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Assessment of Textbook Oncologic Outcomes Following Proctectomy for Rectal Cancer.
No full textBACKGROUND
Outcomes of rectal adenocarcinoma vary considerably. Composite "textbook oncologic outcome" (TOO) is a single metric that estimates optimal clinical performance for cancer surgery.
METHODS
Patients with stage II/III rectal adenocarcinoma who underwent single-agent neoadjuvant chemoradiation and proctectomy within 5-12 weeks were identified in the National Cancer Database (NCDB). TOO was defined as achievement of negative distal and circumferential resection margin (CRM), retrieval of ≥ 12 nodes, no 90-day mortality, and length of stay (LOS) < 75th percentile of corresponding year's range. Multivariable logistic regression was used to identify predictors of TOO.
RESULTS
Among 318,225 patients, 8869 met selection criteria. Median age was 62 years (IQR 54-71), and 5550 (62.6%) were males. Low anterior resection was the most common procedure (LAR, 6,037 (68.1%) and 3084 (34.8%) were treated at a high-volume center (≥ 20 rectal resections/year). TOO was achieved in 3967 patients (44.7%). Several components of TOO were achieved commonly, including negative CRM (87.4%), no 90-day mortality (98.0%), no readmission (93.0%), and no prolonged hospitalization (78.8%). Logistic regression identified increasing age, non-private insurance, low-volume centers, open approach, Black race, Charlson score ≥ 3, and abdominoperineal resection (APR) as predictors of failure to achieve TOO. Over time, TOOs were attained more commonly which correlated with increased minimally invasive surgery (MIS) adoption. TOO achievement was associated with improved survival.
CONCLUSIONS
Rectal adenocarcinoma patients achieve TOO uncommonly. Treatment at high-volume centers and MIS approach were among modifiable factors associated with TOO in this study
Successful use of Rituximab (anti CD20- monoclonal antibody ) for IgA Nephropathy in a patient with recessive dystrophic epidermolysis bullosa (RDEB).
No full textEfficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.
No full textOBJECTIVES
Secondary inefficacy with infusion reactions and anti-drug antibodies (2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanised type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab.
METHODS
We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2x1000mg infusions alongside methylprednisolone 100 mg.
RESULTS
All 9 patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (p= 0.014) and total BILAG-2004 score from 21 to 2 (p= 0.009). Complement C3 and dsDNA titres improved significantly (both p= 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10mg/day), 5/8 had their dose reduced at 6 months. 4/9 patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion including 4/4 assessed with highly-sensitive assays. 1/9 obinutuzumab non-responder required cyclophosphamide therapy. 1 unvaccinated patient died from COVID-19.
CONCLUSIONS
Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanised type-2 anti-CD20 therapy is a logical approach
Propensity Score-Matched Analysis Comparing Robotic and Laparoscopic Right and Extended Right Hepatectomy.
No full textImportance
Laparoscopic and robotic techniques have both been well adopted as safe options in selected patients undergoing hepatectomy. However, it is unknown whether either approach is superior, especially for major hepatectomy such as right hepatectomy or extended right hepatectomy (RH/ERH).
Objective
To compare the outcomes of robotic vs laparoscopic RH/ERH.
Design, Setting, and Participants
In this case-control study, propensity score matching analysis was performed to minimize selection bias. Patients undergoing robotic or laparoscopic RH/EHR at 29 international centers from 2008 to 2020 were included.
Interventions
Robotic vs laparoscopic RH/ERH.
Main Outcomes and Measures
Data on patient demographics, tumor characteristics, and short-term perioperative outcomes were collected and analyzed.
