MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome.

Sturge-Weber syndrome (SWS), a neurocutaneous disorder, is characterized by capillary malformations (CM) in the skin, brain, and eyes. Patients may suffer from seizures, strokes, and glaucoma, and only symptomatic treatment is available. CM are comprised of enlarged vessels with endothelial cells (ECs) and disorganized mural cells. Our recent finding indicated that the R183Q mutation in ECs leads to heightened signaling through phospholipase Cß3 and protein kinase C, leading to increased angiopoietin-2 (ANGPT2). Furthermore, knockdown of ANGPT2, a crucial mediator of pro-angiogenic signaling, inflammation, and vascular remodeling, in EC-R183Q rescued the enlarged vessel phenotype in vivo. This prompted us to look closer at the microenvironment in CM-affected vascular beds. We analyzed multiple brain histological sections from patients with GNAQ-R183Q CM and found enlarged vessels devoid of mural cells along with increased macrophage-like cells co-expressing MRC1 (CD206, a mannose receptor), CD163 (a scavenger receptor and marker of the monocyte/macrophage lineage), CD68 (a pan macrophage marker), and LYVE1 (a lymphatic marker expressed by some macrophages). These macrophages were not found in non-SWS control brain sections. To investigate the mechanism of increased macrophages in the perivascular environment, we examined THP1 (monocytic/macrophage cell line) cell adhesion to EC-R183Q versus EC-WT under static and laminar flow conditions. First, we observed increased THP1 cell adhesion to EC-R183Q compared to EC-WT under static conditions. Next, using live cell imaging, we found THP1 cell adhesion to EC-R183Q was dramatically increased under laminar flow conditions and could be inhibited by anti-ICAM1. ICAM1, an endothelial cell adhesion molecule required for leukocyte adhesion, was strongly expressed in the endothelium in SWS brain histological sections, suggesting a mechanism for recruitment of macrophages. In conclusion, our findings demonstrate that macrophages are an important component of the perivascular environment in CM suggesting they may contribute to the CM formation and SWS disease progression.

CD45 Is Sufficient to Initiate Endothelial-to-Mesenchymal Transition in Human Endothelial Cells-Brief Report.

BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) is a dynamic process in which endothelial cells acquire mesenchymal properties and in turn contribute to tissue remodeling and growth. Previously, we found EndMT associated with mitral valve adaptation after myocardial infarction. Furthermore, mitral valve endothelial cells collected at 6 months post-myocardial infarction expressed the pan-leukocyte marker CD45 and EndMT markers. Additionally, mitral valve endothelial cells induced to undergo EndMT with TGF (transforming growth factor)-ß1 strongly coexpressed CD45 but not CD11b or CD14. Pharmacologic inhibition of the CD45 PTPase (protein tyrosine phosphatase) domain in mitral valve endothelial cells blocked TGFß-induced EndMT. This prompted us to speculate that, downstream of TGFß, CD45 induces EndMT. METHODS: We activated the endogenous CD45 promoter in human endothelial colony forming cells (ECFCs) using CRISPR (cluster regularly interspaced short palindromic repeats)/inactive Cas9 (CRISPR-associated protein 9) transcriptional activation. Bulk RNA sequencing was performed on control ECFCs and CD45-positive ECFCs to identify transcriptomic changes. Three functional assays-cellular migration, collagen gel contraction, and transendothelial electrical resistance-were conducted to assess mesenchymal properties in CD45-positive ECFCs. RESULTS: Activation of the endogenous CD45 promoter in ECFC and 3 additional sources of endothelial cells induced expression of several genes implicated in EndMT. In addition, CD45-positive ECFCs showed increased migration, a hallmark of EndMT, increased collagen gel contraction, a hallmark of mesenchymal cells, and decreased cell-cell barrier integrity, indicating reduced endothelial function. CONCLUSIONS: CD45 is sufficient to incite an EndMT phenotype and acquisition of mesenchymal cell properties in normal human ECFCs. We speculate that CD45, through its C-terminal PTPase domain, initiates signaling events that drive EndMT.

