Early Oral Antibiotic Switch Compared with Conventional Intravenous Antibiotic Therapy for Acute Cholangitis with Bacteremia

Background

Biliary decompression with antibiotic therapy is the mainstay treatment for acute cholangitis with bacteremia. A few studies have been conducted to investigate the optimal duration and route of antibiotic therapy in biliary tract infection with bacteremia.

Methods

Patients with acute cholangitis with bacteremia who achieved successful biliary drainage were randomly assigned to an early oral antibiotic switch group (group A, n = 29) and a conventional intravenous antibiotics group (group B, n = 30). Patients were discharged when they were afebrile over 2 days after oral antibiotic switch and showed consecutive improvement in the laboratory index. They were followed up and assessed at 30 days after diagnosis to evaluate the eradication of bacteria, recurrence of acute cholangitis, and 30-day mortality rate.

Results

There were no statistically significant differences between the two groups in baseline characteristics, clinical and laboratory index, severity of acute cholangitis, bacteria isolated from blood cultures, and clinical outcomes. The rate of eradication of bacteria was 93.1 % in group A and 93.3 % in group B, respectively (p = 0.97). Using non-inferiority tests, the rate of eradication of bacteria in group A was not inferior to that in group B (95 % CI ?0.13 to 0.14, p = 0.97). There was no statistically significant difference in the recurrence of acute cholangitis and a 30-day mortality rate between the two groups.

Conclusions

Early switch to oral antibiotic therapy following adequate biliary drainage for treatment of acute cholangitis with bacteremia was not inferior to conventional 10-day intravenous antibiotic therapy.     

Low Prevalence of Microsatellite Instability in Interval Gastric Cancers

Background and Aim

Esophagogastroduodenoscopy (EGD) is recommended at 2-year intervals in countries with a high prevalence of gastric cancer. The aim of this study was to determine whether interval gastric cancers that develop within 2 years of a previous complete screening are associated with microsatellite instability (MSI).

Methods

Newly diagnosed gastric cancer patients who had undergone gastrectomy were included. Of these 459 patients, 177 were classified as interval gastric cancer since they were diagnosed within 2 years of a previous EGD. Noninterval gastric cancer patients were subclassified into 65 patients who underwent previous EGD between the past 2 and 10 years and 217 patients without EGD during the last 10 years. Analysis for MSI was conducted using two mononucleotide and three dinucleotide markers.

Results

MSI was found more frequently in noninterval gastric cancers than in interval gastric cancers (p = 0.009). Interval gastric cancers were associated with a higher prevalence of early gastric cancer (p = 0.006), smaller size (p < 0.001), and lower TNM stages (p = 0.006). On logistic regression analysis, noninterval gastric cancers were related to MSI (p = 0.010) and larger size (≥4 cm) (p = 0.009). Subjects with interval gastric cancer showed better survival than those with noninterval gastric cancer (p = 0.006).

Conclusions

During a 2-year screening interval, noninterval gastric cancers tend to be larger, more advanced, and associated with MSI. Biannual EGD screening is effective for detecting small gastric cancers at an early stage, but is not useful in detecting gastric cancers with MSI.     

Delayed Endoscopic Papillary Large Balloon Dilation After Sphincterotomy for Removing Large Bile Duct Stones in Patients with Acute Cholangitis

Background

Endoscopic papillary large balloon dilation (EPLBD) after an endoscopic sphincterotomy (EST) is an option for endoscopic removal of large common bile duct (CBD) stones. However, risks or fear of severe adverse events remain.

Aims

Our aim was to compare the safety and efficacy of delayed EPLBD after EST with concurrent EST and EPLBD in patients with acute cholangitis by large CBD stones.

Patients and Methods

A total of sixty-eight patients with acute cholangitis from large CBD stones were enrolled in this prospective observational study. Thirty-five patients underwent concurrent EST and EPLBD at the same session (group A). Thirty-three patients underwent only EST at the first session, and EPLBD with stone removal was performed during a second session (group B). The complete stone removal rate and adverse events rate were analyzed.

