Chronic total occlusion percutaneous coronary intervention in heart transplant patients.

Cardiac allograft vasculopathy (CAV) is frequently observed after heart transplant (HT), and represents one of the main causes of chronic rejection, graft loss, and death. While the role of percutaneous coronary intervention (PCI) is well established in the management of CAV in cases of nonocclusive stenoses, the outcomes and technical aspects of this procedure in chronic total occlusions (CTOs) are unknown. We describe our experience with three cases in which CTO PCI was indicated to treat CAV in HT recipients, and we discuss the peculiarities and therapeutic approach to this challenging patient population. In particular, all patients were asymptomatic for angina, and CTO PCI was indicated to promote recovery of left ventricular function, extend graft survival, and/or protect from future ischemic events. CTO PCI was performed using hybrid techniques and was successful in all three cases. Intravascular imaging was used in all cases to maximize the durability of the procedure.

A technology evaluation of the Onyx Frontier drug-eluting stent.

INTRODUCTION: Onyx FrontierTM represents the latest iteration within the family of zotarolimus-eluting stents (ZES), designed for the treatment of coronary artery disease. Approval by the Food and Drug Administration was granted in May 2022, and Conformité Européenne marking followed in August 2022. AREAS COVERED: We hereby review the principal design features of Onyx Frontier, highlighting differences and similarities with other currently available drug-eluting stents. In addition, we focus on the refinements of this newest platform as compared with previous ZES versions, including the attributes yielding its exceptional crossing profile and deliverability. The clinical implications related to both its newest and inherited characteristics will be discussed. EXPERT OPINION: The nuances of the latest Onyx Frontier, together with the continuous refinement previously witnessed throughout the development of ZES, lead to a latest generation device ideal for a diverse spectrum of clinical and anatomical scenarios. In particular, its peculiarities will be of benefit in the settings often offered by a progressively aging population, such as high bleeding risk patients and complex coronary lesions.

Slow updating of the achromatic point after a change in illumination.

For a color constant observer, the color appearance of a surface is independent of the spectral composition of the light illuminating it. We ask how rapidly color appearance judgments are updated following a change in illumination. We obtained repeated binary color classifications for a set of stimuli defined by their reflectance functions and rendered under either sunlight or skylight. We used these classifications to derive boundaries in color space that identify the observer's achromatic point. In steady-state conditions of illumination, the achromatic point lay close to the illuminant chromaticity. In our experiment, the illuminant changed abruptly every 21 s (at the onset of every 10th trial), allowing us to track changes in the achromatic point that were caused by the cycle of illuminant changes. In one condition, the test reflectance was embedded in a spatial pattern of reflectance samples under consistent illumination. The achromatic point migrated across color space between the chromaticities of the steady-state achromatic points. This update took several trials rather than being immediate. To identify the factors that governed perceptual updating of appearance judgments, we used two further conditions, one in which the test reflectance was presented in isolation and one in which the surrounding reflectances were rendered under an inconsistent and unchanging illumination. Achromatic settings were not well predicted by the information available from scenes at a single time point. Instead, the achromatic points showed a strong dependence on the history of chromatic samples. The strength of this dependence differed between observers and was modulated by the spatial context.

Toolbox for Coronary Chronic Total Occlusion Percutaneous Coronary Intervention.

Since the publication of the hybrid algorithm there has been rapid development of new specialty wires, microcatheters, guide extensions, and low-profile balloons to facilitate successful coronary chronic total occlusion percutaneous coronary intervention. With development of new devices, it is best to categorize them by design and intended task. This enables a safe and systematic approach to coronary chronic total occlusion percutaneous coronary intervention and avoid overlap and waste. This article serves as a guide for tool selection for the interventional cardiologist performing coronary chronic total occlusion percutaneous coronary intervention.

Emerging Role of Large-bore Percutaneous Axillary Vascular Access: A Step-by-step Guide.

Advances in transcatheter structural heart interventions and temporary mechanical circulatory support have led to increased demand for alternative sites for large-bore vascular access. Percutaneous axillary artery access is an appealing alternative to femoral access in patients with peripheral arterial disease, obesity or for prolonged haemodynamic support where patient mobilisation may be valuable. In particular, axillary access for mechanical circulatory support allows for increased mobility while using the device, facilitating physical therapy and reducing morbidity associated with prolonged bed rest. This article outlines the basic approach to percutaneous axillary vascular access, including patient selection and procedure planning, anatomic axillary artery landmarks, access techniques, sheath removal and management of complications.

Acute Increase in Deaths Among Patients With Adult Congenital Heart Disease During COVID-19: Single-Center Experience.

Fear of acquiring severe acute respiratory syndrome coronavirus-2 infection is a major contributor to underutilization of the health care system during the current pandemic. In this report, we describe 4 cases of unexpected deaths that occurred within a short time period in patients with adult congenital heart disease without warning symptoms. (Level of Difficulty: Intermediate.).

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1.

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5-1.0 mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II--clinical results.

PURPOSE: To perform a Phase I radiation dose-escalation trial to determine the maximal tolerable dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity. METHODS AND MATERIALS: Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a "sliding-window" technique. Enrollment of 6 patients for each dose level was planned; if DLTs were seen in >2 of 6 patients, the previous dose was to be expanded by an additional 6 patients to confirm that dose level as the MTD. All schedules administered a total of 30 fractions, but with escalating doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same dose in all patients regardless of the GTV dose level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a dose reduction or a treatment break of >5 treatment days. RESULTS: Of 18 men and 2 women (average age, 57 years; range, 37-80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at dose level 1, and 2 of the 6 patients initially enrolled at dose level 2, developed DLT. Both patients treated at dose level 3 required a 3-day treatment break and dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at dose level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received <30 Gy in 14 patients (average, 54% of volume), with an average mean dose of 32 Gy. In contrast, >/=50% of the distal parotid gland volume received <25 Gy in 15 patients (average, 63% of volume), with an average mean dose of 24 Gy. With a median follow-up of 20 months from the date of enrollment and 28 months for surviving patients, the actuarial 2-year local control (primary site), regional control (nodal sites), and distant control rate was 76.3%, 66.7%, and 71.8%, respectively. CONCLUSION: Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.

Monte Carlo source model for photon beam radiotherapy: photon source characteristics.

A major barrier to widespread clinical implementation of Monte Carlo dose calculation is the difficulty in characterizing the radiation source within a generalized source model. This work aims to develop a generalized three-component source model (target, primary collimator, flattening filter) for 6- and 18-MV photon beams that match full phase-space data (PSD). Subsource by subsource comparison of dose distributions, using either source PSD or the source model as input, allows accurate source characterization and has the potential to ease the commissioning procedure, since it is possible to obtain information about which subsource needs to be tuned. This source model is unique in that, compared to previous source models, it retains additional correlations among PS variables, which improves accuracy at nonstandard source-to-surface distances (SSDs). In our study, three-dimensional (3D) dose calculations were performed for SSDs ranging from 50 to 200 cm and for field sizes from 1 x 1 to 30 x 30 cm2 as well as a 10 x 10 cm2 field 5 cm off axis in each direction. The 3D dose distributions, using either full PSD or the source model as input, were compared in terms of dose-difference and distance-to-agreement. With this model, over 99% of the voxels agreed within +/-1% or 1 mm for the target, within 2% or 2 mm for the primary collimator, and within +/-2.5% or 2 mm for the flattening filter in all cases studied. For the dose distributions, 99% of the dose voxels agreed within 1% or 1 mm when the combined source model-including a charged particle source and the full PSD as input-was used. The accurate and general characterization of each photon source and knowledge of the subsource dose distributions should facilitate source model commissioning procedures by allowing scaling the histogram distributions representing the subsources to be tuned.

Tramadol post-marketing surveillance in health care professionals.

Tramadol has been marketed in the US since 1995. The US Food and Drug Administration agreed to release tramadol as a non-scheduled drug if proactive post-marketing surveillance studies would be conducted. This study was one of two phase IV protocols that were part of the overall surveillance program. It focused on impaired health professionals who are a high risk/high access population for drug abuse. All active participants in four state monitoring programs between November 1, 1995 and August 15, 1998 (n = 1,601) were recruited for the study. With the exceptions of implementing a standardized intake interview and urine testing for tramadol metabolites, all states operated their programs in the usual fashion. The programs were alerted to persistent non-prescribed tramadol use so that appropriate interventions could be employed. Despite availability of tramadol and the conditions that might lead to its abuse, the incidence rate for tramadol use in the study population was only 69 per thousand persons per year and the incidence rate for tramadol abuse or dependence was 6.9 per thousand persons per year.

Psychopathology influences treatment retention among drug-dependent women.

Three subgroups of drug dependent women (N = 78) were identified through cluster analysis on MCMI-II scores. Group 1 (26%) presented a relatively benign clinical picture. In contrast, Group 2 (37%) evidenced severe addiction, psychiatric (Axis I), and personality (Axis II) problems. Group 3 (37%) was characterized by fewer Axis I problems, prominent addiction and externalizing (Cluster B) personality deficits. Group membership was significantly associated with retention in a gender-specific day treatment program. Group 2 experienced rapid attrition, with only 36% completing treatment, compared to 57% for Group 1 and 76% for Group 3. Results indicate that drug-dependent women with externalizing psychopathology can be retained in treatment when environmental barriers are removed and an adequate "holding environment" is maintained. However, women with severe psychiatric problems, unstable mood, and interpersonal deficits are less likely to complete treatment. Early identification of women at risk for drop-out affords an opportunity to intervene to prevent its occurrence.

