Pelvic diameter is not associated with positive circumferential resection margin in rectal cancer: retrospective analysis of 78 cases

Objective: To identify if there is an association between pelvic entry and pelvic outlet diameters with increased positive circumferential resection margin (CRM) in rectal cancer. Introduction: Positive CRMin rectalcancerisa majorpredictor forlocal anddistant recurrence. Pelvic diameters may be related to the difficulty of dissection, as well as intrinsic tumor characteristics such as tumor size, location, distance from the anal margin, and T stage, which may compromise the integrity of the mesorectum and circumferential margin involvement. Methods: A retrospective review of the patient's medical records who underwent surgical resection of rectal adenocarcinoma from January 2012 to June 2022 was performed. The patient's preoperative staging, operative characteristics, and histopathologic outcomes were gathered from the medical records. Preoperative MRI scanning was done in all patients. MRI pelvimetry was done by two observers. CRM involvement was recorded as stated in the pathology report. Pelvimetry variables were dichotomized according to their mean values for correlation analysis. The odds ratio (OR) was calculated from a binary logistics regression model to assess the relation between the positive CRM and the independent variables. Results: A total of 78 patients were included in this study. A positive CRM was reported in 10 patients (12.8%). BMI >27.4 + 6.6 (p = 0.02), positive extramural vascular invasion (p = 0.027), positive CRM by MRI scanning (p = 0.004), and anal sphincter involvement (p = 0.03) were associated with positive CRM. Pelvimetry values were not associated with a positive CRM. Conclusion: No association was found between the pelvic diameters measured by MRI pelvimetry with a positive CRM. (AU)

Outcomes and Risk Factors of Interventions for Pediatric Post-operative Pulmonary Vein Stenosis.

Pulmonary vein stenosis (PVS) in children is a challenging condition with poor outcomes. Post-operative stenosis can occur after repair of anomalous pulmonary venous return (APVR) or stenosis within native veins. There is limited data on the outcomes of post-operative PVS. Our objective was to review our experience and assess surgical and transcatheter outcomes. Single-center retrospective study was performed including patients < 18 years who developed restenosis after baseline pulmonary vein surgery that required additional intervention(s) from 1/2005 to 1/2020. Non-invasive imaging, catheterization and surgical data were reviewed. We identified 46 patients with post-operative PVS with 11 (23.9%) patient deaths. Median age at index procedure was 7.2 months (range 1 month-10 years), and median follow-up was 10.8 months (range 1 day-13 years). Index procedure was surgical in 36 (78.3%) and transcatheter in 10 (21.7%). Twenty-three (50%) patients developed vein atresia. Mortality was not associated with number of affected veins, vein atresia, or procedure type. Single ventricle physiology, complex congenital heart disease (CCHD), and genetic disorders were associated with mortality. Survival rate was higher in APVR patients (p = 0.03). Patients with three or more interventions had a higher survival rate compared to patients with 1-2 interventions (p = 0.02). Male gender, necrotizing enterocolitis, and diffuse hypoplasia were associated with vein atresia. In post-operative PVS, mortality is associated with CCHD, single ventricle physiology, and genetic disorders. Vein atresia is associated with male gender, necrotizing enterocolitis, and diffuse hypoplasia. Multiple repeated interventions may offer a patient survival benefit; however, larger prospective studies are necessary to elucidate this relationship further.

Metastatic clear-cell renal carcinoma: an exceptional cause of ileocolonic intussusception in adults

Introduction: Intussusceptions in adults are rare, representing 1% to 5% of intestinal obstructions in this age group. This condition can be caused by benign and malignant lesions acting as lead points, the latter being the most frequent. Furthermore, the diagnosis is challenging due to the non-specific symptoms with variable duration. Case Presentation: A 43-year-old man, with a history of localized clear-cell renal carcinoma (ccRCC) treated 9 years earlier with a right radical nephrectomy, presented with bowel obstruction symptoms. An abdominal computed tomography scan showed an ileocolonic intussusception. Hence, the patient required a right hemicolectomy with ileotransverse anastomosis. The histopathological analysis showed a metastatic ccRC to the terminal ileum causing the intussusception. Discussion: Adult intussusceptions are rare. However, they should be considered in the differential diagnosis of patients with abdominal pain and symptoms of bowel obstruction. Metastases of renal cancer to the small bowel are uncommon and even more so in the form of intussusception. Definitive treatment must be tailored to the patient's condition and underlying cause. (AU)

Outcomes after neonatal cardiac surgery: The impact of a dedicated neonatal cardiac program.

