Association of sexually-transmitted infection and African-American race with Streptococcus agalactiae colonization in pregnancy.

BACKGROUND: Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women. METHODS: A retrospective cohort study was performed at Louisiana State University Health Sciences Center - Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010. RESULTS: Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African-American race (AOR = 2.142; 95% CI = 2.092-3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035-1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African-American race (AOR = 2.13; 95% CI = 1.20-3.78) and younger age (AOR = 0.94; 95% CI = 0.91-0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78-10.41). CONCLUSIONS: This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

Palliative Radiotherapy as a Treatment for Carcinoma Invasion of the Sacrum: An Observational Case Series Study.

BACKGROUND/AIM: Radiotherapy for carcinoma invasion of the sacrum (CIS) is an alternative treatment to surgery in patients with advanced, inoperable tumors or those not medically eligible for resection of the neoplasm. Herein we present an observational study of patients with imaging-confirmed CIS who were treated non-operatively with radiation. PATIENTS AND METHODS: A retrospective chart review of CIS patients treated with palliative radiotherapy (PR) during a 9-year period (2004-2013) was performed. RESULTS: Six women and 13 men with an average age of 60 years took part in this study. Most patients (84%) exhibited extrasacral metastases. Primary tumors included lung (n=6), colorectal (n=6), breast (n=3), bladder or kidney (n=2), and liver carcinoma or a tumor in an unknown primary site (n=2). The mean follow-up time was 10 months with a 2-year survival rate of 9%. The majority (71%) of symptomatic patients obtained relief from pain following PR. Half of those individuals who were non-ambulatory prior to therapy regained mobility. There were no acute ill-effects or later complications after irradiation. CONCLUSION: Despite the small cohort and poor overall survival rate, non-operative radiation treatment is a beneficial method of palliative care in patients with CIS.

Longevity after radiotherapy of stage III lung cancer: superior vena cava obstruction is associated with early mortality.

BACKGROUND: People with locally advanced lung cancer have a poor prognosis. Physicians are unable to accurately predict life expectancy of patients. The aims of this retrospective study were to identify the life spans of individuals after radiotherapy of stage III carcinoma of the lung and to determine whether potential prognostic factors could identify people with distinct life spans. METHODS: Between September 1981 and August 2010, 133 consecutive individuals underwent definitive or palliative radiotherapy (with or without chemotherapy) for stage IIIA/IIIB disease. Analysis of the survival data revealed that 14 patients experienced long-term survival, exceeding 36 months; 94 patients had a short-term life span (STLS), extending between 4 and 36 months, and 25 patients were in the end-of-life (EOL) period, referring to the last 3 months of life. Recognized pre-treatment clinicopathological features were tested for their impact on prognosis. RESULTS: The largest proportion of patients presenting with superior vena cava obstruction (SVCO) (P<0.001) and receiving palliative radiotherapy (P=0.009) were from the EOL group. Most of the individuals with inadequate or no health insurance belonged to the STLS and EOL cohorts (P=0.001). Multivariate analysis revealed that the presence of SVCO was an independent factor predictive of shortened survival/EOL status (P=0.001). CONCLUSIONS: Our study showed that a particular disease characteristic, health insurance status and provision of contemporary therapy can influence individual longevity. Selection and prioritization of health care resources remain important; therefore, identification of influential prognostic factors in lung cancer patients deserves further scrutiny.

Incidence of contralateral-bilateral nodes in the human papillomavirus era.

