Anisotropy of Trabecular Bone from Ultra-Distal Radius Digital X-Ray Imaging: Effects on Bone Mineral Density and Age

Background: When applied to trabecular bone X-ray images, the anisotropic properties of trabeculae located at ultra-distal radius were investigated by using the trabecular bone scores (TBS) calculated along directions parallel and perpendicular to the forearm. Methodology: Data from more than two hundred subjects were studied retrospectively. A DXA (GE Lunar Prodigy) scan of the forearm was performed on each subject to measure the bone mineral density (BMD) value at the location of ultra-distal radius, and an X-ray digital image of the same forearm was taken on the same day. The values of trabecular bone score along the direction perpendicular to the forearm, TBSx, and along the direction parallel to the forearm, TBSy, were calculated respectively. The statistics of TBSx and TBSy were calculated, and the anisotropy of the trabecular bone, which was defined as the ratio of TBSy to TBSx and changed with subjects’ BMD and age, was reported and analyzed. Results: The results show that the correlation coefficient between TBSx and TBSy was 0.72 (p BMD and age was reported. The results showed that decreased trabecular bone anisotropy was associated with deceased BMD and increased age in the subject group. Conclusions: This study shows that decreased trabecular bone anisotropy was associated with decreased BMD and increased age.

Detection of cardiac myosin binding protein-C (cMyBP-C) by a phospho-specific PKD antibody in contracting rat cardiomyocytes

Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.

The size of Metastasis in the Sentinel Node Is a Predictor of Additional Non-Sentinel Node Positivity

Background: The need for axillary lymph node dissection (ALND) when sentinel lymph nodes (SLN) contain micrometastasis is controversial. The purpose of this study was to determine if the size of tumor in the SLN corresponds with additional positive non-sentinel lymph nodes (non-SLN) in pT1 breast cancer. Methods: This retrospective review of 483 patients with pT1 breast cancer identified 96 patients with tumor positive SLN biopsies between June 1999 and February 2010. The size of SLN metastasis and the number of tumor positive non-SLN were recorded using AJCC criteria. Receiver operating characteristic analysis was used to discriminate the SLN size with the optimal sensitivity, specificity and likelihood ratios (LR) for additional positive non-SLN. Results: Among 96 patients with a tumor positive SLN, 41% (n = 39) had micrometastasis, and 59% (n = 57) had macrometastasis. A positive non-SLN was identified after ALND among 18% (n = 7 of 39) with micrometastasis compared with 39% (n = 22 of 57) with macrometastasis (p = 0.04). The size of the SLN metastasis and presence of additional tumor positive non-SLNs corresponds to a positive likelihood ratio of 1.1 for micrometastasis and 1.6 for macrometastasis (95%CI: 0.56 - 0.74). Conclusions: Increased size of tumor in SLN is associated with greater likelihood of non-SLN positivity and should be considered for more aggressive follow-up and therapy.

Safety of gastrointestinal endoscopy in patients with acute coronary syndrome and concomitant gastrointestinal bleeding

BACKGROUND Gastrointestinal bleeding(GIB)is a major concern in patients hospitalized with acute coronary syndrome(ACS)due to the common use of both antiplatelet medications and anticoagulants.Studies evaluating the safety of gastrointestinal endoscopy(GIE)in ACS patients with GIB are limited by their relatively small size,and the focus has generally been on upper GIB and esophago-gastroduodenoscopy(EGD)only.AIM To evaluate the safety profile and the hospitalization outcomes of undergoing GIE in patients with ACS and concomitant GIB using the national database for hospitalized patients in the United States.METHODS The Nationwide Inpatient Sample database was queried to identify patients hospitalized with ACS and GIB during the same admission between 2005 and 2014.The International Classification of Diseases Code,9th Revision Clinical Modification was utilized for patient identification.Patients were further classified into two groups based on undergoing endoscopic procedures(EGD,small intestinal endoscopy,colonoscopy,or flexible sigmoidoscopy).Both groups were compared regarding demographic information,outcomes,and comorbidities.Multivariate analysis was conducted to identify factors associated with mortality and prolonged length of stay.Chi-square test was used to compare categorical variables,while Student’s t-test was used to compare continuous variables.All analyses were performed using SAS 9.4(Cary,NC,United States).RESULTS A total of 35612318 patients with ACS were identified between January 2005 and December 2014.269483(0.75%)of the patients diagnosed with ACS developed concomitant GIB during the same admission.At least one endoscopic procedure was performed in 68%of the patients admitted with both ACS and GIB.Patients who underwent GIE during the index hospitalization with ACS and GIB had lower mortality(3.8%)compared to the group not undergoing endoscopy(8.6%,P<0.001).A shorter length of stay(LOS)was observed in patients who underwent GIE(mean 6.59±7.81 d)compared to the group not undergoing endoscopy(mean 7.84±9.73 d,P<0.001).Multivariate analysis showed that performing GIE was associated with lower mortality(odds ratio:0.58,P<0.001)and shorter LOS(-0.36 factor,P<0.001).CONCLUSION Performing GIE during the index hospitalization of patients with ACS and GIB was correlated with a better mortality rate and a shorter LOS.Approximately twothirds of patients with both ACS and GIB undergo GIE during the same hospitalization.

Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin

BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.

Customizing of Hemodialysates

According to the 22nd edition of "The American Illustrated Medical Dictionary",dialysis[dia=through,apart,across or between;lysis=to loose]is defined as the process of separating crystalloids and colloids in solution by the differences in their rates of diffusion through a semipermeable membrane:crystalloids pass through readily,colloids very slowly or not at all(1).……

Perioperative outcomes and survival of radical cystectomy as a function of body mass index

AIM: To evaluate the perioperative and long term outcomes of cystectomy in obese patients.METHODS: This is a retrospective review of 580 patients for whom radical cystectomy(RC) was performed for primary urothelial bladder cancer between November 1996-April 2013 at a single institution. Body mass index(BMI) was available for 424 patients who were categorized as underweight(< 18.5), normal(18.5-24.9), overweight(25.0-29.9), and obese(≥ 30). Baseline demographics, perioperative outcomes, and survival were assessed. Overall survival(OS) and disease specific survival(DSS) was estimated by Kaplan-Meier method. Medians were compared using the Mann-Whitney U Test. Categorical variables were compared using the χ2 test. A P-value of < 0.05 was considered statistically significant. Statistical analyses were performed using the Software Package for the Social Sciences(SPSS), Version 20(International Business Machines SPSS, Chicago, IL, United States). RESULTS: The median age of all patients was 69 years(inter-quartile range 60-75) and median followup was 23.4 mo(8.7-55.1). Patients were characterized as underweight [9,(2.1%)], normal [113,(26.7%)],overweight [160,(37.8%)], or obese [142,(33.5%)]. Estimated blood loss during RC was higher in the obese group(800 m L) as compared to the normal weight group(500 m L). However, need for transfusion(47.7% vs 52.1%), number of lymph nodes resected(32 vs 30), length of stay(9 d vs 8 d), and 30-d readmission(29.7% vs 25.2%) between obese and normal BMI patients were similar. Obese patients underwent ileal neobladder diversion in 42% of cases, compared to 24% of normal BMI patients(0.003). Normal BMI and obese patients had comparable urinary incontinence(21.4% vs 25.6%, P = 0.343), and need for intermittent catheterization(14.3% vs 5.2%, P = 0.685) at 2 years follow-up. Overall survival was better in obese compared to normal BMI patients on univariate analysis, with median survival of 67 mo vs 37 mo, respectively(P = 0.031). Disease specific survival in these populations followed the same Kaplan Meier curve, with the obese group having a significantly improved OS, P = 0.016. Underweight patients had a significantly worse prognosis, with a median overall survival of 19 mo(P = 0.018). Disease specific survival was significantly worse in the underweight group compared to the obese group, P = 0.007. On multivariate analysis underweight patients remained at increased risk for death(HR = 3.1, P = 0.006), as were older patients(HR = 1.6, P = 0.006), those with multiple nodal metastases(HR = 3.7, P = 0.007), and those who had received neoadjuvant chemotherapy(HR = 2.0, P = 0.015).CONCLUSION: Perioperative outcomes and survival following RC in obese patients is comparable with nonobese patients. Underweight patients have the worst OS and DSS.

