Actual situation of decision-making support from medical staff when cancer patients make treatment choices.

Background: We investigated factors involved in decision-making support provided by physicians, nurses, pharmacists and medical and psychiatric social workers involved in cancer care. Materials & methods: A questionnaire survey on decision-making support was conducted. The level of clinician support was classified as 'supporting patients' 'decision-making process regarding cancer treatment', 'no support for patients' 'decision-making process regarding cancer treatment' or 'team-based support for patients' 'decision-making process regarding cancer treatment'. Results: Physicians estimated that 83.7% of patients made a cancer treatment decision within 1 week, but 45.4% of patients had difficulty making a decision. Conclusion: Medical personnel should support patients who have difficulty making decisions, establish a screening method to identify those needing support and develop a system providing decision-making support through interprofessional work.

We conducted a survey to investigate issues related to the level of decision-making support provided by physicians, nurses, pharmacists medical social workers and psychiatric social workers involved in cancer care. The physicians reported that 83.7% of patients with cancer chose a treatment plan within 1 week, although 45.4% of patients had difficulty making a decision. These decision-making difficulties arose at the time of diagnosis, when having difficulty controlling adverse events and when cancer metastasis or recurrence occurred. Some medical providers supported patients who had particular difficulty in choosing their cancer treatment, others provided no support, while a third group orchestrated a team to support them in their decision-making. To improve the quality of decision-making support, interprofessional work should be promoted and screening tools to identify those who need support should be established.

Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. SUMMARY: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. KEY MESSAGES: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer.

Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.

Cyclin-Dependent Kinase Activity Correlates with the Prognosis of Patients Who Have Gastrointestinal Stromal Tumors.

BACKGROUND: The estimation of recurrence risk remains a critical issue in relation to gastrointestinal stromal tumors (GISTs) treated with adjuvant therapy. The accuracy of the commonly used risk stratifications is not always adequate. METHODS: For this study, data were prospectively collected from 68 patients with GISTs who underwent R0 surgery between 2004 and 2009. The results from this analysis cohort were evaluated using the data obtained from an additional 40 patients in the validation cohort. Cyclin-dependent kinase 1 (CDK1)- and CDK2-specific activities were measured using a non-RI kinase assay system. RESULTS: The specific activities of CDK1 and CDK2, but not their expression, significantly correlated with recurrence. The specific activities of both CDK1 and CDK2 were independently correlated with mitosis and significantly correlated with recurrence-free survival (RFS). In the multivariate analysis, CDK2-specific activity (P = 0.0006), tumor size (P = 0.0347), and KIT deletion mutations (P = 0.0006) were significantly correlated with RFS in the analysis cohort. In the validation cohort, CDK2-specific activity (P = 0.0368) was identified as an independent prognostic factor for tumor recurrences with tumor location (P = 0.0442). CONCLUSION: The results suggest that the specific activities of CDK1 and CDK2 may reflect the proliferative activity of GISTs and that CDK2-specific activity is a good prognostic factor predicting recurrence after macroscopic complete resection of GISTs.

Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement.

Optimization of plasmepsin inhibitor by focusing on similar structural feature with chloroquine to avoid drug-resistant mechanism of Plasmodium falciparum.

The plasmepsins are specific aspartic proteases of the malaria parasite and a potential target for developing new antimalarial agents. Our previously reported peptidomimetic plasmepsin inhibitor with modified 2-aminoethylamino substituent, KNI-10740, was tested against chloroquine sensitive Plasmodium falciparum, D6, to be highly potent, however, the inhibitor exhibited about 5 times less activity against multi-drug resistant parasite (TM91C235). We hypothesized the potency reduction resulted from structural similarity between 2-aminoethylamino substituent of KNI-10740 and chloroquine. Then, we modified the moiety and finally identified compound 15d (KNI-10823), that could avoid drug-resistant mechanism of TM91C235 strain.

Thermodynamic evaluation of the binding of bisphosphonates to human farnesyl pyrophosphate synthase.