OBJECTIVES: Prematurity is a risk factor for in-hospital mortality after cardiac surgery. The structure of intensive care unit models designed to deliver optimal care to neonates including those born preterm with critical congenital heart disease is unknown. The objective of this study was to evaluate in-hospital outcomes after cardiac surgery across gestational ages in an institution with a dedicated neonatal cardiac program. METHODS: This study is a single-center, retrospective review of infants who underwent cardiac surgical interventions from our dedicated neonatal cardiac intensive care program between 2006 and 2017. We evaluated in-hospital mortality and morbidity rates across all gestational ages. RESULTS: A total of 1238 subjects met inclusion criteria over a 11-year period. Overall in-hospital mortality after cardiac surgery was 6.1%. The mortality rate in very preterm infants (n = 68; <34 weeks' gestation at birth) was 17.6% (odds ratio, 3.52 [1.4-8.53]), versus 4.3% in full-term (n = 563; 39-40 weeks) referent/control infants. Very preterm infants with isolated congenital heart disease (without evidence of other affected organ systems) experienced a mortality rate of 10.5% after cardiac surgery. Neither the late preterm (34-36 6/7 weeks) nor the early term (37-38 6/7) groups had significantly increased odds of mortality compared with full-term infants. Seventy-eight percent of very preterm infants incurred a preoperative or postoperative complication (odds ratio, 4.78 [2.61-8.97]) compared with 35% of full-term infants. CONCLUSIONS: In this study of a single center with a dedicated neonatal cardiac program, we report some of the lowest mortality and morbidity rates after cardiac surgery in preterm infants in the recent era. The potential survival advantage of this model is most striking for very preterm infants born with isolated congenital heart disease.

HLA-BAT1 alters migration, invasion and pro-inflammatory cytokines in prostate cancer.

Prostate cancer (PCa) accounts for more than 1 in 5 diagnoses and is the second cause of cancer-related deaths in men. Although PCa may be successfully treated, patients may undergo cancer recurrence and there is a need for new biomarkers to improve the prediction of prostate cancer recurrence and improve treatment. Our laboratory demonstrated that HLA-B-associated transcript 1 (BAT1) was differentially expressed in patients with high Gleason scores when compared to low Gleason scores. BAT1 is an anti-inflammatory gene but its role in PCa has not been identified. The objective of this study is to understand the role of BAT1 in prostate cancer. In vitro studies showed that BAT1 down-regulation increased cell migration and invasion. In contrast, BAT1 overexpression decreased cell migration and invasion. RT-PCR analysis showed differential expression of pro-inflammatory cytokines (TNF-α and IL-6) and cell adhesion and migration genes (MMP10, MMP13, and TIMPs) in BAT1 overexpressed cells when compared to BAT1 siRNA cells. Our in vivo studies demonstrated up-regulation of TNF-α, IL-6, and MMP10 in tumors developed from transfected BAT1 shRNA cells when compared to tumors developed from BAT1 cDNA cells. These findings indicate that BAT1 down-regulation modulates TNF-α and IL-6 expression which may lead to the secretion of MMP-10 and inhibition of TIMP2.

Manejo anestésico de una gestante con síndrome de Morquio / Anesthetic Management for a pregnant woman with Morquio syndrome Sobre los autores:

Introducción: El síndrome de Morquio es una enfermedad hereditaria autosómica recesiva con distintos grados de afectación al metabolismo de los glúcidos, lo que genera incapacidad para romper los enlaces de las cadenas largas de glucosamiglicanos, esto provoca acumulación de mucopolisacáridos en distintos tejidos del cuerpo humano. Objetivo: Describir el manejo anestésico de una gestante con síndrome de Morquio. Presentación del caso: Gestante primigesta de 30 años de edad, de raza negra, de 103 cm de estatura y 33 Kg de peso. Acude a consulta preoperatoria por presentar embarazo a término, baja talla y se realizó interrupción del embarazo por vía alta. Se procede a la valoración preanestésica donde se recoge antecedentes de enfermedad genética e ingreso previo por presentar cifras elevadas de tensión arterial. La paciente padecía de alergia a la dipirona. Conclusiones: Los pacientes con mucopolisacaridosis tienen una alta incidencia de dificultad para la ventilación y la intubación endotraqueal asociada con insuficiencia cardiopulmonar. La afectación de la columna presenta dificultades adicionales para los anestesiólogos. Cualquier cirugía electiva requiere una evaluación preoperatoria de los factores de riesgo anestesiológicos y la disponibilidad de un espectro de equipos para el manejo de las vías respiratorias. La anestesia debe ser realizada por un equipo con experiencia en el manejo de la vía aérea(AU)

