Intracardiac total anomalous pulmonary venous return or septum primum malposition? Complete repair in left atrial isomerism.

Total anomalous pulmonary venous return due to septum primum malposition is a poorly understood condition despite being very common in left atrial isomerism or polysplenia syndrome. Due to the leftward displacement of the septum primum, either the two right pulmonary veins or all four pulmonary veins can drain abnormally into the right atrium, despite their correct position. In other words, the four pulmonary veins (or the two right pulmonary veins), looking from outside the heart, return at the back of the atrium in the normal position. Nevertheless, from the inside of the heart, two or all four pulmonary veins drain into the right atrium due to the leftward displacement of the septum primum. As an example, we report a 5-month-old patient with severe malposition of the septum primum and consequent total anomalous pulmonary venous drainage into the right atrium. The patient underwent surgical correction with resection of the malpositioned septum primum and reconstruction of a normal interatrial septation with a pericardial patch.

Prognostic Implication of Preoperative Anemia in Redo Cardiac Surgery: A Single-Center Propensity-Matched Analysis.

Preoperative anemia has been associated with increased morbidity and mortality after cardiac surgery, but little is known about its prognostic value in the setting of redo procedure. A retrospective, observational cohort study of prospectively collected data was undertaken on 409 consecutive patients referred for redo cardiac procedures between January 2011 and December 2020. The EuroSCORE II calculated an average mortality risk of 25.7 ± 15.4%. Selection bias was assessed with the propensity-adjustment method. The prevalence of preoperative anemia was 41%. In unmatched analysis, significant differences between the anemic and nonanemic groups emerged in the risk for postoperative stroke (0.6% vs. 4.4%, p = 0.023), postoperative renal dysfunction (29.7% vs. 15.6%, p = 0.001), a need for prolonged ventilation (18.1% vs. 7.2%, p = 0.002), and high-dosage inotropes (53.1% vs. 32.9%, p < 0.001) along with both length of ICU and hospital stay (8.2 ± 15.9 vs. 4.3 ± 5.4 days, p = 0.003 and 18.8 ± 17.4 vs. 14.9 ± 11.1, p = 0.012). After propensity matching (145 pairs), preoperative anemia was still significantly associated with postoperative renal dysfunction, stroke, and the need for high-dosage inotrope cardiac morbidity. Preoperative anemia is significantly associated with acute kidney injury, stroke, and the need for high-dosage inotropes in patients referred for redo procedures.

Frozen Elephant Trunk Technique in Acute Type A Aortic Dissection: Is It for All?

Acute type A aortic dissection (ATAAD) is an indisputable emergency with very poor outcomes without surgical treatment. Although the aortic arch is often involved in the aortic dissection, its optimal management during surgical therapy remains uncertain. A conservative tear-oriented approach has traditionally been adopted, limiting the procedure to the ascending aorta (or hemiarch) replacement. However, dilation of the residual dissected aorta and subsequent rupture may occur, requiring further intervention in the future. In the last two decades, the frozen elephant trunk (FET) technique has become a valid and attractive option to treat aortic disease when the arch and the thoracic aorta are involved, both in elective and in emergency settings. Here, we report a review of the contemporary literature regarding the short- and long-term outcomes of the FET technique in ATAAD repair.

Can prosthesis type influence the recurrence of infective endocarditis after surgery for native valve endocarditis? A propensity weighted comparison.

