Colonoscopy follow-up for acute diverticulitis: a multi-centre review.

BACKGROUND: To investigate the value of routine colonoscopy, post-computed tomography (CT) confirmed diverticulitis. The current practice is to scope patients 6-8 weeks post an episode of acute diverticulitis. We hypothesise that this practice has a relatively low value. METHODS: A retrospective cohort study was conducted on adult patients presenting acute diverticulitis n = 1680 (uncomplicated = 1005, complicated = 675) between January 2017 and July 2019 at three tertiary hospitals in Perth. The National Bowel Cancer Screening Program (NBCSP) positive cases were the reference group (n = 1800). Data were analysed using SPSS v.27. RESULTS: One thousand two hundred seventy-two patients had a subsequent colonoscopy during the follow-up period, of which 24% (n = 306) were uncomplicated diverticulitis, 34% (n = 432) complicated diverticulitis, and 42% (n = 534) as the reference cohort. Patient demographics were similar between centres and subgroups. Incidence of primary colorectal cancer (CRC) was n = 3 (1.0%), n = 9 (2.1%), and n = 10 (1.9%) for uncomplicated diverticulitis, complicated diverticulitis, and NBCSP, respectively (p = 0.50). Subgroup analysis by age revealed a statistically significant higher rate of negative colonoscopy in uncomplicated diverticulitis patients aged over 50. CONCLUSION: Routine colonoscopy for patients with uncomplicated diverticulitis is not a cost-effective strategy for colorectal cancer screening patients over 50 years. These patients should participate in the NBCSP with biennial FOBT instead. We suggest continuing routine endoscopic evaluation for patients with uncomplicated diverticulitis under 50 years and all patients admitted with complicated diverticulitis.

Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. METHODS: A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. RESULTS: A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome (n = 30) and pulmonary embolism (n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% (n = 52), respectively 73% (n = 44). CONCLUSIONS: Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed.

Colonic bowel prep and body mass index: does one size fit all? A multi-centre review.

PURPOSE: To investigate whether body mass index (BMI) is a risk factor for inadequate bowel preparation in elective colonoscopy. The null hypothesis being BMI does not affect bowel preparation adequacy. METHODS: A retrospective cohort study of all participants with complete medical records who had an elective colonoscopy was conducted across three tertiary teaching hospitals in Perth, Western Australia, from January 2016 to July 2019. Participants were separated into BMI subgroups of healthy weight, overweight and obese (≥ 30 kg/m2). Data were extracted from medical records, colonoscopy and histopathology reports and were analysed using SPSS v.27. RESULTS: Of the 1082 cases analysed, 52.7% (n = 570) were male. The median age was 61 (range 18-85 years). The median BMI was 27.8 (range 20-52). The median procedure time is 28 (range 2-69 min). Routine follow-up was the clinical indication for 65% of colonoscopy procedures undertaken during the study period. Multivariate logistic regression, controlled for statistically insignificant confounders of age, type of bowel preparation agent, grade of the endoscopist, the indication for procedure and year of procedure, showed that being obese was significantly and independently associated with inadequate bowel preparation (OR 2.0, 95% CI (1.4-2.9) p < 0.001). Another significant factor was male (OR 1.6, 95% CI (1.2-2.1) p = 0.002). CONCLUSION: This study shows that obese patients are more likely to have inadequate bowel preparation at colonoscopy. Given the increased complication rates and health care costs associated with repeating colonoscopies and the increased risk of colorectal cancer in obese patients, it may be worth tailoring a more extensive bowel preparation regimen to ensure adequate visualisation of the colonic mucosa on the first attempt.

Invasive mechanical ventilation in patients with acute respiratory distress syndrome receiving extracorporeal support: a narrative review of strategies to mitigate lung injury.