Bisphosphonates (BPs) are the drug of choice for treating bone diseases such as osteoporosis, Paget's disease, and metastatic bone disease. BPs with nitrogen-containing side chains (N-BPs) are known to act as inhibitors for farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. In this study, we evaluated the effect of different side chains on the binding affinity of BPs to human FPPS using calorimetric techniques. Differential scanning calorimetry (DSC) was used to determine the thermal unfolding of FPPS in the presence of BPs. The addition of a series of clinically available BPs increased the structural stability of human FPPS by preferential binding, as indicated by an increase in the FPPS unfolding temperature. The magnitude of the increase was correlated with in vivo antiresorptive efficacy, suggesting that the stabilization of FPPS underlies the inhibitory effect of the BPs. Isothermal titration calorimetry (ITC) experiments were performed to evaluate the binding thermodynamics of BPs against human FPPS. Analysis of the binding energetics revealed that over 30 years of optimization practiced by different pharmaceutical companies has enhanced the enthalpic contribution as well as binding affinity of BPs. The larger enthalpic contribution observed for newer, more potent BPs derives from both improved hydrogen bonding interactions and shape complementarity based on comparisons of our results with available structure information.

Factors Involved in Shared Decision-making Regarding Treatment Selection by Patients With Cancer.

Background/Aim: Patients diagnosed with cancer are expected to choose one or more treatment modalities after receiving corresponding explanations of the options. When making these choices, patients consider the effects of treatment and aspects related to their quality of life. These concerns can cause confusion and conflict owing to the complicated information provided by medical caregivers. The objective of the study was to identify perceptions of cancer treatment in patients with cancer and the decision-making factors affecting their treatment choices. Patients and Methods: In this observational (cross-sectional) study, an online questionnaire survey was administered to 194 Japanese cancer patients with treatment experience. Patient information, perceptions of explanations provided by healthcare professionals, treatment views, and reasons for treatment decisions were subjected to a simple tabulation. Content and factor analysis was conducted to determine important treatment selection elements. Results: Regarding treatment perception, 60.3% of respondents (n=117) considered treatment a financial and family burden, 47.4% (n=92) had concerns about physical pain, and 40.2% (n=78) were worried about increased stress. Regarding decision-making quality, 95.9% determined their preferred treatment within one week, 49.0% reported difficulties in making their decisions, and 83.0% chose their treatment themselves. Major decisive factors were prolonging life, opinions of medical staff, and accepting treatment risks (68.0%, 68.6%, and 60.3% of patients, respectively). The main attitudes toward treatment were anxiety, expectations of benefit, and expectations of support and care. Conclusion: SDM should enable patients to visualize the changes that their bodies will experience and include discussions on prognosis. Psychological care should be prioritized to alleviate anxiety and improve readiness for decision-making; attention should be paid to the extent and timing of information provision.

Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety.

We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CL(pro). A docking study involving binding between the initial lead compound 1 and the SARS-CoV 3CL(pro) motivated the replacement of a thiazole with a benzothiazole unit as a warhead moiety at the P1' site. This modification led to the identification of more potent derivatives, including 2i, 2k, 2m, 2o, and 2p, with IC(50) or K(i) values in the submicromolar to nanomolar range. In particular, compounds 2i and 2p exhibited the most potent inhibitory activities, with K(i) values of 4.1 and 3.1 nM, respectively. The peptidomimetic compounds identified through this process are attractive leads for the development of potential therapeutic agents against SARS. The structural requirements of the peptidomimetics with potent inhibitory activities against SARS-CoV 3CL(pro) may be summarized as follows: (i) the presence of a benzothiazole warhead at the S1'-position; (ii) hydrogen bonding capabilities at the cyclic lactam of the S1-site; (iii) appropriate stereochemistry and hydrophobic moiety size at the S2-site and (iv) a unique folding conformation assumed by the phenoxyacetyl moiety at the S4-site.

Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.

PURPOSE: Although lidocaine-induced cell toxicity has been reported, its mechanism is unclear. Cell size, morphological change, and membrane resistance are related to homeostasis and damage to the cell membrane; however, the effects of lidocaine on these factors are unclear. Using an identified LPeD1 neuron from Lymnaea stagnalis, we sought to determine how lidocaine affects these factors and how lidocaine is related to damage of the cell membrane. METHODS: Cell size and morphological form were measured by a micrograph and imaging analysis system. Membrane potential and survival rate were obtained by intracellular recording. Membrane resistance and capacitance were measured by whole-cell patch clamp. Phosphatidyl serine and nucleic acid were double stained and simultaneously measured by annexin V and propidium iodide. RESULTS: Lidocaine at a clinical dose (5-20 mM) induced morphological change (bulla and bleb) in the neuron and increased cell size in a concentration-dependent manner. Membrane potential was depolarized in a concentration-dependent manner. At perfusion of more than 5 mM lidocaine, the depolarized membrane potential was irreversible. Lidocaine decreased membrane resistance and increased membrane capacitance in a concentration-dependent manner. Both phosphatidyl serine and nucleic acid were stained under lidocaine exposure in a concentration-dependent manner. CONCLUSIONS: A clinical dose of lidocaine greater than 5 mM destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis.

