Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

BACKGROUND: Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. OBJECTIVE: We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). METHODS: We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. RESULTS: Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). DISCUSSION: Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10 months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

[Relationship between c-kit mRNA expression and prognosis in patients with rectal carcinoma].

Objective: To investigate the correlation between c-kit mRNA expression and prognosis in patients with rectal carcinoma. Methods: The expression of c-kit mRNA in rectal carcinoma tissues(n=66) was detected by multiplex branched-DNA liquid chip method. According to the expression level, the patients were classified into the c-kit mRNA high expression group and the low group. We analyzed the relationship between the c-kit mRNA expression and the clinicopathological characteristics of patients, as well as the factors affecting patients'prognosis. Results: Of the 66 rectal carcinoma patients, 18(27.3%)cases were c-kit mRNA high expression. No significant correlation was found between the c-kit mRNA expression and gender, age, preoperative carcinoembryonic antigen, preoperative hemoglobin, distance to verge, lymph node metastasis, tumor thrombus, T stage, TNM stage and tumor differentiation (P>0.05). In follow-up, 34 patients died, 32 patients and 36 patients were recurrence or metastasis. The 1-, 3-, 5-year overall survival(OS) of c-kit mRNA high expression group were 100.0%, 77.8%, 77.8%, respectively, while those of the low one were 93.8%, 56.3%, 45.8%, respectively. The difference was statistically significant(P=0.025). Lymph node metastasis, T stage and TNM stage were also significant associated with OS(P<0.05). The 1-, 3-, 5-year disease free rate (DFS)of the c-kit mRNA high expression group were 100.0%, 77.8% and 77.8%, respectively, while those of the low one were 77.1%、43.8% and 41.7%, respectively, and the difference between the two groups was significant (P=0.044). As a reslut, c-kit mRNA expression (P=0.038) and TNM stage (P=0.039) were the independent prognostic factors affecting the OS in rectal cancer patients. Conclusions: Low expression of c-kit was associated with poor prognosis of rectal carcinoma. And the mechanism underlying this phenomenon deserves further exploration.

Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer.

OBJECTIVE: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.

Adolescents with Type 1 diabetes mellitus experience psychosensorial symptoms during hypoglycaemia.

AIM: To describe mood and psychosensorial symptoms of hypoglycaemia in adolescents with Type 1 diabetes mellitus in two countries with different cultures, Turkey and the USA. METHODS: We developed a 68-item questionnaire assessing physical, behavioural, mood and psychosensorial symptom frequency and ratings ['good', 'bad', or 'both' (sometimes good, sometimes bad)]. Adolescents with Type 1 diabetes were recruited from paediatric diabetes clinics at the University of North Carolina at Chapel Hill in the USA and Kocaeli University in Turkey. The percentages of participants at each clinic who endorsed individual symptoms, symptom categories and symptom ratings were calculated and compared. RESULTS: Cronbach's α values were > 0.7 for each real symptom category. No symptom items were excluded from the questionnaire analysis based on item-total correlation results which were all > 0.2. Data were collected from 132 participants (69 from University of North Carolina, 63 from Kocaeli University, 54% male). The mean (SD) age of the participants was 14.9 (1.9) years, HbA1c level was 8.7 (1.8) % and duration of Type 1 diabetes was 5.8 (3.7) years. On average, each physical symptom was experienced by 65.2% of participants, each behavioural symptom by 46.5%, each mood symptom by 42.8%, and each psychosensorial symptom by 48.9%. On average, each physical, behavioral, mood and psychosensorial symptom was rated as 'good' or 'both' by 23.0, 29.1, 36.9 and 37.2% of participants, respectively. There were no symptom differences between the groups in each country. CONCLUSIONS: In addition to the classic physical symptoms experienced during hypoglycaemia, adolescents with Type 1 diabetes report psychosensorial, mood and behavioral symptoms, and some describe them as positive experiences. Symptom experiences were similar in these two countries with different cultures.

First Report of Maize chlorotic mottle virus on Sweet Corn in Taiwan.

