Cardiopulmonary exercise testing, computed tomography-derived body composition, systemic inflammation and survival after elective abdominal aortic aneurysm repair: A retrospective cohort study.

BACKGROUND: Cardio-pulmonary exercise testing (CPEX) is selectively used before intervention for abdominal aortic aneurysm (AAA). Sarcopenia, a chronic condition defined by reduced skeletal muscle function and volume, can be assessed radiologically by computed tomography (CT)-derived body composition analysis (CT-BC), and is associated with systemic inflammation. OBJECTIVE: The aim was to describe the association between CT-BC, CPEX, inflammation and survival in patients undergoing elective intervention for AAA. SETTING: Patients were recruited retrospectively from a single, secondary-care centre-operative database. Cases undergoing elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR) between 31 March 2015 and 25 June 2020 were included. PATIENTS: There were 176 patients (130 EVAR, 46 OSR) available for analysis in the final study; median (interquartile range [IQR]) follow-up was 60.5 [27] months, and all completed a minimum of 2 years follow-up. MAIN OUTCOME MEASURES: Preoperative CPEX tests were recorded. CT sarcopenia score [CT-SS, range 0 to 2, calculated based on normal/low SMI (0/1) and normal/low SMD (0/1)] assessed radiological sarcopenia. Preoperative modified Glasgow Prognostic score (mGPS) was used to assess systemic inflammation. RESULTS: Mean [95% confidence interval (CI) survival in the CT-SS 0 vs. CT-SS 1 vs. CT-SS 2 subgroups was 80.1 (73.6 to 86.6) months vs. 70.3 (63.5 to 77.1) months vs. 63.8 (53.4 to 74.2) months] ( P  = 0.01). CT-SS was not associated with CPEX results ( P  > 0.05). Elevated CT-SS [hazard ratio (HR) 1.83, 95% CI, 1.16 to 2.89, P  < 0.01] was independently associated with increased hazard of long-term mortality; however, CPEX results were not ( P  > 0.05). CONCLUSION: CPEX test results were not consistently associated with body composition and did not have significant prognostic value in patients undergoing elective treatment for AAA.

A systematic review of the neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with lower extremity arterial disease.

Lower extremity arterial disease (LEAD) is caused by atherosclerotic plaque in the arterial supply to the lower limbs. The neutrophil to lymphocyte and platelet to lymphocyte ratios (NLR, PLR) are established markers of systemic inflammation which are related to inferior outcomes in multiple clinical conditions, though remain poorly described in patients with LEAD. This review was carried out in accordance with PRISMA guidelines. The MEDLINE database was interrogated for relevant studies. Primary outcome was the prognostic effect of NLR and PLR on clinical outcomes following treatment, and secondary outcomes were the prognostic effect of NLR and PLR on disease severity and technical success following revascularisation. There were 34 studies included in the final review reporting outcomes on a total of 19870 patients. NLR was investigated in 21 studies, PLR was investigated in two studies, and both NLR & PLR were investigated in 11 studies. Relating to increased levels of systemic inflammation, 20 studies (100%) reported inferior clinical outcomes, 13 (92.9%) studies reported increased disease severity, and seven (87.5%) studies reported inferior technical results from revascularisation. The studies included in this review support the role of elevated NLR and PLR as key components influencing the clinical outcomes, severity, and success of treatment in patients with LEAD. The use of these easily accessible, cost effective and routinely available markers is supported by the present review.

The relationship between computed tomography-derived body composition, systemic inflammation, and survival in patients with abdominal aortic aneurysm.

OBJECTIVE: Patient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair or by endovascular aneurysm repair, remain challenging. Computed tomography (CT)-derived body composition analysis (CT-BC) and systemic inflammation-based scoring systems such as the systemic inflammatory grade (SIG) appear to offer prognostic value in patients with AAA undergoing endovascular aneurysm repair. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in noncancer populations are lacking. The present study aimed to examine the relationship between CT-BC, SIG, and survival in patients undergoing elective intervention for AAA. METHODS: A total of 611 consecutive patients who underwent elective intervention for AAA at three large tertiary referral centers were retrospectively recruited for inclusion into the study. CT-BC was performed and analyzed using the CT-derived sarcopenia score (CT-SS). Subcutaneous and visceral fat indices were also recorded. SIG was calculated from preoperative blood tests. The outcomes of interest were overall and 5-year mortality. RESULTS: Median (interquartile range) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) open surgical repair cases, 558 (91%) patients were male, and the median (interquartile range) age was 73.0 (11.0) years. Age (hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.28-2.14, P < .001), elevated CT-SS (HR: 1.58, 95% CI: 1.28-1.94, P < .001), and elevated SIG (HR: 1.29, 95% CI: 1.07-1.55, P < .01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 and SIG 0 subgroup was 92.6 (84.8-100.4) months compared with 44.9 (30.6-59.2) months in the CT-SS 2 and SIG ≥2 subgroup (P < .001). Patients with CT-SS 0 and SIG 0 had 90% (standard error: 4%) 5-year survival compared with 34% (standard error: 9%) in patients with CT-SS 2 and SIG ≥2 (P < .001). CONCLUSIONS: Combining measures of radiological sarcopenia and the systemic inflammatory response offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies.

The prognostic value of preoperative systemic inflammation-based scoring in patients undergoing endovascular repair of abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common condition that is predominantly managed in the United Kingdom by endovascular aneurysm repair (EVAR). Activation of the systemic inflammatory response (SIR) appears to offer prognostic value in patients with vascular disease. The present study examines the relationship between the SIR and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and fenestrated/branched [F/B]-EVAR). METHODS: Consecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centers over a 5-year period. Neutrophil:lymphocyte ratio and modified Glasgow Prognostic Score were calculated from preoperative blood results and combined into the systemic inflammatory grade (SIG). The primary outcome was all-cause mortality during the follow-up period, which was compared between subgroups of SIGs. RESULTS: There were 506 patients included in the final study, with a median follow-up of 68.0 months (interquartile range, 27.3 months), and there were 163 deaths during the follow-up period. Mean survival in the SIG 0 vs SIG 1 vs SIG 2 vs SIG 3 vs SIG 4 subgroups was 80.7 months (95% confidence interval [CI], 76.5-85.0 months) vs 78.7 months (95% CI, 72.7-84.7 months) vs 61.0 months (95% CI, 51.1-70.8 months) vs 65.1 months (95% CI, 45.0-85.2 months) vs 54.9 months (95% CI, 34.4-75.3 months) (P < .05). In the entire cohort, age (P < .001), body mass index (P < .05), high creatinine (P < .05), and SIG (P < .05) were associated with survival on univariate analysis, with retained independent association for age (hazard ratio, 1.72; 95% CI, 1.29-2.31; P < .001) and SIG (hazard ratio, 1.20; 95% CI, 1.02-1.40; P < .05) on multivariate analysis. Increasing SIG (area under the curve, 0.68; 95% CI, 0.58-0.78; P < .01) predicted 1-year mortality. CONCLUSIONS: Markers of the SIR such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for abdominal aortic aneurysms. These findings warrant further investigation in large prospective cohort studies.

The Relationship between Clinical Frailty Score, CT-Derived Body Composition, Systemic Inflammation, and Survival in Patients with Chronic Limb-Threatening Ischemia.

BACKGROUND: Frailty is a chronic condition with complex etiology and impaired functional performance that has been associated with altered body composition and chronic inflammation. Chronic limb-threatening ischemia (CLTI) carries significant morbidity and mortality and is associated with poor quality of life. The present study aims to examine these relationships and their prognostic value in patients with CLTI. METHODS: Consecutive patients presenting as unscheduled admissions to a single tertiary center with CLTI were included over a 12-month period. Frailty was diagnosed using the Clinical Frailty Scale (CFS). Body composition was assessed using computerised tomography (CT) at the L3 vertebral level (CT-BC) to generate visceral and subcutaneous fat indices, skeletal muscle index, and skeletal muscle density. Skeletal muscle index and skeletal muscle density were combined to form the CT-sarcopenia score (CT-SS). Systemic inflammation was assessed by the modified Glasgow prognostic score (mGPS). The primary outcome was overall mortality. RESULTS: There were 190 patients included with a median (interquartile range) follow-up of 22 (6) months (range 15-32 months) and 79 deaths during the follow-up period. One hundred patients (53%) had a CFS >4. CFS >4 (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.25-3.66, P < 0.01), CT-SS (HR 1.47, 95% CI 1.03-2.09, P < 0.05), and mGPS (HR 1.54, 95% CI 1.11-2.13, P < 0.01) were independently associated with increased mortality. CT-SS (odds ratio 1.88, 95% CI 1.09-3.24, P < 0.01) was independently associated with CFS >4. Patients with CT-SS 0 and CFS ≤4 had 90% (standard error [SE] 5%) 1-year survival, compared with 35% (SE 9%) in patients with CT-SS 2 and CFS >4 (P < 0.001). Patients with mGPS 0 and CFS ≤4 had 94% (SE 4%) 1-year survival compared with 44% (SE 6%) in the mGPS 2 and CFS >4 subgroup (P < 0.001). CONCLUSIONS: Frailty assessed by CFS was associated with CT-BC. CFS, CT-SS, and mGPS were associated with poorer survival in patients presenting as unscheduled admissions with CLTI. CT-SS and mGPS may contribute to part of frailty and prognostic assessment in this patient cohort.

