Peroxisome proliferator-activated receptor δ suppresses the cytotoxicity of CD8+ T cells by inhibiting RelA DNA binding activity.

The molecular mechanisms regulating CD8+ cytotoxic T lymphocytes (CTLs) are not fully understood. Here, we show that the peroxisome proliferator-activated receptor ƍ (PPAR-δ) suppresses CTL cytotoxicity by inhibiting RelA DNA binding. Treatment of ApcMin/+ mice with the PPAR-δ agonist GW501516 reduced the activation of normal and tumor-associated intestinal CD8+ T cells and increased intestinal adenoma burden. PPAR-δ knockout or knockdown in CTLs increased their cytotoxicity against colorectal cancer cells, whereas overexpression of PPAR-δ or agonist treatment decreased it. Correspondingly, perforin, granzyme B, and interferon γ (IFN-γ) protein and mRNA levels were higher in PPAR-δ knockout or knockdown CTLs and lower in PPAR-δ overexpressing or agonist-treated CTLs. Mechanistically, we found that PPAR-δ binds to RelA, interfering with RelA-p50 heterodimer formation in the nucleus, thereby inhibiting its DNA binding in CTLs. Thus, PPAR-δ is a critical regulator of CTL effector function.

Word of caution: early life-threatening complication linked to pulmonary flow restrictors.

A 2-month-old female (3.4 kg, 50 cm) with Down syndrome and left-to-right shunting congenital heart defects underwent an unsuccessful transcatheter ductal closure, followed by bilateral implantation of manually modified microvascular plugs (MVP-9Q) from Medtronic (Minneapolis, MN, USA), used as pulmonary flow restrictors. Post-procedure, she developed febrile respiratory distress, leading to admission to the intensive care unit. Despite initial improvement, she was readmitted with respiratory syncytial virus infection, progressing to bilateral pneumonic consolidation. Subsequent complications included pulmonary artery aneurysmal dilatation attributed to pulmonary flow restrictors, which necessitated urgent surgery two months after their implantation. The surgery involved removing the pulmonary flow restrictors and repairing the injuries to the pulmonary artery, followed by management with extracorporeal support and targeted antibiotics. The patient recovered over 12 months.

Ferritin is a potential marker of cardiometabolic risk in adolescents and young adults with sleep-disordered breathing.

Objective: To explore markers that reflect sleep-disordered breathing (SDB) severity and investigate their associations with cardiometabolic risk factors in adolescents and young adults. Methods: Participants were recruited from our SDB epidemiological cohort. They underwent overnight polysomnography and ambulatory blood pressure (BP) monitoring. Complete blood count, ferritin, high-sensitivity C-reactive protein (hs-CRP), fasting blood glucose, and lipid profile were measured. Multiple linear regression was used to examine the association between red cell indices (RCIs), ferritin, and obstructive apnea-hypopnea index (OAHI). Subgroup analyses on participants with SDB were performed for the association of RCIs and ferritin with lipid profile, hs-CRP, and BP. Results: There were 88 participants with SDB and 155 healthy controls aged 16-25 years. Hemoglobin (Hb; p < .001), hematocrit (HCT; p < .001), and ferritin (p < .001) were elevated with increasing SDB severity and were independently associated with OAHI (ß=1.06, p < .001; ß=40.2, p < .001; ß=4.89 × 10-3, p = .024, respectively). In participants with SDB, after adjusting for age, sex, and BMI, significant associations were found between ferritin with low-density lipoprotein (LDL; ß=0.936 × 10-3, p = .008) and triglyceride (TG; ß =1.08 × 10-3, p < .001), as well as between Hb (ß=1.40, p = .007), HCT (ß=51.5, p = .010) and mean arterial pressure (MAP). Ferritin (ß=0.091, p = .002), Hb (ß=0.975, p = .005), and HCT (ß=38.8, p = .004) were associated with hs-CRP independent of age, sex, BMI, plasma LDL, and MAP. OAHI was not associated with LDL and TG in the multivariable models. Conclusions: Serum ferritin, but not OAHI, was associated with LDL and TG in participants with SDB, suggesting it is a potential marker of cardiometabolic risk in patients with SDB.

Three-Decade Experience With Management of Coronary Artery Fistulas in Children.

