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Can anesthetic effects and pain treatment influence the long-term prognosis of early-stage lymph node-negative breast cancer after breast-conserving surgery?
No full textBackground
Breast cancer is currently the leading cause of women's death. It is crucial to further improve the approach to treatment and the long-term survival rate of breast cancer patients, and to reduce the rates of recurrence and metastasis. It has been reported that the possibility of tumor metastasis depends on the metastatic potential of the tumor and the host defense against tumor metastasis, in which cellular immunity and the function of natural killer (NK) cells are critical to maintaining this balance. Surgical stress response and postoperative pain inhibit perioperative immune function in patients and increase the likelihood of dissemination and metastasis of cancer cells after cancer surgery. The study aims to investigate the effect of anesthetic factors and pain treatment on the long-term prognosis of patients with early stage lymph node negative breast preservation surgery.
Methods
A total of 337 patients with early-stage lymph node negative breast cancer (ASA I-II) who had undergone successful breast-conserving surgery in our hospital were included in this retrospective analysis. Cases were divided into general anesthesia with postoperative analgesia group (GA + PCA), general anesthesia without postoperative analgesia group (GA), epidural anesthesia with postoperative analgesia group (EA + PCA), and epidural anesthesia without postoperative analgesia group (EA). The 5-year survival rate and 5-year disease-free survival were recorded in the 4 groups.
Results
The general condition and length of hospital stay of the patients were not statistically different between the 4 groups. However, the 5-year survival rate and 5-year disease-free survival rate of the 4 groups were statistically different. The 5-year survival rate and 5-year disease-free survival rate were the lowest in the GA group, while the EA + PCA group had the highest 5-year disease-free survival rate. The 5-year survival rate and 5-year disease-free survival rate in the GA + PCA group were significantly higher than those in the GA group. The 5-year disease-free survival rate in EA group was significantly higher than GA group.
Conclusions
Epidural anesthesia and postoperative pain treatment maybe beneficial to the long-term prognosis of patients with early-stage lymph node-negative breast cancer
Machine Learning for Health: Algorithm Auditing & Quality Control.
No full textDevelopers proposing new machine learning for health (ML4H) tools often pledge to match or even surpass the performance of existing tools, yet the reality is usually more complicated. Reliable deployment of ML4H to the real world is challenging as examples from diabetic retinopathy or Covid-19 screening show. We envision an integrated framework of algorithm auditing and quality control that provides a path towards the effective and reliable application of ML systems in healthcare. In this editorial, we give a summary of ongoing work towards that vision and announce a call for participation to the special issue Machine Learning for Health: Algorithm Auditing & Quality Control in this journal to advance the practice of ML4H auditing
A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial.
No full textRelapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473
Age at onset predicts outcome in aquaporin-4-IgG positive neuromyelitis optica spectrum disorder from a United Kingdom population.
No full textBACKGROUND
There are few studies exploring the prognostic factors in patients with aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD).
OBJECTIVE
To assess the predictors of outcome in patients with AQP4-antibody positive NMOSD from a United Kingdom (UK) population.
METHODS
A retrospective study of 52 patients from 2 neuroscience centres in the UK Midlands.
RESULTS
The most common initial presentations were acute myelitis and optic neuritis, with 22/52 cases (42.3%) each. Relapsing course was seen in 32 patients (61.5%) with mean annualised relapse rate of 0.43 (standard deviation 0.45) and a mean interval time to first relapse of 31 months (range 2-108). The median Expanded Disability Status Scale (EDSS) score at the last follow up was 4 (range 1-9). Age at onset was an independent predictor of disability in the whole cohort of patients with NMOSD. For every 10-year increase in age at disease onset, the risk of developing an EDSS score of ≥4 increased by 34%. Patients who presented initially with a longitudinally extensive transverse myelitis (LETM) showed a higher risk to develop disability, compared to other clinical presentations (median time of 4 years versus 13 years). Late onset (LO-NMOSD) patients were likely to reach an EDSS score of 4 more quickly, compared to early onset (EO-NMOSD) (median time of 7 years versus 13 years). Higher median EDSS score at last follow up was observed in LO-NMOSD compared to EO-NMOSD (6 versus 2).
