Donor to recipient age matching in lung transplantation: A European experience.

BACKGROUND: The age profile of organ donors and patients on lung transplantation (LT) waiting lists have changed over time. In Europe, the donor population has aged much more rapidly than the recipient population, making allocation decisions on lungs from older donors common. In this study we assessed the impact of donor and recipient age discrepancy on LT outcomes in the UK and France. METHODS: A retrospective analysis of all adult single or bilateral LT in France and the UK between 2010 and 2021. Recipients were stratified into 3 age author groups: young (≤30 years), middle-aged (30-60) and older (≥60). Their donors were also stratified into 2 groups <60, ≥60. Primary graft dysfunction (PGD) rates and recipient survival was compared between matched and mismatched donor and recipient age groups. Propensity matching was employed to minimize covariate imbalances and to improve the internal validity of our results. RESULTS: Our study cohort was 4,696 lung transplant recipients (LTRs). In young and older LTRs, there was no significant difference in 1 and 5-year post-transplant survival dependent on the age category of the donor. Young LTRs who received older donor grafts had a higher risk of severe grade 3 PGD. CONCLUSION: Our findings show that clinically usable organs from older donors can be utilized safely in LT, even for younger recipients. Further research is needed to assess if the higher rate of PGD3 associated with use of older donors has an effect on long-term outcomes.

The effect of lockdown during SARS-CoV-2 pandemic on maxillofacial injuries in a level I trauma centre: a comparative study.

INTRODUCTION: The SARS-CoV-2 pandemic forced many governments to impose nation-wide lockdowns. Government legislation forced limited travel on the population with restrictions on the normal way of life to limit spread of the SARS-CoV-2 virus. The aim of this study is to explore the effects of lockdown on the presentation of maxillofacial trauma in a level I trauma centre. METHODS: Comparative analysis was carried out using prospective and retrospective review of all consecutive patients admitted with any maxillofacial fracture in the lockdown period between 15th March and 15th June 2020 with the same period in 2019 to a Regional Trauma Maxillofacial Surgery Unit. Data included basic demographics and mechanism of injury including alcohol/drug influence, polytrauma, site of injury and treatment modality including escalation of care. RESULTS: Across both periods, there were a total of one hundred and five (n = 105) recorded episodes of traumatic fractures with fifty-three (n = 53) in the pre-lockdown cohort and fifty-two (n = 52) in the lockdown. Included patients were significantly (p = 0.024) older during lockdown (mean age 41.44 years SD 20.70, range 5-96) with no differences in gender distribution between cohorts (p = 0.270). Patients in lockdown were more likely to be involved in polytrauma (p < 0.05) and have sustained their injury by cycling/running or any outdoor related activity (p = 0.013). Lockdown saw a significant reduction in alcohol and drug related violence (p < 0.05). Significantly more patients required operative management (p = 0.038). CONCLUSION: Local lockdowns form part of the governments public health strategy for managing future outbreaks of SARS-CoV-2. Our study showed no significant reduction in volume of trauma during lockdown. It is vital that hospitals maintain trauma capacity to ensure that patients are treated in a timely manner.

Surgical management of advanced pleomorphic dermal sarcoma of the occipital scalp.

Pleomorphic dermal sarcoma is a rare neoplasm of mesenchymal origin that most commonly affects the head. We describe the presentation of a 61-year-old man with a 10-week history of an exophytic lesion affecting the occipital scalp, demonstrating rapid growth. The final histopathology revealed a completely excised 9cm pleomorphic dermal sarcoma (pT2aN0M0, Stage 3), one of the largest such lesions reported in the literature to date. This patient's management involved a wide local subperiosteal excision onto the cranium, with a reconstruction with an Integra dermal regeneration template (Integra LifeSciences, Princeton, NJ, USA) and healing with secondary intention. This was mainly due to poorly defined clinical margins on primary excision, the potential for further excision of involved margins (later confirmed as not needed) and the patient's comorbidities, making a return to theatre for definitive reconstruction undesirable.

The LeVe CPAP System for Oxygen-Efficient CPAP Respiratory Support: Development and Pilot Evaluation.

