Predicting Patient Status in Chronic Thromboembolic Pulmonary Hypertension Using a Biophysical Model.

Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance- Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient's response to surgery can help with clinical decision-making.

Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic lupus erythematosus.

A genetic variant of the killer immunoglobulin-like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA) and 17 healthy control subjects for anti-KIR3DL1 activity by an enzyme-linked immunosorbent assay (ELISA) using recombinant KIR3DL1-enhanced green fluorescent protein (EGFP) and EGFP proteins. Anti-KIR3DL1 antibodies were detected in 22 (79%) of the 28 patients with SLE, whereas they were present in only three (27%) of the 11 patients with RA examined. Notably, 10 (91%) of the 11 samples from patients with SLE prior to therapy had anti-KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti-KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti-KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases.

Clinical and clinicopathological characteristics of acute lymphoblastic leukaemia in six cats.

OBJECTIVES: To investigate the clinical characteristics of feline acute lymphoblastic leukaemia patients diagnosed according to the recent diagnostic criteria for the equivalent canine condition. MATERIALS AND METHODS: The medical records of six cats diagnosed with acute lymphoblastic leukaemia were retrospectively reviewed to extract data on clinicopathological characteristics and outcomes. The lymphoid origin of the tumour cells was confirmed by polymerase chain reaction for antigen receptor gene rearrangement, flow cytometry or immunohistochemistry. RESULTS: Non-specific clinical signs such as lethargy and anorexia were common, and anaemia and thrombocytopenia were also commonly identified. Leucocytosis was observed in four cats and leucopenia was observed in two; the number of lymphoblasts in the peripheral blood samples varied among the cases. Lymphoblasts originated from B-cell lineage in four cats and T-cell lineage in one, and those of another cat were positive for both B-cell marker CD21 and T-cell marker CD8. Five of the six cats were treated with cytotoxic chemotherapy, and a partial response was obtained in two. The median overall survival was 55 days (range: 1 to 115). CLINICAL SIGNIFICANCE: Acute lymphoblastic leukaemia should be considered if lymphoblasts are observed in peripheral blood, even if their number is small. The prognosis for cats that have acute lymphoblastic leukaemia is as poor as that for dogs, and further studies are needed to develop effective treatment.

Alteraciones neuropsicológicas y hallazgos neurorradiológicos en pacientes con conmoción cerebral postraumática. Resultados de un estudio piloto / Neuropsychological alterations and neuroradiological findings in patients with post-traumatic concussion: Results of a pilot study

INTRODUCCIÓN: Los traumatismos craneoencefálicos leves (TCE-L) han sido tradicionalmente considerados acontecimientos sin repercusiones cerebrales significativas, cuya sintomatología remite espontáneamente en unos días. Sin embargo, estos hechos son cada vez más cuestionados. Este estudio pretende objetivar la existencia de alteraciones cognitivas precoces en una serie de pacientes con TCE-L y relacionar los hallazgos con distintos marcadores de lesión cerebral. MÉTODOS: Estudio prospectivo de una cohorte de pacientes con un TCE-L valorados de forma consecutiva durante 12 meses. De un total de 1.144 pacientes, se seleccionó a 41 (3,7%) que habían presentado una conmoción cerebral. Además de la valoración clínica habitual y de la práctica de una tomografía computarizada (TC) cerebral, los pacientes fueron estudiados mediante un test estandarizado para síntomas posconmocionales en las primeras 24h después del TCE-L y al cabo de 1-2 semanas y, coincidiendo con la segunda valoración, mediante una batería neuropsicológica. Los resultados se compararon con los de un grupo de 28 voluntarios sanos de características parecidas. En 20 pacientes se practicó una resonancia magnética (RM) craneal. RESULTADOS: En este análisis exploratorio, la memoria y el aprendizaje verbal fueron las funciones cognitivas más afectadas después del TCE-L. Siete de los 20 pacientes con TC cerebral normal presentaron alteraciones estructurales visibles por RM, que en 2 casos fueron compatibles con la presencia de lesión axonal difusa. CONCLUSIONES: Los resultados de este estudio piloto sugieren la presencia de alteraciones cognitivas precoces y lesiones cerebrales estructurales en un porcentaje no despreciable de pacientes que han presentado una conmoción cerebral recuperada después de un TCE-L