Introduction: Morquio syndrome is an autosomal recessive hereditary disease that affects, to different extents, carbohydrate metabolism, which obstructs the ability to break bonds of long chains of glycosaminoglycans, causing mucopolysaccharides accumulation in different tissues of the human body. Objective: To describe the anesthetic management of a pregnant woman with Morquio syndrome. Case presentation: This is the case of a 30-year-old primigravid pregnant woman, of black skin, 103 cm of height and 33 kg of weight. She came for preoperative consultation because she was pregnant at term and had low body size; the pregnancy was terminated through the abdominal route. A preanesthetic assessment was performed, which permitted to observe a history of genetic disease and previous admission for high blood pressure. The patient was allergic to dipyrone. Conclusions: Among patients with mucopolysaccharidosis, there is a high incidence of difficulty for ventilation and endotracheal intubation associated with cardiopulmonary insufficiency. Spinal involvement represents additional difficulties for anesthesiologists. Any elective surgery requires preoperative assessment of anesthesiologic risk factors and the availability of a spectrum of airway management equipment. Anesthetic managment should be performed by a team experienced in airway management(AU)

MiR-30a-5p Alters Epidermal Terminal Differentiation during Aging by Regulating BNIP3L/NIX-Dependent Mitophagy.

Chronological aging is characterized by an alteration in the genes' regulatory network. In human skin, epidermal keratinocytes fail to differentiate properly with aging, leading to the weakening of the epidermal function. MiR-30a is particularly overexpressed with epidermal aging, but the downstream molecular mechanisms are still uncovered. The aim of this study was to decipher the effects of miR-30a overexpression in the human epidermis, with a focus on keratinocyte differentiation. We formally identified the mitophagy receptor BNIP3L as a direct target of miR-30a. Using a 3D organotypic model of reconstructed human epidermis overexpressing miR-30a, we observed a strong reduction in BNIP3L expression in the granular layer. In human epidermal sections of skin biopsies from donors of different ages, we observed a similar pattern of BNIP3L decreasing with aging. Moreover, human primary keratinocytes undergoing differentiation in vitro also showed a decreased expression of BNIP3L with age, together with a retention of mitochondria. Moreover, aging is associated with altered mitochondrial metabolism in primary keratinocytes, including decreased ATP-linked respiration. Thus, miR-30a is a negative regulator of programmed mitophagy during keratinocytes terminal differentiation, impairing epidermal homeostasis with aging.

Procedimiento anestésico - quirúrgico en un lactante con higrohematoma subdural / Anesthetic - surgical procedure in an infant with subdural hygrohematoma

Se describe el caso clínico de un lactante de 47 días de nacido, quien fue atendido en el Cuerpo de Guardia de Pediatría del Hospital Provincial General Docente Antonio Luaces Iraola de Ciego de Ávila, por presentar aumento de la circunferencia cefálica, irritabilidad y agitación. Los exámenes realizados mostraron signos de hipertensión endocraneana descompensada, secundaria a colección del espacio subdural izquierdo. Se eliminó el higroma subdural y la recuperación fue favorable en las primeras 36 horas; luego comenzó a convulsionar y apareció nuevamente el deterioro neurológico, por lo cual se decidió reintervenir. Se realizó inducción anestésica con tiopental sódico fentanilo y rocuronio. El paciente evolucionó sin complicaciones.