PURPOSE: Nerve growth factor (NGF) has been reported to affect synaptic transmission and cause neuropathic pain. In contrast, lidocaine has been used to reduce neuropathic pain; however, the effect of NGF and lidocaine on spontaneous transmitter release and synapse excitation has not been fully defined. Therefore, the effect of NGF and lidocaine on nerve regeneration, synapse reformation, and subsequent spontaneous transmitter release was investigated. We used Lymnaea stagnalis soma-soma-identified synaptic reconstruction to demonstrate that a transient increase in both frequency and amplitude of spontaneous events of miniature endplate potentials (MEPPs) occurs following NGF treatment and a short burst of action potentials in the presynaptic cell; in addition, the effect of lidocaine on NGF-induced synapse reformation was investigated. METHODS: Using a cell culture and electrophysiological and FM-143 imaging techniques for exocytosis on unequivocally identified presynaptic visceral dorsal 4 (VD4) and postsynaptic somata left pedal (LPeE) neurons from the mollusc Lymnaea stagnalis, the effects of NGF and lidocaine on nerve regeneration, synapse reformation, and its electrophysiological spontaneous synaptic transmission between cultured neurons were described. RESULTS: NGF increased axonal growth, frequency, and amplitudes of MEPPs. Lidocaine exposure during synapse reformation periods was drastically and permanently reduced axonal growth and the incidence of synapse excitation by NGF. CONCLUSION: NGF increased amplitudes and frequencies of MEPPs and induced synaptic excitation by increasing axonal growth and exocytosis. Lidocaine exposure during synapse reformation periods permanently suppressed NGF-induced excitation by suppressing axonal growth and exocytosis of presynaptic neurons in the identified reconstructed synapse of L. stagnalis.

Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases.

A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (K(i)=880 nM) and significant selectivity against other human related serine proteases like trypsin (K(i)=729 µM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.

The cell cycle profile test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy.

OBJECTIVE: The cell cycle profile test is suggested to be an independent prognostic indicator for breast cancer patients. To further clarify the prognostic value, we applied this to breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy. METHODS: A total of 153 breast cancer patients, who were treated with postoperative 5-fluorouracil-based chemotherapies, were randomly selected. Specific activities of cyclin-dependent kinases 1 and 2 in the tumor samples were analyzed. Patients were divided into three categories (low, intermediate or high risk) based on cell cycle profile analysis. RESULTS: The proportions of the cell cycle profile categories were 39% for low risk, 10% for intermediate risk and 45% for high risk, respectively. Although the cell cycle profile test did not show a significant predictive power for relapse-free survival (high vs. low risk; P = 0.052), the cell cycle profile categories were significant prognostic factors in a subgroup of 98 patients with fewer than three involved nodes (high vs. low risk, P = 0.004). Multivariate analyses also indicated that a cell cycle profile parameter (high vs. low risk) was an independent prognostic indicator from the number of involved nodes and clinical stage in this subgroup (hazard ratio = 2.46, P = 0.01). Interestingly, the prognostic power of the cell cycle profile test was significant in 75 patients treated with oral 5-fluorouracil derivatives alone (hazard ratio = 6.29 for high vs. low risk, P = 0.02). CONCLUSIONS: These findings suggest that the cell cycle profile test is useful for predicting a higher risk of relapse in patients treated with postoperative 5-fluorouracil-based chemotherapy.

Capsaicin indirectly suppresses voltage-gated Na+ currents through TRPV1 in rat dorsal root ganglion neurons.

BACKGROUND: Capsaicin is used to treat a variety of types of chronic pain, including arthritis and trigeminal neuralgia. Although the cellular effects of capsaicin have been widely studied, little is known about the effects of capsaicin on intracellular sodium ([Na(+)]i) concentrations and voltage-gated Na(+) currents (INa(+)) in nociceptive afferent neurons. Therefore, in this study we sought to characterize the effect of capsaicin on tetrodotoxin-sensitive (TTX-s) and resistant (TTX-r) INa(+). METHODS: The effects of capsaicin on INa(+) in rat dorsal root ganglion neurons were studied for both TTX-s and TTX-r components using whole-cell patch-clamp techniques and intracellular sodium imaging. RESULTS: In both TTX-s and TTX-r INa(+) of capsaicin-sensitive neurons, capsaicin (0.1 to 10 µM) reduced inward currents in a dose-dependent manner. Capsaicin induced a hyperpolarization shift in the steady-state inactivation curves. SB366791 (10 µM), a potent and selective transient receptor potential vanilloid member1 (TRPV1) antagonist, significantly attenuated the reduction in INa(+). Capsaicin induced an increase in the [Na(+)]i, and SB366791 (10 µM) significantly reduced the [Na(+)]i increase. An increase in [Na(+)]i with gramicidin also dependently suppressed INa(+) and induced a hyperpolarization shift in the steady-state inactivation curves by increasing the [Na(+)]i. CONCLUSION: The findings suggest that capsaicin decreases both TTX-s and TTX-r INa(+) as a result of an increase in [Na(+)]i through TRPV1.

Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution.

We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (K(i)<0.1 nM). Moreover, among our peptidomimetic Plm inhibitors, we identified the compounds with the highest antimalarial activity using a SYBR Green I-based fluorescence assay.

Local anesthetics depolarize mitochondrial membrane potential by intracellular alkalization in rat dorsal root ganglion neurons.

BACKGROUND: Although it has been reported that local anesthetics, especially lidocaine, are cytotoxic, the mechanism is unclear. Depolarization of the mitochondrial membrane potential (DeltaPsim), one of the markers of mitochondrial failure, is regulated by the proton electrochemical gradient (Delta H(+)). Therefore, intracellular pH ([pH]in) and mitochondrial pH ([pH]m) are important factors for modifying DeltaPsim. However, the effects of local anesthetics on [pH]in and [pH]m are unclear. To investigate mitochondrial responses to local anesthetics, we simultaneously measured [pH]m and [pH]in, along with DeltaPsim. METHODS: The ratiometric fluorescent probe JC-1 and HPTS were used for the simultaneous measurements of DeltaPsim with [pH]in in rat dorsal root ganglion neurons. A carboxy-SNARF-1 fluorescent probe was used to measure [pH]m. Lidocaine, mepivacaine, bupivacaine, procaine, QX-314, a charged form of lidocaine, and ammonium chloride (NH(4)Cl) were evaluated. RESULTS: DeltaPsim was depolarized and [pH]in was increased by lidocaine, mepivacaine, bupivacaine, and procaine in a dose-dependent manner. Significantly, a relationship between DeltaPsim and [pH]in was observed for lidocaine, mepivacaine, bupivacaine, procaine, and NH(4)Cl perfusion. In contrast, QX-314 did not change DeltaPsim or [pH]in. In low-pH saline (pH6) and in the presence of a weak acid, lidocaine failed to increase [pH]in or depolarize DeltaPsim. The [pH]m was also increased by lidocaine, mepivacaine, bupivacaine, procaine, and NH(4)Cl. CONCLUSION: These results demonstrate that uncharged (base) forms of local anesthetics induce DeltaPsim depolarization. One of the causes is intracellular and mitochondrial alkalization.

Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells.

INTRODUCTION: Paclitaxel is used widely in the treatment of breast cancer. Not all tumors respond to this drug, however, and the characteristics that distinguish resistant tumors from sensitive tumors are not well defined. Activation of the spindle assembly checkpoint is required for paclitaxel-induced cell death. We hypothesized that cyclin-dependent kinase (CDK) 1 activity and CDK2 activity in cancer cells, which reflect the activation state of the spindle assembly checkpoint and the growth state, respectively, predict sensitivity to paclitaxel. METHODS: Cell viability assays and DNA and chromatin morphology analyses were performed in human breast cancer cell lines to evaluate sensitivity to paclitaxel and the cell cycle response to paclitaxel. We then examined the specific activities of CDK1 and CDK2 in these cell lines and in xenograft models of human breast cancer before and after paclitaxel treatment. Protein expression and kinase activity of CDKs and cyclins were analyzed using a newly developed assay system. RESULTS: In the cell lines, biological response to paclitaxel in vitro did not accurately predict sensitivity to paclitaxel in vivo. Among the breast cancer xenograft tumors, however, tumors with significantly increased CDK1 specific activity after paclitaxel treatment were sensitive to paclitaxel in vivo, whereas tumors without such an increase were resistant to paclitaxel in vivo. Baseline CDK2 specific activity was higher in tumors that were sensitive to paclitaxel than in tumors that were resistant to paclitaxel. CONCLUSIONS: The change in CDK1 specific activity of xenograft tumors after paclitaxel treatment and the CDK2 specific activity before paclitaxel treatment are both associated with the drug sensitivity in vivo. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting paclitaxel sensitivity.

