Search

Peritonitis is a serious complication of Peritoneal Dialysis (PD). At our hospital, PD- related peritonitis is treated empirically with intraperitoneal cefazolin plus ceftazidime.

Rationale and objective Sleep problems affect more than half of patients receiving dialysis and are associated with increased risk of mortality, cardiovascular events, depression and impaired functioning and quality of life. Symptoms such as fatigue and exhaustion may be attributed to sleep problems or sleep disorders, as well as the burden of kidney disease and treatment. This study aims to describe the patient perspectives on the reasons, impact and management of sleep problems in dialysis. Study design Systematic review and thematic synthesis of qualitative studies that report patient experience and perspectives on sleep in dialysis. Setting and population Patients receiving dialysis. Search strategy and sources MEDLINE, Embase, PsycINFO, CINAHL, reference lists and PhD dissertations were searched from inception to August 2019. Data extraction All text from the results/conclusion of the primary studies. Analytical approach Thematic synthesis. Results We included 48 studies involving 1156 participants from 16 countries. We identified six themes: dominating demands of treatment (with subthemes of: demanding and relentless schedule, regret for wasted time); scheduling and control (managing sleep routines, napping and nocturnal sleep disruption, meditative aids); disruptions due to dialysis (unsettled sleep, hypervigilance and worry); symptoms depriving sleep (difficulty falling asleep, constant waking); overwhelmed and without choice (futility of sleep, uncontrollable exhaustion, restlessness is irrepressible); and as a coping mechanism (avoiding anxiety, alleviating symptoms, combating boredom). Limitations Most studies were conducted in high-income, English-speaking countries. Conclusion The treatment and symptom burden of dialysis disrupts and deprives patients of sleep, which leads to overwhelming and uncontrollable exhaustion. Better management of symptoms and effective strategies to manage sleep routines may improve sleep quality for better overall health in patients receiving dialysis.

Background: Intraperitoneal (IP) vancomycin is recommended as one of the treatment options for gram-positive coverage in the management of peritoneal dialysis (PD)-associated peritonitis. There is a lack of literature supporting the optimal dose and approach to vancomycin therapeutic drug-level monitoring. Methods: A retrospective chart review was conducted using the BC Renal Agency PROMIS Database and our hospital records from 1 June 2011 to 1 July 2019. Adult patients with PD-associated peritonitis who received IP vancomycin and had at least one serum vancomycin level drawn were included. All patients received a loading dose of 30 mg/kg, which was repeated every 3–5 days depending on PD modality. Serum vancomycin levels were drawn prior to the second vancomycin dose, then at the discretion of the prescriber. The primary end point was the rate of therapeutic serum vancomycin levels ≥15 mg/L. Results: Twenty-three episodes of PD-associated peritonitis in 20 patients met the eligibility criteria. Only 15/23 serum vancomycin levels were drawn appropriately after the first dose. Sixty per cent of these levels were subtherapeutic at Conclusions: An IP vancomycin regimen of 30 mg/kg every 3–5 days resulted in subtherapeutic serum vancomycin levels in most patients following the loading dose but therapeutic levels thereafter. A large percentage of vancomycin levels were drawn inappropriately due to misalignment of outpatient follow-up visits and timing of blood work.

Objective To evaluate the relationship between the timing of infant cereal introduction between 4 and 6 months of age and growth and dietary intake in later childhood. Study design A longitudinal cohort study was conducted among healthy children 0-10 years of age participating in The Applied Research Group for Kids cohort study between June 2008 and August 2019 in Toronto, Canada. Results Of 8943 children included, the mean (SD) age of infant cereal introduction was 5.7 (2.1) months. In the primary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.17 greater body mass index z score (95% CI 0.06-0.28; P = .002) and greater odds of obesity (OR 1.82; 95% CI 1.18-2.80; P = .006) at 10 years of age. In the secondary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.09 greater height-for-age z score (95% CI 0.04-0.15; P = .002) at 1 year of age, an association that was not observed at 5 or 10 years of age. Children who were introduced to infant cereal at 4 vs 6 months had greater nutrition risk which was primarily determined by a less-favorable eating behavior score at 18 months to 5 years of age (0.18 units higher; 95% CI 0.07-0.29; P = .001). Conclusions Introduction of infant cereal at 4 vs 6 months was associated with greater body mass index z score, greater odds of obesity, similar height-for-age z score, and less favorable eating behavior. These findings support recommendations for introducing solid food around 6 months of age.

