Cardiac magnetic resonance imaging in dilated cardiomyopathy in adults��towards identification of myocardial inflammation

Objective

To assess active myocardial inflammation by cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB) amongst adult patients with dilated cardiomyopathy (DCM).

Methods

We evaluated 23 adults with chronic DCM, who had successfully undergone both CMR and EMB within 3.5?±?2.6?days. EMB was considered the gold standard. CMR assessment of myocardial inflammation used the following parameters as recommended by the recently published ??Lake Louise Criteria??: global myocardial oedema, global relative enhancement (RE), and late gadolinium enhancement (LGE). According to ??Lake Louise Criteria??, myocardial inflammation was diagnosed if two or more of the three above-mentioned parameters were positive.

Results

Myocardial inflammation was confirmed by immunohistology in 12 patients (52.2%). Sensitivity, specificity, and diagnostic accuracy of CMR to detect immunohistologically confirmed myocardial inflammation were 75.0%, 72.7%, and 73.9%, respectively. Sensitivity, specificity, and diagnostic accuracy of the individual CMR parameters to detect myocardial inflammation were as follows: global myocardial oedema, 91.7%, 81.8%, and 87.0%, respectively; global RE, 58.3%, 63.6%, and 60.9%, respectively; LGE, 58.3%, 45.4%, and 52.2%, respectively.

Conclusion

Global myocardial oedema was identified as a promising CMR parameter for assessment of myocardial inflammation in patients with DCM. In these patients, global myocardial oedema yielded superior diagnostic performance compared to ??Lake Louise Criteria??.     

Peroneus longus ligamentoplasty for chronic instability of the distal tibiofibular syndesmosis

The distal tibiofibular syndesmosmotic ligament complex is important for dynamic stability and congruency of the ankle joint. Syndesmotic lesions in the ankle fracture-dislocations are well recognized and classified systematically. Chronic insufficiency of the syndesmosis leads to a lateral shift of the talus and under eversion stress permits a pathological rotation of the talus. There is also retroversion of the distal fibula representing a painful deformity. Little experience exists with surgical reconstruction of the syndesmosis. This article describes a new ligamentoplasty with a split peroneus longus tendon graft that mimics the normal anatomic conditions of the syndesmotic complex in 16 patients with symptomatic chronic syndesmotic insufficiency after pronation-external rotation and pronation abduction injuries to the ankle joint. Postoperatively, no infections or hematomas were seen. One patient had asymptomatic breakage of the syndesmosis screw; one patient had a 10 degree decrease of dorsiflexion at the ankle because of a partial anterior tibiofibular synostosis. Fifteen of 16 patients had pain relief at a mean follow-up period of 16.4 months (range, 13-29 months); all patients had relief of the chronic swelling of the ankle and the giving way. The mean Karlsson score at follow-up was 88 (range, 70-100) points. It may be concluded that peroneus longus ligamentoplasty in a preliminary series resulted in reliable ankle stability and considerable pain relief in patients with chronic syndesmotic instability.     

In-Flight Transmission of a SARS-CoV-2 Lineage B.1.617.2 Harbouring the Rare S:E484Q Immune Escape Mutation

We describe a flight-associated infection scenario of seven individuals with a B.1.617.2 (Delta) lineage, harbouring an S:E484Q point mutation. In Sweden, at least 10% of all positive SARS-CoV-2 samples were sequenced in each county; the B.1.717.2 + S:E484Q combination was not detected in Sweden before and was imported within the scenario described in this report. The high transmission rate of the delta lineage combined with the S:E484Q mutation, associated with immune escape in other lineages, makes this specific genetic combination a possible threat to the global fight against the COVID-19 pandemic. Even within the Omicron wave, the B.1.617.2 + S:E484Q variant appeared in community samples in Sweden, as it seems that this combination has an evolutionary gain compared to other B.1.617.2 lineages. The here described genomic combination was not detectable with the common fasta file-based Pango-lineage analysis, hence increasing the probability of the true global prevalence to be higher.     