INTRODUCTION: Mild traumatic brain injury (mTBI) has traditionally been considered to cause no significant brain damage since symptoms spontaneously remit after a few days. However, this idea is facing increasing scrutiny. The purpose of this study is to demonstrate the presence of early cognitive alterations in a series of patients with mTBI and to link these findings to different markers of brain damage. METHODS: We conducted a prospective study of a consecutive series of patients with mTBI who were evaluated over a 12-month period. Forty-one (3.7%) of the 1144 included patients had experienced a concussion. Patients underwent a routine clinical evaluation and a brain computed tomography (CT) scan, and were also administered a standardised test for post-concussion symptoms within the first 24 hours of mTBI and also 1 to 2 weeks later. The second assessment also included a neuropsychological test battery. The results of these studies were compared to those of a control group of 28 healthy volunteers with similar characteristics. Twenty patients underwent an MRI scan. RESULTS: Verbal memory and learning were the cognitive functions most affected by mTBI. Seven out of the 20 patients with normal CT findings displayed structural alterations on MR images, which were compatible with diffuse axonal injury in 2 cases. CONCLUSIONS: Results from this pilot study suggest that early cognitive alterations and structural brain lesions affect a considerable percentage of patients with post-concussion syndrome following mTBI

Shorter duration of antibiotic treatment for acute bacteraemic cholangitis with successful biliary drainage: a retrospective cohort study.

OBJECTIVES: To assess the effectiveness of short duration antimicrobial therapy for acute cholangitis with bacteraemia. METHODS: We conducted a retrospective cohort study of patients with acute bacteraemic cholangitis with successful biliary duct drainage at a single centre in Japan. We compared short-course antimicrobial therapy (SCT, ≤7 days) and long-course therapy (LCT, ≥8 days), with a primary outcome of 30-day mortality. We constructed logistic regression models for mortality and a composite outcome, including mortality, recurrence, recrudescence, new bacteraemia, liver abscess or other complications related to cholangitis. We also developed a propensity score for SCT with inverse probability weighting for both the primary outcome and the composite outcome. RESULTS: We identified 263 patients in our cohort; 86 (32.7%) patients received SCT and the remaining 177 (67.3%) received LCT. The median durations of SCT and LCT were 6 days (range 2-7 days) and 12 days (range 8-46 days), respectively. The 30-day mortalities of SCT and LCT were 4.7% (4/85) and 5.7% (10/176), respectively (p 1.00). Logistic regression analysis showed that the odds ratio of SCT for 30-day mortality and the composite outcome were 1.07 (95% CI 0.25-4.52, p 0.93) and 1.08 (95% CI 0.48-2.45, p 0.85), respectively. Propensity score analyses for both 30-day mortality and the composite outcome did not demonstrate a difference between SCT and LCT (p 0.65 and p 0.95, respectively). CONCLUSIONS: SCT with a median duration of 6 days did not have worse outcomes than LCT with a median duration of 12 days. Shortening the duration of antimicrobial therapy may be a reasonable option when treating acute bacteraemic cholangitis following successful biliary drainage.

Detection of colonization by carbapenem-resistant organisms by real-time polymerase chain reaction from rectal swabs in patients with chronic renal disease.

BACKGROUND: Carbapenem-resistant organism (CRO) colonization is a serious problem that increases the risk of infection and contributes to dissemination of antimicrobial resistance in healthcare-associated environments. The risk of acquisition and dissemination of CRO is high in chronic renal failure patients and the surveillance culture is recommended as a component of infection control programmes. AIM: To assess colonization by CRO, comparing phenotypic and molecular-based methods of diagnostics, in rectal swabs in a large population of chronic renal failure patients. METHODS: A total of 1092 rectal swabs (ESwab™) were collected at two different times from 546 chronic kidney disease (CKD) patients from a specialized tertiary care university centre. They were divided into three groups: conservative treatment (N = 129), dialysis (N = 217), and transplanted patients (N = 200). A chromogenic (CHROMagar™) KPC agar and the multiplex real-time polymerase chain reaction (qPCR) targeting carbapenemase-encoding genes were tested as phenotypic and molecular screening for carbapenemase production. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and conventional PCR were also performed on the isolates grown on chromogenic agar. FINDINGS: Among the 1092 samples, 150 (13.7%) were identified as CRO producers according to chromogenic agar. Only 26 (2.4%) were confirmed as KPC by conventional PCR. According to qPCR direct from swab, 31 (2.8%) were positive for KPC, 39 (3.6%) for GES, and three (0.3%) for SPM with kappa index of 0.256. CONCLUSION: The qPCR technique provides faster results when compared to culture method and enables rapid implementation of control measures and interventions to reduce the spread of CRO in healthcare settings, especially among CKD patients.