This study explored short-term healthcare costs of men managed with observation strategies (OBS) vs immediate treatment (IMT) for favorable risk prostate cancer (PCa) from the Geisinger Health System, a single integrated health system in Pennsylvania, as evidence from the community setting is limited.A retrospective cohort study was conducted using electronic health records from men aged ≥40 years diagnosed with favorable risk PCa (T1 or 2, PSA ≤15 ng/mL, Gleason ≤7 [3 + 4]) between January 2005 and October 2013. Prostate-specific healthcare costs were compared between the OBS and IMT cohorts in men with ≥3 years of follow-up and available linked claims data. Sub-group analyses focused on those men with low-risk PCa (T1-2a, PSA ≤10 ng/mL, Gleason ≤6). Sensitivity analysis stratified the study sample in three cohorts: OBS, switched from OBS to definitive treatment (OBS switch), and IMT.A total of 352 patients were included (OBS = 70 and IMT = 282). Compared with IMT, OBS resulted in significantly lower cumulative PCa-related healthcare costs for the first 3 years ($15,785 vs $23,177; p-value.001). The main cost drivers were outpatient procedures. The OBS cohort had the lowest incremental PCa-related healthcare costs in the first 3 years (OBS: $5,011 vs OBS switch: $26,040, net cost savings = $21,029, p .001; OBS: $5,011 vs IMT: $24,064, net cost savings = $19,053, p .001).In favorable risk PCa, half of the patients who initially chose OBS eventually underwent treatment after their PCa diagnosis. As expected, OBS was associated with reduced disease management costs compared with IMT.

To determine the association between cow's milk-fat and non-high-density lipoprotein (non-HDL) cholesterol, a marker of cardiovascular disease (CVD) risk in young children, and whether this association is mediated by the typical volume of cow's milk consumed.A longitudinal study in 2- to 8-year-old children (n = 2890) was conducted through The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Generalized estimating equations were used to examine the relationship between parent-reported cow's milk-fat percentage intake and serum non-HDL cholesterol concentrations as well as having high non-HDL cholesterol (≥3.75 mmol/L [145 mg/dL]), adjusting for covariates including age, sex, body mass index z score, breastfeeding duration, mother's ethnicity, and parental history of CVD. Bootstrap resampling (10 000 repetitions) was used to assess whether typical volume consumed mediated the association between cow's milk-fat percentage and non-HDL cholesterol.In total, 156 (5.4%) had high non-HDL cholesterol. Each percent increase in cow's milk-fat was associated with a 0.035 mmol/L (1.35 mg/dL) (P .001) and 0.024 mmol/L (0.92 mg/dL) (P = .01) increase in non-HDL cholesterol, unadjusted and adjusted for covariates respectively. Cow's milk-fat percentage was not associated with greater odds of having high non-HDL cholesterol. Volume of cow's milk partially mediated the association between cow's milk-fat percentage and non-HDL cholesterol, accounting for 28% of the relationship (P .001).Consumption of higher-fat cow's milk was associated with a small increase in non-HDL cholesterol but not greater odds of having high non-HDL cholesterol. Further research is needed to assess this relationship with other CVD risk factors in young children.ClinicalTrials.gov: NCT01869530.

Background The objective of this study was to describe overall survival and the management of men with favorable risk prostate cancer (PCa) within a large community-based health care system in the United States. Methods A retrospective cohort study was conducted using linked electronic health records from men aged ≥40 years with favorable risk PCa (T1 or 2, PSA ≤15, Gleason ≤7 [3 + 4]) diagnosed between January 2005 and October 2013. Cohorts were defined as receiving any treatment (IMT) or no treatment (OBS) within 6 months after index PCa diagnosis. Cohorts’ characteristics were compared between OBS and IMT; monitoring patterns were reported for OBS within the first 18 and 24 months. Cox Proportional Hazards models were used for multivariate analysis of overall survival. Results A total of 1425 men met the inclusion criteria (OBS 362; IMT 1063). The proportion of men managed with OBS increased from 20% (2005) to 35% (2013). The OBS group was older (65.6 vs 62.8 years, p

To examine the association between body mass index (BMI) and iron deficiency in early childhood, while considering the influence of low-grade systemic inflammation.Healthy children ages 1-3 years were included in a cross-sectional analysis. Age- and sex-standardized World Health Organization BMI z score (zBMI) was calculated using height/length and weight measurements; iron status was assessed by serum ferritin; inflammation was assessed by C-reactive protein (CRP). Children with CRP ≥10 mg/L were excluded because this may indicate acute systemic inflammation. Adjusted multivariable regression analyses were used to investigate the association between zBMI and both serum ferritin (µg/L), and iron deficiency (serum ferritin12 µg/L). We performed prespecified subgroup analyses according to CRP level (normal [≤1.0 mg/L] and low-grade inflammation [1.0 mg/L to10.0 mg/L]).Of 1607 children included, 20% were categorized as with zBMI1, 13% had iron deficiency, and 18% had low-grade inflammation. Higher zBMI was associated with lower serum ferritin (-1.51 µg/L, 95% CI -2.23, -0.76, P .0001) and increased odds of iron deficiency (OR 1.28, 95% CI 1.10, 1.50, P = .002). Though there was no interaction between zBMI and CRP for the adjusted linear regression model (P = .79) or logistic regression model (P = .43), children with low-grade inflammation had a higher serum ferritin (P .0001).Higher zBMI is associated with increased risk for iron deficiency in children between 1 and 3 years, and should be considered as a risk factor in targeted screening. Further research is needed to better understand the relationship between serum ferritin and CRP for children in all weight categories.ClinicalTrials.gov: NCT01869530.