OBJECTIVES: Our goal was to investigate whether the incidence of valve-related adverse events might be different depending on the valve substitute after valve replacement for left-sided native valve endocarditis. METHODS: We assessed the long-term freedom from recurrence, reoperation and survival of 395 patients who had valve replacements for native valve endocarditis (314 mechanical vs 81 biological). Age <18 years, reoperation, prosthetic endocarditis, right valve involvement, valve repair and homograft implants were the main exclusion criteria. The balance between the 2 groups was addressed by weighting the results on the inverse of the propensity score. RESULTS: After inverse probability of treatment weighting (IPTW), freedom from recurrence of infective endocarditis was not significantly different (mechanical 84.1 ± 3.2% vs 50.6 ± 21.7%; P = 0.29) nor was freedom from reoperation different (mechanical 85.7 ± 3.1% vs biological 50.9 ± 21.9%; P = 0.29). Excluding competing deaths, patients receiving a bioprosthesis had a similar subdistribution hazard of the above end points compared to recipients of a mechanical valve [recurrence IPTW: hazard ratio (HR) 1.631, 95% confidence interval (CI) 0.756-3.516; P = 0.21; reoperation IPTW-HR 1.737, 95% CI 0.780-3.870; P = 0.18]. Mechanical valves were associated with improved long-term survival (34.9 ± 5.8% vs 10.5 ± 7.4% at 30 years; P = 0.0009; in particular: aortic valve subgroup 41.6 ± 9.3% vs 10.1 ± 8.2%; P < 0.0001), although the hazard of cardiovascular mortality did not favour either valve type (IPTW: HR 1.361, 95% CI 0.771-2.404; P = 0.29). CONCLUSIONS: Our analysis showed a clinical trend in favour of mechanical valves as valve substitutes for native valve endocarditis, especially in the aortic position. In view of long-term freedom from adverse events, the choice of the valve type should be tailored according to patient characteristics and specific clinical conditions.

Implications of abnormal ascending aorta geometry for risk prediction of acute type A aortic dissection.

OBJECTIVES: Recently, increased length of the ascending aorta has been suggested as a possible risk factor for acute type A aortic dissection (ATAAD). Our goal was to identify measurable aortic geometrical characteristics associated with elongation that could differentiate ATAAD from uncomplicated aortic dilation (>45 mm). METHODS: In angiographic computed tomography scans performed in 180 patients having cardiac surgery, aortic diameters, root length, length of the ascending aorta at both the centreline and the greater curvature (convexity) and the root-ascending (root-asc) angle (that between the root axis and the axis of the ascending tract) and the ascending-arch (asc-arch) angle (that between the axis of the ascending aorta and the arch axis) were measured and compared among 3 patient groups: normal aorta (diameter < 45 mm), dilation/aneurysm (>45 mm) and ATAAD. Correlations between diameters and angles, diameters and lengths and lengths and angles were analysed; multivariable analysis including geometrical factors was performed to identify independent predictors of ATAAD. RESULTS: Both patients with aneurysms and patients with ATAAD showed significantly elongated ascending aortas (P < 0.001 vs normal). However, in the aneurysms, the root-asc angle (136° ± 20° vs 147° ± 17°; P < 0.001) and in ATAAD the asc-arch angle were uniquely narrower than that in the normal aorta (116° ± 11° vs 132° ± 19°; P < 0.001). All patients with an ATAAD had an asc-arch angle ≤130°. Both in patients with ATAAD and in those without ATAAD, narrowing of the asc-arch angle was associated with elongation of the root segment (P < 0.001). In multivariable analysis, the asc-arch angle and the total length of the ascending aorta (root + tubular) were significant predictors of ATAAD. CONCLUSIONS: The asc-arch angle is a promising measurement that could help predict aortic dissection along with aortic diameter and length: further verification is warranted.

Histopathological findings in systemic sclerosis-related myopathy: fibrosis and microangiopathy with lack of cellular inflammation.

OBJECTIVES: The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients. METHODS: A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor ß (TGF-ß)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM). RESULTS: Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p < 0.05) and with NIM (18%, p < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p < 0.05) and with NIM (p < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p < 0.05) and NIM (p < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p < 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell 'swelling' coupled to endomysial/perimysial fibrosis. CONCLUSIONS: Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies.

Proteomic Investigation of Dermal Fibroblasts Isolated from Affected and Unaffected Skin Samples from Patients with Limited Cutaneous Systemic Sclerosis: 2 Distinct Entities?