The case report of a 47 days infant is described. He was assisted in the children emergency room of Antonio Luaces Iraola Teaching General Provincial Hospital in Ciego de Ávila, due to an increase of the cephalic circumference, irritability and agitation. The exams showed signs of upset endocranial hypertension, secondary to collection of the left subdural space. The subdural hygroma was eliminated and the recovery was favorable in the first 36 hours; then a covulsion began and the neurological deterioration appeared again, reason why it was decided to operate once more. Anesthetic induction was carried out with fentanyl sodium thiopental and rocuronium. The patient had a favorable clinical course without complications.

Reintervention and Survival After Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Transcatheter pulmonary valve (TPV) replacement (TPVR) has become the standard therapy for postoperative pulmonary outflow tract dysfunction in patients with a prosthetic conduit/valve, but there is limited information about risk factors for death or reintervention after this procedure. OBJECTIVES: This study sought to evaluate mid- and long-term outcomes after TPVR in a large multicenter cohort. METHODS: International registry focused on time-related outcomes after TPVR. RESULTS: Investigators submitted data for 2,476 patients who underwent TPVR and were followed up for 8,475 patient-years. A total of 95 patients died after TPVR, most commonly from heart failure (n = 24). The cumulative incidence of death was 8.9% (95% CI: 6.9%-11.5%) 8 years after TPVR. On multivariable analysis, age at TPVR (HR: 1.04 per year; 95% CI: 1.03-1.06 per year; P < 0.001), a prosthetic valve in other positions (HR: 2.1; 95% CI: 1.2-3.7; P = 0.014), and an existing transvenous pacemaker/implantable cardioverter-defibrillator (HR: 2.1; 95% CI: 1.3-3.4; P = 0.004) were associated with death. A total of 258 patients underwent TPV reintervention. At 8 years, the cumulative incidence of any TPV reintervention was 25.1% (95% CI: 21.8%-28.5%) and of surgical TPV reintervention was 14.4% (95% CI: 11.9%-17.2%). Risk factors for surgical reintervention included age (0.95 per year [95% CI: 0.93-0.97 per year]; P < 0.001), prior endocarditis (2.5 [95% CI: 1.4-4.3]; P = 0.001), TPVR into a stented bioprosthetic valve (1.7 [95% CI: 1.2-2.5]; P = 0.007), and postimplant gradient (1.4 per 10 mm Hg [95% CI: 1.2-1.7 per 10 mm Hg]: P < 0.001). CONCLUSIONS: These findings support the conclusion that survival and freedom from reintervention or surgery after TPVR are generally comparable to outcomes of surgical conduit/valve replacement across a wide age range.

Manejo de un paciente clase III ósea con cirugía ortognática tardía: reporte de caso clínico / Management of an orthognathic surgery treatment in a skeletal class IIIpatient: case report

Antecedentes: El tratamiento establecido como el estándar de oro para las malformaciones óseas del complejo cráneo facial es el tratamiento de ortodoncia compaginado con cirugía ortognática, para alcanzar estabilidad oclusal, eliminar discrepancia ósea, armonía facial, mejora en la masticación, fonación y respiración. El protocolo de cirugía ortognática tardía consiste en 3 fases: tratamiento de ortodoncia pre-quirúrgica, cirugía ortognática y ortodoncia post-quirúrgica. Objetivo:El objetivo del caso clínico es trasmitir que el enfoque de cirugía tardía puede dar excelentes resultados, ser eficaz y rápido si existe un buen diagnóstico, manejo y una comunicación estrecha entre el ortodoncista y el cirujano maxilofacial. Reporte de caso:Paciente femenino de 18 años de edad clase III ósea. Presenta molestia ocasional, crepitación y luxación de la articulación temporomandibular, laterognasia. El tratamiento establecido fue cirugía ortognática tardía de ambos maxilares con osteotomía sagital unilateral. Resultados:Los objetivos del plan de tratamiento se cumplieron a 1 año 9 meses de haber iniciado el tratamiento ortodóncico. Conclusión:Con un buen diagnóstico y planificación del tratamiento de ortodoncia ­cirugía ortognática asegura excelentes resultados, así como, estabilidad ósea y armonía oclusal post-cirugía.