Long-term outcomes after using retrievable vena cava filters in major trauma patients with contraindications to prophylactic anticoagulation.

PURPOSE: To investigate the long-term outcomes of using vena cava filters to prevent symptomatic pulmonary embolism (PE) in major trauma patients who have contraindications to prophylactic anticoagulation. METHODS: This was an a priori sub-study of a randomized controlled trial (RCT) involving long-term outcome data of 223 patients who were enrolled in Western Australia. State-wide clinical information system, radiology database and death registry were used to assess long-term outcomes, including incidences of venous thromboembolism, venous injury and mortality beyond day-90 follow-up. RESULTS: The median follow-up time of 198 patients (89%) who survived beyond 90 days was 65 months (interquartile range 59-73). Ten patients (5.1%) died after day-90 follow-up; and four patients developed venous thromboembolism, including two with symptomatic PE, all allocated to the control group (0 vs 4%, p = 0.043). Inferior vena cava injuries were not recorded in any patients. The mean total hospitalization cost, including the costs of the filter and its insertion and removal, to prevent one short- or long-term symptomatic PE was A$284,820 (€193,678) when all enrolled patients were considered. The number of patients needed to treat (NNT = 5) and total hospitalization cost to prevent one symptomatic PE (A$1,205 or €820) were, however, substantially lower when the filter was used only for patients who could not be anticoagulated within seven days of injury. CONCLUSION: Long-term complications related to retrievable filters were rare, and the cost of using filters to prevent symptomatic PE was acceptable when restricted to those who could not be anticoagulated within seven days of severe injury.

Clinicians' perceptions of medical student teaching in a tertiary hospital.

Background: Medical student placements in teaching hospitals are a cornerstone for gaining clinical experience. However, the ever-evolving nature of health care has also changed the delivery of student education. Few studies have examined clinicians' perspectives toward teaching students in this setting. We sought to explore the attitudes of clinicians involved in teaching medical students at an Australian tertiary hospital. Methods: Clinicians were invited by email to complete an anonymous online survey developed using a combination of questions from previously validated surveys. The questions utilized 5-point Likert scale statements and were based around the themes of "personal purpose and enjoyment of teaching" and "barriers and challenges to teaching." Results for each question are presented as frequency and percentage. Results: Of 490 invited, 67 (13.7%) consultant clinicians from various specialties responded. The majority (>92%) enjoy teaching and see it as part of their work. However, approximately half thought that medical student teaching was under-recognized and half did not have adequate time to teach due to workload. Approximately 60% responded that there was insufficient time to get to know students to provide feedback and approximately 40% indicated that the scope of student knowledge and desired outcomes are not clearly defined by medical schools. Discussion: Our contemporary survey identifies modifiable factors which should be targeted. If these factors are addressed successfully, it may allow the hospital and university medical school to harness the valuable resource of clinical teachers. This could enhance the medical student experience and promote a culture of teaching and learning in hospitals.

A prospective ex vivo biomechanical analysis of retrievable inferior vena cava filters.

OBJECTIVE: In the present study, we investigated the structural integrity of inferior vena cava (IVC) filters after their retrieval. METHODS: A prospective ex vivo biomechanical analysis was performed of the structural integrity of 100 IVC filters used in a randomized controlled trial to evaluate the effectiveness of prophylactic IVC filters in preventing mortality or symptomatic pulmonary embolism in major trauma patients. RESULTS: Of the 100 included patients, 7 (7%) had required more than one attempt to remove the filter. The median duration of the filter left in situ was 54 days (interquartile range, 17-101 days). During the initial attempt to remove six filters (6%), thrombi were found entrapped and required 4 weeks of systemic anticoagulation therapy before the filters could be removed in a second attempt. A positive correlation was found between the duration of the filter left in situ and the loss in metallic elasticity of the nitinol alloy of the filter struts (Pearson correlation coefficient, 0.232; P = .008). One filter was adherent to the IVC wall and required open surgical removal 227 days after its initial placement. One of the six long struts of the filter had been fractured during the removal process, with evidence of hardening to bending stress in the remaining five struts of the fractured filter compared with the struts of the 25 intact filters. Fibrous endothelial tissue (73%) and thrombi (33%) adherent to the retrieved filters were frequently observed. The presence of adherent fibrous tissue was not significantly related statistically to the duration of the filter left in situ (P = .353) but was more common among the patients who had had a delay in receiving prophylactic anticoagulation therapy (mean difference, 2 days; 95% confidence interval, 0.6-3.3; P = .039). CONCLUSIONS: Metallic fatigue might account for IVC filter strut fractures. Fibrous endothelial tissue adherent to the filters was common, especially for those with a delay in receiving prophylactic anticoagulation therapy.