A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain.

BACKGROUND: Intradiscal electrothermal therapy (IDET) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested. PURPOSE: To compare the efficacy of IDET with that of a placebo treatment. STUDY DESIGN/SETTING: Randomized, placebo-controlled, prospective trial. PATIENT SAMPLE: Patients were recruited by referral and the media. No inducements were provided to any patient in order to have them participate. Of 1,360 individuals who were prepared to submit to randomization, 260 were found potentially eligible after clinical examination and 64 became eligible after discography. All had discogenic low back pain lasting longer than 6 months, with no comorbidity. Thirty-seven were allocated to IDET and 27 to sham treatment. Both groups were satisfactorily matched for demographic and clinical features. METHODS: IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Thirty-two (85%) of the patients randomized to the IDET group and 24 (89%) of those assigned to the sham group complied fully with the protocol of the study, and complete follow-up data are available for all of these patients. OUTCOME MEASURES: The principal outcome measures were pain and disability, assessed using a visual analog scale for pain, the Short Form (SF)-36, and the Oswestry disability scale. RESULTS: Patients in both groups exhibited improvements, but mean improvements in pain, disability and depression were significantly greater in the group treated with IDET. More patients deteriorated when subjected to sham treatment, whereas a greater proportion showed improvements in pain when treated with IDET. The number needed to treat, to achieve 75% relief of pain, was five. Whereas approximately 40% of the patients achieved greater than 50% relief of their pain, approximately 50% of the patients experienced no appreciable benefit. CONCLUSIONS: Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The results of this trial cannot be generalized to patients who do not fit the strict inclusion criteria of this study, but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain.

Psychopathology and treatment outcome of drug dependent women in a perinatal program.

One hundred and five drug-dependent women in outpatient perinatal addiction treatment were classified by cluster analysis of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles into high and low psychopathology (HP and LP) groups that differed on three validation measures. The HP group (n=29, 27.6%) had elevations on MMPI-2 Scales F, 2, 4, 6, 7, and 8, while the LP group (n=76, 72.4%) generated a normal range profile with elevations on Scales F and 4. Psychological outcomes differed by group. HP participants showed reduced alcohol, family, and psychiatric severity, and reduced depressive symptoms, while LP subjects showed reduced drug, self-debasing, and acting-out problems. Data suggest the need for lower intensity services for the majority of the perinatal drug dependent population with LP.

Defining medical posttraumatic stress among young adult survivors in the Childhood Cancer Survivor Study.

OBJECTIVE: To examine the implications of use of differential thresholds for studying medical Posttraumatic Stress Disorder (PTSD). METHODS: Self-report data from 6,542 young adult survivors of childhood cancer and 374 of their siblings were used to create clearly differentially defined groups to compare prevalence, correlations and predictors of posttraumatic stress. RESULTS: Prevalence of posttraumatic stress in survivors compared to siblings differed by definition used, ranging from an odds ratio of 4.21 (95% CI 2.11-8.38) when posttraumatic stress was defined as meeting full symptoms plus functional impairment to 1.42 (95% CI 0.79-2.56) for partial symptoms with functional impairment. Re-experiencing symptoms did not substantially contribute to the ability to identify functional impairment and emotional distress. Although most of the variables associated with posttraumatic stress symptoms and impairment were consistent across definitions of PTSD, marital status and employment demonstrated nonproportional relationships. CONCLUSIONS: Choice of the definition used in studying posttraumatic stress after serious illness alters not only epidemiological findings, but also associations with correlates and predictors. This is important in the current debate about the criteria for PTSD in the upcoming DSMV. Further study is needed to determine if these findings are applicable to people exposed to other types of traumatic events.

Air travel by individuals with active tuberculosis: reporting patterns and epidemiologic characteristics, Canada 2006-2008.

BACKGROUND: Investigations related to tuberculosis (TB) cases on airline flights have received increased attention in recent years. In Canada, reports of air travel by individuals with active TB are sent to the Public Health Agency of Canada (PHAC) for public health risk assessment and contact follow-up. A descriptive analysis was conducted to examine reporting patterns over time. METHOD: Reports of air travel by individuals with active TB received by PHAC between January 2006 and December 2008 were reviewed. Descriptive analyses were performed on variables related to reporting patterns, characteristics and actions taken. RESULTS: The number of reports increased each year with 18, 35 and 51 reports received in 2006, 2007 and 2008, respectively. Of the 104 total cases, most were male (63%) and born outside of Canada (87%). Ninety-eight cases (97%) met the criteria for infectiousness and a contact investigation was initiated for 136 flights. CONCLUSIONS: Reports of air travel by individuals with active TB have been increasing annually in Canada in recent years. Outcomes of the subsequent contact investigations, including passenger follow-up results and evidence of TB transmission, is necessary to further evaluate the effectiveness of the Canadian guidelines.

