Embracing change, quickly. A hospital finds success by rapidly implementing new processes to curb costs and boost quality.

The speed with which process improvements are implemented can be critical to their success.

ID family protein expression and regulation in hypoxic pulmonary hypertension.

Bone morphogenetic protein (BMP) signaling has been linked to the development of pulmonary hypertension (PH). Inhibitors of differentiation (ID) proteins (ID1-4) are a family of basic helix-loop-helix transcription factors that are downstream targets of the BMP signaling pathway, but the role that ID proteins play in the development of PH is unknown. To address this, we evaluated pulmonary expression of ID proteins in a mouse model of hypoxia-induced PH. There is selective induction of ID1 and ID3 expression in hypoxic pulmonary vascular smooth muscle cells (VSMCs) in vivo, and ID1 and ID3 expression are increased by hypoxia in cultured pulmonary VSMCs in a BMP-dependent fashion. ID4 protein is barely detectable in the mouse lung, and while ID2 is induced in hypoxic peripheral VSMCs in vivo, it is not increased by hypoxia or BMP signaling in cultured pulmonary VSMCs. In addition, the PH response to chronic hypoxia is indistinguishable between wild type and Id1 null mice. This is associated with a compensatory increase in ID3 but not ID2 expression in pulmonary VSMCs of Id1 null mice. These findings indicate that ID1 is dispensable for mounting a normal pulmonary vascular response to hypoxia, but suggest that ID3 may compensate for loss of ID1 expression in pulmonary VSMCs. Taken together, these findings indicate that ID1 and ID3 expression are regulated in a BMP-dependent fashion in hypoxic pulmonary VSMCs, and that ID1 and ID3 may play a cooperative role in regulating BMP-dependent VSMC responses to chronic hypoxia.

Effect of risk-adjusted, non-dialysis-dependent renal dysfunction on mortality and morbidity following coronary artery bypass surgery: a multi-centre study.

OBJECTIVE: As little is known about the impact of non-dialysis-dependent renal dysfunction on short- and mid-term outcomes following coronary surgery we have conducted a large multi-centre study comparing patients with no history of renal dysfunction to those with preoperative renal dysfunction. METHODS: Data was prospectively collected on 19,625 consecutive patients undergoing isolated coronary surgery between 1997 and 2003 from four institutions. Sixty-seven patients had a history of dialysis support prior to coronary surgery, and were excluded from the main analysis of the study. The remaining 19,558 patients were divided into two groups based on preoperative serum creatinine level, patients with preoperative renal dysfunction with serum creatinine levels >200 micromol/L without dialysis support and control patients with preoperative serum creatinine levels <200 micromol/L. Case-mix was accounted for by developing a propensity score, which was the probability of belonging to the non-dialysis-dependent renal dysfunction group, and included in the multivariable analyses. RESULTS: There were 19,172 patients with preoperative serum creatinine levels <200 micromol/L and 386 patients with serum creatinine levels >200 micromol/L without dialysis support. The propensity score included sex, body mass index, co-morbidity factors (respiratory disease, diabetes, cerebrovascular disease, hypertension, and hypercholesterolemia), ejection fraction, left main stem stenosis, emergency status, prior cardiac surgery, off-pump surgery, and the logistic EuroSCORE. After adjusting for the propensity score, patients with preoperative non-dialysis-dependent renal dysfunction had significantly higher in-hospital mortality (adjusted odds ratio 3.0, p < 0.001), stroke (adjusted odds ratio 2.0, p = 0.033), atrial arrhythmia (adjusted odds ratio 1.5, p = 0.003), prolonged ventilation (adjusted odds ratio 2.1, p < 0.001), and post-op stay > 6 days (adjusted odds ratio 2.6, p < 0.001). One thousand one hundred and eighty-three (6.1%) deaths occurred during 58,062 patient-years follow-up. After adjusting for the propensity score, the adjusted hazard ratio of mid-term mortality for non-dialysis-dependent renal dysfunction was 2.7 (p < 0.001). CONCLUSIONS: Patients undergoing coronary surgery with non-dialysis-dependent renal dysfunction have significantly increased perioperative morbidity and mortality. Mid-term survival is also significantly reduced at 5-years.

Congenital unilateral pulmonary artery agenesis and aspergilloma.

