Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients

Abstract

Background and purpose

We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients.

Materials and methods

Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0–10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires.

Results

In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00).

Conclusion

Acute toxicity after IORT and EB-APBI treatment is acceptable.

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T-614 Promotes Osteoblastic Cell Differentiation by Increasing Dlx5 Expression and Regulating the Activation of p38 and NF-κB

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation has been identified as an important initiator of skeletal damage in RA. Iguratimod (T-614) is an anti-inflammatory agent which has been reported to show the inhibitory effect of bone destruction in RA. However, the role of T-614 in osteoblast differentiation is still not clear. In this study, we intended to find the effect of T-614 on the osteogenesis process. We detected osteogenesis markers and transcription factors associated with osteoblastic lineage and bone formation in the culture of mesenchymal stem cells which differentiate osteoblast. The contents and activity of alkaline phosphatase, levels of collagen type I and bone gla protein, and calcium nodule formation were increased significantly after T-614 treated. Meanwhile, the mRNAs expressions of Osterix and Dlx5 were also found to be increased significantly by real-time PCR. The changes of levels of phosphorylation of p38 and NF-κB were also detected by Western blot. The results showed that T-614 promotes osteoblastic differentiation by increasing the expression of Osterix and Dlx5 and increasing the activation of P38. T-614 could advance the ectopic expression of NF-κB to suppress inflammation, which indirectly inhibits the damage of the osteoblasts.

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Soft tissue balancing in total knee arthroplasty using sensor-guided assessment: is there a learning curve?

Background

Sensor-guided assessment for soft tissue balance in total knee arthroplasty (TKA) has been reported to improve patient satisfaction and self-reported outcome scores. As more surgeons adopt this technology in TKA, we performed this study to identify if there is a learning curve with its use.

Methods

Analysis of a total of 90 consecutive cases was performed in this study. Initial and final intercompartmental pressure differences were recorded before and after knee ligament balancing. The first 45 patients (group 1) were compared to the last 45 patients (group 2) in terms of operative time and the final state of knee balance. A balanced knee was defined as pressure difference between medial and lateral compartments of ≤15 pounds.

Results

Group 1 had 10 unbalanced knees in the final pressure difference assessment, while all cases in group 2 were balanced (P < 0.001). There was no statistically significant difference in mean operative time between the two groups. A scatter plot of intercompartmental pressure difference identified that after 30 cases, the capacity to achieve knee ligament balance improved.

Conclusion

This study suggests that there is a learning curve with the use of sensor-guided assessment in TKA in achieving knee balance; however, the differences noted between initial and final groups were small and may not be of clinical significance.

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Establishing a successful perioperative geriatric service in an Australian acute surgical unit

Background

The purpose of this study was to assess the impact of a perioperative geriatric service (PGS) in an acute surgical unit (ASU) on patient and organizational outcomes.

Methods

Single centre retrospective cohort study. Inclusion criteria were patients over the age of 65 admitted to the ASU between January and June 2014 (pre-PGS) and 2015 (post-PGS). Chart reviews were performed to identify outcomes of interest including in-hospital morbidity and mortality, length of stay (LOS), 30-day representation and mortality.

Results

Geriatric admissions increased by 32% over the two study periods (154 pre-PGS and 203 post-PGS). Surgical intervention increased by 11% (P = 0.01). Significantly more medical complications (14% versus 33%, P < 0.001) were identified after the implementation of the PGS. Recognition of delirium in the over 80s also increased by 57%. Rate of surgical complications was unchanged over the study (28% pre-PGS and 34% post-PGS, P = 0.6). In-hospital (<1%, P = 0.5) and 30-day mortality (<1%, P = 0.6) remained low, as did 30-day representation (10% versus 8%, P = 0.5). A trend towards decreased LOS of 1 day was identified after the implementation of the PGS (P = 0.07).