The inaugural Youth Olympic Games 2010 was one of the major sporting events held in Singapore. It brought together 3,600 young athletes from 295 countries to compete in 26 sport events. Conducted during the Games, this study sought to evaluate the impact of the Games on local residents by using a total of 34 impact statement items. An exploratory factor analysis was conducted to categorize the impact statements under a smaller number of meaningful factors. Specifically, the impact statement items related to the positive impact were categorized under the following three factors: Long-Term Social Benefits to Singapore, Tourism Benefits, and Economic Benefits. The impact statements pertaining to the negative impact were placed under the following three factors: Quality of Life, Social Behavior, and Preparation for the Games. A cluster analysis was also performed: there were three clusters of residents—Enthusiasts, Enthusiasts With Reservations, and Skeptics. In general, residents were supportive of the Games and perceived the Games to have a positive impact on the country. But there are negative perceptions of the Games too, such as its negative impact on the environment, the inconveniences created, and the disruptiveness to their lives.

The Formula 1 Grand Prix was held in Singapore for the first time in September 2008. While Singapore had previous experience hosting international events, nothing in the past could be compared to this inaugural event because it brought with it a unique set of impacts, as evidenced by past research into car races held elsewhere. For this reason, this study explores how this major motor sport event impacted its host residents through their perceptions of social-cultural aspects. This is important because it can affect the well-being and quality of the life of local residents, two necessary antecedents for their continued support of the car race in the future. A survey of 96 residents was conducted to elicit responses to host residents' perceptions of social-cultural impacts of the F1. Chi-square analysis was used to explore relationships between different types of respondents and their perceived social-cultural impacts. Residents were largely homogenous with regard to attitudes toward the positive and negative impacts, although there were more discrepancies associated with the negative issues. Results were compared to previous studies of car race events and social exchange and social representation theories were used to help contextualize the data. While residents largely supported the F1 event suggestions were provided so as to better manage the social-cultural impacts.

The inhibitors of the mammalian target of rapamycin (mTOR) improve outcomes in patients with advanced renal cell carcinoma. These agents are associated with unusual class-adverse events that represent a challenge to the clinician, making it critical to recognize and treat them appropriately. This study aims to highlight the clinical management of these toxicities by presenting evidence from the literature and suggesting treatment recommendations. A critical review of the literature is performed and a summary of the most relevant emergent toxicities and their management is presented. Treatment recommendations of metabolic disturbances induced by mTOR inhibitors, such as hypophosphatemia, hyperglycemia, and hyperlipidemia along with the management of drug-induced pneumonitis and possible pharmacological interactions are presented. Most of these toxicities, if recognized and treated accordingly, should resolve with minimal impact on patients' quality of life and in the efficacy of this anticancer therapy. Oncologists should be familiar with the recognition and appropriate medical management of these clinical scenarios.

Usual interstitial pneumonia (UIP) is characterized by extracellular matrix deposition and the development of pulmonary fibrosis. Fibroblastic foci found in the lung are believed to represent an early stage in the evolution of this disease.To compare gene expression profiles in different components of lung tissue (fibroblastic foci, adjacent epithelium, and areas of type 2 pneumocyte hyperplasia) from patients with UIP, and contrast these profiles to distal, uninvolved (control) alveolar tissue from patients undergoing lung resection for cancer.Lung resection tissue (UIP, n = 11; controls, n = 11) was snap-frozen for subsequent laser capture microdissection, followed by mRNA extraction, linear amplification, and quantitative real-time polymerase chain reaction.In patients with UIP, tissue inhibitor of matrix metalloprotease-1 and matrix metalloprotease (MMP)-2 gene expression was up-regulated within the fibroblastic foci compared with the overlying epithelium (p = 0.03, p = 0.02), and to control alveoli (p = 0.001, p = 0.04), respectively. MMP-9 and MMP-7, as well as osteopontin, were up-regulated in fibroblastic foci (p = 0.01, p = 0.08, p = 0.08), the adjacent epithelium (p = 0.001, p = 0.001, p = 0.03), and the hyperplastic type 2 pneumocytes (p = 0.02, p = 0.001, p = 0.08), respectively, compared with control alveoli.Altered gene expression of important profibrotic mediators in the different cellular lung compartments in patients with UIP likely plays an important role in pathogenesis of the deranged extracellular matrix deposition and subsequent fibrosis in this condition.

