bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Options for the Diagnosis, Staging and Therapeutic Management of Colorectal Cancer
Authors: Nakayama Goro , Tanaka Chie , Kodera Yasuhiro
Published: February 2014

Background: Colorectal cancer (CRC) is the one of the most common malignancies and is a leading cause of cancer death worldwide. The incidence of mortality from CRC has decreased in Western countries because of earlier diagnosis and improved treatment modalities; however, mortality is still increasing in most other regions of the world. Summary: Progress in the development of imaging modalities has enabled more accurate staging based on the TNM classification. The therapeutic management of CRC should involve a multi-modal approach, including high-quality surgery and an optimal choice of chemotherapy and radiotherapy regimens according to disease characteristics and patient preferences. Even in the case of metastatic disease, the optimal multi-modal treatments could achieve potential cure or long-term survival benefit in some patients. The aim of this review is to present current options regarding the diagnosis, staging and treatment management for CRC based on published research reports and the current management guidelines. Key Message The management of colorectal cancer (CRC) should be undertaken using a multi-modal approach, taking into account the extent, localization and biology of the tumor, as well as individual patient factors. Practical Implications The initial diagnosis of CRC is generally done using colonoscopy, accompanied by histological confirmation of the biopsy. Important staging factors are the depth of tumor invasion, regional lymph node (LN) involvement and distant metastases. The standard curative treatment for colon cancer is surgical resection including colectomy with optimal LN dissection. For rectal cancer, an accurate diagnosis of tumor location, T stage, N stage and relationship of the tumor to the mesorectal fascia are important for defining a therapeutic strategy. Surgery, however, is also the mainstay of treatment. For patients with stage III colon cancer, the benefits of adjuvant therapy using the FOLFOX regimen are well-established. However, this has not been formally demonstrated for rectal cancer patients. For those with resectable liver metastases, the use of perioperative FOLFOX4 regimen resulted in improved 3-year disease-free survival, though the optimal sequence of chemotherapy still remains to be defined. Finally, the management of metastatic CRC involves the use of various drugs used either alone or in combination, including 5-FU/LV, capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, ziv-aflibercept and regorafenib.
Rhegmatogenous Retinal Detachment: A Reappraisal of Its Pathophysiology and Treatment
Authors: Kuhn Ferenc , Aylward Bill
Published: February 2014

This article represents a synthesis of an extensive literature review and the authors' decades-long personal experience with both scleral buckling (SB) and vitrectomy for rhegmatogenous retinal detachment (RD). Presenting a coherent understanding of the pathophysiology and treatment of RD, the authors confirm numerous findings described in earlier publications but also challenge certain long-standing dogmas. The key argument made here is that it is extremely rare for the chain of events leading to an RD to start with a retinal pathology. Rather, the initial pathology is syneresis of the vitreous, which then allows gel movement (intraocular currents). At the point of vitreoretinal adhesion, dynamic traction is exerted on the retina, which may be sufficient to tear it. If the tear is operculated and the dynamic traction overcomes the forces keeping the neuroretina and retinal pigment epithelium (RPE) together, the heretofore virtual subretinal space becomes accessible through the retinal tear. The intraocular currents allow the free (nonbound) intravitreal fluid to enter the subretinal space, and once the amount of the incoming fluid overwhelms the draining capacity of the RPE, an RD ensues. Detachment of the posterior cortical vitreous (PVD) is not a necessary prerequisite to RD development; furthermore, PVD cannot be diagnosed preoperatively with adequate certainty with current technology such as biomicroscopy, ultrasonography or optical coherence tomography. The surgeon should expect no or only partial (anomalous) PVD at the time of surgical repair in over half of eyes. The treatment's primary goal must thus be weakening (pneumatic retinopexy, SB) or eliminating (vitrectomy) this dynamic traction. If vitrectomy is employed, it must be a truly complete vitreous removal. This includes a surgically induced PVD if one is not present, close shaving at the periphery, and removing the vitreous immediately behind the lens. The vitrectomy is followed by the creation of a chorioretinal scar around the tear and aided by some form of intraocular tamponade. The main function of the tamponade is not to temporarily cover the break but to significantly reduce the intraocular currents and thus prevent fluid entry through the break until the chorioretinal adhesion will have become sufficiently strong to seal the retinal edge around the tear; postoperative positioning is therefore not as important as currently assumed.
Small Bowel Neoplasias: Current Options for Diagnosis, Staging and Therapeutic Management
Authors: Fry Lucia C. , Gutierrez Juan Pablo , Jovanovic Ivan , Mönkemüller Klaus
Published: February 2014