In February 2014, a severe disease on maize (Zea mays L.) broke out in the fields of central and southwestern Taiwan and caused yield losses in sweet corn production. Chlorotic spots first appeared at the base of infected leaves and later developed into systemic mottling. Diffused necrotic patches were also found on leaves or husks of the diseased plants. Moreover, severe rosetting and stunting accompanied by abnormalities in ear production were observed on mature plants. Eighteen leaf samples from symptomatic plants were collected and submitted to our Plant Diagnostic Clinic for virus diagnosis. All of the samples were first tested by reverse transcriptase (RT)-PCR to detect Maize stripe virus (MSpV) and by indirect ELISA to detect Maize dwarf mosaic virus (MDMV) or Sugarcane mosaic virus (SCMV), which were endemic to this area (1). Only 2 out of 18 samples were positive for MDMV, SCMV, or mixed infection of both viruses. Sap inoculation tests conducted on seedlings of sweet corn cv. Honey 236 indicated that the MDMV- and SCMV-negative samples still had an unknown pathogen causing original symptoms in the receptor plants. The isolate from Yunlin county reacted only with the antibody to Maize chlorotic mottle virus (MCMV) (AC Diagnostics, Fayetteville, AR) in ELISA. For further identification, the MCMV-specific primers (forward: MCMVg3514F-GGGAACAACCTGCTCCA; reverse MCMVg4014R-GGACACGGAGTACGAGA) were designed from the nucleotide sequence of MCMV coat protein (CP) gene. In RT-PCR using the AccuPower RT/PCR PreMix kit (Bioneer, Daejeon, Korea), an expected 500-bp DNA fragment was observed. This PCR product was cloned and its nucleotide sequence was determined by Mission Biotech Co., Taipei, Taiwan. BLAST analysis of the CP gene of the MCMV-Yunlin revealed the maximum nucleotide identities (99%) with Chinese Sichuan isolates (GenBank Accession No. JQ984270) and 98% identities to four Chinese Yunnan isolates (GU138674, JQ982468, JQ982469, and KF010583) and one Kenya isolate (JX286709), compared with 97% to Kansas isolate (X14736) and 96% to Nebraska isolate (EU358605). Subsequently, the complete nucleotide sequence of the viral genome (KJ782300) was determined from five overlapping DNA fragments obtained from independent RT-PCR amplification. The virus isolate was infectious to sweet corn cultivars Bai-long-wang, Devotion, SC-34, SC2015, and Zheng-zi-mi, on which similar symptoms were developed after mechanical inoculation. During the spring of 2014, a total of 224 sweet corn samples were collected from the epidemic areas of Taichung, Yunlin, Chiayi, and Kaohsiung counties. Samples (n= 161) reacted positive for MCMV in ELISA and/or RT-PCR. In the field survey, more than 20 adult thrips might be observed on an MCMV-infected plant. Two species of Frankliniella were found on maize plants: F. williamsi Hood and F. intonsa Trybom. Maize thrips (F. williamsi), an occasional pest of maize occurring during winter and spring in Taiwan, was characterized by its abdominal sternite II on which 1 or 2 discal setae of equal length with posteromarginal setae were borne (2). Samples with 1, 5, 10, and 30 F. williamsi collected in the field were tested by RT-PCR; MCMV was detectable not only in the pooled crushed bodies but also in a single maize thrips. This is the first report of MCMV occurrence on maize in Taiwan and of the virus transmitted by maize thrips. References: (1) C. T. Chen et al. Taiwan Sugar 37(4):9, 1990. (2) C.-L. Wang et al. Zool. Stud. 49:824, 2010.

Characterizing hepatitis B virus infection in children in the Democratic Republic of Congo to inform elimination efforts.

Objective: Despite global reductions in hepatitis B virus (HBV) prevalence, an estimated 6.2 million children are infected, two-thirds of whom live in the WHO Africa region. We sought to characterize childhood HBV to inform elimination efforts in the Democratic Republic of Congo (DRC), one of the largest and most populous African countries. Methods: Using the most recent (2013-14) nationally representative Demographic and Health Survey in the DRC, we analyzed HBV surface antigen (HBsAg) on dried blood spots and associated survey data from children aged 6-59 months. We estimated HBsAg-positivity prevalence nationally, regionally, and by potential correlates of infection. We evaluated spatial variation in HBsAg-positivity prevalence, overall and by age, sex, and vaccination status. Findings: Using data from 5,679 children, we found national HBsAg-positivity prevalence was 1.3% (95% CI: 0.9%-1.7%), but ranged from 0.0% in DRC's capital city province, Kinshasa, to 5.6% in northwestern Sud-Ubangi Province. Prevalence among boys (1.8%, 95% CI: 1.2%-2.7%) was double that among girls (0.7%, 95%CI: 0.4%-1.3%). Tetanus antibody-negativity, rurality, and lower household wealth were also significantly associated with higher HBsAg-positivity prevalence. We observed no difference in prevalence by age. Children had higher HBsAg-positivity odds if living with ≥1 HBsAg-positive adult household member (OR: 2.3, 95%CI: 0.7-7.8), particularly an HBsAg-positive mother (OR: 7.2, 95%CI:1.6-32.2). Conclusion: In the largest national survey of HBV among children and household contacts in the DRC, we found that childhood HBV prevalence was 10-60 times the global target of 0.1%. We highlight specific regions and populations for further investigation and focused prevention efforts.

Palliative care for persons with late-stage Alzheimer's and related dementias and their caregivers: protocol for a randomized clinical trial.

BACKGROUND: Limited access to specialized palliative care exposes persons with late-stage Alzheimer's disease and related dementias (ADRD) to burdensome treatment and unnecessary hospitalization and their caregivers to avoidable strain and financial burden. Addressing this unmet need, the purpose of this study was to conduct a randomized clinical trial (RCT) of the ADRD-Palliative Care (ADRD-PC) program. METHODS: The study will use a multisite, RCT design and will be set in five geographically diverse US hospitals. Lead investigators and outcome assessors will be masked. The study will use 1:1 randomization of patient-caregiver dyads, and sites will enroll N = 424 dyads of hospitalized patients with late-stage ADRD with their family caregivers. Intervention dyads will receive the ADRD-PC program of (1) dementia-specific palliative care, (2) standardized caregiver education, and (3) transitional care. Control dyads will receive publicly available educational material on dementia caregiving. Outcomes will be measured at 30 days (interim) and 60 days post-discharge. The primary outcome will be 60-day hospital transfers, defined as visits to an emergency department or hospitalization ascertained from health record reviews and caregiver interviews (aim 1). Secondary patient-centered outcomes, ascertained from 30- and 60-day health record reviews and caregiver telephone interviews, will be symptom treatment, symptom control, use of community palliative care or hospice, and new nursing home transitions (aim 2). Secondary caregiver-centered outcomes will be communication about prognosis and goals of care, shared decision-making about hospitalization and other treatments, and caregiver distress (aim 3). Analyses will use intention-to-treat, and pre-specified exploratory analyses will examine the effects of sex as a biologic variable and the GDS stage. DISCUSSION: The study results will determine the efficacy of an intervention that addresses the extraordinary public health impact of late-stage ADRD and suffering due to symptom distress, burdensome treatments, and caregiver strain. While many caregivers prioritize comfort in late-stage ADRD, shared decision-making is rare. Hospitalization creates an opportunity for dementia-specific palliative care, and the study findings will inform care redesign to advance comprehensive dementia-specific palliative care plus transitional care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04948866. Registered on July 2, 2021.

Pneumocystis jiroveci pneumonia in patients with systemic lupus erythematosus after rituximab therapy.

Pneumocystis jiroveci pneumonia (PCP) is an uncommon but potentially life-threatening infection in immunocompromised patients with low blood T cells. Rituximab, a chimeric human/murine monoclonal antibody against the B cell-specific antigen CD20, has been increasingly used and appears to be effective in the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE). PCP has been reported in some patients with autoimmune diseases or lymphoma subjected to rituximab treatment, but has not yet been reported in SLE patients. We report PCP in two patients with SLE after rituximab treatment. Fever and respiratory symptoms associated with diffuse pulmonary infiltrates developed within weeks after rituximab therapy. One patient died of respiratory failure. Another patient recovered uneventfully after treatment with clindamycin and primaquine.

