Proposed Treatment Strategies Research Articles

47 Inadequacy of Existing Clinical Prediction Models for Predicting Mortality Post Transcatheter Aortic Valve Implantation

Introduction Clinical prediction models (CPMs) form the cornerstone of risk stratification for patients undergoing invasive procedures, helping to guide both treatment allocation and the consent process by enabling discussion of the magnitude of risks associated with the proposed treatment strategy. Several CPMs are used to predict mortality after Transcatheter Aortic Valve Implantation (TAVI). However, their performance in national cohorts distinct from those where they have been derived is unknown. We examined the performance of the Logistic EuroSCORE (LES), EuroSCORE II, Society of Thoracic Surgeons (STS), German Aortic Valve, FRANCE-2 TAVI and OBSERVANT-TAVI risk models in the British Cardiovascular Intervention Society UK TAVI registry, to examine if any can be used for practical use in external national cohorts of TAVI patients. Methods The risk of 30-day mortality given by each CPM was retrospectively calculated, based on the published regression coefficients, for all 3980 patients in the UK TAVI registry from 2007 to 2012. Life status information was provided by the Office for National Statistics for each patient. Performance of each CPM was investigated through calibration and discrimination. Calibration is the agreement between the expected and observed event rates and was analysed by a calibration plot. Discrimination is how well the CPM can distinguish between those who will experience an event and those who will not, which was analysed by the area under the ROC curve (AUC). Furthermore, the level of agreement in risk classification between each of the considered CPMs was analysed at an individual patient level. Results The observed 30-day mortality rate was 6.23%. All of the CPMs were miscalibrated and grossly over-predicted risk of 30-day mortality; the LES over predicted by a factor of three, while the STS underestimated risk. Discrimination was also poor, with AUC values of 0.58, 0.57, 0.62, 0.60, 0.62 and 0.57 for the LES, EuroSCORE II, STS, the German Aortic Valve, FRANCE-2 TAVI and OBSERVANT models, respectively. Additionally, risk classification agreement was low in both the surgical models and the TAVI specific models, an example is given in Figure 1. Conclusions The performance of CPMs currently used in TAVI risk prediction was low when applied in a cohort of TAVI patient independent to those they were developed on. The TAVI specific FRANCE-2 CPM performed better than cardiac surgery based CPMs. Thus, development of TAVI CPMs are recommended either by updating existing CPMs or developing new risk scores in populations of interest.

Non tuberculous mycobacterial lesion of the parotid gland and facial skin in a 4 year old girl: A proposed treatment strategy

ObjectiveWe report a case of a parotid-facial caseating granulomatous infection caused by atypical mycobacteria (Mycobacterium avium) in an immuno-competent child. The size and depth of the lesion and its proximity to the facial nerve present a challenge for a purely surgical treatment strategy. An alternative treatment strategy is developed to avoid severe disfigurement. Study design/subjectAtypical mycobacterial infection of the parotid region in a 5year old girl: timeline and definition of a planned combined treatment strategy with antibiotics and surgical excision. Results/conclusionCervicofacial infections caused by non-tuberculous mycobacteria (NTM) may present surgical challenges due to the size and depth of the lesion and its proximity to the facial nerve and major vascular structures. Even minor scars are highly visible and poorly tolerated. Close clinical monitoring combined with judicious treatment strategies is necessary for successful treatment and good cosmesis. Recent literature provides insufficient guidance in formulating the best treatment strategy for the individual patient. Comparisons of antibiotic therapy with variations of surgical excision are abundant but poorly formulated. Our case presented with a lesion involving skin, superficial and deep lobe of the parotid gland. Lesion was in immediate proximity to the distribution of the facial nerve through the parotid gland. The risk of surgical damage to the facial nerve in the acute phase of the inflammation and the required extent of skin excision were significant. We decided to start treatment with combination antimycobacterial antibiotics in close cooperation with the pediatric infectious disease specialists. We observed and documented the regress and executed a delayed surgical excision when the lesion was reduced to skin only. In our opinion this was the best treatment strategy that helped us avoid extensive dissection in the vicinity of the facial nerve as well as a parotidectomy. Excision of the involved skin with the deep portion was performed 6.5months after initial diagnosis.

Aggression After Traumatic Brain Injury: A Review of the Current Literature

Traumatic brain injury (TBI) results in an increase in aggression in nearly one-third of patients. Aggressive behaviors can be severe and impede rehabilitation and quality of life. This study reviews current literature on the definitions, subtypes, predisposing factors, neuroanatomy, and proposed treatment strategies for aggression after TBI. Post-TBI aggression has been found to be associated with higher rates of premorbid anger and impulsivity. It has been linked to damage in the orbitofrontal and ventromedial prefrontal cortices and associated with higher levels of norepinephrine and lower levels of serotonin post-injury. Although medications are often used to address management of post-TBI aggression, large-scale studies are still needed to determine the appropriate indications for medication use. [ Psychiatr Ann . 2015;45(8):422–426.]

Saddle nose: Autologous augmentation techniques and their relevant patient satisfaction

IntroductionThe analysis and treatment of saddle nose have always been a surgical challenge. The study describes the three-stage classification of this deformity as well as a treatment algorithm adapted to each case. Materials and methodsA prospective study was carried out on 46 patients with saddle nose. The patients were divided into 3 groups according to the severity of saddling; minimal, moderate and major. The authors describe the treatment protocol adopted for each stage. ResultsThis series comprised 16 cases of minimal saddle nose, 20 cases of moderate saddle nose and 10 cases of major saddle nose. Minimal saddle nose was treated by enforcing and reconstructive septoplasty and dorsal septal augmentation grafts, conchal grafts were used to treat moderate saddle nose, and costal cartilage was used to reconstruct major saddle nose. We have used the open rhinoplasty approach to correct saddle nose in all cases. Surgical revision was never required. ConclusionSaddle nose is a condition that is quite commonly faced by Otolaryngologists. The proposed treatment strategy is based on a meticulous analysis of the saddle nose, resulting in a graduated reconstruction adapted to each stage according to the severity of deformity. Level of evidenceIV.

Observer-Based Output Feedback Linearization Control with Application to HIV Dynamics

This paper presents the feedback linearization control of HIV infection. A multi-input multi-output (MIMO) dynamic nonlinear HIV infection model for this purpose has been used. For this purpose, three widely used drugs are considered. A Luenberger-like nonlinear observer (LNO) is designed for estimation of unavailable states. To minimize the side effects of drugs, the concentration of ZDV which has the highest side effect is fixed to a minimum value and the external controllers parameters are obtained by maximizing an objective function. In the control design, limitations on drug consumption and unavailability of all states are taken into account. The closed-loop stability has been established in the presence of the observer dynamics and input limitations. Robustness of the proposed treatment strategy against model parameter uncertainties, noise, or sparse measurements has been demonstrated through simulation study. Finally, by including pharmacological models, an impulsive control strategy for HIV treatment has been considered.

Classifications in Brief: The Hawkins Classification for Talus Fractures.

As reported by Coltart [5], Fabricius von Hilden first described talus injuries in 1608, and in 1919, Anderson et al. [1] reported a series of talus fracture dislocations in which they emphasized dorsiflexion as the mechanism of injury and coined the term ‘‘aviator’s astragalus’’ (astragalus being another term for talus) because of the impressive frequency with which the mechanism—aircraft accidents— was associated with the injury in question. In 1952, Coltart [5] reported on 228 talus injuries treated by surgeons in the British Royal Air Force in an attempt to describe the variety of injuries that occur to the talus and surrounding joints. He described various talus fracture patterns, fracture-dislocation combinations, and isolated peritalar dislocations [5]. Others have presented case series of talus injuries and associated rarely used classification schemes [15, 19], but all have noted high complication rates with injuries to the talus [5, 11, 15, 19]. In 1970, proposed treatment strategies for vertical fractures of the talar neck ranged from nonoperative management to urgent open reduction internal fixation, bone graft augmentation, fusion of the dorsal talus to the distal tibia, and even complete talectomy [11]. Although the importance of early, anatomic reduction of these injuries was noted at that time, the incidence of avascular necrosis (AVN) was not. In 1970 Hawkins [11] described injury patterns and AVN rates in a series of 57 vertical talar neck fractures in 55 patients from three different institutions. All 55 patients sustained forced dorsiflexion injuries, similar to the mechanism described by Anderson et al. [1] in pilots.

Radiotherapy treatment of non-melanoma skin cancer: a survey of current UK practice and commentary.

