Contribution of prophylactic administration of flurbiprofen for mesenteric traction syndrome to postoperative leakage or bleeding in gastrointestinal surgery: a retrospective observational study.

PURPOSE: Mesenteric traction syndrome (MTS) sometimes occurs during abdominal surgery. Prophylactic administration of flurbiprofen, a non-steroidal anti-inflammatory drug, prevents the development of MTS. However, administration of non-steroidal anti-inflammatory drugs for postoperative pain increases the incidence of postoperative bleeding. Our aim was to examine the effect of prophylactic flurbiprofen administration on postoperative leakage or bleeding after gastrointestinal surgery. METHODS: A retrospective observational study on patients who underwent open or laparoscopic abdominal surgery was conducted. Perioperative, anesthesia and medical records were reviewed. Patients who did (Flurbio-Group) or did not receive (Control-Group) prophylactic flurbiprofen administration were compared. Then, the Flurbio-Group and Control-Group were each divided into two groups according to whether the patients did or did not develop MTS (Flurbio-MTS-Group and Flurbio-no-MTS-Group, respectively, Control-MTS-Group and Control-no-MTS-Group, respectively). RESULTS: This study included 188 patients (Flurbio-MTS-Group, 1 patient; Flurbio-no-MTS-Group, 31 patients; Control-MTS-Group, 59 patients; Control-no-MTS-Group, 97 patients). Seventeen patients developed postoperative leakage or bleeding. Eleven Flurbio-MTS-Group patients (18.6%), 4 Flurbio-no-MTS-Group patients (12.9%, 4/31), and only 2 Control-no-MTS-Group patients (2%, 2/97) developed postoperative leakage or bleeding. Multivariate logistic regression analysis demonstrated that there was a qualitative interaction effect between prophylactic administration of flurbiprofen and the development of MTS on postoperative leakage or bleeding. CONCLUSION: Prophylactic flurbiprofen administration increased the risk of postoperative leakage or bleeding among patients who did not develop MTS.

Myocarditis associated with immune-checkpoint inhibitors diagnosed by cardiac magnetic resonance imaging.

Myocarditis associated with immune-checkpoint inhibitors (ICIs) is a rare, but critical adverse event. Although endomyocardial biopsy (EMB) is the standard for diagnosis of myocarditis, there is a possibility of false negatives due to sampling errors and local nonavailability of EMB, which may hamper the appropriate diagnosis of myocarditis. Therefore, an alternative criterion based on cardiac magnetic resonance imaging (CMRI) combined with clinical presentation has been proposed, but not emphasized sufficiently. We report a case of myocarditis after ICIs administration, which was diagnosed using CMRI in a 48-year-old male with lung adenocarcinoma. CMRI provides an opportunity to diagnose myocarditis during cancer treatment.

Case Report: A Case of Trimethoprim/Sulfamethoxazole-Triggered Hypotensive Shock: Cytokine Release Syndrome Related to Immune Checkpoint Inhibitors and Drug-Induced Hypersensitivity Syndrome.

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

Quality indicators of palliative care for acute cardiovascular diseases.

BACKGROUND: Although recent attention to palliative care for patients with cardiovascular diseases has been increasing, there are no specific recommendations on detailed palliative care practices. We proceed on a discussion of the appropriateness and applicability of potential quality indicators for acute cardiovascular diseases according to our previous systematic review. METHODS: We created a multidisciplinary panel of 20 team members and 7 external validation clinicians composed of clinical cardiologists, a nutritionist, a physiotherapist, a clinical psychologist, a critical and emergent care specialist, a catheterization specialist, a primary care specialist, a palliative care specialist, and nurses. After crafting potential indicators, we performed a Delphi rating, ranging from "1 = minimum" to "9 = maximum". The criterion for the adoption of candidate indicators was set at a total mean score of seven or more. Finally, we subcategorized these indicators into several domains by using exploratory factor analysis. RESULTS: Sixteen of the panel members (80%) were men (age, 49.5 ± 13.7 years old). Among the initial 32 indicators, consensus was initially reached on total 23 indicators (71.8%), which were then summarized into 21 measures by selecting relatively feasible time variations. The major domains were "symptom palliation" and "supporting the decision-making process". Factor analysis could not find optimal model. Narratively-developed seven sub-categories included "presence of palliative care team", "patient-family relationship", "multidisciplinary team approach", "policy of approaching patients", "symptom screening and management", "presence of ethical review board", "collecting and providing information for decision-maker", and "determination of treatment strategy and the sharing of the care team's decision". CONCLUSION: In this study we developed 21 quality indicators, which were categorized into 2 major domains and 7 sub-categories. These indicators might be useful for many healthcare providers in the initiation and enhancement of palliative care practices for acute cardiovascular diseases in Japan.

Correction: Enzyme-mediated dual-targeted-assembly realizes a synergistic anticancer effect.

Correction for 'Enzyme-mediated dual-targeted-assembly realizes a synergistic anticancer effect' by Dingze Mang et al., Chem. Commun., 2019, 55, 6126-6129.