S2 Heart Sound Detects Aortic Valve Calcification Independent of Hemodynamic Changes in Mice.

Background: Calcific aortic valve disease (CAVD) is often undiagnosed in asymptomatic patients, especially in underserved populations. Although artificial intelligence has improved murmur detection in auscultation exams, murmur manifestation depends on hemodynamic factors that can be independent of aortic valve (AoV) calcium load and function. The aim of this study was to determine if the presence of AoV calcification directly influences the S2 heart sound. Methods: Adult C57BL/6J mice were assigned to the following 12-week-long diets: (1) Control group (n = 11) fed a normal chow, (2) Adenine group (n = 4) fed an adenine-supplemented diet to induce chronic kidney disease (CKD), and (3) Adenine + HP (n = 9) group fed the CKD diet for 6 weeks, then supplemented with high phosphate (HP) for another 6 weeks to induce AoV calcification. Phonocardiograms, echocardiogram-based valvular function, and AoV calcification were assessed at endpoint. Results: Mice on the Adenine + HP diet had detectable AoV calcification (9.28 ± 0.74% by volume). After segmentation and dimensionality reduction, S2 sounds were labeled based on the presence of disease: Healthy, CKD, or CKD + CAVD. The dataset (2,516 S2 sounds) was split subject-wise, and an ensemble learning-based algorithm was developed to classify S2 sound features. For external validation, the areas under the receiver operating characteristic curve of the algorithm to classify mice were 0.9940 for Healthy, 0.9717 for CKD, and 0.9593 for CKD + CAVD. The algorithm had a low misclassification performance of testing set S2 sounds (1.27% false positive, 1.99% false negative). Conclusion: Our ensemble learning-based algorithm demonstrated the feasibility of using the S2 sound to detect the presence of AoV calcification. The S2 sound can be used as a marker to identify AoV calcification independent of hemodynamic changes observed in echocardiography.

Incremental cost of venous thromboembolism in trauma patients with contraindications to prophylactic anticoagulation: a prospective economic study.

Venous thromboembolism (VTE) is common in patients after major trauma. Attributable cost of VTE and whether this is related to the severity of injury have not been thoroughly investigated. We aimed to define the hospitalization costs of VTE and assess whether the costs were related to the severity of injury in this prospective economic study. Cost data of each patient enrolled in the da Vinci trial were drawn from hospital finance departments and standardized to 2020 Australian dollars (A$); and Injury Severity Score and Trauma Embolic Scoring System were used to quantify the severity of injury. Of the 223 patients who had complete financial cost data available until day-90 follow-up, 37 (16.6%) developed VTE, including upper limb (n = 3) and lower limb deep vein thrombosis (n = 25), pulmonary embolism (n = 7) and clots entrapped in a vena cava filter. The median total radiology (A$4307) as well as the hospitalization costs (A$138,526) of those who had VTE were significantly higher than those without VTE (A$1210; p < 0.001 and A$105,842; p = 0.023, respectively). The incremental hospitalization cost attributable to VTE was most apparent among those who had sustained extremely severe injuries, and estimated to be between A$43,292 (95% confidence interval [CI] 12,624-73,961, p = 0.006) and 41,680 (95%CI 7766-75,594, p = 0.016) after adjusted for Trauma Embolic Scoring System and Injury Severity Scores, respectively. VTE was common after major trauma and incurred a substantial incremental financial cost to the healthcare system, especially among those who had extremely severe injuries.