In the ongoing absence of available trial data, a national survey was carried out to provide details on radiotherapy treatment strategy for non-melanoma skin cancer (NMSC). A survey of clinical oncologists treating NMSC was performed. The respondents were asked for basic information on workload as well as a proposed treatment strategy for various clinical scenarios for patients of varying fitness. A total of 43 completed and 20 partially completed surveys were received. There was a wide variation in the workload and additional disease sites that respondents had responsibility for. Kilovoltage radiotherapy was available to 81% of responders. The respondents' approach was affected by the fitness of patients, with longer fractionation regimes proposed for younger, fitter patients and shorter or non-standard fractionations more likely for the infirm elderly. Four daily fractionation regimes (18-20 Gy in 1 fraction, 35 Gy in 5 fractions, 45 Gy in 10 fractions and 55 Gy in 20 fractions) were most commonly suggested. There was a large degree of variation in non-standard fractions proposed with significant potential differences in radiobiological effect. Concern over the use of kilovoltage photons on skin over cartilage was apparent, as was a reluctance to use radiotherapy in areas of increased risk of poor wound healing. The survey results largely showed practice to be in line with available published evidence. The variation seen in some areas, such as non-standard fractionation, would benefit from the publication of local outcomes to achieve a more consistent approach. This study provides information on national practices and identifies variations, particularly within widespread use of non-standard fractionation.

Have We Changed the Natural History of Pediatric Crohn's Disease with Biologics?

Considerable debate exists as to whether the risk of complications and need for surgery has truly decreased in Crohn's disease (CD) over time. A recent systematic review and meta-analysis reported that after the year 2000, the surgical rates at 1, 5 and 10 years have significantly decreased. It is unclear whether this decrease can be solely attributable to the introduction of biologics, the more effective use of thiopurine dosing with monitoring or perhaps earlier disease recognition and early use of effective interventions. Uncontrolled observational studies confirmed that scheduled maintenance treatment with anti-TNF as compared to episodic or discontinued use of anti-TNF resulted in fewer surgeries. Recent population-based studies have shown similar improved disease outcomes with early immunomodulator use. There is a dearth of pediatric-specific natural history studies for both short and long term. Multiple pediatric observational cohort studies have reported that up to one third of pediatric-onset CD patients progress to surgery within 5 years. This is a slightly higher proportion than that of adult patients followed in the same time frame. This discrepancy may be explained by less early biologic use in pediatric patients. More data are needed to follow all CD patients for longer follow-up periods with an emphasis on pediatric onset to better gauge whether our proposed treatment strategies are actually altering the natural history of disease and what role biologics play in this regard.

Integrated Next-Generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment

Current technology permits an unbiased massive analysis of somatic genetic alterations from tumor DNA as well as the generation of individualized mouse xenografts (Avatar models). This work aimed to evaluate our experience integrating these two strategies to personalize the treatment of patients with cancer. We performed whole-exome sequencing analysis of 25 patients with advanced solid tumors to identify putatively actionable tumor-specific genomic alterations. Avatar models were used as an in vivo platform to test proposed treatment strategies. Successful exome sequencing analyses have been obtained for 23 patients. Tumor-specific mutations and copy-number variations were identified. All samples profiled contained relevant genomic alterations. Tumor was implanted to create an Avatar model from 14 patients and 10 succeeded. Occasionally, actionable alterations such as mutations in NF1, PI3KA, and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and, accordingly, treatment of the patients with these drugs was not effective. To date, 13 patients have received a personalized treatment and 6 achieved durable partial remissions. Prior testing of candidate treatments in Avatar models correlated with clinical response and helped to select empirical treatments in some patients with no actionable mutations. The use of full genomic analysis for cancer care is encouraging but presents important challenges that will need to be solved for broad clinical application. Avatar models are a promising investigational platform for therapeutic decision making. While limitations still exist, this strategy should be further tested.

