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European Heart Journal. Case Reports Aug 2023Caseous mitral annular calcification (CMAC) is a rare variant of mitral annular calcification. Symptoms can be related to mitral valvular dysfunction, arterial...
BACKGROUND
Caseous mitral annular calcification (CMAC) is a rare variant of mitral annular calcification. Symptoms can be related to mitral valvular dysfunction, arterial embolization, and transient aortic outflow tract obstruction. CMAC usually affects the posterior fibrous mitral annulus and is commonly diagnosed in elderly patients with a history of hypertension, dyslipidaemia, and renal failure.
CASE SUMMARY
A 68-year-old patient was transferred to our department for late presenting acute myocardial infarction and acute heart failure. Coronary angiography revealed a significant extrinsic compression of the circumflex artery. Transthoracic echocardiography revealed an ovoid calcified mass of 3.6 cm × 2 cm originating from the posterior mitral annulus causing moderate mitral stenosis as well as akinesia of the inferolateral wall, reduced left ventricle ejection fraction (35%), and a low-flow low-gradient severe aortic stenosis. Cardiac computed tomography scan confirmed the presence of a large calcified mass, inserted to the posterior mitral annulus evocating caseous necrosis. The patient underwent a double valve replacement with implantation of both aortic and mitral bioprostheses. Histopathology of the excised mass revealed a chronic mitral valve fibrocalcification with aseptic necrosis, consistent with a caseous calcification of the posterior mitral annulus.
DISCUSSION
Extrinsic coronary artery compression is a rare disease entity. We report a rather peculiar cause of extrinsic artery compression: CMAC inducing significant mitral stenosis and compressing the circumflex artery leading to myocardial infarction. To the best of our knowledge, this is the first case of extrinsic artery compression caused by CMAC.
PubMed: 37547368
DOI: 10.1093/ehjcr/ytad329 -
Journal of Parkinson's Disease 2023Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current... (Clinical Trial)
Clinical Trial
BACKGROUND
Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.
OBJECTIVE
To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.
METHODS
As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory.
RESULTS
An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages.
CONCLUSION
We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.
Topics: Humans; Consensus; Disease Progression; Outcome Assessment, Health Care; Parkinson Disease; Quality of Life
PubMed: 37545260
DOI: 10.3233/JPD-230051 -
Cell & Bioscience Aug 2023Parkinson's disease (PD), a highly prevalent neuro-motor disorder is caused due to progressive loss of dopaminergic (DAergic) neurons at substantia nigra region of...
BACKGROUND
Parkinson's disease (PD), a highly prevalent neuro-motor disorder is caused due to progressive loss of dopaminergic (DAergic) neurons at substantia nigra region of brain. This leads to depleted dopamine (DA) content at striatum, thus affecting the fine tuning of basal ganglia. In patients, this imbalance is manifested by akinesia, catalepsy and tremor. PD associated behavioral dysfunctions are frequently mitigated by l-DOPA (LD) therapy, a precursor for DA synthesis. Due to progressive neurodegeneration, LD eventually loses applicability in PD. Although DA is cytotoxic, it is unclear whether LD therapy can accelerate PD progression or not. LD itself does not lead to neurodegeneration in vivo, but previous reports demonstrate that LD treatment mediated excess DA can potentiate neurotoxicity when PD associated genetic or epigenetic aberrations are involved. So, minimizing DA toxicity during the therapy is an absolute necessity to halt or slowdown PD progression. The two major contributing factors associated with DA toxicity are: degradation by Monoamine oxidase and DAquinone (DAQ) formation.
RESULTS
Here, we report that apoptotic mitochondrial fragmentation via Calcineurin (CaN)-DRP1 axis is a common downstream event for both these initial cues, inhibiting which can protect cells from DA toxicity comprehensively. No protective effect is observed, in terms of cell survival when only PxIxIT domain of CaN is obstructed, demonstrating the importance to block DRP1-CaN axis specifically. Further, evaluation of the impact of DA exposure on PD progression in a mice model reveal that LD mediated behavioral recovery diminishes with time, mostly because of continued DAergic cell death and dendritic spine loss at striatum. CaN inhibition, alone or in combination with LD, offer long term behavioral protection. This protective effect is mediated specifically by hindering CaN-DRP1 axis, whereas inhibiting interaction between CaN and other substrates, including proteins involved in neuro-inflammation, remained ineffective when LD is co-administered.
CONCLUSIONS
In this study, we conclude that DA toxicity can be circumvented by CaN inhibition and it can mitigate PD related behavioral aberrations by protecting neuronal architecture at striatum. We propose that CaN inhibitors might extend the therapeutic efficacy of LD treatment.
PubMed: 37528492
DOI: 10.1186/s13578-023-01068-6 -
Biomedicines Jul 2023Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle...
Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle responses to postural disturbance in three conditions: normal DA level (wild-type rats, WT), mild DA deficiency (WT after administration of α-methyl-p-tyrosine-AMPT, that blocks DA synthesis), and severe DA depletion (DAT-KO rats after AMPT). The horizontal displacements in WT rats elicited a multi-component EMG corrective response in the flexor and extensor muscles. Similar to the gradual progression of DA-related diseases, we observed different degrees of bradykinesia, rigidity, and postural instability after AMPT. The mild DA deficiency impaired the initiation pattern of corrective responses, specifically delaying the extensor muscles' activity ipsilaterally to displacement direction and earlier extensor activity from the opposite side. DA depletion in DAT-KO rats after AMPT elicited tremors, general stiffness, and akinesia, and caused earlier response to horizontal displacements in the coactivated flexor and extensor muscles bilaterally. The data obtained show the specific role of DA in postural reactions and suggest that this experimental approach can be used to investigate sensorimotor control in different dopamine-deficient states and to model DA-related diseases.
PubMed: 37509596
DOI: 10.3390/biomedicines11071958 -
Case Reports in Genetics 2023Arthrogryposis multiplex congenita (AMC) is characterized by nonprogressive symmetric contractures of multiple joints with normal intellect and normal systemic...
Arthrogryposis multiplex congenita (AMC) is characterized by nonprogressive symmetric contractures of multiple joints with normal intellect and normal systemic examination. AMC is often due to fetal akinesia, which has neurologic, muscular, and connective tissue etiologies. We present a case of AMC due to a variant in the titin (TTN) gene in a term neonate. The infant is homozygous for this variant, , which is predicted to result in a truncated protein (∗). A literature search (PubMed) failed to find reports of this TTN variant. The variant was classified as pathogenic and submitted to ClinVar. Titin is the body's largest protein, expressed in skeletal and cardiac muscles and encoded by the TTN gene. Due to its large size (364 exons), the TTN gene has been difficult to sequence; the number of variants in the TTN gene and the spectrum of titinopathies are probably underestimated.
PubMed: 37497165
DOI: 10.1155/2023/5535083 -
Brain and Behavior Aug 2023Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown...
INTRODUCTION
Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied.
METHODS
In this study, we included 12 PD patients (6 male and 6 female) who underwent STN-DBS surgery and had both F-FDG and C-CFT PET/CT imaging before and 1 year after the surgery. We used paired t-tests to identify changes in cerebral metabolism and calculated PD-related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of C-CFT in the striatum using striatal-to-occipital ratios (SORs).
RESULTS
One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p < .01, p < .001, p < .001, p < .001, and p < .001, respectively). Hamilton Depression Rating Scale and quality of life (PDQ-39 SI) were also significantly reduced (p < .05 and p < .01, respectively). The mean PDRP score decreased by 37% from 13.0 ± 6.6 to 8.2 ± 7.9 after STN-DBS surgery (p < .05). We observed decreased F-FDG uptake in several areas, including the temporal lobe (BA22), thalamus, putamen, and cingulate gyrus (BA24), whereas it was increased in the supplementary motor area, postcentral gyrus, lingual gyrus, and precuneus (p < .05). SORs of C-CFT in the bilateral caudate nucleus and ipsilateral posterior putamen were significantly decreased compared to preoperative levels (p < .05).
CONCLUSION
Our findings suggest that STN-DBS surgery modifies the metabolic network of PD patients and improves motor symptoms, depression, and quality of life. However, it does not prevent the decrease of DAT in striatal areas.
Topics: Humans; Male; Female; Subthalamic Nucleus; Parkinson Disease; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Quality of Life; Dopamine Plasma Membrane Transport Proteins; Deep Brain Stimulation; Treatment Outcome; Glucose
PubMed: 37459244
DOI: 10.1002/brb3.3172 -
European Heart Journal. Case Reports Jul 2023Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during...
BACKGROUND
Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department.
CASE SUMMARY
Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities.
DISCUSSION
These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications.