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments. Technical Development + Testing: The LeVe ("Light") CPAP system was developed using principles of frugal innovation to produce a solution of low complexity and high resource efficiency. The LeVe system exploits the air flow dynamics of electric fan blowers which are inherently suited to delivery of positive pressure at appropriate flow rates for CPAP. Laboratory evaluation demonstrated that performance of the LeVe system was equivalent to other commercially available systems used to deliver CPAP, achieving a 10 cm H2O target pressure within 2.4% RMS error and 50-70% FiO2 dependent with 10 L/min oxygen from a commercial concentrator. Pilot Evaluation: The LeVe CPAP system was tested to evaluate safety and acceptability in a group of ten healthy volunteers at Mengo Hospital in Kampala, Uganda. The study demonstrated that the system can be used safely without inducing hypoxia or hypercapnia and that its use was well-tolerated by users, with no adverse events reported. Conclusions: To provide respiratory support for the high patient numbers associated with the COVID-19 pandemic, healthcare providers require resource efficient solutions. We have shown that this can be achieved through frugal engineering of a CPAP ventilation system, in a system which is safe for use and well-tolerated in healthy volunteers. This approach may also benefit other respiratory conditions which often go unaddressed in Low and Middle Income Countries (LMICs) for want of context-appropriate technology designed for the limited oxygen resources available.

Adult Comorbidity Evaluation-27 as a predictor of postoperative complications, two-year mortality, duration of hospital stay, and readmission within 30 days in patients with squamous cell carcinoma of the head and neck.

The Adult Comorbidity Evaluation (ACE)-27 is a validated scoring system for comorbid conditions. We have evaluated the correlation between it and the duration of hospital stay, readmission within 30 days, complications, and two-year survival in patients having primary surgical treatment for squamous cell carcinoma (SCC) of the head and neck. We studied patients with SCC who had selective neck dissection, resection of the tumour, and reconstruction between 2007 and 2013. Patients who had palliative procedures were excluded. We studied the casenotes of 231 patients and recorded the following outcome measures: TNM staging, ACE-27 score, number of days spent in hospital, readmission within 30 days, complications, and mortality at two years.The relation between the ACE-27 score and duration of hospital stay was significant (p=0.000001). The relations between complications and ACE-27 score, and complications and tumour stage, were also significant (p<0.002, and p<0.008, respectively). Two year mortality is significantly related to stage of tumour and ACE-27 score (p=0.001 and p=0.000246 respectively). We conclude that ACE-27 is a validated, relevant, scoring system for patients being operated on for SCC of the head and neck. It is a better prognostic indicator of two-year mortality than TNM stage, and is a good reflection of complications. We therefore suggest that it is used when discussing surgical outcomes, taking consent from newly-diagnosed patients, and when calculating the costs of head and neck oncological surgery.

Small bowel obstruction caused by vas deferens: a first documented report.

Small bowel obstruction (SBO) is one of the most common causes for an acute surgical admission. Most of the time SBO is a result of common causes such as postoperative adhesions. However, rare and unusual causes of SBO do exist which can be challenging for surgeons. We report a first documented case of SBO caused by a remnant of the vas deferens in a 24-year-old patient with a history of gastroschisis and left orchidectomy. Clinical presentation, investigations, imaging and management of this case are described. To summarise, clinicians should keep an open mind in dealing with patients with intestinal obstruction due to the rare and atypical causes.

Could Sentinel Skin Transplants Have Some Utility in Solid Organ Transplantation?

Accurate diagnosis of allograft rejection can be hazardous and challenging. A strategy that has emerged from experience with vascularized composite allografts (VCAs) is the use of sentinel skin transplants (SSTs)-portions of donor skin transplanted synchronously to an allograft. Work in nonhuman animal models and experience with VCAs suggest concordance between rejection occurring in the primary allograft and the SST, and that appearance of rejection in the SST may precede rejection in the primary allograft, permitting early therapeutic intervention that may improve outcomes with lower rates of chronic rejection. The encouraging findings reported in VCA transplantation raise the possibility that SST may also be useful in solid organ transplantation. Some evidence is provided by experience with abdominal wall transplantation in some intestinal and multivisceral transplant recipients. Results from those reports raise the possibility that rejection may manifest in the skin component before emergence in the intestinal allograft, providing a "lead time" during which treatment of rejection of the abdominal wall could prevent the emergence of intestinal rejection. It is plausible that these findings may be extrapolated to other solid organ allografts, especially those for which obtaining an accurate diagnosis of acute rejection can be hazardous and challenging, such as the lung or pancreas. However, more data are required to support widespread adoption of this technique.

