Head, neck cancer screenings at Naval Hospital Camp Lejeune
Camp Lejeune Globe Other types of tumors arising from the salivary glands in the face and neck, and the nose and sinus cavities are also included in this group. April is Head and Neck Cancer Awareness Month and Naval Hospital Camp Lejeune Ear, Nose, Throat Clinic is open ... and more » |
This study aimed to acquire knowledge about the factors affecting smartphone adoption for accessing information in medical settings in Iranian Hospitals.
A qualitative and quantitative approach was used to conduct this study. Semi-structured interviews were conducted with 21 medical residents and interns in 2013 to identify determinant factors for smartphone adoption. Afterwards, nine relationships were hypothesised. We developed a questionnaire to test these hypotheses and to evaluate the importance of each factor. Structural equation modelling was used to analyse the causal relations between model parameters and to accurately identify determinant factors.
Eight factors were identified in the qualitative phase of the study, including perceived usefulness, perceived ease of use, training, internal environment, personal experience, social impacts, observability and job related characteristics. Among the studied factors, perceived usefulness, personal experience and job related characteristics were significantly associated with attitude to use a smartphone which accounted for 64% of the variance in attitude. Perceived usefulness had the strongest impact on attitude to use a smartphone.
The factors that emerged from interviews were consistent with the Technology Acceptance Model (TAM) and some previous studies. TAM is a reliable model for understanding the factors of smartphone acceptance in medical settings.
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Flame Retardants Tied to Thyroid Cancer Risk
WebMD TUESDAY, April 11, 2017 (HealthDay News) -- Flame retardants used in many home furnishings may boost the risk for thyroid cancer, researchers report. "Thyroid cancer is the fastest increasing cancer in the U.S., with most of the increase in new cases ... Fireproof chemicals in sofas linked to thyroid cancerYOU.co.za Ask Dr. Nandi: Your sofa could be causing this cancerWXYZ all 5 news articles » |
Head, neck cancer screenings at Naval Hospital Camp Lejeune
Camp Lejeune Globe Risk factors for head and neck cancer include tobacco use– both smoked and smokeless - and alcohol. Due to the overall decrease in smoking in the United States since the 1980s, the incidence of vocal cord (larynx) cancer has steadily decreased over the ... and more » |
Histone deacetylase (HDAC)/phosphatidylinositol 3-kinase (PI3K) dual inhibition is a promising strategy for the treatment of intractable cancers because of the advantages of overcoming potential resistance and exhibiting synergistic effects. Therefore, development of an HDAC/PI3K dual inhibitor is reasonably attractive. Romidepsin (FK228, depsipeptide) is a potent HDAC inhibitor. We have previously reported that depsipeptide and its analogs have an additional activity as PI3K inhibitors and are defined as HDAC/PI3K dual inhibitors. Subsequently, we identified FK-A11 as the most potent analog and reported its biochemical, biological, and structural properties as an HDAC/PI3K dual inhibitor. In this study, we demonstrated in vitro and in vivo efficacy of FK-A11 in HT1080 fibrosarcoma and PC3 prostate cancer cell xenograft mouse models. FK-A11 showed in vivo antitumor activity by both intravenous and intraperitoneal administration in a dose-dependent manner. In both xenograft models, FK-A11 showed superior antitumor effects compared to other depsipeptide analogs in accordance with in vitro anti-cell proliferation effects and the potency of HDAC/PI3K dual inhibition. In addition, we showed evidence of HDAC/PI3K dual inhibition accompanying antitumor efficacy in xenograft tumor tissues by immunohistochemistry. We also detailed pharmacokinetic characterization of FK-A11 in mice. These findings will be essential for guiding further preclinical and clinical studies.
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Focal adhesion kinase (FAK) overexpression is related to the invasive and metastatic property in different kind of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatment, but its effect in human osteosarcoma has not yet well studied. In present study, we analyzed the anti-tumor efficacy of PF562271, a FAK inhibitor, against osteosarcoma in vitro and vivo. p-FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed the proliferation, colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and down-regulated the activity of AKT/mTOR pathway. Furthermore, PF562271 impaired tube formation ability of endothelial cells in vitro. Finally, oral administration of PF562271 in mice dramatically reduced tumor volume, weight and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma.