The prognostic value of clinical frailty and American Society of Anesthesiology score in patients with chronic limb threatening ischaemia.

Background: Frailty is a complex multisystem syndrome associated with increased comorbidity and decreased physiological reserve. There are associations between frailty and adverse outcome in surgical patients. Chronic limb threatening ischemia (CLTI) is increasingly prevalent, with a typically frail patient population. Existing frailty scoring systems focus on functional measures and do not reliably assess comorbidities. The present study aims to describe the prognostic value of multimodal frailty assessment in patients with CLTI. Patients and methods: Patients >50 years old admitted as an emergency with CLTI between May 2020 to June 2021 were included. Frailty was measured using Clinical Frailty Score (CFS), and comorbidities with American Society of Anesthiologists score (ASA). A composite score combining CFS and ASA was derived and the prognostic value compared with each component score. The primary outcome was overall survival. Results: There were 249 eligible patients, 53.4% (n=133) had CFS>4. The mean (95% CI) overall survival for the CFS>4 cohort was 15.9 (13.6-18.3) months vs. 28.5 (26.1-30.9) months for CFS≤4 cohort (p<0.001). Increasing CFS-ASA score was associated with inferior survival on univariate (HR=2.84, 95% CI [1.96-4.11], p<0.001) and multivariate (HR=1.78, 95% CI [1.20-2.64], p<0.01) analyses. ROC-analysis showed comparable prognostic value of CFS and CFS-ASA to predict one-year survival. Conclusions: Frailty is highly prevalent and a poor prognostic indicator in patients with CLTI admitted as an emergency. Our results suggest that incorporating assessment of comorbidities into frailty assessment may offer prognostic value, but comparable to existing clinical frailty assessment. Further work to identify patients with inferior prognosis is required.

Laparoscopic subtotal cholecystectomy; change in practice over a 10-year period.

BACKGROUND: Laparoscopic subtotal cholecystectomy is a recognised safe, alternative strategy when a critical view of safety cannot be obtained. This study audits the change in practice at a District General Hospital following the adoption of subtotal cholecystectomy in 2013. METHODS: Retrospective case series included consecutive cholecystectomies over a ten-year period in a single institution. Cases were divided into subgroups based on operation date. Primary outcome was the proportion of patients undergoing laparoscopic total cholecystectomy, laparoscopic subtotal and laparoscopic converted to open cholecystectomy. Secondary outcomes included incidence of bile leak, complication rate, return to theatre, and length of stay. RESULTS: There were 4217 cases: 1381 in Group A (pre-adoption of subtotal cholecystectomy 2009-2012), and 2836 in Group B (post-adoption of subtotal cholecystectomy 2013-2019). The rate of laparoscopic total cholecystectomy was higher in Group A than Group B (95.4% vs. 92.8%, p < 0.001). In the subtotal group (n = 114, 14 (12.3%) patients had bile leak, 6 (5.3%) underwent re-laparoscopy, and median length of stay was 2 days. CONCLUSION: Laparoscopic subtotal cholecystectomy appears to be an acceptable alternative technique at this centre, reducing the rate of open conversion and length of stay, with a low reintervention rate for bile leak.

Postimplantation syndrome in endovascular aortic aneurysm repair - a systematic review.

Postimplantation syndrome (PIS) following endovascular aortic aneurysm repair (EVAR) is a poorly understood phenomenon occurring in the early post-operative course. The underlying aetiology, risk factors, clinical sequalae, and treatment options, are largely unknown. The lack of any standardised diagnostic criteria limits current research in this field. The MEDLINE database was interrogated using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search strategy. Five search terms were used; "postimplantation syndrome" AND "aneurysm", AND "infection", AND "complications", AND "biomarkers", AND "outcomes". 19 studies were included in the review process, reporting a 17.4%-39.0% incidence of PIS. IL-6 was the most commonly elevated biomarker in PIS vs. non-PIS patients. There was a higher incidence of PIS in patients who received polyester rather than expanded-polytetrafluoroethylene (ePTFE) grafts. There was a lower rate of type 2 endoleaks observed in patients who developed PIS. Early major adverse cardiovascular events (MACE) were higher in PIS patients, however there were no studies reporting long-term MACE. Length of stay was higher in PIS patients. Current data support the role of IL-6 as being key to the development of PIS following EVAR. Further work describing the effect that PIS has on long-term clinical outcomes is needed. Lack of standardised diagnostic criteria limit the reporting of PIS between centres, the criteria proposed by this review may resolve this.

CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

BACKGROUND: Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. METHODS: Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). RESULTS: 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. CONCLUSIONS: Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

Evaluation of the prognostic value of computed tomography-derived body composition in patients undergoing endovascular aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) is the most common mode of repair of abdominal aortic aneurysms (AAA) in the UK. EVAR ranges from standard infrarenal repair to complex fenestrated and branched EVAR (F/B-EVAR). Sarcopenia is defined by lower muscle mass and function, which is associated with inferior perioperative outcomes. Computed tomography-derived body composition analysis offers prognostic value in patients with cancer. Several authors have evaluated the role of body composition analysis in predicting outcomes in patients undergoing EVAR; however, the evidence base is limited by heterogeneous methodology. METHODS: Six hundred seventy-four consecutive patients (58 (8.6%) female, mean (SD) age 74.4 (6.8) years) undergoing EVAR and F/B-EVAR at three large tertiary centres were retrospectively recruited. Subcutaneous and visceral fat indices (SFI and VFI), psoas and skeletal muscle indices, and skeletal muscle density were measured at the L3 vertebral level from pre-operative computed tomographies. The maximally selected rank statistic technique was used to define optimal thresholds to predict mortality. RESULTS: There were 191 deaths during the median follow-up period of 60.0 months. Mean (95% CI) survival in the low SMI versus high SMI subgroups was 62.6 (58.5-66.7) versus 82.0 (78.7-85.3) months (P < 0.001). Mean (95% CI) survival in the low SFI versus high SFI subgroups was 56.4 (48.2-64.7) versus 77.1 (74.2-80.1) months (P < 0.001). One-year mortality in the low SMI versus high SMI subgroups was 10% versus 3% (P < 0.001). Low SMI was associated with increased odds of one-year mortality (OR 3.19, 95% CI 1.60-6.34, P < 0.001). Five-year mortality in the low SMI versus high SMI subgroups was 55% versus 28% (P < 0.001). Low SMI was associated with increased odds of five-year mortality (OR 1.54, 95% CI 1.11-2.14, P < 0.01). On multivariate analysis of all patients, low SFI (HR 1.90, 95% CI 1.30-2.76, P < 0.001) and low SMI (HR 1.88, 95% CI 1.34-2.63, P < 0.001) were associated with poorer survival. On multivariate analysis of asymptomatic AAA patients, low SFI (HR 1.54, 95% CI 1.01-2.35, P < 0.05) and low SMI (HR 1.71, 95% CI 1.20-2.42, P < 0.01) were associated with poorer survival. CONCLUSIONS: Low SMI and SFI are associated with poorer long-term survival following EVAR and F/B-EVAR. The relationship between body composition and prognosis requires further evaluation, and external validation of the thresholds proposed in patients with AAA is required.

Comparison of Deep Space Navigation Using Optical Imaging, Pulsar Time-of-Arrival Tracking, and/or Radiometric Tracking.

Recent advances with space navigation technologies developed by NASA in space-based atomic clocks and pulsar X-ray navigation, combined with past successes in autonomous navigation using optical imaging, brings to the forefront the need to compare space navigation using optical, radiometric, and pulsar-based measurements using a common set of assumptions and techniques. This review article examines these navigation data types in two different ways. First, a simplified deep space orbit determination problem is posed that captures key features of the dynamics and geometry, and then each data type is characterized for its ability to solve for the orbit. The data types are compared and contrasted using a semi-analytical approach with geometric dilution of precision techniques. The results provide useful parametric insights into the strengths of each data type. In the second part of the paper, a high-fidelity, Monte Carlo simulation of a Mars cruise, approach, and entry navigation problem is studied. The results found complement the semi-analytic results in the first part, and illustrate specific issues such as each data type's quantitative impact on solution accuracy and their ability to support autonomous delivery to a planet.