Conclusion

This study demonstrated successful implementation of a PGS into an ASU. This multi-disciplinary approach has been effective in maintaining low numbers of surgical complications, in-hospital mortality, LOS and patient representations despite an increased number of medical complications. This likely reflects more timely recognition and intervention of medically unwell patients with the PGS.

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Update on mitochondria and muscle aging: all wrong roads lead to sarcopenia

Journal Name: Biological Chemistry
Issue: Ahead of print


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The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through regulation of HOXA7

Journal Name: Biological Chemistry
Issue: Ahead of print


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Determination of selenium during pathogenesis of hepatic fibrosis employing hydride generation and inductively coupled plasma mass spectrometry

Journal Name: Biological Chemistry
Issue: Ahead of print


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Inflammatory Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Stem Cell-Like Characteristics of Cancer Cells in an IL-1β-Dependent Manner

To ensure the safety of clinical applications of MSCs, thorough understanding of their impacts on tumor initiation and progression is essential. Here, to further explore the complex dialog between MSCs and tumor cells, umbilical cord-derived mesenchymal stem cells (UC-MSCs) were employed to be cocultured with either breast or ovarian cancer cells. Though having no obvious influence on proliferation or apoptosis, UC-MSCs exerted intense stem cell-like properties promoting effects on both cancer models. Cocultured cancer cells showed enriched side population, enhanced sphere formation ability, and upregulated pluripotency-associated stem cell markers. Human cytokine array and real-time PCR revealed a panel of MSC-derived prostemness cytokines CCL2, CXCL1, IL-8, and IL-6 which were induced upon coculturing. We further revealed IL-1β, a well-characterized proinflammatory cytokine, to be the inducer of these prostemness cytokines, which was generated from inflammatory UC-MSCs in an autocrine manner. Additionally, with introduction of IL-1RA (an IL-1 receptor antagonist) into the coculturing system, the stem cell-like characteristics promoting effects of inflammatory UC-MSCs were partially blocked. Taken together, these findings suggest that transduced inflammatory MSCs work as a major source of IL-1β in tumor microenvironment and initiate the formation of prostemness niche via regulating their secretome in an IL-1β-dependent manner.

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Liver X Receptor Inverse Agonist SR9243 Suppresses Nonalcoholic Steatohepatitis Intrahepatic Inflammation and Fibrosis

Abnormal metabolism of cholesterol may be a contributing factor in nonalcoholic steatohepatitis (NASH) pathogenesis. Accumulating evidence has shown that liver X receptor (LXR) is closely related to intrahepatic inflammation and fibrosis. In this study, we evaluated the effects of a novel liver-specific LXR inverse agonist, SR9243, on antifibrosis in NASH mice. A high-cholesterol diet was employed to induce NASH in BALB/c mice by either carbon tetrachloride (CCL4) administration or bile-duct ligation (BDL). Once NASH was induced, mice were treated with SR9243 for one month by intraperitoneal (i.p.) injection. Liver tissues were collected to determine the degree of fibrosis and intrahepatic inflammation via pathological examination and QPCR; serum was collected to analyze the plasma lipid levels and liver function by clinical biochemistry. The mice developed hepatic steatosis, severe hepatic inflammation, and fibrosis by BDL or CCL4. Treatment with SR9243 significantly reduced the severity of hepatic inflammation and ameliorated hepatic fibrosis; simultaneously, body weight, serum glucose, and plasma lipid levels were controlled effectively. Our data demonstrate that SR9243 exerts an antifibrotic and anti-inflammatory effect in NASH mice; hence these findings highly suggest that LXR inverse agonist could be therapeutically important in NASH treatment.

