Immunofluorescence findings in a reactivating lichenoid photoallergic chronic dermatitis (actinic reticuloid).

BACKGROUND: Chronic photosensitivity dermatitis (CPD) (also named actinic reticuloid) is an unusual disease classically referred often in elderly men. Affected patients have severely itchy, thickened dry skin in areas exposed to the sun throughout the years. METHOD: A Caucasian female patient who worked most of her life outside who had "chronic dermatitis" in her neck started planting chrysanthemum in her garden on a sunny day. Later, she presented edema, erythema, papules, and a few vesicles in her neck with severe pruritus. STUDIES: A skin biopsy revealed the diagnosis of CPD, along with positive testing for ultraviolet B (UVB), minimal erythema doses (MED) for UVB (MEDB) UVA (MEDA) and PhotoPath. RESULTS: Direct immunofluorescence (DIF) stains using anti-human antibodies against fibrinogen, albumin, IgG, IgM, lambda, kappa, and C3c and C1q were positive at the base membrane area of the dermal epidermal junction, in the papillary dermis, as well as the neurovascular bundles in all the dermis and the extracellular matrix, especially those under the blisters. CONCLUSION: With this case, we suggest not forgetting the importance of using DIF in reactivated CPD cases in addition to the photo patch testing.

Invasive phaeohyphomycosis co-infection with Alternaria spp. and Curvularia spp. in a neutropenic host.

Phaeohyphomycoses are infections caused by dark-walled dematiaceous fungi. Alternaria and Curvularia are two genera of dematiaceous molds known to cause invasive fungal rhinosinusitis, particularly in immunocompromised patients. Co-infection with two dematiaceous fungi is rarely reported in the literature. This report describes a case of biopsy proven invasive fungal rhinosinusitis with Alternaria spp. and Curvularia spp. co-infection in a neutropenic host. The infection characteristics, microbiologic findings, and treatment are described.

Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.

Background: Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. Methods: In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Results: Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. Conclusions: A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.

Safety and Outcomes With Combination Therapy With Sarilumab and Baricitinib for Severe COVID-19 Respiratory Infection in Cancer Patients.

OBJECTIVES: This study aims to describe the clinical outcomes of combination therapy with sarilumab and baricitinib for severe novel Coronavirus-19 (COVID-19) infection in cancer patients. With this study, we aim to evaluate the role of expanded immunotherapy for severely ill patients with COVID-19 respiratory infections with limited options. The secondary objective is to assess the safety of combination therapy with sarilumab and baricitinib for severe COVID-19 infection. METHODS: This was a retrospective cohort study of patients admitted to Moffitt Cancer Center with COVID-19 infection between January 2020 and April 2022. Our research received a waiver to sign consent by the patients according to our institutional IRB because it was free of any risk for the patients and respected the patient's privacy. Following the Institutional IRB approval and relevant Equator guidelines, we collected information on patients with severe COVID-19 infection and received sarilumab and baricitinib. We evaluated the survival rate and safety of combination therapy. All the patient's information was de-identified to protect their information according to Health Insurance Portability and Accountability Act (HIPAA). RESULTS: Four patients were included in the data analysis. Two survived, and two of them died (Table 1). All the patients that survived were previously vaccinated. Among the two patients who died, one was vaccinated, and the other was unvaccinated. All the patients tolerated the combination therapy well, and none of the patients who survived developed secondary infections or COVID-19-associated complications beyond 12 months of discharge. CONCLUSION: Our study explores the potential safe combination use of different immune modulators targeting multiple pathways of the inflammatory cascade for severe and refractory COVID-19 respiratory infections in high-risk oncology patients. The small number of patients in our observational study was a limitation. A larger sample of patients will be needed to conclude more precisely the efficacy of the combination therapy of sarilumab and baricitinib for refractory cases of severe COVID-19 respiratory infection. Moreover, exploring other cytokine release signaling pathway targets may be the key to significantly reducing inflammation and further pulmonary fibrosis with chronic unbearable respiratory sequela.

Acute Epstein-Barr virus infection: Diagnostic challenge in young children, risk factors for hospitalisation and cytomegalovirus co-detection.