Ferroelectric-like metallic state in electron doped BaTiO3.

We report that a ferroelectric-like metallic state with reduced anisotropy of polarization is created by the doping of conduction electrons into BaTiO3, on the bases of x-ray/electron diffraction and infrared spectroscopic experiments. The crystal structure is heterogeneous in nanometer-scale, as enabled by the reduced polarization anisotropy. The enhanced infrared intensity of soft phonon along with the resistivity reduction suggests the presence of unusual electron-phonon coupling, which may be responsible for the emergent ferroelectric structure compatible with metallic state.

The validity of three sputum smears taken in one day for discontinuing isolation of tuberculosis patients.

We conducted a retrospective comparative study of acid-fast bacilli (AFB) smear sensitivity according to time of specimen collection to assess whether three consecutive AFB smears collected in 1 day are useful when deciding to discontinue respiratory isolation of patients with pulmonary tuberculosis (TB). A total of 236 sputum specimens from 119 patients with pulmonary TB were used for the analysis. There was no statistical difference in AFB smear sensitivity of early-morning sputum and those collected later (P = 0.186). This may allow us to collect all specimens in a single day and discontinue respiratory isolation of TB patients earlier.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Gordonia terrae kidney graft abscess in a renal transplant patient.

We present the first report, to our knowledge, of a renal abscess cause by an infection from Gordonia terrae in a kidney transplant patient. The patient simultaneously had pulmonary tuberculosis and a perirenal allograft abscess caused by G. terrae. After treatment with imipenem, in addition to anti-tuberculous drugs, the patient was cured.

Terahertz phase contrast imaging of sorption kinetics in porous coordination polymer nanocrystals using differential optical resonator.

The enhancement of light-matter coupling when light is confined to wavelength scale volumes is useful both for studying small sample volumes and increasing the overall sensing ability. At these length scales, nonradiative interactions are of key interest to which near-field optical techniques may reveal new phenomena facilitating next-generation material functionalities and applications. Efforts to develop novel chemical or biological sensors using metamaterials have yielded innovative ideas in the optical and terahertz frequency range whereby the spatially integrated response over a resonator structure is monitored via the re-radiated or leaked light. But although terahertz waves generally exhibit distinctive response in chemical molecules or biological tissue, there is little absorption for subwavelength size sample and therefore poor image contrast. Here, we introduce a method that spatially resolves the differential near-field phase response of the entire resonator as a spectral fingerprint. By simultaneously probing two metallic ring resonators, where one loaded with the sample of interest, the differential phase response is able to resolve the presence of guest molecules (e.g. methanol) as they are adsorbed or released within the pores of a prototypical porous coordination polymer.

Lung transplantation as rescue therapy in patients too sick to be discharged from acute care.

BACKGROUND: There is an increasing demand for lung transplantation in patients in advanced respiratory failure. Although many of these patients do not require mechanical ventilation or extracorporeal membrane oxygenation, an increasing number are critically ill. In this single-center study, we have analyzed our experience with lung transplantation in subjects who were inpatients at the time of their transplant and not expected to survive to discharge. METHODS: Between July 2006 and March 2012, we performed 274 bilateral sequential lung transplants and 34 single-lung transplants. Twenty-six patients who were inpatients at the time of their transplant, and were not expected to survive to hospital discharge, formed the inpatient group in this retrospective review. The remaining 281 outpatient lung transplant patients formed the comparison group. RESULTS: The inpatient group spent significantly fewer days on the waiting list compared to the outpatient group. Postoperative survival was significantly poorer in the inpatient group compared to the outpatient group (P = .001), and this was most noticeable in the first 90 days. There was no significant difference in survival between the inpatient transplant cohort and a historically comparable wait list cohort (P = .614). CONCLUSION: Lung transplantation in critically ill inpatients, although associated with a survival advantage compared to not transplanting them, does give poorer survival results compared to postoperative survival in outpatient patients.

Effect of cell permeable peptide of c-Jun NH2-terminal kinase inhibitor on the attenuation of renal ischemia-reperfusion injury in pigs.

The outcomes of organ transplantation have improved due to better immunosuppressive drugs, surgical techniques, and management of complications. However, ischemia-reperfusion injury remains a challenge affecting graft survival. In this study, we employed injection of a protein transduction domain (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was administered into the renal artery, allowing it to be taken into various elements including vascular endothelial cells by endocytosis via the PTD. Serum creatinine and blood urea nitrogen concentrations were lower among PTD-JNKI than controls. In addition, renal tissue blood flow was maintained in the PTD-JNKI group, resulting in less tissue injury and fewer apoptotic cells. These results suggested that the PTD technique improved renal transplantation outcomes.

