Crossing signals: bioactive lipids in the microvasculature.

The primary function of the arterial microvasculature is to ensure that regional perfusion of blood flow is matched to the needs of the tissue bed. This critical physiological mechanism is tightly controlled and regulated by a variety of vasoactive compounds that are generated and released from the vascular endothelium. Although these substances are required for modulating vascular tone, they also influence the surrounding tissue and have an overall effect on vascular, as well as parenchymal, homeostasis. Bioactive lipids, fatty acid derivatives that exert their effects through signaling pathways, are included in the list of vasoactive compounds that modulate the microvasculature. Although lipids were identified as important vascular messengers over three decades ago, their specific role within the microvascular system is not well defined. Thorough understanding of these pathways and their regulation is not only essential to gain insight into their role in cardiovascular disease but is also important for preventing vascular dysfunction following cancer treatment, a rapidly growing problem in medical oncology. The purpose of this review is to discuss how biologically active lipids, specifically prostanoids, epoxyeicosatrienoic acids, sphingolipids, and lysophospholipids, contribute to vascular function and signaling within the endothelium. Methods for quantifying lipids will be briefly discussed, followed by an overview of the various lipid families. The cross talk in signaling between classes of lipids will be discussed in the context of vascular disease. Finally, the potential clinical implications of these lipid families will be highlighted.

High rates of recurrence of gallstone associated episodes following acute cholecystitis during long term follow-up: a retrospective comparative study of patients who did not receive surgery.

INTRODUCTION: Patients who are admitted with acute cholecystitis (AC) and do not undergo urgent cholecystectomy, are usually referred for interval cholecystectomy. Many do not have surgery for various reasons, and some of those do not suffer from any recurrent symptoms. The primary objective of this study was to assess the rate and nature of recurrent gallstone-related events in this population over a long period, and its association with demographic and clinical parameters. A secondary objective was to assess the reasons for not undergoing surgery. METHODS: This is a retrospective cohort study, where the study group were adult patients admitted with AC. Patients that have suffered recurrent episodes were compared with those who did not. A control group of patients that had undergone cholecystectomy following an admission with AC was used for comparison. Demographic and clinical parameters were recorded for all patients, and the association with a recurrent episode was analyzed using univariate analysis. RESULTS: The study population was 197 patients. The group of patients who did not undergo surgery were significantly older (68.7 vs 54.2) and sicker (ASA > 3 50% vs 19%). The rate of recurrent episodes in the study group was 38.5%, and it was not found to be associated with the studied parameters. There was a trend towards higher gallstone disease specific mortality in the study group (5.5% vs 1.45% p = 0.062). CONCLUSIONS: This is a study of long-term follow-up of patients following an episode of AC we showed that the rate of recurrent episodes is quite high and involves severe inflammatory diseases, such as obstructive jaundice and pancreatitis.

Is acute appendicitis more severe in foreign workers of northern Israel? A retrospective cohort study.

BACKGROUND: Acute appendicitis (AA) is one of the most common surgical emergencies worldwide. It's classified into simple or complicated disease. Due to the high prevalence of the disease, AA has been studied as a marker to assess the quality of care afforded to minority groups. The purpose of this study was to compare AA outcomes in foreign workers (FW) to the general population in northern Israel. METHODS: This is a retrospective cohort study. We identified all patients aged 18-50 who were admitted to our institution between January 1st, 2013 and October 31st, 2018, with the diagnosis of acute appendicitis. The study group included all FW and the control group included citizens of Israel. Study patients were matched based on age, sex, and co-morbidities. We compared time to presentation, admission parameters and disease outcomes. Our study outcomes were disease severity and length of hospital stay. RESULTS: We identified 20 FW and 97 matched local patients. FW presented with significantly higher heart rate, temperature, and white blood cell count (WBC). Duration of symptoms was comparable between the two groups. The rates of complicated disease were significantly higher among FW (45 vs 17.5%, p < 0.0001). Length of hospitalization was significantly longer in the FW group (4.8 vs. 3.9 days, p = 0.01). The odds ratio of FWs for having a complicated disease was OR = 3.85 [95% CI: 1.38, 10.72], p = 0.01. Multivariate analysis identified FW and duration of symptoms as significantly contributing to a complicated disease outcome. CONCLUSIONS: Although duration of symptoms was comparable to the local population, FW in northern Israel are at increased risk for a complicated disease which resulted in longer hospital stay. Further studies may enlighten the reason for this disparity.

MBTPS1 regulates proliferation of colorectal cancer primarily through its action on sterol regulatory element-binding proteins.

Among the main metabolic pathways implicated in cancer cell proliferation are those of cholesterol and fatty acid synthesis, both of which are tightly regulated by sterol regulatory element-binding proteins (SREBPs). SREBPs are activated through specific cleavage by membrane-bound transcription factor protease 1 (MBTPS1), a serine protease that cleaves additional substrates (ATF6, BDNF, CREBs and somatostatin), some of which are also implicated in cell proliferation. The goal of this study was to determine whether MBTPS1 may serve as a master regulator in proliferation of colorectal cancer (CRC). Tumors from CRC patients showed variable levels of MBTPS1 mRNA, which were in positive correlation with the levels of SREBPs and ATF6, and in reverse correlation with BDNF levels. Chemical inhibition of MBTPS1 activity in two CRC-derived cell lines resulted in a marked decrease in the levels of SREBPs, but not of its other substrates and a marked decrease in cell proliferation, which suggested that MBTPS1 activity is critical for proliferation of these cells. In accordance, CRISPR/Cas9 targeted knockout (KO) of the MBTPS1 gene resulted in the survival of only a single clone that presented a phenotype of severely attenuated proliferation and marked downregulation of several energy metabolism pathways. We further showed that survival of the MBTPS1 KO clone was dependent upon significant upregulation of the type-1 interferon pathway, the inhibition of which halted proliferation entirely. Finally, rescue of the MBTPS1 KO cells, resulted in partial restoration of MBTPS1 levels, which was in accordance with partial recovery in proliferation and in SREBP levels. These finding suggest that MBTPS1 plays a critical role in regulating colon cancer proliferation primarily through SREBP-associated lipid metabolism, and as such may serve as a possible therapeutic target in CRC.

