Intracorporeal Anastomosis Using Linear Stapler in Laparoscopic Distal Gastrectomy: Comparison between Gastroduodenostomy and Gastrojejunostomy

Purpose: Intracorporeal anastomosis during laparoscopic gastrectomy is becoming increasingly prevalent. However, selection of the anastomosis method after laparoscopic distal gastrectomy is equivocal because of a lack of technical feasibility and safety. We compared intracorporeal gastroduodenostomy with gastrojejunostomy using linear staplers to evaluate the technical feasibility and safety of intracorporeal anastomoses as well as its' minimally invasiveness. Materials and Methods: Retrospective analyses of a prospectively collected database for gastric cancer revealed 47 gastric cancer patients who underwent laparoscopic distal gastrectomy with either intracorporeal gastroduodenostomy or gastrojejunostomy from March 2011 to June 2011. Perioperative outcomes such as operation time, postoperative complication, and hospital stay were compared according to the type of anastomosis. Postoperative inflammatory response was also compared between the two groups using white blood cell count and high sensitivity C-reactive protein. Results: Among the 47 patients, 26 patients received gastroduodenostomy, whereas 21 patients received gastrojejunostomy without open conversion or additional mini-laparotomy incision. There was no difference in mean operation time, blood loss, and length of postoperative hospital stays. There was no statistically significant difference in postoperative complication or mortality between two groups. However, significantly more staplers were used for gastroduodenostomy than for gastrojejunostomy (n=6) than for gastroduodenostomy and (n=5). Conclusions: Intracorporeal anastomosis during laparoscopic gastrectomy using linear stapler, either gastroduodenostomy or gastrojejunostomy, shows comparable and acceptable early postoperative outcomes and are safe and feasible. Therefore, surgeons may choose either anastomosis method as long as oncological safety is guaranteedope

A Case of Pathologic Splenic Rupture as the Initial Manifestation of Acute Myeloid Leukemia M2

A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy

Deubiquitination Reactions on the Proteasome for Proteasome Versatility

The 26S proteasome, a master player in proteolysis, is the most complex and meticulously contextured protease in eukaryotic cells. While capable of hosting thousands of discrete substrates due to the selective recognition of ubiquitin tags, this protease complex is also dynamically checked through diverse regulatory mechanisms. The proteasome’s versatility ensures precise control over active proteolysis, yet prevents runaway or futile degradation of many essential cellular proteins. Among the multi-layered processes regulating the proteasome’s proteolysis, deubiquitination reactions are prominent because they not only recycle ubiquitins, but also impose a critical checkpoint for substrate degradation on the proteasome. Of note, three distinct classes of deubiquitinating enzymes—USP14, RPN11, and UCH37—are associated with the 19S subunits of the human proteasome. Recent biochemical and structural studies suggest that these enzymes exert dynamic influence over proteasome output with limited redundancy, and at times act in opposition. Such distinct activities occur spatially on the proteasome, temporally through substrate processing, and differentially for ubiquitin topology. Therefore, deubiquitinating enzymes on the proteasome may fine-tune the degradation depending on various cellular contexts and for dynamic proteolysis outcomes. Given that the proteasome is among the most important drug targets, the biology of proteasome-associated deubiquitination should be further elucidated for its potential targeting in human diseases. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Safety and optimal neuroprotection of neu2000 in acute ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial

BACKGROUND: The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome. METHODS: This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ≥ 19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8, Alberta Stroke Program Early CT score ≥ 6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0-2, and Barthel Index > 90 at 1 and 4 weeks, and 3 months. DISCUSSION: The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT

Myofilament Ca2+ desensitization mediates positive lusitropic effect of neuronal nitric oxide synthase in left ventricular myocytes from murine hypertensive heart

AbstractNeuronal nitric oxide synthase (NOS1 or nNOS) exerts negative inotropic and positive lusitropic effects through Ca2+ handling processes in cardiac myocytes from healthy hearts. However, underlying mechanisms of NOS1 in diseased hearts remain unclear. The present study aims to investigate this question in angiotensin II (Ang II)-induced hypertensive rat hearts (HP). Our results showed that the systolic function of left ventricle (LV) was reduced and diastolic function was unaltered (echocardiographic assessment) in HP compared to those in shams. In isolated LV myocytes, contraction was unchanged but peak [Ca2+]i transient was increased in HP. Concomitantly, relaxation and time constant of [Ca2+]i decay (tau) were faster and the phosphorylated fraction of phospholamban (PLN-Ser16/PLN) was greater. NOS1 protein expression and activity were increased in LV myocyte homogenates from HP. Surprisingly, inhibition of NOS1 did not affect contraction but reduced peak [Ca2+]i transient; prevented faster relaxation without affecting the tau of [Ca2+]i transient or PLN-Ser16/PLN in HP, suggesting myofilament Ca2+ desensitization by NOS1. Indeed, relaxation phase of the sarcomere length–[Ca2+]i relationship of LV myocytes shifted to the right and increased [Ca2+]i for 50% of sarcomere shortening (EC50) in HP. Phosphorylations of cardiac myosin binding protein-C (cMyBP-C282 and cMyBP-C273) were increased and cardiac troponin I (cTnI23/24) was reduced in HP. Importantly, NOS1 or PKG inhibition reduced cMyBP-C273 and cTnI23/24 and reversed myofilament Ca2+ sensitivity. These results reveal that NOS1 is up-regulated in LV myocytes from HP and exerts positive lusitropic effect by modulating myofilament Ca2+ sensitivity through phosphorylation of key regulators in sarcomere

Results from the safety interim analysis of the adjuvant chemoradiotherapy in stomach tumors 2 trial: a multicenter, randomized phase III clinical trial

Purpose The Adjuvant chemoRadioTherapy In Stomach Tumors 2 (ARTIST 2) trial was conducted to compare the efficacy between adjuvant chemotherapy regimens and chemoradiotherapy in D2-resected, node-positive, stage 2 or 3 gastric cancer. Methods In this prospective, multicenter, phase IIItrial, we randomly assigned patients to three treatment arms: patients who receive adjuvant S-1 for 1 year, S-1 plus oxaliplatin (SOX) for 6 months, or SOX plus chemoradiotherapy (SOXRT). Herein, we report the safety outcomes of patients who received adjuvant chemotherapy or chemoradiotherapy. Results Among a total of 514 patients registered between February 2013 and December 2017, 499 patients who either completed or discontinued the assigned study treatments were included in the present analysis. Allthe three treatment arms were generally well-tolerated, with the overall treatment completion rate of 94% (96% in S-1, 93% in SOX, and 92% in SOXRT). The median delivered dose of radiotherapy in the SOXRT arm was 4,500 cGy (range, 0 to 4,500 cGy). The most frequently observed adverse events were fatigue (29%) in S-1 arm and peripheral neuropathy in the SOX and SOXRT arms (59% and 50%,respectively). Conclusion Our preliminary data confirm that there are no significant safety concerns in ARTIST 2 trial (ClinicalTrials.gov, NCT0176146). According to the Independent Data Monitoring Committee, patient accrual is underway