Introduction: The treatment established as the gold standard for skeletal deformities of the craniofacial complex is orthodontic treatment combined with orthognathic surgery, to achieve occlusal stability, facial harmony, improved mastication, phonation and breathing. The conventional orthognathic surgery protocol consists of 3 phases: pre-surgical orthodontic treatment, orthognathic surgery and post-surgical orthodontics. Case Report: 18-year-old female patient with skeletal class III. She presents occasional pain, crepitation and luxation of the temporomandibular joint, laterognathia. Treatment: Conventional orthognathic surgery of both jaws with unilateral sagittal osteotomy. Results: The objectives of the treatment plan were achieved 1 year and 9 months after starting orthodontic treatment.Conclusion: With a good diagnosis and treatment planning orthodontic -maxillofacial surgery ensures excellent results, as well as bone stability and occlusal harmony post-surgery.

Multicenter Study of Endocarditis After Transcatheter Pulmonary Valve Replacement.

BACKGROUND: Endocarditis has emerged as one of the most impactful adverse events after transcatheter pulmonary valve replacement (TPVR), but there is limited information about risk factors for and outcomes of this complication. OBJECTIVES: The purpose of this study was to evaluate risk factors for and outcomes of endocarditis in a large multicenter cohort. METHODS: The authors established an international registry focused on characterizing endocarditis after TPVR, including the incidence, risk factors, characteristics, and outcomes. RESULTS: Investigators submitted data for 2,476 patients who underwent TPVR between July 2005 and March 2020 and were followed for 8,475 patient-years. In total, 182 patients were diagnosed with endocarditis a median of 2.7 years after TPVR, for a cumulative incidence of 9.5% (95% CI: 7.9%-11.1%) at 5 years and 16.9% (95% CI: 14.2%-19.8%) at 8 years (accounting for competing risks: death, heart transplant, and explant) and an annualized incidence of 2.2 per 100 patient-years. Staphylococcus aureus and Viridans group Streptococcus species together accounted for 56% of cases. Multivariable analysis confirmed that younger age, a previous history of endocarditis, and a higher residual gradient were risk factors for endocarditis, but transcatheter pulmonary valve type was not. Overall, right ventricular outflow tract (RVOT) reintervention was less often to treat endocarditis than for other reasons, but valve explant was more often caused by endocarditis. Endocarditis was severe in 44% of patients, and 12 patients (6.6%) died, nearly all of whom were infected with Staphylococcus aureus. CONCLUSIONS: The incidence of endocarditis in this multicenter registry was constant over time and consistent with prior smaller studies. The findings of this study, along with ongoing efforts to understand and mitigate risk, will be critical to improve the lifetime management of patients with heart disease involving the RVOT. Although endocarditis can be a serious adverse outcome, TPVR remains an important tool in the management of RVOT dysfunction.

Transcatheter Pulmonary Valve Replacement With the Sapien Prosthesis.

BACKGROUND: There are limited published data focused on outcomes of transcatheter pulmonary valve replacement (TPVR) with either a Sapien XT or Sapien 3 (S3) valve. OBJECTIVES: This study sought to report short-term outcomes in a large cohort of patients who underwent TPVR with either a Sapien XT or S3 valve. METHODS: Data were entered retrospectively into a multicenter registry for patients who underwent attempted TPVR with a Sapien XT or S3 valve. Patient-related, procedural, and short-term outcomes data were characterized overall and according to type of right ventricular outflow tract (RVOT) anatomy. RESULTS: Twenty-three centers enrolled a total of 774 patients: 397 (51%) with a native/patched RVOT; 183 (24%) with a conduit; and 194 (25%) with a bioprosthetic valve. The S3 was used in 78% of patients, and the XT was used in 22%, with most patients receiving a 29-mm (39%) or 26-mm (34%) valve. The implant was technically successful in 754 (97.4%) patients. Serious adverse events were reported in 67 patients (10%), with no difference between RVOT anatomy groups. Fourteen patients underwent urgent surgery. Nine patients had a second valve implanted. Among patients with available data, tricuspid valve injury was documented in 11 (1.7%), and 9 others (1.3%) had new moderate or severe regurgitation 2 grades higher than pre-implantation, for 20 (3.0%) total patients with tricuspid valve complications. Valve function at discharge was excellent in most patients, but 58 (8.5%) had moderate or greater pulmonary regurgitation or maximum Doppler gradients >40 mm Hg. During limited follow-up (n = 349; median: 12 months), 9 patients were diagnosed with endocarditis, and 17 additional patients underwent surgical valve replacement or valve-in-valve TPVR. CONCLUSIONS: Acute outcomes after TPVR with balloon-expandable valves were generally excellent in all types of RVOT. Additional data and longer follow-up will be necessary to gain insight into these issues.

Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates.

Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a ρ0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogrammed non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, after reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble unmanipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch "pipeline" enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types.

Consideraciones sobre las condiciones neuropsiquiátricas del Quijote de la Mancha / Considerations about the Neuropsychiatry Conditions of Quixote of La Mancha

RESUMEN Don Quijote de la Mancha, el pintoresco personaje creado por Miguel de Cervantes Saavedra en su obra inmortal El Ingenioso Hidalgo Don Quijote de la Mancha, presenta varias condiciones neuropsiquiátricas que incluyen tremor, trastornos del sueño, síntomas neuropsiquiátricos, síncope, trastornos de la percepción y traumatismo craneoencefálico. A lo largo de la obra, se presentan episodios en los que se hacen evidentes los diferentes trastornos mencionados. El artículo hace un recuento de ellos a través de la novela y un análisis a la luz de los conocimientos actuales sobre dichas condiciones.

ABSTRACT Don Quixote of La Mancha, the picturesque character created by Miguel de Cervantes Saavedra in his immortal book The Ingenious Nobleman Sir Quixote of La Mancha, presents several neuropsychiatric conditions, including tremor, sleep disturbances, neuropsychiatric symptoms, syncope, perception disorders and traumatic brain injury. Throughout the masterpiece, there are episodes where the aforementioned disorders are evident. This paper makes a list of them and analyses them in the light of the current knowledge of those conditions.

Neonates With Complex Cardiac Malformation and Congenital Diaphragmatic Hernia Born to SARS-CoV-2 Positive Women-A Single Center Experience.

BACKGROUND: Our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnancies and perinatal outcomes is limited. The clinical course of neonates born to women who acquired coronavirus disease 2019 (COVID-19) during their pregnancy has been previously described. However, the course of neonates born with complex congenital malformations during the COVID-19 pandemic is not known. METHODS: We report a case series of seven neonates with congenital heart and lung malformations born to women who tested positive for SARS-CoV-2 during their pregnancy at a single academic medical center in New York City. RESULTS: Six infants had congenital heart disease and one was diagnosed with congenital diaphragmatic hernia. In all seven infants, the clinical course was as expected for the congenital lesion. None of the seven exhibited symptoms generally associated with COVID-19. None of the infants in our case series tested positive by nasopharyngeal test for SARS-CoV-2 at 24 hours of life and at multiple points during their hospital course. CONCLUSIONS: In this case series, maternal infection with SARS-CoV-2 during pregnancy did not result in adverse outcomes in neonates with complex heart or lung malformations. Neither vertical nor horizontal transmission of SARS-CoV-2 was noted.

The Insomnia Plague in Fictional Macondo.

Disease and medicine are found throughout Gabriel García Márquez's work. This article examines the insomnia plague described in the novel One Hundred Years of Solitude and performs a differential diagnosis exercise with conditions that affect both sleep and memory. The main finding is that the insomnia plague narrated by García Márquez, with its clinical manifestations, the sequence of symptoms, and its resolution, cannot be associated with any specific diagnosis. However, similarities to and differences from several clinical conditions are discussed, as well as the relation between the neurophysiologic phenomena of sleep and memory.

Identification of Risk Factors for Early Fontan Failure.

Despite improvements in operative and perioperative care, the risk of significant morbidity and mortality for children undergoing Fontan procedures persists. Previous investigations have identified peri-Fontan characteristics that may predict early adverse events. The purpose of this study was to identify characteristics from throughout a patient's lifespan, including all perioperative stages, that might predict early Fontan failure-defined as death, Fontan takedown, or listing for cardiac transplantation before hospital discharge or within 30 postoperative days. A single-center retrospective study of all patients undergoing a Fontan procedure was performed. Patient and intervention-related characteristics were examined from birth through Fontan. Data were described using standard summary statistics. Univariable, logistic regression was used to examine associations with early Fontan failure. In total, 191 patients met inclusion criteria. The incidence of early Fontan failure was 4% (n = 8: 6 deaths, 2 Fontan takedowns). Neonatal balloon atrial septostomy was the only patient characteristic significantly associated with Fontan failure. Patients who underwent balloon septostomy had 8.5 times higher odds of Fontan failure (confidence interval (CI) 2.6-28.1, P < 0.001) than those who did not. Children who require balloon septostomy as neonates remain at higher risk of Fontan takedown, listing for heart transplantation, or death in the early post-Fontan period.

