Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

Transurethral Foley catheter misplacement into the upper urinary tract in a patient with a history of lung cancer and chemotherapy: a case report and considerations to keep in mind

Indwelling urethral catheter placement is a common and comparatively safe procedure. Misplacement of a urethral catheter into the upper urinary tract is unusual, and only a few cases have been reported. We describe the case of a 43-year-old man who presented with oliguria and had a history of chemotherapy for known metastatic lung cancer. As he had no history of urological disease, urethral catheterization was expected to be uneventful. The catheter was unable to be pulled back to the bladder neck once the balloon was inflated, and the patient expressed discomfort. Subsequent computed tomography revealed that the tip of the catheter was placed in the middle of the right ureter. Unbeknownst to the physicians before urethral catheterization, the patient had severe lower urinary tract symptoms and urinary bladder dysfunction with hydronephrosis, likely due to chemotherapy. Based on the patient’s symptoms and imaging results, we judged the possibility of severe ureteral injury to be low. The malpositioned catheter was removed uneventfully after complete balloon deflation and then reinserted properly. He was admitted to the medical department but died as a result of an exacerbation of the underlying disease unrelated to the incident. If urethral catheter placement seems abnormal, physicians should aspirate and irrigate to confirm correct positioning before balloon inflation; then, they should carefully pull the inflated balloon near the neck of the bladder while monitoring the patient’s symptoms. Although urethral catheter placement is comparatively safe, physicians must keep in mind that patients who have undergone chemotherapy might be at a risk for this rare complication.     

Evaluation of the 2016–2020 regional tuberculosis response framework,WHO Western Pacific Region

ObjectiveTo assess the implementation of the Regional framework for action on implementation of the End TB Strategy in the Western Pacific, 2016–2020 in countries and areas in the World Health Organization Western Pacific Region.MethodsWe used a mixed methods approach to assess the framework’s measurable and perceived impact. We conducted an analysis of national tuberculosis strategic plans, a cross-sectional survey of senior staff of tuberculosis programmes, key informant interviews and some country case studies.FindingsOf the 37 countries and areas of the Western Pacific Region, 14 had a national tuberculosis strategic plan, including all countries and areas with a high incidence of tuberculosis. Most senior tuberculosis programme staff who responded to the survey (16/23) found the regional framework useful when developing their national targets and grant applications. Programmatic challenges identified included financing, human resources, public–private mix, active case finding, and paediatric and drug-resistant tuberculosis. Most of the 17 key informants thought that the regional framework’s categorization of actions (for all settings, for specific settings and for pre-elimination settings) was useful, but that the added value of the regional framework over other relevant documents was not obvious because of overlap in content.ConclusionThe regional framework influenced national level tuberculosis control planning and implementation in a positive way. A future regional framework should provide a longer-term strategic horizon and specifically address emerging trends and persistent problems faced by countries or areas of the region.     

Risk of insomnia and hypnotics use among emergency physicians

This study investigated the risk of insomnia and hypnotics use among emergency physicians. This cross-sectional study recruited physicians working in Taiwanese hospitals in 2015 and the general population as the participants. Data from 1,097 emergency physicians obtained from the National Health Insurance Research Database were grouped into the case group, whereas 14,112 nonemergency physicians and 4,388 people from the general population were categorized into the control groups. This study used logistic regression and conditional logistic regression to compare the risks of insomnia between emergency and nonemergency physicians and between emergency physicians and the general population, respectively. The prevalence of insomnia among emergency physicians, nonemergency physicians and general population was 5.56%, 4.08%, and 1.73%, respectively. Compared with nonemergency physicians and the general population, emergency physicians had a significantly higher risk of insomnia. The proportions of emergency physicians, nonemergency physicians, and general population using hypnotics were 19.96%, 18.24%, and 13.26%, respectively. Among emergency physicians who used hypnotics, 49.77%, 25.57%, and 24.66% used only benzodiazepines, only nonbenzodiazepines, and both benzodiazepines and nonbenzodiazepines, respectively. Nonpharmacological interventions to improve insomnia and reminder of safe use of hypnotics to emergency physicians can serve as references for hospitals in developing health-promoting activities.     

Effect of protease inhibitors on degradation of recombinant human epidermal growth factor in skin tissue

Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at 37°C for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p<0.05), while the other protease inhibitors had no significant inhibitory effects or, even resulted in deleterious effects. Therefore, the formulation containing one or several inhibitors among these effective inhibitors would be a promising topical preparation of rhEGF for the treatment of open wound.     

Metabolism of liriodendrin and syringin by human intestinal bacteria and their relation toin vitro cytotoxicity

When liriodendrin or syringin was incubated for 24 h with human intestinal bacteria, two metabolites, (+)-syringaresinol-beta-D-glucopyranoside and (+)-syringaresinol, from liriodendrin and one metabolite, synapyl alcohol, from syringin were produced. The metabolic time course of liriodendrin was as follows: at early time, liriodendrin was converted to (+)-syringaresinol-beta-D-glucopyranoside, and then (+)-syringaresinol. The in vitro cytotoxicities of these metabolites, (+)-syringaresinol and synapyl alcohol, were superior to those of liriodendrin and syringin.     

ABSENCE OF "RECURARIZATION" IN PATIENTS WITH DEMONSTRATED PROLONGED NEUROMUSCULAR BLOCK

The possibility of "recurarization" after antagonism of thecompetitive neuromuscular block with anticholinesterases wasstudied. Observations were made on the time-course of the blockin five patients at risk from recurarization because of multipleorgan failure and who demonstrated unusually prolonged blockade.In none of these patients did the block recur. We conclude that,provided spontaneous recovery of neuromuscular transmissionhas made progress before the antagonism, and that the patientdoes not deteriorate or become exhausted afterwards, recurarizationis unlikely.     

Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system.

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content.     

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.