Although small bowel polyps and tumors are rare, their incidence has increased significantly over the past 30 years. Small bowel malignancies can be classified depending upon their cellular origin into four principal histologic types: adenocarcinomas, lymphomas, neuroendocrine tumors or carcinoids and lymphomas, which also include gastrointestinal stromal tumors. The relative ‘rarity' of these tumors has led to stagnation in the development of effective curative or adjuvant therapies. Thus, the prognosis of most of these tumors is still dismal. Nevertheless, hope is now on the horizon as new methods such as capsule endoscopy and balloon-assisted enteroscopy have contributed to a rise in the diagnosis of these lesions and a diagnosis at earlier stages. Using balloon-assisted enteroscopy methods it is possible to resect most small bowel polyps such as adenomas and hamartomas. Improved imaging methods have led to a better understanding of these pathologies and hopefully will bring new hopes in therapy. In addition, multi-center studies are being performed to determine the best therapeutic options for small bowel tumors. Key Message New imaging techniques such as capsule endoscopy and balloon-assisted endoscopy have facilitated the early diagnosis of small bowel malignancies, leading to a better understanding of the biology of these tumors and to improved clinical outcomes for the patient. Practical Implications Although relatively rare, the incidence of tumors and polyps in the small intestine has increased over the past 20 years. The use of endoscopic or radiologic techniques is crucial for the detection and resection of polyps. It is highly recommended to perform a submucosal injection of epinephrine-saline solution prior to endoscopic resection. Due to their non-specific symptoms, neuroendocrine tumors are often diagnosed in advanced stages; surgical excision of the primary tumor is key to a better prognosis. The main therapies for neuroendocrine tumors are surgery, chemoembolization, chemotherapy and the use of somatostatin analogues. Small bowel adenocarcinomas are extremely rare but can be highly fatal. Surgical resection is still the core treatment, though fluoropyrimidine and oxaliplatin-based chemotherapy have shown beneficial effects for the treatment of metastatic disease. Amongst the gastrointestinal stromal tumors, 30% are located in the small intestine. The management of gastrointestinal stromal tumors requires a combination of surgery, pathology techniques and pharmacological interventions, including the use of tyrosine kinase inhibitors.
Treatment for Outpatients with Comorbid Schizophrenia and Substance Use Disorders: A Review
Authors: De Witte Nele A.J. , Crunelle Cleo L. , Sabbe Bernard , Moggi Franz , Dom Geert
Published: February 2014

Aims: This review provides evidence of which interventions need to be part of effective outpatient integrated treatment for patients with comorbid schizophrenia and substance use disorders. Methods: A total of 14 randomized controlled trials were included. Effect sizes are provided to assess the magnitude of the treatments' efficacy. Results: Despite the studies' heterogeneity, we can conclude that certain programs (e.g. Behavioral Treatment for Substance Abuse in Severe and Persistent Mental Illness ) and specific interventions (e.g. motivational interviewing, family interventions) seem to be effective. Moreover, programs integrating multiple interventions are more likely to be positively related to better outcomes than single interventions. Finally, the lack of difference between effect sizes of assertive community treatment compared to case management suggests that a lower caseload is not necessary for positive treatment outcomes. Conclusion: Integrated treatment seems advantageous, although effect sizes are mostly modest. More homogeneous and qualitative sound studies are needed.
Hyalinizing Trabecular Tumor Masquerading as Papillary Thyroid Carcinoma on Fine-Needle Aspiration
Authors: Howard Brittany E. , Gnagi Sharon H. , Ocal I. Tolgay , Hinni Michael L.
Published: February 2014

Background/Aims: Hyalinizing trabecular tumors are rare neoplasms of the thyroid gland often mistaken for thyroid carcinoma on fine-needle aspiration. We review the distinguishing characteristics of hyalinizing trabecular tumors and their management. Methods: We present the case of a patient diagnosed with papillary thyroid carcinoma on fine-needle aspiration as well as a review of the literature. Results: Intraoperative findings were felt to be inconsistent with papillary thyroid carcinoma and only a thyroid lobectomy was performed pending the results from pathologic evaluation, which confirmed a benign process and a diagnosis of hyalinizing trabecular tumor. Due to the diagnostic difficulty in distinguishing hyalinizing trabecular tumors from thyroid carcinomas on fine-needle aspiration, many patients receive overtreatment for what is primarily a benign disease. Conclusions: Recognition of hyalinizing trabecular tumors as a possible benign etiology of a thyroid mass can facilitate appropriate management.
Intake of Fatty Acids in General Populations Worldwide Does Not Meet Dietary Recommendations to Prevent Coronary Heart Disease: A Systematic Review of Data from 40 Countries
Authors: Harika Rajwinder K. , Eilander Ans , Alssema Marjan , Osendarp Saskia J.M. , Zock Peter L.
Published: February 2014