Pigmentation Affects Elastic Fiber Patterning and Biomechanical Behavior of the Murine Aortic Valve.

The aortic valve (AoV) maintains unidirectional blood distribution from the left ventricle of the heart to the aorta for systemic circulation. The AoV leaflets rely on a precise extracellular matrix microarchitecture of collagen, elastin, and proteoglycans for appropriate biomechanical performance. We have previously demonstrated a relationship between the presence of pigment in the mouse AoV with elastic fiber patterning using multiphoton imaging. Here, we extended those findings using wholemount confocal microscopy revealing that elastic fibers were diminished in the AoV of hypopigmented mice (KitWv and albino) and were disorganized in the AoV of K5-Edn3 transgenic hyperpigmented mice when compared to wild type C57BL/6J mice. We further used atomic force microscopy to measure stiffness differences in the wholemount AoV leaflets of mice with different levels of pigmentation. We show that AoV leaflets of K5-Edn3 had overall higher stiffness (4.42 ± 0.35 kPa) when compared to those from KitWv (2.22 ± 0.21 kPa), albino (2.45 ± 0.16 kPa), and C57BL/6J (3.0 ± 0.16 kPa) mice. Despite the striking elastic fiber phenotype and noted stiffness differences, adult mutant mice were found to have no overt cardiac differences as measured by echocardiography. Our results indicate that pigmentation, but not melanocytes, is required for proper elastic fiber organization in the mouse AoV and dictates its biomechanical properties.

Effect of rectal washout on local recurrence of rectal cancer in the era of total mesorectal excision: Meta-analysis.

INTRODUCTION: Presence of intraluminal viable cancer cells implanting into the anastomosis has been proposed as a potential cause for developing local recurrence in patients undergoing anterior resection for rectal cancer. Rectal washout has been proposed as a method to prevent this from happening. There have been conflicting reports in literature regarding the effect of rectal washout on local recurrence. We aim to look at the role of rectal washout in preventing local recurrence of rectal cancer in patients undergoing total or tumor-specific mesorectal excision (TME). MATERIALS AND METHODS: A literature review of studies evaluating the role of rectal washout on rectal cancer local recurrence was performed using PubMed, Scopus, EMBASE and non-English language literature search using CiNii (Japanese) and CNKI (Chinese). Inclusion criteria were use of TME, comparison of rectal washout with no washout, and evaluation of local recurrence as outcome. RESULTS: Four studies were identified according to inclusion criteria. The meta-analysis showed a protective effect of rectal washout on local recurrence (OR 0.45 95% CI 0.45-0.75). However, one of the studies included had more than 90% weightage. Excluding this study from analysis showed no difference on local recurrence with rectal washout (OR 0.94, 95% CI 0.37-2.36). CONCLUSION: The effect of rectal washout on rectal cancer local recurrence in patients who undergo TME is questionable and needs to be evaluated further by prospective studies.

Validation of the geriatric trauma outcome scores in predicting outcomes of elderly trauma patients.

