential to search for more effective diagnostic and therapeutic methods for CRC. Abnormal nicotinamide adenine dinucleotide (NAD) metabolism has been considered as a characteristic of cancer cells. In this study, nicotinamide mononucleotide adenylyl transferases (NMNATs) as well as p53-mediated cancer signaling pathways were investigated in patients with colorectal cancer. The CRC tissues and adjacent normal tissues were obtained from 95 untreated colorectal cancer patients and were stained for expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) and p53. The survival rate was analyzed by the Kaplan-Meier method and the log-rank test. The multivariate Cox proportional hazard regression analysis was conducted as well. Our data demonstrated that expression of NMNAT2 and p53 was significantly higher in CRC tissues, while NMNAT2 expression is in correlation with the invasive depth of tumors and TNM stage. Significant positive correlation was found between the expression of NMNAT2 and the expression of p53. However, NMNAT2 expression was not a statistically significant prognostic factor for overall survival. In conclusion, our results indicated that NMNAT2 might participate in tumorigenesis of CRC in a p53-dependent manner and NMNAT2 expression might be a potential therapeutic target for CRC.
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Background: Discharge planning is a care process that aims to secure the transfer of care for the patient at transition from home to the hospital and back home. Information exchange and collaboration between care providers are essential, but deficits are common. A wide range of initiatives to improve the discharge planning process have been developed and implemented for the past three decades. However, there are still high rates of reported medical errors and adverse events related to failures in the discharge planning. Using theoretical frameworks such as Normalization Process Theory (NPT) can support evaluations of complex interventions and processes in healthcare. The aim of this study was to explore the embedding and integration of the DPP from the perspective of registered nurses, district nurses and homecare organizers. Methods: The study design was explorative, using the NPT as a framework to explore the embedding and integration of the DPP. Data consisted of written documentation from; workshops with staff, registered adverse events and system failures, web based survey and individual interviews with staff. Results: Using the NPT as a framework to explore the embedding and integration of discharge planning after 10 years in use showed that the staff had reached a consensus of opinion of what the process was (coherence) and how they evaluated the process (reflexive monitoring). However, they had not reached a consensus of opinion of who performed the process (cognitive participation) and how it was performed (collective action). This could be interpreted as the process had not become normalized in daily practice. Conclusion: The result shows necessity to observe the implementation of old practices to better understand the needs of new ones before developing and implementing new practices or supportive tools within healthcare to reach the aim of development and to accomplish sustainable implementation. The NPT offers a generalizable framework for analysis, which can explain and shape the implementation process of old practices, before further development of new practices or supportive tools.
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Variability in the amount of fluorine-18 fluorodeoxyglucose excreted in urine measured from oncology patients during PET/computed tomography imaging.
Nucl Med Commun. 2016 Apr 25;
Authors: Soliman K, Alenezi A, Alqahtani S
Abstract
The objectives of this work were to estimate the amount of fluorine-18 fluorodeoxyglucose (F-FDG) excreted (AFE) in the patient urine during the uptake phase as percentage of the injected activity and to examine the effect of blood glucose levels (BGL) on the excreted amount and whether it varies among men and women using statistical analysis methods. Radiation dose rates were measured at 1 m from 50 patients, 24 men and 26 women, before and after the first void using a calibrated ionization chamber. The F-FDG was injected in the patients using a calibrated automatic dose injection system. Statistical analysis using hypothesis testing was carried out. Patients with BGL above 5 mmol/l had a higher AFE of 12.3% in comparison with 8.3% of the patients with BGL below 5 mmol/l. A statistically nonsignificant correlation (r=0.183, P<0.249) between AFE and BGL was found; a nonsignificant difference was found in the AFE measured among the male and female patients. The AFE measured was 12±6%, with a range of (2-30%). There was a wide variation in the first void time of 39±8 min, with a range of (17-68) min. A simple noninvasive measurement method is presented that enabled the estimation of the amount of F-FDG excreted from the patient during voiding. Statistical analysis concluded that the amount of F-FDG excreted does not depend on sex, but is perhaps influenced by BGL.
PMID: 27115066 [PubMed - as supplied by publisher]
Radiation dose of 18F-FDG to lactating breasts, its effect on the effective dose and a more accurate effective dose from 18F-FDG.