Robotic-assisted laparoscopic partial nephrectomy: A comparison of approaches to the posterior renal mass

AIM: To evaluate outcomes of robotic-assisted laparoscopic partial nephrectomy performed for posterior renal tumors via a transperitoneal or retroperitoneal approach.METHODS: Retrospective review was performed for patients who underwent robotic-assisted laparoscopic partial nephrectomy(RALPN) for a posterior renal tumor between 2009-2015. Patient demographic characteristics, operative factors, pathology, oncologic outcomes, renal function, and tumor complexity were obtained. Radius of the tumor, exophytic/endophytic properties of the tumor, nearness of tumor to the collecting system, anterior/posterior position, location relative to the polar line(RENAL) nephrometry scores were calculated. nephrometry scores were calculated. The operative approach was determined by the primary surgeon. RESULTS: A total of 91 patients were identified who underwent RALPN for a posterior renal tumor. Fifty-four procedures were performed via the retroperitoneal(RP) approach, and 37 via the transperitoneal(TP) approach. There were no significant differences in patient factors(race, sex, age and body mass index), RENAL nephrometry scores, tumor size, conversion rates, or margin status. Among procedures performed on-clamp, therewas no significant difference in warm ischemia times. Total operative time(180.7 min for RP vs 227.8 min for TP, P < 0.001), robotic console time(126.9 min for RP vs 164.3 min for TP, P < 0.001), and median estimated blood loss(32.5 m L for RP vs 150 mL for TP, P < 0.001) were significantly lower via the RP approach. Off-clamp RALPN was performed for 31(57.4%) of RP procedures vs 9(24.3%) of TP procedures. Oncologic and renal functional outcomes were equivalent.CONCLUSION: The RP approach to RALPN for posterior renal tumors is superior with regard to operative time and blood loss and the ability to be performed off-clamp.

The role of direct laryngoscopy in the diagnosis of laryngeal cleft

Objective: To identify the presenting features of a laryngeal cleft in children. To compare rigid and flexible endoscopic methods available for identifying laryngeal cleft and determine their utility. Methods: The charts of all patients diagnosed with laryngeal cleft in a tertiary care institution between 2009 and 2010 were evaluated retrospectively for age, gender, comorbidity, presenting features, and results of bedside swallow evaluation. Findings on flexible and direct laryngoscopy, both performed under general anesthesia, were compared. Results: Eleven patients had a diagnosis of laryngeal cleft, confirmed by direct laryngoscopy. Nine of eleven had signs of aspiration on modified barium swallow study (MBSS). Of the eight subjects who underwent flexible laryngoscopy by a pulmonologist, a deep interarytenoid groove was only reported in four cases. In all eleven cases, the arytenoids could be physically separated during direct laryngoscopy, allowing for definitive diagnosis of the cleft and identification of its type and severity. Conclusion: Video swallow studies and flexible laryngoscopy may raise suspicion or even diagnose a laryngeal cleft, however, a laryngeal cleft must be confirmed by direct laryngscopy in which the interarytenoid space is palpated. Furthermore, a patient in whom symptoms persist but no laryngeal cleft is identified on flexible examination should have a direct laryngoscopy to rule out a cleft.

Imaging Analysis of Trabecular Bone Texture Based on the Initial Slope of Variogram of Ultra-Distal Radius Digital X-Ray Imaging: Effects on Bone Mineral Density and Age

