BMI: does it predict the need for component separation?

PURPOSE: Patient optimization and selecting the proper technique to repair large incisional hernias is a multifaceted challenge. Body mass index (BMI) is a modifiable variable that may infer higher intra-abdominal pressures and, thus, predict the need for component separation (CS) at the time of surgery, but no data exist to support this. This paper assesses if the ratio of anterior-posterior (AP): transverse (TRSV) abdominal diameter, from pre-operative CT imaging, indicates a larger proportion of intra-abdominal fat and correlates with a hernia defect requiring a component separation for successful tension-free closure. METHODS: Ninety patients were identified who underwent either an open hernia repair with mesh by primary closure (N = 53) or who required a component separation at the time of surgery (N = 37). Pre-operative CT images were used to measure hernia defect width, AP abdominal diameter, and TRSV abdominal diameter. Quantitative data, nominal data, and logistic regression was used to determine predictors associated with surgical group categorization. RESULTS: The average hernia defect widths for primary closure and CS were 7.7 ± 3.6 cm (mean ± SD) and 9.8 ± 4.5, respectively (p = 0.015). The average BMI for primary closure was 33.9 ± 7.2 and 33.8 ± 4.9 for those requiring CS (p = 0.924). The AP:TRSV diameter ratios for primary closure and CS were 0.41 ± 0.08 and 0.49 ± 0.10, respectively (p < 0.001). In a multivariate analysis including both defect width and AP:TRSV diameter ratio, only AP:TRSV diameter ratio predicted the need for a CS (p = 0.001) while BMI did not (p = 0.92). CONCLUSION: Intraabdominal fat distribution measured by AP:TRSV abdominal diameter ratio correlates with successful tension-free fascial closure during incisional hernia repair, while BMI does not.

Exercise on-transition uncoupling of ventilatory, gas exchange and cardiac hemodynamic kinetics accompany pulmonary oxygen stores depletion to impact exercise intolerance in human heart failure.

AIM: In contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on-transition is unclear. This study tested whether exercise on-transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O2 pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O2store ) contributions to V˙O2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF. METHODS: Beat-to-beat HR and breath-to-breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square-wave ergometry at 60% V˙O2peak (46 ± 14 vs 125 ± 54-W, P < .001). Temporal responses across V˙E , V˙O2 and O2 pulse were assessed for the exercise on-transition using single exponential model Phase II on-kinetic time constants (τ = time to reach 63% steady-state rise). Breath-to-breath gas fractions and respiratory flows were used to determine O2stores . RESULTS: HF vs controls: τ for V˙E (137 ± 93 vs 74 ± 40-seconds, P = .03), V˙O2 (60 ± 40 vs 23 ± 5-seconds, P = .03) and O2 pulse (28 ± 18 vs 23 ± 15-seconds, P = .59). Within HF, τ for V˙E differed from O2 pulse (P < .02), but not V˙O2 . Exercise V˙E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88-mL min-1 W-1 , P < .001). Exercise on-transition O2store depletion in HF exceeded controls, generally persisting to end-exercise. CONCLUSION: These data suggest HF demonstrated exercise on-transition O2store depletion (high O2store contribution to V˙O2 ) coupled with dyssynchronous V˙E , V˙O2 and O2 pulse kinetics-not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise on-transition.

αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.

Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRß) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRß+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRß+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFß activation in primary human skeletal muscle and cardiac PDGFRß+ cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.

Incidental findings in CT angiograms for free DIEP flap breast reconstruction - Do they change our management?

BACKGROUND: Abdominal CT angiography (CTA) has become an integral part of the pre-operative evaluation of patients undergoing free Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction. It aids accurate delineation of perforator anatomy, assists pre-operative decision making and reduces operative time. However, such detailed imaging invariably yields a variety of incidental findings, with quoted figures of 13-36% in this setting. The purpose of this study was to identify the rate of "incidentalomas" when using DIEP CT angiography and, review how such findings influence our management. METHOD: A retrospective review was performed, looking at pre-operative scan reports of 154 consecutive patients undergoing free DIEP flap breast reconstructions between July 2008 and June 2012. RESULTS: Of 154 CTA's reviewed, 116 (75.3%) demonstrated incidental findings. In 71 patients (46.1%), these "incidentalomas" were inconsequential. However, in 37 patients (24.0%) the CTA prompted further investigations, and notably in a further 8 patients (5.2%) metastatic disease or other significant pathology was discovered which changed the operative plan. CONCLUSION: The overall rate of "incidentalomas" presented in this study is substantially higher than other similar published series, and most importantly, significantly altered the surgical management plan in 5.2% of cases. As such we would advocate that a pre-operative "staging" CTA, imaging the chest, abdomen and pelvis is useful for more than just delineation of vascular anatomy in patients undergoing DIEP flap reconstruction.

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes.

INTRODUCTION: Dissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales. METHODS: A 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications. RESULTS: A total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively. CONCLUSIONS: Funnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.

Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.