The role of lymphocyte subsets and adhesion molecules in T cell-dependent cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies

The cure of human Hodgkin's tumors heterotransplanted into SCID mice can be achieved by two bispecific monoclonal antibodies (Bi-mAb) directed against the tumor-associated CD30 antigen and CD3 and CD28, respectively, and normal peripheral human blood T cells. We investigated the role of lymphocyte subsets and adhesion molecules in this Bi-mAb-mediated cytolysis. CD4⁺ lymphocytes were the most rapidly expanding subpopulation, but Bi-mAb-directed cytotoxicity was mediated preferentially by CD8⁺ lymphocytes and effector cells belonging to the CD45RO⁺ “memory” pool. Blocking of the LFA-1/ICAM-1 or CD2/LFA-3 adhesion pathways by mAb decreased Bi-mAb-mediated cytotoxicity. This was not due to inhibition of aggregate formation between Bi-mAb-coated T lymphocytes and target cells. Cross-linking of LFA-1 or CD2 molecules on lymphocytes prestimulated with Bi-mAb bound to CD3 and CD28 antigen lead to a more pronounced and prolonged rise in the intracellular concentration of free Ca²⁺. Additional CD2 cross-linking resulted in the tyrosine phosphorylation of distinct proteins. These findings indicate that adhesion molecules play a critical role and function as co-stimulatory signals rather than as cellular contact mediators in CD3 and CD28 Bi-mAb-stimulated T lymphocytes.     

The Soliga, an isolated tribe from Southern India: genetic diversity and phylogenetic affinities

India's role in the dispersal of modern humans can be explored by investigating its oldest inhabitants: the tribal people. The Soliga people of the Biligiri Rangana Hills, a tribal community in Southern India, could be among the country's first settlers. This forest-bound, Dravidian speaking group, lives isolated, practicing subsistence-level agriculture under primitive conditions. The aim of this study is to examine the phylogenetic relationships of the Soligas in relation to 29 worldwide, geographically targeted, reference populations. For this purpose, we employed a battery of 15 hypervariable autosomal short tandem repeat loci as markers. The Soliga tribe was found to be remarkably different from other Indian populations including other southern Dravidian-speaking tribes. In contrast, the Soliga people exhibited genetic affinity to two Australian aboriginal populations. This genetic similarity could be attributed to the 'Out of Africa' migratory wave(s) along the southern coast of India that eventually reached Australia. Alternatively, the observed genetic affinity may be explained by more recent migrations from the Indian subcontinent into Australia.     

Evaluation of the female urethra with intraurethral magnetic resonance imaging

The purpose of this study was to demonstrate feasibility of intraurethral magnetic resonance imaging (MRI) for in vivo assessment of the female urethra and to determine the anatomy of the urethra and periurethral attachments as depicted using an endourethral MR coil. Twenty-three continent volunteers were studied with a 14F endourethral MR coil. Intraurethral MRI allowed detailed visualization and measurements of the muscular layers of the urethral sphincter and permitted the evaluation of supporting ligaments. This technique may become useful in the evaluation of anatomical defects associated with female urethral sphincter deficiency.     

Maximized song learning of juvenile male zebra finches following BDNF expression in the HVC

During song learning, vocal patterns are matched to an auditory memory acquired from a tutor, a process involving sensorimotor feedback. Song sensorimotor learning and song production of birds is controlled by a set of interconnected brain nuclei, the song control system. In male zebra finches, the beginning of the sensorimotor phase of song learning parallels an increase of the brain‐derived neurotrophic factor (BDNF) in just one part of the song control system, the forebrain nucleus HVC. We report here that transient BDNF‐mRNA upregulation in the HVC results in a maximized copying of song syllables. Each treated bird shows motor learning to an extent similar to that of the selected best learners among untreated zebra finches. Because this result was not found following BDNF overexpression in the target areas of HVC within the song system, HVC‐anchored mechanisms are limiting sensorimotor vocal learning.     

Expression of adhesion molecules on peripheral lymphocytes predicts future lesion development in MS

The expression of adhesion molecules (alpha4beta1-integrin, LFA-1, ICAM-1) on T cells, measured by flow cytometry, was compared in different subtypes of multiple sclerosis (MS) and related to future lesion development as seen as delta T1 and T2 lesion load per year on magnetic resonance imaging (MRI). LFA-1 and alpha4beta1-integrin showed higher expression on CD4 and CD8 T lymphocytes in the secondary progressive compared to the relapsing-remitting (CD4: p<0.01, p=ns, p<0.05; CD8: p<0.001, p<0.001, p<0.001, respectively) and primary progressive MS phase (CD4: p<0.001, p<0.01, p<0.05; CD8: p<0.01, p<0.01, p<0.001, respectively). The adhesion molecule expression of alpha4- (r=0.31; p<0.05) and beta1-integrin (r=0.38; p<0.01) on CD4+ cells and of LFA-1beta on both CD4+ and CD8+ (r=0.28, p<0.05) and r=0.29; p<0.05, respectively) cells was significantly related to increase in T2 lesion load. Our study provides further evidence for the involvement of integrins in lesion development, shown as T2 lesions on MRI in MS.