Nucl Med Commun. 2016 Apr 25;
Authors: Pencharz D, McMeekin H, Wagner T, Wickham F
Abstract
INTRODUCTION: Lactating breasts have greater uptake of fluorine-18 fluorodeoxyglucose (F-FDG) than nonlactating breasts; however, there are no published data on the radiation dose from F-FDG to lactating breasts or this effect on the effective dose (ED). In addition, the International Commission on Radiological Protection's (ICRP) most recently published ED of 1.9×10 mSv/MBq from F-FDG was calculated using weighting factors that have since been superseded. We therefore calculated the F-FDG radiation dose to the lactating breast, its effect on the ED and calculated more up-to-date EDs from F-FDG for nonlactating patients.
METHODS: Breast uptake of F-FDG and volume were determined from PET/CT images of a lactating patient. These data, together with previously published biokinetic data on F-FDG, were used to calculate a radiation dose to the lactating breasts and its effect on the ED. In addition, tissue weighting factors and organ doses from the ICRP publications 103 and 106 were used to calculate more up-to-date EDs from F-FDG in nonlactating patients.
RESULTS: The absorbed dose to the lactating breast from F-FDG is 1.75×10 mGy/MBq, which results in an increase in the ED of 6%. In nonlactating patients, a more up-to-date ED from F-FDG is 1.77×10 mSv/MBq for women and 1.64×10 mSv/MBq for men.
CONCLUSION: This is the first reported dosimetry of F-FDG in lactating breasts, data that are required when justifying the radiation dose from an F-FDG PET scan in lactating patients. In addition, we calculated more up-to-date EDs from F-FDG that are lower than the current widely reported ED and should be used in future publications on F-FDG.
PMID: 27115065 [PubMed - as supplied by publisher]
Publication date: July 2016
Source:Free Radical Biology and Medicine, Volume 96
Author(s): Yi Xu, Xiaoyu Yang, Pinjing Zhao, Zhongyu Yang, Changhui Yan, Bin Guo, Steven Y. Qian
Cyclooxygenase (COX), commonly overexpressed in cancer cells, is a major lipid peroxidizing enzyme that metabolizes polyunsaturated fatty acids (ω-3s and ω-6s). The COX-catalyzed free radical peroxidation of arachidonic acid (ω-6) can produce deleterious metabolites (e.g. 2-series prostaglandins) that are implicated in cancer development. Thus, COX inhibition has been intensively investigated as a complementary therapeutic strategy for cancer. However, our previous study has demonstrated that a free radical-derived byproduct (8-hydroxyoctanoic acid) formed from COX-catalyzed peroxidation of dihomo-γ-linolenic acid (DGLA, the precursor of arachidonic acid) can inhibit colon cancer cell growth. We thus hypothesize that the commonly overexpressed COX in cancer (~90% of colon cancer patients) can be taken advantage to suppress cell growth by knocking down delta-5-desaturase (D5D, a key enzyme that converts DGLA to arachidonic acid). In addition, D5D knockdown along with DGLA supplement may enhance the efficacy of chemotherapeutic drugs. After knocking down D5D in HCA-7 colony 29 cells and HT-29 cells (human colon cancer cell lines with high and low COX levels, respectively), the antitumor activity of DGLA was significantly enhanced along with the formation of a threshold range (~0.5–1.0μM) of 8-hydroxyoctanoic acid. In contrast, DGLA treatment did not inhibit cell growth when D5D was not knocked down and only limited amount of 8-hydroxyoctanoic acid was formed. D5D knockdown along with DGLA treatment also enhanced the cytotoxicities of various chemotherapeutic drugs, including 5-fluorouracil, regorafenib, and irinotecan, potentially through the activation of pro-apoptotic proteins, e.g. p53 and caspase 9. For the first time, we have demonstrated that the overexpressed COX in cancer cells can be utilized in suppressing cancer cell growth. This finding may provide a new option besides COX inhibition to optimize cancer therapy. The outcome of this translational research will guide us to develop a novel ω-6-based diet-care strategy in combination with current chemotherapy for colon cancer prevention and treatment.