Primary gastric plasmacytoma refractory to Helicobacter pylori eradication therapy.

A 49-year-old woman underwent upper gastrointestinal endoscopic examination for epigastric discomfort, revealing giant folds on the greater curvature of the stomach. Histological examinations of biopsy specimens taken from the giant folds showed signs of chronic inflammation, and Helicobacter pylori was also identified. She underwent first-step H. pylori eradication. On follow-up endoscopy, H. pylori was not identified. However, endoscopic findings were unchanged and repeated biopsies showed dense infiltration of atypical plasma cells. No proliferation of centrocyte-like cells was seen. Immunohistochemically, plasma cells were positive for lambda-chain. Primary gastric plasmacytoma was diagnosed. Total gastrectomy was carried out with splenectomy and regional lymph node dissection. The patient remains disease free as of 6 years postoperatively.

Ferrous chloride and ferrous sulfate improve the fungicidal efficacy of cold atmospheric argon plasma on melanized Aureobasidium pullulans.

Since cold atmospheric pressure plasma (CAP) has not only bactericidal activity but also fungicidal activity without toxic residues and thermal damage, it is considered as an alternative method for sterilization of fungi on the surfaces of perishable foodstuffs and human bodies. Aureobasidium pullulans is a ubiquitous yeast-like fungus and called black yeast because it produces melanin, a dark biological pigment. It is well known that various melanized fungi show hyper-resistance to extreme stress conditions including high levels of radioactivity. Curiously, however, there is very little information about the fungicidal effects of CAP on melanized fungi. Therefore, we herein investigated the effects of CAP on A. pullulans, using cold atmospheric argon plasma (Ar plasma). We found that ammonium sulfate repressed the synthesis of melanin in A. pullulans as well as Aureobasidium melanogenum. Although the non-melanized A. pullulans cells were efficiently killed by the exposure of Ar plasma, the melanized cells showed the significant resistance to Ar plasma as well as to hydrogen peroxide and thermal stress. In order to improve the fungicidal efficacy of Ar plasma, we examined the combination of Ar plasma and Fenton reaction. We realized that FeCl2 and FeSO4 significantly improved the sterilization efficacy of Ar plasma on the melanized A. pullulans.

Early induction of PMX-DHP improves oxygenation in severe sepsis patients with acute lung injury.

Direct hemoperfusion with polymyxin B-immobilized fibers (PMX-DHP) has been widely regarded as a treatment modality for septic shock in Japan. Recently, it was reported that PMX significantly improved the P/F (PaO2/FiO2) ratio in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aim of this study was to examine whether the phase of sepsis is related to the effects of PMX-DHP treatment on oxygenation in patients with ALI and ARDS. Thirty-four patients who had ALI or ARDS with severe sepsis were included in this study, and split into two groups: a high-risk for septic shock (H-R) group and a septic shock (S-S) group, based on the cut-off value at a mean arterial pressure of 60 mmHg. We analyzed the modified APACHE-II score, the sepsis-related organ failure assessment (SOFA) score, mean blood pressure (mBP), catecholamine index (CAI), P/F ratio, and 28 days mortality before and after PMX-DHP treatment. SOFA and modified APACHE-II scores showed no significant difference between the two groups. In both groups, mBP and CAI increased significantly following PMX-DHP. In the H-R group, P/F ratio increased from 194 +/- 83 to 262 +/- 113 after PMX-DHP treatment, with a statistical significance, whereas no difference was found in the S-S group. There was no difference in the 28 days survival rate between the groups. It was suggested that early introduction of PMX-DHP for severe sepsis may improve oxygenation.