Results
Of 989 individuals who met study criteria, 220 underwent robotic and 769 underwent laparoscopic surgery. The median (IQR) age in the robotic RH/ERH group was 61.00 (51.86-69.00) years and in the laparoscopic RH/ERH group was 62.00 (52.03-70.00) years. Propensity score matching resulted in 220 matched pairs for further analysis. Patients' demographics and tumor characteristics were comparable in the matched cohorts. Robotic RH/ERH was associated with a lower open conversion rate (19 of 220 [8.6%] vs 39 of 220 [17.1%]; P = .01) and a shorter postoperative hospital stay (median [IQR], 7.0 [5.0-10.0] days; mean [SD], 9.11 [7.52] days vs median [IQR], 7.0 [5.75-10.0] days; mean [SD], 9.94 [8.99] days; P = .048). On subset analysis of cases performed between 2015 and 2020 after a center's learning curve (50 cases), robotic RH/ERH was associated with a shorter postoperative hospital stay (median [IQR], 6.0 [5.0-9.0] days vs 7.0 [6.0-9.75] days; P = .04) with a similar conversion rate (12 of 220 [7.6%] vs 17 of 220 [10.8%]; P = .46).
Conclusion and Relevance
Robotic RH/ERH was associated with a lower open conversion rate and shorter postoperative hospital stay compared with laparoscopic RH/ERH. The difference in open conversion rate was associated with a significant decrease for laparoscopic but not robotic RH/ERH after a center had mounted the learning curve. Use of robotic platform may help to overcome the initial challenges of minimally invasive RH/ERH
The diagnosis and management of Cushing's syndrome in pregnancy.
No full textEndogenous Cushing's syndrome (CS) is rarely encountered during pregnancy. Clinical and biochemical changes in healthy pregnancy overlap with those seen in pregnancy complicated by CS; the diagnosis is therefore challenging and can be delayed. During normal gestation, adrenocorticotrophic hormone, corticotrophin-releasing hormone, cortisol, and urinary free cortisol levels rise. Dexamethasone administration fails to fully suppress cortisol in pregnant women without CS. Localisation may be hindered by non-suppressed adrenocorticotrophic hormone levels in a large proportion of those with adrenal CS; smaller corticotroph adenomas may go undetected as a result of a lack of contrast administration or the presence of pituitary hyperplasia; and inferior petrosal sinus sampling is not recommended given the risk of radiation and thrombosis. Yet, diagnosis is essential; active disease is associated with multiple insults to both maternal and foetal health, and those cured may normalise the risk of maternal-foetal complications. The published literature consists mostly of case reports or small case series affected by publication bias, heterogeneous definitions of maternal or foetal outcomes or lack of detail on severity of hypercortisolism. Consequently, conclusive recommendations, or a standardised management approach for all, cannot be made. Management is highly individualised: the decision for surgery, medical control of hypercortisolism or adoption of a conservative approach is dependent on the timing of diagnosis (respective to stage of gestation), the ability to localise the tumour, severity of CS, pre-existing maternal comorbidity, and, ultimately, patient choice. Close communication is a necessity with the patient placed at the centre of all decisions, with risks, benefits, and uncertainties around any investigation and management carefully discussed. Care should be delivered by an experienced, multidisciplinary team, with the resources and expertise available to manage such a rare and challenging condition during pregnancy
Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management.
No full textINTRODUCTION
The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors.
PATIENTS AND METHODS
Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial.
RESULTS
Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks.
CONCLUSION
Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population
Factors Influencing Surgical Outcomes for Intradural Spinal Tumours: A Single-Centre Retrospective Cohort Study.