OBJECTIVE: To identify using proteomic analysis the proteins of altered abundance in the affected and unaffected limited cutaneous systemic sclerosis (lcSSc) skin fibroblasts. METHODS: Excision biopsies (3 mm) were obtained from the affected and unaffected skin of 5 patients with lcSSc. Dermal fibroblasts were isolated enzymatically. Two-dimensional gel electrophoresis was used to separate and define proteins in affected and unaffected fibroblast lysates. Proteins of altered abundance were identified by mass spectrometry. Differences among skin samples were confirmed also by immunohistochemistry (IHC) and by quantitative real-time PCR (qRT-PCR) for type I collagen (Col-1) and vimentin (VIM). RESULTS: Proteomic analysis revealed different expressions of proteins involved in cytoskeleton organization (27%), extracellular matrix remodeling (11%), response to oxidative stress (22%), energy metabolism (19%), protein metabolism (5%), cellular homeostasis (5%), signal transduction (3%), and protein transcription, synthesis, and turnover (8%). IHC analysis showed that SSc-affected epidermis is thickened and the dermis is strongly reactive to Col-1 and VIM (typical markers of activated myofibroblasts) compared to SSc-unaffected skin, whose stainings are comparable to those of control healthy skin. Overexpression of Col-1 and VIM mRNA levels in affected lcSSc fibroblasts compared to unaffected lcSSc ones was confirmed by qRT-PCR. CONCLUSION: Consistent with previous studies, these findings are important for 2 reasons: first, because they reveal the opposite behavior of dermal fibroblasts in the unaffected and affected skin areas of the same patient with lcSSc; second, because they demonstrate the histological/histochemical similarities between unaffected skin from patients with lcSSc and healthy control skin.

Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study.

BACKGROUND: Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro. METHODS: Ten women with limited SSc were enrolled. They underwent double skin biopsy (affected and nonaffected skin). Fibroblasts and microvascular endothelial cells (MVECs) were isolated from biopsies. We performed mono- or coculture of MVECs (isolated from nonaffected skin) with fibroblasts (isolated from affected skin and stimulated with ET-1 and transforming growth factor beta [TGF-ß]). In cocultures, the MVEC layer was left undisturbed or was preincubated with BOS or MAC. After 48 h of coculture, MVECs were analyzed for their tube formation ability and for messenger RNA and protein expression of different vascular (CD31, vascular endothelial growth factor-A [VEGF-A], VEGF-A165b) and profibrotic (alpha-smooth muscle actin [α-SMA], collagen type I [Col I], TGF-ß) molecules. RESULTS: After 48 h, MVECs showed a reduced tube formation ability when cocultured with SSc fibroblasts. CD31 and VEGF-A resulted in downregulation, while VEGF-A165b, the antiangiogenic isoform, resulted in upregulation. At the same time, mesenchymal markers α-SMA, Col I, and TGF-ß resulted in overexpression in MVECs. Tube formation ability was restored when MVECs were preincubated with BOS or MAC, also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b. CONCLUSIONS: With this innovative EndoMT in vitro model realized by coculturing nonaffected MVECs with affected SSc fibroblasts, we show that the presence of a myofibroblast phenotype in the fibroblast layer, coupled with an ET-1-TGF-ß synergic effect, is responsible for EndoMT. BOS and MAC seem able to antagonize this phenomenon in vitro, confirming previous evidence of endothelium-derived fibrosis in SSc and possible pharmacological interference.

Erythema nodosum associated with Staphylococcus xylosus septicemia.

Staphylococcus xylosus is a coagulase-negative staphylococcus. It is a commensal bacterium associated with skin and mucous membranes and occasionally it can cause human infections. We report the first case of erythema nodosum developed in a young woman with S. xylosus septicemia and specific serum antibody response.

Pulmonary hypertension: a correct diagnosis for a suitable therapy in scleroderma patients.

Systemic sclerosis (SSc) is a heterogeneous disorder characterised by dysfunction of the endothelium and dysregulation of fibroblasts, resulting in excessive production of collagen, and abnormalities of the immune system. Progressive fibrosis of the skin and internal organs is a pathologic hallmark of the disease, resulting in major organ damage and failure. Pulmonary hypertension (PH) is frequent in patients with SSc and, pulmonary arterial hypertension (PAH) represents one of the main causes of death. PH is not a specific disease, but a haemodynamic condition characterized by a mean pulmonary pressure ≥25mmHg. In SSc, because of the great variability in clinical manifestation, it is possible to identify pulmonary hypertension due to left heart disease, PH due to respiratory disease or pulmonary arterial hypertension. The knowledge of PH and the right diagnosis are crucial to assess the most appropriate therapeutic strategy. In this article, the new classification criteria of PH have been examined taking into account the SSc clinical evolution and focusing on the different underlying pathogenetic mechanisms.