Evaluation of a novel index by tissue Doppler imaging in patients with advanced heart failure: relation to functional class and prognosis.

BACKGROUND: Despite the ability of tissue Doppler imaging (TDI) to detect left ventricular (LV) systolic and diastolic myocardial functions in patients with heart failure, the added value of TDI to clinical variables and conventional echocardiography in predicting the symptoms and outcome of advanced heart failure has not been clearly defined. METHODS AND RESULTS: Two hundred and thirty adult patients diagnosed with congestive heart failure were assigned to study groups based on the New York Heart Association functional classes. Pulsed-wave TDI (PWTDI), including average of peak systolic (Sm), early (Em) and late diastolic (Am) velocities from six mitral annular sites was evaluated. PWTDI was also calculated to create a combined index (EAS index) of diastolic and systolic performances. All patients were followed up for cardiac-related death and hospitalisation as a result of heart failure. Patients with functional class III-IV had a significantly higher EAS index (0.21 ± 0.19 vs. 0.13 ± 0.08, p < 0.05) than those with class I-II and the control (0.10 ± 0.04, p < 0.05). Except for Sm and Em, all conventional echocardiographic Doppler parameters and TDI variables significantly correlated with functional class. Moreover, according to multiple stepwise analysis, EAS index and percentage of chronic renal insufficiency (CRF) were the only two independent predictors of functional class (EAS index, p = 0.006; CRF, p = 0.019). During follow-up (median, 30 months), 93 participants had cardiac events. EAS index, LV mass index and CRF were significant predictors of cardiac mortality and hospitalisation [EAS index, hazard ratio (HR) 4.962, p = 0.006; LV mass index, HR 1.007, p = 0.003; CRF, HR 1.616, p = 0.040]. CONCLUSIONS: The EAS index, which reflects systolic and diastolic performances, is a highly effective means of differentiating between patients with functional class I-II and those with III-IV. The index also correlates with cardiac mortality and hospitalisation for worsening heart failure, thus providing additional value to conventional echocardiographic measures.

Tumor length assessed by miniprobe endosonography can predict the survival of the advanced esophageal squamous cell carcinoma with stricture receiving concurrent chemoradiation.

There were tumor strictures commonly encountered in the esophageal squamous cell carcinoma (ESCC) to limit the conventional echoendoscope for exact tumor staging and size measurements. This study evaluated the role of miniprobe endosonography (EUS) to predict the survival of ESCC patients after concurrent chemoradiation therapy (CCRT). This study prospectively enrolled ESCC patients to receive high-frequency miniprobe EUS for the assessments of the tumor size and tumor-node-metastasis (TNM) stage. For the patients defined with advanced stages to receive CCRT as initial therapy, the tumor size parameters assessed by EUS were analyzed for their correlation with the treatment response and the patients' survivals. Fifty-four patients, >96% with advanced TNM stage III or IV, were enrolled with a medium follow-up of 320.5 days. Almost all of the 54 cases had partial or complete stricture of the esophageal lumens due to the tumor obstructions at enrollment. The overall median survival was 18.6 months, and the 1- and the 2-year survival rates were 64.9 and 45.2%, respectively. Patients with initial tumor length <6 cm assessed by the pre-CCRT EUS had a better survival than those with length ≥6 cm (median survival: >56.5 months vs. 11.5 months, P= 0.006). The patients with initial tumor length <6 cm had a higher rate of downstage than those with tumor length ≥6 cm after the first course of CCRT (80.0% vs. 16.7%, P= 0.035). Multivariate Cox regression confirmed the initial tumor length (hazard ratio [HR]= 1.21, P= 0.034) as well as the presence of distal metastasis are both independent predictors of the survival in ESCC patients receiving CCRT. For the ESCC patients, commonly with tumor stricture, the miniprobe EUS to assess tumor length before CCRT can predict the treatment response and the survivals.

Synthesis of Fibrils in Vitro by a Solubilized Cellulose Synthase from Acetobacter xylinum.