Aim: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). Methods: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. Results: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. Conclusions: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.
The Role of Systematic Reviews and Meta-Analyses of Incidence and Prevalence Studies in Neuroepidemiology
Authors: Fiest K.M. , Pringsheim T. , Patten S.B. , Svenson L.W. , Jetté N.
Published: February 2014

Background: Systematic reviews and meta-analyses on the incidence and prevalence of neurological conditions are important methods of quantifying the burden and risk of disease. Methods: The rigorous methodology required in order to minimize publication bias, account for study heterogeneity, and variation in study quality are described. When appropriate, a meta-analysis is a powerful statistical tool that can help synthesize a vast literature quantitatively, taking into account study heterogeneity. As the epidemiology of neurological conditions continue to be widely studied internationally, systematic reviews and meta-analyses have become essential. Results: If not conducted carefully, systematic reviews and meta-analyses in neuroepidemiology may lead to erroneous conclusions. It is important to consider various methodological, clinical and statistical factors at all stages of the review and analysis process. Detailed documentation should be kept to assist in the reporting process. Conclusions: Published reporting standards should be consulted when conducting systematic reviews and meta-analyses of the incidence and prevalence of neurological conditions, though reporting standards specific to neuroepidemiology are urgently needed.
Surgical Treatment of Patients with Rasmussen Encephalitis
Authors: Guan Yuguang , Zhou Jian , Luan Guoming , Liu Xingzhou
Published: February 2014

Background: Rasmussen encephalitis (RE) is a rare progressive encephalitis that results in intractable seizures, cognitive decline and hemiparesis. Surgery seems to be the only effective way to control seizures in RE patients. Objective: To describe the clinical, electrophysiological, neuroradiological and histological findings of our patients with RE and to evaluate the outcome of their surgical treatment. Methods: A total of 20 patients were identified by the criteria of RE. Surgery was conducted in the left hemisphere in 6 patients and in the right hemisphere in 14. The surgical methods included anatomical hemispherectomy, functional hemispherectomy, hemispherotomy, lesion resection, multilobar resection, selective resection and bipolar electrocoagulation of functional cortexes. Results: The mean follow-up period was 5.45 years (range 3-8). After surgery, 16 patients (80%) were evaluated as being Engel class I. All of the patients had increases in cognitive abilities after surgery except 1 patient with bilateral RE. After surgery, most patients could walk independently, but the fine movement of the hands was lost. Postoperative hydrocephalus was observed in 1 patient after functional hemispherectomy, and there was no death in this series. Conclusion: Hemispherectomy and hemispherotomy were both confirmed as beneficial procedures in controlling seizures and improving quality of the life in RE cases.
Methodological Difficulties in the Conduct of Neuroepidemiological Studies in Low- and Middle-Income Countries
Authors: Bharucha Nadir , Odermatt Peter , Preux Pierre-Marie
Published: February 2014

Background: The majority of people with epilepsy (PWE) live in low- and middle-income countries (LMICs). However, they remain largely untreated and the bulk of resources are used to treat patients in the developed world. This disparity constitutes a challenge for neuroepidemiological studies on a global scale. In the past, several studies have focused on diverse populations in disparate countries at various periods of time and for particular purposes. The specificity of different contexts and circumstances makes it difficult to analyse PWE as a group either qualitatively or quantitatively. Such methodological limitations are further complicated by a lack of logistical support. There is a lack of interest in conducting studies, which results in inadequate funding and, in addition, there is the considerable challenge of publishing research reports from LMICs in peer-reviewed international journals. Methods: This paper focuses on methodological problems related to studies in LMICs and attempts to give the reasons for their limitations using epilepsy as an example. Results: Regional conditions and environmental factors must be given careful consideration in the research design because of the importance of understanding the challenges of living in these environments. There are further limitations to the successful implementation of studies. Existing information on epilepsy is often not readily accessible; there is a lack of census data, and migratory patterns into cities make enumeration and sampling even more challenging. As there is usually no well-developed healthcare system a door-to-door screening process is often the only way to identify those with convulsive epilepsy. The questionnaire and study design should preferably be adapted from standardized protocols, and pre-tested and validated in local conditions. Conclusions: Systematic reviews and meta-analyses of studies in LMICs can provide data on the burden, risk factors, treatment and outcome of epilepsy only if the primary studies used are properly conducted using uniform and comparable methodology. The use of consistent replicable neuroepidemiological methods in primary studies and systematic reviews enable reduction of the treatment gap and better epilepsy care.
An Integrated Stroke Model with a Consistent Penumbra for the Assessment of Neuroprotective Interventions
Authors: Yang Dong , Nakajo Yukako , Iihara Koji , Kataoka Hiroharu , Nakagawara Jyoji , Zhao Qiang , Yanamoto Hiroji
Published: February 2014