Primary malignant cardiac tumors

The literature on primary malignant cardiac tumors is relatively limited because of their rare incidence. This study aimed to provide a proposed treatment strategy for primary malignant cardiac tumors. The follow-up outcomes of 29 patients with primary malignant cardiac tumors operated, and 8 primary malignant cardiac tumors considered not operable from 1985 to 2013 in the First Affiliated Hospital of China Medical University were retrospectively analyzed. Of operation receivers, ten patients had positive surgical margins and nineteen patients had negative surgical margins. Eleven patients received a post-operative neoadjuvant chemotherapy. Patients rejected to surgery had a lower survival compared with operation receivers (15 vs 23 months, P = 0.011). However, there were no significant differences in survival in patients rejected to surgery than in patients who had positive surgical margins (15 vs 16 months, P = 0.874). Patients who had positive surgical margins had a median overall survival duration of only 16 months, whereas patients with negative surgical margins had a median overall survival duration of 27 months (P = 0.002). There were no significant differences in survival in patients with receiving a post-operative adjuvant chemotherapy than in the rest of the population (20 vs 25 months, P = 0.150). The prognosis for patients with primary malignant cardiac tumors remains very poor. Each patient should be managed on an individual basis, and variety of treatment strategy should be performed. Maximizing the possibility of obtaining negative surgical margins may prolong survival.

The Case of "Sonia" Through the Lens of Dialectical Behavior Therapy

Scherb (2014) describes the case of Sonia, a 44-year-old woman with severe and complex presentation of borderline personality disorder, along with diagnoses of bipolar disorder, trichotillomania, borderline intellectual functioning, and obesity. At the end of 10 years of therapy with decreasing frequency, Sonia has made a dramatic recovery from almost all of her presenting symptoms. Scherb's therapeutic approach was based on Fernández-Álvarez's Integrative Psychotherapy Model, which incorporates behavioral, cognitive, and emotional components. In this commentary we look at Sonia's psychopathology and treatment through the lens of Dialectical Behavior Therapy, a highly developed treatment model that has shown impressive success in treating individuals with borderline personality disorder and that also combines behavioral, cognitive, and emotional components. A comparison of a DBT approach to Sonia's case with the approach Scherb actually employed reveals many similarities in proposed treatment strategies, as well as differences in the format and delivery of treatment.

Effect Of Different Methods Of Surgical Treatment On Quality Of Life Of Patients With Acute Thrombosis Associated With Varicose Veins Of Lower Limbs

A comprehensive quality of life analysis was carried out in 138 patients with superficial vein thrombosis associated with varicose veins of lower limbs estimating the short- and medium-term results of surgical treatment on the basis of “CIVIQ- 2” Interviewer. Patients were divided into 2 groups: control and basic. The treatment tactics of these groups differed: in the basic group the indication of different doses of anticoagulation drugs (therapeutic or prophylactic) was based on the initial D-dimer blood levels and during operation all areas of great and small saphenous vein remained unaffected by abnormal reflux. The results showed that thrombotic postoperative complications occurred during the proposed treatment tactics statistically significantly less, no pathological reflux was found in any the remained unaffected areas of great or small saphenous vein within a year after operation and, which is the most important, statistically significant more pronounced improvement of patients’ quality of life was provided. It enables to recommend the proposed treatment strategy as the method of choice in patients with superficial vein thrombosis associated with varicose veins.

Saddle nose: Classification and therapeutic management

The understanding and treatment of saddle nose have always been a surgical challenge. The authors propose a three-stage classification of this deformity as well as a treatment strategy adapted to each case. A retrospective study was carried out on 25 patients with saddle nose. After defining the three stages of saddle nose: minimal, moderate and major, the authors describe the treatment protocol adopted for each stage. This series comprised 3 cases of minimal saddle nose, 17 cases of moderate saddle nose and 5 cases of major saddle nose. Minimal saddle nose was treated by extracorporeal rhinoplasty, an inverted U-shaped conchal graft was used to treat moderate saddle nose, and costal cartilage was used to reconstruct major saddle nose. Surgical approaches varied according to the technique adopted. Surgical revision was never required. Saddle nose is a classical condition in facial reconstructive surgery. The proposed treatment strategy is based on detailed analysis of the clinical signs, resulting in a graduated solution adapted to each clinical case according to the severity of the deformity.