BACKGROUND: Using three patient characteristics, including age, Injury Severity Score (ISS) and transfusion within 24 h of admission (yes vs. no), the Geriatric Trauma Outcome Score (GTOS) and Geriatric Trauma Outcome Score II (GTOS II) have been developed to predict mortality and unfavourable discharge (to a nursing home or hospice facility), of those who were ≥65 years old, respectively. OBJECTIVES: This study aimed to validate the GTOS and GTOS II models. For the nested-cohort requiring intensive care, we compared the GTOS scores with two ICU prognostic scores - the Acute Physiology and Chronic Health Evaluation (APACHE) III and Australian and New Zealand Risk of Death (ANZROD). METHODS: All elderly trauma patients admitted to the State Trauma Unit between 2009 and 2019 were included. The discrimination ability and calibration of the GTOS and GTOS II scores were assessed by the area under the receiver-operating-characteristic (AUROC) curve and a calibration plot, respectively. RESULTS: Of the 57,473 trauma admissions during the study period, 15,034 (26.2%) were ≥65 years-old. The median age and ISS of the cohort were 80 (interquartile range [IQR] 72-87) and 6 (IQR 2-9), respectively; and the average observed mortality was 4.3%. The ability of the GTOS to predict mortality was good (AUROC 0.838, 95% confidence interval [CI] 0.821-0.855), and better than either age (AUROC 0.603, 95%CI 0.581-0.624) or ISS (AUROC 0.799, 95%CI 0.779-0.819) alone. The GTOS II's ability to predict unfavourable discharge was satisfactory (AUROC 0.707, 95%CI 0.696-0.719) but no better than age alone. Both GTOS and GTOS II scores over-estimated risks of the adverse outcome when the predicted risks were high. The GTOS score (AUROC 0.683, 95%CI 0.591-0.775) was also inferior to the APACHE III (AUROC 0.783, 95%CI 0.699-0.867) or ANZROD (AUROC 0.788, 95%CI 0.705-0.870) in predicting mortality for those requiring intensive care. CONCLUSIONS: The GTOS scores had a good ability to discriminate between survivors and non-survivors in the elderly trauma patients, but GTOS II scores were no better than age alone in predicting unfavourable discharge. Both GTOS and GTOS II scores were not well-calibrated when the predicted risks of adverse outcome were high.

Effectiveness of Laparoscopic Skills Workshop on Enhancing Knowledge and Skills of Surgical Residents and Its Comparison with DOPS (Direct Observation of Procedural Skills) Scores: Prospective Cohort Study.

INTRODUCTION: Simulation-based surgical skills workshops are commonly used in the surgical training programs to enhance the knowledge and psychomotor skills of the residents, but there is scarcity of objective data on their effectiveness. The aim of our study was to explore if a 1-day laparoscopic skills workshop enhanced the knowledge and skills of surgical residents in minimal access surgery and if it had any correlation with the Direct Observation of Procedural Skills (DOPS) scores. METHODS: This was a quasi-experimental, single-arm, repeat measure, prospective cohort study design. Thirty-three residents from general surgery and obstetrics/gynecology programs of Aga Khan University participated in the study. A daylong laparoscopic skills workshop consisting of lectures, videos, and hands-on practice was offered. The pre-workshop knowledge and skills scores of residents were assessed and compared with immediate post-workshop scores and scores of repeat assessment at 2 months. The scores of DOPS on laparoscopic procedures before and after the workshop were also compared. RESULTS: The results of our study indicated that mean post-workshop (p < 0.001) and interval scores (p < 0.001) for both cognitive and psychomotor skills were significantly higher compared with mean pre-workshop scores. Similarly, post-workshop DOPS scores were significantly higher (p < 0.011) compared with pre-workshop DOPS scores. CONCLUSIONS: One-day laparoscopic skills workshop resulted in significant improvement in knowledge and psychomotor skills of the surgical residents. The skills gained from the workshop also resulted in improvement of DOPS scores reflecting the transfer of skills to real-life performance. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT03982927.

Evaluation of the trauma triage accuracy in a Level 1 Australian trauma centre.

OBJECTIVES: To assess the rate of undertriage of major trauma patients and to assess factors contributing to undertriage in a modern Australian Level 1 trauma centre. METHODS: A retrospective case series of 600 consecutive major trauma (injury severity score [ISS] >15) patients admitted to Royal Perth Hospital (RPH) during 2015 was performed. Data were compiled via the prospectively maintained hospital trauma registry for all patients admitted with a major trauma during the study period. Results were analysed for patient demographics, mechanism and outcomes. The primary outcome of the study was to determine the rate of undertriage of major trauma at RPH by establishing whether or not the trauma team activation page was correctly sent at the time of patient arrival based on hospital criteria. RESULTS: The average age of patients in the study population was 46.5 (±21.5) years and the mean ISS was 24.7 (±9.3). The most common mechanism of injury was falls, motor vehicle accidents and motorbike accidents. One hundred and sixty-nine patients (28%) did not have trauma team activation on arrival to the ED. Among these patients, 132 did not fulfil the RPH trauma activation criteria. The remaining 37 patients (6.1%) did meet the criteria and were considered undertriaged. Subgroup analysis showed a statistically significant difference in age between the patients who had trauma team activation (42.7 ± 19.5 years) and those who did not (55.9 ± 23.3 years). CONCLUSION: In this cohort of major trauma, a 6.1% undertriage performance of the triage tool was observed. Sub-analysis of the data showed that elderly patients were more likely to be undertriaged.

Stem Cell Cytoskeletal Responses to Pulsatile Flow in Heart Valve Tissue Engineering Studies.

Heart valve replacement options remain exceedingly limited for pediatric patients because they cannot accommodate somatic growth. To overcome this shortcoming, heart valve tissue engineering using human bone marrow stem cells (HBMSCs) has been considered a potential solution to the treatment of critical congenital valvular defects. The mechanical environments during in vitro culture are key regulators of progenitor cell fate. Here, we report on alterations in HBMSCs, specifically in their actin cytoskeleton and their nucleus under fluid-induced shear stresses of relevance to heart valves. HBMSCs were seeded in microfluidic channels and were exposed to the following conditions: pulsatile shear stress (PSS), steady shear stress (SS), and no flow controls (n = 4/group). Changes to the actin filament structure were monitored and subsequent gene expression was evaluated. A significant increase (p < 0.05) in the number of actin filaments, filament density and angle (between 30° and 84°), and conversely a significant decrease (p < 0.05) in the length of the filaments were observed when the HBMSCs were exposed to PSS for 48 h compared to SS and no flow conditions. No significant differences in nuclear shape were observed among the groups (p > 0.05). Of particular relevance to valvulogenesis, klf2a, a critical gene in valve development, was significantly expressed only by the PSS group (p < 0.05). We conclude that HBMSCs respond to PSS by alterations to their actin filament structure that are distinct from SS and no flow conditions. These changes coupled with the subsequent gene expression findings suggest that at the cellular level, the immediate effect of PSS is to initiate a unique set of quantifiable cytoskeletal events (increased actin filament number, density and angle, but decrease in filament length) in stem cells, which could be useful in the fine-tuning of in vitro protocols in heart valve tissue engineering.

Serial lipase for pancreatitis: not enough evidence.

BACKGROUND: Lipase is both a sensitive and specific marker for diagnosing pancreatitis. However, the benefit of serial lipase in both monitoring and defining prognosis remains undetermined. This systematic review was conducted to further evaluate this potential application. In addition, this review also looked into the benefits of serial lipase in the subgroup of traumatic pancreatitis. METHODS: PubMed, Cochrane Library and Google Scholar were systematically searched for related articles, between January 1995 and December 2015, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses standards. Data was extracted and analysed by two authors. RESULTS: Seven studies were included in the final analysis: six retrospective and one prospective studies were identified. Five studies (all retrospective) concluded no benefits in serial lipase for prognostication, while two studies identified serial lipase as a beneficial prognostic factor for acute pancreatitis. Of the included studies, only two involved traumatic pancreatitis (both dedicated to the paediatric population). CONCLUSION: The evidence supporting or opposing serial lipase as a prognostic factor for pancreatitis is weak and consists mainly of retrospective analyses. The only prospective data identified suggested benefits to serial lipase in prognosis. Further prospective studies evaluating the prognostic value of serial lipase in the adult population with both traumatic and non-traumatic pancreatitis are required given the paucity of available evidence.

A "sweet-spot" for fluid-induced oscillations in the conditioning of stem cell-based engineered heart valve tissues.