Veno-venous extracorporeal membrane oxygenation is indicated in patients with acute respiratory distress syndrome and severely impaired gas exchange despite evidence-based lung protective ventilation, prone positioning and other parts of the standard algorithm for treating such patients. Extracorporeal support can facilitate ultra-lung-protective ventilation, meaning even lower volumes and pressures than standard lung-protective ventilation, by directly removing carbon dioxide in patients needing injurious ventilator settings to maintain sufficient gas exchange. Injurious ventilation results in ventilator-induced lung injury, which is one of the main determinants of mortality in acute respiratory distress syndrome. Marked reductions in the intensity of ventilation to the lowest tolerable levels under extracorporeal support may be achieved and could thereby potentially mitigate ventilator-induced lung injury and theoretically patient self-inflicted lung injury in spontaneously breathing patients with high respiratory drive. However, the benefits of this strategy may be counterbalanced by the use of continuous deep sedation and even neuromuscular blocking drugs, which may impair physical rehabilitation and impact long-term outcomes. There are currently a lack of large-scale prospective data to inform optimal invasive ventilation practices and how to best apply a holistic approach to patients receiving veno-venous extracorporeal membrane oxygenation, while minimising ventilator-induced and patient self-inflicted lung injury. We aimed to review the literature relating to invasive ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal support and discuss personalised ventilation approaches and the potential role of adjunctive therapies in facilitating lung protection.

Defining the limits of detection for chromosome rearrangements in the preimplantation embryo using next generation sequencing.

STUDY QUESTION: Is next generation sequencing (NGS) capable of detecting smaller sub-chromosomal rearrangements in human embryos than the manufacturer's quoted resolution suggests? SUMMARY ANSWER: NGS was able to detect unbalanced chromosome segments smaller than the manufacturer's resolution. WHAT IS KNOWN ALREADY: Array Comparative Genomic Hybridization (array-CGH) has been the gold standard platform used for PGD of chromosome rearrangements. NGS is a viable alternative to array-CGH for PGD of chromosome arrangements given that the manufacturer's guidelines quote a resolution of ≥20 Mb. However, as many patients carry a chromosome rearrangement <20 Mb, the detection limits of NGS warrant further investigation. STUDY DESIGN, SIZE, DURATION: This study involved a retrospective assessment of stored DNA samples from embryos that had previously been diagnosed as unbalanced by array-CGH as part of routine PGD in two separate IVF clinics between November 2013 and April 2017. SurePlex whole genome amplification (WGA) products derived from DNA extracted from an embryo biopsy sample known to carry an unbalanced form of a chromosome rearrangement were subjected to a specific NGS workflow (VeriSeq PGS). The results from the two technologies were compared for each sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: WGA products from 200 embryos known to carry unbalanced rearrangements were sequenced and analysed. These embryos had been created by 75 patients known to carry a chromosome rearrangement (68 reciprocal translocations, 3 pericentric inversions, 1 paracentric inversion, 2 insertions and 1 dual reciprocal and inversion). Each sample was assessed for the size of the segmental gain/loss (Mb), copy number for each segment and chromosome, segregation pattern, the number of bins in the analysis software used and concordance with array-CGH results. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 294 unbalanced chromosome segments were assessed. NGS was capable of detecting 285/294 (97%) unbalanced segments previously identified using array-CGH. The final PGD diagnosis was concordant for 200/200 (100%) embryos. In total, 44/75 (59%) patients contained an unbalanced chromosome segment below the quoted 20 Mb manufacturer's stated resolution. Of these, 35/44 (80%) patients had segments that were able to be detected using NGS, whilst maintaining clinical outcome concordance. LIMITATIONS, REASONS FOR CAUTION: Our study subset did not include any rearrangements involving the Y chromosome. NGS has less available bins per chromosome compared to the array-CGH platform used, thus it remains possible that chromosome rearrangements predicted to be small but still detectable by array-CGH may not be feasible for testing using NGS. This should be considered when undertaking a theoretical feasibility assessment for detecting the chromosome rearrangement in question. Only one specific workflow for WGA and NGS was investigated in this study. WIDER IMPLICATIONS OF THE FINDINGS: This study has shown that NGS is available for the detection of unbalanced chromosome rearrangements ≥10 Mb. STUDY FUNDING/COMPETING INTEREST(S): Part sponsorship of the VeriSeq PGS kits used was provided by Illumina. The remainder of the kits were provided by two commercial IVF clinics. None of the authors has any conflicting interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-ß1.

Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM), preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis, and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity; however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a three-dimensional (3D) ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and cocultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6 ± 5.9% vs. coculture: 65.2 ± 7.1% contraction; P < 0.01) and increased local ECM remodeling quantified by confocal microscopy. Under coculture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9 ± 11.1% vs. 6.4 ± 7.0% increase, respectively; P < 0.01). When cells were cultured under direct contact conditions, multiplex analysis of the coculture media revealed an increase in the paracrine factors TGF-ß1 and matrix metalloproteinase 9 compared with baseline (122.9 ± 10.1 pg/ml and 3,496.0 ± 190.4 pg/ml, respectively, vs. 21.5 ± 16.3 pg/ml and 183.3 ± 43.9 pg/ml; P < 0.001). TGF-ß blockade abolished the monocyte-induced increase in cardiac myofibroblast activity. These data suggest that direct cell-cell interaction between monocytes and cardiac myofibroblasts stimulates TGF-ß-mediated myofibroblast activity and increases remodeling of local matrix. Peripheral blood monocyte interaction with human cardiac myofibroblasts stimulates myofibroblast activity through release of TGF-ß1. These data implicate inflammation as a potential driver of cardiac fibrosis.

Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling.

BACKGROUND: Tissue fibrosis and chamber remodeling is a hallmark of the failing heart and the final common pathway for heart failure of diverse etiologies. Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1 (TGFß1) induces cardiac myofibroblast-mediated fibrosis and progressive structural tissue remodeling. OBJECTIVES: We examined the effects of low molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac myofibroblast-mediated extracellular matrix (ECM) dysregulation and remodeling. METHODS: Human cardiac biopsies were obtained during open-heart surgery and myofibroblasts were isolated, passaged, and seeded within type I collagen matrices. To induce myofibroblast activation and ECM remodeling, myofibroblast-seeded collagen gels were exposed to TGFß1. The extent of ECM contraction, myofibroblast activation, ECM dysregulation, and cell apoptosis was determined in the presence of LMW-FGF-2 and compared to its absence. Using a novel floating nylon-grid supported thin collagen gel culture platform system, myofibroblast activation and local ECM remodeling around isolated single cells was imaged using confocal microscopy and quantified by image analysis. RESULTS: TGFß1 induced significant myofibroblast activation and ECM dysregulation as evidenced by collagen gel contraction, structural ECM remodeling, collagen synthesis, ECM degradation, and altered TIMP expression. LMW-FGF-2 significantly attenuated TGFß1 induced myofibroblast-mediated ECM remodeling. These observations were similar using either ventricular or atrial-derived cardiac myofibroblasts. In addition, for the first time using individual cells, LMW-FGF-2 was observed to attenuate cardiac myofibroblast activation and prevent local cell-mediated ECM perturbations. CONCLUSIONS: LMW-FGF-2 attenuates human cardiac myofibroblast-mediated ECM remodeling and may prevent progressive maladaptive chamber remodeling and tissue fibrosis for patients with diverse structural heart diseases.

Extracorporeal membrane oxygenation use in patients with traumatic brain injury.

Venovenous extracorporeal membrane oxygenation (ECMO) is used for patients with severe, potentially reversible, respiratory failure unresponsive to conventional management. It is relatively contraindicated in patients with traumatic brain injury (TBI) due to bleeding complications and use of anticoagulation. We report two cases of TBI patients treated with ECMO.

Extracorporeal carbon dioxide removal for refractory status asthmaticus: experience in distinct exacerbation phenotypes.

Extracorporeal carbon dioxide removal (ECCO2R) may be indicated for refractory status asthmaticus when severe dynamic hyperinflation or life-threatening respiratory acidosis persists despite optimal medical and ventilator management. Most prior reports describe the application of ECCO2R to rapid-onset asthma exacerbation, requiring a short duration of extracorporeal support. We report two patients with refractory status asthmaticus managed with ECCO2R, emphasizing the use of modern extracorporeal technology, cannulation technique and management protocols, which may improve the risk-to-benefit profile of this strategy. This report highlights the challenges in managing patients with distinct asthma exacerbation phenotypes. The potential need for prolonged device support may alter provider expectations and offers a new perspective of the role of ECCO2R for status asthmaticus.

Venoarterial extracorporeal membrane oxygenation for the management of massive amlodipine overdose.

A 50-year-old man was admitted to the intensive care unit with respiratory failure and shock after suffering a massive overdose of amlodipine, lisinopril and hydrochlorothiazide. Despite mechanical ventilation, vasopressors, calcium gluconate, hyperinsulinemia-euglycemia therapy, methylene blue and intravenous fat emulsion, the patient's respiratory and hemodynamic status deteriorated. Venoarterial extracorporeal membrane oxygenation (ECMO) was initiated to provide cardiopulmonary support in the setting of profound respiratory failure and refractory shock. The patient was placed on ECMO 19 hours after arrival to the hospital, after which vasopressor and ventilatory requirements decreased significantly. The patient was decannulated from ECMO after 8 days and was discharged home after a 56-day hospitalization. Early institution of ECMO should be considered for the management of respiratory failure and refractory shock in the setting of calcium channel blocker overdose when medical therapies are insufficient.