Background: When applied to trabecular bone X-ray images, a method for analyzing trabecular bone texture based on the initial slope of variogram (ISV) was used to assess the trabecular bone health. Methodology: Data from more than two hundred subjects were retrospectively studied. For each subject, a DXA (GE Lunar Prodigy) scan of the forearm was performed, and bone mineral density (BMD) value was measured at the location of ultra-distal radius, X-ray digital image of the same forearm was taken on the same day, and ISV value over the same location of ultra-distal radius was calculated. Pearson’s correlation coefficients were calculated to examine the correlation between BMD and ISV of the trabecular bones located at the same ultra-distal radius. ISV values changed with subjects’ age were also reported. Results: The results show that ISV value was highly correlated with the DXA-measured BMD of the same trabecular bone located at the ultra-distal radius. The correlation coefficient between ISV and BMD with the 95% confident was 0.79 ± 0.09. They also demonstrated that the age-related changes in trabecular bone health and differentiated age patterns in males and females, respectively. The results showed that the decrease in BMD was accompanied by a decrease in the initial slope of variogram (ISV). Conclusions: This study suggests that ISV might be used to quantitatively evaluate trabecular health for osteoporosis and bone disease diagnosis.

Primary Intimal Sarcoma of the Pulmonary Vein with Extension into the Left Atrium: A Case Report

Sarcoma originating from the pulmonary veins represents one of the rarest subtypes of sarcoma. We report the case of a 52-year-old woman presenting with cough and scant hemoptysis and ultimately diagnosed with a primary intimal sarcoma of the left inferior pulmonary vein extending into the left lower lobe of the lung. To our knowledge, this is the first reported case of such pathology in the literature. We present the case and critically appraise the literature for sarcomas of the great vessels.

On the immunological limitations of hibernation and synthetic torpor as a supporting technique for astronauts’ radioprotection in deep space missions

Although human hibernation has been introduced as an effective technique in space exploration,there are concerns regarding the intrinsic risks of the approach(i.e.,synthetic torpor)and other factors involved in this procedure.Besides concerns about the brain changes and the state of consciousness during hibernation,an"Achilles heel"of the hibernation is the negative impact of torpor on factors such as the number of circulating leukocytes,complement levels,response to lipopolysaccharides,phagocytotic capacity,cytokine production,lymphocyte proliferation,and antibody production.Moreover,increased virulence of bacteria in deep space can significantly increase the risk of infection.The increased infection risk during long-term space missions with the combined effects of radiation and microgravity affect the astronauts’immune system.With these additional immune system stressors,torpor-induced extraimmunosuppression can be potentially life threatening for astronauts.

Anti-Interference Study on Radiographic Bone Age Estimation Based on Artificial Intelligence Model

In this paper, the interferences of X-ray image noise on a bone age model, Xception model, were studied. We conduct a comparative experiment test according to the output performance of the neural network model using both the original image training and noise-added (Gaussian noise plus salt-pepper noise) training, and analyze the anti-interference ability of the Xception model, hoping to improve it through noise enhancement training and generalize the application ability of the model. The results show that the model trained with noise-added (Gaussian noise plussalt-pepper noise) images can make predictions that are more robust and less affected by the image disturbances, such as image noise.

Image-Based Ultrasound Speed Estimation: Phantom and Human Liver Studies

Purpose: A novel image-based method for speed of sound (SoS) estimation is proposed and experimentally validated on a tissue-mimicking ultrasound phantom and normal human liver in vivo using linear and curved array transducers. Methods: When the beamforming SoS settings are adjusted to match the real tissue’s SoS, the ultrasound image at regions of interest will be in focus and the image quality will be optimal. Based on this principle, both a tissue-mimicking ultrasound phantom and normal human liver in vivo were used in this study. Ultrasound image was acquired using different SoS settings in beamforming channels ranging from 1420 m/sec to 1600 m/sec. Two regions of interest (ROIs) were selected. One was in a fully developed speckle region, while the other contained specular reflectors. We evaluated the image quality of these two ROIs in images acquired at different SoS settings in beamforming channels by using the normalized autocorrelation function (ACF) of the image data. The values of the normalized ACF at a specific lag as a function of the SoS setting were computed. Subsequently, the soft tissue’s SoS was determined from the SoS setting at the minimum value of the normalized ACF. Results: The value of the ACF as a function of the SoS setting can be computed for phantom and human liver images. SoS in soft tissue can be determined from the SoS setting at the minimum value of the normalized ACF. The estimation results show that the SoS of the tissue-mimicking phantom is 1460 m/sec, which is consistent with the phantom manufacturer’s specification, and the SoS of the normal human liver is 1540 m/sec, which is within the range of the SoS in a healthy human liver in vivo. Conclusion: Soft tissue’s SoS can be determined by analyzing the normalized ACF of ultrasound images. The method is based on searching for a minimum of the normalized ACF of ultrasound image data with a specific lag among different SoS settings in beamforming channels.