Background/Aim: A longer period of vessel occlusion reduces the coefficient of variation of the infarct lesion size [‘infarct variation coefficient' (IVC)] due to a gradual expansion of the lesion within a limited territory defined by the vascular anatomy, but it increases the mortality rate. A crucial issue in the induction of experimental focal cerebral ischemia has been to achieve a low IVC value and a low mortality rate. We attempted to improve IVC and mortality using the 3-vessel occlusion model. Methods: We introduced a new, transtemporal fascia approach to expose the zygomatic arch, in which the fascia of the temporal muscle is cut and retracted dorsally together with the facial nerve and the vein en bloc. Results/Conclusion: The approach avoided traumatic venous bleeding around the zygomatic arch. We established a bloodless model of focal ischemia that can produce a consistent degree of reduction in the regional cerebral blood flow within the ischemic penumbra. The model, characterized by a 15-min ischemia, an IVC of 15-21%, and low mortality after ischemia, is expected to produce reliable preclinical evidence in the assessment of neuroprotective interventions for ischemic stroke. The entire procedure is presented in the online supplementary video (www. karger.com/doi/10.1159/000356048).
Monitoring Dialysis Outcomes across the World - The MONDO Global Database Consortium
Authors: von Gersdorff Gero D. , Usvyat Len , Marcelli Daniele , Grassmann Aileen , Marelli Cristina , Etter Michael , Kooman Jeroen P. , Power Albert , Toffelmire Ted , Haviv Yosef S. , Guinsburg Adrian , Barth Claudia , Schaller Mathias , Bayh Inga , Scatizzi Laura , Tashman Adam , Thijssen Stephan , Levin Nathan W. , van der Sande Frank M. , Pusey Charles , Wang Yuedong , Kotanko Peter
Published: February 2014

Background/Aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.
Significance of Background Coloration in Endoscopic Detection of Early Esophageal Squamous Cell Carcinoma
Authors: Minami H. , Isomoto H. , Inoue H. , Akazawa Y. , Yamaguchi N. , Ohnita K. , Takeshima F. , Hayashi T. , Nakayama T. , Nakao K.
Published: February 2014

Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo-esophageal region have dramatically improved together with development of less invasive endoscopic treatment. It is essential for gastrointestinal endoscopists to detect lesions when they are still endoscopically treatable, especially in this region since surgical approach can still be extremely invasive. Pioneers have found some notable fundamental alterations in early SCC and created several classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the intrapapillary capillary (IPCL) classification, which focused on the microvascular change of the mucosal surface. One of the significances of this classification is that it clearly distinguished the lesions that require further pathological evaluation by categorizing the diameter change of the IPCLs. On the other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of microvessels as well as change of the vascular arrangement in the area. Most recently, the Japan Esophageal Society constructed a new classification uniting these two exemplary classifications as the ‘Japanese Classification of Magnifying Endoscopy for Early Squamous Cell Carcinoma'. This classification was intended to be simple and easily applicable in general clinical practice. Brownish color change between the IPCLs has reported to be one of the useful findings in distinguishing early SCC from benign changes such as inflammatory change and low-grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon remains unclear. We recently examined the association of color change with hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of Hb in superficial vessels in the gastrointestinal tract. This review article also describes our examination of a distinct finding in esophageal cancer, namely, ‘background coloration'.
Biomarkers for Predicting the Efficacy of Anti-Epidermal Growth Factor Receptor Antibody in the Treatment of Colorectal Cancer
Authors: Okada Yasuyuki , Miyamoto Hiroshi , Goji Takahiro , Takayama Tetsuji
Published: February 2014