Treatment of wastewater contaminated with detergents and mineral oils using effective and scalable technology

In this work, effective, cheap and scalable methodology is introduced to treat oily wastewater. The water produced from car-wash processes was utilized as a model because it has various pollutants - oil, lubricants, detergents, solid particles, etc. The results showed that the turbidity and chemical oxygen demand (COD) values dramatically decrease by using the proposed treatment process, which consists of coagulation, flocculation, sand filtration, and oxidation followed by sand as well as activated carbon filtration. Moreover, the operating conditions were optimized. Without adjustment of the pH value of car-wash wastewater, it was found that 200 ppm of ferric chloride, as a coagulant, and 1 ppm of potassium permanganate, as an oxidant, are the optimum doses. The COD and turbidity values of the final treated wastewater were reduced by almost 88 and 100%, respectively. A prototype with 15 L capacity was designed and fabricated to investigate the scaling up and continuity of the proposed treatment strategy. The results were very promising and indicated that the introduced methodology can be industrially applied.

Clinical course and proposed treatment strategy for ERCP-related duodenal perforation: a multicenter analysis

Endoscopic retrograde cholangiopancreatography (ERCP)-related duodenal perforation is rare but can cause high mortality. Our aim was to assess the clinical outcomes of these events. A total of 59 patients who were diagnosed as having ERCP-related duodenal perforation at six institutions between 2000 and 2007 were enrolled in this multicenter retrospective study. We evaluated complications and mortality associated with ERCP-related duodenal perforation according to injury detection time (IDT), peritoneal irritation signs (PIS), systemic inflammation signs (SIS), and treatment modality in these patients. Of the 59 patients, 41 (69.5 %) and 18 (30.5 %) underwent medical and surgical treatment, respectively. Duodenal perforation-related death was observed in five patients, who had received medical therapy (n = 2) and surgical therapy (n = 3). Among medically treated patients, seven patients (17.1 %) underwent endoscopic clipping immediately after the injury; surgery was not required as a salvage therapy and there were no complications or deaths among these patients. The remaining 34 patients received antibiotics combined with therapeutic fasting and intravenous hydration. Duodenal perforation-related complications depended significantly on IDT (P = 0.0001), treatment modality (P = 0.008), PIS (P = 0.003), and SIS (P = 0.010). The duodenal perforation-related mortality was significantly related to IDT (P = 0.008) and PIS (P = 0.001). IDT, PIS, and SIS appear to be important prognostic factors following ERCP-related duodenal perforation. Medical therapy can be suggested as an initial treatment strategy for ERCP-related duodenal perforation, and if possible, endoscopic clipping is strongly recommended. However, surgical treatment should be considered if the perforation is not expected to seal spontaneously, or if the continuing leakage causes PIS or SIS.

Mechanisms of Intervertebral Disk Degeneration/Injury and Pain: A Review

Degeneration of the intervertebral disk and its treatments are currently intensely investigated topics. Back pain is a condition whose chronic and debilitating nature combined with its prevalence make it a major health issue of substantial socioeconomic importance. Although researchers, and even sometimes clinicians, focus on the degenerated disk as the problem, to most patients, pain is the factor that limits their function and impacts their well-being. The purpose of this review is to delineate the changes associated with disk degeneration and to outline mechanisms by which they could be the source of back pain. Although the healthy disk is only innervated in the external layer of its annulus fibrosus, adjacent structures are plentiful with nociceptive receptors. Stimulation of such structures as a consequence of processes initiated by disk degeneration is explored. The concept of discogenic pain and possible mechanisms such as neoinnervation and solute transport are discussed. Finally, how such pain mechanisms may relate to current and proposed treatment strategies is discussed.

Integrated genomics and avatar mouse models for personalized cancer treatment.

2511 Background: Every cancer has its unique set of molecular changes and the knowledge of such alterations is enabling an individualized approach to cancer treatment. The great intellectual challenge lies in linking confirmed mutations to protein function. Methods: Using massive parallel sequencing we performed whole exome sequencing analysis of 30 patients (pts) with advanced solid tumors to identify putatively actionable tumor-specific genomic alterations. We used 2 in silico methods (Polyphen and SIFT) to estimate the functional significance of a given confirmed mutation. Avatar models generated by direct engraftment of tumor samples from the patients into immunocompromised mice were used as an in vivo platform to test proposed treatment strategies. Results: Successful exome sequencing analyses has been obtained for 28 pts. Tumor specific mutations (Muts) and copy number variations were identified ranging from 5 to 952 and 0 to 956 respectively. All samples profiled contained relevant genomic alterations. Some of the most relevant actionable alterations were: CHEK1, FGFR2, IGF1R, MET, BRCA1, XPC, NOTCH, CREB3LB, GNA11, SMAD4, NF1, PTPRC, PI3KA, DDR2 and EGFR. An Avatar model was generated for 15 patients. In occasions actionable alterations such as muts in NF1, PTPRC, PI3KA and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and accordingly treatment of the pts with these drugs was not effective. So far 13 pts have received a personalized treatment: two, as expected based on the avatar model, did not response; 5 resulted in durable partial remissions. Eight pts are currently on treatment with at least disease stabilization. Bench testing of candidate treatments in Avatar models correlated with clinical response and helped to select empirical treatments in patients with no actionable mutations. Conclusions: The use of full genomic analysis for cancer care is promising but presents important challenges that will need to be solved for broad clinical application. Avatar models are a powerful investigational platform for therapeutic decision making and help to guide cancer treatment in the clinic. While limitations still exist, this strategy should be tested in prospective randomized clinical trials.