BACKGROUND: The treatment approach for coronary artery fistulas (CAFs) is debatable, and long-term outcomes are unknown. METHODS: This was a retrospective institutional data review of children in whom echocardiographically suspected CAFs were confirmed during cardiac catheterisation from 1997 to 2023. Treatment approach and outcomes were assessed. RESULTS: We identified 94 CAFs in 78 patients (42.3% male), median age 3.4 years (interquartile range [IQR] 0.9-6.6 y). Twenty-five patients (32%) had other congenital anomalies; 41 (78.8%) of the 52 patients with isolated CAFs were asymptomatic. The most common site of CAF origin and drainage was the left system (62.8%) and right cardiac cavities (80.8%). Overall median follow-up was 101 months (IQR 41-185 mo); 23 patients (29.5%) with 35 (37.2%) small or nonshunting CAFs had conservative management, and 20 (87%) of those 23 patients had an uneventful follow-up; 8 patients (10.2%) with 9 (9.6%) complex CAFs were directly sent for surgery; 1 patient had early surgical patch failure needing surgical reintervention; 47 patients (60.3%) had catheter closure of 50 (53.2%) medium- or large-sized CAFs with the use of coils (30%), vascular plugs (20%), nitinol duct occluders (40%), or material combination (10%). Six serious complications occurred. Two of the 3 patients with unsuccessful catheter procedures had subsequent surgeries. Two of the 3 patients with mild shunts had successful redo closures. One asymptomatic patient had recanalisation after 12 years and is under watchful observation. CONCLUSIONS: CAFs have various anatomies and clinical presentations. Transcatheter closure is effective in carefully selected patients but is not complication free. Surgery is a valuable up-front option in complex CAFs or bailout of unsuccessful transcatheter closures, although it is not frequently used.

Systematic approach to obtain axillary arterial access for pediatric heart catheterizations.

Background: Axillary arterial access (AAA) in pediatric heart catheterizations is undervalued. Methods: We retrospectively reviewed children with congenital heart diseases (CHDs) who received trans-axillary arterial catheterizations between January 2019 and February 2023. We aimed ultrasound-guided punctures in the proximal two-thirds of axillary arteries with diameters ≥2 mm to insert 7 cm/4 Fr short introducers. We administrated intra-arterial verapamil (1.25 mg) and heparin (100 UI/kg). We infiltrated per-operatively 2% lignocaine (10 mg) for arterial spasms, long sheaths use (≥5 Fr), and ≥60 min procedures in <3 kg patients. Results: We identified 30 patients (66.7% males) with a median age of 1.1 months (IQR, 0.3-5.4), and a median weight of 3.1 kg (IQR, 2.7-3.7). 5/30 patients had six redo interventions after a median of 3.9 months (IQR, 1.7-5.1). Overall, 27/36 procedures were interventional, including 6 aortic valvuloplasties, 6 balloon angioplasties, and 15 stenting procedures. The median arterial axillary angiographic diameter was 2.6 mm (IQR, 2.4-3). Access was right-sided in 23/36 (63.9%) procedures and obtained using 21G/2.5 cm bevel needles in 25/36 (69.4%) procedures. No hemodynamical change occurred after introducing spasmolytic drugs. The median fluoroscopy time was 26.1 min (IQR, 19.2-34.8). There were two self-resolving arterial dissections, one sub-occlusive arterial thrombosis (resolved with 6 weeks of enoxaparin), and one occlusive arterial thrombosis (resolved with alteplase thrombolysis and 6 weeks of enoxaparin). Median follow-up was 11.7 months (IQR, 8-17.5). Four patients with complex univentricular hearts died from non-procedural causes at a median of 40 days (IQR, 31-161) postoperative. Conclusion: Systematic approach for AAA is the key to success and unlocks the many potentials of trans-axillary pediatric cardiology interventions.

Postoperative catheter thrombaspiration to open an occluded right ventricle-to-pulmonary artery conduit in child.

We report on a 6-year-old girl (18 kg/120 cm) who was diagnosed on day 6 postoperative with an occlusive thrombosis of a right ventricle-to-pulmonary artery conduit in the setting of a Ross procedure that was performed for severe native aortic valve insufficiency secondary to late diagnosis of bacterial endocarditis. We applied the Indigo® aspiration system from Penumbra® (Alameda, USA) to mechanically dissolve and remove the thrombus, restore flow, gradually wean from extracorporeal support, and replace the conduit after 4 days. The patient experiences good surgical outcomes at 3 months of follow-up.