Anti-epidermal growth factor receptor (EGFR) antibodies have been widely utilized as a standard treatment for metastatic colorectal cancer (CRC). Anti-EGFR antibodies bind competitively to EGFRs to inhibit receptor activation and subsequent signal transduction of the RAS/RAF/MEK pathway and PI3K/AKT pathway. By inhibiting EGFR-mediated signal transduction, anti-EGFR antibodies inhibit cell growth, invasion, metastasis and angiogenesis, and they induce apoptosis. The IgG1-type antibody cetuximab is also capable of inducing antibody-dependent cellular cytotoxicity. Several studies have shown that KRAS mutation is a useful biomarker for predicting the efficacy of anti-EGFR agents, and the major guidelines for the treatment of CRC recommend the use of anti-EGFR antibody only for the cancers with wild-type KRAS. Alterations of other genes, including BRAF, NRAS, PTEN and AKT, and EGFR expression/gene copy number have also been reported to be candidate biomarkers for predicting the efficacy of anti-EGFR agents. The predictive values of these biomarkers are still controversial and further investigations are required.
Advancing Magnetic Resonance Imaging in Crohn's Disease
Authors: Fujii Toshimitsu , Naganuma Makoto , Kitazume Yoshio , Saito Eiko , Nagahori Masakazu , Ohtsuka Kazuo , Watanabe Mamoru
Published: February 2014

Crohn's disease (CD) is a lifelong chronic inflammatory bowel disease associated with diarrhea, abdominal pain, bloody stool and often perianal fistulae. Inflammation in CD involves the entire gastrointestinal tract, especially including the small and large bowels, causing irreversible bowel damage. Frequent imaging examinations are necessary to monitor disease activity and to evaluate response to therapeutic interventions, and, furthermore, to predict recurrence in order to provide appropriate treatment. The suitable imaging modality should be reproducible, well tolerated, safe and free of ionizing radiation. In recent years, imaging used in CD has dramatically changed. Cross-sectional imaging techniques such as computed tomography and magnetic resonance imaging (MRI) are used to investigate not only extraluminal abnormalities, but also intraluminal changes. Recently, new techniques such as MR enteroclysis, enterography, colonography and enterocolonography have been developed. These recent advances enable the use of MRI to assess bowel disorders with high sensitivity, specificity and accuracy. MRI can evaluate simultaneously the bowel surface, bowel wall, abdominal abscesses and perianal lesions, such as perianal fistulae and perianal abscesses, without the problem of overlapping bowel loops. Therefore, MRI has the potential for evaluation of the overall disease activity of CD without radiation exposure. We believe that MRI is a suitable first choice imaging modality in the assessment of CD.
Prediction of the Remnant Liver Hypertrophy Ratio after Preoperative Portal Vein Embolization
Authors: Kasai Y. , Hatano E. , Iguchi K. , Seo S. , Taura K. , Yasuchika K. , Mori A. , Kaido T. , Tanaka S. , Shibata T. , Shibata T. , Uemoto S.
Published: February 2014

Background: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. Methods: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. Results: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). Conclusions: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.
Gender Differences in the Quality of Life of Patients with Liver Cirrhosis Related to Hepatitis C after Liver Transplantation
Authors: Bianco Tonino , Cillo Umberto , Amodio Piero , Zanus Giacomo , Salari Annalisa , Neri Daniele , Bombonato Giancarlo , Schiff Sami , Baggio Giovannella , Ronco Claudio , Brocca Alessandra , Soni Sachin , Minazzato Lina
Published: February 2014

Background: Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, which adversely affects the quality of life (QoL) of the patient. The gender of the patient may be an important variable in the way severity of the disease is perceived. The aim of our study is to evaluate the effect of the gender variable on QoL in HCV-positive patients. Methods: This study included a total of 52 patients (26 men and 26 women) who completed a 1-year follow-up after liver transplantation. QoL was assessed using the SF-36 questionnaire. Results: Male subjects have significantly higher scores on physical role functioning, bodily pain and physical activity compared with females. Females have a better QoL compared to males with regard to the emotional state and mental health. Conclusions: These results show a significant effect of the gender variable on QoL in HCV patients.
Fluid Management in the Intensive Care Unit: Bioelectrical Impedance Vector Analysis as a Tool to Assess Hydration Status and Optimal Fluid Balance in Critically Ill Patients
Authors: Basso Flavio , Berdin Giovanna , Virzì Grazia Maria , Mason Giacomo , Piccinni Pasquale , Day Sonya , Cruz Dinna N. , Wjewodzka Marzena , Giuliani Anna , Brendolan Alessandra , Ronco Claudio
Published: February 2014