Abstract 2205: Integrated next generation sequencing and patient-derived xenografts to personalized cancer treatment.

Abstract Background: The knowledge of actionable somatic genomic alterations present in human tumors is enabling the new era of personalized cancer treatment. The great intellectual challenge lies in linking confirmed mutations to protein function. Personalized tumor graft models (Avatars) can aid in the process of genomic analyses interpretation to ultimately move from molecular profile to medication. Methods: Using massive parallel sequencing we performed whole exome sequencing analysis of tumor and matched normal blood samples of 23 patients (pts) with advanced solid tumors (7 lung cancer, 7 pancreatic cancer, 1 neuroendocrine tumor, 2 glioblastoma, 1 uveal melanoma, 2 melanomas and 3 colon cancer) to identify putatively actionable tumor-specific genomic alterations. Avatar models generated by direct engraftment of tumor samples from the pts into immunocompromised mice were used as an in vivo platform to test proposed treatment strategies. Results: Successful exome sequencing analyses has been obtained for 21 pts (1 patient died prematurely, 1 sample was insufficient). Tumor specific mutations (Muts) and copy number variations were identified ranging from 5 to 952 and 0 to 36 respectively. All samples profiled contained clinically meaningful genomic alterations. A successful Avatar model was generated for 10 out of 17 pts. Two engraftment failures corresponded to EGFR mutant lung tumors resected while pts were receiving erlotinib, which initially grew but then regressed. Some of the most relevant drugabble alterations were: KRAS, CHEK1, FGFR2, IGF1R, MET, BRCA1, XPC, NOTCH, CREB3LB, GNA11, SMAD4 and EGFR. In occasions druggable alterations such as muts in NF1, PTPRC, PI3KA and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and accordingly treatment of the pts with these drugs was not effective. In one case, loss of STK11 lead to testing of mTOR and SRC inhibitors resulting in tumor regression both in the Avatar and in the clinic. At present time 10 pts have received a personalized treatment: 2 pts, as expected based on the Avatar model, did not response; 4 pts resulted in durable partial remissions and 4 pts are currently on treatment with disease stabilization. In one of the EGFR mutant lung pts the genomic analysis revealed traces of an acquired mutation and allowed decision making at an earlier time point, prior to relapse. Overall, there was a remarkable correlation between drug activity in the Avatar and clinical outcome in the pts, in terms of drug resistance and sensitivity. Conclusion: The detection of actionable tumor-specific genomic alterations in the clinical setting is feasible. However predicting treatment response to known oncogenes is complex and requires detailed information of how different genetic backgrounds function. Avatar models are a powerful investigational platform for therapeutic decision making and help to guide cancer treatment in the clinic. Citation Format: Elena Garralda, Keren Paz, Pedro P. López-Casas, Siân Jones, Amanda Katz, Lisa M. Kann, Fernando López-Rios, Francesca Sarno, Fátima Al-Shahrour, David Vasquez, Elizabeth Bruckheimer, Samuel V. Angiuoli, Luis A. Diaz, Alfonso Valencia, Victor E. Velculescu, David Sidransky, Manuel Hidalgo. Integrated next generation sequencing and patient-derived xenografts to personalized cancer treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2013-2205

Survival of patients evaluated for intestinal and multivisceral transplantation – the Scandinavian experience