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Publication date: July 2016
Source:Free Radical Biology and Medicine, Volume 96
Author(s): Viktor M. Pastukh, Olena M. Gorodnya, Mark N. Gillespie, Mykhaylo V. Ruchko
Mitochondria of mammalian cells contain multiple copies of mitochondrial (mt) DNA. Although mtDNA copy number can fluctuate dramatically depending on physiological and pathophysiologic conditions, the mechanisms regulating mitochondrial genome replication remain obscure. Hypoxia, like many other physiologic stimuli that promote growth, cell proliferation and mitochondrial biogenesis, uses reactive oxygen species as signaling molecules. Emerging evidence suggests that hypoxia-induced transcription of nuclear genes requires controlled DNA damage and repair in specific sequences in the promoter regions. Whether similar mechanisms are operative in mitochondria is unknown. Here we test the hypothesis that controlled oxidative DNA damage and repair in the D-loop region of the mitochondrial genome are required for mitochondrial DNA replication and transcription in hypoxia. We found that hypoxia had little impact on expression of mitochondrial proteins in pulmonary artery endothelial cells, but elevated mtDNA content. The increase in mtDNA copy number was accompanied by oxidative modifications in the D-loop region of the mitochondrial genome. To investigate the role of this sequence-specific oxidation of mitochondrial genome in mtDNA replication, we overexpressed mitochondria-targeted 8-oxoguanine glycosylase Ogg1 in rat pulmonary artery endothelial cells, enhancing the mtDNA repair capacity of transfected cells. Overexpression of Ogg1 resulted in suppression of hypoxia-induced mtDNA oxidation in the D-loop region and attenuation of hypoxia-induced mtDNA replication. Ogg1 overexpression also reduced binding of mitochondrial transcription factor A (TFAM) to both regulatory and coding regions of the mitochondrial genome without altering total abundance of TFAM in either control or hypoxic cells. These observations suggest that oxidative DNA modifications in the D-loop region during hypoxia are important for increased TFAM binding and ensuing replication of the mitochondrial genome.
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Towards the synthesis of symmetrical and unsymmetrical β,β-diarylacroleins for assembling diarylmethine fragments present in biologically important molecules, we have developed a new Weinreb amide (WA) based building block, derived from propiolic acid. The WA functionality present in this compound allowed the sequential addition of various arylmagnesium bromide reagents in a controlled manner. The developed methodology for the access to β,β-diarylacroleins has been utilised for the synthesis of biologically important 3-arylindanone molecules.
Synthesis of both symmetrical and unsymmetrical β,β-diarylacrolein and diarylmethine fragments, have been achieved via easily accessible and hitherto unknown Weinreb Amide (WA) based building block 11. The WA functionality allowed the sequential addition of nucleophiles such as arylmagnesium bromide in a controlled manner, which has enabled the synthesis of an important 3-arylindanone molecule.
Thanks to their unique properties, such as (i) renewability, (ii) high aspect ratios, (iii) low density, (iv) biodegradability, (v) high strength, and (vi) stiffness, there have been many reports in recent years detailing the isolation and functionalization of cellulose nanowhiskers from cellulose. Moreover, nanocellulose can be produced in large quantities in a cost-effective manner and can be easily functionalized due to its high density of hydroxy groups. In the present work, alkynyl-dendrons of the PAMAM family were covalently attached to azide-functionalized cellulose nanocrystals by click chemistry (Huisgen cycloaddition). The resulting cycloadducts were then used as templates for the preparation of stable and monodispersed gold nanoparticles in aqueous media. The catalytic capabilities of these hybrid materials were studied in the sodium borohydride mediated reduction of 4-nitrophenol to 4-aminophenol, which served as a model reaction.
Alkynyl-dendrons of the PAMAM family were covalently attached to azide-linked cellulose nanocrystals using click chemistry and then used as templates for the preparation of stable and monodispersed gold nanoparticles in aqueous media. The new materials were evaluated as catalysts for the reduction of 4-nitrophenyl and displayed enhanced activity relative to other supported AuNPs.
A highly efficient copper-catalyzed three-component reaction of cyanamides, amines, and diaryliodonium triflates was developed for the synthesis of guanidines. The mild reaction accommodates both aromatic and aliphatic amines and provides the products in good yields with good functional group tolerance. Moreover, it was demonstrated that C–H activation of the arenes could be realized for the direct preparation of guanidines.