Background: Fluid balance disorders are a relevant risk factor for morbidity and mortality in critically ill patients. Volume assessment in the intensive care unit (ICU) is thus of great importance, but there are currently few methods to obtain an accurate and timely assessment of hydration status. Our aim was to evaluate the hydration status of ICU patients via bioelectric impedance vector analysis (BIVA) and to investigate the relationship between hydration and mortality. Methods: We evaluated 280 BIVA measurements of 64 patients performed daily in the 5 days following their ICU admission. The observation period ranged from a minimum of 72 h up to a maximum of 120 h. We observed the evolution of the hydration status during the ICU stay in this population, and analyzed the relationship between mean and maximum hydration reached and mortality - both in the ICU and at 60 days - using logistic regression. Results: A state of overhydration was observed in the majority of patients (70%) on admission, which persisted during the ICU stay. Patients who required continuous renal replacement therapy (CRRT) were more likely to be overhydrated starting from the 2nd day of observation. Logistic regression showed a strong and significant correlation between mean/maximum hydration reached and mortality, both independently and correcting for severity of prognosis. Conclusions: Fluid overload measured by BIVA is a frequent condition in critically ill patients - whether or not they undergo CRRT - and a significant predictor of mortality. Hence, hydration status should be considered as an additional prognosticator in the clinical management of the critically ill patient. Key Messages: (i) On the day of ICU admittance, patients showed a marked tendency to overhydration (>70% of total). This tendency was more pronounced in patients on CRRT. (ii) Hyperhydration persisted during the ICU stay. Patients who underwent CRRT showed significantly higher hyperhydration from the 2nd day of hospitalization. (iii) Nonsurvivors showed worse hyperhydration patterns in comparison to survivors in logistic univariate analysis (p < 0.05). This relationship between hydration and mortality is confirmed even when controlling for the effect of a worse prognosis approximated by any of three ICU scoring systems (APACHE II, SAPS II and SOFA). Mean and maximum hydration levels present a stronger correlation with mortality than with mean and maximum cumulative fluid balance reached during the observation period.
Cardiorenal Syndrome Type 4: Management
Authors: Clementi Anna , Virzì Grazia Maria , Brocca Alessandra , de Cal Massimo , Vescovo Giorgio , Granata Antonio , Ronco Claudio
Published: February 2014

Cardiorenal syndrome (CRS) type 4, or chronic renocardiac syndrome, has been defined as ‘chronic abnormalities in renal function leading to cardiac disease' and recognizes the extreme burden of cardiovascular (CV) disease (CVD) risk in patients with chronic kidney disease (CKD). CKD is common and increasingly recognized as a risk factor for CVD. Although during the past 10 years CV morbidity and mortality have decreased markedly in the general population, their rates still remain high among CKD patients. For this reason, CKD patients should be evaluated thoroughly for CV risk factors which require an aggressive management, given the significant implications of CRS type 4 at both individual and societal level. We will review the management of the most important conventional and nonconventional CVD risk factors related to CKD.
Cytotoxic Effects of p-Cresol in Renal Epithelial Tubular Cells
Authors: Brocca Alessandra , Virzì Grazia Maria , de Cal Massimo , Cantaluppi Vincenzo , Ronco Claudio
Published: February 2014

Background: The uremic syndrome is characterized by a deterioration of kidney function due to the accumulation of uremic toxins. Currently, 100 different uremic toxins have been identified. Uremic toxins are particularly difficult to remove by conventional dialysis treatments and are the major causes of mortality in patients with chronic kidney disease (CKD). p-Cresol is a well-known uremic toxin which accumulates in uremic serum. Our aim was to evaluate the in vitro effect of p-cresol on apoptosis and necrosis in renal tubular cells (RTCs) to better understand the pathophysiological effect of this toxin on the kidney. Methods: We studied apoptosis and necrosis in RTCs, which were incubated for 24 h with increasing concentrations of p-cresol. A DNA ladder was noted in treated cells as a qualitative marker of the apoptotic process. Furthermore, we performed quantitative analysis of cell viability using a flow cytometer and assessed caspase-3 activity. Results: Incubation with p-cresol for 24 h resulted in a significant reduction in RTC viability. DNA isolated from RTCs incubated with increasing p-cresol concentrations for 24 h showed a ‘ladder' pattern of apoptosis at p-cresol concentrations of 10, 5 and 2.5 mg/l. However, we did not observe any significant changes in apoptosis levels detected by annexin V and caspase-3 compared with untreated cells. Cytofluorimetric analysis of necrosis highlighted significantly higher cell death rates in RTCs incubated with the higher p-cresol concentrations (range 40-10 mg/l) compared with other concentrations (5-2.5 mg/l) and untreated cells (p < 0.05). Necrosis induction was stronger at higher p-cresol concentrations. Conclusion: It is necessary to develop new therapeutic and dialytic strategies to manage p-cresol concentrations in CKD.
Potential for Biomarkers of Chronic Kidney Disease-Mineral Bone Disorder to Improve Patient Care
Authors: Alderson H.V. , Ritchie J.P. , Green D. , Chiu D. , Kalra P.A.
Published: February 2014

