When pancreata fly: Outcomes and lessons learned from the development of a Pancreas Transplant Import Program.

BACKGROUND: To address long waitlist times and increase pancreas transplantation, our center has implemented a protocol for long-distance importation of pancreata. METHODS: We conducted a retrospective review of pancreas transplantation at our institution from January 1, 2014, the start of our importation program, through September 30, 2021. Outcomes were compared between locally procured grafts and imported grafts, defined as grafts procured greater than 250 nautical miles (NM) from our center. RESULTS: Eighty-one patients underwent pancreas transplantation during the study time period; 19 (23.5%) received imported grafts. There were no significant differences in recipient demographics or type of transplant received. Mean distance of import was 644.2 ± 234.0 NM. Imported grafts were more likely to be from pediatric donors <18 years old (p = .02) and a significantly higher proportion of imported grafts came from donors weighing <30 kg (26.3 vs. 3.2%, p = .007). Cold ischemic time was longer for imported grafts than for local grafts (13.4 ± 2.3 h vs. 9.8 ± 2.2 h, p < .01). There was no significant difference in deaths or graft losses within 90 days or at 1 year between groups. CONCLUSION: Centers should consider expanding criteria for acceptance of imported pancreata to increase the number of transplants and combat organ nonutilization.

The best insulin delivery is a human pancreas.

PURPOSE: We wanted to compare glycemic control post pancreas transplantation with newer therapeutic options. METHODS: We conducted a retrospective analysis of pancreas transplantation at our institution from January 1, 2008, through September 30, 2021. All patients who underwent pancreatic transplantation were 18 years and older. We compared pre-transplant glycemic control of those patients, whether self-monitoring or continuous glucose monitor to their post-transplant glycemic control. Outcomes were assessed by HgbA1C level at evaluation (eval), pretransplant (pre), within the first 5 months posttransplant (post) and 1 year post transplant (1 year). RESULTS: One hundred and thirty-four patients underwent pancreas transplantation during the 14-year study period. Overall, 1-year patient and graft survival were 95% and 88%. The mean HgbA1C (%) for eval and pre were 8.5(SD ± 1.7) and 8.3(SD ± 1.7), which was significantly higher than post, and 1 year at 5.1(SD ± .6, p < .01) and 5.2(SD ± .6, p < .01). Of those, 38 patients presented with continuous glucose monitors (CGM) +/- pump. Their mean HgbA1C(%) was 8.2(SD ± 1.5) at eval 8.1(SD ± 1.3). These were also significantly higher than post 5.0(SD ± .6, p < .01), and 1 year 5.1(SD ± .5, p < .01). CONCLUSION: Pancreas transplant provides superior glycemic control to continuous glucose monitoring and remains the optimal therapy for appropriately selected patients with diabetes.

Access to kidney transplantation among pediatric candidates with prior solid organ transplants in the United States.

BACKGROUND: Pediatric kidney transplant candidates require timely access to transplant to optimize growth and neurodevelopmental outcomes. We studied access to transplant for pediatric candidates with prior organ transplants. METHODS: We used US registry data to identify pediatric kidney transplant candidates added to the waiting list 2015-2019 and used competing risk regression to study the association between prior transplant status and probability of receiving a kidney transplant, treating wait-list removal and death as competing events. RESULTS: Of 4962 pediatric kidney transplant candidates included, 89% had no prior transplant and 11% had received a prior organ transplant (kidney 87%, liver 5%, heart 5%). Prior transplant recipients were older at listing (median 15 vs. 12 years) and more likely to have PRA≥98% (22% vs. 0.3%) (both p < .001). There was no significant difference in the proportion of candidates from each group who were preemptively wait-listed. Unadjusted competing risk regression showed a lower risk of kidney transplant after wait-listing among candidates with prior organ transplant (HR 0.52, 95%CI 0.47-0.59, p < .001). This association remained significant after adjusting for candidate characteristics (HR 0.73, 95%CI 0.63-0.83, p < .001). Among deceased donor kidney recipients, median KDPI was similar between groups, but recipients with prior transplants were more likely to receive kidneys from donors with hypertension (4% vs. 1%, p = .01) and donors after cardiac death (11% vs. 4%, p < .001). CONCLUSIONS: Pediatric kidney transplant candidates with prior organ transplants have reduced access to transplant after wait-listing. Allocation system changes are needed to improve timely access to transplant for this vulnerable group.

Space-time dynamics in monitoring neotropical fish communities using eDNA metabarcoding.