The lost stone - Laparoscopic exploration of abscess cavity and retrieval of lost gallstone post cholecystectomy: A case series and review of the literature.

BACKGROUND: Laparoscopic cholecystectomy (LC) is considered the gold standard operation for symptomatic gallstones. Gallbladder perforation occurs in 6-40% of operations. It can lead to spillage of gallstones into the abdominal cavity with possible consequences of long-term complications. We report two cases where a unique use of laparoscopic technique was used to explore abscess cavity and retrieve lost gallstones without penetrating the peritoneal cavity. CASE PRESENTATION: We report two cases of peri-hepatic abscess treated with laparoscopic cavity exploration, using 5 mm and 10 mm ports, to retrieve lost gallstones. It was done without entering the peritoneal cavity. DISCUSSION: Today, minimally invasive technique is used in a variety of surgical cases. We report a novel technique, using laparoscopic skills, to drain abscesses caused by lost gallstones post LC without entering the peritoneal cavity. The use of minimally invasive surgery techniques in order to explore abscess cavities not only help us to extract the cause of the abscess but also prevents another surgery in the abdominal cavity. CONCLUSION: Laparoscopic exploration of an abscess cavity is a feasible and safe technique treating long-term complications of gallbladder perforation post LC.

Solitary splenic metastasis of ovarian carcinoma: a case report.

INTRODUCTION: Splenic metastasis from ovarian carcinoma generally presents as peritoneal spread with multiorgan involvement. Fewer than 30 cases of solitary parenchymal splenic metastasis from ovarian carcinoma have been published in the literature. The presentation is often asymptomatic. CASE PRESENTATION: An increase in tumor marker CA-125 from 18.1 to 132.6 units/ml (normal < 35 units/ml) was measured in a 56-year-old Israeli Jewish woman who had undergone, six years previously, a total abdominal hysterectomy with bilateral salpingo-oophorectomy due to right ovarian carcinoma. An abdominal computed tomography scan revealed a mass of 6 × 8 cm at the anterior of the spleen, with close proximity to the wall of the stomach. A gastroscopy demonstrated exterior pressure on the stomach body. An open splenectomy was performed to exclude a peritoneal carcinomatosis. No intraoperative evidence of tumoral spreading in the abdominal cavity was observed, other than the spleen. The final histologic result demonstrated a high-grade carcinoma consistent with metastatic endometrioid-type ovarian carcinoma grade 3. CONCLUSIONS: This case highlights the importance of cancer antigen 125 assessment and medical imaging in the follow-up of ovarian carcinoma. Open laparotomy, or laparoscopy, enables exclusion of a peritoneal carcinomatosis, which is more common than solitary parenchymal splenic metastasis, as was presented in the current case.

Continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury.

BACKGROUND: Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of continuous fluid resuscitation and splenectomy on the hemodynamic response and survival in rats. METHODS: The animals were randomized into seven groups: group 1 (n = 8), sham-operated; group 2 (n = 8), MSI untreated; group 3 (n = 8), MSI treated with 7.5 mL/kg/h of 7.5% NaCl (hypertonic saline [HTS]) for 1 hour; group 4 (n = 8), MSI treated with 7.5 mL/kg/h hydroxyethyl starch (HES-7.5) for 1 hour; group 5 (n = 8) MSI treated with 35 mL/kg/h Ringer's lactate (RL) solution (RL-35) for 1 hour; group 6 (n = 8) MSI treated with 70 mL/kg/h RL for 1 hour (RL-70); and group 7 (n = 8), MSI treated with 105 mL/kg/h RL for 1 hour (RL-105). In all MSI groups, splenectomy was performed 45 minutes after injury. RESULTS: MSI in untreated group 2 resulted in a fall of mean arterial pressure from 105.9 +/- 10.7 mm Hg to 27.0 +/- 6.7 mm Hg (p < 0.001) in 60 minutes. Mean survival time after splenectomy in this group was 160.7 +/- 29.7 minutes, and total blood loss was 34.8 +/- 4.7% of blood volume. Continuous HTS infusion with splenectomy in group 3 was followed by a total blood loss of 38.7 +/- 4.4% and mean survival time was 176.5 +/- 23.2 minutes. HES-7.5 infusion and splenectomy was followed by a total blood loss of 39.6 +/- 2.5% and survival time was 171.6 +/- 19.5 minutes. Continuous infusion of increasing volumes of RL in groups 5, 6, and 7 was followed by increase in blood loss to 29.0 +/- 4.1%, 50.2 +/- 3.1% (p < 0.001), and 62.7 +/- 7.1% (p < 0.002) of total blood volume, respectively. Mean survival time in groups 5, 6, and 7 was 233.5 +/- 6.5 minutes (p < 0.04), 207.6 +/- 17.0 minutes (p < 0.05), and 158 +/- 26 minutes, respectively. CONCLUSION: Continuous infusion of large-volume RL and splenectomy after massive splenic injury resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared with small-volume RL infusion.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation.

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 +/- 35.3%) and vagal afferent firing (21.6 +/- 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.