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Candida krusei Empyema Thoracis: A Community-Acquired Infection Requiring a High Index of Suspicion

Empyema thoracis is a serious condition characterized by the accumulation of purulent fluid in the pleural cavity, typically following a pneumonia, subdiaphragmatic abscess, or esophageal rupture. Fungal empyema thoracis is a rare form of this condition with especially high mortality, in which the most frequently isolated fungus is Candida spp. This article presents a 74-year-old female with Candida krusei pneumonia and a complicated hospital course, initially presenting with nausea, vomiting, and dysphagia. She was initially suspected to have community-acquired pneumonia and was started on azithromycin and ceftriaxone. Worsening respiratory function led to the diagnosis of hydropneumothorax. Pleural fluid and an independent sample of pus and pleural tissue grew Candida krusei, giving the diagnosis of fungal empyema. With further respiratory deterioration, the patient was intubated and switched to piperacillin/tazobactam and micafungin. Decortication with extensive pleural peel and removal of foul-smelling pus and food particles within the chest was performed. This further lead to confirmation of esophageal perforation, and she was started on voriconazole and meropenem. After developing septic shock, the patient was managed with phenylephrine and vasopressin. Finally, after improving she was weaned off pressors and extubated, followed by an esophagogastroduodenoscopy (EDG) with pneumatic balloon dilation and WallFlex stent placement. This patient's case demonstrated an example of empyema thoracis, which required a high index of suspicion since the presentation was with a community-acquired infection. Candida empyema thoracis may be a complication of operation, gastroesophageal fistula, and spontaneous esophageal rupture. On the other hand, the course of this patient's hospital stay progressed from esophageal perforation to Candida krusei pneumonia, empyema, and pneumothorax. Thus, community-acquired fungal empyema should be considered in patients with respiratory symptoms and suspected esophageal perforation; nevertheless, after a diagnosis of fungal empyema, esophageal perforation should also be ruled out in addition to other causes like pneumonia, subphrenic abscess, and hematogenous spread. Improved communication between clinicians and microbiologists can lead to early diagnosis and a reduction in the morbidity and mortality of this condition.

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Coexistence of Cervical Leiomyosarcoma and Gastric-Type Adenocarcinoma In Situ with Extensive Extension to the Endometrium and Fallopian Tube

Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.

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Mitochondrial Genome Mutations Associated with Myocardial Infarction

Myocardial infarction is one of the clinical manifestations of coronary heart disease. In some cases, the cause of myocardial infarction may be atherosclerotic plaques which occurred in the human aorta. The association of mtDNA mutations with atherosclerotic lesions in human arteries was previously detected by our research group. In this study, we used samples of white blood cells collected from 225 patients with myocardial infarction and 239 control persons with no health complaints. DNA was isolated from the blood leukocyte samples. Then, PCR fragments of DNA were obtained. They contained the investigated regions of 11 mitochondrial genome mutations (m.5178C>A, m.3336T>C, m.652delG, m.12315G>A, m.14459G>A, m.652insG, m.14846G>A, m.13513G>A, m.1555A>G, m.15059G>A, m.3256C>T). According to the obtained results, three mutations of the human mitochondrial genome correlated with myocardial infarction. A positive correlation was observed for mutation m.5178C>A. At the same time, a highly significant negative correlation with myocardial infarction was observed for mutation m.14846G>A. One single-nucleotide substitution of m.12315G>A had a trend towards negative correlation. These mutations can potentially be useful for creating molecular/cellular models for studying the mechanisms of myocardial infarction and designing novel therapies. Moreover, these mutations can possibly be used for diagnostic purposes.

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TGF-β Polymorphisms Are a Risk Factor for Chagas Disease

Transforming growth factor β1 (TGF-β1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF-β1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (−800 G>A, −509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position −509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, −509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population.

