To scope or not - the challenges of managing patients with positive fecal occult blood test after recent colonoscopy.

BACKGROUND: Colorectal cancer (CRC) is a major health problem. There is minimal consensus of the appropriate approach to manage patients with positive immunochemical fecal occult blood test (iFOBT), following a recent colonoscopy. AIM: To determine the prevalence of advanced neoplasia in patients with a positive iFOBT after a recent colonoscopy, and clinical and endoscopic predictors for advanced neoplasia. METHODS: The study recruited iFOBT positive patients who underwent colonoscopy between July 2015 to March 2020. Data collected included demographics, clinical characteristics, previous and current colonoscopy findings. Primary outcome was the prevalence of CRC and advanced neoplasia in a patient with positive iFOBT and previous colonoscopy. Secondary outcomes included identifying any clinical and endoscopic predictors for advanced neoplasia. RESULTS: The study included 1051 patients (male 53.6%; median age 63). Forty-two (4.0%) patients were diagnosed with CRC, 513 (48.8%) with adenoma/sessile serrated lesion (A-SSL) and 257 (24.5%) with advanced A-SSL (AA-SSL). A previous colonoscopy had been performed in 319 (30.3%). In this cohort, four (1.3%) were diagnosed with CRC, 146 (45.8%) with A-SSL and 56 (17.6%) with AA-SSL. Among those who had a colonoscopy within 4 years, none had CRC and 7 had AA-SSL. Of the 732 patients with no prior colonoscopy, there were 38 CRCs (5.2%). Independent predictors for advanced neoplasia were male [odds ratio (OR) = 1.80; 95% confidence interval (CI): 1.35-2.40; P < 0.001), age (OR = 1.04; 95%CI: 1.02-1.06; P < 0.001) and no previous colonoscopy (OR = 2.07; 95%CI: 1.49-2.87; P < 0.001). CONCLUSION: A previous colonoscopy, irrespective of its result, was associated with low prevalence of advanced neoplasia, and if performed within four years of a positive iFOBT result, was protective against CRC.

Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases.

History of Integral Fixation for Anterior Lumbar Interbody Fusion (ALIF): The Hartshill Horseshoe.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) is a common spinal fusion option for different spinal pathologies. In the early years, implant migrations/expulsions were potential complications of ALIFs due to the lack of integral fixation. We present a historical vignette on the inception and development of the first stand-alone ALIF (SA-ALIF) implant-the Hartshill Horseshoe (HH). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic search was carried out for 3 online databases focusing on implant development for ALIF, refining the search to before 1995. A personal communication with the original patent holders of the HH was used due to the lack of formal publication of the HH during its early years. RESULTS: Since 1932, the idea of anterior lumbar fusion was proposed and was carried out in 1933 using a tibial peg. Autografts were first reported in 1936 as interbody spacers for ALIF. Since then, bone grafts were commonly used for ALIF. However, ALIFs were not commonly performed due to variable reported outcomes. A pilot study in 1971 reported the use titanium mesh blocks as interbody implants in 6 patients. No articles reporting the use of integral fixation for SA-ALIF implants were found before the development of the HH in 1984. CONCLUSIONS: The HH was the first synthetic SA-ALIF implant developed. Since the HH, multiple SA-ALIF implants have been designed. The benefits of integral fixation in a SA-ALIF device include immediate implant stability, ability to reduce and correct deformity postimplantation, prevention of implant migration, and increased implant-bony endplate contact for early osseointegration.

An update on gastrointestinal endoscopy-associated infections and their contributing factors.