A Cu-catalyzed three-component reaction of cyanamides, amines, and diaryliodoniums is established for the synthesis of guanidines under mild reaction conditions. Guanidines are easily prepared in high yields with broad functional group compatibility. Moreover, C–H activation of the arenes is also realized to make guanidines directly through a one-pot, two-step reaction from cyanamides and amines.
Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.
Nutr Cancer. 2016 Apr 26;:1-10
Authors: Tripathi R, Singh P, Singh A, Chagtoo M, Khan S, Tiwari S, Agarwal G, Meeran SM, Godbole MM
Abstract
Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy.
PMID: 27116040 [PubMed - as supplied by publisher]
Aqueous Extracts of Toona sinensis Leaves Inhibit Renal Carcinoma Cell Growth and Migration Through JAK2/stat3, Akt, MEK/ERK, and mTOR/HIF-2α Pathways.
Nutr Cancer. 2016 Apr 26;:1-13
Authors: Chen YC, Chien LH, Huang BM, Chia YC, Chiu HF
Abstract
Toona sinensis (TS) is a type of deciduous tree, which is distributed widely in Asia and used as a traditional herb medicine. Previously, we demonstrated that aqueous extracts of TS leaves (TSL-1) induce apoptosis in two clear types of human renal carcinoma cells (ccRCC) via mitochondria-dependent pathway. In this study, we further investigated the more detailed mechanism of TSL-1-induced antitumor effects on ccRCCs. TSL-1 treatment arrested ccRCC cells in G0/G1 phase through the decrease of cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 as well as induction of p53 and FOXO3a protein expressions. On the other hand, the inhibitory effects of TSL-1 on migration were also observed in 786-O and A-498 cells. Mechanically, we presented that TSL-1 could suppress cell cycle progression and motility via inhibiting the phosphorylation of JAK2/stat3, Akt, MEK/ERK, and mTOR in a concentration- and time-dependent manner. Moreover, we found that TSL-1 inhibited p21, HIF-2α, c-Myc, VEGF, and MMP9 protein expressions in both cell lines. In conclusion, these findings suggested that TS-induced apoptosis and its antimigration activity in ccRCC cells were accompanied by inactivation of several oncogenic pathways.
PMID: 27115866 [PubMed - as supplied by publisher]
Perioperative ω-3 Polyunsaturated Fatty Acid Nutritional Support in Gastrointestinal Cancer Surgical Patients: A Systematic Evaluation.
Nutr Cancer. 2016 Apr 26;:1-9
Authors: Ma YJ, Liu L, Xiao J, Cao BW
Abstract
This study was a systematic evaluation of the beneficial effects of n-3 polyunsaturated fatty acid (PUFA) in abdominal cancer surgical patients. A literature search of the databases PubMed, Medline, Cochrane, and EMBASE was conducted for studies published up to November 2014 in English language journals. Randomized controlled trials (RCTs) examining the effects of n-3 PUFA intake relative to conventional nutrition in surgical patients were included. The main outcomes were the duration of systemic inflammatory response syndrome (SIRS), length of hospital stay (LOS), serum C-reactive protein (CRP) levels, and postoperative complications. We identified 15 RCTs among 158 relevant trials. The results indicated the associations between n-3 PUFA intake and reduced LOS [mean differences (MDs), -2.47 d; 95% confidence intervals (CIs), -3.25 to -1.69], duration of SIRS (MD, -0.57 d; 95% CI, -0.92 to -0.22), and serum CRP levels (MD, -3.97 mg/l; 95% CI, -7.88 to -0.07) compared with consumption of conventional nutrition, as well as reduced incidence of postoperative infectious complications (risk ratio, 0.66; 95% CI, 0.49-0.87). This systematic evaluation suggests that n-3 PUFA significantly reduces the postoperative infectious complication rate, and shortens hospitalization and SIRS duration, particularly in malnourished gastrointestinal cancer patients.