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Searching for Clinically Relevant Biomarkers in Geriatric Oncology

Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

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Morbidity Parameters Associated with Gastrointestinal Tract Nematodes in Sheep in Dabat District, Northwest Ethiopia

Gastrointestinal nematode (GIN) infections of sheep and their interaction with selected morbidity parameters were studied in smallholder farms. 120 faecal samples were collected and examined using faecal flotation to determine nematode infection in sheep. Thus, the study demonstrated overall prevalence of 57.5% GIN infections, while the mean faecal egg count (FEC) was 517.5 EPG. The severity of GIN infection was determined based on EPG as a mild infection (EPG 1500), 14.6%. Five genera of nematodes were identified using coproculture: Haemonchus (33.3%), Trichostrongylus (26.7%), Bunostomum (20%), Oesophagostomum (13.3%), and Cooperia (6.7%). A significant difference was observed in the mean FEC among the FC (), FAMACHA© score (), and the BCS of the animals (). FEC was positively correlated with the FAMACHA© score (FS), while FC and BCS were negatively correlated. Thus, FAMACHA© chart can suggest well the severity of nematode infections and can serve as a suitable on-farm tool to identify nematode-infected sheep and gives a guide to identify sheep that need to be treated with an anthelmintic.

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Lymphatic Drainage of Legs Reduces Edema of the Arms in Children with Lymphedema

Objective. The aim of the present study is to report on the reduction of edema of lymphedematous arms just by treating the lower limbs. Methods. A 16-year-old girl reported that she has started having right lower limb edema at the age of three. At age 13, she performed a lymphoscintigraphy that confirmed the diagnosis of primary lymphedema of the four limbs. Recently she sought treatment at the Clínica Godoy in São Jose do Rio Preto where she was submitted to intensive treatment for eight hours per day for five days using manual (Godoy & Godoy technique) and mechanical lymphatic therapy (RA Godoy®) of the lower limbs, cervical lymphatic therapy (cervical stimulation), and the continuous use of a grosgrain stocking. Results. At the end of treatment, reductions in the sizes of both arms and legs were noted even without the use of any specific therapy for the arms. After four years, the size of the arms was normal. Conclusion. Treatment of lymphedema of the legs has systemic repercussions that may lead to the reduction in swelling of other untreated regions of the body.

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Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients). According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm), moderate (CAL 3-4 mm), and severe (CAL > 5 mm) forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease), a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization of CP.

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Relationship between Joint Position Sense, Force Sense, and Muscle Strength and the Impact of Gymnastic Training on Proprioception

The aims of this study were (1) to assess the relationship between joint position (JPS) and force sense (FS) and muscle strength (MS) and (2) to evaluate the impact of long-term gymnastic training on particular proprioception aspects and their correlations. 17 elite adult gymnasts and 24 untrained, matched controls performed an active reproduction (AR) and passive reproduction (PR) task and a force reproduction (FR) task at the elbow joint. Intergroup differences and the relationship between JPS, FS, and MS were evaluated. While there was no difference in AR or PR between groups, absolute error in the control group was higher during the PR task (7.15 ± 2.72°) than during the AR task (3.1 ± 1.93°). Mean relative error in the control group was 61% higher in the elbow extensors than in the elbow flexors during 50% FR, while the gymnast group had similar results in both reciprocal muscles. There was no linear correlation between JPS and FS in either group; however, FR was negatively correlated with antagonist MS. In conclusion, this study found no evidence for a relationship between the accuracy of FS and JPS at the elbow joint. Long-term gymnastic training improves the JPS and FS of the elbow extensors.

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Apparent Diffusion Coefficient of Diffusion-Weighted Imaging in Evaluation of Cervical Intervertebral Disc Degeneration: An Observational Study with 3.0 T Magnetic Resonance Imaging

Aims. To investigate the correlation between the apparent diffusion coefficient (ADC) value and cervical intervertebral disc degeneration in adult symptomatic patients. Methods. A total of 52 symptomatic and 40 healthy volunteers were included. DWI and routine MRI examinations were performed to their cervical spines. The cervical discs (from C2-C3 to C6-C7) were graded according to the Pfirrmann grading system, and ADC values of the nucleus pulposus (NP) were measured. Differences of the ADC values between different genders and anatomic levels were analyzed; the correlation between the ADC value and the Pfirrmann grade was investigated. The cut-off ADC values of each Pfirrmann grade were calculated. Results. The mean ADC value of the NP decreased with increasing Pfirrmann grade (I–V) upon both patients and asymptotic volunteers. The ADC value decreased descendingly from C2-C3 to C5-C6 () and then increased at C6-C7 (). Additionally, the comparison of the ADC values between different genders achieved statistical significance at each anatomical level (), except at C6-C7 (). Significant negative correlations between the ADC value and either age or Pfirrmann grade were observed. Conclusions. Our preliminary findings suggest that the ADC value obtained by DWI can provide a reliable indicator to evaluate the cervical disc degeneration.