Enzyme-mediated dual-targeted-assembly realizes a synergistic anticancer effect.

We designed and synthesized homochiral-peptide-based boron diketonate complexes. Co-administration of the two stereoisomers in cancer cells led to molecular assembly targeting both the plasma membrane and the lysosomes mediated via membrane-bonded enzymes. The dual-targeted-assembly generates a synergistic anticancer effect with amplified cancer spheroid toxicity and enhanced inhibition efficacy on cancer cell migration.

Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

Cell division and cadherin-mediated adhesion regulate lens epithelial cell movement in zebrafish.

In vertebrates, lens epithelial cells cover the anterior half of the lens fiber core. During development, lens epithelial cells proliferate, move posteriorly and differentiate into lens fiber cells after passing through the equator. To elucidate the mechanisms underlying lens epithelial cell movement, we conducted time-lapse imaging of zebrafish lens epithelium. Lens epithelial cells do not intermingle but maintain their relative positions during development. Cell division induces epithelial rearrangement, which subsequently promotes cell movement towards the equator. These data suggest that cell division is the major driving force for cell movement. In zebrafish, E-cadherin is expressed in lens epithelium, whereas N-cadherin is required for lens fiber growth. E-cadherin reduced lens epithelial cell movement, whereas N-cadherin enhanced it. Laser ablation experiments revealed that lens epithelium is governed by pulling tension, which is modulated by these cadherins. Thus, cell division and cadherin-mediated adhesion regulate lens epithelial cell movement via modulation of epithelial tension.

Ornithine transcarbamylase deficiency that developed at the age of 19 years with acute brain edema.

Case: A 19-year-old man had nausea, diarrhea, and general malaise the day before requesting emergency transport to his former primary physician. The patient became restless and had tonic seizures after admission. The patient was transferred to our hospital as there had been no improvement in his level of consciousness. On arrival, cranial computed tomography showed generalized swelling, and blood ammonia concentration was ≥500 µg/dL. After admission, seizures recurred continually despite careful monitoring and increased doses of sedatives and antiseizure drugs. Dilated pupils and a flat electroencephalogram were evident on day 4 of admission, and the patient died on day 11. Ornithine transcarbamylase deficiency was diagnosed at postmortem based on fractionation of blood and urine amino acids and orotic acid. Outcome: Urea cycle disorders need to be treated urgently to prevent irreversible neurological damage when accompanied by hyperammonemia. Conclusion: In cases of hyperammonemia, early dialysis should be considered to reduce the ammonia level.

Anisakiasis presenting to the ED: clinical manifestations, time course, hematologic tests, computed tomographic findings, and treatment.

BACKGROUND: The prevalence of anisakiasis is rare in the United States and Europe compared with that in Japan, with few reports of its presentation in the emergency department (ED). This study describes the clinical, hematologic, computed tomographic (CT) characteristics, and treatment in gastric and small intestinal anisakiasis patients in the ED. METHODS: We retrospectively reviewed the data of 83 consecutive anisakiasis presentations in our ED between 2003 and 2012. Gastric anisakiasis was endoscopically diagnosed with the Anisakis polypide. Small intestinal anisakiasis was diagnosed based on both hematologic (Anisakis antibody) and CT findings. RESULTS: Of the 83 cases, 39 had gastric anisakiasis and 44 had small intestinal anisakiasis based on our diagnostic criteria. Although all patients had abdominal pain, the gastric anisakiasis group developed symptoms significantly earlier (peaking within 6 hours) than the small intestinal anisakiasis group (peaking within 48 hours), and fewer patients with gastric anisakiasis needed admission therapy (5% vs 57%, P<.01). All patients in the gastric and 40 (91%) in the small intestinal anisakiasis group had a history of raw seafood ingestion. Computed tomographic findings revealed edematous wall thickening in all patients, and ascites and phlegmon of the mesenteric fat were more frequently observed in the small intestinal anisakiasis group. CONCLUSIONS: In the ED, early and accurate diagnosis of anisakiasis is important to treat and explain to the patient, and diagnosis can be facilitated by a history of raw seafood ingestion, evaluation of the time-to-symptom development, and classic CT findings.

The BH3-only SNARE BNip1 mediates photoreceptor apoptosis in response to vesicular fusion defects.

Intracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish ß-soluble N-ethylmaleimide-sensitive factor attachment protein (ß-SNAP) mutant. ß-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the ß-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis.

[A case of an unexpected difficult nasal intubation, caused by hypertrophied lingual tonsil].

We experienced a case of unexpected difficult nasal intubation due to lingual tonsil hyperplasia. A 43-year-old man was scheduled for pharyngoplasty because of sleep apnea syndrome. After induction of general anesthesia, Macintosh laryngoscopy failed to expose his glottis by two experienced anesthesiologists. We also found that the view of his larynx by fiberoptic bronchoscope (FOB) was poor, and nasal intubation guided by FOB was difficult. Finally, we made an oral intubation with Macintosh laryngoscopy under a gum elastic bougie guide. Ventilation and oxygenation were maintained throughout the procedure. A FOB guided intubation under general anesthesia is often difficult, because identification of glottis is interfered by deviated pharyngeal tissue and epiglottis, which are affected by the use of muscle relaxants. At present, a selective relaxant binding agent, sugammadex, is available in anesthesia, to reverse the effect of non-depolarizing muscle relaxant and to restore spontaneous breathing in this situation.