Dynamic Modeling of the Interaction Between Autophagy and Apoptosis in Mammalian Cells.

Autophagy is a conserved biological stress response in mammalian cells that is responsible for clearing damaged proteins and organelles from the cytoplasm and recycling their contents via the lysosomal pathway. In cases of mild stress, autophagy acts as a survival mechanism, while in cases of severe stress cells may switch to programmed cell death. Understanding the decision process that moves a cell from autophagy to apoptosis is important since abnormal regulation of autophagy occurs in many diseases, including cancer. To integrate existing knowledge about this decision process into a rigorous, analytical framework, we built a mathematical model of cell fate decisions mediated by autophagy. Our dynamical model is consistent with existing quantitative measurements of autophagy and apoptosis in rat kidney proximal tubular cells responding to cisplatin-induced stress.

Influence of thyroid hormone disruption on the incidence of shingles.

The reactivation of dormant alpha-human herpesvirus (αHHV) has been attributed to various causes often referred to as stressors. However, no clinical study investigating the relationship between stressors and reactivation exists in humans at this time. Herpes simplex virus type-1 (HSV-1), an important αHHV, was shown to have its gene expression and replication regulated by thyroid hormone (TH) using molecular biology approaches. Varicella zoster virus (VZV) is categorized in αHHV superfamily and shares similar homology with HSV-1. We hypothesize that a history of TH imbalance may be associated with the incidence of shingles (VZV reactivation). This current pilot study, based on a hospital medical claims database, was conducted as a retrospective case-controlled investigation to determine if a putative link between TH imbalance and incidence of shingles is present. An odds ratio of 2·95 with a χ 2 value of 51·74 was calculated for the total population diagnosed with TH disruption and shingles. Further analyses indicated that African American males exhibited a much higher chance of simultaneous diagnoses. These results show that a TH imbalance history may affect VZV reactivation at different incidence rates in different races and age groups.

Comparison of aldosterone production among human adrenocortical cell lines.

Several human adrenocortical cell lines have been used as model systems for aldosterone production. However, these cell lines have not been directly compared with each other. Human adrenal cell lines SW13, CAR47, the NCI-H295 and its sub-strains and sub-clones were compared with regard to aldosterone production and aldosterone synthase (CYP11B2) expression. Culture media was collected 48 h after incubation, aldosterone secretion was measured and the data were normalized to the amount of cell protein. RNA was isolated for microarray analysis and quantitative RT-PCR (qPCR). The cell lines with the highest aldosterone production were further tested with regard to angiotensin II (Ang II) stimulation. Neither aldosterone nor CYP11B2 transcript were detected in SW13 or CAR47 cells. The aldosterone production by the NCI-H295, H295A, H295R-S1, H295R-S2, H295R-S3, HAC13, HAC15 and HAC50 were 119, 1, 6, 826, 18, 139, 412, and 1 334 (pmol/mg protein/48 h), respectively. H295A and H295R-S1 expressed less CYP11B2 than the commonly used H295R-S3 cells; while NCI-H295, H295R-S2, HAC13, HAC15 and HAC50 expressed 24-, 14-, 3-, 10-, and 35-fold higher CYP11B2 compared with the H295R-S3 cells. When treated with Ang II, NCI-H295, H295R-S2, HAC13, HAC15 and HAC50 showed significantly higher aldosterone production than the basal level (p<0.05). A comparison of the available human adrenal cell lines indicates that the H295R-S2 and the clonal cell lines, HAC13, HAC15 and HAC50 produced the highest levels of aldosterone and responded well to Ang II.

Development of Chitosan-based Dry Powder Inhalation System of Cisplatin for Lung Cancer.

Cisplatin, a platinum compound, exerts its cytotoxic effects by coordinating to DNA where it inhibits both replication and transcription, and induces programmed cell death. It is used in the treatment of non-small cell lung cancer. In the present study, an attempt was made to achieve better treatment of lung cancer by direct lung delivery of cisplatin microparticulate systems, which helps to localize the drug in the lungs, and also provide sustained action. Cisplatin-loaded chitosan microspheres were prepared by emulsification and ionotropic gelation method, and characterized for drug content, particle size, densities, flow properties, moisture content, and surface topography by SEM and in vitro drug release was evaluated in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction (FPF) was determined by using twin stage impinger (TSI). Further stability evaluation of cisplatin-loaded DPI systems was carried out at 25°/60% RH and at 40°/75% RH.