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Syphilis-Related Eye Disease Presenting as Bilateral Papilledema, Retinal Nerve Fiber Layer Hemorrhage, and Anterior Uveitis in a Penicillin-Allergic Patient

Purpose. Treponema pallidum is known as the "great masquerader" for its many presentations and ocular findings in patients who are infected and develop secondary and tertiary stage of syphilis. Syphilitic ocular manifestations include uveitis, chorioretinitis, retinitis, vasculitis, vitritis, and panuveitis all with or without decreased visual acuity. Human immunodeficiency virus (HIV) is known to expedite the progression of syphilis when patients are coinfected, thus compounding the potential ophthalmic presentations. This report summarizes the presentation, management, and clinical course of a patient with known HIV and penicillin allergy that presented with bilateral optic nerve edema, retinal hemorrhages, and iritis without vision loss.

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Short-Term Treatment with Esmolol Reverses Left Ventricular Hypertrophy in Adult Spontaneously Hypertensive Rats via Inhibition of Akt/NF-κB and NFATc4

Our group has previously demonstrated that short-term treatment with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). The present study aimed to assess the molecular mechanisms related to this effect. Fourteen-month-old male were treated intravenously with saline as vehicle (SHR) or esmolol (SHR-E) (300 μg/kg/min). Age-matched vehicle-treated male Wistar-Kyoto (WKY) rats served as controls. After 48 hours of treatment, the hearts were harvested and left ventricular tissue was separated and processed for Western blot analysis to determine the levels of Akt, NF-κB, NFATc4, Creb1, Serca2a, Erk1/2, and Sapk/Jnk. Biomarkers of oxidative stress, such as catalase, protein carbonyls, total thiols, and total antioxidant capacity were evaluated. Esmolol reversed the levels of p-NFATc4, p-Akt, and p-NF-κB in SHRs to the phospholevels of these proteins in WKY rats without modifying p-Erk1/2, p-Sapk/Jnk, p-Creb1, or Serca2a in SHR. Compared with SHR, esmolol increased catalase activity and reduced protein carbonyls without modifying total thiols or total antioxidant capacity. Short-term treatment with esmolol reverses LVH in aged SHRs by downregulation of Akt/NF-κB and NFATc4 activity. Esmolol treatment also increases catalase activity and reduces oxidative stress in SHRs with LVH.

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Association of Maternal and Fetal Single-Nucleotide Polymorphisms in Metalloproteinase (MMP1, MMP2, MMP3, and MMP9) Genes with Preeclampsia

Background. Metalloproteinases (MMPs) play a pivotal role during the process of trophoblast invasion and placentation. The appearance of five functional single-nucleotide polymorphisms (SNP) in the genes of the metalloproteinases most commonly implicated in the implantation process may influence the development of preeclampsia. Methods. Blood samples were collected from 86 mothers and 86 children after preeclampsia and 85 mothers and 85 children with uncomplicated pregnancies. The distribution of genotypes for −1607 1G/2G MMP1, −735 C/T MMP2, −1306 C/T MMP2, −1171 5A/6A MMP3, and −1562C/T MMP9 polymorphisms was determined by RFLP-PCR. Results. The occurrence of 1G/1G MMP1 or 5A/5A MMP3 genotype in the mother or 1G/1G MMP1 or 5A/6A MMP3 genotype in the child is associated with preeclampsia development. Moreover, simultaneous maternal and fetal 1G/1G homozygosity increases the risk of preeclampsia development 2.39-fold and the set of maternal 5A/5A and fetal 5A/6A MMP3 genotypes by over 4.5 times. No association between the carriage of studied MMP2 or MMP9 polymorphisms and the predisposition to preeclampsia was found. Conclusion. The maternal 1G/1G MMP1 and 5A/5A MMP3 and fetal 1G/1G MMP1 and 5A/6A MMP3 gene polymorphisms may be strong genetic markers of preeclampsia, occurring either individually or together.