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Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) criteria B, BCLC-B) hepatocellular carcinoma (HCC). However, patients with BCLC-B HCC can differ in background factors related to hepatic function as well as tumor size and number. In the present study, we clarified the role of hepatic resection in patients with BCLC-B HCC. A total of 489 BCLC-B HCC patients with Child-Pugh class A disease initially treated with hepatic resection or TACE were included. In patients after propensity score matching (n=264), hepatic resection (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.35–0.91) was independently associated with survival in the multivariate analysis. We then divided patients into 2 groups based on the results of statistical analysis. There were 170 patients treated with resection and 319 with TACE. Child-Pugh score and number of tumors (cut-off, 3 tumors) were independently associated with type of HCC treatment in the multivariate analysis. We then divided patients in Group A (Child-Pugh score of 5 and ≤3 tumors; n=186) and Group B (Child-Pugh score of 6 or ≥4 tumors; n=303). In Group A, cumulative survival was significantly higher in the hepatic resection group than in the TACE group (p=0.014). In Cox proportional hazards models, hepatic resection (HR, 0.38; 95% CI, 0.23–0.64) was independently associated with survival in Group A patients. In Group B, treatment status was not associated with overall survival. Hepatic resection should be considered in patients with a Child-Pugh score of 5 and ≤3 tumors, despite having BCLC-B HCC.
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To make oribatid mites an applicable tool in monitoring programs it is necessary to find a molecular species marker that allows distinct, rapid and easy species identification. In previous studies, the common barcoding sequence COI showed to be too variable to serve as species marker in oribatid mites. The aim of the present study is to evaluate the potential use of the D3 region of the nuclear 28S rDNA gene for species identification. Therefore, we generated a reference DNA library of 28S D3 to identify specimens of the Oribatida from Germany, with focus on species occurring in peatlands being one of the most endangered habitats in Europe. New DNA sequences were obtained from 325 individuals and 64 species (58 genera, 34 families). By adding 28S D3-sequences from GenBank we altogether analysed 385 sequences from 89 German species, 32 of them restricted to peatlands and further 42 occurring in peatlands occasionally, representing 46 and 33% of the oribatids in German peatlands, respectively. P-distances were measured between species within families as well as for intraspecific divergence. 28S D3 showed low intraspecific genetic p-distances between 0 and 0.5%, interspecific distances within families varied between 0 and 9.7%. Most species pairs within families were further separated by one to four indels in addition to substitutions. Altogether, 93% of all analysed species are clearly delineated by 28S D3. Our study emphasises that 28S D3 rDNA is a useful barcode for the identification of oribatid mite specimens and represents an important step in building-up a comprehensive barcode library to allow metabarcoding analyses of environmental peatland samples for Oribatida in Germany as well as in Central Europe.
In order to study the function of peroxidase (POD) and polyphenol oxidase (PPO) in cassava resistance to spider mites, we tested the changes of transcription levels and activities of these two protective enzymes in both cassava and Tetranychus urticae (=T. cinnabarinus) during the interaction. The results showed that after damage of the mite-susceptible cassava cultivar BRA900 by T. urticae for 1 and 8 days, the transcription levels of MePOD and MePPO and the activities of POD and PPO showed no significant difference compared with those in undamaged leaves. However, the corresponding transcription levels and activities in 1- and 8-day-damaged leaves of mite-resistant cassava cultivar C1115 increased to a significant level of approximately twofold. When T. urticae fed on BRA900 for 1 and 8 days, the transcription levels of TcPPO and TcPOD and the activities of PPO and POD showed no significant difference compared with those before feeding. However, the corresponding transcription levels and activities of these two protective enzymes in T. urticae feeding on C1115 significantly decreased by about half. This study preliminarily validates the function of POD and PPO in cassava resistance to T. urticae, and provides candidate gene resource for molecular breeding of spider mite-resistant cassava.
Genetic identity and morphological features of a human biting tick, Amblyomma testudinarium, were determined for the first time in Taiwan. Morphological features of adult male and female ticks of Am. testudinarium were observed and photographed by a stereo- microscope. The genetic identity was analyzed by comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 18 strains of ticks representing 10 species of Amblyomma, and four outgroup species of Dermacentor and Rhipicephalus ticks. Nine major clades could be easily distinguished by neighbour-joining analysis and were congruent by maximum-parsimony method. All these Am. testudinarium ticks collected from Taiwan and Japan were genetically affiliated to a monophyletic group with highly homogeneous sequence (99.8–100% similarity), and can be discriminated from other species of Amblyomma and other genera of ticks (Dermacentor and Rhipicephalus) with a sequence divergence ranging from 6.9 to 23.9%. Moreover, intra- and inter-species analysis based on the genetic distance (GD) values indicated a lower level (GD < 0.003) within the same lineage of Am. testudinarium ticks collected from Taiwan and Japan, as compared with other lineage groups (GD > 0.108) of Amblyomma ticks, as well as outgroup (GD > 0.172) species. Our results provide the first distinguished features of adult Am. testudinarium ticks and the first genetic identification of Am. testudinarium ticks collected from humans in Taiwan. Seasonal prevalence, host range, and vectorial capacity of this tick species in Taiwan need to be further clarified.
Acaricidal and sublethal effects of the biopesticide Requiem®EC (containing an essential oil extract of Chenopodium ambrosioides near ambrosioides) on the two-spotted spider mite, Tetranychus urticae Koch, were evaluated in laboratory bioassays. The biopesticide was applied to bean leaves or leaf discs using a Potter spray tower. Acaricidal activity against eggs and immatures was evaluated in successive acute toxicity bioassays. Concentration-mortality data were subjected to probit analysis and the following LC50 values (ml/l) were calculated: 2.47 (eggs), 0.71 (larvae), 1.13 (protonymphs), 2.23 (female deutonymphs), and 6.02 (female teleiochrysalises). In adult bioassay, in which pre-ovipositional females were treated with a series of concentrations (0.31–10 ml/l), a run-off effect ranging 4–80% (after 24 h) and 8–93% (after 72 h) was observed. In two-choice bioassay, T. urticae females preferred the untreated halves of leaves over the halves treated with 1.25–10 ml/l biopesticide and they laid significantly more eggs on the untreated halves in the first 24 h and summed over 72 h. The indices of repellency and oviposition deterence ranged 11.2–77.3 and 14.8–87.9%, respectively. In age-stage two-sex life table bioassay, the females that hatched from eggs treated with 2.5 ml/l biopesticide and reached adulthood on treated leaf surface showed a significantly reduced the intrinsic rate of increase (r = 0.222), compared to the control (r = 0.317). The reduction of population growth was mainly due to a reduced preadult survival rate (0.42 ± 0.04) and extended juvenile developmental time (9.27 ± 0.11 days), compared to the control (0.93 ± 0.03 and 7.70 ± 0.06 days, respectively).
Estimating the impact of heat waves on human mortality is key when it comes to the design of effective climate change adaptation measures. As the usual approach—relying on detailed health data in form of hospital records—is not feasible for many countries, a different methodology is needed. This work presents such an approach. Based on singular spectrum analysis and using monthly mortality rates—partly ranging back to 1960—it derives excess mortality estimates for 27 European countries. Excess mortality is then regressed against a heat wave measure in order to assess the health impacts of extreme heat. The analysis demonstrates that many European countries are severely affected by heat waves: On average, 0.61%—and up to 1.14% in case of Portugal—of all deaths are caused by extreme heat events. This finding confirms the understanding that climate change is a major environmental risk to public health: In the 27 examined European countries, over 28,000 people die every year due to exposure to extreme heat.
Open reduction and internal fixation of distal humerus fractures is standard of care with good to excellent outcome for most patients. However, nonunions of the distal humerus still occur. These are severely disabling problems for the patient and a challenge for the treating physician. Fortunately, a combination of standard nonunion techniques with new plate designs and fixation methods allow even the most challenging distal humeral nonunion to be treated successfully.
