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Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation "MSC-FFM"-Outcome Report of 92 Patients.
No full text(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD
Outcomes of patients with Nelson's syndrome after primary treatment: a multicenter study from 13 UK Pituitary centers.
No full textCONTEXT
Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era.
OBJECTIVE
To elucidate tumor control rates, effectiveness of various treatments and markers of prognostic relevance in patients with NS.
PATIENTS, DESIGN, AND SETTING
Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis.
RESULTS
Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n=30, eight patients had two and one had three pituitary operations), surgery+radiotherapy+adrenalectomy (n=17, two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n=2) and adrenalectomy (n=19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (HR 4.6; 95% CI, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor.
CONCLUSIONS
At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis
Comparing the Management of Eye Injuries by Coalition Military Surgeons during the Iraq and Afghanistan Conflicts.
No full textPURPOSE
To compare incidences, ocular injury types, and treatment performed on United States and United Kingdom military service members and host nation civilians within the Iraq and Afghanistan conflicts to inform future military surgical training requirements and military medical planning. The United States routinely deployed ophthalmologists, whereas the United Kingdom did not.
DESIGN
Retrospective cohort study of the United States and United Kingdom military Joint Theatre Trauma Registries.
PARTICIPANTS
All patients with eye injuries treated at a deployed Military Treatment Facility between March 2003 and October 2011.
METHODS
An adjusted multiple logistic regression model was performed using enucleation or evisceration and primary open-globe repair as dependent variables and casualty nationality, location, and the presence of an ophthalmic surgeon as independent variables.
MAIN OUTCOME MEASURES
Incidence of eye removal (enucleation or evisceration) or primary repair for open globe injury.
RESULTS
Five thousand seven hundred nineteen of 67 586 (8%) survivors or those who died of wounds were recorded to have sustained eye injuries. The most common eye injuries were open-globe injury without intraocular foreign body (3201/5719 [56%]). Adnexal injuries (eyelid lacerations and damage to lacrimal apparatus) were recorded in 1265 of 5719 patients (22%). The odds of undergoing evisceration or enucleation for open-globe injury was highest in host nation civilians (odds ratio [OR], 9.23; P < 0.001), but there was no evidence of a difference between United States and United Kingdom military service member casualties (P = 0.38). The presence of an ophthalmic surgeon (OR, 16.3; P < 0.001) significantly affected the odds of eye removal.
CONCLUSIONS
Eye injuries were more likely to have been treated definitively in United States Medical Treatment Facilities (MTFs), reflecting the absence of ophthalmologists in most deployed United Kingdom MTFs. The Iraq and Afghan conflicts were notable for coalition air dominance; the shape of future conflicts may mandate delays in evacuation, which may affect visual outcomes negatively, particularly if primary repair of patients with open-globe injuries is delayed. This study provides evidence to support the maintenance of specialist ophthalmic surgical competencies in deployed coalition MTFs for future conflicts
Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.
No full textCardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated
Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry.
No full textBACKGROUND
This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD).
METHODS
We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model.
RESULTS
The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61).
CONCLUSION
This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality
Global and mitosis-specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging.
No full textAIMS
Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8 edition of the AJCC staging manual was removal of mitotic count. We explore the extent that this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions.
METHODS AND RESULTS
In a cohort of 476 patients with melanoma ≤ 1.0 mm, a mitotic count of 0 vs 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9 to 1.0 mm thick, the mitotic count intra-class correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists across cases (p = 0.04). Every case had a range that crossed the AJCC8 0.8 mm pT1a/pT1b staging boundary. Ulceration was only identified in 2 out the 10 cases. For ulceration, kappa agreement score was 0.31 (fair).
CONCLUSION
This study supports the removal of mitotic count from staging but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value
Geriatric medicine and old age psychiatry joint training pre-feasibility pilot study: an innovative approach to collaborative postgraduate training.
No full textBACKGROUND
Physical and psychological health problems are prevalent in older adults and rarely exist in isolation. Treating these problems in isolation is resourceful and can be potentially harmful to patients due to delays in diagnosis and treatment and incomplete holistic care plans. Historically, trainees in geriatric medicine and old age psychiatry within the United Kingdom have completed very different training programmes.
METHODS
We undertook a pre-feasibility pilot study of collaborative postgraduate training between trainees in geriatric medicine and old age psychiatry within the West Midlands training region, United Kingdom. Trainees in each specialty were paired with each other and advised to arrange appropriate training opportunities for their counterpart; these included shadowing each other in their workplace and arranging opportunities to attend training opportunities with their consultants. Pre- and post-pilot surveys were completed by all trainees and reflections from trainees were collated.
RESULTS
Five trainee pairs were formed and arranged shadowing and training opportunities between October 2017 and May 2018. This included a combination of inpatient, outpatient, and community work. For both specialties, trainees' confidence in topics relating to their counterparts' specialty increased between the pre- and post-pilot surveys. Recurrent themes included within reflections included the benefits of collaborative training.
CONCLUSIONS
Our pilot has demonstrated that it is feasible to implement a programme of joint training into postgraduate medical training, and that this can have a positive impact upon the confidence of both specialties. An extended pilot is planned for the training year 2018-2019
A literature review of the complications following anterior and posterior ankle arthroscopy.
No full textINTRODUCTION
There is a wealth of studies reporting the complications of anterior and posterior ankle arthroscopy. The aim of this study is to summarise and review the complication rate(s) associated with both anterior and posterior ankle arthroscopy, as described in the literature.
MATERIAL AND METHODS
The authors carried out a comprehensive review of the literature up until March 2018. An extensive search of the MEDLINE, Cochrane library and EMBASE databases was undertaken using the following keywords: complications of ankle arthroscopy, anterior ankle arthroscopy, and posterior ankle arthroscopy.
RESULTS
A total of 107 papers were identified and 55 were deemed appropriate for analysis. The overall complication rate of ankle arthroscopy was found to be between 3.4- 9%.
CONCLUSIONS
No life threatening complications were identified in the literature with both anterior and posterior ankle arthroscopy. The commonest complication after anterior and posterior ankle arthroscopy is superficial peroneal nerve injury and temporary Achilles tendon tightness, respectively