The progression of non-small cell lung cancer from diagnosis to surgery.

OBJECTIVES: The IASLC 8th TNM Staging 8th differentiates between a greater number of T-stages. Resection remains the mainstay of curative treatment with often significant waiting times. This study aims to quantify the T-stage progression and growth of non-small cell lung cancers (NSCLCs) between radiological diagnosis and resection, and its impact on disease recurrence and survival. MATERIALS AND METHODS: A retrospective analysis of NSCLC resections (289) in a high-volume centre between July 01, 2015 and June 30, 2016. Baseline demographics, time from diagnostic CT to surgery, tumour size (cm) and T-stage from diagnostic CT, PET-CT and post-operative histopathology reports were recorded. The primary outcome was increase in T-stage from diagnostic CT to resection. Kaplan-Meier and cox proportional hazard analyses were used to determine recurrence-free survival and survival. RESULTS: Median increase in tumour size between diagnosis and resection was 0.3 cm (p < 0.0001). Median percentage increase in size was 13%. T-stage increased in 133 (46.0%) patients. N stage increased in 51 patients (17.7%), 32 (11.1%) to N2 disease. Mean survival in those upstaged was 43.5 (39.9-47.1) months versus 53.4 (50.0-56.8) months in patients not upstaged (p = 0.025). Mean recurrence-free survival in those upstaged was 39.1 (35.2-43.0) months versus 47.7 (43.9-51.4) months in patients not upstaged (p = 0.117). Upstaging was independently associated with inferior survival (HR 1.674, p = 0.006) and inferior recurrence-free survival (HR 1.423, p = 0.038). CONCLUSIONS: A significant number of patients are upstaged between diagnostic and resection resulting in reduced survival and recurrence-free survival. A change in management pathways are required to improve outcomes in NSCLC.

Safer pharmacy practice: a preliminary study of significant event analysis and peer feedback.

OBJECTIVES: The aim was to investigate the effectiveness of significant event analyses (SEAs) undertaken by pharmacists as judged by a new system of independent peer feedback. METHOD: The setting was a convenience sample of 37 pharmacists working in community pharmacy, secondary care and academic settings in NHS Scotland. Preliminary study involved the content analysis of pharmacists' SEAs and written feedback reports, which were generated by pharmacists trained in using a validated instrument to facilitate peer feedback. The content of reports and feedback letters were systematically coded and categorised by identifying and quantifying key words and phrases. Data collected included the range and severity of significant events identified; the reported reasons for the events occurring; types of learning needs identified; action(s) taken; and learning issues raised by peer feedback. KEY FINDINGS: A total of 37 pharmacists submitted 43 SEA reports during the study period. All events submitted were classified as having a negative impact on the quality and safety of patient care. Most events related to prescribing, dispensing, administration, communication and patient-/relative-centred issues. Patients reportedly came to harm in 13% of cases. Sixty-three per cent of reported learning needs related to personal awareness/responsibilities when undertaking work tasks, and 58% of implemented change involved amending existing protocols or introducing new procedures. Seventy per cent of SEAs were judged to be 'satisfactory' by the peer reviewers. The effectiveness of change implementation and providing a clear description of an event were highlighted as key issues which required improvement in those event analyses judged to be 'unsatisfactory'. CONCLUSIONS: The findings demonstrate that most pharmacists in this study were able to apply SEA in a satisfactory manner by demonstrating reflective learning, undertaking insightful analyses and implementing necessary change. SEA and peer feedback may have a potential role to play in enhancing the quality and safety of pharmacy practices.

The downstaging approach to irresectable oesophageal and gastric cancer: a single centre experience.