Isolated unilateral pulmonary artery agenesis is a rare condition, which in most patients is asymptomatic. Occasionally patients present with symptoms that are nonspecific and not necessarily attributable to disease of the respiratory system. In these individuals the clue to the diagnosis is found in a plain chest roentgenogram, often revealing a hyperlucent contracted hemithorax. We present an unusual case of isolated unilateral pulmonary artery agenesis associated with the opportunistic organism Mycobacterium kansasii and Aspergillus fumigatus in which the diagnosis was made 10 years after initial presentation. Clinicians should be aware of this condition and include it in their differential diagnosis of a hyperlucent lung field on the chest roentgenogram.

Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction?

OBJECTIVES: We aimed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction. The latter included older patients or those with pre-existing renal disease, elevated preoperative serum creatinine (Cr), poor ventricular function, hypertension, diabetes mellitus and unstable angina requiring intravenous therapy. METHODS: Fifty patients undergoing cardiopulmonary bypass (CPB) who fulfilled the entry criteria were prospectively randomized into two groups: Group 1 received a 'renal-dose' (3 microg kg(-1) min(-1)) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2. The anaesthetic and CPB regimes were standardized. Urinary excretion of retinol binding protein (RBP) indexed to Cr, an accurate and sensitive marker of early renal tubular damage, was assessed daily for 6 days. Additional outcome measures included daily fluid balance, blood urea and serum Cr. Statistical comparisons were made using ANOVA and Mann-Whitney U-test. RESULTS: No significant difference was found between the groups in their age, gender, preoperative NYHA class, ejection fraction, baseline serum Cr and duration of CPB and aortic cross-clamping. Renal replacement therapy was not required in any instance. Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period. Dopamine-treated patients achieved more negative average fluid balance than those on placebo (5 vs. 229 ml, P<0.05). CONCLUSIONS: Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB.

FIASCO II failure to achieve a satisfactory cardiac outcome study: the elimination of system errors.

OBJECTIVES: Death in low-risk cardiac surgical patients provides a simple and accessible method by which modifiable causes of death can be identified. In the first FIASCO study published in 2009, local potentially modifiable causes of preventable death in low-risk patients with a logistic EuroSCORE of 0-2 undergoing cardiac surgery were inadequate myocardial protection and lack of clarity in the chain of responsibility. As a result, myocardial protection was improved, and a formalized system introduced to ensure clarity of the chain of responsibility in the care of all cardiac surgical patients. The purpose of the current study was to re-audit outcomes in low-risk patients to see if improvements have been achieved. METHODS: Patients with a logistic EuroSCORE of 0-2 who had cardiac surgery from January 2006 to August 2012 were included. Data were prospectively collected and retrospectively analysed. The case notes of patients who died in hospital were subject to internal and external review and classified according to preventability. RESULTS: Two thousand five hundred and forty-nine patients with a logistic EuroSCORE of 0-2 underwent cardiac surgery during the study period. Seven deaths occurred in truly low-risk patients, giving a mortality of 0.27%. Of the seven, three were considered preventable and four non-preventable. Mortality was marginally lower than in our previous study (0.37%), and no death occurred as a result of inadequate myocardial protection or communication failures. CONCLUSION: We postulate that the regular study of such events in all institutions may unmask systemic errors that can be remedied to prevent or reduce future occurrences. We encourage all units to use this methodology to detect any similarly modifiable factors in their practice.

Is type and screen only policy safe for patients undergoing elective lobectomy?