Effect of naringenin and its combination with cisplatin in cell death, proliferation and invasion of cervical cancer spheroids.

The main treatment alternative for cervical cancer is cisplatin chemotherapy. However, the resistance of tumor cells to cisplatin, in addition to side effects, limits its use. The flavonoid naringenin has shown cytotoxic effects on tumor cells and may be considered as a coadjuvant in the treatment of cervical cancer. In the present study, the effect of naringenin on cell viability, cytotoxicity, proliferation, apoptosis and invasion was evaluated in HeLa spheroid cultures. Naringenin impaired the cell viability as indicated by low ATP levels and caused concentration- and time-dependent cytotoxicity via the loss of cell membrane integrity. Furthermore, it did not activate caspases 3, 7, 8, and 9, suggesting that the cytotoxic effect was by necrotic cell death instead of apoptosis. Additionally, proliferation in the G0/G1 phase of the cell cycle was inhibited. Cell invasion also decreased as time progressed. Later, we determined if naringenin could improve the anti-tumor effect of cisplatin. The combination of naringenin with low concentrations of cisplatin improved the effect of the drug by significantly decreasing cell viability, potentiating the induction of cytotoxicity and decreasing the invasive capacity of the spheroids. Since these effects are regulated by some key proteins, molecular docking results indicated the interaction of naringenin with RIP3 and MLKL, cyclin B and with matrix metalloproteases 2 and 9. The results showed the anti-tumor effect of naringenin on the HeLa spheroids and improved effect of the cisplatin at low concentrations in combination with naringenin, placing flavonoids as a potential adjuvant in the therapy against cervical cancer.

Mid-Term Valve-Related Outcomes After Transcatheter Tricuspid Valve-in-Valve or Valve-in-Ring Replacement.

BACKGROUND: Transcatheter aortic and pulmonary valves have been used to treat stenosis or regurgitation after prior surgical tricuspid valve (TV) replacement or repair. Little is known about intermediate-term valve-related outcomes after transcatheter tricuspid valve replacement (TTVR), including valve function, thrombus, and endocarditis. OBJECTIVES: The authors sought to evaluate mid-term outcomes in a large cohort of patients who underwent TTVR after surgical TV repair or replacement, with a focus on valve-related outcomes. METHODS: Patients who underwent TTVR after prior surgical TV replacement or repair were collected through an international registry. Time-related outcomes were modeled and risk factors assessed. RESULTS: Data were collected for 306 patients who underwent TTVR from 2008 through 2017 at 80 centers; 52 patients (17%) had a prior history of endocarditis. Patients were followed for a median of 15.9 months after implantation (0.1 to 90 months), with 64% of patients estimated to be alive without TV reintervention or a valve-related event at 3 years. The cumulative 3-year incidence of death, reintervention, and valve-related adverse outcomes (endocarditis, thrombosis, or significant dysfunction) were 17%, 12%, and 8%, respectively. Endocarditis was diagnosed in 8 patients 2 to 29 months after TTVR, for an annualized incidence rate of 1.5% per patient-year (95% confidence interval: 0.45% to 2.5%). An additional 8 patients were diagnosed with clinically relevant valve thrombosis, 3 in the short term, 2 within 2 months, and 3 beyond 6 months. Only 2 of these 8 patients received anticoagulant therapy before thrombus detection (p = 0.13 vs. patients without thrombus). Prior endocarditis was not a risk factor for reintervention, endocarditis, or valve thrombosis, and there was no difference in valve-related outcomes according to TTVR valve type. CONCLUSIONS: TV dysfunction, endocarditis, and leaflet thrombosis were uncommon after TTVR. Patients with prior endocarditis were not at higher risk for endocarditis or other adverse outcomes after TTVR, and endocarditis occurred with similar frequency in different valve types. Though rare, leaflet thrombosis is an important adverse outcome, and further study is necessary to determine the appropriate level of prophylactic therapy after TTVR.