BACKGROUND: There is uncertainty over optimal management of locally advanced non-metastatic oesophageal and gastric (OG) adenocarcinomas which are deemed irresectable at time of diagnosis due to local tumour or nodal burden. Current practice in our regional centre is to administer chemotherapy in a "downstaging" strategy in the hope of achieving tumour shrinkage to allow radical treatment. Patients without sufficient response to downstaging are treated palliatively. The aim of this study was to review our single unit outcomes of this treatment strategy. METHODS: Data was collected retrospectively from electronic patient records on all cases discussed at regional MDT over a 32-month period (January 2015-August 2017). RESULTS: A total of 44 patients [70.5% male, median age 70 years, 13 (29.5%) oesophageal, 12 (27.3%) junctional and 19 (43.2%) gastric] were included in the study. Thirty-six (81.8%) of patients received the full number of planned cycles of chemotherapy; toxicity and disease progression (both 6.8% of cases) were the most common reasons for early cessation of treatment. Seventeen (38.6%) patients underwent resection and an R0 resection was achieved in 13 (76.5%) of these patients. After median follow up of 16.8 months, the median overall survival (OS) in the resection vs. palliative cohorts was 42.6 vs. 16.4 months (P<0.05). CONCLUSIONS: Our data show that a downstaging approach can be successfully implemented (R0 resection achieved) in up to a third of patients with good survival results. Further prospective data identifying patient and pathological characteristics predicting response to treatment are needed to optimise selection into a downstaging programme.

Clinical audit and quality improvement - time for a rethink?

RATIONALE AND AIM: Evidence of the benefits of clinical audit to patient care is limited, despite its longevity. Additionally, numerous attitudinal, professional and organizational barriers impede its effectiveness. Yet, audit remains a favoured quality improvement (QI) policy lever. Growing interest in QI techniques suggest it is timely to re-examine audit. Clinical audit advisors assist health care teams, so hold unique cross-cutting perspectives on the strategic and practical application of audit in NHS organizations. We aimed to explore their views and experiences of their role in supporting health care teams in the audit process. METHOD: Qualitative study using semi-structured and focus group interviews. Participants were purposively sampled (n = 21) across health sectors in two large Scottish NHS Boards. Interviews were audio-taped, transcribed and a thematic analysis performed. RESULTS: Work pressure and lack of protected time were cited as audit barriers, but these hide other reasons for non-engagement. Different professions experience varying opportunities to participate. Doctors have more opportunities and may dominate or frustrate the process. Audit is perceived as a time-consuming, additional chore and a managerially driven exercise with no associated professional rewards. Management failure to support and resource changes fuels low motivation and disillusionment. Audit is regarded as a 'political' tool stifled by inter-professional differences and contextual constraints. CONCLUSIONS: The findings echo previous studies. We found limited evidence that audit as presently defined and used is meeting policy makers' aspirations. The quality and safety improvement focus is shifting towards 'alternative' systems-based QI methods, but research to suggest that these will be any more impactful is also lacking. Additionally, identified professional, educational and organizational barriers still need to be overcome. A debate on how best to overcome the limitations of audit and its place alongside other approaches to QI is necessary.

Multicentre evaluation of stable reference whole blood for enumeration of lymphocyte subsets by flow cytometry.

BACKGROUND: Clinical indications for lymphocyte subset enumeration by flow cytometry include monitoring of disease progression and timing of therapeutic intervention in infection with human immunodeficiency virus. Until recently international standardisation has not been possible due to a lack of suitable stable reference material. METHODS: This study consisted of two trials of a stabilised whole blood preparation. Eleven participants were sent two standard protocols for staining plus gating strategy and asked to report absolute counts for lymphocyte subsets. RESULTS: No significant difference was detected between the two methods when results from the two assays and all partners were pooled. Significant differences in results from the different partners were observed. However, representative mean counts were obtained for geometric means, geometric coefficient of variation, and 95% confidence interval for CD3 910 cells/mul, 9%, and 888 to 933, respectively), CD4 (495 cells/mul, 12%, and 483 to 507), and CD8 (408 cells/mul, 13%, and 393 to 422). CONCLUSION: We have introduced a stabilised blood preparation and a well-characterized biological standard. The availability of this reference material greatly simplifies the validation of new techniques for CD4(+) T-cell enumeration and the expansion of external quality assurance programmes for clinical laboratories, including those that operate in resource-restricted environments. (c) 2005 Wiley-Liss, Inc.

Long-term results of distal pancreatectomy for chronic pancreatitis in 90 patients.