Fluid-induced shear stresses are involved in the development of cardiovascular tissues. In a tissue engineering framework, this stimulus has also been considered as a mechanical regulator of stem cell differentiation. We recently demonstrated that the fluid-oscillating effect in combination with a physiologically-relevant shear stress magnitude contributes to the formation of stem cell-derived de novo heart valve tissues. However, the range of oscillations necessary to induce favorable gene expression and engineered tissue formation is unknown. In this study, we took a computational approach to establish a range of oscillatory shear stresses that may optimize in vitro valvular tissue growth. Taking a biomimetic approach, three physiologically-relevant flow waveforms from the human: (i) aorta, (ii) pulmonary artery and (iii) superior vena cava were utilized to simulate pulsatile flow conditions within a bioreactor that housed 3 tissue specimens. Results were compared to non-physiological pulsatile flow (NPPF) and cyclic flexure-steady flow (Flex-Flow) conditions. The oscillatory shear index (OSI) was used to quantify the fluid-induced oscillations occurring on the specimen surfaces. The range of mean OSI under the physiological conditions investigated was found to be 0.18 ≤ OSI ≤ 0.23. On the other hand, NPPF and Flex-Flow environments yielded a mean OSI of 0.37 and 0.11 respectively, which were 46% higher and 45% lower than physiological conditions. Moreover, we subsequently conducted OSI-based human bone marrow stem cell (HBMSC) culture experiments which resulted in preferential valvular gene expression and phenotype (significant upregulation of BMP, KLF2A, CD31 and α-SMA using an OSI of 0.23 in comparison to a lower OSI of 0.10 or a higher OSI of 0.38; p < .05). These findings suggest that a distinct range or a "sweet-spot" for physiological OSI exists in the mechanical conditioning of tissue engineered heart valves grown from stem cell sources. We conclude that in vitro heart valve matrix development could be further enhanced by simultaneous exposure of the engineered tissues to physiologically-relevant magnitudes of both fluid-induced oscillations and shear stresses.

Surgical management of inflammatory bowel disease: A low prevalence, developing country perspective.

OBJECTIVE: To determine the outcomes of surgical management of inflammatory bowel disease. METHODS: The retrospective case series was conducted at Aga Khan University Hospital, Karachi, and comprised medical record of adult patients operated between January 1986 and December 2010 for inflammatory bowel disease. Outcomes consisted of complications till last follow-up and 30-day mortality (disease or procedure related). Functional status of patients with ileal pouch was determined via telephone. SPSS 16 was used to analyse data. RESULTS: Of the 36 patients whose records were reviewed, 21(58%) were males, and body mass index was less than 23 in 34(91%). A total of 27(75%) patients underwent elective surgery for their condition. Ileal pouch was formed in 9(25%). Overall mortality was 14(38.8%). Overall incidence of complications was 26(72%), with wound infection being the most common early morbidity in 11(30.5%). Late morbidity included pouchitisin 4/9 (44.9%) and strictures 2/36 (5.5%).On telephonic follow-up, 6 of the remaining 7patients (85%) with ileal pouch were satisfied with the functional results of the procedure. CONCLUSIONS: The retrospective case series represents results from a developing country with low prevalence of inflammatory bowel disease and hence limited experience.

Intra abdominal hypertension; incidence, prevalence and outcomes in a mixed intensive care unit: Prospective cohort study.

BACKGROUND: This study was conducted primarily to determine the prevalence and incidence of intra-abdominal hypertension (IAH) in a mixed ICU (medical & surgical) population and, secondarily, to compare outcomes between patients with and without IAH. METHODS: The prospective cohort study was conducted from April to July 2011 on adult patients admitted in ICU, on mechanical ventilation and with an indwelling urinary catheter. Intra-vesicular pressure was measured. Primary endpoint was IAH and it was defined as Intra-abdominal pressure>12 mm Hg on two consecutive readings 6 h apart. RESULTS: Total 83 patients were enrolled in the study; 61% from medical services and 39% from surgical services. Mean age in years±SD was 47 ± 17.5 with male preponderance (66%). IAH was detected in 23/83 (28%) at the time of admission, while six out of remaining 60 patients (10%) developed the condition during their ICU stay; the incidence and prevalence was 10% and 35%, respectively. Secondary end points of the study comparing outcomes between patients with and without IAH, though different in the two groups, did not achieve statistical significance. In-hospital mortality 65.5% vs. 44.4% p-value 0.054. New onset renal failure 34.5% vs. 16.7% p-value 0.054%. Difficulty in weaning from mechanical ventilation 37.9% vs. 25.9% p-value 0.008. CONCLUSION: IAH is a poorly recognized clinical entity with potentially devastating impact on patient outcomes. Since majority of patients had IAH at the time of admission, all ICU patients especially on ventilator should have baseline intra-abdominal pressures measured at the time of admission and subjected to appropriate management to prevent them from developing abdominal compartment syndrome.