CONCLUSION
Increasing age at onset and LETM predict disability in AQP-4-IgG positive NMOSD patients
Exploring the awareness, attitudes, and actions (AAA) of UK adults at high risk of severe illness from COVID-19.
No full textBACKGROUND
People at high risk of severe illness from COVID-19 have experienced greater restrictions during the pandemic, yet there is a paucity of research exploring their lived experience.
OBJECTIVES
This study explored the impact of COVID-19 on people identified as at high risk of severe illness by UK Government, and in particular, the impact of the first lockdown on access to healthcare, medications and use of technological platforms.
METHODS
1038 UK adults who identified as at high risk of severe illness from COVID-19 in line with UK Government guidance or self-identified with acute or other chronic health conditions, completed the Awareness, Attitudes and Actions survey which explored the impact of COVID-19 on access to healthcare, management of long-term health condition, mental health, and health behaviours.
RESULTS
Most participants reported feelings of vulnerability, anxiety and isolation, noticed that other people changed their behaviour towards them including a feeling of being stigmatised by people not categorised as high risk. Participants described the largely negative impact that the COVID-19 lockdown had on to health-related behaviours and access to healthcare, which had resulted in large declines in mental health and wellbeing. Participants also indicated disappointment at the UK Governments response and handling of the COVID-19 lockdown.
IMPLICATIONS
This study provides novel evidence of the lived experience of the first COVID-19 lockdown for people identified as at high risk of severe illness. In the context of behavioural health interventions, the ubiquity of digital technologies and their adoption into day-to-day life translates into greater potential reach than traditional interventions, and consequently, greater potential for positive public health impact. Findings should be considered by policymakers and healthcare professionals to support people now and as we transition through the recovery phase with a particular emphasis on supporting mental health and changes to the management of long-term health conditions
International multicentre propensity score-matched analysis comparing robotic versus laparoscopic right posterior sectionectomy.
No full textBACKGROUND
Minimally invasive right posterior sectionectomy (RPS) is a technically challenging procedure. This study was designed to determine outcomes following robotic RPS (R-RPS) and laparoscopic RPS (L-RPS).
METHODS
An international multicentre retrospective analysis of patients undergoing R-RPS versus those who had purely L-RPS at 21 centres from 2010 to 2019 was performed. Patient demographics, perioperative parameters, and postoperative outcomes were analysed retrospectively from a central database. Propensity score matching (PSM) was performed, with analysis of 1 : 2 and 1 : 1 matched cohorts.
RESULTS
Three-hundred and forty patients, including 96 who underwent R-RPS and 244 who had L-RPS, met the study criteria and were included. The median operating time was 295 minutes and there were 25 (7.4 per cent) open conversions. Ninety-seven (28.5 per cent) patients had cirrhosis and 56 (16.5 per cent) patients required blood transfusion. Overall postoperative morbidity rate was 22.1 per cent and major morbidity rate was 6.8 per cent. The median postoperative stay was 6 days. After 1 : 1 matching of 88 R-RPS and L-RPS patients, median (i.q.r.) blood loss (200 (100-400) versus 450 (200-900) ml, respectively; P 500 ml; P = 0.001), need for intraoperative blood transfusion (10.2 versus 23.9 per cent, respectively; P = 0.014), and open conversion rate (2.3 versus 11.4 per cent, respectively; P = 0.016) were lower in the R-RPS group. Similar results were found in the 1 : 2 matched groups (66 R-RPS versus 132 L-RPS patients).
