Uncontrolled donation after cardiac death (uDCD) has the potential to ameliorate the shortage of suitable lungs for transplant. To date, no lung transplant data from these donors are available from ...North America. We describe the successful use of these donors using a simple method of in situ lung inflation so that the organ can be protected from warm ischemic injury. Forty‐four potential donors were approached, and family consent was obtained in 30 cases (68%). Of these, the lung transplant team evaluated 16 uDCDs on site, and 14 were considered for transplant pending ex vivo lung perfusion assessment. Five lungs were ultimately used for transplant (16.7% use rate from consented donors). The mean warm ischemic time was 2.8 hours. No primary graft dysfunction grade 3 was observed at 24, 48, or 72 hours after transplant. Median intensive care unit stay was 5 days (range: 2‐78 days), and median hospital stay was 17 days (range: 8‐100 days). The 30‐day mortality was 0%. Four of 5 patients are alive at a median of 651 days (range: 121‐1254 days) with preserved lung function. This study demonstrates the proof of concept and the potential for uDCD lung donation using a simple donor intervention.
The authors describe a successful lung transplantation from uncontrolled donation after cardiac death. Van Raemdonck et al's editorial is on page 1475.
Organ donation after medical assistance in dying (MAID) has only been possible for patients having the MAID procedure performed at a hospital facility due to prohibitive warm ischemic times. Herein, ...we describe a protocol for lung donation following MAID at home and demonstrate excellent postoperative outcomes. Lung donation following MAID at home is possible and should be considered by transplant programs.
This report describes the successful use of lungs from a donor who elected to undergo medically assisted death at home.
Lung donation after medical assistance in dying at home Healey, Andrew; Cypel, Marcelo; Pyle, Helen ...
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
01/2021, Letnik:
21, Številka:
1
Report
Objective
To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved.
Background
Disability in IIH is ...predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need.
Methods
A prospective, open‐label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4‐weekly (assessments were 3‐monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30‐day pretreatment period) compared to 12 months.
Results
Fifty‐five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) 95% CI 10.8 (4.0) 9.5, 11.9, p < 0.001 and MHD reduced by 13.0 (9.5) 10.2, 15.7, p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) 9.6, 15.3, p < 0.001, headache severity (scale 0–10) fell by 1.3 (1.7) 0.9, 1.9, p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) 1.6, 6.9, p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test‐6 score and quality of life Short Form‐36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients).
Conclusions
This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene‐related peptide is likely a modulator driving headache and a useful therapeutic target.
Purpose
Idiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an ...unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets.
Findings
IIH is becoming more common, with the incidence rising in parallel with the global obesity epidemic. Current medical management remains centred around weight management, which is challenging. Metabolic investigations of patients have identified specific androgen profiles in cerebrospinal fluid (CSF), which suggest an endocrine dysfunction impacting CSF secretion in IIH. Glucagon-like peptide-1 (GLP-1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been found to play a role in CSF dynamics in IIH and have formed the basis of the first clinical trials looking at new treatments.
Conclusions
Identification of novel molecular targets thought to underlie IIH pathology is now being translated to clinical trials.
The World Health Organization (WHO) defines an effective round of mass drug administration (MDA) for lymphatic filariasis (LF) as one that reaches at least 65% of the target population. In its first ...round of MDA in 2011-2012, the National Program to Eliminate LF in Haiti achieved a 79% epidemiological coverage in urban Port-au-Prince. In 2013, coverage dropped below the WHO threshold and has declined year-over-year to a low of 41% in 2017. We conducted a retrospective qualitative case study to identify key factors behind the decline in coverage in Port-au-Prince and ways to address them. Our findings suggest that the main contributors to the decline in MDA coverage appear to be the absence of effective documentation of practices, reporting, analysis, and program quality improvement-i.e., learning mechanisms-within the program's MDA design and implementation strategy. In addition to their contribution to the program's failure to meet its coverage targets, these deficits have resulted in a high cost for the MDA campaign in both lost momentum and depleted morale. Through a proposed operating logic model, we explore how the pathway from program inputs to outcomes is influenced by a wide array of mediating factors, which shape potential participants' experience of MDA and, in turn, influence their reasoning and decisions to take, or not take, the pills. Our model suggests that the decisions and behavior of individuals are a reflection of their overall experience of the program itself, mediated through a host of contextual factors, and not simply the expression of a fixed choice or preference. This holistic approach offers a novel and potentially valuable framing for the planning and evaluation of MDA strategies for LF and other diseases, and may be applicable in a variety of global health programs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and ...prevent relapse. OBJECTIVE: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. DESIGN, SETTING, AND PARTICIPANTS: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. INTERVENTIONS: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). MAIN OUTCOMES AND MEASURES: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. RESULTS: Of the 66 female participants (mean SD age, 32.0 7.8 years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −6.0 1.8 cm cerebrospinal fluid CSF; 95% CI, −9.5 to −2.4 cm CSF; P = .001) and at 24 months (adjusted mean SE difference, −8.2 2.0 cm CSF; 95% CI, −12.2 to −4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −7.2 1.8 cm CSF; 95% CI, −10.6 to −3.7 cm CSF; P < .001) and at 24 months (adjusted mean SE difference, −8.7 2.0 cm CSF; 95% CI, −12.7 to −4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean SE difference, −21.4 5.4 kg; 95% CI, −32.1 to −10.7 kg; P < .001) and at 24 months (adjusted mean SE difference, −26.6 5.6 kg; 95% CI, −37.5 to −15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean SE difference, 7.3 3.6; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean SE difference, 10.4 3.8; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02124486
Background
Migraine is a highly prevalent disorder with significant economical and personal burden. Despite the development of effective therapeutics, the causes which precipitate migraine attacks ...remain elusive. Clinical studies have highlighted altered metabolic flux and mitochondrial function in patients. In vivo animal experiments can allude to the metabolic mechanisms which may underlie migraine susceptibility. Understanding the translational relevance of these studies are important to identifying triggers, biomarkers and therapeutic targets in migraine.
Main body
Functional imaging studies have suggested that migraineurs feature metabolic syndrome, exhibiting hallmark features including upregulated oxidative phosphorylation yet depleted available free energy. Glucose hypometabolism is also evident in migraine patients and can lead to altered neuronal hyperexcitability such as the incidence of cortical spreading depression (CSD). The association between obesity and increased risk, frequency and worse prognosis of migraine also highlights lipid dysregulation in migraine pathology. Calcitonin gene related peptide (CGRP) has demonstrated an important role in sensitisation and nociception in headache, however its role in metabolic regulation in connection with migraine has not been thoroughly explored. Whether impaired metabolic function leads to increased release of peptides such as CGRP or excessive nociception leads to altered flux is yet unknown.
Conclusion
Migraine susceptibility may be underpinned by impaired metabolism resulting in depleted energy stores and altered neuronal function. This review discusses both clinical and in vivo studies which provide evidence of altered metabolic flux which contribute toward pathophysiology. It also reviews the translational relevance of animal studies in identifying targets of biomarker or therapeutic development.
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