Results

Both groups resulted in similar outcomes in terms of overall successful stone removal (100 % in both groups) and the use of additional lithotripsy (22.9 % in group A and 24.2 % in group B). Six patients (17.1 %) in group A had procedural-related adverse events including one patient with death by perforation, one with significant bleeding, and four with pancreatitis, including one moderate grade. However, there was no procedure-related complication in group B (p < 0.05).

Conclusions

Delayed EPLBD after EST may reduce complications associated with EPLBD and extraction of large bile duct stones in patients with acute cholangitis.     

Fetal neural stem cells from a mouse model of 15q11-13 duplication syndrome exhibit altered differentiation into neurons and astrocytes

The duplication of human chromosome 15q11-13 is known to be associated with an estimated 1.1% of autism cases. Here, we investigated whether differentiation into neurons and astrocytes is altered in fetal neural stem cells (FNSCs) isolated from the mouse model of 15q11-13 duplication syndrome (patDp/+ mice). In patDp/+ mice-derived FNSCs, multipotency was maintained for a longer period, the population of neurons was downregulated, and that of astrocytes was upregulated significantly after differentiation induction. These results suggest that the dysregulation of FNSCs differentiation could affect cortical development and behavioral deficits in the early postnatal stage shown in the patDp/+ mice.     

Long-term oncological outcomes of laparoscopic gastrectomy for grossly early gastric cancer-mimicking advanced gastric cancer: Propensity score matching analysis

Laparoscopic gastrectomy became an option in the treatment of early gastric cancer (EGC) in clinical practice. However, whether laparoscopic surgery for grossly EGC-mimicking advanced gastric cancer (AGC) patients is oncologically safe long-term is still controversial.We retrospectively analyzed 472 patients with AGC who were diagnosed as clinical EGC. Patients received laparoscopic or open gastrectomy with standard lymph node (LN) dissection from January 2007 to February 2015. We used a 1:3 propensity score matching method for the analysis. The matching factors were age, sex, body mass index, American Society of Anesthesiologists score and pathologic stage. After the matching process, we evaluated the 5-year overall survival and the cumulative incidence curve of recurrence.All of the analyzed patients were pathologically diagnosed with AGC after surgery (grossly EGC-mimicking AGC). The median (range) duration of follow-up was 58.0 (0–132) months. After propensity score matching, 31.5% of patients in the laparoscopy group had D1+ LN dissection and 99.2% of patients in the open group had D2 LN dissection. The 5-year overall survival rate between the laparoscopy (n = 92) and open groups (n = 244) were not significantly different (95.3% versus 91.4%, P = .224). There was no significant difference between the cumulative recurrence incidence curves of the matched groups (P = .319).Laparoscopic surgery for grossly EGC-mimicking AGC might be safe in terms of long-term survival outcome. After confirming grossly EGC-mimicking AGC in the final pathology report, no additional surgery might be required.     

From the Cover: Salt stress-induced Ca2+ waves are associated with rapid,long-distance root-to-shoot signaling in plants

Their sessile lifestyle means that plants have to be exquisitely sensitive to their environment, integrating many signals to appropriate developmental and physiological responses. Stimuli ranging from wounding and pathogen attack to the distribution of water and nutrients in the soil are frequently presented in a localized manner but responses are often elicited throughout the plant. Such systemic signaling is thought to operate through the redistribution of a host of chemical regulators including peptides, RNAs, ions, metabolites, and hormones. However, there are hints of a much more rapid communication network that has been proposed to involve signals ranging from action and system potentials to reactive oxygen species. We now show that plants also possess a rapid stress signaling system based on Ca²⁺ waves that propagate through the plant at rates of up to ∼400 µm/s. In the case of local salt stress to the Arabidopsis thaliana root, Ca²⁺ wave propagation is channeled through the cortex and endodermal cell layers and this movement is dependent on the vacuolar ion channel TPC1. We also provide evidence that the Ca²⁺ wave/TPC1 system likely elicits systemic molecular responses in target organs and may contribute to whole-plant stress tolerance. These results suggest that, although plants do not have a nervous system, they do possess a sensory network that uses ion fluxes moving through defined cell types to rapidly transmit information between distant sites within the organism.Plants are constantly tailoring their responses to current environmental conditions via a complex array of chemical regulators that integrate developmental and physiological programs across the plant body. Environmental stimuli are often highly localized in nature, but the subsequent plant response is often elicited throughout the entire organism. For example, soil is a highly heterogeneous environment and the root encounters stimuli that are presented in a patchy manner. Thus, factors including dry or waterlogged regions of the soil, variations in the osmotic environment, and stresses such as elevated levels of salt are all likely to be encountered locally by individual root tips, but the information may have to be acted on by the plant as a whole.In animals, long-range signaling to integrate activities across the organism occurs through rapid ionic/membrane potential-driven signaling through the nervous system in addition to operating via long-distance chemical signaling. Plants have also been proposed to possess a rapid, systemic communication network, potentially mediated through signals ranging from changes in membrane potential/ion fluxes (1–3) and levels of reactive oxygen species (ROS) (4, 5) to altered hydraulics in the vasculature (6). Even so, the molecular mechanisms behind rapid, systemic signaling in plants and whether such signals indeed carry regulatory information remains largely unknown. Suggestions that Ca²⁺ channels play a role in signals that occlude sieve tube elements (7), or that mediate systemic electrical signaling (2) in response to remote wounding, highlight Ca²⁺-dependent signaling events as a strong candidate for mediating some of these long-range responses. Similarly, cooling of roots elicits Ca²⁺ increases in the shoot within minutes (8), suggesting systemic signals can elicit Ca²⁺-dependent responses at distal sites within the plant. However, despite extensive characterization of Ca²⁺ signals (reviewed in ref. 9), their roles in a possible plant-wide communication network remain poorly understood. Therefore, to visualize how Ca²⁺ might act in local and systemic signaling, we generated Arabidopsis plants expressing the highly sensitive, GFP-based, cytoplasmic Ca²⁺ sensor YCNano-65 (10). We observed that a range of abiotic stresses including H₂O₂, touch, NaCl, and cold shock triggered Ca²⁺ increases at the point of application. However, NaCl also elicited a Ca²⁺ increase that moved away from the point of stress application. Propagation of this Ca²⁺ increase was associated with subsequent systemic changes in gene expression. We also report that this salt stress-induced long-distance Ca²⁺ wave is dependent on the activity of the ion channel protein Two Pore Channel 1 (TPC1), which also appears to contribute to whole-plant stress tolerance.     

Distinct roles of DKK1 and DKK2 in tumor angiogenesis

Tumor angiogenesis is essential for tumor invasive growth and metastasis, and generates abnormal vascular structures unlike developmental neovessel formation. To reduce tumor vascular abnormalities such as leakage and perivascular cell coverage deficiency that limit cancer therapy effectiveness, novel therapeutic approaches focus on vessel normalization. We have previously shown that Dickkopf-1 (DKK1), a Wnt antagonist, inhibits and its homolog DKK2 enhances, angiogenesis in normal tissues. In the present study, we investigated the effects of DKK1 and DKK2 on tumor growth and angiogenesis. Treatment of B16F10 melanoma-bearing mice with adenovirus expressing DKK1 significantly reduced tumor growth but DKK2 increased growth compared with controls. Similar pattern of tumor growth was observed in endothelial-specific DKK1 and DKK2 transgenic mice. Interestingly, tumor vascular density and perfusion were significantly decreased by DKK1 but increased by DKK2. Moreover, coverage of blood vessels by pericytes was reduced by DKK1, while DKK2 increased it. We further observed that DKK1 diminished retinal vessel density and increased avascular area in an in vivo murine model of oxygen-induced retinopathy, whereas DKK2 showed opposite results. These findings demonstrate that DKK1 and DKK2 have differential roles in normalization and functionality of tumor blood vessels, in addition to angiogenesis.     

MR image phenotypes may add prognostic value to clinical features in IDH wild-type lower-grade gliomas

European Radiology - To identify significant prognostic magnetic resonance imaging (MRI) features and their prognostic value when added to clinical features in patients with isocitrate...