Human osteoarthritic chondrocytes exposed to extremely low-frequency electromagnetic fields (ELF) and therapeutic application of musically modulated electromagnetic fields (TAMMEF) systems: a comparative study.

Osteoarthritis (OA) is the most common joint disease, characterized by matrix degradation and changes in chondrocyte morphology and metabolism. Literature reported that electromagnetic fields (EMFs) can produce benefits in OA patients, even if EMFs mechanism of action is debated. Human osteoarthritic chondrocytes isolated from femoral heads were cultured in vitro in bidimensional (2-D) flasks and in three-dimensional (3-D) alginate beads to mimic closely cartilage environment in vivo. Cells were exposed 30 min/day for 2 weeks to extremely low-frequency electromagnetic field (ELF) with fixed frequency (100 Hz) and to therapeutic application of musically modulated electromagnetic field (TAMMEF) with variable frequencies, intensities, and waveforms. Cell viability was measured at days 7 and 14, while healthy-cell density, heavily vacuolized (hv) cell density, and cluster density were measured by light microscopy only for 3-D cultures after treatments. Cell morphology was observed for 2-D and 3-D cultures by transmission electron microscopy (TEM). Chondrocyte exposure to TAMMEF enhances cell viability at days 7 and 14 compared to ELF. Light microscopy analysis showed that TAMMEF enhances healthy-cell density, reduces hv-cell density and clustering, compared to ELF. Furthermore, TEM analysis showed different morphology for 2-D (fibroblast-like) and 3-D (rounded shape) cultures, confirming light microscopy results. In conclusion, EMFs are effective and safe for OA chondrocytes. TAMMEF can positively interfere with OA chondrocytes representing an innovative non-pharmacological approach to treat OA.

The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and is often associated with disability and impaired quality of life. OBJECTIVE: The aim of the study was to assess the efficacy and tolerability of glucosamine sulfate (GS) in the treatment of knee OA. METHODS: Consecutive outpatients affected by primary monolateral or bilateral knee OA were enrolled in this double-blind, double-dummy, prospective, randomized, placebo-controlled trial. One group received GS 1500 mg QD for 12 weeks, and the other group received placebo QD for 12 weeks. The treatment period was followed by a 12-week treatment-free observation phase. Each patient was examined at baseline and at weeks 4, 8, 12, 16, 20, and 24. The primary efficacy criteria were pain at rest and during movement, assessed on a visual analog scale (VAS) of 0 to 100 mm. The secondary criteria included the Western Ontario and McMaster Universities (WOMAC) index for total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). VAS, W-TPS, W-TSS, and W-TPFS were evaluated at baseline and at weeks 4, 8, 12, 16, 20, and 24. Analgesic drug consumption (ie, acetaminophen or NSAIDs) was also assessed. RESULTS: Patient demographics were similar in the GS and placebo groups. Of 60 randomized patients (30 per group), 56 completed the study (28 treated with GS and 28 who received placebo). Statistically significant improvements in symptomatic knee OA were observed, as measured by differences in resting pain at weeks 8, 12, and 16 (all, P < 0.05 vs placebo) and in pain during movement at weeks 12 and 16 (both, P < 0.05). W-TPS was lower with GS than placebo at weeks 8, 12, and 16 (all, P < 0.01), and at week 20 (P < 0.05). W-TSS was also lower with GS than placebo at weeks 8, 12, 16, and 20 (all, P < 0.05). W-TPFS was lower with GS than placebo at weeks 8 (P < 0.05), 12 (P < 0.01), 16 (P < 0.05), and 20 (P < 0.05). Drug consumption was lower in the GS group than the placebo group at weeks 8, 12, 16, and 20 (all, P < 0.05). The incidence of adverse events was 36.7% with GS and 40.0% with placebo. CONCLUSIONS: GS 1500 mg QD PO for 12 weeks was associated with statistically significant reductions in pain and improvements in functioning, with decreased analgesic consumption, compared with baseline and placebo in these patients with knee OA. A carryover effect was detected after treatment ended.