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Human Epidermal Growth Factor Receptor 2 Status in Gastric Carcinomas with Distinctive Prevalent Cribriform Component

Objectives. A cribriform architectural pattern has been reported in 9% of one unselected consecutively collected series of gastric carcinomas (GC) with unfavourable prognostic outcome. Taking into consideration the biological relevance of the human epidermal growth factor receptor 2 (HER2) status, we have analyzed a cohort of GC with a cribriform component more than 40% (CGC) to evaluate the HER2 amplification rate as a potential target for therapy with trastuzumab. Results. HER2 overexpression was encountered in 21 of 100 (21%) GC; a progressive increase in HER2 amplification was appreciated moving from non-CGC (20.6%) towards CGC cases (21.6%), although this difference does not reach a statistical significance. Nevertheless, either in univariate or in multivariate analyses, stage and HER2 status showed a significant value (

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A Challenging Case of Acute Mercury Toxicity

Background. Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. Clinical Case. A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters) of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Conclusion. Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices.

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Metastases to Both Parotid Glands Six and Twelve Years after Resection of Renal Cell Carcinoma

Metastases of renal cell carcinoma (RCC) involving the parotid gland are very rare. We present to our knowledge the first case of a 74-year-old woman with metastases of an RCC which affected both parotid glands six and twelve years following curative therapy.

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Cortical Bone Trajectory Screws in Posterior Lumbar Interbody Fusion: Minimally Invasive Surgery for Maximal Muscle Sparing—A Prospective Comparative Study with the Traditional Open Technique

Introduction. A prospective comparative study between classical posterior interbody fusion with peduncular screws and the new technique with divergent cortical screws was conducted. Material and Methods. Only patients with monosegmental degenerative disease were recruited into this study. We analyzed a cohort of 40 patients treated from January 2015 to March 2016 divided into 2 groups (20 patients went to traditional open surgery and 20 patients under mini-invasive strategy). Primary endpoints of this study are fusion rate and muscular damage; secondary endpoints analyzed were three different clinical scores (ODI, VAS, and EQ) and the morbidity rate of both techniques. Results. There was no significant difference in fusion rate between the two techniques. In addition, a significant difference in muscular damage was found according to the MRI evaluation. Clinical outcomes, based on pain intensity, Oswestry Disability Index status, and Euroquality-5D score, were found to be also statistically different, even one year after surgery. This study also demonstrated a correlation between patients' muscular damage and their clinical outcome. Conclusions. Cortical bone trajectory screws would provide similar outcomes compared to pedicle screws in posterior lumbar interbody fusion at one year after surgery, and this technique represents a reasonable alternative to pedicle screws.

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Impact of United States Preventive Services Task Force Recommendations on Utilization of Prostate-specific Antigen Screening in Medicare Beneficiaries