Chronic kidney disease (CKD) is a growing public health problem. Cardiovascular disease is common in CKD, but standard risk assessment tools perform poorly in this population. Equally, despite CKD being associated with an increased risk for death and dialysis, standard biochemical measurements have limited prognostic value. Novel serum biomarkers may aid risk assessment; however, studies have shown varying clinical utility in relation to progression of CKD, incident cardiovascular disease and death. This inconsistency may relate to limitations in our understanding of the biological actions and interactions of these biomarkers. This review discusses a range of biomarkers in relation to these clinical endpoints in CKD-mineral bone disorder. We consider where biomarkers may enhance risk stratification and improve clinical management, but also highlight where they fall short of achieving this objective.
Existence of Ipsilateral Hemiparesis in Ischemic and Hemorrhagic Stroke: Two Case Reports and Review of the Literature
Authors: Saada F. , Antonios N.
Published: February 2014

Supratentorial stroke presenting as contralateral hemiparesis is predominantly related to contralateral projection of the corticospinal tract. While most corticospinal fibers decussate at the level of the medulla, some tracts continue descending as ipsilateral ventral corticospinal fibers. In this systematic review of the literature and 2 case reports specifically seen in our institute, we describe the presence of ipsilateral hemiparesis in ischemic and hemorrhagic stroke patients. We compiled available information about the existence of uncrossed corticospinal tracts and/or the presence of bilateral operating motor cortical networks. There was an association in patients with congenital uncrossed corticospinal tracts and posterior fossa malformations. There was also a high correlation of ipsilateral hemiparesis in patients with remote infarction. A previous stroke was seen in 50% of the patients, all except for 1 case were ischemic in nature. Patients with previous infarcts do demonstrate an adaptive compensation for damaged or disconnected regions of an injured area. This emphasizes the need to consider the investigation for previous infarctions or underlying genetic structural defects by using certain imaging modality.
Cannabis Finds Its Way into Treatment of Crohn's Disease
Authors: Schicho Rudolf , Storr Martin
Published: February 2014

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn's disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions.
Autoantibodies to Glutamate Receptor Antigens in Multiple Sclerosis and Rasmussen's Encephalitis
Authors: Trippe Juergen , Steinke Katja , Orth Angela , Faustmann Pedro M. , Hollmann Michael , Haase Claus G.
Published: February 2014

Background: Glutamate and its specific ionotropic receptors, including N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, are supposed to play an important role in neurodegeneration as well as neuronal regeneration. Although autoantibodies (aab) to glutamate receptors (GluR) have been identified in several neurologic diseases, including paraneoplastic encephalitis and Rasmussen's encephalitis (RE) with an increasing prevalence, the presence and role of anti-GluR aab in multiple sclerosis (MS) have not been studied yet. Objectives and Methods: In this study, we tested the serum samples of 56 subjects, including patients with relapsing-remitting MS (n = 25), patients with RE (n = 8), and healthy donors (HD; n = 23), for anti-GluR aab by immunoblot analysis of a panel of recombinantly expressed GluR proteins, including GluN1, GluN2C, GluA3, GluK2, and GluD2. Results: aab were mainly found directed against GluN1 and, except for one aab positive to GluK2 in 1 MS patient and 2 HD controls positive for GluA3, no other anti-GluR aab were detected. In the sera of RE patients, no anti-GluR aab were found. In patients with MS, 8 of the 25 sera (32%) tested positive for GluN1. Compared to the HD (6/23; 26%), this difference was not statistically significant (p = 0.28). Conclusions: Our study showed that if anti-GluR aab were detectable in HD and MS patients, they were mainly directed against GluN1 (in particular to oligomeric protein complexes) and were not found in RE. Those antibodies may have low titers and low affinities and might be considered an immune epiphenomenon. Hence, further studies will have to clarify their potential role as a surrogate marker for the extent of neuronal destruction or regeneration, respectively.
Peritoneal Dialysis as a Mode of Treatment for Acute Kidney Injury in Sub-Saharan Africa
Authors: Callegari John , Antwi Sampson , Wystrychowski Grzegorz , Żukowska-Szczechowska Ewa , Levin Nathan W. , Carter Mary
Published: February 2014