A digitonin-solubilized cellulose synthase was prepared from Acetobacter xylinum. When this enzyme was incubated under conditions known to lead to active synthesis of 1,4-beta-D-glucan polymer (cellulose), electron microscopy revealed that clusters of fibrils were assembled within minutes. Individual fibrils are 17 +/- 2 angstroms in diameter. Evidence that the fibrils were freshly synthesized and cellulosic in nature was their incorporation of the tritium from UDP-[(3)H]glucose (UDP, uridine 5'-diphosphate), their binding of gold-labeled cellobiohydrolase, and an electron diffraction pattern with 004, 200, and 012 reflections (characteristic of cellulose synthesized in vivo) but missing 110 and 110 reflections. The small size of the fibrils is atypical of native A. xylinum cellulose microfibrils. The fibrils synthesized in vitro resemble, in morphology and size, the fibrillar cellulose produced when A. xylinum is cultured in the presence of agents that interfere with the normal process of crystallization of the microfibrils. The solubilized enzyme unit may therefore be producing a basic fibrillar structure that, in vivo, interacts laterally with other fibrils to produce native cellulose microfibrils.

Cavitary Plaques in Otospongiosis: CT Findings and Clinical Implications.

BACKGROUND AND PURPOSE: Cavitary plaques have been reported as a manifestation of otospongiosis. They have been related to third window manifestations, complications during cochlear implantation, and sensorineural hearing loss. However, their etiology and clinical implications are not entirely understood. Our purpose was to determine the prevalence, imaging findings, and clinical implications of cavitary plaques in otospongiosis. MATERIALS AND METHODS: We identified patients with otospongiosis at a tertiary care academic medical center from January 2012 to April 2017. Cross-sectional CT images and clinical records of 47 patients (89 temporal bones) were evaluated for the presence, location, and imaging features of cavitary and noncavitary otospongiotic plaques, as well as clinical symptoms and complications in those who underwent cochlear implantation. RESULTS: Noncavitary otospongiotic plaques were present in 86 (97%) temporal bones and cavitary plaques in 30 (35%). Cavitary plaques predominated with increasing age (mean age, 59 years; P = .058), mostly involving the anteroinferior wall of the internal auditory canal (P = .003), and their presence was not associated with a higher grade of otospongiosis by imaging (P = .664) or with a specific type of hearing loss (P = .365). No patients with cavitary plaques had third window manifestations, and those with a history of cochlear implantation (n = 6) did not have complications during the procedure. CONCLUSIONS: Cavitary plaques occurred in one-third of patients with otospongiosis. Typically, they occurred in the anteroinferior wall of the internal auditory canal. There was no correlation with the degree of otospongiosis, type of hearing loss, or surgical complications. Cavitary plaques tended to present in older patients.

Diffusion tensor imaging in the assessment of normal-appearing brain tissue damage in relapsing neuromyelitis optica.

BACKGROUND AND PURPOSE: Normal-appearing brain tissue (NABT) damage was established in multiple sclerosis by histology, MR spectroscopy, magnetization transfer imaging and diffusion tensor imaging (DTI). However, whether this phenomenon can be detected in relapsing neuromyelitis optica (RNMO) remains unclear. The aim of this study was to use DTI to investigate the presence of NABT damage in RNMO patients and its possible mechanism. METHODS: Conventional MR imaging and DTI scans were performed in 16 patients with RNMO without visible lesions on brain MR imaging and in 16 sex- and age-matched healthy control subjects. Histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA) was performed in the entire brain tissue (BT), white matter (WM), and gray matter (GM). Region of interest (ROI) analysis of MD and FA was also performed in WM regions connected with the spinal white matter tracts or optic nerve (including medulla oblongata, cerebral peduncle, internal capsule, and optic radiation), in corpus callosum without direct connection with them, and in some GM regions. RESULTS: From histogram analysis, we found the RNMO group had a higher average MD of the BT, WM, and GM, a lower average MD peak height and a higher average MD peak location of the GM, and a higher average FA peak height of the WM than did the control group. From ROI analysis, compared with control subjects, RNMO patients had a higher average MD and a lower average FA in ROIs of WM connected with the spinal white matter tracts or optic nerve and a normal average MD and FA in corpus callosum without direct connection with them. In addition, a high average MD was found in parietal GM in these patients. CONCLUSIONS: Our findings confirm the presence of abnormal diffusion in brain tissue in patients with RNMO and suggest that secondary degeneration caused by lesions in the spinal cord and optic nerve might be an important mechanism for this abnormality.

Procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia.

UNLABELLED: Essentials The procoagulant effects of microparticles (MPs) on coagulation in endotoxemia are not known. MPs from endotoxemia volunteers were evaluated for procoagulant activity in a plasma milieu. MPs from endotoxemia volunteers shortened clotting times and enhanced thrombin generation. MP procoagulant effects were mediated in a factor XI-dependent manner. SUMMARY: Background Human endotoxemia is characterized by acute inflammation and activation of coagulation, as well as increased numbers of circulating microparticles (MPs). Whether these MPs directly promote coagulation and through which pathway their actions are mediated, however, has not been fully explored. Objectives In this study, we aimed to further characterize endotoxin-induced MPs and their procoagulant properties using several approaches. Methods Enumeration and characterization of MPs were performed using a new-generation flow cytometer. Relative contributions of the extrinsic and intrinsic pathways in MP-mediated procoagulant activity were assessed using plasmas deficient in factor (F) VII or FXI or with blocking antibodies to tissue factor (TF) or FXIa. Results Total MPs and platelet MPs were significantly elevated in plasma at 6 h after infusion of endotoxin in healthy human subjects. MPs isolated from plasma following endotoxin infusion also demonstrated increased TF activity in a reconstituted buffer system. When added to recalcified platelet-poor plasma, these MPs also promoted coagulation, as judged by a decreased clotting time with shortening of the lag time and time to peak thrombin using calibrated automated thrombography (CAT). However, the use of FVII-deficient plasma or blocking antibody to TF did not inhibit these procoagulant effects. In contrast, plasma clotting time was prolonged in FXI-deficient plasma and a blocking antibody to FXIa inhibited all MP-mediated parameters in the CAT assay. Conclusions The initiation of coagulation by cellular TF in endotoxemia is in contrast to (and presumably complemented by) the intrinsic pathway-mediated procoagulant effects of circulating MPs.

Complete sinoatrial block in two patients with bradycardia-tachycardia syndrome.

Electrophysiologic studies with recordings of sinus node electrograms were performed in two patients with bradycardia-tachycardia syndrome. In both patients, the rest electrocardiogram showed apparent sinus bradycardia. Patient 1 had frequent paroxysms of atrial tachycardia with long pauses of up to 10 seconds; Patient 2 had paroxysmal atrial flutter and atrial pauses of up to 8 seconds. Multiple, repetitive, low frequency deflections, with a cycle length ranging from 730 to 960 ms in Case 1 and 570 to 750 ms in Case 2, suggestive of sinus node electrograms, were recorded at a critical area at the junction between the superior vena cava and the right atrium. These low frequency deflections had no relation to spontaneous junctional beats or the spontaneous atrial beats that showed high frequency deflections on the atrial electrogram. However, they could be suppressed by spontaneous or paced atrial beats. Pharmacologic interventions in Case 2 showed that the cycle length of the low frequency deflections shortened after administration of isoproterenol and did not change after propranolol or atropine. Thus, complete sinoatrial exit block with intact entrance conduction can occur in patients with bradycardia-tachycardia syndrome. Under such circumstances, the surface electrocardiographic manifestation of sinus bradycardia may not be of sinus origin.

Double atrial responses to a single ventricular impulse due to simultaneous conduction via two retrograde pathways.