Background: Previous studies assessing the impact of United States Preventive Services Task Force (USPSTF) recommendations on utilization of prostate-specific antigen (PSA) screening have not investigated longer-term impacts of 2008 recommendations nor have they investigated the impact of 2012 recommendations in the Medicare population. This study aimed to evaluate change in utilization of PSA screening, post-2008 and 2012 USPSTF recommendations, and assessed trends and determinants of receipt of PSA screening in the Medicare population. Methods: This retrospective study of male Medicare beneficiaries utilized Medicare Current Beneficiary Survey data and linked administrative claims from 2006 to 2013. Beneficiaries aged ≥65 years, with continuous enrollment in parts A and B for each year they were surveyed were included in the study. Beneficiaries with self-reported/claims-based diagnosis of prostate cancer were excluded. The primary outcome was receipt of PSA screening. Other measures included age groups (65 to 74 and ≥75), time periods (pre-2008/post-2008 and 2012 recommendations), and sociodemographic variables. Results: The study cohort consisted of 11,028 beneficiaries, who were predominantly white (87.56%), married (69.25%), and unemployed (84.4%); 52.21% beneficiaries were aged ≥75. Declining utilization trends for PSA screening were observed in men aged ≥75 after 2008 recommendations and in both age groups after 2012 recommendations. The odds of receiving PSA screening declined by 17% in men aged ≥75 after 2008 recommendations and by 29% in men aged ≥65 after 2012 recommendations. Conclusions: The 2008 and 2012 USPSTF recommendations against PSA screening were associated with declines in utilization of PSA screening during the study period. USPSTF recommendations play a significant role in affecting utilization patterns of health services. E.O. receives funding from Bayer Healthcare Pharmaceuticals and Pfizer Inc. and consults Novo Nordisk. M.V.M. is a PCORI Patient Engagement Advisory Panel Member. R.K. declares no conflicts of interest. Reprints: Rahul Khairnar, MS, BPharm, 220 N Arch Street, 12th Floor, Saratoga Office Building, Baltimore, MD 21201. E-mail: rahul.khairnar@umaryland.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study

Objectives: Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored. Materials and Methods: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review. Results: Twenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue. Conclusions: Pembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/1hexVwJ Presented in part at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 3 to 7, 2016, Chicago, IL. Supported by Merck & Co. Inc., Kenilworth, NJ. R.B.C., S.V.L., P.T.: analysis and acquisition of the data and interpretation of the results. J.P.D., J.G., S.D., C.L.T., E.E., B.K.: acquisition of the data and interpretation of the results. T.D., S.A.P-P., A.P.A., R.-L.H., D.D., A.V., J.W.: acquisition of the data. S.S.: analysis of the data and interpretation of the results. J.C.: conception, design or planning of the study, analysis of the data and interpretation of the results. All authors: critically reviewed or revised the manuscript for important intellectual content and approved the final manuscript for submission. R.B.C. received a research grant from Merck & Co. Inc., paid to the University of Pennsylvania and was a member of an advisory board for Bristol-Myers Squibb. T.D. received research funding from Taiho, Novartis, Merck Serono, Astellas Pharma, Merck & Co. Inc., Janssen, Boehringer Ingelheim, Takeda, Pfizer, Eli Lilly Sumitomo Group, Chugai Pharma, Bayer, Kyowa Hakko Kirin, Daiichi Sankyo, Celgene, and Amgen. S.A.P-P. received research funding to the institution from the National Institutes of Health (grant number P30CA016672). S.V.L. was a member of an advisory board for Genentech, Boehringer Ingelheim, Celgene, Ariad, and Pfizer. J.G. received a research grant paid to the institution from Merck & Co. Inc., AstraZeneca, Novartis, Bristol-Myers Squibb, Karyopharm, and Pfizer. A.P.A. received a research grant from Merck & Co. Inc., paid to the institution. C.L.T. was a member of an advisory board for Merck & Co. Inc. S.S., J.C. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ. P.T. is currently an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, and was previously an employee of Boehringer Ingelheim, from May 2012 to August 2014, and owned stock in Gilead from June 2014 to June 2016. J.P.D., S.D., R.-L.H., D.D., A.V., E.E., J.W., B.K. declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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How Surrogate Decision-Makers for Patients With Chronic Critical Illness Perceive and Carry Out Their Role