PMID: 27115734 [PubMed - as supplied by publisher]
Fruit Extract from Pyropolyporus fomentarius (L. ex Fr.) Teng Induces Mitochondria-Dependent Apoptosis in Leukemia Cells but Enhances Immunomodulatory Activities of Splenic Lymphocytes.
Nutr Cancer. 2016 Apr 26;:1-10
Authors: Li Y, Zhou Y, Wang X, Wang P, Xiao Y, Cheng X, Zhang Y, Liu Y, Liu Q
Abstract
Pyropolyporus fomentarius (L. ex Fr.) Teng is a unique woody mushroom due to its medicinal value with numerous pharmacological activities. This study presented the potential antitumor and immunomodulatory properties of ethanol extract of P. fomentarius. The results showed that P. fomentarius extract inhibited the viability of murine leukemia L1210 cells in a dose-dependent manner with IC50 value of 69.35 μg/ml. Flow cytometry analysis demonstrated that the extract induced apoptosis in L1210 cells. Additionally, the decline of mitochondrial membrane potential was observed as well as the changes of caspase-3, caspase-9, Bcl-2, and Bax, suggesting that proapoptosis effect of the extract involved mitochondria-related pathway. Simultaneously, the P. fomentarius extract significantly enhanced the proliferation and activation of splenic lymphocytes in a dose-dependent manner. This P. fomentarius extract has potential applications as a natural antitumor agent with immunomodulatory activity.
PMID: 27115601 [PubMed - as supplied by publisher]
Anticlastogenicity and Anticarcinogenicity of Purple Rice Extract in Rats.
Nutr Cancer. 2016 Apr 26;:1-8
Authors: Punvittayagul C, Sankam P, Taya S, Wongpoomchai R
Abstract
Oryza sativa L. var. indica cv. Kum Doi Saket is a pigmented rice variety grown in northern Thailand. Our previous study found that the methanol extract of purple rice seed had the highest level of antimutagenicity in a Salmonella mutation assay. The present study was designed to evaluate its in vivo anticlastogenic and anticarcinogenic potentials. The purple rice extract had no acute toxicity on rats. The oral administration of 1,000 mg/kg body weight (bw) of the extract for 28 days did not increase the number of micronucleated hepatocytes. Interestingly, it significantly reduced the amount of micronucleus formation in the liver of diethylnitrosamine (DEN)-treated rats. The inhibitory mechanism involved the induction of hepatic glutathione S-transferase (GST) activity. In addition, oral administration of 500 mg/kg bw extract for 10 weeks significantly decreased the number of hepatic GST placental form positive foci, but did not modulate the number of colonic aberrant crypt foci in DEN- and dimethylhydrazine-initiated rats. In conclusion, the methanol extract of purple rice seed showed no toxicity, clastogenicity, or carcinogenicity in laboratory rats. It did display chemopreventive activity against the early stages of rat hepatocarcinogenesis.
PMID: 27115481 [PubMed - as supplied by publisher]
Admissions for isolated non-operative mild head injuries: Sharing the burden among trauma surgery, neurosurgery, and neurology.
J Trauma Acute Care Surg. 2016 Apr 26;
Authors: Zhao T, Mejaddam AY, Chang Y, DeMoya MA, King DR, Yeh DD, Kaafarani HM, Alam HB, Velmahos GC
Abstract
BACKGROUND: Isolated non-operative mild head injuries (INOMHI) occur with increasing frequency in an aging population. These patients often have multiple social, discharge and rehabilitation issues, which far exceed the acute component of their care. This study aims to compare the outcomes of patients with INOMHI admitted to three services: Trauma Surgery, Neurosurgery, and Neurology.
METHODS: Retrospective case series (01/01/2009-08/31/2013) at an academic Level I Trauma Center. According to an institutional protocol, INOMHI patients with Glasgow Coma Scale (GCS) of 13-15 were admitted on a weekly rotational basis to Trauma Surgery, Neurosurgery, and Neurology. The three populations were compared and the primary outcomes were survival rate to discharge, neurological status at hospital discharge as measured by the Glasgow Outcome Score (GOS), and discharge disposition.