The biodiverse Neotropical ecoregion remains insufficiently assessed, poorly managed, and threatened by unregulated human activities. Novel, rapid and cost-effective DNA-based approaches are valuable to improve understanding of the biological communities and for biomonitoring in remote areas. Here, we evaluate the potential of environmental DNA (eDNA) metabarcoding for assessing the structure and distribution of fish communities by analysing water and sediment from 11 locations along the Jequitinhonha River catchment (Brazil). Each site was sampled twice, before and after a major rain event in a five-week period and fish diversity was estimated using high-throughput sequencing of 12S rRNA amplicons. In total, 252 Molecular Operational Taxonomic Units (MOTUs) and 34 fish species were recovered, including endemic, introduced, and previously unrecorded species for this basin. Spatio-temporal variation of eDNA from fish assemblages was observed and species richness was nearly twice as high before the major rain event compared to afterwards. Yet, peaks of diversity were primarily associated with only four of the locations. No correlation between ß-diversity and longitudinal distance or presence of dams was detected, but low species richness observed at sites located near dams might that these anthropogenic barriers may have an impact on local fish diversity. Unexpectedly high α-diversity levels recorded at the river mouth suggest that these sections should be further evaluated as putative "eDNA reservoirs" for rapid monitoring. By uncovering spatio-temporal changes, unrecorded biodiversity components, and putative anthropogenic impacts on fish assemblages, we further strengthen the potential of eDNA metabarcoding as a biomonitoring tool, especially in regions often neglected or difficult to access.

From metabarcoding to metaphylogeography: separating the wheat from the chaff.

Metabarcoding is by now a well-established method for biodiversity assessment in terrestrial, freshwater, and marine environments. Metabarcoding data sets are usually used for α- and ß-diversity estimates, that is, interspecies (or inter-MOTU [molecular operational taxonomic unit]) patterns. However, the use of hypervariable metabarcoding markers may provide an enormous amount of intraspecies (intra-MOTU) information-mostly untapped so far. The use of cytochrome oxidase (COI) amplicons is gaining momentum in metabarcoding studies targeting eukaryote richness. COI has been for a long time the marker of choice in population genetics and phylogeographic studies. Therefore, COI metabarcoding data sets may be used to study intraspecies patterns and phylogeographic features for hundreds of species simultaneously, opening a new field that we suggest to name metaphylogeography. The main challenge for the implementation of this approach is the separation of erroneous sequences from true intra-MOTU variation. Here, we develop a cleaning protocol based on changes in entropy of the different codon positions of the COI sequence, together with co-occurrence patterns of sequences. Using a data set of community DNA from several benthic littoral communities in the Mediterranean and Atlantic seas, we first tested by simulation on a subset of sequences a two-step cleaning approach consisting of a denoising step followed by a minimal abundance filtering. The procedure was then applied to the whole data set. We obtained a total of 563 MOTUs that were usable for phylogeographic inference. We used semiquantitative rank data instead of read abundances to perform AMOVAs and haplotype networks. Genetic variability was mainly concentrated within samples, but with an important between seas component as well. There were intergroup differences in the amount of variability between and within communities in each sea. For two species, the results could be compared with traditional Sanger sequence data available for the same zones, giving similar patterns. Our study shows that metabarcoding data can be used to infer intra- and interpopulation genetic variability of many species at a time, providing a new method with great potential for basic biogeography, connectivity and dispersal studies, and for the more applied fields of conservation genetics, invasion genetics, and design of protected areas.

The impact of bariatric surgery on the resolution of obstructive sleep apnoea.

OBJECTIVE: Obesity is associated with a high incidence of obstructive sleep apnoea (OSA). Bariatric surgery is postulated to lead to OSA resolution, but there is inconclusive evidence on its efficacy. We used objective measurements to determine the rate of resolution or improvement of OSA in patients who had bariatric procedures in our unit. RESULTS: Data was analysed on all patients with OSA who underwent bariatric procedures [laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG)] between June 2012 and September 2016 in our unit. 47 patients (26.7%) were diagnosed with OSA. Mean age was 48.5 years. 63.8% were female. 43 required nocturnal continuous positive airway pressure (CPAP) support. Procedures were LRYGB (n = 26) and LSG (n = 21). Mean excess weight loss was 56.1%. Mean start apnoea-hypopnoea index (AHI) on CPAP was 6.4 events/hr and end AHI was 1.4 events/h. 14 patients (32.6%) had complete OSA resolution and 12 (27.9%) showed improvement in pressure support requirements. We demonstrated that 55.3% of patients had resolution or improvement in OSA following bariatric surgery. However, there was a high rate of non-attendance of follow-up appointments. Future efforts will involve analysis of the reasons for this to ensure more robust monitoring.

A Chemical-Biological-Radio-Nuclear (CBRN) Filter can be Added to the Air-Outflow Port of a Ventilator to Protect a Home Ventilated Patient From Inhalation of Toxic Industrial Compounds.

OBJECTIVES: Chemical-biological-radio-nuclear (CBRN) gas masks are the standard means for protecting the general population from inhalation of toxic industrial compounds (TICs), for example after industrial accidents or terrorist attacks. However, such gas masks would not protect patients on home mechanical ventilation, as ventilator airflow would bypass the CBRN filter. We therefore evaluated in vivo the safety of adding a standard-issue CBRN filter to the air-outflow port of a home ventilator, as a method for providing TIC protection to such patients. METHODS: Eight adult patients were included in the study. All had been on stable, chronic ventilation via a tracheostomy for at least 3 months before the study. Each patient was ventilated for a period of 1 hour with a standard-issue CBRN filter canister attached to the air-outflow port of their ventilator. Physiological and airflow measurements were made before, during, and after using the filter, and the patients reported their subjective sensation of ventilation continuously during the trial. RESULTS: For all patients, and throughout the entire study, no deterioration in any of the measured physiological parameters and no changes in measured airflow parameters were detected. All patients felt no subjective difference in the sensation of ventilation with the CBRN filter canister in situ, as compared with ventilation without it. This was true even for those patients who were breathing spontaneously and thus activating the ventilator's trigger/sensitivity function. No technical malfunctions of the ventilators occurred after addition of the CBRN filter canister to the air-outflow ports of the ventilators. CONCLUSIONS: A CBRN filter canister can be added to the air-outflow port of chronically ventilated patients, without causing an objective or subjective deterioration in the quality of the patients' mechanical ventilation. (Disaster Med Public Health Preparedness. 2018;12:739-743).

Impact of adding a filter for protection from toxic inhalational compounds to the ventilation circuit of mechanically ventilated patients.

BACKGROUND: Standard-issue Chemical-Biological-Radio-Nuclear (CBRN) gasmasks, as used for protection from non-conventional warfare agents or toxic industrial compounds, cannot be used by ventilated patients, leaving them exposed to toxic agents inhaled via their ventilators. This study was conducted to determine the safety of a CBRN filter added to the patient circuit of a ventilator, as a method for affording inhalational protection to ventilated patients. METHODS: A Landrace pig was ventilated sequentially with 3 types of ventilators according to 17 different ventilation protocols, with and without a CBRN filters added in-line to the ventilation tubing for each protocol. For each protocol, physiological parameters, including oxygen saturation, inspired CO2, end tidal CO2, inspired oxygen, respiratory rate, and pulse rate, as well as airflow parameters including peak inspiratory pressure, positive end expiratory pressure and tidal volume were measured. The impact on the ventilator's trigger/sensitivity function was evaluated in vitro using a Michigan test lung. RESULTS: On average, the addition of the CBRN filter resulted in a 16 ml (5 %) decrease (range 0-50 ml) in the tidal volume, a 1.7 cm H2O (10 %) decrease (range 1-3 cm H2O) in the peak inspiratory pressure, and a 0.1 cm H2O (3 %) decrease (range 0-1 cm H2O) in the positive end expiratory pressure delivered to the animal. Some ventilators compensated for these airflow changes while others did not, depending on the design of the ventilator's pressure/flow sensing mechanism. Significant rebreathing occurred when the filter was positioned directly on the animal's endotracheal tube, but not when positioned on the air outflow port of the ventilator. In vitro measurements showed that the addition of the CBRN filter added a mean pressure gradient of 0.45 cm H2O to the trigger/sensitivity function of the system. CONCLUSIONS: In-line addition of a CBRN filter to ventilation tubing is a feasible strategy for affording inhalational protection to ventilated patients.

Deep-Sea, Deep-Sequencing: Metabarcoding Extracellular DNA from Sediments of Marine Canyons.

Marine sediments are home to one of the richest species pools on Earth, but logistics and a dearth of taxonomic work-force hinders the knowledge of their biodiversity. We characterized α- and ß-diversity of deep-sea assemblages from submarine canyons in the western Mediterranean using an environmental DNA metabarcoding. We used a new primer set targeting a short eukaryotic 18S sequence (ca. 110 bp). We applied a protocol designed to obtain extractions enriched in extracellular DNA from replicated sediment corers. With this strategy we captured information from DNA (local or deposited from the water column) that persists adsorbed to inorganic particles and buffered short-term spatial and temporal heterogeneity. We analysed replicated samples from 20 localities including 2 deep-sea canyons, 1 shallower canal, and two open slopes (depth range 100-2,250 m). We identified 1,629 MOTUs, among which the dominant groups were Metazoa (with representatives of 19 phyla), Alveolata, Stramenopiles, and Rhizaria. There was a marked small-scale heterogeneity as shown by differences in replicates within corers and within localities. The spatial variability between canyons was significant, as was the depth component in one of the canyons where it was tested. Likewise, the composition of the first layer (1 cm) of sediment was significantly different from deeper layers. We found that qualitative (presence-absence) and quantitative (relative number of reads) data showed consistent trends of differentiation between samples and geographic areas. The subset of exclusively benthic MOTUs showed similar patterns of ß-diversity and community structure as the whole dataset. Separate analyses of the main metazoan phyla (in number of MOTUs) showed some differences in distribution attributable to different lifestyles. Our results highlight the differentiation that can be found even between geographically close assemblages, and sets the ground for future monitoring and conservation efforts on these bottoms of ecological and economic importance.