OBJECTIVE: The purpose of this study was to establish the safety and feasibility of a recently adopted policy to type and screen (TS) (group and save) only for selected patients who had low likelihood of transfusion requirement. METHODS: The TS only policy was applied to patients undergoing first-time elective lobectomy with Hb of >11 g/dl, aged <70 years, with no clotting abnormality and no history of neoadjuvant therapy. A retrospective analysis of prospectively collected data was made of 208 consecutive patients undergoing elective lobectomy from November 2009 to October 2010. The patients who were only type and screened (Group TS, n = 87) were compared with those who had preoperative cross matching (XM) (Group XM, n = 121). The perioperative characteristics, transfusion requirements and outcomes were compared between the two groups. RESULTS: Preoperative characteristics of the two groups were similar, except that the XM group were significantly older, with lower mean preoperative haemoglobin levels. Postoperative complications (9 vs 13%, P = 0.24) and hospital mortality (0 vs 0.8%, P = 0.5) were similar between TS and XM, respectively. On the day of operation, 16 patients (13%) required transfusion in the XM group. Six patients in the TS group were cross matched, of whom only 3 (3.4%) actually required transfusion. The mean postoperative Hb levels in XM were also significantly lower (12.96 vs 10.88 gm/dl). In the XM group, 260 units of blood were unnecessarily cross matched and had to be returned to the blood bank compared with zero units in the TS group. There was no delay caused by unavailability of blood at the time of clinical need. CONCLUSION: Our data suggest that it is safe and feasible to adopt a policy of type and screen only in selected patients undergoing elective lobectomy, who have low likelihood of transfusion requirement.

Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence--a National Centre's experience.

BACKGROUND: Surgery for pulmonary aspergillosis is infrequent and often challenging. Risk assessment is imprecise and new antifungals may ameliorate some surgical risks. We evaluated the medical and surgical management of these patients, including perioperative and postoperative antifungal therapy. METHODS: Retrospective study of patients who underwent surgery for pulmonary aspergillosis between September 1996 and September 2011. RESULTS: 30 patients underwent surgery with 23 having a preoperative tissue diagnosis while 7 were confirmed post-resection. The median age was 57 years (17-78). The commonest presenting symptoms were cough (40%, n = 12) and haemoptysis (43%, n = 13). Twelve (40%) patients had simple aspergilloma (including 2 with Aspergillus nodules) while the remaining 18 (60%) had chronic cavitary pulmonary aspergillosis (CCPA) (complex aspergilloma). Most of the patients had underlying lung disease: tuberculosis (20%, n = 6), asthma (26%, n = 8) and COPD (20%, n = 6). The procedures included lobectomy 50% (n = 15), pneumonectomy 10% (n = 3), sublobar resection 27% (n = 8), decortication 7% (n = 2), segmentectomy 3% (n = 1), thoracoplasty 3% (n = 1), bullectomy and pleurectomy 3% (n = 1), 6% (n = 2) lung transplantation for associated disease. Median hospital stay was 9.5 days (3-37). There was no operative and 30 day mortality. Main complications were prolonged air leak (n = 7, 23%), empyema (n = 6, 20%), respiratory failure requiring tracheostomy /reintubation (n = 4, 13%). Recurrence of CCPA was noted in 8 patients (26%), most having prior CCPA (75%). Taurolidine 2% was active against all 9 A. fumigatus isolates and used for pleural decontamination during surgery. CONCLUSIONS: Surgery in patients with chronic pulmonary aspergillosis offered good outcomes with an acceptable morbidity in a difficult clinical situation; recurrence is problematic.

A randomized study comparing three groups of vein harvesting methods for coronary artery bypass grafting: endoscopic harvest versus standard bridging and open techniques.

OBJECTIVES: The use of an open vein harvesting (OVH) technique for saphenous vein harvesting (SVH) is associated with wound complications and delayed patient mobilization. This has led to the development of minimally invasive vein harvesting (MIVH) techniques, such as standard bridging and endoscopic SVH (EVH). This randomized trial was established to assess immediate clinical outcome and patient satisfaction in our centre. METHODS: A total of 150 consecutive patients were prospectively randomized into three groups. Group 1 consisted of 50 patients who underwent OVH, Group 2 consisted of 50 patients who underwent a standard bridging technique (SBT) and Group 3 consisted of 50 patients who underwent EVH. Each group was assessed for the incidence of wound infection, postoperative pain and satisfaction and the number of vein repairs using previously validated scoring systems. RESULTS: The MIVH techniques reduced the pain at hospital (P < 0.001) and at 6 weeks (P < 0.001), and improved cosmesis (P < 0.001), compared with the OVH group. Patient satisfaction was greatest in the EVH group followed by the SBT and then the OVH group. The clinical markers of inflammation were reduced with an MIVHt. There were more vein repairs in the EVH compared with the OVH (P < 0.001) and the SBT (P = 0.04) groups. CONCLUSIONS: This study demonstrates that MIVH reduces wound morbidity. We believe that each technique has advantages and disadvantages, which should be considered during the selection of a harvesting procedure by both the patient and the surgeon.

Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues.

Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing) arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.

Active treatment rates for lung cancer in south Manchester: are we doing enough?

In an effort to improve the current lung cancer treatment outcomes in Britain, National guidelines were published followed by the introduction of National Lung Cancer Audit (LUCADA) project. LUCADA has defined active treatment as any therapeutic intervention with the aim of improving the quality or length of patients' survival irrespective of whether it is curative or palliative. From August 2003 to December 2006, all patients diagnosed to be new primary lung cancer referrals were enrolled into a prospective study. Out of the total of 433 patients the majority of patients were male (62%) and the mean age was 69 years. The histologies were small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and other cancers in 67 (15.5%), 306 (70.7%) and 11 (2.5%) patients, respectively, while 49 (11.3%) patients had no histological confirmation. Overall, the active treatment rate was 72% with 74 (18%), 158 (36%), 66 (15%) and 11 (3%) undergoing surgery, chemotherapy, radiotherapy and other methods, respectively. The active treatment rates for histologically proven SCLC, NSCLC and all lung cancers excluding SCLC were 83%, 77% and 71%, respectively, compared to the LUCADA national average of 73.5%, 66% and 56.5%, respectively. Among the NSCLC patients overall five-year survival was 27.4%. The stage specific survivals were 64.0%, 58.3%, 24.1% and 11.5%, respectively, for stages I, II, III and IV. These reassuring results show that south Manchester has good active treatment rates for lung cancer with survival outcomes comparable to other major series.

Death in low-risk cardiac surgery: the failure to achieve a satisfactory cardiac outcome (FIASCO) study.

Death in low-risk patients is not studied as frequently as it is in other cardiac patients. We, therefore, sought to determine why some low-risk patients die after cardiac surgery. All low-risk patients (EuroSCORE

Implications of a negative bronchoscopy on waiting times to treatment for lung cancer patients: results of a prospective tracking study.

OBJECTIVE: To ascertain the causes of delays in treatment to all patients presenting to our centre with a working diagnosis of lung cancer. All were entered prospectively into a 'tracking study'. METHODS: Of 342 consecutive confirmed cases of newly diagnosed lung cancer presenting between September 2003 and December 2005, 193 were general practitioner referrals and 149 presented through casualty and internal referrals. The former group formed the basis of the study. Of GP referral patients, 92 had a positive diagnostic bronchoscopy (group Bronch+). Their waiting times were compared with 94 others with negative result (group Bronch-). For uniformity of comparison the non-GP referral patients were excluded from this study. RESULTS: There were no significant differences in the age, clinical presentation or clinical staging of the two groups. Bronch+ had higher proportion of male patients (p=0.05). Bronch+ group had higher proportion of small cell and squamous cell carcinoma whereas Bronch- group had higher prevalence of adenocarcinoma (p=0.02). More patients in Bronch- underwent curative (36 vs 18, p=0.01) intent treatment. Though the median intervals (days) between the referral to first chest outpatient appointments were similar between the two groups (1 vs 1, p=0.89), the intervals from out-patient to decision-to-treat (33 vs 57, p=0.001) and decision-to-treat to treatment (8 vs 12, p=0.05) were significantly longer for Bronch- group. Overall the median referral to treatment interval for Bronch- was significantly longer compared to Bronch+ (45 vs 75, p=0.001). Most of these delays occurred in the intervals from outpatient appointments to decision-to-treat. CONCLUSIONS: A negative initial bronchoscopy in a suspected lung cancer patient implies a greater potential for excessive delays in diagnosis and treatment in spite of a greater chance of curative treatment. Most of the delay occurs in the interval from the outpatient appointment to decision-to-treat. Patients with negative bronchoscopy require a more concerted effort to achieve a timely diagnosis and treatment.

Primary cardiac sarcoma: reports of two cases and a review of current literature.