The purpose of this manuscript is to describe our current technique in treating distal humeral nonunion as it has evolved over the last four decades. We have now follow-up on 62 treated patients.
A few key steps are essential to obtain bone healing while regaining or preserving elbow motion. These include careful planning, extensile exposure, release of the ulnar nerve, capsular release and mobilization of the distal fragment, debridement, and finally stable fixation after alignment with application of bone graft.
The vast majority of distal humeral nonunions can be treated successfully with open reduction and internal fixation.
Important components of the treatment plan are careful preoperative planning, extensile approach, debridement, and solid fixation with—locking—plates and liberal use of bone graft.
Osteoarthritis (OA) of the hip and knee continues to increase in prevalence with the increasing age of our population. This condition is characterized by joint pain, stiffness, and limitations in activities of daily living. Management options are initially aimed at preventing the progression of disease and delaying the need for total joint arthroplasty (TJA). This includes nonoperative measures, as well as surgical interventions, including arthroscopy, osteotomy, and arthrodesis. However, once patients fail alternative therapy, TJA is indicated. Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are highly effective procedures at reducing pain and improving functional status. Patients report high satisfaction rates after TJA and experience minimal complications. Moreover, these procedures are cost effective. Significant research into patient-specific implants (PSI) and computer-navigation-assisted surgery shows improved component positioning; however, further research is needed to determine the clinical effect of this innovation. Wear rates in both TKA and THA have improved significantly over the past decade, with highly cross-linked ultra-high molecular-weight polyethylene showing promising results. New minimally invasive surgical techniques are also showing excellent short-term results, but long-term data is still lacking. Overall, hip and knee OA is a debilitating condition that can be effectively managed with TKA or THA. Indications continue to expand for these procedures and innovation continues to aim for improved outcomes.
A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic–hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (NGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of α-/β-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.—Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture.
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMC that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of GAPDH-overexpressing cells to DNA damage and apoptosis, which indicated that Ape1 is indispensable for GAPDH-dependent protective effects. GAPDH bound Ape1 in the SMC nucleus, and blocking (or oxidation) of GAPDH active site cysteines suppressed GAPDH/Ape1 interaction and potentiated apoptosis. GAPDH up-regulated Ape1 via a transcription factor homeobox protein Hox-A5–dependent mechanism. GAPDH levels were reduced in atherosclerotic plaque SMCs and this effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated that nuclear GAPDH/Ape1 interaction preserved Ape1 activity, reduced DNA damage, and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of nuclear GAPDH/Ape1 interactions may be a novel therapy to increase atherosclerotic plaque stability.—Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.
The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN- and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1 knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography–mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.—Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O’Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.
In most avian species, the early embryo suspends development when the ambient temperature is too low; the resultant dormant state is called cold torpor. However, very little is known about dormant avian embryos at the cellular level. To investigate the molecular processes that occur in the chicken blastoderm during cold torpor, we performed transcriptome analysis and investigated cellular responses in dormant embryos. In embryos stored at low temperature, we observed up-regulation of genes and proteins related to endoplasmic reticulum stress and stress-activated protein kinase signaling. In addition, the proportion of early apoptotic cells rose dramatically during torpor, whereas the proportion of late apoptotic cells was unchanged. Cell cycle analysis revealed that mitotic arrest occurred at the G2 phase in a DNA damage–independent manner and that the arrest was alleviated after incubation at 37°C. Our data suggest that the dormant avian embryo tolerates cold stress by inducing stress-tolerance pathways, inhibiting late apoptosis, and triggering cell cycle arrest at the G2 phase.—Ko, M. H., Hwang, Y. S., Rim, J. S., Han, H. J., Han, J. Y. Avian blastoderm dormancy arrests cells in G2 and suppresses apoptosis.
Background: Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. Methods: A single-institution, Institutional Review Board–approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30–60 Gy) in 27 fractions (range, 5–30). Primary outcomes were regional control and overall survival by RSI GES status. Results: Median follow-up was 69 months (range, 13–180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; P=.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05–0.43; P<.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; P=.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P<.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24–92.14). Conclusions: Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.