OBJECTIVES/HYPOTHESIS: HPV-positive oropharyngeal squamous cell carcinoma has a more favorable prognosis when compared to HPV-negative disease, regardless of the presence of nodal metastases. However, the importance of contralateral neck treatment based on HPV status has not been well studied. Given the historically poor prognostic implications of cervical nodal metastases, this study sought to elucidate the relationship between HPV status and contralateral/bilateral nodal metastasis in patients with oropharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective cohort analysis. METHODS: Data were collected on patients with oropharyngeal squamous cell carcinoma from 2001 to 2014. Nodal status was determined by contrast-enhanced computed tomography, positron emission tomography, or surgical pathology when available. Survival rates and associations between HPV status and demographic/tumor characteristics were assessed. RESULTS: Of 178 total patients, 46 (26.0%) had contralateral/bilateral metastases. There was no significant difference in incidence of contralateral/bilateral nodal metastases between HPV-positive and HPV-negative patients (24.6% vs. 29.1%, P = .53). Tonsil primaries had significantly lower incidence of contralateral/bilateral nodal metastases compared to tongue base (20.9% vs. 34.3%, P = .048). On multivariate regression, tumor size was the only factor associated with contralateral/bilateral nodal metastases (T4 vs. T1-3 odds ratio = 5.15, 95% confidence interval: 2.4-11.2). Five-year overall survival among all patients with and without contralateral/bilateral nodal metastases was 45.4% and 65.2%, respectively (P = .007). CONCLUSIONS: Our results did not show a significantly different incidence of contralateral/bilateral nodal metastases between HPV-positive and HPV-negative patients. T4 stage and tongue base location, however, were associated with contralateral disease. These data suggest treatment of bilateral necks might be warranted in these cases, regardless of HPV status. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1328-1333, 2017.

Predicting feeding tube and tracheotomy dependence in laryngeal cancer patients.

CONCLUSIONS: The two scales reliably measure laryngeal edema and dysfunction in laryngeal cancer patients. The eight categories from these scales, and abnormal pharyngeal squeeze, can be used to form a new rating scale intended to help clinicians identify and circumvent swallowing complications after chemo-irradiation. OBJECTIVES: The objectives were to compare two laryngeal edema rating scales in laryngeal cancer patients and determine if post-radiation +/- chemotherapy edema predicts dependence on a feeding tube and/or tracheostomy. METHODS: A retrospective chart review between 2005-2008 revealed 28 laryngeal cancer patients status post-radiation +/- chemotherapy, with video laryngoscopies performed within 6 months after treatment. Four raters evaluated videos based on the Laryngopharyngeal Edema Scale (LES) and the Reflux Finding Score (RFS). Tracheostomy and feeding tube outcomes were then correlated with the two scales. RESULTS: Feeding tube and tracheostomy dependence were associated with pre-treatment vocal cord paralysis, advanced T stage, and chemoradiation. Eight categories from the LES and RFS scales were significantly associated with the need for a feeding tube.

Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival.

BACKGROUND: Laparoscopic surgery for colon cancer has been demonstrated in clinical trials to have short-term benefits when compared to the open surgical approach. Guidelines of the National Comprehensive Cancer Network recommend that patients with stage III or high-risk stage II colon cancer undergo adjuvant chemotherapy. We hypothesized that laparoscopic colectomy is associated with increased compliance to recommendations for chemotherapy, a lesser time to start of chemotherapy, and increased overall survival. METHODS: The National Cancer Data Base was queried to identify patients with stage III or high-risk stage II colon cancer (T4, positive margins, <12 lymph nodes, or high tumor grade) diagnosed 2010-2012. Patients were divided into laparoscopic colectomy and open colectomy groups. Intent-to-treat analysis was used with converted cases included in the laparoscopic colectomy group. Rates of receiving adjuvant chemotherapy, time from diagnosis and date of operation to start of chemotherapy, and overall survival were compared. RESULTS: A total of 48,257 patients were included for analysis; 18,801 patients underwent laparoscopic colectomy and 29,456 underwent open colectomy. Laparoscopic colectomy patients received adjuvant chemotherapy at a somewhat greater rate than open colectomy (66.2% vs 59.4%, P < .01). Among patients who received chemotherapy, mean time to start of chemotherapy after definitive resection was somewhat less for laparoscopic colectomy than open colectomy (48.7 vs 52.7 days, P < .01). Two-year overall survival was greater for laparoscopic colectomy than open colectomy (81.9% vs 73.2%, P < .01). CONCLUSION: Compared to open colectomy, laparoscopic colectomy is associated with somewhat greater rates of compliance with guidelines for adjuvant chemotherapy for stage III and high-risk stage II colon cancer, as well as a slightly lesser time to start of chemotherapy and improved overall survival.

FDG PET Imaging of Extremities in Rheumatoid Arthritis.

BACKGROUND: The primary objective of this study was to evaluate the utility of fluorodeoxyglucose positive emission tomography imaging in assessing the degree of joint inflammation and response to therapy in patients with rheumatoid arthritis using standard PET parameters. METHODS: Five subjects with newly diagnosed RA were enrolled in this IRB-approved prospective study. After standard conventional workup that included clinical and laboratory evaluation and disease activity score (DAS3v) calculation, subjects underwent baseline FDG PET scans of their hands and feet prior to initiation of treatment and after six months of standard treatment. The uptake of FDG in involved joints was assessed qualitatively (visual evaluation) as well as semi quantitatively using standardized uptake value (SUV). Findings from the FDG PET scans were correlated with clinical and laboratory parameters including DAS and ESR. RESULTS: In all five patients, increased FDG uptake was noted in various joints affected by RA. The intensity of uptake varied from mild to intense (SUVmax values from 3.10 to 6.0). Overall, these correlated well with the clinical evaluation of involved joints. FDG PET imaging provided additional information by showing involvement in joints that were difficult to evaluate clinically (e.g. mid foot joints). The PET data also provided a distribution of joint involvement with varying degrees of severity in the same subject. On objective analysis using Spearman rank correlation coefficient for statistical analysis, no significant correlations were observed (p>0.05) between DAS, ESR, and the different PET parameters at baseline (before treatment) despite large calculated positive correlation coefficients. This was due to the small sample size (n=5). At post-treatment, the significant correlations were those between DAS and Maximum metabolic disease burden (MDB max) (RS=0.9, p=0.04) and between ESR and MDB max (RS=0.9, p=0.04). The positive correlations between total metabolic disease burden (Total MDB) and DAS (RS=0.7) and between Total MDB and ESR were also large (RS=0.7) but not significant. The non-significance was due to the small sample size. CONCLUSIONS: FDG PET imaging provides a unique noninvasive quantitative method in assessing disease status and response to therapy and can serve as a useful adjunct to clinical evaluation in management of patients with rheumatoid arthritis.

DNA damage response and repair data with pharmacological modulators of Tousled.

Human Tousled kinase 1 (TLK1) plays an important role in chromatin remodeling, replication, and DNA damage response and repair. TLK1 activity is immediately, but transiently, downregulated after genotoxic insult, and its recovery is important for exit from checkpoint arrest and cell survival after radiation. The data in this article compliments research presented in the paper titled, "Tousled kinase activator, gallic acid, promotes DNA repair and suppresses radiation cytotoxicity in salivary gland cells" [1]. The identification of small molecule activators and inhibitors of TLK1 provided an opportunity to pharmacologically alter the protein׳s activity to elucidate its role in DNA damage response pathways. TLK1 effectors, gallic acid (GA) and thioridazine (THD) activate and inhibit the kinase, respectively, and the data report on the impact of these compounds and the significance of TLK1 to DNA break repair and the survival of human salivary acinar cells.

Ten-year Survivors After Contemporary Management of Advanced 'Horseshoe' Anterior Commissure Laryngeal Cancer.

BACKGROUND: Combinations of treatment modalities for locally extensive carcinomas of the larynx constitute the standard of care. Advanced 'horseshoe' anterior commissure laryngeal cancer (HACLC) is a disease entity that has not received much attention in the literature. The aims of this study were to evaluate prolonged survival in patients after standard combined therapy for HACLC and to identify clinicopathological factors influential towards an extended outcome. PATIENTS AND METHODS: Fourteen patients (10-year survivors) with stage III or IV laryngeal cancer involving the anterior commissure and both true vocal cords were treated with total laryngectomy (and postoperative radiotherapy in 11 individuals). RESULTS: During follow-up, ranging from 123 to 256 months, locoregional recurrent disease and distant metastasis were not observed. Complications after therapy were manageable and few. The long-term survivors were particularly difficult to characterize. CONCLUSION: The optimal treatment for advanced HACLC has not been clarified; however, in this study, total laryngectomy and the indicated use of postoperative radiotherapy, were successful in achieving long-term disease-free survival. Predictive factors for longevity were not detected in this limited experience.