RESULTS: Four hundred and eighty-eight INOMHI patients were admitted (Trauma Surgery 172; Neurosurgery 131; Neurology 185). The mean age of the study population was 65.3 years and 58.8% of patients were male. Seventy-seven percent of patients has a GCS score of 15. Age, gender, mechanism of injury, Charlson Comorbidity Index, Injury Severity Score, Abbreviated Injury Scale in head and neck, and GCS were similar among three groups. Patients who were admitted to Trauma Surgery, Neurosurgery and Neurology services had similar proportions of survivors (98.8% vs 95.7% vs 94.7%), and discharge disposition (Home: 57.0% vs 61.6% vs 55.7%). The proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to Trauma (97.7% vs 93.0% vs 92.4%). In a logistic regression model adjusting for CCI and AIS head and neck score, patients who were admitted to Neurology or Neurosurgery had significantly lower odds being discharged with GOS 4 or 5. While Trauma group had the lowest proportion of repeat brain CT (61.6%), Neurosurgery group had the highest proportion of ICU admission (29.8%), and Neurology group had the longest ED stay (7.5 h), there were no significant differences in duration of hospital stay, in-hospital complications and readmission within 30 days.
CONCLUSIONS: Although there were differences in utilization of health care resources, and the proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to Trauma, the majority of clinical outcomes were similar in INOMHI patients admitted to Trauma Surgery, Neurosurgery, or Neurology in our institution. A rotational policy of admitting INOMHI patients is feasible among services with expertise in and commitment to the care of these patients.
LEVEL OF EVIDENCE: IV, therapeutic/care management.
PMID: 27116408 [PubMed - as supplied by publisher]
Sinus surgery postpones chronic Gram-negative lung infection: cohort study of 106 patients with cystic fibrosis.
Rhinology. 2016 Apr 26;
Authors: Alanin MC, Aanaes K, Høiby N, Pressler T, Skov M, Nielsen KG, Taylor-Robinson D, Waldmann E, Krogh Johansen H, von Buchwald C
Abstract
BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency of pulmonary samples positive for GNB. We investigated whether the effect is sustained.
METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined by Leeds criteria.
RESULTS: One hundred and six CF patients underwent ESS; 27 had improved lung infection status after three years. The prevalence of patients free of lung colonization with GNB significantly increased from 16/106 patients (15%) preoperatively to 35/106 patients (33%) after three years. The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%).
CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three years in our cohort of patients with CF and may postpone chronic lung infection with GNB and thus stabilize lung function.
PMID: 27116399 [PubMed - as supplied by publisher]
Non-AIDS Defining Cancer Mortality: Emerging Patterns in the Late HAART Era.
J Acquir Immune Defic Syndr. 2016 Apr 21;
Authors: Zucchetto A, Virdone S, Taborelli M, Grande E, Camoni L, Pappagallo M, Regine V, Grippo F, Polesel J, Dal Maso L, Suligoi B, Frova L, Serraino D
Abstract
BACKGROUND: Non-AIDS defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared to people without AIDS (non-PWA).
METHODS: A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15-74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death (MCoD) data were retrieved up to December 2011. Excess mortality, as compared to non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs).
RESULTS: Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%) and liver (1.4%) cancers. A 7.3-fold (95% CI: 6.1-8.7) excess mortality was observed for all non-ADCs combined. Statistically significant SMRs emerged for specific non-ADCs, i.e., anus (5 deaths, SMR=227.6, 95% CI: 73.9-531.0), Hodgkin lymphoma (12 deaths, SMR=122.0, 95% CI: 63.0-213.0), unspecified uterus (4 deaths, SMR=52.5, 95% CI: 14.3-135.0, liver (17 deaths, SMR=13.2, 95% CI: 7.7-21.1), skin melanoma (4 deaths, SMR=10.9, 95% CI: 3.0-27.8), lung (38 deaths, SMR=8.0, 95% CI: 5.7-11.0), head and neck (9 deaths, SMR=7.8, 95% CI: 3.6-14.9), leukemia (5 deaths, SMR=7.6, 95% CI: 2.4-17.7), and colon-rectum (10 deaths, SMR=5.4, 95% CI: 2.6-10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use.
CONCLUSION: This population-based study documented extremely elevated risks of death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non virus-related cancers among HIV-infected individuals.
PMID: 27116048 [PubMed - as supplied by publisher]