Inhibition of protein-tyrosine phosphatases by mild oxidative stresses is dependent on S-nitrosylation.

Previous studies have shown that a Ca(2+)-dependent nitric-oxide synthase (NOS) is activated as part of a cellular response to low doses of ionizing radiation. Genetic and pharmacological inhibitor studies linked this NO signaling to the radiation-induced activation of ERK1/2. Herein, a mechanism for the radiation-induced activation of Tyr phosphorylation-dependent pathways (e.g. ERK1/2) involving the inhibition of protein-Tyr phosphatases (PTPs) by S-nitrosylation is tested. The basis for this mechanism resides in the redox-sensitive active site Cys in PTPs. These studies also examined oxidative stress induced by low concentrations of H(2)O(2). S-Nitrosylation of total cellular PTP and immunopurified SHP-1 and SHP-2 was detected as protection of PTP enzymatic activity from alkylation by N-ethylmaleimide and reversal by ascorbate. Both radiation and H(2)O(2) protected PTP activity from alkylation by a mechanism reversible by ascorbate and inhibited by NOS inhibitors or expression of a dominant negative mutant of NOS-1. Radiation and H(2)O(2) stimulated a transient increase in cytoplasmic free [Ca(2+)]. Radiation, H(2)O(2), and the Ca(2+) ionophore, ionomycin, also stimulated NOS activity, and this was associated with an enhanced S-nitrosylation of the active site Cys(453) determined by isolation of S-nitrosylated wild type but not active site Cys(453) --> Ser SHP-1 mutant by the "biotin-switch" method. Thus, one consequence of oxidative stimulation of NO generation is S-nitrosylation and inhibition of PTPs critical in cellular signal transduction pathways. These results support the conclusion that a mild oxidative signal is converted to a nitrosative one due to the better redox signaling properties of NO.

Factors influencing treatment enrollment by pregnant substance abusers.

Despite potentially devastating consequences to both mother and child, many pregnant substance abusers refuse treatment. To understand why, the present study compared women who enrolled in (N = 102) vs. declined (N = 23) day treatment. Participants were primarily African American, unemployed, high school graduates with a mean age of 27 years. Although demographic characteristics did not differ between groups, treatment enrollees had greater drug severity and were more likely to identify crack cocaine as their drug of choice. They also manifested more family and psychiatric problems, emotional distress, and Axis II psychopathology. In addition, treatment enrollees had greater legal severity and higher rates of criminal justice system involvement (46% vs. 13%). The women who declined perinatal addiction services may have perceived less need for intensive treatment due to lower problem severity and less distress. Development of alternative treatment approaches, such as limited perinatal addiction services provided in conjunction with prenatal care, is warranted.

Temperatures within the lumbar disc and endplates during intradiscal electrothermal therapy: formulation of a predictive temperature map in relation to distance from the catheter.

STUDY DESIGN: Temperatures were measured in human cadaveric lumbar discs during intradiscal electrothermal therapy. OBJECTIVES: To determine if sufficient temperatures for collagen denaturation and nociceptive ablation can be achieved at clinically significant distances from the intradiscal electrothermal therapy heating catheter. SUMMARY OF BACKGROUND DATA: Previous cadaveric studies have contested the ability of the intradiscal electrothermal therapy catheter to produce sufficient temperatures to denature collagen and cause neural ablation within the posterior anulus of the disc. However, these experiments used clinically unrepresentative device placements along the anterolateral anulus. METHODS: Intradiscal electrothermal therapy was performed in 14 human cadaveric discs. Devices were inserted using a standard posterolateral approach to orient the heating catheter along the posterior anulus. Temperature recordings were collected using multiple sensors placed along the posterior anulus, anterior anulus, and endplates. RESULTS: Temperatures greater than 60 C and 65 C were achieved in 14 and 5 specimens, respectively, at distances up to 2 mm from the catheter. Between 2 and 4 mm, more than 60 C was achieved in all specimens. More than 45 C was achieved in all specimens at distances of 9 to 14 mm from the device. CONCLUSIONS: Temperatures sufficient for collagen denaturation and nociceptive ablation were detected at distances greater than previously documented. These data suggest that intradiscal electrothermal therapy's proposed heat-dependent mechanisms of action are achievable in most discs. Among other factors, interspecimen variability of maximum temperatures may help explain the somewhat inconsistent clinical results following intradiscal electrothermal therapy.