Objectives: Family members commonly make medical decision for patients with chronic critical illness. This study examines how family members approach this decision-making role in real time. Design: Qualitative analysis of interviews with family members in the intervention arm of a randomized controlled communication trial. Settings: Medical ICUs at four U.S. hospitals. Participants: Family members of patients with chronic critical illness (adults mechanically ventilated for ≥ 7 d and expected to remain ventilated and survive for ≥ 72 hr) who participated in the active arm of a communication intervention study. Interventions: Family members participated in at least two content-guided, informational, and emotional support meetings led by a palliative care physician and nurse practitioner. Measurements and Main Results: Grounded theory was used for qualitative analysis of 66 audio recordings of meetings with 51 family members. Family members perceived their role in four main ways: voice of the patient, advocate for the patient, advocate for others, and advocate for oneself. Their decision-making was characterized by balancing goals, sharing their role, keeping perspective, remembering previous experiences, finding sources of strength, and coping with various burdens. Conclusions: Family members take a multifaceted approach as they participate in decision-making. Understanding how surrogates perceive and act in their roles may facilitate shared decision-making among clinicians and families during critical care. The views expressed here do not necessarily reflect the policies of the National Institutes of Health. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported, in part, by Administrative Supplement R01 NR012413-02S1 from the Office of the Director, National Institutes of Health, to R01 NR012413 from the National Institute of Nursing Research and by the Department of Bioethics in the Clinical Center, an intramural program of the National Institutes of Health. Additional funding received from the Medical Research Scholars Program, an enrichment program for medical, dental, and veterinary students at the National Institutes of Health. Drs. Nelson, Hanson, Cox, Carson, Chai, Keller, Tulsky, and Danis received support for article research from the National Institutes of Health (NIH). Dr. Carson and Ms. Keller's institution received funding from National Institute of Nursing Research (NINR). Dr. Chai's institution received funding from NIH/NINR R01 NR 012413. Dr. Tulsky received funding Recap Information Systems (he has 5% ownership, which makes audio analysis software; this product had nothing to do with the writing of this paper or this research). Dr. Li disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: mdanis@nih.gov Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Cancers, Vol. 10, Pages 55: Towards a Clinical Decision Support System for External Beam Radiation Oncology Prostate Cancer Patients: Proton vs. Photon Radiotherapy? A Radiobiological Study of Robustness and Stability

Cancers, Vol. 10, Pages 55: Towards a Clinical Decision Support System for External Beam Radiation Oncology Prostate Cancer Patients: Proton vs. Photon Radiotherapy? A Radiobiological Study of Robustness and Stability

Cancers doi: 10.3390/cancers10020055

Authors: Seán Walsh Erik Roelofs Peter Kuess Yvonka van Wijk Ben Vanneste Andre Dekker Philippe Lambin Bleddyn Jones Dietmar Georg Frank Verhaegen

We present a methodology which can be utilized to select proton or photon radiotherapy in prostate cancer patients. Four state-of-the-art competing treatment modalities were compared (by way of an in silico trial) for a cohort of 25 prostate cancer patients, with and without correction strategies for prostate displacements. Metrics measured from clinical image guidance systems were used. Three correction strategies were investigated; no-correction, extended-no-action-limit, and online-correction. Clinical efficacy was estimated via radiobiological models incorporating robustness (how probable a given treatment plan was delivered) and stability (the consistency between the probable best and worst delivered treatments at the 95% confidence limit). The results obtained at the cohort level enabled the determination of a threshold for likely clinical benefit at the individual level. Depending on the imaging system and correction strategy; 24%, 32% and 44% of patients were identified as suitable candidates for proton therapy. For the constraints of this study: Intensity-modulated proton therapy with online-correction was on average the most effective modality. Irrespective of the imaging system, each treatment modality is similar in terms of robustness, with and without the correction strategies. Conversely, there is substantial variation in stability between the treatment modalities, which is greatly reduced by correction strategies. This study provides a 'proof-of-concept' methodology to enable the prospective identification of individual patients that will most likely (above a certain threshold) benefit from proton therapy.

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