Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk

Deceased organ donation activity and efficiency in Switzerland between 2008 and 2017: achievements and future challenges.

Various actions have been taken during the last decade to increase the number of organs from deceased donors available for transplantation in Switzerland. This study provides an overview on key figures of the Swiss deceased organ donation and transplant activity between 2008 and 2017. In addition, it puts the evolution of the Swiss donation program's efficiency in relation to the situation in the neighboring countries. This study is an analysis of prospective registry data, covering the period from 1 January 2008 to 31 December 2017. It includes all actual deceased organ donors (ADD) in Switzerland. Donor data were extracted from the Swiss Organ Allocation System. The "donor conversion index" (DCI) methodology and data was used for the comparison of donation program efficiency in Switzerland, Germany, Austria, Italy and France. During the study period there were 1116 ADD in Switzerland. The number of ADD per year increased from 91 in 2008 to 145 in 2017 (+ 59%). The reintroduction of the donation after cardiocirculatory death (DCD) program in 2011 resulted in the growth of annual percentages of DCD donors, reaching a maximum of 27% in 2017. The total number of organs transplanted from ADD was 3763 (3.4 ± 1.5 transplants per donor on average). Of these, 48% were kidneys (n = 1814), 24% livers (n = 903), 12% lungs (n = 445), 9% hearts (n = 352) and 7% pancreata or pancreatic islets (n = 249). The donation program efficiency assessment showed an increase of the Swiss DCI from 1.6% in 2008 to 2.7% in 2017 (+ 69%). The most prominent efficiency growth was observed between 2012 and 2017. Even though Swiss donation efficiency increased during the study period, it remained below the DCI of the French and Austrian donation programs. Swiss donation activity and efficiency grew during the last decade. The increased donation efficiency suggests that measures implemented so far were effective. The lower efficiency of the Swiss donation program, compared to the French and Austrian programs, may likely be explained by the lower consent rate in Switzerland. This issue should be addressed in order to achieve the goal of more organs available for transplantation

High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor

BACKGROUND Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). METHODS A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC

Swelling of the right thigh for over 30 years—The rare finding of a De Garengeot hernia

INTRODUCTION: Femoral hernias may – in some rare cases – contain the appendix, a phenomenon called de Garengeot hernia. It is usually an incidental finding in hernia repair. We found our case to be of interest because of the long standing femoral swelling before peracute appendicitis led to its removal. PRESENTATION OF CASE: We present the case of a 71-year-old woman with a swelling of the right medial thigh for over more than 30 years. When the swelling suddenly grew in size and became tender, she was referred to our emergency department. Sonographically as well as clinically a femoral hernia was diagnosed. Intraoperatively, the appendix was found and open appendectomy as well as a hernioplasty was performed. DISCUSSION: Open appendectomy is an elegant and safe procedure to repair a long standing de Garengeot hernia. Most case reports call for extensive diagnostics such as CT scan etc. We found a sonography of the femoral region to be conclusive. CONCLUSION: Apart from the inherent risk of sudden incarceration in hernias, De Garengeot hernias can also develop peracute appendicitis years after their formation. This differential diagnosis needs to be taken into consideration in patients presenting with the clinical signs of a femoral hernia

In the eye of the hurricane: the Swiss COVID-19 pandemic stepwise shutdown approach in organ donation and transplantation.

The Swiss stepwise shutdown approach in organ donation and transplantation helped to maintain a limited national organ procurement and vital organ transplant activity, avoiding a complete nationwide shutdown of organ donation and transplant activity.&nbsp

Early versus delayed cholecystectomy in patients with biliary acute pancreatitis

BACKGROUND: In patients with biliary acute pancreatitis (AP), cholecystectomy is mandatory to prevent further biliary events, but timing of cholecystectomy remains a subject of ongoing debate. The objective of the present, retrospective study was to compare the outcomes of early (within 2 weeks after onset of disease) versus delayed cholecystectomy in patients with biliary AP. METHODS: Between January 2000 and December 2005, 112 patients underwent cholecystectomy because of biliary AP. Thirteen patients were excluded from analysis because of necrotizing pancreatitis on the initial computed tomography. Thirty-two were operated within 14 days (group A) and 67 after a longer time period (group B). The primary end point of the study was the rate of biliary complications before cholecystectomy. RESULTS: There were no differences regarding conversion rates to open surgery (6% vs 3%; P = .59), local (3% vs 4%; P = 1.00), or systemic complications (0% vs 3%; P = 1.00), and mean postoperative stay (4.7 vs 5.7 days; P = .40). Nevertheless, a greater rate of recurrent biliary pancreatitis was found in the group undergoing cholecystectomy later (0% vs 13%; P > .03). CONCLUSION: The timing of cholecystectomy seems to have no clinically relevant effect on local or systemic complications, but delaying cholecystectomy is associated with an increase of biliary complications in patients with non-necrotizing biliary AP

Histone Deacetylase Inhibitors and Colorectal Cancer: what is new?