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London.

BACKGROUND: Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging. AIMS: Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data. METHODS: All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4-5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a 'care package' for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance. RESULTS: The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base. CONCLUSIONS: Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians.

Overdrinking-induced hyponatraemia in the 2007 London Marathon.

We report a case of overdrinking-induced hyponatraemia from the 2007 London Marathon. The patient was a 37-year-old experienced female marathon runner. She was brought to the emergency room more than 6 h after completing the marathon suffering from diarrhoea, vomiting and confusion, and was unable to recall any detail of the race. An arterial blood sample confirmed hyponatraemia ([Na(+)] 117 mmol.l(-1)) associated with hypokalaemia (serum potassium concentration 3.4 mmol.l(-1)) and respiratory alkalosis (pH 7.62, bicarbonate 16.1 mmol.l(-1) and Pco(2) 2.14 kPa). A diagnosis of uncomplicated exercise-associated hyponatraemia due to voluntary overdrinking was made and the patient was catherised and treated with a slow (1 h) intra-venous infusion of 500 ml of 1.8% sodium chloride (NaCl) solution. The following morning her serum [Na(+)] had normalised at 135 mmol.l(-1) and she was discharged in the afternoon. She has recovered fully without sequelae.

Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease.

Relationships between high-resolution computed tomography (HRCT) findings in chronic obstructive pulmonary disease (COPD) and bacterial colonization, airway inflammation, or exacerbation indices are unknown. Fifty-four patients with COPD (mean [SD]: age, 69 [7] years; FEV(1), 0.96 [0.33] L; FEV(1) [percent predicted], 38.1 [13.9]%; FEV(1)/forced vital capacity [percent predicted], 40.9 [11.8]%; arterial partial pressure of oxygen, 8.77 [1.11] kPa; history of smoking, 50.5 [33.5] smoking pack-years) underwent HRCT scans of the chest to quantify the presence and extent of bronchiectasis or emphysema. Exacerbation indices were determined from diary cards over 2 years. Quantitative sputum bacteriology and cytokine measurements were performed. Twenty-seven of 54 patients (50%) had bronchiectasis on HRCT, most frequently in the lower lobes (18 of 54, 33.3%). Patients with bronchiectasis had higher levels of airway inflammatory cytokines (p = 0.001). Lower lobe bronchiectasis was associated with lower airway bacterial colonization (p = 0.004), higher sputum interleukin-8 levels (p = 0.001), and longer symptom recovery time at exacerbation (p = 0.001). No relationship was seen between exacerbation frequency and HRCT changes. Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.

Relationship between chronic nasal and respiratory symptoms in patients with COPD.

The relationship between the upper and lower airways in chronic obstructive pulmonary disease (COPD) is unknown. We examined the prevalence of chronic nasal symptoms and the correlation with lower respiratory symptoms and parameters of severity of COPD such as exacerbation frequency and spirometry. 61 COPD patients from the East London COPD cohort were studied. [Mean (SD) age 70 (6.96) years, FEV1 0.98 (0.38) l, FVC 2.45 (0.72) l, FEV1%Pred 37.0 (12.3), and 47.6 (31.8) smoking pack years, 14 current smokers, 36 males]. COPD patients had a high prevalence of nasal symptoms (75%), more than half reporting nasal discharge (52.5%) and sneezing (45.9%). Associations were found between nasal score and daily sputum production (P = 0.005) and post-nasal drip and sputum production (P = 0.046) with a trend to increased nasal symptoms in frequent exacerbators compared to infrequent exacerbators. No significant relationship was found between nasal symptoms and FEV1 or any other lower respiratory airway symptom. Associations between nasal and respiratory symptoms were found suggesting that there is a relationship between the upper and lower airway in COPD.

Spirocyclic NK(1) antagonists II: [4.5]-spiroethers.

A series of novel spiroether-based neurokinin-1 (NK(1)) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration.

Spirocyclic NK(1) antagonists I: [4.5] and [5.5]-spiroketals.

A series of novel spiroketal-based NK(1) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration.