Somatic and germline analysis of a familial Rothmund-Thomson syndrome in two siblings with osteosarcoma

Rothmund–Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted

Investigating the Tribological Behaviours of a Jet Engine’s Abrasive Rotor and Stator Vane Contact

Plasma-Sprayed ceramic coatings are an appealing alternative to shrouded vane interstage labyrinth seals, as they offer a simpler architecture and a significant drop in aero-engine’s weight. Historically, aero-engine sizes have not allowed manufacturers to mount vanes in cantilever. Due to their length, stresses have had to be diminish by securing their inner ends to a shroud; then using an abradable lining to limit gas recirculation around the stator. Currently, engine sizes have decreased, allowing to improve the weight penalties introduced by this design by removing the shroud and directly applying an abrasive lining on the rotating drum, with sealing achieved by the liner on the drum wearing the stator blades. Whilst abradable based sealing systems where the blade cuts the liner are well researched, little work has been undertaken on abrasive systems where the static blade is now worn. The initial focus of this research has been to develop a high-speed rig and a monitoring system that allows the evaluation of different contact scenarios under more representative in-service conditions. The gathered data, during and post-test, has served to identify metrics that describe the tribological system and holds the opportunity to link aero-engine conditions with the ceramic lining performance. Cutting speed, incursion rate, ceramic material, abrasive surface finish, and coatings’ porosity have been identified as system variables, and a statistically planned test matrix has allowed to identify the significance and dependencies of each, along with building the required knowledge to optimise the tribological system. The wear mechanism was defined as rubbing, with it exhibiting a progressive and thermally driven adhesion. Zirconia’s outcome was dragged down by its low conductivity, whilst alumina was found to delaminate. Extending the arc of contact and triggering surface renewal were seen to delay the progressive process. Further investigation with added porosity (e.g. through polyester) showed that the coating’s microstructure can be tuned for the applied stresses, and when self-renew the outcome does not depend on coatings’ conductivity

Predictors of diffuse alveolar damage in patients with acute respiratory distress syndrome: a retrospective analysis of clinical autopsies

Abstract Background Although diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark. Patients with DAD may have higher mortality than those without DAD. Therefore, we aimed to identify the factors associated with DAD in patients with ARDS. Methods We analyzed autopsy samples of 356 patients who had ARDS at the time of death. DAD was assessed by two pathologists, and ARDS criteria were evaluated by two intensivists. Criteria for severe ARDS included the degree of hypoxemia and the ancillary variables of the current Berlin definition assessed within 48 h before death: radiographic severity, high positive end-expiratory pressure (PEEP) level, and physiological variables (i.e., altered respiratory system compliance and large anatomic dead space). Results After multivariable analysis, high PEEP levels, physiological variables, and opacities involving only three quadrants on chest radiographs were not associated with DAD. The four markers independently associated with DAD were (1) duration of evolution (OR 3.29 [1.95–5.55] for patients with ARDS ≥ 3 days, p < 0.001), (2) degree of hypoxemia (OR 3.92 [1.48–10.3] for moderate ARDS and 6.18 [2.34–16.3] for severe ARDS, p < 0.01 for both), (3) increased dynamic driving pressure (OR 1.06 [1.04–1.09], p = 0.007), and (4) radiographic severity (OR 2.91 [1.47–5.75] for patients with diffuse opacities involving the four quadrants, p = 0.002). DAD was found in two-thirds of patients with a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 100 mmHg and opacities involving the four quadrants. Conclusions In addition to severe hypoxemia, diffuse opacities involving the four quadrants were a strong marker of DAD

Somatic and germline analysis of a familial Rothmund-Thomson syndrome in two siblings with osteosarcoma

