Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients

Background

Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention.

Aims

To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR).

Methods

We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient.

Results

All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit.

Conclusion

The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.     

Occupational allergic contact dermatitis from champignon and Polish mushroom

Capsicum peppers are widespread both in and out the kitchen. "Human hand" is a contact dermatitis resulting from the direct handling of peppers. Capsaicin also is found in topical agents for treatment of postherpetic neuralgia, diabetic neuropathy and arthritis. The oleoresin of capsicum is considered a powerfull irritant capable to induce irritant contact dermatitis and non‐immunological contact urticaria. A 81 year‐old man with a severe itchy macular and papular rash induced by Capsidol® initially located over the shoulder and sudden spread over the thorax is presented. A dense dermal mononuclear cell infiltrate and spongiosis suggested the diagnosis of contact dermatitis. Negative open tests and a positive patch test reaction (++ 96 hours) using the trade cream Capsidol®(capsaicin 5%) led us to contact with the Pharmaceutical Company Viñas. They provided us the components of the cream: capsaicin, isopropyl myristate, estearic acid (DERVACID 3148), propylene glycol, glycerin monomyristate (ESTOL3650GMM), AMPHISOL K, Cetyl alcohol (NACOL 16–85), benzyl alcohol, diazolidinyl urea (GERMALL II), p‐hydroxybenzoate–methylsodium (NIPAGIN M sódic), p‐hydroxybenzoate propyl (NIPASOL M). Capsaicin in benzyl alcohol at 0,075% was open tested with negative results. Only patch test with capsaicin was positive (++) at 48/96 hours and the excipient components at the appropiate concentrations were all negative. Patch test biopsy showed an eczematous pattern. Twenty controls showed negative results. This case is probably an allergic reaction but shows how still remains difficult to distinguish among allergic and irritative cutaneous reactions.     

Effect of upper eyelid blepharoplasty on corneal biomechanical,topographic and tomographic parameters 4 weeks after surgery

International Ophthalmology - To investigate the effect of “skin-only” upper eyelid blepharoplasty on corneal biomechanics and central as well as peripheral topographic/tomographic...     

Inflammation and exercise (INFLAME): study rationale, design, and methods

PurposeThe INFLAME study is designed to determine the effect of exercise training on elevated high-sensitivity C-Reactive Protein (CRP) concentrations in initially sedentary women and men.MethodsINFLAME will recruit 170 healthy, sedentary women and men with elevated CRP (≥ 2.0 mg/L) to be randomized to either an exercise group or non-exercise control group. Exercising individuals will participate in four months of supervised aerobic exercise with a total energy expenditure of 16 kcal kg^− 1 week^− 1 (KKW). Exercise intensity will be 60–80% of maximal oxygen consumption (VO₂ max).OutcomeThe primary outcome will be changed in plasma CRP concentration. Secondary outcomes include visceral adiposity, the cytokines IL-6 and TNF-α, and heart rate variability (HRV) in order to examine potential biological mechanisms whereby exercise might affect CRP concentrations.SummaryINFLAME will help us understand the effects of moderate-to-vigorous exercise on CRP concentrations in sedentary individuals. To our knowledge this will be the largest training study specifically designed to examine the effect of exercise on CRP concentrations. This study has the potential to influence therapeutic applications since CRP measurement is becoming an important clinical measurement in Coronary Heart Disease risk assessment. This study will also contribute to the limited body of literature examining the effect of exercise on the variables of visceral adiposity, cytokines, and heart rate variability.     