The current study retrospectively reviewed the cases of 68 patients who had undergone total laryngectomy and tracheoesophageal puncture (TEP) over a 16-year period. Fifty-one patients underwent primary TEP and 17 underwent secondary TEP. Nearly 80% of patients who received TEP at the time of laryngectomy achieved excellent voice quality perceptually. In contrast, only 50% of secondary TEP patients achieved excellent voice ratings. This difference was statistically robust (p = 0.03). Although both surgical and prosthesis-related complications occurred more frequently following primary TEP, statistically significant differences were not achieved. Neither pre- nor postoperative radiotherapy had any effect on voice restoration or complication rates. Based on these data, primary TEP may be preferable for several reasons, including a greater likelihood of successful voice restoration, a shorter duration of postoperative aphonia, and the elimination of the need for a second operation and interim tube feedings.

Objective To evaluate the association between breastfeeding duration and early childhood cardiometabolic risk. Study design A cross-sectional study of 1539 healthy children, 3-6 years of age, recruited through The Applied Research Group for Kids! practice-based research network between October 2009 and August 2015. Adjusted multivariable linear regression was used to examine the association between breastfeeding duration and cardiometabolic risk z score and individual cardiometabolic risk factors of waist circumference, systolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides. Results The mean breastfeeding duration was 12.5 months (SD = 8.4). Breastfeeding duration was associated with lower cardiometabolic risk z score (beta = −0.03; 95% CI −0.05, −0.01). In analysis of cardiometabolic risk factors, each additional 3 months of breastfeeding was associated with a 0.13 cm (95% CI −0.20, −0.05) lower waist circumference and 0.16 mm Hg (95% CI −0.30, −0.02) lower systolic blood pressure. Compared with children who breastfed for 6-12 months, those who breastfed for 12-24 months had a lower systolic blood pressure of 1.07 mm Hg (95% CI −2.04, −0.10). There was no association between breastfeeding duration and cardiometabolic risk for those who breastfed beyond 24 months. Conclusions Breastfeeding duration is associated with lower cardiometabolic risk, although the magnitude of association is small. Causation cannot be inferred. Breastfeeding beyond 24 months may not have an added benefit for cardiometabolic health.

654 Background: Guidelines for managing patients with metastatic colorectal cancer (mCRC) were updated in Denmark in 2013, and anti-epidermal growth factor receptor (EGFR) inhibitors were promoted from third-line to first-line treatment for KRAS wildtype mCRC patients. As a result, more patients became eligible for EGFR antibody therapy. Weexamined KRAS testing practice among patients with mCRC who received systemic cancer treatment in Denmark during 2009-2013. Methods: We linked data from several population registries with nationwide coverage - the Danish Cancer Registry, the Danish National Patient Registry, and the Danish National Pathology Registry - to identify patients diagnosed with mCRC (primary or recurrent) between 2009 and 2013, their systemic cancer treatment, and their KRAS testing status. We obtained all KRAS test results through 2014 and calculated proportions of KRAS-tested patients by year of mCRC diagnosis. Results: There were 7,245 mCRC patients, among whom 4,272 (59%) had a record of systemic cancer treatment within 6 months of mCRC diagnosis and were included in the analysis. The proportion of men was 57%; median age at mCRC diagnosis was 67 years (range 20-94 years). Overall, 2,099/4,272 (49%) of the treated mCRC patients had a recorded KRAS test result, with similar proportions for patients with primary and recurrent mCRC. Among patients diagnosed with mCRC in 2009, the proportion with a recorded KRAS test result was 374/900 (42%). Corresponding proportions for patients diagnosed in 2010, 2011, 2012, and 2013 were 411/891 (46%), 457/870 (52%), 430/807 (53%), and 427/804 (53%). Conclusions: Among patients in Denmark diagnosed with mCRC who received systemic cancer treatment, the proportion of patients with a KRAS test result recorded in the Danish National Pathology Registry increased from 2009 to 2013. This may have resulted from increased testing or increased recording, or both.

A female patient with malignant hyperthermia experiencing arrhythmias, temperature elevation, and muscle spasm is described. Diagnosis was confirmed by muscle biopsy. Complications can be prevented with early identification and treatment with dantrolene. Elective surgery can be managed safely with careful team planning. (J GYNECOL SURG 12:61, 1996)

Right-sided diverticulitis remains an exceedingly rare condition in the pediatric population. The clinical presentation mimics acute appendicitis, and the correct diagnosis is often difficult to make prior to operative exploration. We report two cases of cecal diverticulitis, and discuss the diagnosis and management of this disease, with a review of the literature.