Colorectal cancer is the third most common cancer in humans. Cancer has always been regarded as a disease of genetic defects such as gene mutations and deletions, chromosomal abnormalities, which lead to the loss of function of tumor-suppressor genes and/or gain of function or hyperactivation of oncogenes. Modifications on chromatin are considered to be the result of the opposing activities of histone acetyltransferases and histone deacetylases, which affect gene expression. Targeting histone deacetylases, histone deacetylase inhibitors are promising agents, as in solid tumors they are characterized by relatively low toxicity profile and antiproliferative activities. In colorectal cancer, the current experience is mainly experimental but promising. Histone deacetylase inhibitors are currently being admitted as monotherapy or combination therapy either with the conventional chemotherapy or with other agents. Valproic acid combined with ionization may enhance tumor response. Vorinostat was the first drug of this group used in clinical trial in combination with conventional chemotherapy and managed to stabilize advanced colorectal cancer. Experimental results show that combination therapy of vorinostat and decitabine (DNA methyl transferase inhibitor) may have optimal results. However, patients with colorectal cancer need to be recruited in randomized clinical trials in order to evaluate the potential efficiency of these agents

Innovative Methods for the Benefit of Public Health Using Space Technologies for Disaster Response

Space applications have evolved to play a significant role in disaster relief by providing services including remote sensing imagery for mitigation and disaster damage assessments; satellite communication to provide access to medical services; positioning, navigation, and timing services; and data sharing. Common issues identified in past disaster response and relief efforts include lack of communication, delayed ordering of actions (eg, evacuations), and low levels of preparedness by authorities during and after disasters. We briefly summarize the Space for Health (S4H) Team Project, which was prepared during the Space Studies Program 2014 within the International Space University. The S4H Project aimed to improve the way space assets and experiences are used in support of public health during disaster relief efforts. We recommend an integrated solution based on nano-satellites or a balloon communication system, mobile self-contained relief units, portable medical scanning devices, and micro-unmanned vehicles that could revolutionize disaster relief and disrupt different markets. The recommended new system of coordination and communication using space assets to support public health during disaster relief efforts is feasible. Nevertheless, further actions should be taken by governments and organizations in collaboration with the private sector to design, test, and implement this system

In the eye of the hurricane: the Swiss COVID-19 pandemic stepwise shutdown approach in organ donation and transplantation

AIMS OF THE STUDY Coronavirus disease 2019 (COVID-19) pandemic has an ongoing severe impact on health care, but there is a lack of information on COVID-19 and its effect on organ donation and solid organ transplantation. Early in the pandemic, Swisstransplant, the Swiss National Foundation for Organ Donation and Transplantation, set up a national stepwise shutdown approach to avoid a collapse of transplant activities during phases of the pandemic with sufficient available healthcare capacities. The approach allowed regional adaptation of transplant-associated activities depending on available healthcare capacities, instead of implementing a rigid centralistic system. The aim of this study was to describe the stepwise shutdown approach and to determine whether this flexible approach would be helpful for avoiding complete cessation of transplant activities during a pandemic. METHODS A retrospective nationwide study was conducted to evaluate donor procurement and solid organ transplantation activity in Switzerland during the COVID-19 pandemic (1 January to 31 May 2020). To assess the impact of the flexible stepwise shutdown plan on overall transplantation activity in Switzerland, we compared total and individual numbers of transplanted organs during the first wave of the pandemic with the transplant activity immediately before the pandemic. RESULTS The pandemic evolved heterogeneously across Swiss cantons, severely affecting western cantons and the Ticino. Overall, there was a reduction in deceased donor transplants in Switzerland of 16.7% in March and April 2020 (during the pandemic) compared with January and February 2020 (prior to the pandemic), the decline mostly driven by kidney transplants (−27.6%) and to a lesser extent by transplants of vital organs (heart, lungs, liver) (−5.9%). In May 2020, solid organ transplantation activity in Switzerland again exceeded the average of pre-pandemic months (January and February), with 35 transplanted organs, but the increase from April to May 2020 was exclusively driven by liver and kidney transplants. CONCLUSION The Swiss stepwise shutdown approach in organ donation and transplantation helped to maintain a limited national organ procurement and vital organ transplant activity, avoiding a complete nationwide shutdown of organ donation and transplant activity. We therefore propose a flexible shutdown approach that regulates transplant activities dependent on regional healthcare resources rather than uniform centralistic regulations. This approach proved to be especially useful during a regional heterogeneously evolving pandemic