Treatment with the glycogen synthase kinase-3beta inhibitor, TDZD-8, affects transient cerebral ischemia/reperfusion injury in the rat hippocampus

The serine/threonine glycogen synthase kinase 3beta (GSK-3beta) is abundant in the central nervous system, particularly in the hippocampus, and plays a pivotal role in the pathophysiology of a number of diseases, including neurodegeneration. This study was designed to investigate the effects of GSK-3beta inhibition against I/R injury in the rat hippocampus. Transient cerebral ischemia (30 min) followed by 1 h of reperfusion significantly increased generation of reactive oxygen species and modulated superoxide dismutase activity; 24 h of reperfusion evoked apoptosis (determined as mitochondrial cytochrome c release and Bcl-2 and caspase-9 expression), resulted in high plasma levels of TNF-alpha and increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and intercellular adhesion molecule-1. The selective GSK-3beta inhibitor, 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), was administered before and after ischemia or during reperfusion alone to assess its potential as prophylactic or therapeutic strategy. Prophylactic or therapeutic administration of TDZD-8 caused the phosphorylation (Ser(9)) and hence inactivation of GSK-3beta. Infarct volume and levels of S100B protein, a marker of cerebral injury, were reduced by TDZD-8. This was associated with a significant reduction in markers of oxidative stress, apoptosis, and the inflammatory response resulting from cerebral I/R. These beneficial effects were associated with a reduction of I/R-induced activation of the mitogen-activated protein kinases JNK1/2 and p38 and nuclear factor-kappaB. The present study demonstrates that TDZD-8 protects the brain against I/R injury by inhibiting GSK-3beta activity. Collectively, our data may contribute to focus the role of GSK-3beta in cerebral I/R.     

Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy

The aim of this study was to evaluate the efficacy of genetic vaccination with rat ErbB2 antigen in a therapeutic setting for the BALB-neuT mouse model of mammary carcinoma and to establish immunological correlates with vaccine efficacy. To define an early therapeutic setting we performed imaging studies of mouse mammary glands with a high-frequency ultrasound system that allowed the diagnosis of tumor lesions before they become palpable, starting from week 13 after mouse births. An intensive immunization protocol of vaccination was implemented at this stage, consisting of four weekly DNA injections with electroporation followed by two injections of adenovirus carrying the codon usage-optimized cDNA encoding the extracellular-transmembrane domain of rat ErbB2. Immunological parameters were monitored in each individual mouse by analyzing peripheral blood leukocytes. The appearance of the first palpable tumor in vaccinated mice was delayed and there was a statistically significant time gap before additional masses developed, indicating disease stabilization. As a result of the immunization, antibodies and CD8(+) T cells to rat ErbB2 were detected and the amplitude of elicited responses correlated with the efficacy of vaccination. Moreover, the vaccination regimen specifically halted the rise in circulating myeloid suppressor cells (MSCs). All three parameters, that is, CD8(+) T cells, antibodies to rat ErbB2, and circulating MSCs, measured at the end of vaccination could be used as predictive biomarkers for future tumor development. This study emphasizes the potential of genetic vaccines for the therapeutic treatment of malignancies and suggests possible predictive biomarkers to be further validated in the clinic for the follow-up of vaccinated cancer patients.     

Compliance, attitudes and barriers to post-operative colorectal cancer follow-up

Rationale Meta‐analyses demonstrate that surveillance following curative‐intent colorectal cancer (CRC) surgery can improve survival. Our multidisciplinary team adopted a stringent CRC follow‐up (FU) guideline in 2000. The purpose of this study was to assess adherence and barriers to FU for CRC. Methods Patients with primary CRC aged 19–75 years, treated with curative intent surgery from July 2000 to December 2002 were identified from a prospective database. Compliance with FU was assessed primarily by chart review. We also surveyed patients and providers to explore attitudes and barriers to surveillance adherence using tenets of the Health Belief Model. Results 96 patients met inclusion criteria and were appropriate for FU. Median FU was 34 months. Guideline targets were met for 70% of clinic visits; 49% of carcinoembryonic antigen (CEA) determinations; and 62% of abdominal imaging studies. Post‐operative colonoscopy did not occur in 6/93 patients. Seventy per cent of health care providers and 55% of patients completed a survey. Access to testing and confusion about which provider orders investigations were identified as important barriers to FU. Conclusion Patterns of CRC FU were widely variable despite implementation of a guideline. Despite patient and provider agreement with the principles of CRC FU, adoption was inhibited by confusion among multiple providers regarding investigation coordination.