What works? Interventions for maternal and child undernutrition and survival

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.     

Tumor-related factors and patient’s age influence survival after resection for ampullary adenocarcinoma

Background/Purpose

The majority of surgeons agree that ampullary adenocarcinoma should be removed by partial pancreatoduodenectomy. Favoring extended resection, based on the uncertainty of the preoperative diagnosis and the higher probability of clear resection margins, we aimed to disclose the results of this surgical procedure in terms of postoperative morbidity and mortality, and to identify prognosticators of long-term survival.

Methods

We documented, prospectively, 25 consecutive patients with adenocarcinoma of the papilla of Vater in whom pylorus-preserving pancreatoduodenectomy was performed. Clinical data, pathology reports, International Union Against Cancer (UICC) tumor stage, postoperative morbidity, mortality, and long-term follow-up results were evaluated. The Kaplan-Meier method and log-rank test were applied for univariate analysis. The Cox proportional hazard model was used for multivariate analysis.

Results

Postoperative mortality was 4%, overall morbidity was 32%, and pancreas-associated morbidity was 8%. Mean survival time was 53.8 months. Tumor size, N status, UICC stage, lymphatic invasion, blood vessel infiltration, R0 resection, and age of patient at the cutoff of 70 years were independent predictors of survival on univariate analysis. Multivariate analysis, however, disclosed no independent predictors of prognosis.

Conclusions

Pancreatoduodenectomy for ampullary carcinoma is reasonable in terms of postoperative morbidity and mortality. Tumor-related factors, R0 resection, and advanced age appeared as the main predictors of survival.     

Intraislet SLIT–ROBO signaling is required for beta-cell survival and potentiates insulin secretion

We previously cataloged putative autocrine/paracrine signaling loops in pancreatic islets, including factors best known for their roles in axon guidance. Emerging evidence points to nonneuronal roles for these factors, including the Slit–Roundabout receptor (Robo) family, in cell growth, migration, and survival. We found SLIT1 and SLIT3 in both beta cells and alpha cells, whereas SLIT2 was predominantly expressed in beta cells. ROBO1 and ROBO2 receptors were detected in beta and alpha cells. Remarkably, even modest knockdown of Slit production resulted in significant beta-cell death, demonstrating a critical autocrine/paracrine survival role for this pathway. Indeed, recombinant SLIT1, SLIT2, and SLIT3 decreased serum deprivation, cytokine, and thapsigargin-induced cell death under hyperglycemic conditions. SLIT treatment also induced a gradual release of endoplasmic reticulum luminal Ca²⁺, suggesting a unique molecular mechanism capable of protecting beta cells from endoplasmic reticulum stress-induced apoptosis. SLIT treatment was also associated with rapid actin remodeling. SLITs potentiated glucose-stimulated insulin secretion and increased the frequency of glucose-induced Ca²⁺ oscillations. These observations point to unexpected roles for local Slit secretion in the survival and function of pancreatic beta cells. Because diabetes results from a deficiency in functional beta-cell mass, these studies may contribute to therapeutic approaches for improving beta-cell survival and function.Emerging evidence highlights the important role of locally released pancreatic islet peptide factors on beta-cell mass growth, maintenance, and survival (1–12). We have published a list of 233 ligands and 234 receptors expressed in islets and/or beta cells (12). Although our list is undoubtedly not comprehensive, it provides a starting point for the investigation of factors in adult islets that had previously only been reported in other cell types or in fetal pancreas (12). We identified a group of secreted molecules known to provide axonal guidance cues during neuronal development, comprising members of the netrin, slit, semaphorin, and ephrin families (13). The parallels between cell fate decisions in neurons and the endocrine pancreas prompted us to examine some factors in detail and discover that netrin treatment modulates beta-cell survival signaling (12).The Slit ligands and their Roundabout receptors (Robo) were discovered in Drosophila as regulators of axon guidance during development (14–17). Mammalian homologs of Slit and Robo with functions outside of axon guidance have since been identified (18, 19). Slit ligands have been implicated in liver, kidney, lung, and mammary development by modulating cell adhesion, migration, differentiation, and death (18, 20, 21). It was not known whether Slit–Robo signaling functions in beta cells. Here, we report that Slit expression can be regulated by stress and that local Slit production is required for beta-cell survival and optimal function via a mechanism involving endoplasmic reticulum (ER) Ca²⁺ homeostasis and actin remodeling. Our work provides examples of local guidance factors that are required for beta-cell survival and suggests avenues for protecting functional beta-cell mass.     