Antibiotics remain the cornerstone of treatment for infectious diseases, but their excessive use has resulted in the emergence of resistant strains of bacteria—an ever-increasing problem among hospitalized patients. The inappropriate use of antibiotics can also cause severe bloodstream infections and a potentially devastating condition known as pseudomembranous colitis. These complications are thought to arise from alterations in the microbial flora that populate intestinal mucosal surfaces, leading to the overgrowth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus (VRE), Acinetobacter species, Pseudomonas aeruginosa , and Clostridium difficile . Using high-throughput DNA sequencing technologies, Ubeda et al. now characterize the antibiotic-induced changes in the intestinal flora as well as the effects of these changes on intestinal colonization and bloodstream invasion by VRE. The researchers treated mice with various antibiotic regimens and then harvested stool samples and intestinal contents for analysis. They found that antibiotic treatment decreased total bacterial density and dramatically altered the bacterial composition of the small and large intestines. The frequency of bacteria from the Clostridium and Enterococcus families significantly increased, an effect that persisted even after cessation of therapy. Concomitantly, populations that prevent VRE colonization, such as the Lactobacilli and Bacteroides species, were lost and did not recover for up to two months after cessation of antibiotic treatment. Lastly, in human patients undergoing bone marrow transplantation, the predominance of Enterococcus in the intestinal flora preceded bloodstream infection with VRE. The findings of this study demonstrate the dramatic changes in microbial diversity after antibiotic therapy, with loss of normal bacterial populations and overwhelming expansion of resistant strains such as VRE. These alterations in the intestinal flora not only predispose patients to invasive bloodstream infections but have also been implicated in the pathogenesis of obesity and inflammatory bowel diseases. Because intestinal colonization by pathogenic strains of bacteria precedes their invasion into the bloodstream, using high-throughput DNA sequencing technologies to characterize the microbial composition in the intestines may help us to identify patients at risk for developing systemic infections. C. Ubeda et al ., Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J. Clin. Invest. 120 , 4332–4341 (2010). [[Full Text]][1] [1]: http://www.jci.org/articles/view/43918

Yield on specific designs often falls far short of predicted yield, especially at new technology nodes. Product-specific yield ramp is particularly challenging because the defects are, by definition, specific to the design, and often require some degree of design knowledge to isolate the failure. Despite the wide variety of advanced electrical failure analysis (EFA) techniques available today, they are not routinely applied during yield ramp. EFA techniques typically require a significant amount of test pattern customization, fixturing modification, or design knowledge. Unless the problem is critical, there is usually not time to apply advanced EFA techniques during yield ramp, despite the potential of EFA to provide valuable defect insight. We present a volume-oriented workflow integrating a limited set of electrical failure analysis (EFA) techniques. We believe this workflow will provide significant benefit by improving defect localization and identification beyond what is available using test-based techniques.

Both autoimmune and allergic diseases are caused by dysregulation of the immune response. Regulatory T cells (Treg cells) can repress the response of other immune cells and, as such, play a central role in the maintenance of immune tolerance and in the prevention of autoimmune and allergic diseases. Foxp3 is the master transcription factor critical for the development and function of Treg cells; Foxp3 deficiency results in an autoimmune syndrome in both mice and humans. However, attempts to treat disease by delivering Foxp3 via virus-mediated gene transfer or transferring Treg cells in vivo have met with limited success thus far. Now, Choi et al. offer a novel therapeutic strategy for autoimmune and allergic disease, constructing and administering a cell-permeable form of the Foxp3 protein. Choi et al . generated a recombinant fusion protein by joining Foxp3 and a human-derived protein transduction domain peptide. This fusion protein readily penetrated CD4+ T cells and inhibited their proliferation and cytokine production. The intracellular delivery of Foxp3 also converted conventional CD4+ T cells into Treg cells with a suppressor function. In mouse models of Foxp3 deficiency, the systemic administration of the fusion protein ameliorated autoimmune manifestations and improved survival. Furthermore, the local delivery of the Foxp3 fusion protein through intranasal administration substantially decreased allergic airway inflammation. The therapeutic potential of Treg cells has been investigated in a number of clinical entities, such as autoimmune disorders and allergic diseases, and in the prevention of transplantation rejection. In this study, Choi et al . demonstrated that the nonspecific intracellular delivery of Foxp3 inhibits T cell activation and induces the generation of Treg cells, controlling inflammation in autoimmune and allergic diseases. As protein delivery technologies continue to improve, it is expected that Foxp3 will be able to be targeted specifically to the subset of autoreactive T cells. Targeted delivery would limit global immunosuppression and its unwanted side effects, such as infection and malignancy, and the combination of target delivery with the cell-permeable Foxp3 fusion peptide offers a more clinically acceptable strategy for curtailing undesired immune responses. J.-M. Choi et al ., Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proc. Natl. Acad. Sci. U.S.A. 11 October 2010 (10.1073/pnas.1000400107). [[Abstract]][1] [1]: http://www.pnas.org/content/early/2010/10/05/1000400107.abstract

Spinal cord injury (SCI) can result in paralysis with devastating physical and emotional consequences. Unfortunately, there are no treatments available to reverse damage to the spinal cord, and the body itself has limited capacity to regenerate the nervous system. Neural stem cells (NSCs)