Word of caution: silent late device embolisation after perimembranous ventricular septal defect closure in a 6-Kg infant.

We report on a 6-month-old infant (6 Kg/ 64 cm) with perimembranous ventricular septal defect (absent sub-aortic rim, 10 mm left ventricular entry, and 4 and 6 mm right ventricular exists) and successful retrograde closure using an 8x6 mm KONAR-MF™ VSD occluder (Lifetech, China). Immediate and 48 hours post-procedure ultrasounds showed an accurately positioned device and two jets of mild-to-moderate residual shunts. At the 2-week follow-up, the device did not change position and the shunt was stable and intra-prosthetic. The scheduled 3-month follow-up was skipped for familial reasons. The patient came back without alarming symptoms for the regular 6-month follow-up, and the device was found embolised to the left pulmonary artery. The device was retrieved surgically, and the defect was patch-closed with excellent outcomes. There was a pseudoaneurysm involving the tricuspid valve chordae and the device was endothelialized partially on one edge suggesting that embolization occurred somewhere between 3 months and 6 months post-operative. Defects with compromised anatomies should be closed surgically to avoid suboptimal results, especially in small infants.

Proof of Concept: A New Solution for Low-Profile Transcatheter Implantation of Optimus-L Stents in Small Children.

BACKGROUND: There is no stent designed or approved for use in infants. We sought to obtain in vitro and in vivo data on a new concept conceived to implant Optimus-L stents at infant vessel diameters and offer a potential long term stent solution. METHODS: Nineteen Optimus-L stents were mounted on 8 types of angioplasty balloons with diameters 6, 8, and 10 mm with the use of an injection-moulded hand crimper. We evaluated balloon-stent unit (BSU) stability before insertion and advancement through short Terumo introducers with incremental French size and possibility of side-arm contrast injections. Three types of long sheaths were tested. Stents were inflated to balloon nominal diameters and re-expanded to 18 and 23 mm. Stent recoil, foreshortening, and fracture were evaluated. In vivo implantations were performed afterward. RESULTS: In vitro: Medtronic Evercross balloons and modified Terumo Destination sheaths were the best combination: BSUs were inserted in 6 F sheaths with possible injections (for 6 and 8 mm balloons), and 7 F sheaths without injections (for the 10 mm balloon). Retrieving BSUs inside the sheath required 1 additional F-size. Boston Scientific Sterling and Balton Lovix balloons, as well as APT Braidin L guiding sheaths showed unsatisfactory performance. Dilation up to 23 mm was possible, and stent shortening was < 24% at 18 mm and < 37% at 23 mm. Recoil was limited, and no stent fractured. In vivo: Optimus-L stents were used to treat 2 infants with aortic coarctation and 2 children with pulmonary artery stenosis with the use of 8 mm balloons and low-profile access. CONCLUSIONS: Optimus-L stents can be implanted safely in small patients with a low-profile approach. These stents have the potential to achieve adult size while maintaining structural integrity.

Cerebral embolic protection during transcatheter stent expansion of restrictive extra-cardiac Fontan conduit.

We report a 20-year-old female patient (76 Kg/164 cm) with an extra-cardiac Fontan circulation who was referred to our institution for exertional dyspnoea and desaturation. The patient was diagnosed with a large calcified thrombus at the level of the Fontan fenestration, protruding inside the lumen of the conduit and reducing the diameter by half with a 3 mmHg pressure gradient. Transcatheter stent expansion of the obstructed extra-cardiac conduit was done with a 48 mm long XXL PTFE-covered Optimus-CVS® under temporary cerebral embolic protection with a TriGUARD-3™ deflection filter device (Keystone Heart). There was no procedural complication and the 3 months clinical outcomes are good.

Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.

Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated. Deleting Sox9 from the epicardial cell lineage impairs the ability of EPDCs to invade both the ventricular myocardium and the developing AV valves. After birth, the mitral valves of these mice become myxomatous with associated abnormalities in extracellular matrix organization. This phenotype is reminiscent of that seen in humans with myxomatous mitral valve disease (MVD). An RNA-seq analysis was conducted in an effort to identify genes associated with this myxomatous degeneration. From this experiment, Cd109 was identified as a gene associated with myxomatous valve pathogenesis in this model. Cd109 has never been described in the context of heart development or valve disease. This study highlights the importance of SOX9 in the regulation of epicardial cell invasion-emphasizing the importance of EPDCs in regulating AV valve development and homeostasis-and reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.