Terahertz spectroscopy of the reactive and radiative near-field zones of split ring resonator.

A terahertz microscope has been used to excite and observe the resonant modes of a single split ring resonator in the reactive and radiative near-field zones. The two lowest resonant modes of an isolated split ring resonator with their corresponding radiation patterns are reported; they showed good agreement to simulations. The passage from the reactive to radiative near-field zone is also discussed. Further, our result introduced a novel technique to perform terahertz time-domain spectroscopy of samples a few tens of micrometers in size by measuring the in-plane radiative near-field zone.

The cellular building blocks of breathing.

Respiratory brainstem neurons fulfill critical roles in controlling breathing: they generate the activity patterns for breathing and contribute to various sensory responses including changes in O2 and CO2. These complex sensorimotor tasks depend on the dynamic interplay between numerous cellular building blocks that consist of voltage-, calcium-, and ATP-dependent ionic conductances, various ionotropic and metabotropic synaptic mechanisms, as well as neuromodulators acting on G-protein coupled receptors and second messenger systems. As described in this review, the sensorimotor responses of the respiratory network emerge through the state-dependent integration of all these building blocks. There is no known respiratory function that involves only a small number of intrinsic, synaptic, or modulatory properties. Because of the complex integration of numerous intrinsic, synaptic, and modulatory mechanisms, the respiratory network is capable of continuously adapting to changes in the external and internal environment, which makes breathing one of the most integrated behaviors. Not surprisingly, inspiration is critical not only in the control of ventilation, but also in the context of "inspiring behaviors" such as arousal of the mind and even creativity. Far-reaching implications apply also to the underlying network mechanisms, as lessons learned from the respiratory network apply to network functions in general.

Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke.

Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4(+)T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4(+)T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4(+)T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4(+)GITR(+)T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR-GITR ligand (GITRL) interaction by GITR-Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4(+)T cells, GITR(+)CD4(+)T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR-GITRL interaction may be a novel immune-based therapy in stroke.

Real-time terahertz near-field microscope.

We report a terahertz near-field microscope with a high dynamic range that can capture images of a 370 x 740 µm2 area at 35 frames per second. We achieve high spatial resolution (14 µm corresponding to λ/30 for a center frequency at 0.7 THz) on a large area by combining two novel techniques: terahertz generation by tilted-pulse-front excitation and electro-optic balanced imaging detection using a thin crystal. To demonstrate the microscope capability, we reveal the field enhancement at the gap position of a dipole antenna after the irradiation of a terahertz pulse.

Effects of Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-Sen-Qi-Wan) on hyperinsulinemia induced in rats fed a sucrose-rich diet.

We investigated the effects of a Chinese herbal medicine, Gosha-jinki-gan (GJG), on the regulation of insulin levels in rats fed a sucrose-rich diet (SRD). Normal Wistar rats in the SRD group were fed an SRD for 4 weeks. Increased dietary sucrose did not alter plasma glucose levels but it increased plasma insulin levels at 2 and 4 weeks in the SRD-fed rats relative to control rats that were fed standard chow. GJG treatment significantly suppressed the SRD-induced elevation in plasma insulin levels. These results suggest that GJG improves hyperinsulinemia caused by an SRD.

Living donor renal transplantation using grafts with multiple arteries procured by laparoscopic nephrectomy.

OBJECTIVE: Kidney grafts with multiple renal arteries (MRAs) are not uncommon, but they do make transplantation more difficult. Laparoscopic graft nephrectomy has become the standard; however, the safety and reliability must be maintained for both a donor and a recipient even in case of MRAs. This study evaluated the short-term outcomes of living donor renal transplant using grafts with MRAs procured by laparoscopic nephrectomy. PATIENTS AND METHODS: This study reviewed all living donor kidney transplantations performed from January 2008 to June 2009, which were divided into 3 groups according to the number of renal graft arteries. The serum creatinine level, warm ischemic time (WIT), rewarming time, total ischemic time (TIT), operative time, acute rejection episodes, and complications in each group were evaluated. RESULTS: The serum creatinine level showed no difference among the groups. Longer TIT was observed in the MRAs group, but WIT and rewarming time did not differ. The acute rejection rate was not different. There were no vessel complications in any donors and recipients. CONCLUSION: Harvesting kidney grafts with MRAs by laparoscopic nephrectomy requires a longer TIT; however, transplantation can be performed safely and reliably for both donors and recipients.