Cancer survival statistics for patients and healthcare professionals – a tutorial of real-world data analysis

Monitoring survival of cancer patients using data collected by population-based cancer registries is an important component of cancer control. In this setting, patient survival is often summarized using net survival, that is survival from cancer if there were no other possible causes of death. Although net survival is the gold standard for comparing survival between groups or over time, it is less relevant for understanding the anticipated real-world prognosis of patients. In this review, we explain statistical concepts targeted towards patients, clinicians and healthcare professionals that summarize cancer patient survival under the assumption that other causes of death exist. Specifically, we explain the appropriate use, interpretation and assumptions behind statistical methods for competing risks, loss in life expectancy due to cancer and conditional survival. These concepts are relevant when producing statistics for risk communication between physicians and patients, planning for use of healthcare resources, or other applications when consideration of both cancer outcomes and the competing risks of death is required. To reinforce the concepts, we use Swedish population-based data of patients diagnosed with cancer of the breast, prostate, colon and chronic myeloid leukaemia. We conclude that when choosing between summary measures of survival it is critical to characterize the purpose of the study and to determine the nature of the hypothesis under investigation. The choice of terminology and style of reporting should be carefully adapted to the target audience and may range from summaries for specialist readers of scientific publications to interactive online tools aimed towards lay persons.     

IL-7 is critical for homeostatic proliferation and survival of na?ve T cells

In T cell-deficient conditions, naive T cells undergo spontaneous "homeostatic" proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naive T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naive T cells underwent homeostatic proliferation in IL-4(-) and IL-15(-) hosts but proliferated minimally in IL-7(-) hosts. In addition to homeostatic proliferation, the prolonged survival of naive T cells requires IL-7. Thus, na?ve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation.     

MELD vs Child-Pugh and creatinine-modified Child-Pugh score for Dredicting survival in patients with decompensated cirrhosis

AIM: Model of End-stage Liver Disease (MELD) score has recently gained wide acceptance over the old Child-Pugh score in predicting survival in patients with decompensated cirrhosis, although it is more sophisticated. We compared the predictive values of MELD, Child-Pugh and creatinine-modified Child-Pugh scores in decompensated cirrhosis. METHODS: A cohort of 102 patients with decompensated cirrhosis followed-up for a median of 6 mo was studied. Two types of modified Child-Pugh scores estimated by adding 0-4 points to the original score using creatinine levels as a sixth categorical variable were evaluated. RESULTS: The areas under the receiver operating characteristic curves did not differ significantly among the four scores, but none had excellent diagnostic accuracy (areas: 0.71-0.79). Child-Pugh score appeared to be the worst, while the accuracy of MELD was almost identical with that of modified Child-Pugh in predicting short-term and slightly better in predicting medium-term survival. In Cox regression analysis, all four scores were significantly associated with survival, while MELD and creatinine-modified Child-Pugh scores had better predictive values (c-statistics: 0.73 and 0.69-0.70) than Child-Pugh score (c-statistics: 0.65). Adjustment for gamma-glutamate transpeptidase levels increased the predictive values of all systems (c-statistics: 0.77-0.81). Analysis of the expected and observed survival curves in patients subgroups according to their prognosis showed that all models fit the data reasonably well with MELD probably discriminating better the subgroups with worse prognosis. CONCLUSION: MELD compared to the old Child-Pugh and particularly to creatinine-modified Child-Pugh scores does not appear to offer a clear advantage in predicting survival in patients with decompensated cirrhosis in daily clinical practice.     

Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma

Purpose

Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte–macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

Methods

In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

Results

Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

Conclusions

Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.     

The immune profiles and “minimizing tacrolimus” strategy for long-term survival recipients after liver transplantation

正To the Editor : Liver transplantation (LT) has become a major and effective therapeutic approach for end-stage liver disease [1] . However, 10- year graft and patient survival rates remained low with 54% and 61%, respectively [2] . Improving the outcome of long-term LT has become a major focus of the transplantation community.     