SwiftNINJA steerable microcatheter: a new kid on the block for selective catheterization of vascular and valvular congenital lesions.

Background: SwiftNINJA (Merit Medical Systems, USA) is a novel steerable microcatheter intended for coronary and peripheral vascular interventions. We evaluate and report the first use of SwiftNINJA in pediatric catheterization of congenital heart defects (CHDs). Methods: We performed a retrospective clinical data review of children with CHDs in whom SwiftNINJA was used during cardiac catheterization between April 2022 and June 2023. Utility, application, and standard safety were described comprehensively. Results: We identified 19 patients (78.9% males) with a median age of 5.3 months (IQR, 2-13.9), and a median weight of 5.3 kg (IQR, 4-7.7). 36.8% of the catheterizations were transarterial and 78.9% were interventional. SwiftNINJA was applied upfront in 3/19 patients to cannulate precisely the right pulmonary artery and eliminate the risk of dislocating a freshly implanted left pulmonary flow restrictor. In 16/19 patients, SwiftNINJA was applied after a median of 5 (IQR, 5-7) failed catheterization attempts using various combinations of catheters, microcatheters, and wires to cannulate challenging vasculature in seven, engage the lumen of stented vessels in five, cross complex aortic valve stenosis in three, and cross an apical ventricular septal defect in one patient with Damus-Kaye-Stansel repair. After the SwiftNINJA application, catheterization was done from the first attempt in 12/16 patients and from the second attempt in 4/16 patients. The median applied tip angulation was 90 degrees (IQR, 85-95). All procedures were completed successfully. No device malfunction or adverse events occurred. Conclusions: SwiftNINJA is a valuable addition for selective catheterization of challenging vasculatures or valvular anatomies in children with CHDs.

High efficacy of chlorfenapyr-based net Interceptor® G2 against pyrethroid-resistant malaria vectors from Cameroon.

BACKGROUND: The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of piperonyl-butoxide (PBO)-pyrethroid [Permanet 3.0 (P3.0)] and dual active ingredients (AI) nets [Interceptor G2 (IG2): containing pyrethroids and chlorfenapyr and Royal Guard (RG): containing pyrethroids and pyriproxyfen] compared to pyrethroid-only net Royal Sentry (RS) against pyrethroid-resistant malaria vectors in Cameroon. METHODS: The efficacy of these tools was firstly evaluated on Anopheles gambiae s.l. and Anopheles funestus s.l. from Gounougou, Mibellon, Mangoum, Nkolondom, and Elende using cone/tunnel assays. In addition, experimental hut trials (EHT) were performed to evaluate the performance of unwashed and 20 times washed nets in semi-field conditions. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to the nets to evaluate the impact of these markers on net performance. The XLSTAT software was used to calculate the various entomological outcomes and the Chi-square test was used to compare the efficacy of various nets. The odds ratio and Fisher exact test were then used to establish the statistical significance of any association between insecticide resistance markers and bed net efficacy. RESULTS: Interceptor G2 was the most effective net against wild pyrethroid-resistant An. funestus followed by Permanet 3.0. In EHT, this net induced up to 87.8% mortality [95% confidence interval (CI): 83.5-92.1%) and 55.6% (95% CI: 48.5-62.7%) after 20 washes whilst unwashed pyrethroid-only net (Royal Sentry) killed just 18.2% (95% CI: 13.4-22.9%) of host-seeking An. funestus. The unwashed Permanet 3.0 killed up to 53.8% (95% CI: 44.3-63.4%) of field-resistant mosquitoes and 47.2% (95% CI: 37.7-56.7%) when washed 20 times, and the Royal Guard 13.2% (95% CI: 9.0-17.3%) for unwashed net and 8.5% (95% CI: 5.7-11.4%) for the 20 washed net. Interceptor G2, Permanet 3.0, and Royal Guard provided better personal protection (blood-feeding inhibition 66.2%, 77.8%, and 92.8%, respectively) compared to pyrethroid-only net Royal Sentry (8.4%). Interestingly, a negative association was found between kdrw and the chlorfenapyr-based net Interceptor G2 (χ2 = 138; P < 0.0001) with homozygote-resistant mosquitoes predominantly found in the dead ones. CONCLUSIONS: The high mortality recorded with Interceptor G2 against pyrethroid-resistant malaria vectors in this study provides first semi-field evidence of high efficacy against these major malaria vectors in Cameroon encouraging the implementation of this novel net for malaria control in the country. However, the performance of this net should be established in other locations and on other major malaria vectors before implementation at a large scale.

Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors.

While the role of prostaglandin E2 (PGE2) in promoting malignant progression is well established, how to optimally block the activity of PGE2 signaling remains to be demonstrated. Clinical trials with prostaglandin pathway targeted agents have shown activity but without sufficient significance or dose-limiting toxicities that have prevented approval. PGE2 signals through four receptors (EP1-4) to modulate tumor progression. EP2 and EP4 signaling exacerbates tumor pathology and is immunosuppressive through potentiating cAMP production. EP1 and EP3 signaling has the opposite effect through increasing IP3 and decreasing cAMP. Using available small-molecule antagonists of single EP receptors, the cyclooxygenase-2 (COX-2) inhibitor celecoxib, or a novel dual EP2/EP4 antagonist generated in this investigation, we tested which approach to block PGE2 signaling optimally restored immunologic activity in mouse and human immune cells and antitumor activity in syngeneic, spontaneous, and xenograft tumor models. We found that dual antagonism of EP2 and EP4 together significantly enhanced the activation of PGE2-suppressed mouse and human monocytes and CD8+ T cells in vitro as compared with single EP antagonists. CD8+ T-cell activation was dampened by single EP1 and EP3 antagonists. Dual EP2/EP4 PGE2 receptor antagonists increased tumor microenvironment lymphocyte infiltration and significantly reduced disease burden in multiple tumor models, including in the adenomatous polyposis coli (APC)min+/- spontaneous colorectal tumor model, compared with celecoxib. These results support a hypothesis that redundancy of EP2 and EP4 receptor signaling necessitates a therapeutic strategy of dual blockade of EP2 and EP4. Here we describe TPST-1495, a first-in-class orally available small-molecule dual EP2/EP4 antagonist. Significance: Prostaglandin (PGE2) drives tumor progression but the pathway has not been effectively drugged. We demonstrate significantly enhanced immunologic potency and antitumor activity through blockade of EP2 and EP4 PGE2 receptor signaling together with a single molecule.

Improvised bespoke technique for atrial septostomy in the shortage of atrioseptostomy balloon catheters.

Atrioseptostomy balloon catheter is an essential item to have on our shelves. However, the recall and shortage in production of the commonly used balloon atrioseptostomy catheters posed an imminent threat to our patients. Herein, we present the case of a newborn with a post-natal diagnosis of simple transposition of great arteries and restrictive atrial communication where repeated static balloon atrial septostomy using a 9 mm x 20 mm Sterling balloon failed to improve his status. We had to improvise per-operatively a new bespoke technique to perform a vital pull-through balloon atrial septostomy. The distal third of a 10 mm x 20 mm semi-compliant Cristal balloon was exteriorised out the tip of a 6-Fr 55 cm Cook Flexor sheath in the left atrium, and both were simultaneously pulled back to the right atrium to create an 8 mm septal defect. The procedure was successful without any complications. The baby was weaned off prostaglandin on day 3 and surgically repaired on day 5 with excellent results.

Outcomes of manually modified microvascular plugs to pulmonary flow restrictors in various congenital heart lesions.

Background: The development of microvascular plugs (MVPs) has enabled novel transcatheter deliverable endoluminal pulmonary flow restrictors (PFRs) with the potential to treat newborns and infants with life-threatening congenital heart diseases (CHDs) in a minimally invasive manner. We present our experience to evaluate the efficacy of this concept in controlling pulmonary blood flow in various CHDs. Methods: Retrospective clinical data review of patients with CHD and pulmonary over-circulation who received bilateral PFRs percutaneously. Results: Twenty-eight PFRs (7 MVP-5Q, 12 MVP-7Q, and 9 MVP-9Q) were finally implanted in 14 patients with a median age of 1.6 months (IQR, 0.9-2.3) and a median weight of 3.1 Kg (IQR, 2.7-3.6). Nine patients had large intra-cardiac left-to-right shunts (including 3 with fatal trisomy and palliative programs), 2 had borderline left ventricles, 2 had Taussig-Bing anomaly, and one had a hypoplastic left heart. Four patients had concomitant ductal stenting. Two MVP-5Qs were snare-removed and upsized to MVP-7Q. Patients experienced a significant drop in oxygen saturation and Qp/Qs. All patients were discharged from the ICU after a median of 3.5 days (IQR, 2-5.8) postoperative. Five patients had routine inter-stage catheterization and no device embolization or pulmonary branch distortion was seen. Fourteen (50%) PFRs were surgically explanted uneventfully on a median of 4.3 months (IQR, 1.2-6) post-implantation during biventricular repair in 6 patients and stage-2 palliation in one patient. The latter died 1 month post-operative from severe sepsis. Four patients are scheduled for surgical PFR removal and biventricular repair. Two patients with trisomy 18 died at 1 and 6.8 months post-procedure from non-cardiac causes. One patient with trisomy 13 is alive at 2.7 months post-procedure. Conclusion: It is feasible to bespoke MVPs and implant them as effective PFRs in various CHDs. This approach enables staged left ventricular recruitment, comprehensive stage-2 or biventricular repair with lower risk by postponing surgeries to later infancy. Device explantation is uneventful, and the outcomes afterward are promising.

Six states of Enterococcus hirae V-type ATPase reveals non-uniform rotor rotation during turnover.

The vacuolar-type ATPase from Enterococcus hirae (EhV-ATPase) is a thus-far unique adaptation of V-ATPases, as it performs Na+ transport and demonstrates an off-axis rotor assembly. Recent single molecule studies of the isolated V1 domain have indicated that there are subpauses within the three major states of the pseudo three-fold symmetric rotary enzyme. However, there was no structural evidence for these. Herein we activate the EhV-ATPase complex with ATP and identified multiple structures consisting of a total of six states of this complex by using cryo-electron microscopy. The orientations of the rotor complex during turnover, especially in the intermediates, are not as perfectly uniform as expected. The densities in the nucleotide binding pockets in the V1 domain indicate the different catalytic conditions for the six conformations. The off-axis rotor and its' interactions with the stator a-subunit during rotation suggests that this non-uniform rotor rotation is performed through the entire complex.

Comparative outcomes of two competitive devices for retrograde closure of perimembranous ventricular septal defects.

Background: Retrograde closure of perimembranous ventricular septal defects (pmVSDs) is a well-established procedure. However, interventionists are still looking for the best closure device. Methods: We performed a single-center retrospective review of 5-year-experience (from July 2015 to July 2020) with retrograde closure of pmVSDs using AmplatzerTM Duct Occluder II (ADOII) and KONAR-MF™ VSD occluder (MFO). Deficient sub-aortic rim (SAR) (≤2.5 mm for MFO and ≤3 mm for ADOII) was an exclusion criterion in defects with a diameter ratio (right-side exit/left-side entry) > 0.5. Results: We identified 77 patients (57.1% males) with a median age of 4.3 years (IQR, 2.2-8.3) and a median weight of 16 kg (IQR, 11.2-24.5). 44 (57.1%) defects (22.7% with deficient SARs) with a median left-side defect diameter of 8.7 mm (IQR, 5.7-10) were closed with ADOIIs. 33 (42.9%) defects (51.5% with deficient SARs) with a median left-side defect diameter of 10.8 mm (IQR, 8.8-13.5) were closed with MFOs. One 7/5 MFO was removed before release and upsized to a 12/10 MFO. Implantation success rate was 100% with ADOII and 90.9% with MFO devices. Two MFOs were snare-recaptured after embolization, and one 9/7 MFO was snare-retrieved for a new onset of grade-2 aortic regurgitation that persisted afterward. Median follow-up was 3.3 years (IQR, 2.1-4.2) for ADOII and 2.3 years (IQR, 1.7-2.5) for MFO. No permanent heart block or death occurred. Freedom from left ventricular dilation was 94.62% at 36 months of follow-up. Freedom from residual shunt was 90.62% for MFO and 89.61% for ADOII at 24 months of follow-up. One 2.6-year-old patient with baseline mild aortic valve prolapse and trivial aortic regurgitation developed a grade-2 aortic regurgitation after 9/7 MFO implantation. He was treated surgically after two years without device extraction. One new grade-2 asymptomatic tricuspid regurgitation persisted at the last follow-up in the ADOII group. Conclusions: ADOII and MFO are complementary devices for effective retrograde closure of pmVSDs in children, including defects with absent or deficient SAR. ADOII is limited to smaller defects but offers a lower profile and a flexible left-side disk for better maneuverability over the aortic valve during retrograde implantation.