TRAF2-MLK3 interaction is essential for TNF-α-induced MLK3 activation

混合的系 kinase (MLK3 ) 3 是被肿瘤坏死因素激活的激活 mitogen 的蛋白质 kinase kinase kinase -- 伪(TNF- 伪) 并且明确地在 TNF- 伪刺激上激活 c6 月 N 终端 kinase (JNK ) 。TNF- 伪由激活 MLK3 的机制不被知道。TNF 联系受体的因素(TRAF ) 是被招募到 TNF 受体的细胞质的结束并且调停的改编者分子，包括 JNK 的激活下游的发信号。这里，我们报导 MLK3 与 TRAF2， TRAF5 和 TRAF6 联系；然而，仅仅 TRAF2 能显著地导致 MLK3 的 kinase 活动。到 TRAF 领域并且为到它的 C 终端一半(氨基酸 511-847 ) 的 MLK3 的 TRAF2 地图的相互作用领域。与对方一起的内长的 TRAF2 和响应以一种时间依赖者方式的 TNF- 伪处理的 MLK3 伙伴。在 MLK3 和 TRAF2 之间的协会调停有绑在 MLK3 的 TRAF2 删除异种的 MLK3 激活和竞争以一种剂量依赖者方式稀释 MLK3 kinase 活动，在 TNF- 伪处理上。而且 MLK3 的下游的目标， JNK 被 TNF- 伪以一种 TRAF2 依赖的方式激活。因此，我们在 TRAF2 和 MLK3 之间的直接相互作用为 TNF- 伪 - 被要求的数据表演导致了 MLK3 和它的下游的目标的激活， JNK。

Cardiac Remote Conditioning and Clinical Relevance:All Together Now!

Ac ute myocardial infarction(AMI) is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure(HF) after myocardial infarction(MI) and 50% of these will die within fi ve years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning(IPC) and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia—known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning(RIPC) has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation(spinal and vagal), and electroacupuncture(EA). We discovered and, with others, have elucidated mechanistic aspects of a nonischemic phenomenon we termed remote preconditioning of trauma(RPCT). RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline(EA-like treatment) and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus(when applied at reperfusion). Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms aresimilar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective "conditioning" phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specifi c mediators and effectors of myocardial cell survival, including NF-κB, Stat3/5, protein kinase C, bradykinin, and the mi to K ATP channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

Intersecting pathways in inflammation and cancer: Hepatocellular carcinoma as a paradigm

Viral infection and chemical carcinogens trigger somatic changes resulting in activation of oncogenes during tumor initiation in the development of cancer. However, a critical interaction resides in the synergism between these somatic changes and an inflamed tumor microenvironment where myeloid and hematopoietic cells are subverted to enhance tumor progression. The causative molecular mechanisms leading to the development of hepatocellular cancer remain incompletely understood but appear to result from multiple factors related to direct hepatocyte injury and the ensuing inflammatory changes mediated by the host response to tissue injury, DNA damage, repair of cellular damage, and chronic, repetitive injury. In this review, the molecular and cellular changes that regulate inflammation and tissue repair will be compared to the activated local tumor microenvironment. Cell-cell signaling within this microenvironment that enhances tumor progression and inhibits anti-tumor immunity will be

The ORC Patient/Tumor Classification—A New Approach: A New Challenge with Special Consideration for the Lung