No full textIntroduction Intradural spinal tumours are relatively uncommon tumours of the central nervous system. In this study, we sought to assess our current practice and determine the factors which affect the surgical outcomes of intradural spinal tumour resection. Methods All consecutive patients who underwent surgical resection of intradural spinal tumours from December 2011 to November 2018 were retrospectively reviewed. The Modified McCormick Scale (MMS) was used to grade patients' neurological status both pre-operatively and at the latest follow-up. The associations between changes in MMS and variables such as patient demographics, tumour location, number and experience of consultants involved in the procedure, use of intraoperative neuro-monitoring, bony spinal exposure and dural closure methods were assessed. A multivariable binary logistic regression model was performed to identify independent predictors of improvements in MMS. All analyses were performed using IBM SPSS 22 (IBM Corp. Armonk, NY), with p<0.05 deemed to be indicative of statistical significance throughout. Results A total of 145 patients met the inclusion criteria, with a median age of 56.5 years; of whom 119 had extramedullary tumours and 26 had intramedullary tumours. Methods of dural closure were variable, and there was an increasing trend over time towards using the laminoplasty approach for bony exposure. Neither the experience of consultants (p=0.991) nor the number of consultants involved (p=0.084) was found to be significantly associated with the change in MMS, with the strongest predictor being the baseline MMS (p<0.001). Patients who had adjuvant therapy were also significantly more likely to have a poorer neurological outcome (p=0.001). Conclusion A good neurological baseline is a significant positive predictor of an improved functional outcome. The number and seniority of consultant surgeons involved in intradural spinal tumour resections did not significantly alter the postoperative outcomes of patients in our single-unit retrospective study
Regional variations in nephrology trainee confidence with clinical skills may relate to the availability of local training opportunities in the UK: results from a national survey.
No full textBACKGROUND
The United Kingdom offers a standardised training program for nephrology fellows. However, local training opportunities vary resulting in mismatches between trainee interests and accessible opportunities. This may impact trainee confidence, satisfaction, and future service provision.
METHODS
A survey assessing confidence with key procedures and sub-specialities was disseminated. Associations with region of training were probed using Chi square tests, with significance set at p < 0.0008 following a Bonferroni correction. Results were compared to trainee views on available opportunities for development.
RESULTS
139 responses were received (32% response rate, demographics representative of the UK nephrology trainee cohort). Procedural independence varied from 98% for temporary femoral vascular catheters to 5% for peritoneal dialysis catheters (PDIs). Independence with inserting tunnelled vascular catheters varied with region (p < 0.0001). Trainees expressed a desire for formal training in kidney ultrasound scanning and PDIs, corresponding with procedures they had least opportunity to become independent with. Trainees felt least confident managing kidney disease in pregnancy. Suggestions for improving training included protected time for garnering sub-speciality knowledge, developing procedural skills and for experiencing practice in other nephrology units.
CONCLUSIONS
A mismatch between trainee interests and professional development opportunities exists, which may threaten trainee autonomy and impact patient care particularly with regards to peritoneal dialysis. Provisions to facilitate trainee directed development need to be made while balancing the rigors of service provision. Such measures could prove critical to promoting trainee well-being and preventing attrition within the nephrology workforce
Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows.
No full textBACKGROUND
The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice.
METHODS
Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2).
RESULTS
We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; =0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; =0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; =0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; =0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; =0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; =0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; =0.047).
CONCLUSIONS
In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials
Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.
No full textBACKGROUND
Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes.
METHODS
Phase 1 is a multicentre open-label dose-escalation pilot trial. Patients will receive a single infusion of REALIST ORBCEL-C (100 × 10 cells, 200 × 10 cells or 400 × 10 cells) in a 3 + 3 design. Phase 2 is a multicentre randomised, triple blind, allocation concealed placebo-controlled trial. Two cohorts of patients, with ARDS due to COVID-19 or ARDS due to other causes, will be recruited and randomised 1:1 to receive either a single infusion of REALIST ORBCEL-C (400 × 10 cells or maximal tolerated dose in phase 1) or placebo. Planned recruitment to each cohort is 60 patients. The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is oxygenation index at day 7. The trial will be reported according to the Consolidated Standards for Reporting Trials (CONSORT 2010) statement.
DISCUSSION
The development and manufacture of an advanced therapy medicinal product to Good Manufacturing Practice standards within NHS infrastructure are discussed, including challenges encountered during the early stages of trial set up. The rationale to include a separate cohort of patients with ARDS due to COVID-19 in phase 2 of the trial is outlined.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03042143. Registered on 3 February 2017. EudraCT Number 2017-000584-33