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Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.
No full textOBJECTIVE
To investigate the effect of low-dose aspirin in primary adult liver transplantation LT on acute cellular rejection ACR as well as arterial patency rates.
BACKGROUND
The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis HAT, although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after liver transplantation has a protective effect against ACR.
METHODS
This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up.
RESULTS
In this cohort of 2,365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1,436 recipients 61%. One-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group HR 0.77, 95% CI 0.63-0.94, p=0.01. One-year primary arterial patency rates were 99% in the aspirin and 96% in the no-aspirin group with a HR of 0.23 95% CI: 0.13-0.40; p<0.001.
CONCLUSION
Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency
Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma.
No full textBACKGROUND
Para-aortic lymph nodes (PALN) are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma (PDAC). The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis, while others not sharing the same results. PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.
AIM
To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.
METHODS
This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020. Statistical comparison of the data between PALN+ and PALN- subgroups, survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed, specifically assessing oncological outcomes such as median overall survival (OS) and disease-free survival (DFS).
RESULTS
81 cases had PALN sampling and 17 (21%) were positive. Pathological N stage was significantly different between PALN+ and PALN- patients ( = 0.005), while no difference was observed in any of the other characteristics. Preoperative imaging diagnosed PALN positivity in one case. OS and DFS were comparable between PALN+ and PALN- patients with lymph node positive disease (OS: 13.2 mo 18.8 mo, = 0.161; DFS: 13 mo 16.4 mo, = 0.179). No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting (OS: 23.4 mo 20.6 mo, = 0.192; DFS: 23.9 mo 20.5 mo, = 0.718). On the contrary, when patients did not receive chemotherapy, PALN disease had substantially shorter OS (5.5 mo 14.2 mo; = 0.015) and DFS (4.4 mo 9.8 mo; < 0.001). PALN involvement was not identified as an independent predictor for OS after multivariable analysis, while it was for DFS doubling the risk of recurrence.
CONCLUSION
PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC, surgery and chemotherapy, and should not be considered as a contraindication to resection
Understanding the Intensive Care Unit Experience of Patients and Relatives at the End-of-Life During the Coronavirus Disease 2019 Pandemic.
No full textThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on patients and relatives' experiences of end-of-life care, as well as changing the provision of these services in intensive care units (ICUs) across the world. Established methods for assisting relatives through the grieving process have required modification due to the unique features and circumstances surrounding deaths from this disease. This mixed-methods study from the United Kingdom (UK) aims to review data from patients who died in a large ICU (the unit had a capacity for more than 100 ventilated patients), over the course of approximately 1 year. The inpatient noting of these patients was reviewed specifically for details of visiting practices, chaplaincy support, and patient positioning (prone vs supine) prior to death. Using this data, recommendations are made to improve end-of-life care services. To allow relatives the opportunity to attend the ICU, there is a need for early recognition of patients approaching the end of life. Clear explanations of the need for prone positioning and increased access to chaplaincy services were also identified
Clinical standards for drug-susceptible pulmonary TB.
No full textThe aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB). A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants. Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB. These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB
Femoral neck system reduces surgical time and complications in adults with femoral neck fractures: A systematic review and meta-analysis.
No full textPurpose
Femoral neck fractures (FNF) in adults are conventionally managed with surgical options. This paper is aimed to assess the safety, and functional outcomes of the novel Femoral neck system (FNS) for FNF treatment in adult population.
Methods
An organized quest of four literature databases (PubMed, Scopus, Web of Science, and Cochrane Library) was performed on March 1, 2022 using the term "femoral neck system". Fixed or random-effect meta-analysis was used to analyse the outcome measures after selecting relevant studies and assessing their quality. Heterogeneity was considered when calculating pooled effect sizes and 95% confidence ranges.
Results
On comparing FNS with cannulated cancellous screws (CCS) or other methods, in a total of 762 patients (351 FNS and 411 CCS) in the 11 comparative studies considered for meta-analysis, blood loss was pointedly higher overall in the FNS group, mean difference 115.77 ml; 95% CI 3.11 ml, 28.42 ml; test of overall effect: z = 1.68, p = 0.09); with considerable heterogeneity. However, in the FNS group the operative time was substantially lower (Mean difference -7.91 min; 95% CI -15.01, -0.80; test of overall effect: z = 2.18, p = 0.03, with marked heterogeneity). Moreover, complications such as infections, non-union, osteonecrosis, implant cut-out were significantly lower in the FNS group with a Mantel Haenszel Odds ratio of 0.20 (95% CI 0.12, 0.34: Z = 6.01, p < 0.0001).
Conclusion
Keeping in mind the heterogenicity of the studies, -management of adult patients with FNF with FNS can provide results comparable to traditional fixation methods with significantly lower rate of complications
Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.
No full textIn March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort
Receptor Status after Neoadjuvant Therapy of Breast Cancer: Significance and Implications.
No full textNeoadjuvant chemotherapy (NACT) is now established in routine management of early breast cancer. Alterations in oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) following NACT are reported, with wide variation in results across series. In larger series, changes in ER status are identified in 5-23%, whilst changes in PR status are more frequent (14.5-67%). HER2 status changes less frequently with loss being more common than gain, and higher rates of change with immunohistochemistry are observed compared to in situ hybridization and following HER2-targeted therapy compared with chemotherapy alone. Triple negative is the most stable molecular subtype with combined ER, and HER2-positive cancers show the highest rate of change. Neoadjuvant endocrine therapy is used less commonly than NACT, and whilst loss of ER is rare, changes in PR status can occur in up to 40% of cases. There is relatively little published data on the impact of change in receptor status on survival outcomes. In patients whose tumours become ER or HER2 positive post-NACT, endocrine or anti-HER2 therapy can be initiated, although evidence from clinical trials is lacking. Most guidelines do not currently recommend routine retesting; however it should be considered in some circumstances
Increased systemic and adipose 11β-HSD1 activity in idiopathic intracranial hypertension.
No full textContext Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown aetiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism yet to be assessed. Objective To determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype. Design A retrospective case-control study and a separate exploratory analysis of a prospective randomised intervention study. Methods The case-control study compared female IIH patients to body mass index, age, and sex-matched controls. The randomised intervention study, different IIH patients were randomized to either a community weight management intervention, or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilising 24-hour urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity. Results Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls. Conclusion We demonstrate that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point towards metabolic dysregulation as a feature of IIH
Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.
No full textBACKGROUND
Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice.
OBJECTIVE
We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors.
MATERIALS AND METHODS
Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBV) and corrected (rCBV) relative cerebral blood volume, and the leakage parameter, K. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types.
RESULTS
Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBV was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBV was higher (mean = 1.49 vs. 0.49; P=0.015) and K lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference.
CONCLUSION
Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors