Background
The largest age group among children and adolescents referred for lung transplantation for cystic fibrosis (CF) have been those in the pubertal or postpubertal age range. However, over 100 ...younger patients with CF have undergone lung transplantation over the last three decades in the United States.
Methods
We performed a retrospective review of our experience with 18 children with CF who underwent lung transplantation in our center before the age of 11 years and compared them to our older CF lung transplant recipients and our larger CF Center population.
Results
The transplant population was demographically distinct from our CF center in terms of ethnicity, country of origin, and insurance status. Other notable findings were a high prevalence of methicillin‐resistant Staphylococcus aureus, a high prevalence of CF‐related diabetes mellitus, and a high prevalence of consolidated lobar or whole lung disease. Posttransplant outcomes were comparable to those older than 10 years of age in our center until 5 years after transplant after which the younger cohort showed a superior enduring survival.
Conclusions
In an era of increasingly effective medications modifying the natural history of CF, identification of risk factors for early severe lung disease in CF remains relevant to permit interventions to prevent or postpone the time of future lung transplantation.
Pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterial hypertension (PAH) show similarities to cancer cells. Due to the growth-suppressive and pro-apoptotic effects of p53 and its ...inactivation in cancer, we hypothesized that the p53 pathway could be altered in PAH. We therefore explored the involvement of p53 in the monocrotaline (MCT) rat model of pulmonary hypertension (PH) and the pathophysiological consequences of p53 inactivation in response to animal treatment with pifithrin-α (PFT, an inhibitor of p53 activity).
PH development was assessed by pulmonary arterial pressure, right ventricular hypertrophy and arterial wall thickness. The effect of MCT and PFT on lung p53 pathway expression was evaluated by western blot. Fourteen days of daily PFT treatment (2.2 mg/kg/day), similar to a single injection of MCT (60 mg/kg), induced PH and aggravated MCT-induced PH. In the first week after MCT administration and prior to PH development, p53, p21 and MDM2 protein levels were significantly reduced; whereas PFT administration effectively altered the protein level of p53 targets. Anti-apoptotic and pro-proliferative effects of PFT were revealed by TUNEL and MTT assays on cultured human PA-SMCs treated with 50 μM PFT.
Pharmacological inactivation of p53 is sufficient to induce PH with a chronic treatment by PFT, an effect related to its anti-apoptotic and pro-proliferative properties. The p53 pathway was down-regulated during the first week in the rat MCT model. These in vivo experiments implicate the p53 pathway at the initiation stages of PH pathogenesis.
Pediatric pulmonary hypertension (PAH) is a rare disease that carries a poor prognosis if left untreated. Although there are published guidelines for the treatment of children with pulmonary ...hypertension, due to the limited number of robust pediatric clinical trials, recommendations are often based on limited data or clinical experience. Furthermore, many practical aspects of care, particularly for the pediatric patient, are learned through experience and best navigated with a multidisciplinary team. While newer PAH therapies have been approved for adults, there is still limited but expanding experience in pediatrics. This new information will help improve the targets of goal‐oriented therapy. Lastly, this review highlights practical aspects in the use of the different therapies available for the treatment of pediatric pulmonary hypertension.
The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and ...additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT).
We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021.
One hundred grafts from 14 donor hospitals were accepted by 6 LT centers. The median duration of the agonal phase was 20 minutes 2-166. The median duration from circulatory arrest to pulmonary flush was 62 minutes 20-90. Ten lung grafts were not retrieved due to prolonged agonal phases (n = 3), failure of NRP insertion (n = 5), or poor in situ evaluation (n = 2). The remaining 90 lung grafts were all evaluated on EVLP, with a conversion rate of 84% and a cDCD transplantation rate of 76%. The median total preservation time was 707 minutes 543-1038. Seventy-one bilateral LTs and 5 single LTs were performed for chronic obstructive pulmonary disease (n = 29), pulmonary fibrosis (n = 21), cystic fibrosis (n = 15), pulmonary hypertension (n = 8), graft-versus-host disease (n = 2), and adenosquamous carcinoma (n = 1). The rate of PGD3 was 9% (n = 5). The 1-year survival rate was 93.4%.
After initial acceptance, cDCD lung grafts led to LT in 76% of cases, with outcomes similar to those already reported in the literature. The relative impacts of NRP and EVLP on the outcome following cDCD LT should be assessed prospectively in the context of comparative studies.
Pleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented.
We conducted a nation-wide multicentric ...retrospective study in patients who underwent lung or heart-lung transplantation for chronic end-stage lung disease secondary to PPFE between 2012 and 2022 in France.
Thirty-one patients were included. At transplantation, median age was 48 years IQR 35–55. About 64.5% were women. Twenty-one (67.7%) had idiopathic PFFE. Sixteen (52%) had bilateral LT, 10 (32%) had single LT, 4 (13%) had lobar transplantation and one (3%) had heart-lung transplantation. Operative mortality was 3.2%. Early mortality (<90 days or during the first hospitalization) was 32%. Eleven patients (35.5%) underwent reoperation for hemostasis. Eight (30.8%) experienced bronchial complications. Mechanical ventilation time was 10 days IQR 2–55. Length of stay in intensive care unit and hospital were 34 IQR 18–73 and 64 IQR 36–103 days, respectively. Median survival was 21 months. Post-transplant survival rates after 1, 2, and 5 years were 57.9%, 42.6% and 38.3% respectively. Low albuminemia (p = 0.046), FVC (p = 0.021), FEV1 (p = 0.009) and high emergency lung transplantation (p = 0.04) were associated with increased early mortality. Oversized graft tended to be correlated to a higher mortality (p = 0.07).
LT for PPFE is associated with high post-operative morbi-mortality rates. Patients requiring high emergency lung transplantation with advanced disease, malnutrition, or critical clinical status experienced worse outcomes.
NCT05044390.
T4 non-small cell lung carcinomas (NSCLC) were deemed unresectable. Advances in surgery have challenged this dogma. We describe technical aspects and result on superior vena cava (SVC), carinal, ...thoracic inlet tumor surgeries, and resection under cardiopulmonary bypass (CPB). SVC reconstruction requires hemodynamic control to reverse SVC clamping cerebral effects and excellent cephalic venous bed patency. Among 50 SVC resections, including 25 carinal pneumonectomies, post-operative mortality rate was 8%. In the N0–N1 group, 5- and 10-year survival rates were 46.6 and 37.7%, respectively. Right carinal pneumonectomy was performed through right thoracotomy. Sternotomy was favored for left carinal pneumonectomy or carinal resection alone. Among 138 carinal resections, including eight right upper lobectomies, 123 right pneumonectomies, four left pneumonectomies, and three isolated carinal resections, the post-operative mortality rate was 9.4%. In the N0–N1 patients, 5-year survival rate was 47%. 191 patients underwent resections of thoracic inlet tumors through a transclavicular cervicothoracic anterior approach combined in 63 patients with a posterior midline incision for limited spine invasion. In N0–N1 group, 5- and 10-year survival rates were 41.5 and 29.7%, respectively. CPB allowed resection of tumors invading the heart or great vessels in 13 patients. R0 resection and post-operative mortality rate were 94.4 and 5.5%, respectively. In this series of 388 T4 NSCLC, the post-operative mortality rate was 4%. In the R0 and N0–N1 groups, the 5-year survival rates were 44 and 41%, respectively. Surgical resection of T4 locally advanced NSCLC is worth being performed in selected N0–N1 patients, provided that a radical resection is expected.
Cystic Fibrosis Foundation guidelines recommend annual diabetes screening by oral glucose tolerance test (OGTT) in pediatric patients with cystic fibrosis (CF) starting at the age of 10 years. ...Adherence to these guidelines proves to be challenging, and the nationwide screening rates are still considered suboptimal. The aim of this study was to assess and improve the screening rates at our large pediatric center.
A 4-year retrospective audit of OGTT completion among pediatric patients with CF of age ≥10 years who are not yet diagnosed with diabetes was conducted. A collaborative working group was formed to identify the barriers to screening and formulate a quality improvement plan, which was monitored and evaluated for a 9-month period.
Diabetes screening rates determined by OGTT completion at our center showed a gradual decline during the COVID-19 pandemic from 2019 to 2022. Following the implementation of the quality improvement plan during the summer of 2023, there was a marked increase in OGTT ordering compliance by providers as well as test completion by patients. Notably, the fractional OGTT completion rate rose from 45% during the preintervention phase (January-April 2023) to 70% during the postintervention phase (May-September 2023).
Diabetes screening in pediatric patients with CF can be effectively improved by refining practices related to patient experience, care coordination, and laboratory testing strategies.
Radiotherapy for Tracheal–Bronchial Cystic Adenoid Carcinomas Levy, A.; Omeiri, A.; Fadel, E. ...
Clinical oncology (Royal College of Radiologists (Great Britain)),
January 2018, 2018-Jan, 2018-01-00, 2018-01, Volume:
30, Issue:
1
Journal Article
Peer reviewed
Primary tracheal–bronchial adenoid cystic carcinoma (thoracic adenoid cystic carcinoma; TACC) is a rare and aggressive malignant tumour. Radiotherapy results have not been previously individualised ...in this setting.
Records of 31 patients with TACC (74% tracheal and 26% bronchial) who received radiotherapy between February 1984 and September 2014 were retrospectively analysed.
Surgical removal of the primary tumour was carried out for most (71%) patients, and 13/22 (59%) had R1 or R2 (1/22) margins. The mean tumour size was 4.1 cm, 10 (32%) had associated lymph node involvement and 13 (41%) had perineural invasion (PNI). Adjuvant and definitive radiotherapy were delivered for 22 (71%) and nine patients, respectively. The mean delivered dose was 62 Gy (40–70 Gy) and eight patients had a radiotherapy boost (mean 19 Gy, range 9–30 Gy, two with endobronchial brachytherapy). At a median follow-up of 5.7 years, the 5 year overall survival and progression-free survival (PFS) rates were 88% and 61%, respectively. There were three local relapses and 10 metastatic relapses (mean delay 3.2 years), resulting in 5 year local and metastatic relapse rates of 10% and 26%, respectively. The prognostic factors in the univariate analysis for both decreased overall survival and PFS were: age ≥50 years (hazard ratio 6.2 and 3.8) and the presence of PNI (hazard ratio 10.3 and 4.1); and for PFS only: a radiotherapy dose ≤ 60 Gy (hazard ratio 3.1). Late toxicities were: tracheotomy due to symptomatic tracheal stenosis (n = 5), G3 dyspnoea (n = 4), hypothyroidism (n = 5) and pericarditis (n = 4).
Radiotherapy dose may affect local control and the presence of PNI should be considered as an adverse prognostic factor. TACC irradiation conferred good local control rates, when comparing these results with historical series.
•Retrospective study of patients with thoracic adenoid cystic carcinoma (TACC).•With median follow-up of 5.7 years, the 5 year OS and PFS rates were 88% and 61%, respectively.•There were three local relapses and 10 metastatic relapses.•Age ≥ 50 years, perineural invasion and radiotherapy dose ≤ 60 Gy were associated with decreased PFS.•TACC irradiation conferred good local control rates.
Nanonetworks consist of nano-sized communicating devices which are able to perform simple tasks at the nanoscale. The limited capabilities of individual nanomachines and the Terahertz (THz) band ...channel behavior lead to error-prone wireless links. In this paper, a cross-layer analysis of error-control strategies for nanonetworks in the THz band is presented. A mathematical framework is developed and used to analyze the tradeoffs between Bit Error Rate, Packet Error Rate, energy consumption and latency, for five different error-control strategies, namely, Automatic Repeat reQuest (ARQ), Forward Error Correction (FEC), two types of Error Prevention Codes (EPC) and a hybrid EPC. The cross-layer effects between the physical and the link layers as well as the impact of the nanomachine capabilities in both layers are taken into account. At the physical layer, nanomachines are considered to communicate by following a time-spread on-off keying modulation based on the transmission of femtosecond-long pulses. At the link layer, nanomachines are considered to access the channel in an uncoordinated fashion, by leveraging the possibility to interleave pulse-based transmissions from different nodes. Throughout the analysis, accurate path loss, noise and multi-user interference models, validated by means of electromagnetic simulation, are utilized. In addition, the energy consumption and latency introduced by a hardware implementation of each error control technique, as well as, the additional constraints imposed by the use of energy-harvesting mechanisms to power the nanomachines, are taken into account. The results show that, despite their simplicity, EPCs outperform traditional ARQ and FEC schemes, in terms of error correcting capabilities, which results in further energy savings and reduced latency.
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