Primary cardiac sarcomas are rare tumors with an unfavourable prognosis. Complete surgical resection is currently the only mode of therapy proven to show any benefit. We report the cases of two patients presenting with features of obstruction and embolism and a presumed diagnosis of left atrial myxoma. At operation they were unexpectedly found to have large tumours raising strong suspicions of malignancy. Due to the extensive involvement of intracardiac structures with little possibility of reconstruction together with poor general condition of the patient, debulking was deemed to be the only viable option. Subsequent histology confirmed the diagnosis of sarcoma in both patients. Surgery produced immediate and effective symptom relief. The first patient died four months after the operation and second patient is still alive at 12 months after her operation. A brief review of literature on cardiac sarcoma is presented.

Are we achieving the current waiting time targets in lung cancer treatment? Result of a prospective study from a large United kingdom teaching hospital.

BACKGROUND: Recent United Kingdom National Cancer Plan guidelines have specified a number of waiting time targets to prevent delays in the treatment of lung cancer. This study was performed to compare our waiting times with national recommendations. METHODS: All newly diagnosed cases of lung cancer presenting to our institution were entered into a prospective tracking study by a dedicated audit officer. From September 2003 to December 2005, a total of 342 patients were entered into the study. Of these, 193 (56%) were referred by general practitioners; the remaining 114 (46%) were internal referrals. The Cancer Plan waiting time targets are mainly applicable to general practitioners referrals, which formed the study group. RESULTS: All the patients were seen in chest outpatient clinics within the recommended 2-week period. However, there was a delay in starting all forms of treatment. The median waiting time to any form of treatment was 60 days (recommendation, 62 days for all patients). From specialist referrals, the median waiting times for radiotherapy, surgery, and chemotherapy were 43, 25, and 16.5 days compared with recommended maximums of 28, 28, and 7 days, respectively. CONCLUSION: These data demonstrate that although patients receive outpatient consultation in the recommended time period, the National Cancer Plan treatment target of 62 days for patients referred by general practitioners is not being achieved. A concerted effort by all clinicians is required to meet the prescribed target times.

Lung cancer resection rate in south Manchester: is it comparable to international standards? Results of a prospective tracking study.

The UK has been reported to have the lowest resection and survival rates for lung cancer patients. These reports were based largely on retrospective data from the cancer registry and are now outdated. To monitor the present day surgical resection rate at our institution all newly diagnosed cases of lung cancer presenting to us were enrolled into a prospective tracking study. From September 2003 to March 2005 all suspected primary lung cancer referrals to the North West Lung Centre were tracked to identify patients with newly diagnosed lung cancer. The histology of 247 patients confirmed to be new lung cancer cases were small cell (SCLC), non-small cell (NSCLC) and mixed cancers in 33 (16%), 170 (83.5%) and 1 (0.5%) patients, respectively, while 43 patients had no histological confirmation. Overall, 43 patients (17%) underwent surgery while chemotherapy and radiotherapy were used in 91 (38%) and 43 (17%), respectively. Out of 170 confirmed NSCLC patients, 43 (25%), 65 (38%) and 27 (16%) patients underwent surgery, chemotherapy and radiotherapy, respectively. The remaining 35 (20%) did not receive any treatment because of patient wishes or poor condition. The surgical resection rates were 17% for all lung cancers and 25% for NSCLC. Current surgical resection rates at the South Manchester University Hospital are comparable to international standards. Similar data from the rest of the UK are required to determine the national resection rate, which may not be as low as once thought to be.

UK waiting time targets in lung cancer treatment: are they achievable? Results of a prospective tracking study.

BACKGROUND: Recent guidelines have specified a number of waiting time targets to prevent delay in the treatment of lung cancer. This study was carried out to assess the quality of lung cancer services and compare with national recommendations. METHODS: All newly diagnosed cases of lung cancer presenting to our institution via general practitioner referral were entered into a prospective tracking study by a dedicated audit officer. From September 2003 to March 2005 a total of 247 patients were entered into the study. Of these 133 (54%) were referred by general practitioners and the remainder 114 (46%) were internal referrals. The Cancer Plan waiting time targets are mainly applicable to GP referrals, which formed the study group. RESULTS: All the patients were seen in chest out-patients clinic within the recommended two weeks period. However there was a delay in starting all forms of treatment. The median waiting time to any form of treatment was 60 days (recommendation 62 days for all patients). CONCLUSION: This data demonstrates that although patients receive out patient consultation in the recommended time period, the National Cancer Plan 62 days GP referral to treatment target is not being achieved. A concerted effort by all clinicians is required to meet the prescribed target times.