Single-Centre Retrospective Audit of Clostridium difficile Infections Post Ileostomy Reversal.

Background Clostridium difficile (C. difficile) infection can have serious implications on patient outcomes, especially post ileostomy reversal. The symptoms can range from asymptomatic/mild to severe, with significant morbidity or mortality. Thus far, no study has been published to determine the role and impact of preoperative C. difficile testing prior to ileostomy reversal. The aim of this audit was to identify risk factors for the development of post-ileostomy reversal C. difficile infection and provide further improvements and direction for future research. Methods All patients undergoing ileostomy reversal at the General Surgery Department at Sir Charles Gairdner Hospital, a tertiary centre in Perth, Western Australia, were retrospectively identified between January 2019 and June 2021. Demographics and key data points, such as specific types of antibiotic usage, were extracted from patient notes and analysed using IBM SPSS Statistics for Windows, version 27 (released 2020; IBM Corp., Armonk, New York, United States). Results Sixty-nine patients were identified in the audit period, with 8.70% of patients testing positive for C. difficile infection post ileostomy reversal. At the index ileostomy formation operation, postoperative use of quinolone antibiotics was statistically associated with an increased risk of developing C. difficile on ileostomy reversal (odds ratio (OR) = 15.25, confidence interval (CI) 95%, p = 0.035). Intraoperative nitroimidazole use was statistically associated with a reduced risk of C. difficile infection on ileostomy reversal (OR = 0.16, CI 95%, p = 0.045). Patients who had diverticulitis as their underlying disease pathology were 10 times more likely to develop C. difficile infection post ileostomy reversal, although this finding was not statistically significant in our study. Conclusion Several risk factors were identified, such as the use of quinolone antibiotics or having underlying diverticulitis as causes for ileostomy formation. The results from this audit provides further direction in designing further research studies into the role and impact of C. difficile testing and treatment in the perioperative period around ileostomy reversal.

Cost analysis of a watch-and-wait approach in patients with a complete clinical response to chemoradiotherapy for rectal cancer.

BACKGROUND: There is increasing interest in the watch-and-wait approach for patients with rectal cancer who have had a complete clinical response following neoadjuvant long course chemoradiotherapy. This study is a cost analysis of expenditure on patients in the watch-and-wait program versus patients who underwent standard rectal resection followed by routine surveillance. METHODS: Data were prospectively collated and retrospectively analysed in all patients who presented with rectal cancer from January 2016 to January 2018 at Sir Charles Gairdner Hospital, Perth, Western Australia. Software developed by the North Metropolitan Health Service was used to capture comprehensive data to calculate the in-hospital expenditure for an individual patient throughout their treatment journey. RESULTS: For a patient enrolled in the watch-and-wait pathway, the total cost of surveillance over a 5-year period was $45 246. This was compared with the cost of an ultra-low anterior resection/loop ileostomy/closure of loop and routine postoperative surveillance which came to a total of $87 473. While a patient who had an abdominoperineal resection followed by routine 5-year surveillance had an expenditure of $82 290. CONCLUSION: There is growing evidence that the watch-and-wait strategy is a valid management option. In the cost-conscious environment of the current health care system, the watch-and-wait pathway is a cost-effective and economically advantage treatment.

Activation of Both TLR and NOD Signaling Confers Host Innate Immunity-Mediated Protection Against Microbial Infection.

The detection of microbial pathogens relies on the recognition of highly conserved microbial structures by the membrane sensor Toll-like receptors (TLRs) and cytosolic sensor NOD-like receptors (NLRs). Upon detection, these sensors trigger innate immune responses to eradicate the invaded microbial pathogens. However, it is unclear whether TLR and NOD signaling are both critical for innate immunity to initiate inflammatory and antimicrobial responses against microbial infection. Here we report that activation of both TLR and NOD signaling resulted in an augmented inflammatory response and the crosstalk between TLR and NOD led to an amplified downstream NF-κB activation with increased nuclear transactivation of p65 at both TNF-α and IL-6 promoters. Furthermore, co-stimulation of macrophages with TLR and NOD agonists maximized antimicrobial activity with accelerated phagosome maturation. Importantly, administration of both TLR and NOD agonists protected mice against polymicrobial sepsis-associated lethality with increased serum levels of inflammatory cytokines and accelerated clearance of bacteria from the circulation and visceral organs. These results demonstrate that activation of both TLR and NOD signaling synergizes to induce efficient inflammatory and antimicrobial responses, thus conferring protection against microbial infection.

Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways.

Myeloid-related protein 8 (Mrp8) is the active component of Mrp8/14 protein complex released by phagocytes at the site of infection and stimulates inflammatory responses. However, it is unclear whether Mrp8 could induce self-tolerance and cross-tolerance to bacterial infection. Here we report that Mrp8 triggered TNF-α and IL-6 release via a Toll-like receptor 4 (TLR4)-dependent manner. Pre-stimulation of murine macrophages and human monocytes with Mrp8 induced self-tolerance to Mrp8 re-stimulation and cross-tolerance to lipopolysaccharide (LPS), bacterial lipoprotein (BLP), gram-negative and gram-positive bacterial challenges, with substantially attenuated TNF-α and IL-6 release. Moreover, Mrp8 tolerisation significantly reduced serum TNF-α and IL-6, increased polymorphonuclear neutrophil (PMN) recruitment and accelerated bacterial clearance, thus protecting mice against LPS-induced lethality and cecal ligation and puncture (CLP)-induced polymicrobial sepsis. In addition to TLR4, TLR2 also contributed to Mrp8-induced inflammatory response and tolerance. Down-regulation of phosphorylated p38 by Mrp8 pre-stimulation was predominantly responsible for the intracellular mechanism of Mrp8-induced tolerance. Thus, our findings of Mrp8-induced self-tolerance and cross-tolerance may provide a potential strategy for attenuating an overwhelming proinflammatory cascade and enhancing antimicrobial responses during microbial sepsis.

A large un-ruptured abdominal aortic aneurysm causing pulmonary embolism.

A 79 years old woman presented in a peripheral hospital with dyspnea, right-sided pleuritic chest pain and cough for 3 days. On examination, she was tachycardiac and tachypneic. She had reduced air entry bilaterally on auscultation. Computed tomography-pulmonary angiogram, performed in peripheral Hospital, confirmed the diagnosis of pulmonary embolism, and she was commenced on warfarin. Ultrasonography showed no evidence of deep venous thrombosis in legs; however, ultrasound of the abdomen revealed an aortic aneurysm. She was hemodynamically stable on transfer to vascular surgery department, and her complete clinical examination revealed a pulsatile mass in the central abdomen. Computed tomography angiogram of aorta showed 8.7-cm abdominal aortic aneurysm. Venogram performed during inferior vena cava (IVC) filter insertion showed that IVC was displaced and compressed due to this large aortic aneurysm, causing thromboembolism. An open repair of the aneurysm was performed with uneventful recovery.

An iatrogenic popliteal pseudoaneurysm masked under compartment syndrome of leg.

This case describes a 60-year-old gentleman who presented with a pulsating mass behind his knee. Before this, he had a fasciotomy for suspected compartment syndrome of leg following knee arthroscopy, but this failed to resolve his leg symptoms. He was hemodynamically stable on presentation. His left calf was swollen with a circumference of 3 cm greater than right. There was a large pulsating mass palpable in his left popliteal fossa. Distal neurovascular status of the leg was intact. He had a normal cardiovascular, respiratory, abdominal and neurological examination. Ultrasound showed a cystic mass in the popliteal fossa suggestive of aneurysm. CT angiogram demonstrated a 6 × 5 × 4 cm pseudoaneurysm compressing and displacing the left popliteal artery with satisfactory three-vessel run-off. An emergency repair was performed. An arteriotomy was identified at the proximal end of pseudoaneurysm and it was closed with a patch of small saphenous vein. It led to a good clinical outcome.

Context dependent memory in two learning environments: the tutorial room and the operating theatre.