Postoperative port-site pain after gall bladder retrieval from epigastric vs. umbilical port in laparoscopic cholecystectomy: a randomized controlled trial.

OBJECTIVE: To determine whether gall bladder (GB) retrieval from umbilical port is associated with more pain at port site as compared to GB retrieval from epigastric port in adult patients undergoing four port elective laparoscopic cholecystectomy at a tertiary care hospital. METHODS: Adult patients, who were undergoing elective laparoscopic cholecystectomy during a six month period in 2010 at our institute, were randomized to either group A (n = 60, GB retrieval through epigastric port) or group B (n = 60, GB retrieval through umbilical port). VAS for pain was assessed by a registered nurse at 1, 6, 12, 24 and 36 h after surgery. RESULTS: The VAS for pain at umbilical port was less than epigastric port at 1, 6, 12, 24 and 36 h after surgery (5.9 ± 1.1 vs. 4.1 ± 1.5, 4.6 ± 0.94 vs. 3.5 ± 1.05, 3.9 ± 0.85 vs. 2.4 ± 0.79, 3.05 ± 0.87 vs. 2.15 ± 0.87, respectively) and the difference was statistically significant (p-value < 0.001). Multiple linear regression was done for port site pain at 24 h and the VAS at umbilical port was less than epigastric port with VAS difference of 0.9 after adjusting for age, sex, duration of surgery and additional analgesia use (r2 = 0.253, p-value < 0.001). CONCLUSION: Gall bladder retrieval from umbilical port is associated with lower port site pain than GB retrieval from epigastric port in patients undergoing elective laparoscopic cholecystectomy. We recommend umbilical port for gall bladder retrieval.

Emerging indications for percutaneous cholecystostomy for the management of acute cholecystitis--a retrospective review.

UNLABELLED: Acute cholecystitis is a frequent cause of general surgical admissions with a mortality risk that is related to the age of the patient. Percutaneous cholecystostomy (PC) has been used as a bridging technique while awaiting resolution of sepsis. We evaluated the outcome of our study population following percutaneous cholecystostomy for acute cholecystitis due to benign etiologies. METHODS: Retrospective review of patients undergoing PC from January 1988 to December 2008. Patients were reviewed for demographic features, co-morbidity, resolution of symptoms, hospital stay, outcome, complications and ASA class. RESULTS: 62 patients underwent PC for acute cholecystitis. 49 patients had calculous cholecystitis. 61% (n = 38) were ≥ 60 years old. 92% had resolution of symptoms within 48 h, and 8% had partial or no resolution. 84% had a decline in total leucocyte counts. The mean hospital stay was 10.6 days and 30-day mortality was 15%. 69% patients had no post-procedure complication. Of the remainder, 1 patient had post-procedure hemorrhage and the remaining developed complications that included pneumonia, hypotension and vasovagal reactions. The duration of drainage ranged from 1 to 3 months. 3 patients underwent emergency cholecystectomy during the same admission, 20 patients underwent interval cholecystectomy. 22 patients had no further intervention and had no recurrent symptoms, of these 73% (n = 16) had calculous cholecystitis. In this sub-group of non-operated patients, 76% were ASA III & IV. CONCLUSIONS: PC is a low risk management option for high risk patients with acute cholecystitis. It can be used as a temporizing measure while awaiting resolution of sepsis and optimization of co-morbidities, or as a definitive therapeutic option for acalculous cholecystitis. We also conclude that it has a good potential to be used as a definitive therapy for high risk (ASAIII & IV) patients with acute calculous cholecystitis.