Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.     

A survey of nine years heart transplantation at Erasme Hospital, University of Brussels.

Between March 1982 and March 1991, 225 heart transplantations (HTx) have been performed in 220 patients suffering end stage cardiac disease. Thirteen percent were females and 87% were males. Age range was from 5 to 68 years. The underlying cardiac disease was ischemic cardiopathy in 51.5%, congestive dilated cardiomyopathy in 42%, valvular cardiomyopathy in 3.5%, toxic myocarditis (post-adriamycin) in 1.5% and chronic rejection in 2.5% (retransplantation). Selection of the recipients was done following the currently well established criteria also taking into account the absolute major contraindications for HTx. Due to the still increasing demand of donor organs, currently donor age has been extended up to 50 years for male and 55 years for female donors. One quarter of the grafts were harvested on site in our institution, two other quarters were harvested somewhere else in Belgium and the last quarter provided by other countries cooperating with Eurotransplant. All patients have undergone orthotopic cardiac transplantation using the standard Lower and Shumway technique. Immunosuppression protocols have changed four times throughout the years. Nevertheless all were based on the use of Ciclosporine variously combined with other current immunosuppressive drugs. Rejection monitoring relied on routine endocardiac biopsy and was diagnosed according to the Billingham criteria. The in-hospital mortality is currently 11%. Infection, early right heart graft failure and acute rejection were the leading causes of death. The major causes of early morbidity were several curable infections, reversible rejection episodes, transient acute renal failure and controllable arterial hypertension. Among the survivors followed for at least one month up to nine years, half of late mortality was caused by chronic rejection followed by infection, sudden death, metabolic disorders, stroke and malignancy. Late morbidity involves cases of mild coronary graft diseases, biological renal insufficiency, some degree of arterial hypertension, dislipidemia. Current actuarial survival rate is 87% at one year, 76% at 5 years up to 9 years. Our experience confirms that HTx represents today and effective therapy for selected patients suffering end stage cardiac disease.     

A hybrid image fusion system for endovascular interventions of peripheral artery disease

Purpose

Interventional endovascular treatment has become the first line of management in the treatment of peripheral artery disease (PAD). However, contrast and radiation exposure continue to limit the feasibility of these procedures. This paper presents a novel hybrid image fusion system for endovascular intervention of PAD. We present two different roadmapping methods from intra- and pre-interventional imaging that can be used either simultaneously or independently, constituting the navigation system.

Methods

The navigation system is decomposed into several steps that can be entirely integrated within the procedure workflow without modifying it to benefit from the roadmapping. First, a 2D panorama of the entire peripheral artery system is automatically created based on a sequence of stepping fluoroscopic images acquired during the intra-interventional diagnosis phase. During the interventional phase, the live image can be synchronized on the panorama to form the basis of the image fusion system. Two types of augmented information are then integrated. First, an angiography panorama is proposed to avoid contrast media re-injection. Information exploiting the pre-interventional computed tomography angiography (CTA) is also brought to the surgeon by means of semiautomatic 3D/2D registration on the 2D panorama. Each step of the workflow was independently validated.

Results

Experiments for both the 2D panorama creation and the synchronization processes showed very accurate results (errors of 1.24 and \(2.6 \pm 1.4\) mm, respectively), similarly to the registration on the 3D CTA (errors of \(1.5 \pm 0.7\) mm), with minimal user interaction and very low computation time. First results of an on-going clinical study highlighted its major clinical added value on intraoperative parameters.

Conclusion

No image fusion system has been proposed yet for endovascular procedures of PAD in lower extremities. More globally, such a navigation system, combining image fusion from different 2D and 3D image sources, is novel in the field of endovascular procedures.

     

Diagnosis,follow-up and management of sleep-disordered breathing in children with osteogenesis imperfecta

Objectives

Osteogenesis imperfecta (OI) is the most common genetic skeletal disorder. Extraskeletal findings are common but an association with sleep-disordered breathing (SDB) has never been described. The aim of this study was to investigate clinical features of children with OI and suspected SDB.

Semi-automatic detection of myocardial trabeculation using cardiovascular magnetic resonance: correlation with histology and reproducibility in a mouse model of non-compaction

Background

The definition of left ventricular (LV) non-compaction is controversial, and discriminating between normal and excessive LV trabeculation remains challenging. Our goal was to quantify LV trabeculation on cardiovascular magnetic resonance (CMR) images in a genetic mouse model of non-compaction using a dedicated semi-automatic software package and to compare our results to the histology used as a gold standard.

Methods

Adult mice with ventricular non-compaction were generated by conditional trabecular deletion of Nkx2–5. Thirteen mice (5 controls, 8 Nkx2–5 mutants) were included in the study. Cine CMR series were acquired in the mid LV short axis plane (resolution 0.086?×?0.086x1mm³) (11.75 T). In a sub set of 6 mice, 5 to 7 cine CMR were acquired in LV short axis to cover the whole LV with a lower resolution (0.172?×?0.172x1mm3). We used semi-automatic software to quantify the compacted mass (M_c), the trabeculated mass (M_t) and the percentage of trabeculation (M_t/M_c) on all cine acquisitions_. After CMR all hearts were sliced along the short axis and stained with eosin, and histological LV contouring was performed manually, blinded from the CMR results, and M_t, M_c and M_t/M_c were quantified. Intra and interobserver reproducibility was evaluated by computing the intra class correlation coefficient (ICC).

Results

Whole heart acquisition showed no statistical significant difference between trabeculation measured at the basal, midventricular and apical parts of the LV. On the mid-LV cine CMR slice, the median M_t was 0.92 mg (range 0.07–2.56 mg), M_c was 12.24 mg (9.58–17.51 mg), M_t/M_c was 6.74% (0.66–17.33%). There was a strong correlation between CMR and the histology for M_t, M_c and M_t/ M_c with respectively: r²?=?0.94 (p?<?0.001), r²?=?0.91 (p?<?0.001), r²?=?0.83 (p?<?0.001). Intra- and interobserver reproducibility was 0.97 and 0.8 for M_t; 0.98 and 0.97 for M_c; 0.96 and 0.72 for M_t/M_c, respectively and significantly more trabeculation was observed in the M_c Mutant mice than the controls.

Conclusion

The proposed semi-automatic quantification software is accurate in comparison to the histology and reproducible in evaluating M_c, M_t and M_t/ M_c on cine CMR.

     

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study

Purpose

Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality.

Methods

A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up).

Results

Among the 306 included patients, 126 (41.2%; 95% CI 35.6–46.9) died and 180 (58.8%; 95% CI 53.3–64.3) survived during the follow-up period [13 (3–24) days], including 51/180 patients (28.3%, 95% CI 21.9–35.5) who eventually required limb amputations, with a median number of 3 (1–4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR)?=?1.03 (1.02–1.04); p?<?0.001], lower leucocytes [HR 0.83 (0.69–0.99); p?=?0.034] and platelet counts [HR 0.77 (0.60–0.91); p?=?0.007], and arterial blood lactate levels [HR 2.71 (1.68–4.38); p?<?0.001] were independently associated with hospital death, while a neck stiffness [HR?0.51 (0.28–0.92); p?=?0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06–3.38); p?=?0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis.

Conclusion

Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation.

Trials registration

NCT03216577.

     

Complications from Administration of Vasopressors Through Peripheral Venous Catheters: An Observational Study

Background

The placement of a central venous catheter for the administration of vasopressors is still recommended and required by many institutions because of concern about complications associated with peripheral administration of vasopressors.