Tongue Blade Bite Test Predicts Mandible Fractures.

The aim of the study is to evaluate the utility of a simple tongue blade bite test in predicting mandible fractures and use this test as an alternative screening tool for further workup. This is a retrospective chart review. An institutional review board approved the retrospective review of patients evaluated by the Department of Otolaryngology at a single institution for facial trauma performed from November 1, 2011, to February 27, 2014. Patients who had a bite test documented were included in the study. CT was performed in all cases and was used as the gold standard to diagnose mandible fractures. Variables analyzed included age, sex, fracture type/location on CT, bite test positivity, and operative intervention. A total of 86 patients met the inclusion criteria and of those 12 were pediatric patients. Majority of the patients were male (80.2%) and adult (86.0%; average age: 34.3 years). Fifty-seven patients had a negative bite test and on CT scans had no mandible fracture. Twenty-three patients had a positive bite test and a CT scan confirmed fracture. The bite test revealed a sensitivity of 88.5% (95% CI: 69.8-97.6%), specificity of 95.0% (95% CI:86.1-99%), positive predictive value [PPV] of 88.5% (95% CI: 69.8-97.6%), and negative predictive value [NPV] of 95.0% (95% CI: 86.1-99.0%). Among pediatric patients, the sensitivity was 100% (95% CI: 29.9-100%), specificity was 88.9% (95% CI: 68.4-100%), PPV was 75.0% (95% CI: 19.4-99.4%), and NPV was 100% (95% CI: 63.1-100%). The tongue blade bite test is a quick inexpensive diagnostic tool for the otolaryngologist with high sensitivity and specificity for predicting mandible fractures. In the pediatric population, where avoidance of unnecessary CT scans is of highest priority, a wider range of data collection should be undertaken to better assess its utility.

Biomarker and Pathologic Predictors of Cutaneous Squamous Cell Carcinoma Aggressiveness.

OBJECTIVE: Aggressive cutaneous squamous cell carcinoma (cSCC) patients are at increased risk of metastasis. Currently, there are no accepted criteria or biomarkers for reliably predicting individuals at risk for recurrence and metastasis. Our objective is to determine if pS6 and pERK can predict cSCC aggressiveness and to identify primary tumor characteristics that may predict parotid metastasis. STUDY DESIGN: Retrospective case series. SETTINGS: Tertiary care center. SUBJECTS AND METHODS: An Institutional Review Board-approved retrospective review was performed for patients with facial cSCC, with and without metastasis to the parotids. Subjects for the study were identified through the Louisiana Tumor Registry, Veterans Medical Records, and LSU Health-Shreveport pathology database. Tumor specimens from patients with cSCC and cSCC with parotid metastasis were analyzed for pERK and pS6 expression through immunohistochemistry. To identify risk factors for tumor aggressiveness, multiple logistic regression analysis was used to evaluate patients with cSCC that was metastatic to the parotid and managed surgically. RESULTS: cSCC with parotid metastasis specimens exhibited significantly higher average pS6 but not pERK positivity than those from cSCC without metastasis (P < .05). Primary lesion-positive margins (P < .01), size of the skin tumor (P < .01) and degree of tumor differentiation (P < .01) were significantly associated with parotid metastasis. CONCLUSION: Surgical history of cSCC, primary lesion-positive margins, degree of differentiation, and lesion size together with pS6 positivity appear to be predictors of cSCC aggressiveness and should prompt increased monitoring or elective parotidectomy.

Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells.