BACKGROUND: Psychologists have previously demonstrated that information recall is context dependent. However, how this influences the way we deliver medical education is unclear. This study aimed to determine if changing the recall context from the learning context affects the ability of medical students to recall information. METHODS: Using a free recall experimental model, fourteen medical student participants were administered audio lists of 30 words in two separate learning environments, a tutorial room and an operating theatre. They were then asked to recall the words in both environments. While in the operating theatre participants wore appropriate surgical clothing and assembled around an operating table. While in the tutorial room, participants dressed casually and were seated around a table. Students experienced the same duration (15 minutes) and disruption in both environments. RESULTS: The mean recall score from the 28 tests performed in the same environment was 12.96 +/- 3.93 (mean, SD). The mean recall score from the 28 tests performed in an alternative environment to the learning episode was 13.5 +/- 5.31(mean, SD), indicating that changing the recall environment from the learning environment does not cause any statistical difference (p=0.58). The average recall score of participants who learned and recalled in the tutorial room was 13.0 +/- 3.84 (mean, SD). The average recall score of participants who learnt and recalled in the operating theatre was 12.92 +/- 4.18 (mean, SD), representing no significant difference between the two environments for learning (p=0.4792). CONCLUSIONS: The results support the continued use of tutorial rooms and operating theatres as appropriate environments in which to teach medical students, with no significant difference in information recall seen either due to a same context effect or specific context effect.

Inefficient antimicrobial functions of innate phagocytes render infant mice more susceptible to bacterial infection.

Neonates and infants, due to the immaturity in their adaptive immunity, are thought to depend largely on the innate immune system for protection against bacterial infection. However, the innate immunity-mediated antimicrobial response in neonates and infants is incompletely characterized. Here, we report that infant mice were more susceptible to microbial sepsis than adult mice, with significantly reduced bacterial clearance from the circulation and visceral organs. Infant PMNs exhibited less constitutive expression of the chemokine receptor CXCR2, and bacterial infection caused further reduction of PMN CXCR2 in infant mice compared with adult mice. This correlates with diminished in vitro chemotaxis of infant PMNs toward the chemoattractant CXCL2 and impaired in vivo recruitment of infant PMNs into the infectious site. Furthermore, consistent with the reduced antimicrobial response in vivo, infant macrophages displayed an impaired bactericidal activity with a defect in phagosome maturation after ingestion of either gram-positive or gram-negative bacteria. Thus, infant mice exhibit an increased vulnerability to microbial infection with delayed bacterial clearance, which is associated with the inefficiency in their innate phagocyte-associated antimicrobial functions characterized by defects in PMN recruitment and macrophage phagosome maturation during microbial sepsis.

Use of magnetic resonance imaging in detection of breast cancer recurrence: a systematic review.

BACKGROUND: Diagnosis of breast cancer recurrence can be difficult as a result of the presence of scar tissue in the breast. Magnetic resonance imaging (MRI) may be superior to traditional imaging in diagnosis of recurrence because of its ability to differentiate malignancy from scarring. Current guidelines on investigation of suspected breast cancer recurrence recommend MRI when other investigations have equivocal findings. We performed the first systematic review on this topic. METHODS: Literature search revealed 35 potentially relevant studies; 10 were included in final analysis. Included were clinical studies comparing MRI with another diagnostic modality for diagnosis of breast cancer recurrence, with at least 10 patients, in the English language. Data extraction focused on sensitivity and specificity of standard diagnostic modalities and MRI for diagnosis of local disease recurrence. RESULTS: In total 494 patients were assessed across 10 studies; all were case series. Sensitivity of MRI for detection of recurrence ranged 75-100 %, while specificity ranged 66.6-100 %. Both sensitivity and specificity increased when MRI was performed after a longer time interval from the original surgery, although the longest follow-up reported was only 36 months. A negative MRI can avoid the need for further biopsy. CONCLUSIONS: Available data are based on clinically heterogeneous case series and superiority over standard triple assessment for breast cancer recurrence has not been proven. At present, MRI cannot be recommended in the routine diagnostic assessment for breast cancer recurrence but has a potentially useful role as a second-line investigation. A negative MRI is more useful than a positive MRI as positive MRIs require further investigation.