AIM: Acute Epstein-Barr virus (aEBV) and cytomegalovirus (CMV) infections frequently have similar manifestations. We aim to evaluate the characteristics of aEBV infection, risk factors for hospitalisation and differences according to CMV IgM detection (EBV-CMV co-detection) in children. METHODS: Retrospective, single-centre study including patients <16 years diagnosed with aEBV infection (positive anti-EBV IgM/Paul-Bunnell test and acute symptomatology). EBV-CMV co-detection was defined as positive CMV IgM. Factors associated with age, hospitalisation and EBV-CMV co-detection were analysed in a multivariate analysis. RESULTS: A total of 149 patients were included (median age 4.6 years). Most frequent manifestations were fever (77%), cervical lymphadenopathy (64%) and elevated liver enzymes (54%). Younger children had lower rate of positive Paul-Bunnell test (35% vs. 87%; p < 0.01), but higher rate of EBV-CMV co-detection (54% vs. 29%; p = 0.03). These children tended to have less typical symptoms of infectious mononucleosis and higher hospitalisation rate. The overall antibiotic prescription was 49%. Hospitalisation (27 children; 18%) was independently associated with prior antibiotic therapy and anaemia. Sixty-two cases (42%) had EBV-CMV co-detection, which was independently associated with elevated liver enzymes and younger age. CONCLUSION: In this study, younger children with aEBV infection presented more frequently with atypical clinical symptoms, had higher EBV-CMV co-detection rates and were more often hospitalised. Hospitalisation was associated with prior antibiotic prescription.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Chylothorax in newborns after cardiac surgery: a rare complication?

The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: • Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: •Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.

Multiple Arterial Graft Use in Coronary Artery Bypass Surgery: Surgeon Perspective vs Practice.

BACKGROUND: Despite supportive evidence and guidelines, the use of multiple arterial grafts (MAGs) in coronary artery bypass grafting remains low. We sought to determine surgeon perception of personal MAG use and compare this with actual MAG use. METHODS: We conducted a statewide surgeon survey of MAG use, presence of a hospital MAG protocol, and barriers for MAG use, with a response rate of 78% (n = 25). Surgeon survey responses were compared with actual Society of Thoracic Surgeons patient data from January 1, 2017, to December 31, 2020 using χ2 or Fisher's exact tests. RESULTS: Of 5299 patients who had first-time, nonemergent, isolated coronary artery bypass grafting (≥2 grafts) by responding surgeons, 16% received MAG (n = 825). MAG use in patients whose surgeons self-designated as "routine" MAG users was 21% vs 7% for "nonroutine" users. Surgeons with a hospital protocol for MAG use utilized MAG more often (18% vs 14%, P = .001). Surgeons who were unconvinced by the data on the benefits of MAGs used MAGs in 11% vs 22% in surgeons who were convinced. MAG use increased over time, particularly from before to after the survey (13.1% vs 30.5%, P < .001). CONCLUSIONS: Although MAG use increased over time, barriers to routine use remain. In surgeons who reported routine use, only 21% of their patients received MAGs. Hospital protocols, education, and increased awareness may reduce barriers to use and encourage evidence-based clinical practice.

Ketamine Mitigates Neurobehavioral Deficits in a Canine Model of Hypothermic Circulatory Arrest.

Hypothermic circulatory arrest is a protective technique used when complete cessation of circulation is required during cardiac surgery. Prior efforts to decrease neurologic injury with the NMDA receptor antagonist MK801 were limited by unacceptable side effects. We hypothesized that ketamine would provide neuroprotection without dose-limiting side effects. Canines were peripherally cannulated for cardiopulmonary bypass, cooled to 18°C, and underwent 90 minutes of circulatory arrest. Ketamine-treated canines (n = 5; total dose 2.85 mg/kg) were compared to untreated controls (n = 10). A validated neurobehavioral deficit score was obtained at 24, 48, and 72 hours (0 = no deficits/normal exam; higher score represents increasing deficits). Biomarkers of neuronal injury in the cerebrospinal fluid were examined at baseline and at 8, 24, 48, and 72 hours. Brain histopathologic injury was scored at 72 hours (higher score indicates more necrosis and apoptosis). Ketamine-treated canines had significantly improved, lower neurobehavioral deficit scores compared to controls (overall P = 0.003; 24 hours: median 72 vs 112, P = 0.030; 48 hours: 47 vs 90, P = 0.021; 72 hours: 30 vs 89, P = 0.069). Although the histopathologic injury scores of ketamine-treated canines (median 12) were lower than controls (16), there was no statistical difference (P = 0.10). Levels of phosphorylated neurofilament-H and neuron specific enolase, markers of neuronal injury, were significantly lower in ketamine-treated animals (P = 0.010 and = 0.039, respectively). Ketamine significantly reduced neurologic deficits and biomarkers of injury in canines after hypothermic circulatory arrest. Ketamine represents a safe and approved medication that may be useful as a pharmacologic neuroprotectant during cardiac surgery with circulatory arrest.