Accidental or medical radiation exposure of the salivary glands can gravely impact oral health. Previous studies have shown the importance of Tousled-like kinase 1 (TLK1) and its alternate start variant TLK1B in cell survival against genotoxic stresses. Through a high-throughput library screening of natural compounds, the phenolic phytochemical, gallic acid (GA), was identified as a modulator of TLK1/1B. This small molecule possesses anti-oxidant and free radical scavenging properties, but in this study, we report that in vitro it promotes survival of human salivary acinar cells, NS-SV-AC, through repair of ionizing radiation damage. Irradiated cells treated with GA show improved clonogenic survival compared to untreated controls. And, analyses of DNA repair kinetics by alkaline single-cell gel electrophoresis and γ-H2AX foci immunofluorescence indicate rapid resolution of DNA breaks in drug-treated cells. Study of DR-GFP transgene repair indicates GA facilitates homologous recombinational repair to establish a functional GFP gene. In contrast, inactivation of TLK1 or its shRNA knockdown suppressed resolution of radiation-induced DNA tails in NS-SV-AC, and homology directed repair in DR-GFP cells. Consistent with our results in culture, animals treated with GA after exposure to fractionated radiation showed better preservation of salivary function compared to saline-treated animals. Our results suggest that GA-mediated transient modulation of TLK1 activity promotes DNA repair and suppresses radiation cytoxicity in salivary gland cells.

Enhanced Systemic Bioavailability of Curcumin Through Transmucosal Administration of a Novel Microgranular Formulation.

BACKGROUND/AIM: Curcumin is a promising nutraceutical for chemoprevention of head and neck squamous cell carcinoma (HNSCC). Capsular formulations of curcumin demonstrate low systemic bioavailability. We aimed to determine if curcumin levels were higher in healthy volunteers and cancer patients with microgranular curcumin that allows for transmucosal absorption and identify a consistent biomarker. PATIENTS AND METHODS: Eight healthy volunteers and 15 HNSCC patients completed the trials. Serum levels of curcumin were measured by HPLC. Biological activity of curcumin was assessed with Multiplex Immunoassay and immunohistochemistry. RESULTS: We achieved higher serum levels of curcumin compared to trials using capsular formulation. In cancer patients a significant decrease in expression of fibroblast growth factor-2 (FGF-2) in post-biopsy samples and decreased serum levels of FGF-2, granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-17 (IL-17) (p<0.05) was observed. CONCLUSION: Transmucosal administration of microgranular curcumin leads to enhanced curcumin bioavailability that is associated with significant biological effects.

A pilot study: portable out-of-center sleep testing as an early sleep apnea screening tool in acute ischemic stroke.

INTRODUCTION: Prompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but in-laboratory conventional polysomnograms (PSG) are not routinely practical. Though portable out-of-center type III cardiopulmonary sleep studies (out-of-center cardiopulmonary sleep testing [OCST]) are widely available, these studies have not been validated in patients who have recently suffered from AIS. We hypothesized that OCST in patients with AIS would yield similar results when compared to conventional PSG. METHODS: Patients with AIS had simultaneous type III OCST and PSG studies performed within 72 hours from symptom onset. The accuracy of OCST was compared to PSG using: chi-square tests, receiver operatory characteristic curves, Bland-Altman plot, paired Student's t-test/Wilcoxon signed-rank test, and calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Twenty-one out of 23 subjects with AIS (age 61±9.4 years; 52% male; 58% African-American) successfully completed both studies (9% technical failure). Nearly all (95%) had Mallampati IV posterior oropharynx; the mean neck circumference was 16.8±1.6 in. and the mean body mass index (BMI) was 30±7 kg/m(2). The apnea hypopnea index (AHI) provided by OCST was similar to that provided by PSG (19.8±18.0 vs 22.0±22.7, respectively; P=0.49). On identifying subjects by OCST with an AHI ≥5 on PSG, OCST had the following parameters: sensitivity 100%, specificity 85.7%, PPV 93%, and NPV 100%. On identifying subjects with an AHI ≥15 on PSG, OCST parameters were as follows: sensitivity 100%, specificity 83.3%, PPV 81.8%, and NPV 100%. Bland-Altman plotting showed an overall diagnostic agreement between OCST and PSG modalities for an AHI cutoff >5, despite fine-grained differences in estimated AHIs. CONCLUSION: Compared with PSG, OCST provides similar diagnostic information when run simultaneously in AIS patients. OCST is a reliable screening tool for early diagnosis of OSA in AIS patients.