Prognostic factors for survival in patients with advanced renal cell carcinoma treated with interleukin-2 and interferon-α

A group of 73 patients with advanced renal cell carcinoma, treated in different phase II trials with interferon and/or interleukin-2, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were very similar across studies and included ECOG performance status 2, measurable or evaluable disease and no CNS metastases. The overall response rate was 8%. The overall survival was 33% at 2 years and 18% at 1 year. In the univariate analysis three prognostic factors were correlated with disease outcome: ECOG performance status (0 versus 1), time from diagnosis to treatment (12 months versus >12 months) and number of metastatic sites (1 versus 2). Multivariate analysis identified ECOG performance status and number of metastatic sites as important prognostic factors for survival. The true impact on patient survival of the selection of patients rather than the treatment itself should be evaluated in controlled trials.Abbreviations IFN interferon - IL interleukin - RCC renal cell carcinoma - PS performance status     

Improved local control and survival with the “sandwich” technique of pelvic radiotherapy for resectable rectal cancer

PURPOSE: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients. METHODS: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination. RESULTS: Operative mortality was 2 percent in the sandwich radiotherapy groupvs.7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P=0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P=0.05). CONCLUSIONS: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.     

Conversion of laparoscopic colorectal resection for cancer: What is the impact on short-term outcomes and survival?

Laparoscopic resection for colon and rectal cancer is associated with quicker return of bowel function, reduced postoperative morbidity rates and shorter length of hospital stay compared to open surgery, with no differences in long-term survival. Conversion to open surgery is reported in up to 30% of patients enrolled in randomized control trials comparing open and laparoscopic colorectal resection for cancer. In this review, reasons for conversion are anatomical-related factors, disease-related-factors and surgeon-related factors. Body mass index, local tumour extension and co-morbidities are independent predictors of conversion. The current evidence has shown that patients with converted resection for colon cancer have similar outcomes compared to patients undergoing a laparoscopic completed or open resection. The few studies that have assessed the outcomes after conversion of laparoscopic rectal resection reported significantly higher rates of complications and longer length of hospital stay in converted patients compared to laparoscopically treated patients. No definitive conclusions can be drawn when converted and open rectal resections are compared. Early and pre-emptive conversion appears to have more favourable outcomes than reactive conversion; however, further large studies are needed to better define the optimal timing of conversion. With regard to long-term oncologic outcome, overall and disease-free survival in the case of conversion in laparoscopic colorectal cancer surgery seems to be worse than those achieved in patients in whom resection was successfully completed by laparoscopy. Although a worse long-term oncologic outcome has been suggested, it remains difficult to draw a proper conclusion due to the heterogeneity of the long-term outcomes as well as the inclusion of both colon and rectal cancer patients in most of the studies. Therefore, we discuss the currently available evidence of the impact of conversion in laparoscopic resection for colon and rectal cancer on both short-term outcomes and long-term survival.     

Does N ratio affect survival in D1 and D2 lymph node dissection for gastric cancer？

AIM:To identify whether there could have been changes in survival if lymph node ratio (N ratio) had been used.METHODS:We assessed 334 gastric adenocarcinoma cases retrospectively between 2001 and 2009.Two hundred and sixteen patients out of 334 were included in the study.Patients were grouped according to disection1 (D1) or dissection 2 (D2) dissection.We compared the estimated survival and actual survival determined by Pathologic nodes (pN) class and N ratio,and SPSS 15.0 software was used for statistical ...     

Abl kinases are required for vascular function,Tie2 expression,and angiopoietin-1–mediated survival

Endothelial dysfunction is associated with diverse cardiovascular pathologies. Here, we show a previously unappreciated role for the Abelson (Abl) family kinases (Abl and Arg) in endothelial function and the regulation of angiogenic factor pathways important for vascular homeostasis. Endothelial Abl deletion in Arg-null mice led to late-stage embryonic and perinatal lethality, with mutant mice displaying focal loss of vasculature and tissue necrosis. Loss of Abl kinases led to increased endothelial cell apoptosis both in vitro and in vivo, contributing to vascular dysfunction, infarction, and tissue damage. Mechanistically, we identify a unique dual role for Abl kinases in the regulation of angiopoietin/Tie2 protein kinase signaling. Endothelial Abl kinases modulate Tie2 expression and angiopoietin-1–mediated endothelial cell survival. These findings reveal a critical requirement for the Abl kinases in vascular development and function, which may have important implications for the clinical use of Abl kinase inhibitors.     

Does blood group affect survival following pancreatoduodenectomy for periampullary malignancy?

Background

Blood group is reported to have an effect upon survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma. The effect of blood group is not known, however, among patients with other periampullary cancers. This study sought to review this.