Trombosis venosa profunda posterior a cirugía ortognática bimaxilar. Reporte de caso / Deep vein thrombosis following bimaxillary orthognathic surgery. Case report

Introducción: la enfermedad trombótica venosa es una de las principales complicaciones mortales en pacientes internados y en pacientes operados. Tiene dos presentaciones: trombosis venosa profunda (TVP) y tromboembolia pulmonar (TEP). La TVP es una afección en la que se desarrolla un coágulo de sangre generalmente en las venas de las piernas. La incidencia del TVP en cirugía maxilofacial ha sido pobremente reportada y se considera poco común. Objetivo: describir caso de TVP en una paciente joven a quien se le realizó cirugía ortognática, con el fin de destacar el uso de anticonceptivos no orales como posible factor de riesgo para el desarrollo de esta inusual complicación posterior a una cirugía craneomaxilofacial. Caso clínico: paciente femenina de 24 años, con diagnóstico de anomalía dentofacial de clase II, sometida a cirugía ortognática bimaxilar + mentoplastia con antecedente de anticoncepción subcutánea con Etonogestrel 68 mg hace 3 años. El día 10 del postoperatorio asistió a la unidad de urgencias por dolor y edema en miembro inferior izquierdo; se sospecha TVP y se inicia anticoagulación con 1 mg/kg de heparina de bajo peso molecular subcutáneo (HBPM) cada 12 horas. El diagnóstico de TVP fue confirmado por medio de ecografía doppler de miembros inferiores. Posteriormente, a los 7 días del evento, medicina interna suspendió manejo con cumarínico y continuó anticoagulación con Rivaroxaban 20 mg VO cada 24 horas. Conclusión: el diagnóstico de TVP debe considerarse en mujeres a quienes se les practica cirugía ortognática y presentan antecedentes de tratamiento con anticonceptivos hormonales, incluidas las formas no orales.

Introduction: Venous thrombotic disease is one of the main fatal complications in hospitalized patients and in operated patients. It has two presentations: deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). DVT is a condition in which a blood clot usually develops in the veins of the legs. The incidence of DVT in maxillofacial surgery has been poorly reported and is considered uncommon. Objective: To describe a case of DVT in a young female patient undergoing orthognathic surgery in order to highlight the use of non-oral contraceptives as a possible risk factor for the development of this unusual complication in craneomaxilofacial surgery. Clinical case: 24-year-old female patient, diagnosed with class II dentofacial anomaly, underwent bimaxillary orthognathic surgery + mentoplasty with a history of subcutaneous contraception with Etonogestrel 68 mg 3 years ago. On postoperative day 10 she attended the emergency department for pain and edema in the left lower limb, DVT was suspected, and anticoagulation was started with 1 mg/kg of subcutaneous low molecular weight heparin (LMWH) every 12 hours. The diagnosis of DVT was confirmed by lower limb Doppler ultrasound. Subsequently, 7 days after the event, Internal Medicine suspended management with coumarin and continued anticoagulation with Rivaroxaban 20 mg OV every 24 hours. Conclusion: Remember that the diagnosis of DVT should be considered in women with a history of recent orthognathic surgery in treatment with hormonal contraceptives, including non-oral forms.

Riesgo suicida y estrategias de afrontamiento al estrés en población campesina colombiana / Suicidal risk and strategies for coping with stress in Colombian rural population

Resumen Introducción: El comportamiento suicida hace referencia a las diversas conductas para dejar de vivir es un fenómeno multifactorial ampliamente estudiado en población urbana, sin embargo, la población campesina, especialmente agricultores y trabajadores agrícolas están entre los grupos de alto riesgo. Objetivo: Evaluar las relaciones entre el riesgo suicida y las estrategias de afrontamiento al estrés en una muestra de 76 campesinos entre los 18 y 79 años del municipio de El Santuario, Colombia, durante la emergencia sanitaria por Covid-19. Método: Para este estudio se utilizó un diseño descriptivo correlacional de corte transversal y se emplearon como instrumentos la Escala de Evaluación de Riesgo Suicida -ERS- y la Escala de Estilos y Estrategias de Afrontamiento (EEEAE). Resultados: Los resultados encontrados en la Escala ERS no indicaron niveles clínicos de riesgo suicida. Y respecto a la EEEAE casi siempre los participantes usaban las estrategias de Reevaluación positiva, Apoyo social, Desconexión cognitiva y Resolver el problema. Hubo correlaciones negativas entre todas las dimensiones de la escala ERS con EEEAE, menos entre las dimensiones Depresión/Desesperanza y Aislamiento/Soporte social (ERS) con la Desconexión cognitiva (EEEAE) y especialmente la estrategia de Reevaluación Positiva tuvo un peso significativo sobre riesgo suicida. Conclusiones: La Reevaluación Positiva es una estrategia de afrontamiento que puede proteger la salud mental ante situaciones de estrés asociados con el riesgo suicida de la población campesina, los agricultores y trabajadores agrícolas.