CONCLUSION
R-RPS and L-RPS can be performed in expert centres with good outcomes in well selected patients. R-RPS was associated with reduced blood loss and lower open conversion rates than L-RPS
Prognostic indicators in clinically node-negative malignant primary salivary tumours of the parotid: A multicentre experience.
No full textOBJECTIVES
Nodal metastasis is an important prognosticator in primary parotid cancers. The management of the clinically node-negative neck is an area lacking consensus. This study investigates the occult nodal metastasis rate, and prognostic indicators in primary parotid cancers.
MATERIALS AND METHODS
We performed a multicentre retrospective case note review of patients diagnosed and treated surgically with curative intent between 1997 and 2020. Demographic, clinic-pathological and follow-up data was recorded.
RESULTS
After exclusions, 334 patients were included for analysis, with a median follow-up of 48 months. The overall rate of occult lymph node metastasis amongst patients undergoing elective neck dissection was 22.4%, with older age, high-grade and more advanced primary tumours being associated with higher rates. On multivariable analysis, age ≥ 60 years (HR = 2.69, p = 0.004), high-grade tumours (HR = 2.70, p = 0.005) and advanced primary tumours (pT3-4, HR = 2.06, p = 0.038) were associated with worse overall survival. Occult nodal metastasis on final pathology was associated with a close-to-significant reduction in regional recurrence free survival (HR = 3.18, p = 0.076).
CONCLUSION
This large series confirms the significant occult lymph node metastasis rate in primary parotid cancer, and demonstrates the importance of primary histology, tumour grade and stage in predicting survival outcome. This data supports the use of elective neck dissection in patients with high-risk tumours
Immune tolerance induction in severe haemophilia A: A UKHCDO inhibitor and paediatric working party consensus update.
No full textINTRODUCTION
In good risk patients (historic inhibitor peak < 200BU), the International Immune Tolerance Study demonstrated equal efficacy to induce tolerance between high (200iu/kg/day) and low dose (50iu/kg ×3 times/week) immune tolerance induction (ITI) regimens. However, the trial stopped early on account of the excessive bleed rate in the low dose ITI arm.
METHODS
United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO) Paediatric and Inhibitor working parties considered available ITI data alongside the bi-phenotypic antibody emicizumab (Hemlibra®) efficacy and safety data to develop a consensus guideline for the future UK ITI guideline.
RESULTS
This revision of UKHCDO ITI guidance incorporates the recommendation to use emicizumab as a prophylaxis haemostatic agent to reduce bleeding rates and to facilitate low dose and reduced frequency of FVIII CFC for ITI in the majority of children.
CONCLUSION
This consensus protocol will facilitate future evaluation of ITI outcomes in the evolving landscape of haemophilia therapeutics and ITI strategies
Addressing high-risk antipoaching roles in Central Africa: lessons from delivery of remote advanced first-aid teaching for trauma care and snakebite first aid.
No full textImmune infiltration and prognostic and diagnostic use of LGALS4 in colon adenocarcinoma and bladder urothelial carcinoma.
No full textColon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of colonic adenocarcinoma (COAD). We analysed 17 overlapping gene expression profiles of COAD and healthy samples obtained from TCGA-COAD and public single-cell sequencing resources, to identify potential therapeutic COAD targets. We evaluated the abundance of immune infiltration with those genes using the TIMER (Tumor Immune Estimation Resource) deconvolution method. Subsequently, we developed predictive and survival models to assess the prognostic value of these genes. The LGALS4 (Galectin-4) gene was found to be significantly (P<0.05) downregulated in COAD and bladder urothelial carcinoma (BLCA) compared to healthy samples. We identified LGALS4 as a prognostic and diagnostic marker for multiple cancer types, including COAD and BLCA. Our analysis reveals a series of novel candidate drug targets, as well as candidate molecular markers, that may explain the pathogenesis of COAD and BLCA. LGALS4 gene is associated with multiple cancer types and is a possible prognostic, as well as diagnostic, marker of COAD and BLCA