Reliability of anion gap calculated from data obtained using a blood gas analyzer: is the probability of error predictable?

BACKGROUND: Anion gap (AG) is a useful index for assessing the clinical condition of critically ill patients especially in intoxication. Recently, AG can be obtained easily using a blood gas analyzer (BGA); however, its reliability requires validation. METHODS: We enrolled patients who simultaneously underwent blood gas analysis and blood test in the central hospital laboratory and patients who visited the emergency department of our hospital from January 1, 2004, to December 31, 2007. The deviation of AG calculated using the BGA and that calculated by the central hospital laboratory were extracted. From the data obtained using the BGA, the independent risk factor causing a significant error in AG was statistically analyzed. RESULTS: A total of 2922 patients were enrolled, of which 339 were defined as the significant error group. Male sex, abnormal Hco(3)(-), abnormal lactate, abnormal K, abnormal Cl, and abnormal Na were the independent risk factors producing the significant error. The results indicate that regardless of whether the original electrolyte data of the patients are abnormal, when the electrolyte measurement results obtained using the BGA are abnormal, the calculated AG might show a significant error. In addition, the fact that lactate was determined as a risk factor indicates that AG might be more useful in patients who have intoxication than in those under an unstable state in terms of vital signs. CONCLUSION: When risk factors are present, the medical condition of a patient should be reevaluated by comparing results without heavily relying on the AG obtained by a BGA.

Xenopus NM23-X4 regulates retinal gliogenesis through interaction with p27Xic1.

BACKGROUND: In Xenopus retinogenesis, p27Xic1, a Xenopus cyclin dependent kinase inhibitor, functions as a cell fate determinant in both gliogenesis and neurogenesis in a context dependent manner. This activity is essential for co-ordination of determination and cell cycle regulation. However, very little is known about the mechanism regulating the context dependent choice between gliogenesis versus neurogenesis. RESULTS: We have identified NM23-X4, a NM23 family member, as a binding partner of p27Xic1. NM23-X4 is expressed at the periphery of the ciliary marginal zone of the Xenopus retina and the expression overlaps with p27Xic1 at the central side. Our in vivo functional analysis in Xenopus retina has shown that knockdown of NM23-X4 activates gliogenesis. Furthermore, co-overexpression of NM23-X4 with p27Xic1 results in the inhibition of p27Xic1-mediated gliogenesis, through direct interaction of NM23-X4 with the amino-terminal side of p27Xic1. This inhibitory effect on gliogenesis requires serine-150 and histidine-148, which correspond to the important residues for the kinase activities of NM23 family members. CONCLUSION: This study demonstrates that NM23-X4 functions as an inhibitor of p27Xic1-mediated gliogenesis in Xenopus retina and suggests that this activity contributes to the proper spatio-temporal regulation of gliogenesis.

Nitric oxide donor, NOC7, reveals biphasic effect on contractile force of isolated rat heart after global ischemia.

PURPOSE: Our purpose was to investigate whether the NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), restored cardiac function following global ischemia in an isolated rat heart model and whether intracellular messengers were involved in its effect. METHODS: Isolated rat hearts (n = 36) were randomly divided into six groups. The sham control group was perfused with modified Krebs-Henseleit bicarbonate buffer (KHB) alone. The ischemic control group and the NOC7 groups were subjected to 35 min of global ischemia, followed by 30 min of reperfusion with KHB alone, or reperfusion with KHB including NOC7 at 0.2, 2, 20, or 200 microM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (+/-dP/dt), and coronary flow were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA) methods. RESULTS: NOC7 at 2 and 20 microM rescued myocardial performance (LVDP, 111.9 +/- 10.5% and 124.3 +/- 12.5% of baseline, respectively; P < 0.05 vs ischemic control) at 30 min after reperfusion. However, NOC7 at 200 microM reduced the LVDP to 55.3 +/- 6.0% of baseline. Coronary flows remain unchanged. The cAMP levels increased significantly from 0.83 +/- 0.44 pmol x mg(-1) protein in the ischemic control group to 1.79 +/- 0.39, 1.86 +/- 0.25, and 2.63 +/- 0.24 pmol x mg(-1) protein, in the groups with NOC7 at 2, 20, and 200 microM, respectively (P < 0.05). The cGMP level increased from 1.49 +/- 0.61 pmol x mg(-1) protein in the ischemic control group to 3.92 +/- 0.66 pmol x mg(-1) protein in the group with NOC7 at 200 microM alone (P < 0.05). CONCLUSION: NOC7 appeared to exert a biphasic effect on the contractile force of the isolated rat heart after 35-min global ischemia. The balance between intracellular cAMP and cGMP levels seemed to be involved in its mechanism.