Lung transplantation remains the treatment of choice for disabling end-stage lung disease from chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary hypertension. However, the supply of donor lungs is severely limited, and only one out of three patients on the waiting list undergo transplantation. Outcomes after lung transplantation are further impaired by chronic rejection by the recipient’s immune system and the adverse effects of immunosuppressive therapies. Now, Ott et al. seek to engineer a functional bioartificial lung that can be transplanted without the concern for immunologic rejection. The authors first removed cells from cadaveric lungs using detergent perfusion, leaving a decellularized whole-lung scaffold composed of extracellular matrix proteins. The extracellular matrix not only defines the lung’s architecture and physical properties, but also plays a critical role in pulmonary cell differentiation. The lung scaffold was then repopulated by incubation with fetal lung cells and human umbilical cord endothelial cells. The microanatomy of regenerated lung constructs resembled the native lung and demonstrated nearly physiologic ventilation mechanics and gas exchange capacity in vitro. Upon transplantation into rats, the regenerated lung restored gas exchange and allowed the animals to breathe without ventilatory support for up to 6 hours. This proof-of-concept study by Ott et al. has demonstrated that viable, bioartificial lungs can be generated, providing functional gas exchange in vitro and in vivo. The differentiation and maturation of cells in the regenerated lung graft, however, will require further investigation—for instance, the bioartificial lungs developed pulmonary edema just hours after transplantation, which is probably secondary to the lack of lymphatics and/or capillary leak from immature blood vessels. Nonetheless, the generation of bioartificial lung grafts represents a promising strategy for increasing the organ supply for transplantation in the treatment of end-stage lung diseases. H. C. Ott et al ., Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16 , 927–933 (2010). [[Abstract]][1] [1]: http://www.nature.com/nm/journal/v16/n8/abs/nm.2193.html

According to Susan G. Komen for the Cure, a woman dies from breast cancer every 75 seconds worldwide. Yet, effective strategies are lacking for the prevention of this disease that routinely robs us of our mothers, wives, sisters, daughters, and friends. Cancer vaccines have the potential to effectively hinder tumor formation, but their development has been hampered by the fact that tumor antigens are often altered or overexpressed versions of proteins found in normal cells. Thus, vaccines directed at these so-called “self” proteins can generate an autoimmune response against normal tissue. This bottleneck has limited the use of cancer vaccines to those that have been designed specifically to target cancer-causing viruses. Now, Jaini et al. have successfully designed a novel vaccine with the added ability to prevent the formation of breast carcinomas. The researchers constructed a vaccine that targets α-lactalbumin, a protein expressed by most breast tumors. This protein is also expressed in normal breast tissues only during lactation and is not expressed anywhere else in the body. A single injection of their α-lactalbumin vaccine effectively prevented spontaneous breast tumor formation in cancer-prone transgenic mice and inhibited the growth of established tumors. The α-lactalbumin vaccine also protected against tumor growth after inoculation of breast tumor cells into normal mice. Because α-lactalbumin is only expressed in normal breast tissues during lactation, this vaccine provides breast cancer prophylaxis without causing any detectable inflammation in normal, nonlactating breasts. This study by Jaini et al. has introduced a new perspective in selecting targets for cancer vaccine development. Although it has been shown that human breast cancers also often express α-lactalbumin, the ability of this vaccine to induce an adequate immune response against human breast tumors has yet to be demonstrated. Clinical trials designed to evaluate the efficacy of the vaccine in women over 40 years of age—and, therefore, largely past the child-bearing phase of their lives—could begin as early as next year. Compared with the currently available cancer vaccines, the α-lactalbumin vaccine offers the possibility of preventing the de novo formation of breast carcinomas and therefore holds potential for decreasing the incidence of this pervasive disease. R. Jaini et al ., An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nat. Med. 16 , 799–803 (2010). [[Abstract]][1] [1]: http://www.nature.com/nm/journal/v16/n7/abs/nm.2161.html

In organ transplantation, the ability to monitor the host’s immune response to a graft is essential for the clinician to tailor immunosuppressive therapy. Currently, heart transplant recipients routinely undergo serial invasive biopsies, which increase the risk of complications such as bleeding

"An ounce of prevention is worth a pound of cure." This old adage can apply to cancer in which agents that prevent cancer development, called chemoprevention, could avoid complications associated with the treatment of late-stage malignancies. It has been hard, however, to find effective chemoprevention agents with limited toxicity, and few are used in patients. Now, Zhang et al . raise hopes for chemoprevention and describe a unique approach for the prevention of colon cancer by targeting premalignant cells in colonic polyps for apoptotic cell death. The investigators took advantage of the fact that cells in colonic polyps often harbor a loss-of-function mutation of the APC gene, an early step in forming colon. APC deficiency sensitizes these cells to apoptosis via the tumor necrosis factor–related ligand TRAIL. Short-term, intermittent cycles of treatment with TRAIL and all- trans -retinyl acetate (RAc), another agent that sensitizes cells to TRAIL, led to increased apoptotic cell death within intestinal polyps and improved survival in mice. The researchers also demonstrated that TRAIL and RAc treatment induced cell death within human colonic polyps without affecting normal tissues. Furthermore, in mouse stem cells no toxicities were observed after the long-term administration of TRAIL and RAc together. Because currently available treatments for late-stage malignancies are often associated with toxic side effects and still produce disappointing results, finding ways to prevent cancer from developing in the first place would be a much better approach. Although the efficacy and safety of TRAIL and RAc combination therapy has yet to be evaluated in human trials, Zhang et al . have introduced a promising strategy for the prevention of colon cancer by targeting premalignant cells in colonic polyps for apoptotic cell death. L. Zhang et al ., Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis. Nature 464 , 1058–1061 (2010). [[Abstract]][1] [1]: http://www.nature.com/nature/journal/v464/n7291/abs/nature08871.html