The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key cochaperone CDC37. We sought an improved understanding of protein kinase chaperoning by CDC37 in cancer cells. CDC37 overexpression in human colon cancer cells increased CDK4 protein levels, which was negated upon CDC37 knockdown. Overexpressing CDC37 increased CDK4 protein half-life and enhanced binding of HSP90 to CDK4, consistent with CDC37 promoting kinase loading onto chaperone complexes. Against expectation, expression of C-terminus-truncated CDC37 (ΔC-CDC37) that lacks HSP90 binding capacity did not affect kinase client expression or activity; moreover, as with wild-type CDC37 overexpression, it augmented CDK4-HSP90 complex formation. However, although truncation blocked binding to HSP90 in cells, ΔC-CDC37 also showed diminished client protein binding and was relatively unstable. CDC37 mutants with single and double point mutations at residues M164 and L205 showed greatly reduced binding to HSP90, but retained association with client kinases. Surprisingly, these mutants phenocopied wild-type CDC37 overexpression by increasing CDK4-HSP90 association and CDK4 protein levels in cells. Furthermore, expression of the mutants was sufficient to protect kinase clients CDK4, CDK6, CRAF and ERBB2 from depletion induced by silencing endogenous CDC37, indicating that CDC37's client stabilising function cannot be inactivated by substantially reducing its direct interaction with HSP90. However, CDC37 could not compensate for loss of HSP90 function, showing that CDC37 and HSP90 have their own distinct and non-redundant roles in maintaining kinase clients. Our data substantiate the important function of CDC37 in chaperoning protein kinases. Furthermore, we demonstrate that CDC37 can stabilise kinase clients by a mechanism that is not dependent on a substantial direct interaction between CDC37 and HSP90, but nevertheless requires HSP90 activity. These results have significant implications for therapeutic targeting of CDC37.

A systematic review of patient reported outcomes and patient experience in enhanced recovery after orthopaedic surgery.

INTRODUCTION: Orthopaedic enhanced recovery after surgery (ERAS) providers are encouraged to estimate the actual benefit of ERAS according to the patient's opinion by using patient generated data alongside traditional measures such as length of stay. The aim of this paper was to systemically review the literature on the use of patient generated information in orthopaedic ERAS across the whole perioperative pathway. METHODS: Publications were identified using Embase(™), MEDLINE(®), AMED, CINAHL(®) (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library and the British Nursing Index. Search terms related to experiences, acceptance, satisfaction or perception of ERAS and quality of life (QoL). FINDINGS: Of the 596 abstracts found, 8 papers were identified that met the inclusion criteria. A total of 2,208 patients undergoing elective hip and knee arthroplasty were included. Patient satisfaction was reported in 6 papers. Scores were high in all patients and not adversely affected by length of stay. QoL was reported in 2 papers and showed that QoL scores continued to increase up to 12 months following ERAS. Qualitative methods were used in one study, which highlighted problems with support following discharge. There is a paucity of data reporting on patient experience in orthopaedic ERAS. However, ERAS does not compromise patient satisfaction or QoL after elective hip or knee surgery. The measurement of patient experience should be standardised with further research.

Placental site trophoblastic tumours and the concept of fertility preservation.

The standard management of placental site trophoblastic tumours (PSTTs) is a radical hysterectomy with pelvic lymph node sampling. We present five cases to demonstrate a modified Strassman procedure (MSP), which is an alternative fertility-sparing technique. Each had a presumed solitary uterine PSTT. Following surgery, one patient remained in remission with her fertility intact. The other four underwent a completion hysterectomy because of incomplete excision of the disease. No residual disease was later found in two of these four uteri. This treatment should only be offered after extensive counselling. We intend to investigate the use of intraoperative frozen section analysis with cold-knife dissection in future.

Abdominal radical trachelectomy in West London.

OBJECTIVE: Traditionally, the surgical management of invasive cervical carcinoma that has progressed beyond microinvasion has been a radical abdominal hysterectomy. However, this results in the loss of fertility, with significant consequences for the young patient. This report describes abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with stage IA2-IIA cervical cancer who desire a fertility-sparing procedure without decreasing the curative rates. DESIGN: Observational, retrospective study. SETTING: Teaching hospital and regional cancer centre in London, UK. POPULATION: Patients undergoing ART. METHODS: Patients presenting during the period 2000-2009 with cervical cancer stage IA2-IIA were offered a trachelectomy, if they expressed a desire to preserve fertility. The type of trachelectomy (vaginal/abdominal) was chosen based on patient anatomy and neoplastic and magnetic resonance imaging characteristics. Each patient was counselled as to the experimental nature of the procedure. MAIN OUTCOME MEASURES: Survival, recurrence and fertility issues among ART patients. RESULTS: A total of 30 patients underwent ART (open and laparoscopic) between 2001 and 2009. Three patients presented with a recurrence, two of which have died (median follow-up: 24 months). Only three patients required further surgical re-intervention because of operative complications. Ten patients attempted to conceive, resulting in three conceptions (30%) and two live children. CONCLUSIONS: Abdominal radical trachelectomy provides a feasible, cost-effective and safe treatment option for young women who have been diagnosed with early-stage cervical cancer and wish to preserve their fertility.