PubMed: 37457052
DOI: 10.1093/ehjcr/ytad284 -
Indian Journal of Ophthalmology Jul 2023Cataract surgery ranks among the commonest procedures performed worldwide. Approximately 51% of blindness worldwide is related to cataracts, affecting about 65.2 million... (Review)
Review
Cataract surgery ranks among the commonest procedures performed worldwide. Approximately 51% of blindness worldwide is related to cataracts, affecting about 65.2 million people worldwide and more so in developing countries. Over the years, there has been a significant evolution in the surgical techniques of cataract extraction. The advancement in phacoemulsification machines, phaco-tips, and the availability of ophthalmic viscoelastic devices have played a substantial role in cataract surgery such that they are faster and more controlled than before. Similarly, anesthetic techniques in cataract surgery have advanced significantly from retrobulbar, peribulbar, and sub-Tenon's blocks to topical anesthesia. Though topical anesthesia eliminates the possible complications of injectable anesthesia, it is not suitable for use in uncooperative, anxious patients, pediatric age groups, and patients with cognitive disabilities. Hyaluronidase is an enzyme that breaks down hyaluronic acid in the retrobulbar tissue, facilitating uniform diffusion of the anesthetic drug and hastening the onset of anesthesia and akinesia. Hyaluronidase has been used in the last 80 years successfully as an adjuvant in retrobulbar, peribulbar, and sub-Tenon's blocks. Initially, the hyaluronidase enzyme was animal-derived and of bovine and ovine sources. Recombinant human-derived hyaluronidase, which has lesser allergic reactions, impurities, and toxicity, is now available. There is conflicting evidence regarding the efficacy of hyaluronidase as an adjuvant in retrobulbar and peribulbar blocks. This article summarizes a brief review of the literature on the role of hyaluronidase as an adjuvant in local anesthetic blocks in ophthalmic surgeries.
Topics: Humans; Animals; Cattle; Sheep; Child; Anesthesia, Local; Hyaluronoglucosaminidase; Anesthetics, Local; Cataract Extraction; Cataract; Lidocaine
PubMed: 37417102
DOI: 10.4103/IJO.IJO_2515_22 -
JACC. Case Reports Jun 2023A 76-year-old man with stage IV urothelial carcinoma who was receiving atezolizumab presented with dyspnea, elevated cardiac biomarkers, new negative T waves, and left...
A 76-year-old man with stage IV urothelial carcinoma who was receiving atezolizumab presented with dyspnea, elevated cardiac biomarkers, new negative T waves, and left ventricular apical akinesia. Coronary angiography results were normal. Immune checkpoint inhibitor-related myocarditis was suspected, and high-dose corticosteroid treatment was started. Cardiac magnetic resonance showed apical edema, suggesting stress cardiomyopathy. ().
PubMed: 37396332
DOI: 10.1016/j.jaccas.2023.101881 -
European Heart Journal. Case Reports Jun 2023Coronary artery spasm (CAS) is a pathological condition resulting from transient functional narrowing of the coronary arteries leading to myocardial ischaemia and in...
BACKGROUND
Coronary artery spasm (CAS) is a pathological condition resulting from transient functional narrowing of the coronary arteries leading to myocardial ischaemia and in some rare cases even to sudden cardiac arrest (SCA). The most important preventable risk factor is use of tobacco, whereas possible precipitating factors include some medications and psychological stress.
CASE SUMMARY
A 32-year-old woman was hospitalized with burning chest pain. The immediate investigations revealed the diagnosis of non-ST-segment elevation myocardial infarction, because of ST elevations in one single lead and increased high-sensitivity troponin. Due to ongoing chest pain and a severe impaired left ventricular ejection fraction (LVEF) of 30% with apical akinesia, a prompt coronary angiography (CAG) was scheduled. After aspirin administration, she developed anaphylaxis with pulseless electrical activity (PEA). She could be resuscitated successfully. CAG revealed multi-vessel CAS for which she received calcium channel blockers. Five days after, she suffered from a second SCA due to ventricular fibrillation and was resuscitated again. Repeated CAG showed no critical coronary artery occlusion. LVEF improved progressively during hospitalization. Drug therapy was increased, and a subcutaneous implantable cardioverter defibrillator (ICD) was implanted for secondary prevention.
DISCUSSION
CAS may in some instances lead to SCA, especially in case of multi-vessel involvement. Allergic and anaphylactic events can trigger CAS, which are frequently underestimated. Regardless of the cause, cornerstone of CAS prophylaxes remains optimal medical therapy as in the avoidance of predisposing risk factors. In case of life-threatening arrhythmia, the implantation of an ICD should be considered.
PubMed: 37378054
DOI: 10.1093/ehjcr/ytad253