Background: Developing sustainable treatment programs for kidney failure in most countries of sub-Saharan Africa continues to remain an imposing challenge. While long-term renal replacement therapies in end-stage renal disease appear beyond national financial capabilities, there exist opportunities for a short-term and affordable treatment of acute kidney injury (AKI). Peritoneal dialysis (PD) is an effective and simpler modality compared to hemodialysis (HD) and can be performed without the need for machinery or electricity, making it an ideal choice in a low-resource setting. Methods: Since cost of treatment is the major obstacle, the goal is to develop a program that is cost effective. Developing an HD program requires a large capital investment by the hospital, needing water treatment systems and machinery and providing for their ongoing repair and maintenance. Gravity-driven PD is a simple, effective modality and can be performed in low-resource locales. Results: In a pediatric program that we started in the Komfo Anokye Teaching Hospital in Kumasi, Ghana, 28 patients have been treated with PD for AKI so far. Half of them were treated successfully and were discharged having fully recovered kidney function. Seven patients (25%) were determined to have end-stage renal disease, whereas 7 others (25%) died during hospitalization. In these cases, late presentation for dialysis may have contributed to the inability to recover. Conclusion: For individuals and governments alike, who are concerned about the cost of providing or paying for dialysis, using PD to treat AKI is an effective and simpler modality compared to HD and can be performed without the need for machinery or electricity, making it an ideal choice in a low-resource setting.
Measuring Physiological Changes during the Transition to Life after Birth
Authors: van Vonderen Jeroen J. , Roest Arno A.W. , Siew Melissa L. , Walther Frans J. , Hooper Stuart B. , te Pas Arjan B.
Published: February 2014

The transition to life after birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by breathing at birth and clamping of the umbilical cord. Lung aeration leads to the establishment of functional residual capacity, allowing pulmonary gas exchange to commence. This triggers a significant decrease in pulmonary vascular resistance, consequently increasing pulmonary blood flow and cardiac venous return. Clamping the umbilical cord also contributes to these hemodynamic changes by altering the cardiac preload and increasing peripheral systemic vascular resistance. The resulting changes in systemic and pulmonary circulation influence blood flow through both the oval foramen and ductus arteriosus. This eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of our knowledge on human neonatal transition is based on human (fetal) data from the 1970s and extrapolation from animal studies. However, there is renewed interest in performing measurements directly at birth. By using less cumbersome techniques (and probably more accurate), our previous understanding of the physiological transition at birth is challenged, as well as the causes and consequences for when this transition fails to progress. This review will provide an overview of physiological measurements of the respiratory and hemodynamic transition at birth. Also, it will give a perspective on some of the upcoming technological advances in physiological measurements of neonatal transition in infants who are unable to make the transition without support.
Thrombolysis in Acute Stroke Patients with Cerebral Small Vessel Disease
Authors: Pantoni Leonardo , Fierini Fabio , Poggesi Anna
Published: February 2014

Background: Thrombolytic treatment is of proven benefit in acute ischemic stroke. The term cerebral small vessel disease (SVD) refers to a group of pathological processes affecting the small arteries, arterioles, venules and capillaries of the brain, and encompasses both ischemic and hemorrhagic lesions. Lacunar stroke, an expression of SVD, is associated with an unfavorable long-term prognosis for an increased risk of death, recurrent stroke and cognitive dysfunction. Nonetheless, the efficacy and safety of intravenous thrombolysis in patients with lacunar stroke has been debated for two main reasons. First, among all ischemic stroke subtypes, lacunar strokes have been considered the most benign. Second, the efficacy of a pharmacological reperfusion has been questioned given the absence of a clear demonstration of thrombosis. Intracerebral hemorrhage (ICH) remains the most devastating and unpredictable complication related to thrombolysis, and neuroimaging evidence of SVD is nowadays recognized as one of the risk factors for thrombolysis-related ICH. Summary: This review is structured in two parts dealing with the questions whether or not patients with lacunar stroke or SVD should be treated with thrombolysis. In the first part, we revised the literature concerning the efficacy of thrombolysis in patients with acute lacunar stroke. We included two types of studies: those in which patients with lacunar stroke receiving recombinant human tissue plasminogen activator (rt-PA) were compared with lacunar stroke patients receiving placebo, and those in which a comparison was made among different stroke subtype patients treated with rt-PA. In the second part, we reviewed the available evidence on the risk of ICH in patients treated with thrombolysis for ischemic stroke and presenting with neuroimaging evidence of SVD such as white matter lesions (WML) and cerebral microbleeds. We further questioned the extent to which WML and microbleeds could be used as reliable predictors of ICH and the feasibility of their detection in an acute setting. Key Messages: The studies herein reviewed show that thrombolysis is an effective treatment in acute lacunar stroke, and that the presence of cerebral SVD increases the risk of ICH during thrombolysis but does not represent an absolute exclusion criterion. In the future, it can be assumed that the use of MRI on a routine basis might lead to a better quantitative definition of SVD and its correlates, permitting a step forward in thrombolysis decision making.