Abstract Introduction: Suicidal behavior refers to the various behaviors to stop living, it is a multifactorial phenomenon widely studied in the urban population, however, the rural population, especially farmers and agricultural workers, are among the high-risk groups. Objective: Evaluate the relationships between suicidal risk and stress coping strategies in a sample of 76 peasants between 18 and 79 years of age from the municipality of El Santuario, Colombia during the Covid-19 health emergency. Method: For this study, a cross-sectional correlational descriptive design was used. The Suicide Risk Assessment Scale -SRAS- and the Coping Styles and Strategies Scale were used as measurement instruments (CSSS). Results: The results found in the SRAS Scale did not indicate clinical levels of suicidal risk. And regarding the EEEAE, the participants almost always used the strategies of Positive Reappraisal, Social Support, Cognitive Disconnection and Problem-Solving skills. There were negative correlations between all the dimensions of the SRAS scale with CSSS, less between the dimensions Depression/Hopelessness and Isolation/social support (SRAS) with Cognitive Disconnection (CSSS) and especially the Positive Reappraisal had a significant weight on suicidal risk. Conclusions: Positive Reappraisal is a coping strategy that can protect mental health in situations of stress associated with suicidal risk of the rural population, farmers, and agricultural workers.

ATP-Sensitive Potassium Channel Opener Diazoxide Reduces Myocardial Stunning in a Porcine Regional With Subsequent Global Ischemia Model.

Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase-3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; P=0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; P=0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; P<0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure (P<0.01) and maximum change in ventricular pressure during isovolumetric contraction (P<0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.

Disseminated Toxoplasmosis in an Allogeneic Hematopoietic Stem Cell Transplant Recipient: A Case Report and Review of the Current Literature.

Reactivation infections in hematopoietic stem cell transplants are mitigated by prophylactic regimens. Despite high rates of exposure, morbidity and mortality secondary to toxoplasmosis are limited to subsets of patients such as immunocompromised persons. We describe the first case of disseminated toxoplasmosis in a double umbilical cord blood transplant recipient.

Lung recruitment in neonatal high-frequency oscillatory ventilation with volume-guarantee.

BACKGROUND AND OBJECTIVES: The optimal lung volume strategy during high-frequency oscillatory ventilation (HFOV) is reached by performing recruitment maneuvers, usually guided by the response in oxygenation. In animal models, secondary spontaneous change in oscillation pressure amplitude (ΔPhf) associated with a progressive increase in mean airway pressure during HFOV combined with volume guarantee (HFOV-VG) identifies optimal lung recruitment. The aim of this study was to describe recruitment maneuvers in HFOV-VG and analyze whether changes in ΔPhf might be an early predictor for lung recruitment in newborn infants with severe respiratory failure. DESIGN AND METHODS: The prospective observational study was done in a tertiary-level neonatology department. Changes in ΔPhf were analyzed during standardized lung recruitment after initiating early rescue HFOV-VG in preterm infants with severe respiratory failure. RESULTS: Twenty-seven patients were included, with a median gestational age of 24 weeks (interquartile range [IQR]: 23-25). Recruitment maneuvers were performed, median baseline mean airway pressure (mPaw) was 11 cm H2 O (IQR: 10-13), median critical lung opening mPaw during recruitment was 14 cm H2 O (IRQ: 12-16), and median optimal mPaw was 12 cm H2 O (IQR: 10-14, p < 0.01). Recruitment maneuvers were associated with an improvement in oxygenation (FiO2 : 65.0 vs. 45.0, p < 0.01, SpO2/FiO2 ratio: 117 vs. 217, p < 0.01). ΔPhf decreased significantly after lung recruitment (mean amplitude: 23.0 vs. 16.0, p < 0.01). CONCLUSION: In preterm infants with severe respiratory failure, the lung recruitment process can be effectively guided by ΔPhf on HFOV-VG.

A High-Content Screen for C/EBPα Expression Identifies Novel Therapeutic Agents in Dedifferentiated Liposarcoma.

PURPOSE: Dedifferentiated liposarcoma (DDLS), one of the most common and aggressive sarcomas, infrequently responds to chemotherapy. DDLS survival and growth depend on underexpression of C/EBPα, a tumor suppressor and transcriptional regulator controlling adipogenesis. We sought to screen and prioritize candidate drugs that increase C/EBPα expression and may therefore serve as differentiation-based therapies for DDLS. EXPERIMENTAL DESIGN: We screened known bioactive compounds for the ability to restore C/EBPα expression and inhibit proliferation selectively in two DDLS cell lines but not in normal adipose-derived stem cells (ASC). Selected hits' activity was validated, and the mechanism of the most potent, SN-38, was investigated. The in vivo efficacy of irinotecan, the prodrug of SN-38, was evaluated in DDLS xenograft models. RESULTS: Of 3,119 compounds, screen criteria were met by 19. Validation experiments confirmed the DDLS selectivity of deguelin, emetine, and SN-38 and showed that they induce apoptosis in DDLS cells. SN-38 had the lowest IC50 (approximately 10 nmol/L), and its pro-apoptotic effects were countered by knockdown of CEBPA but not of TP53. Irinotecan significantly inhibited tumor growth at well-tolerated doses, induced nuclear expression of C/EBPα, and inhibited HIF1α expression in DDLS patient-derived and cancer cell line xenograft models. In contrast, doxorubicin, the most common treatment for nonresectable DDLS, reduced tumor growth by 30% to 50% at a dose that caused weight loss. CONCLUSIONS: This high-content screen revealed potential treatments for DDLS. These include irinotecan, which induces apoptosis of DDLS cells in a C/EBPα-dependent, p53-independent manner, and should be clinically evaluated in patients with advanced DDLS.

Ochronotic heart disease leading to severe aortic valve and coronary artery stenosis.

Cardiac ochronosis is a rare disease, estimated to affect 1 in 250,000 persons. While there is extensive evidence of the musculoskeletal alterations of the disease, cardiac involvement has not been widely studied and most information we currently have derives from case reports and case series. We report the case of a 64-year old patient with a known history of alkaptonuria who presented with dyspnea and weight loss. On evaluation, he was found to have severe aortic stenosis, coronary artery disease, and interventricular septal hypertrophy. Surgery revealed extensive ochronotic pigment deposition affecting the cardiac septum, both internal thoracic arteries, the native coronary arteries, and the aortic valve. Ochronotic heart disease is an often disregarded presentation of alkaptonuria. More information is needed on the course of the disease, as well as long-term outcomes after valve replacement surgery and/or coronary artery bypass grafting in patients with alkaptonuria.

Measures to Increase Use of Multiple Arterial Grafts for Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Use of multiple arterial grafts (MAGs) provides superior patency and long-term survival benefit compared with venous grafts during coronary artery bypass grafting (CABG). However, MAGs are used infrequently for CABG. We hypothesized that specific measures introduced at our institution would lead to an increase in the use of MAGs. STUDY DESIGN: Use of MAGs before and after introduction of bundled measures was compared. Measures included increased education in arterial graft harvesting, inclusion as a quality metric, and hiring of surgeon champions. Patients younger than 70 years who underwent first time, isolated CABG using at least 1 arterial graft were included. Number and type of grafts used were compared between time periods using chi-square test. Secondary outcomes included postoperative complications. Complications were compared between time periods, as well as between MAG and non-MAG recipients before and after propensity score matching using Fisher exact test and univariate logistic regression. Multivariable logistic regression was used to determine patient characteristics associated with MAG use. RESULTS: There were 2,169 patients included from 2012 to 2019. MAG use increased significantly after introduction of measures (21.1% to 41.9%; p < 0.001). Radial artery use with an internal mammary artery (0.3% to 16%; p < 0.001) and the use of triple arterial grafts increased significantly (0% to 2.4%; p < 0.001). MAG use in the entire cohort was associated with decreased 30-day mortality and postoperative cardiac arrest that was not significant after propensity matching. CONCLUSIONS: A programmatic emphasis on the use of MAGs for CABG is an effective method to increase its use.

Aortitis masquerading as intramural hematoma: When to observe, when to operate? A case report.

Radiologic evidence of aortic disease is not always consistent with the diagnosis. With a lack of accompanying symptoms or with an atypical presentation, diagnosis, and management of aortic pathology rely greatly on imaging techniques. We report the case of a 58-year-old female who presented with incidental radiographic findings consistent with a type A aortic intramural hematoma and a vague left-sided chest discomfort. After follow-up, imaging was consistent with disease progression and hematoma expansion; the affected segment was resected and pathology reported lymphoplasmacytic aortitis as the underlying etiology of the imaging findings rather than an intramural hematoma. The patient lacked symptoms or serology consistent with the rheumatologic disease, and the postoperative course was uneventful. The management of a suspected ascending intramural hematoma is controversial, especially when the patient presents with atypical signs and symptoms. Features of disease progression may warrant urgent surgical intervention.