Rothmund–Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted

Cirugía en la miocardiopatía hipertrófica obstructiva. Resultados a 10 años

Resumen: Introducción: La miocardiopatía hipertrófica obstructiva es una enfermedad infrecuente, el tratamiento quirúrgico con miectomía septal en grandes centros mejora la clínica y la supervivencia. La miectomía septal y, en ocasiones, el reemplazo valvular mitral son las técnicas fundamentales. Métodos: Análisis retrospectivo de 30 pacientes con miocardiopatía hipertrófica obstructiva operados en nuestro centro (2007-2017). Resultados: El grupo presentaba: edad (media) 67,3 ± 12 años; el 56,7% mujeres; EuroSCORE-LOGÍSTICO 6,3 ± 4,4; septo interventricular 24,9 ± 2,9 mm; movimiento sistólico anterior moderado-severo (43,4%); insuficiencia mitral grado iii (46,7%) y iv (33,3%); enfermedad mitral (calcificación, displasia, prolapso) en 17 (56,7%). Procedimientos: miectomía septal (100%); bypass coronario 8 (26,7%), prótesis aórtica 8 (26,7%). El 26,7% (8) recibió reemplazo valvular mitral por enfermedad valvular y persistencia de insuficiencia mitral. Este grupo tenía insuficiencia mitral más severa y peor grado funcional de forma significativa. Hubo una (3,3%) muerte (hemorragia pulmonar) y 2 (6,7%) reoperados por sangrado. El seguimiento medio fue 43,7 ± 36,3 (mediana 30) meses (máximo 116). El grado funcional pasó de: iv (43,3%) y iii (56,7%) precirugía a ii (24,1%) y i (75,9%) poscirugía (p < 0,0001). El gradiente intraventricular descendió de 106,1 ± 27,5 mmHg (mediana 104,5) a 11,9 ± 7,2 mmHg (mediana 10) (p < 0,0001). A 10 años la supervivencia es del 93,1%; del 87,5% si recibieron prótesis mitral y del 95,2% sin prótesis mitral (p = 0,49). Conclusiones: La degeneración valvular mitral obliga con frecuencia a implante protésico mitral, pero con prótesis mitral o sin ella la cirugía en miocardiopatía hipertrófica obstructiva ofrece buena supervivencia y mejoría clínica a largo plazo. Abstract: Introduction: Obstructive hypertrophic myocardiopathy is an uncommon disease. Surgical treatment with septal myectomy in experienced centres improves clinical outcomes and survival. Septal myectomy and, occasionally, mitral valve replacement are the fundamental techniques. Methods: A retrospective analysis carried out on 30 patients with obstructive hypertrophic myocardiopathy operated in our centre (2007-2017). Results: The group variables were: age (mean) 67.3 ± 12 years; 56.7% women; mean EuroSCORE-Logistic 6.3 ± 4.4; interventricular septum 24.9 ± 2.9 mm; moderate-severe septal anterior movement (43.4%); mitral regurgitation grade III (46.7%) and IV (33.3%); mitral disease (calcification, dysplasia, prolapse) in 17 (56.7%). The procedures performed were: septal myectomy (100%); coronary bypass in 8 (26.7%), and aortic valve replacement in 8 (26.7%). The 26.7% (8) that received mitral valve replacement was due to valvular disease and persistence of mitral regurgitation. This group had more severe mitral regurgitation and a significantly worse functional grade. There was one (3.3%) death due to pulmonary haemorrhage, and 2 (6.7%) patients were re-operated due to bleeding. The mean follow-up was 43.7 ± 36.3 (median 30) months (maximum 116). The functional grade went from: IV (43.3%) and III (56.7%) pre-surgery to II (24.1%) and I (75.9%) post-surgery (P < .0001). The intraventricular gradient decreased from 106.1 ± 27.5 mmHg (median 104.5) to 11.9 ± 7.2 mmHg (median 10) (P < .0001). At 10 years, survival was 93.1%. It was 87.5% if they received a MVR and 95.2% without MVR (P = .49). Conclusions: Mitral valve degeneration often requires an implant, but with or without an mitral valve replacement, surgery in obstructive hypertrophic myocardiopathy offers good survival and long-term clinical improvement. Palabras clave: Miocardiopatía hipertrófica obstructiva, Tratamiento quirúrgico, Miectomía septal, Keywords: Obstructive hypertrophic cardiomyopathy, Surgical treatment, Septal myectom