Unexpected Ureter Within an Inguinal Hernia.

Inguinal hernias containing a ureter are a rare occurrence. They are rarely diagnosed pre-operatively and can lead to serious complications if inadvertently damaged during hernia repair. We present the case of a 36-year-old obese male who was found to have a ureter within his inguinal hernia intra-operatively. Due to imaging performed at another hospital, we have both pre and post-operative imaging demonstrating the ureter, its course into the inguinal hernia and its subsequent reduction back into the retroperitoneal space. We discuss the epidemiology of this phenomenon, the clinical implications and methods that have been suggested for pre-operative diagnosis.

Preimplantation genetic diagnosis for chromosome rearrangements - one blastomere biopsy versus two blastomere biopsy.

PURPOSE: Preimplantation Genetic Diagnosis (PGD) has proven to be a useful reproductive option for carriers of some chromosome rearrangements. The data presented in this study compares the impact of one versus two blastomere biopsy on the likelihood of achieving a PGD result, as well as the effect on subsequent embryo development and clinical outcomes. METHODS: IVF-PGD couples had either one or two blastomeres biopsied from all embryos with ≥7 blastomeres on day 3 post oocyte collection. These blastomeres were assessed for the specific chromosome rearrangement using Fluorescent In-situ Hybridisation (FISH). Further embryo development was monitored on days 4 and 5. Clinical outcomes were assessed retrospectively. RESULTS: The data shows that statistically more embryos achieved a PGD result following two blastomere biopsy, compared with one blastomere biopsy (92 % versus 88 %, respectively). Furthermore it was found that embryo development and clinical outcomes were similar between the two biopsy groups. CONCLUSIONS: Based on this analysis it appears that the biopsy of two blastomeres from embryos with ≥7 blastomeres on day 3 is a valid and successful approach for couples presenting for IVF-PGD for a chromosome rearrangement.

Extracorporeal membrane oxygenation for diffuse alveolar hemorrhage and severe hypoxemic respiratory failure from silicone embolism.

Liquid silicone is an inert material that may be used for cosmetic procedures by physicians as well as illegally by non-medical personnel. The use of silicone may result in severe complications, disfigurement, and even death. In addition, the indications for extracorporeal membrane oxygenation (ECMO) support have been increasing as a salvage therapy for a variety of life-threatening conditions. The patient is a 27-year-old woman with no significant medical conditions who developed silicone emboli, and subsequent diffuse alveolar hemorrhage after being injected with silicone in her gluteal region without medical supervision. She became profoundly hypoxemic and suffered a brief asystolic cardiac arrest in this setting. The patient was placed on veno-venous ECMO support for 14 days. Medical care during ECMO was complicated by pulmonary hemorrhage, hemothorax, pneumothorax, and blood clot, resulting in oxygenator change-out. A modified adult ECMO circuit (Jostra QuadroxD, Maquet Cardiopulmonary, Rastatt, Germany) was used to transport the patient from a nearby community affiliate hospital and then reconfigured for the medical intensive care unit on a standard HL-20 heart-lung console. Although the use of ECMO for severe hypoxemic respiratory failure has been widely reported, to our knowledge, this is the first reported successful use of ECMO for silicone embolism syndrome associated with diffuse alveolar hemorrhage and severe hypoxemic respiratory failure.

Bead rings at the endoplasmic reticulum-Golgi complex boundary: morphological changes accompanying inhibition of intracellular transport of secretory proteins in arthropod fat body tissue.