The most common cancer in both men and women is basal cell carcinoma (BCC). Although most primary and recurrent BCCs have high cure rates with standard therapies, advanced BCCs present a greater treatment challenge, especially in cosmetically and functionally sensitive areas. In patients unable to undergo surgery or radiation therapy, hedgehog inhibitors can be used neoadjuvantly to reduce tumor size, decreasing the extent and complexity of any subsequent surgery and providing either a cure or palliation. The goal of this review is to summarize the pharmacology, efficacy, and safety of systemic hedgehog inhibitors, as well as their role in daily practice as neoadjuvant therapy. Relevant English-language literature was identified and evaluated based on results from database searches of PubMed. Terms searched included, but were not limited to, "vismodegib," "Erivedge," "sonidegib," "DE225," "BCC," and "neoadjuvant treatment." Additional literature was identified from the reference lists of previously identified articles. The authors' personal experience in treating advanced BCC using hedgehog inhibitors has been incorporated into the recommendations made herein.
Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor–positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20–0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26–0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25–1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.
Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that some RAS mutations do not provide equivalent resistance to EGFR inhibition compared with the most prevalent mutations at codons 12, 13, and 61. This report describes a case of a patient with metastatic colon cancer harboring the p.A59T variant of KRAS, with objective radiographic response (36% decrease per RECIST 1.1) and carcinoembryonic antigen biomarker response to panitumumab therapy given with FOLFIRI chemotherapy. We propose that A59T represents one potential exception to the guidelines that KRAS mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.
These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor–positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.
Background: In an interdepartmental cooperation, we investigated the feasibility and benefits of implementing dose banding of chemotherapy at our medical center. Based on this concept, chemotherapy doses are clustered into bands of similar dosage levels, thereby allowing the preproduction of frequently used standard doses of drugs, with sufficient physicochemical stability. Although established practice in the United Kingdom, there is little published evidence of its introduction elsewhere. Methods: We performed an analysis of local prescribing practice (22,310 chemotherapies) and identified gemcitabine, 5-fluorouracil, and carboplatin, among various others, as cytotoxic drugs suitable for dose banding. Results: First, we determined the physicochemical stability of the selected chemotherapy drugs during 12-weeks' storage by performing pH analysis and visual examination for color change or particles. No relevant changes were identified. Gemcitabine was selected for quantitative high-performance liquid chromatography analysis and we were able to show that ≥95% remained after 12 weeks' storage, in accordance with international guidelines. To simulate a worst case scenario, we performed microbiological stability testing of simulated cytotoxic compounding by replacing the cytotoxic drug with liquid media. Samples were incubated over defined storage time points (3, 6, and 12 weeks) and evaluated using the direct inoculation method. For the container integrity test, we deposited the samples into highly contaminated broth for 1 hour. Microbiological stability was demonstrated in both tests for the full storage period. Conclusions: Our data show that 12-weeks' storage of selected cytotoxic products is feasible from a microbiological perspective. Sterility of prepared products was maintained under extreme storage conditions. Gemcitabine content was in accordance with international guidelines after 12-weeks' storage. These results support the introduction of dose-banded gemcitabine products with the predicted advantages of optimized pharmacy workflow and reduced patient waiting times. We highlight the need for further research and consensus on the performance of purity analyses in dose-banded drug products.
Background: Patients with cancer are at high risk for severe sepsis and septic shock (SS/SSh), and a delay in receiving effective antibiotics is strongly associated with mortality. Delays are due to logistics of clinic flow and drug delivery. In an era of increasing antimicrobial resistance, combination therapy may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP) program to simplify timely and effective provision of empiric antibiotics and other resuscitative care to outpatients with cancer with suspected SS/SSh before hospitalization. Over a 49-month period from January 1, 2008, through January 31, 2012, a total of 162 outpatients with cancer received the intervention. A retrospective cohort study was conducted to determine outcomes, including mortality and adverse events associated with the use of a novel care bundle designed for compatibility of broad-spectrum antibiotics and other supportive care administered concurrently via rapid infusion at fixed doses. Results: Of 162 sequential patients with cancer and suspected SS/SSh who received the SSP, 71 (44%) were diagnosed with SS/SSh. Median age was 53 years and 65% were men; 141 (87%) had hematologic malignancies, 77 (48%) were transplant recipients, and 80 (49%) were neutropenic. Median time to completion of antibiotics was 111 minutes (interquartile range, 60–178 minutes). A total of 71 patients (44%) had bacteremia and 17% of 93 isolates were multidrug-resistant. Possibly related nephrotoxicity occurred in 7 patients, and 30-day mortality occured in 6 of 160 patients (4%), including 3 of 71 (4%) with SS/SSh. Risk of developing SSh or death within 30 days increased 18% (95% CI, 4%–34%) for each hour delay to completion of antibiotics (P=.01). Conclusions: Rapidly administered combination antibiotics and supportive care delivered emergently to ambulatory patients with cancer with suspected SS/SSh was well-tolerated and associated with excellent short-term survival.