When the British rock band Queen belted out “I Want It All,” they could have been recording an anthem for cancer surgeons. Indeed, complete removal of a tumor, with the absence of cancerous cells at the surgical margins, remains a cornerstone for the successful treatment of most solid-tumor malignancies. Positive margins, or the presence of tumor cells at the cut edge of the surgical specimen, have been associated with increased local recurrence and poorer prognosis in cancers of the head and neck, lung, breast, and colon. In attempts to verify clear margins during initial tumor resection, clinicians currently rely on immediate (frozen) evaluation of small tissue samples taken from the operative site. However, this process is time-consuming and labor-intensive, increases anesthetic risks, and occasionally leads to erroneous conclusions. Now, Nguyen et al. explore the use of activatable cell-penetrating peptides (ACPPs) to improve the visualization of tumor margins during surgery. Using ACPPs carrying fluorescent labels, the researchers successfully delineated tumor margins in mouse models of melanoma, sarcoma, and breast cancer. The ACPPs contain short polycations attached via linkers to neutralizing polyanions. Matrix metalloproteinases, enzymes frequently expressed by tumors to facilitate local invasion and metastasis, cut the linker and release the polyanion. This cleavage allows the polycation, along with its fluorescent label, to adhere to and selectively enter tumor cells in the immediate vicinity. Surgery guided by ACPP labeling reduced residual tumor cells 10-fold and improved overall as well as tumor-free survival. Furthermore, these reagents can be used to facilitate visualization of residual tumor during postoperative magnetic resonance imaging, which allows for evaluation of the completeness of tumor removal in a noninvasive manner. Compared with other targeted fluorescent probes previously described in the literature, the use of ACPPs as described by Nguyen et al. offers improved cancer-cell specificity while being applicable to a wide variety of tumor types. This technology thus holds great promise as a navigational tool for the surgical treatment of large and invasive tumors. Q. T. Nguyen et al ., Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc. Natl. Acad. Sci. U.S.A. 107 , 4317–4322 (2010). [[Abstract]][1] [1]: http://www.pnas.org/content/107/9/4317.abstract

Despite relieving labor pain, epidural analgesia can also paralyze the pelvic muscles, prolonging labor and increasing the risk of fetal distress and cesarean delivery. On the other hand, an anesthetic agent that targets sensory nerves without impairing motor function would allow women in labor to

Small interfering RNAs (siRNAs) have the unique ability to knock down the expression of virtually any gene of interest and therefore harbor great potential for the treatment of human diseases. However, major barriers to the clinical adoption of siRNA-based therapies remain, including the

For decades, epidemiologic studies have reported a connection between obesity and inflammation. For example, proinflammatory gene expression and blood levels of inflammation-associated proteins—including tumor necrosis factor–α, interleukin-6, and C-reactive protein—are elevated among obese subjects. The inflammatory milieu is thought to induce a state of local and systemic insulin resistance, contributing to the development of type 2 diabetes. Despite the abundance of epidemiologic evidence, the biological processes linking obesity to the activation of inflammatory pathways are unclear. The Fas receptor has been well characterized as a regulator of programmed cell death. Now, Wueest et al . propose that Fas may also play an important role in adipose tissue inflammation and obesity-induced metabolic dysregulation. The authors showed that Fas expression is elevated in the adipose tissue of obese and type 2 diabetic patients relative to lean individuals, as well as in mouse models of obesity and insulin resistance. Fas expression was up-regulated in normal mice fed a high-fat diet, which also led to the recruitment of immune cells and the secretion of proinflammatory factors. On the other hand, mice with Fas-deficient adipocytes demonstrated diminished inflammation and were protected from fat accumulation in liver cells and the development of glucose intolerance and systemic insulin resistance, which is normally induced by a high-fat diet. These observations suggest that Fas may activate inflammatory pathways in adipose tissues and contribute to obesity-associated insulin resistance. These data offer an alternative mechanism for the pathogenesis of type 2 diabetes, and suggest that a deeper understanding about the regulation of Fas expression and activation in adipose tissues may lead to new strategies for the prevention and treatment of this prevalent disease S. Wueest et al. , Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J. Clin. Invest. 120 , 191–202 (2010). [[Full Text][1]] [1]: http://www.jci.org/articles/view/38388

Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

To the EditorAlthough germ cell tumors (GCTs) make up only1% of all human malignancies, they are the mostcommon cancers among men aged 15 to 34 [1].Since the introduction of cisplatin-based chemother-apy in the 1970s, long-term survival rates of 80% areachieved even in metastatic settings [2]. This hasplaced greater emphasis on minimizing therapy-related side effects as they significantly impact thequality of life of long-term survivors. Here wepresent two cases of cisplatin-induced arterialthrombosis in patients receiving chemotherapy formetastatic good prognosis GCTs. We then reviewthe incidence and consider possible mechanisms ofthis phenomenon.Case 1A 58-year-old male was diagnosed with a classicseminoma with retroperitoneal metastases (StageIIc). Remarkable past medical history includesmalignant melanoma treated surgically 15 yearsearlier. The patient presented with a three monthhistory of left testicular enlargement with an elevatedbeta fraction of human gonadotrophic hormone(bHCG) of 49 IU/L (normal B2 IU/L). Anabdominal computed tomography (CT) scanshowed enlarged retroperitoneal lymph nodes in-cluding a mass encasing the renal arteries and half ofthe abdominal aorta. The patient underwent aninguinal orchiectomy and was scheduled for fourcourses of etoposide and cisplatin chemotherapy(EP). After the first cycle, the patient experiencedmild symptoms suggestive of intermittent claudica-tion in the distal right lower extremity. After thesecond cycle of treatment these symptoms worsenedand he was diagnosed with acute ischemia secondaryto thrombosis in the right external iliac artery. Nosmoking history or cardiovascular risk factors wereidentified and investigations ruled out heart diseaseas the precipitating cause. A balloon angioplasty ofthe right common iliac artery, right common femoralartery thrombectomy, and patch angioplasty of theright femoral artery were performed. On discharge,the patient was prescribed clopidogrel and low-doseaspirin for thrombosis prophylaxis. Following reso-lution of the ischemic episode, the patient resumedchemotherapy and completed four cycles of treat-ment as initially planned, achieving a completeresponse. On further follow-up his only complaintis mild bilateral residual neuropathy in the feet. Thepatient remains free of disease 12 months after theinitial diagnosis.Case 2A 37-year-old male was diagnosed with good prog-nosis, stage III testicular cancer of mixed seminomaand non-seminoma histology (95% embryonal car-cinoma, 5% seminoma). The past medical historywas unremarkable. The patient initially presentedwith a left testicular mass; scrotal ultrasound re-vealed a large left testicular lesion and a 4.9 cm massin the left inguinal region. The alpha-feto proteinand bHCG were elevated at 17 IU/L (normal B5)and 155 IU/L, respectively. The patient underwentan orchiectomy and started chemotherapy withbleomycin, etoposide, and cisplatin (BEP). Afterthe first cycle he developed a painful, swollen, andcyanotic right foot with significantly decreased bloodflow and was diagnosed with an acute arterialthrombosis. The patient was admitted to hospitaland treated with thromboembolitic therapy withtissue plasmin activator (tPA), followed with lowmolecular weight heparin. After discharge he con-tinued on chemotherapy with prophylactic heparin,and the second cycle of BEP was well tolerated.However, during the third cycle the patient devel-oped a recurrence of arterial embolic disease in theright leg. Despite many interventions including

We have recently reported in this journal a report of two pediatric patients with cecal diverticulitis, a 15-year-old female and a 3-year-old female. There have been no documented reports subsequent to ours; however, we have since encountered an additional pediatric patient with cecal diverticulitis to add to this case series. This most recent patient is a 10-year-old female who presented to the emergency department with a 1-day history of worsening abdominal pain. Her parents reported subjective fevers at home, but denied any nausea or emesis. In the emergency department, her vital signs were within normal limits. Physical examination was notable for tenderness to palpation in the right lower quadrant. Her white blood cell count was 12,500 mm with 72 % neutrophils. An abdominal ultrasound was performed which could not visualize the appendix, and did not demonstrate any free fluid. A computed-tomography scan was then obtained which showed a cecal wall diverticulum with wall thickening and adjacent marked inflammatory changes consistent with cecal diverticulitis. The appendix was visualized and appeared normal. Free fluid was present in the right lower quadrant, however, no pneumoperitoneum was present. The patient was started on intravenous piperacillin/ tazobactam. Based on the radiographic findings and a worsening abdominal examination, the decision was made to proceed with operative exploration. Similar to our prior cases, a transverse abdominal incision was made in the right lower quadrant. The cecal wall was found to be thickened and a rubbery mass was palpated within the wall of the cecum. An ileocecectomy was performed. Pathology revealed a perforated ‘‘false’’ cecal diverticulum with organizing serositis. The patient did well postoperatively and was discharged on postoperative day 6. This case is very similar in presentation, operative findings, and pathology results to the two previous cases we have reported. We are seeing an increased incidence of pediatric cecal diverticulitis. Further investigations are necessary to understand the etiology of this disease in the pediatric population, and to clarify the possibility of an increasing incidence in childhood.