Objective. The current treatment of choice for patients with intestinal failure is parenteral nutrition, whereas medical therapy or resection is preferred for patients with neuroendocrine pancreatic tumors (NEPT) along with liver metastasis. As the survival of patients undergoing intestinal and multivisceral transplantation is improving, the discussion for expansion of treatment options has become a subject of debate. The aim was to investigate the outcome for patients referred for intestinal and multivisceral transplantation and to determine which patient group are the ones most likely to benefit the most from transplantation. Methods. The authors included all patients evaluated for intestinal and multivisceral transplantation at the Sahlgrenska University Hospital and The Queen Silvia Children's Hospital center between February 1998 and November 2009. Patients were classified according to proposed treatment strategy, and the outcome was evaluated. Results. A total of 43 adults and 19 children with either intestinal failure or NEPT with liver metastases were evaluated for transplantation. Of these patients, 15 adults and 5 children were transplanted. Transplantation was lifesaving for most children – all the children survived after transplantation, but 70% (4/6) died while awaiting transplantation. Among the adult patients with intestinal failure, the survival rate for patients considered to be stable on parenteral nutrition was higher than the transplanted adult patients. The survival rate of patients with NEPT was similar to the results seen among patients transplanted for intestinal failure. Conclusion.The results confirm the poor prognosis of patients with intestinal failure awaiting transplantation and indicate that different transplantation criteria may be applied for adults and children, especially when early transplantation is the preferred treatment. The role of multivisceral transplantation in patients with NEPT remains uncertain.

Inflammation in Disease: Mechanism and Therapies

Inflammation in the face of harming stimuli protects the organism; as a result, it is an essential process for survival, in which both innate and adaptive immunity are involved. This process must be tightly controlled and terminated in order to warrant the reestablishment of body homeostasis. Therefore, activation of resident inflammatory cells and the recruitment and modulation of migrating inflammatory cells must be ceased. When failure in neutralising acute inflammation occurs, there is augmented risk for the development of chronic inflammation, leading to several metabolic consequences. In the present special issue, original research studies as well as review articles address the inflammatory process as a key contributor to the development of disease. In addition, pharmacological and nonpharmacological therapies are examined and the molecular and physiological mechanisms of the treatments are discussed. Among the 24 accepted articles, 5 focus on nutritional therapy and inflammation (D. Estadella et al.; L. Ma et al.; M. J. Kim et al.; S. Scolleta et al.; C. Cunha et al.). The selected articles discuss the effects of the consumption of saturated and trans fatty acids upon tissue lipotoxicity, the influence of resveratrol on lung injury, the beneficial effect of genistein on renal damage, the role of vitamin D in the resolution of inflammation, and finally the capacity of green tea extract to counteract the consequences of obesity. The ability of exercise to modulate chronic inflammation is the focus of two articles, the first of which discusses the adaptive response of skeletal muscle to inflammation as induced by eccentric overload resistance training (B. N. Ide et al.), while the other considers exercise effects upon spinal cord injury-associated low grade inflammation (E. S. Alves et al.). Pulmonary diseases and inflammation are the subject debated in 8 from the total of 24 articles selected for this issue, with special emphasis on the possible triggers of inflammation onset in the scenario (Y. Yang et al.; G. Karakiulakis et al.; M. S. Duan et al.; Geve et al.; I. T. Lee et al.; P. Seidel et al.; Y. Shimizu et al.; A. D. Yalcin et al.). In fact, asthma, emphysema, and COPD are extensively discussed in this issue, and studies concerning the effects of treatment with dimethyl fumarate, anti-IgE; activation of muscarinic receptors of immune cells; and proinflammatory signalling are reviewed. Sleep disorders are also contemplated in articles (V. A. Lemos et al.; D. Rosa et al.; Y. Jin et al.) that demonstrate that sleep apnea contributes to the increased inflammatory cytokine content, a response to hypoxia induced by high altitude. Finally, 3 studies investigate the role of PPAR, 41BB/4 1 BBL, and mitochondrial dysfunction in metabolic disease (T. H. Tu et al.; F. Monsalve et al.; A. Hernandez-Aguilera et al.). In addition, inflammation is discussed in the presence of periodontal disease and endotoxaemic shock (J. D. Correa et al.; A. Sampaio et al.). Collectively, this issue aims at providing insight on the role of acute and chronic inflammation in different diseases, as well as at presenting recently proposed treatment strategies. Gustavo Duarte Pimentel Marilia Seelaender Fabio Santos Lira