This selection from the NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.
Background: Patients with cancer have several risk factors for Clostridium difficile infection (CDI), but the impact of CDI on outcomes in this population needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in patients with cancer using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010. Methods: Diagnosis codes were used to identify patients with cancer and CDI events. Demographics, diagnoses, length of stay (LOS), and discharge information were abstracted. Multivariate linear and logistic regression models with weighted analysis were conducted to study CDI incidence and CDI-associated outcomes. Analyses were performed using SAS version 9.4. Results: During the 10-year study period, 20.1 million discharges had a cancer diagnosis. CDI developed in 1.09% of patients with cancer versus 0.77% of patients without cancer (adjusted odds ratio [aOR], 1.28; 95% CI, 1.28–1.29; P<.001). The incidence of CDI in patients with cancer increased during the 10-year study period (64.7 per 10,000 discharges in 2001–2002 to 109.1 in 2009–2010; P<.001). In multivariable analysis, compared with patients with cancer without CDI, patients with cancer and CDI had a longer mean LOS (5.67 days; 95% CI, 5.39–5.94) and higher rates of in-hospital mortality (aOR, 1.18; 95% CI, 1.16–1.20) and discharge to a care facility (aOR, 1.74; 95% CI, 1.72–1.75; all P<.001). Conclusions: In this national database, CDI incidence increased significantly in patients with cancer over the study period and was associated with prolonged hospitalization, increased mortality, and discharge to a care facility. Despite increased attention, CDI remained a serious infection and merits appropriate prevention and management.
This paper aims to critically evaluate recent literature on the epidemiology, pathophysiology, and management of overlap syndrome (OS).
The prevalence of OS is much higher in patients with either chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA) (8.1%–65.9%) than in the general population (1–2%). Maladaptive neural, inflammatory, cardiovascular, and autonomic responses are intensified with the coexistence of both conditions, leading to worse diurnal and nocturnal respiratory function. Careful analysis of the oximetry and capnography findings during polysomnography can detect concomitant sleep-related hypoxemia/hypoventilation. Observational studies report salutary effects of CPAP on gas exchange, COPD exacerbation, sexual dysfunction, and mortality.
COPD or OSA patients should be routinely screened for the presence of OS, since CPAP therapy can improve clinical outcomes. Future studies should investigate the pathophysiological interactions resulting from combined risk factors (smoking and obesity), the impact of oxygen on clinical outcomes, and the role of other positive airway pressure modalities.
With more than 2 million American military personnel deployed and 350,000 traumatic brain injuries since 2001, civilian and military health care providers must recognize the impact and unique considerations for managing combat-related traumatic brain injuries. Here, we will review the etiology and manifestations of combat-related traumatic brain injuries with further discussion of acute management and aeromedical evacuation in the deployed setting.
Traumatic brain injuries have emerged as the signature wound of the recent wars. Previously, lethal assaults on the human body are now routinely survivable due to improvements in protective equipment and battlefield medicine. Management centers on increased recognition and screening for TBI, and advanced imaging techniques are not routinely recommended at this time.
Unlike other physical injuries, traumatic brain injuries can occur in the absence of other physical wounds, making them more difficult to detect. Traumatic brain injuries have several short- and long-term manifestations and consequences that are important to recognize as healthcare providers.