Purpose: The development of malignancy is a life changing concern for many individuals. The classification of the tumor alone does not adequately take into consideration the patient’s physical condition. Thus, a system to classify both the patient and the tumor has been followed-the ORC system. Method: Additional information regarding the patient and their health has been followed by most physicians but not systematically categorized. By using the individuals health information in addition to the TNM classification one can more adequately advise the patient. Thus O-operability, R-resectability, and C-curability are all considered and more appropriately define the patient and his/her tumor condition. Results: The patient’s physical condition must be acceptable for the treatment-whether surgical or nonsurgical. Pulmonary, cardiac, muscular, renal or other disease entities must not be so severe as to prevent treatment (operability). The lesion should be in a location and of a size to afford possible excision-resectability, and the tumor should be potentially curable in order to justify major intervention. Thus, by combining the patient’s specific health status as well as the tumor characteristics (TNM) a better clarification of the treatment, the options, and the prognosis are delineated. Conclusion: When a patient is seen with a tumor-malignant or benign, therapeutic considerations must include the individual’s health status as well as the tumor prior to determining the treatment. Therefore, a system to consider both the health and the tumor is proposed-the ORC system.

Alcohol-induced Wnt signaling inhibition during bone fracture healing is normalized by intermittent parathyroid hormone treatment

Nearly half of orthopaedic trauma patients are intoxicated at the time of injury, and excess alcohol consumption increases the risk for fracture nonunion. Previous studies show alcohol disrupts fracture associated Wnt signaling required for normal bone fracture repair. Intermittent parathyroid hormone(PTH) promotes bone growth through canonical Wnt signaling, however, no studies have investigated the effect of PTH on alcohol-inhibited bone fracture repair. Male C57 BL/6 mice received two-3 day alcohol binges separated by 4 days before receiving a mid-shaft tibia fracture. Postoperatively, mice received PTH daily until euthanasia. Wnt/β-catenin signaling was analyzed at 9 days post-fracture. As previously observed, acute alcohol exposure resulted in a >2-fold decrease in total and the active form of β-catenin and a 2-fold increase in inactive β-catenin within the fracture callus. Intermittent PTH abrogated the effect of alcohol on β-catenin within the fracture callus. Upstream of β-catenin, alcohol-treated animals had a 2-fold decrease in total LRP6, the Wnt co-receptor, which was restored with PTH treatment. Alcohol nor PTH had any significant effect on GSK-3β. These data show that intermittent PTH following a tibia fracture restores normal expression of Wnt signaling proteins within the fracture callus of alcohol-treated mice.

Adjuvant radiotherapy for pathologically advanced prostate cancer improves biochemical recurrence free survival compared to salvage radiotherapy

AIM: To evaluate the long-term outcomes of patients receiving adjuvant and salvage radiotherapy following prostatectomy with adverse pathologic features and an undetectable prostate specific antigen(PSA).METHODS: A retrospective review was performed of patients who received post-prostatectomy radiation at Loyola University Medical Center between 1992 and 2013. Adverse pathologic features(Gleason score ≥ 8, seminal vesicle invasion, extracapsular extension, pathologic T4 disease, and/or positive surgical margins) and an undetectable PSA following prostatectomy were required for inclusion. Adjuvant patients received therapy with an undetectable PSA, salvage patients following biochemical recurrence(BCR). Post-radiation BCR, overall survival, bone metastases, and initiation of hormonal therapy were assessed. Kaplan-Meier time-to-event analyses and stepwise Cox proportional hazards regression(HR) were performed. RESULTS: Post-prostatectomy patients(n = 134) received either adjuvant(n = 47) or salvage(n = 87) radiation. Median age at radiotherapy(RT) was 63 years, and median follow-up was 53 mo. Five-year post-radiation BCR-free survival was 78% for adjuvant vs 50% salvage radiotherapy(SRT)(Logrank P = 0.001). Patients with radiation administered following a detectable PSA had an increased risk of BCR compared to undetectable: PSA > 0.0-0.2: HR = 4.1(95%CI: 1.5-11.2; P = 0.005); PSA > 0.2-1.0: HR = 4.4(95%CI: 1.6-11.9; P = 0.003); and PSA > 1.0: HR = 52(95%CI: 12.9-210; P < 0.001). There was no demonstrable difference in rates of overall survival, bone metastases or utilization of hormonal therapy between adjuvant and SRT patients. CONCLUSION: Adjuvant RT improves BCR-free survival compared to SRT in patients with adverse pathologic features and an undetectable post-prostatectomy PSA.