Golgi complex beads are 10-nm particles arranged in rings on the smooth surface of rough endoplasmic reticulum (ER) makind the forming face of the Golgi complex (GC). In arthropod cells they stain specifically with bismuth. Their morphology has been studied after treatment with reagents known to interfere with GC function. Inhibitors of oxidative phosphorylation (antimycin A, cyanide, and anoxia), but not an inhibitor of glycolysis (iodoacetate), both cause the bead rings to collapse and the GC saccules to round up, and inhibit transition vesicle (TV) formation. Cycloheximide blocks protein synthesis on ribosomes but does not stop TV formation or disrupt bead rings, even after prolonged treatment (6 h) to allow emptying of the rough ER cisternae. Thus the collapse of bead rings is not attributable to inhibition of protein synthesis, and the ring structure of beads does not require continued protein synthesis and secretion for its maintenance. Valinomycin has effects on the GC similar to those of antimycin A, but A23187, monensin, and lasalocid do not affect bead ring structure or TV formation. These results are consistent with valinomycin's secondarily uncoupling mitochondria, which collapses bead rings and prevents TV formation. Thus inhibitors of oxidative phosphorylation do not influence the beads through cation movement. Because mononsin and lasalocid block secretion at the level of the condensing vacuoles, bead rings are not influenced by blocks in secretion distal to them or by the backup of secretory material. These experiments are consistent with inhibitors of oxidative phosphorylation collapsing bead rings by decreasing intracellular ATP. The concomitant block to TV formation and the collapse of bead rings suggests that integrity of the bead rings is essential for the transport of secretory material from the rough ER to the GC.

Need for reform in health professions accrediting.

At least 50 vocational or professional groups, exclusive of specialties within categories, now provide a health service. Many have established accrediting procedures for maintaining educational standards, and the number is increasing. So great is the demand from the accrediting bodies that universities and academic health centers find that the cost in terms of money, time, and duplication of effort has become exhorbitant, and thereby a major problem in the management of educational institutions. The duplication of effort leads to fragmentation of the entire accrediting process, and this, in turn, fosters inadequate sharing of health professions educational experiences. A model is presented that would lessen the burden of accrediting on educational institutions and simultaneously permit testing of the feasibility of a multiprofessional accrediting mechanism.

Aspirin: intestinal damage in rats.

Lesions induced by aspirin in the small intestine of the rat were visualized after 4 hours by the intravenous administration of a 5 percent solution of pontamine sky blue, 6 BX dye. Dose-response curves in fasted and fed rats indicated that the fed rat was about eight times more susceptible to aspirin-induced intestinal damage than was the fasted rat, while the fasted rat was about 13 times more susceptible to aspirin-induced gastric damage than was the fed rat.

Randomized controlled trial of supervised exercise to evaluate changes in cardiac function in patients with peripheral atherosclerotic disease.

INTRODUCTION: Peripheral atherosclerotic disease (PAD) is a condition characterized by low functional capacity which is associated with impaired free living, ambulation and low exercise tolerance. The purpose of this randomized controlled study was to evaluate whether changes in maximal walking time are associated with adaptations in cardiovascular function following supervised exercise. METHODS: After ethics approval, 28 patients (63 +/- 11 years) completed a graded treadmill test (2 min stages, 3.2 km h(-1), with gradient increasing 2% every 2 min) until they reached level three or four on the claudication pain scale. Peak oxygen consumption was assessed on a breath-by-breath basis, by online expiratory gas analysis. Following a 40-min recovery period, peak cardiac output was measured using the non-invasive carbon dioxide rebreathing method described by Defares (J Appl Physiol, 13, 1958, 159). Peak cardiac power output was then computed using the equation described by Cooke et al. (Heart, 1998, 79, 289). Patients were randomly assigned to one of two groups: supervised, who exercised at the hospital twice weekly for 12 weeks or control, who received normal treatment which included encouragement to walk regularly. RESULTS: After 12 weeks, there were no significant changes in body mass, peak oxygen consumption, peak cardiac output, peak heart rate, peak cardiac power output, respiratory exchange ratio or rating of perceived exertion in both the supervised and control group. There was a significant improvement (91%) in maximal walking distance following the supervised exercise programme. Although patients' peak cardiovascular measurements were unchanged, the patients in the supervised exercise group were able to complete a higher workload at the end of the 12 weeks of exercise, for the equivalent demands on the circulation system. CONCLUSIONS: The findings from this study suggest that a short-term period of supervised exercise training results in an improved walking time in patients with limiting claudication because of PAD. It also demonstrated that the cardiovascular system becomes more efficient in meeting the demands of exercise. It is recommended that individuals with PAD should undertake exercise as a form of treatment.

LICOS, a primordial costimulatory ligand?

In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha). Our results define the components of a distinct and novel costimulatory pathway and raise the possibility that LICOS, rather than B7-1 or B7-2, is the contemporary homologue of a primordial vertebrate costimulatory ligand.