OBJECTIVE: To determine the indications for distal pancreatectomy for chronic pancreatitis and to evaluate the risks, functional loss, and outcome of the procedure. SUMMARY BACKGROUND DATA: Chronic pancreatitis is generally associated with continued pain, parenchymal and ductal hypertension. and progressive pancreatic dysfunction, and it is a cause of premature death in patients who receive conservative treatment. Good results have recently been reported by the authors and others for resection of the pancreatic head in this disease, but distal pancreatectomy is a less popular option attended by variable success rates. It remains a logical approach for patients with predominantly left-sided pancreatic disease, however. METHODS: A personal series of 90 patients undergoing distal pancreatectomy for chronic pancreatitis over the last 20 years has been reviewed, with a mean postoperative follow-up of 34 months (range 1-247). Pancreatic function was measured before and after operation in many patients. RESULTS: Forty-eight of 84 patients available for follow-up had a successful outcome in terms of zero or minimal, intermittent pain. There was one perioperative death, but complications developed in 29 patients, with six early reexplorations. Morbidity was unaffected by associated splenectomy or right-to-left dissection. Late mortality rate over the follow-up period was 10%; most of these late deaths occurred because of failure to abstain from alcohol. Preoperative exocrine function was abnormal in two thirds of those tested and was unchanged at follow-up. Diabetic curves were seen in 10% of patients preoperatively, while there was an additional diabetic morbidity rate of 23% related to the procedure and late onset of diabetes (median duration 27 months) in another 23%. Diabetic onset was related to percentage parenchymal resection as well as splenectomy. Outcome was not clearly dependent on the etiology of pancreatitis or on disease characteristics as assessed by preoperative imaging. However, patients with pseudocyst disease alone did better than other groups. Twenty-one of 36 patients who failed to respond to distal pancreatectomy required further intervention, including completion pancreatectomy, neurolysis, and sphincteroplasty. Thirteen of these 21 patients achieved long-term pain relief after their second procedure. CONCLUSIONS: Distal pancreatectomy for chronic pancreatitis from any etiology can be performed with low mortality and a good outcome in terms of pain relief and return to work in approximately 60% of patients. Little effect is seen on exocrine function of the pancreas, but there is a diabetic risk of 46% over 2 years. Pseudocyst disease is associated with the best outcome, but other manifestations of this disease, including strictures, calcification, and limited concomitant disease in the head of the pancreas, can still be associated with a good outcome.

Affordable CD4(+)-T-cell counting by flow cytometry: CD45 gating for volumetric analysis.

The flow cytometers that are currently supported by industry provide accurate CD4(+)-T-cell counts for monitoring human immunodeficiency virus disease but remain unaffordable for routine service work under resource-poor conditions. We therefore combined volumetric flow cytometry (measuring absolute lymphocyte counts in unit volumes of blood) and simpler protocols with generic monoclonal antibodies (MAbs) to increase cost efficiency. Volumetric absolute counts were generated using CD45/CD4 and CD45/CD8 MAb combinations in two parallel tubes. The percentage values for the various subsets were also determined within the leukocyte and lymphocyte populations utilizing a fully automated protocol. The levels of agreement between the newly developed method and the present industry standards, including both volumetric and bead-based systems using a full MAb panel for subset analysis, were tested by Bland-Altman analyses. The limits of agreement for CD4 counts generated by the volumetric methods using either CD45/CD4 (in a single tube) or the full Trio MAb panel (in three tubes) on the CytoronAbsolute flow cytometer were between -29 and +46 cells/mm(3) with very little bias for CD4 counts (in favor of the Trio method: +8 CD4(+) lymphocytes/mm(3); 0.38% of lymphocytes). The limits of agreement for absolute CD4 counts yielded by the volumetric CD45/CD4 method and the bead-based method were between -118 and +98 cells/mm(3), again with a negligible bias (-10 CD4(+) lymphocytes/mm(3)). In the volumetric method using CD45/CD8, the strongly CD8(+) cells were gated and the levels of agreement with the full Trio showed a minor bias (in favor of the Trio; +40 CD8(+) cells/mm(3); 5.2% of lymphocytes) without a significant influence on CD4/CD8 ratios. One trained flow cytometrist was able to process 300 to 400 stained tubes per day. This workload extrapolates to a throughput of >30,000 samples per year if both CD45/CD4 and CD45/CD8 stainings are performed for each patient or a throughput of >60,000 samples if only CD45/CD4 counts are tested in a single tube. Thus, on the basis of the high efficiency and excellent agreement with the present industry standards, volumetric flow cytometers with automated gating protocols and autobiosamplers, complemented by generic CD45, CD4, and CD8 MAbs used in two-color immunofluorescence, represent the most suitable arrangements for large regional laboratories in resource-poor settings.