Prevalence and risk factors determinants of the non-use of insecticide-treated nets in an endemic area for malaria: analysis of data from Cameroon.

BACKGROUND: Malaria is the main cause of morbidity and mortality in Cameroon. Insecticide-treated nets (ITNs) significantly reduce malaria transmission, but their use is not common in the population. This study aimed to estimate the nationwide prevalence of the non-use of ITNs and identify its major determinants. METHODS: A cross-sectional study was conducted on interview data collected in households selected across all the regions of Cameroon through a non-probabilistic, random, 2-stage stratified sampling process. Descriptive statistics were used to describe the distribution of baseline characteristics across the households, and statistical tests assessed if the distribution of these characteristics differed significantly based on the non-use of ITNs, with 0.05 serving as a threshold of the p-value for statistical significance. The prevalence of the non-use of ITNs was estimated, and logistic regression models were used to tally the odds ratios of the associations between various factors and the non-use of ITNs, along with their 95% confidence intervals. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) were determined, and the Hosmer Lemeshow test was used to measure the goodness of fit of each statistical model. RESULTS: Of the 7593 households interviewed, 77% had at least one ITN and 59% of the population used ITNs. Only 72% of the population with at least one ITN used it. The logistic model of the multivariate analysis was significant at a 5% threshold. The AUC was 0.7087 and the error rate was 18.01%. The sensitivity and specificity of the model were 97.56% and 13.70%, respectively. The factors that were associated with ITN use were the presence of sufficient nets in the household (p < 0.0001), the region of residence (p < 0.0001), the level of education of the respondent (p < 0.0001), and the standard of living (p = 0.0286). Sex, age, colour preferences, as well as the shape and size of the nets were not associated with ITN use. CONCLUSIONS: The use of ITNs in Cameroon was low and varied according to specific factors. These identified factors could be used as the foundations of effective sensitization campaigns on the importance of ITNs.

Transcatheter Management of Pulmonary Sequestrations in Children-A Single-Center Experience.

BACKGROUND: A pulmonary sequestration (PS) is an area of bronchopulmonary tissue with aberrant arterial supply. Transcatheter occlusion of PSs is an appealing treatment option, but data on outcomes remain scarce. We aim to describe our experience with transcatheter management of PS in infants and children. METHODS: Retrospective review of clinical data of all patients with suspected PS sent for diagnostic and/or interventional cardiac catheterization at our institution between January 1999 and May 2021. Procedural considerations, techniques, standard safety, and outcomes were assessed. RESULTS: We identified 71 patients (52.1% males), with median age and weight of 4.9 months (IQR, 2.1-26.6) and 4.2 kg (IQR, 3.9-12.1), respectively. Sixty-one (86%) patients had associated congenital heart defects (CHDs). Forty-two (59%) patients had pulmonary arterial hypertension (PAH) at the time of diagnosis. Fifty-three (74.7%) patients underwent embolization of the PS feeding vessel using microcoils and/or vascular plugs, and eight (15.1%) of these were neonates who presented with severe PAH and cardiac failure. Two patients had large feeding vessels and were treated surgically. Sixteen (22.5%) patients with small feeding vessels received conservative management. At median follow-up of 36.4 months (IQR, 2.1-89.9), seven patients had died, 24 patients had CHD corrective surgeries, 26 patients had redo catheterizations, and five patients had persistent PAH. No PS surgical resection was needed, and no infection of the remaining lung tissue occurred. CONCLUSIONS: Transcatheter assessment and treatment of PSs is a safe and effective procedure. Neonates with large PSs are severely symptomatic and improve remarkably after PS closure. PS embolization and surgical repair of associated CHDs generally leads to the normalization of pulmonary pressures.