Electrophysiologic studies were performed in two patients. In one patient (Case 1) with ventricular pre-excitation and paroxysmal supraventricular tachycardia, studies after diltiazem administration showed two QRS responses to a single atrial stimulus during atrial pacing at a cycle length of 300 ms. The first QRS response with full pre-excitation and short PR interval was consistent with accessory pathway conduction, while the second QRS response with a normal duration and an atrio-His bundle interval of 350 ms was consistent with normal pathway conduction. The second QRS response was followed by initiation of supraventricular tachycardia. Studies after verapamil administration on a separate day disclosed two atrial responses to a single QRS complex during ventricular pacing at cycle lengths between 330 and 280 ms, suggesting simultaneous retrograde accessory and normal pathway conduction. In Case 2 with a supraventricular tachycardia using a fast atrioventricular nodal pathway for anterograde and a slow ventriculoatrial pathway for retrograde conduction, two atrial responses to a single QRS complex were observed during ventricular pacing at cycle lengths between 500 and 400 ms. The first atrial response showed a stimulus to atrial interval of 120 ms and an atrial activation sequence with the low septal right atrium being earlier than other atrial sites, suggesting retrograde fast pathway conduction. The second atrial response showed a stimulus to atrial interval of 505 ms and an atrial activation sequence with low septal right atrium being simultaneous with the proximal coronary sinus, suggesting retrograde slow pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular block in the atypical form of junctional reciprocating tachycardia: evidence supporting the atrioventricular node as the site of reentry.

Serial electrophysiologic studies were performed in 19 patients with the atypical form of supraventricular tachycardia having a long RP and short PR interval. In all 19 patients, supraventricular tachycardia was found to have a 1:1 P-QRS relation during initial control electrophysiologic studies, and in all 19 patients, electrophysiologic studies suggested that junctional reentry was the mechanism of supraventricular tachycardia. Seven of the 19 patients developed atrioventricular (AV) block during initiation of supraventricular tachycardia or after induction of supraventricular tachycardia following various drug administrations in subsequent studies. In three patients, second degree block within the His bundle or block distal to the His bundle recording site occurred after administration of quinidine. In one patient it occurred after procainamide, and in another patient it occurred after atropine. In one patient, 2:1 block proximal to the His deflection occurred after verapamil. In the remaining patient, a transient Wenckebach block proximal to the His deflection was noted after adenosine triphosphate. In this latter patient, 2:1 AV block was also noted after propranolol and digoxin. The site of reentry in these seven patients with AV block during supraventricular tachycardia was confined to the AV node area. Their supraventricular tachycardia did not involve a slowly conducting paraseptal accessory pathway because the distal AV node, His bundle and ventricle were not found to be necessary links in the tachycardia circuit.

A simple technique for selective radiofrequency ablation of the slow pathway in atrioventricular node reentrant tachycardia.

OBJECTIVES: A simple technique was designed for radiofrequency ablation therapy of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: This technique was based on the hypothesis that slow pathway conduction reflects conduction through the compact node and its posterior atrial input. METHODS: A total of 100 consecutive patients were studied; there were 37 men and 63 women, with a mean age of 48 +/- 15 years. All 100 patients had induction of sustained tachycardia with (51 patients) or without (49 patients) administration of isoproterenol or atropine, or both. The ablation catheter was initially manipulated to record the largest His bundle deflection from the apex of Koch's triangle. It was then curved downward and clockwise to the area of the compact node when His deflection was no longer visible and the ratio of atrial to ventricular electrogram was < 1. The radiofrequency current was delivered from the 4-mm tip electrode a mean of 5 +/- 7 times at a power of 25 +/- 4 W for a duration of 21 +/- 4 s. The total fluoroscopic time was 19 +/- 11 min. RESULTS: Selective ablation (56 patients) or modification (26 patients) of the slow pathway without affecting anterograde and retrograde fast pathway conduction was achieved in 82 patients. Ablation or modification of both the retrograde fast pathway and the slow pathway but with preservation of anterograde fast pathway conduction was noted in 12 patients. Ablation or modification of the retrograde fast pathway alone or both anterograde and retrograde fast pathway conduction was noted in three patients. Complete AV node block occurred in three patients. Seventy-three patients had no induction of echo beats or tachycardia and 24 patients had induction of a single echo beat after ablation. Follow-up study was performed in 62 patients 76 +/- 18 days after ablation. Thirty-nine patients had no induction of echo beats or tachycardia, 22 had induction of echo beats alone and 1 patient had induction of sustained tachycardia. CONCLUSION: Selective ablation of the slow AV node pathway can be achieved by a simple procedure with a high success rate and few complications.