INTRODUCTION: During clinical use, gastrointestinal endoscopes are grossly contaminated with patient's native flora. These endoscopes undergo reprocessing to prevent infectious transmission upon future use. Endoscopy-associated infections and outbreaks have been reported, with a recent focus on the transmission of multi-drug resistant organisms. This review aims to provide an update on endoscopy-associated infections, and the factors contributing to their occurrence. METHODS: PubMed, ScienceDirect, and CINAHL were searched for articles describing gastrointestinal endoscopy-associated infections and outbreaks published from 2008 to 2018. Factors contributing to their occurrence, and the outcomes of each outbreak were also examined. RESULTS: This review found 18 articles, 16 of which described duodenoscope-associated infections, and the remaining two described colonoscope- and gastroscope-associated infection respectively. Outbreaks were reported from the United States, France, China, Germany, the Netherlands and the United Kingdom. The causative organisms reported were Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Salmonella enteritidis. CONCLUSIONS: A number of factors, including lapses in reprocessing, biofilm formation, endoscope design issues and endoscope damage, contribute to gastrointestinal endoscopy associated infection. Methods of improving endoscope reprocessing, screening for contamination and evaluating endoscope damage may be vital to preventing future infections and outbreaks.

Lumbar Disk Arthroplasty for Degenerative Disk Disease: Literature Review.

Low back pain is the principal cause of long-term disability worldwide. We intend to address one of its main causes, degenerative disk disease, a spinal condition involving degradation of an intervertebral disk. Following unsuccessful conservative treatment, patients may be recommended for surgery. The two main surgical treatments for lumbar degenerative disk disease are lumbar fusion: traditional standard surgical treatment and lumbar disk arthroplasty, also known as lumbar total disk replacement. Lumbar fusion aims to relieve pain by fusing vertebrae together to eliminate movement at the joint, but it has been criticized for problems involving insignificant pain relief, a reduced range of motion, and an increased risk of adjacent segment degeneration. This leads to development of the lumbar total disk replacement technique, which aims to relieve pain replacing a degenerated intervertebral disk with a moveable prosthesis, thus mimicking the functional anatomy and biomechanics of a native intervertebral disk. Over the years a large range of prosthetic disks has been developed. The efficacy and current evidence for these prostheses are discussed in this review. The results of this study are intended to guide clinical practice and future lumbar total disk replacement device choice and design.

Resumption of Antithrombotic Agents in Chronic Subdural Hematoma: A Systematic Review and Meta-analysis.

BACKGROUND: The clinical decision whether and when to resume antithrombotics in patients with chronic subdural hematomas (CSDH) postoperatively is limited by a lack of quality evidence exploring this topic. Our study aims to assess the available evidence of patient complication outcomes, specifically hemorrhagic and thromboembolic events, following the resumption or non-resumption of antithrombotic agents postoperatively in CSDH patients already on these agents before CSDH. METHODS: We followed recommended PRISMA guidelines for systematic reviews. Electronic database searches were performed to identify included studies. Data were extracted and analyzed using meta-analysis. RESULTS: Eight studies were included for analysis. The most common indication for antithrombotic treatment before onset of CSDH was atrial fibrillation (29.6%), followed by prosthetic heart valve (16.6%), recent myocardial infarction (14.1%), prior stroke or transient ischemic attack (11.6%), and finally venous thromboembolism (8.3%). The overall hemorrhagic complication rate was 14.8% in the resumption group versus 18.6% in the no resumption group (P = 0.591). This did not differ between early (<2 weeks) versus late (>1 month) resumption (15% vs. 18.6%, P = 0.97). The rate of thromboembolism however was statistically lower in those who resumed antithrombotics (2.9% vs. 6.8%, P<0.001). There was a non-significant trend towards higher thromboembolic rates with early resumption (5.3% vs. 2.1%, P = 0.23). CONCLUSIONS: The decision to resume antithrombotics postoperatively in the clinical management of CSDH patients is a complex one and should therefore be a highly individualized process. Our meta-analysis demonstrates that in selected cases, it is feasible to resume early antithrombotic treatment without additional hemorrhagic or thromboembolic risk.

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma.

Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM.

Anterior lumbar interbody fusion (ALIF) as an option for recurrent disc herniations: a systematic review and meta-analysis.

BACKGROUND: Recurrent intervertebral disc herniation is a relatively common occurrence after primary discectomy for lumbar intervertebral disc herniation. For recurrent herniations after repeat discectomies, a growing body of evidence suggests that fusion is effective in appropriately selected cases. Theoretically, anterior lumbar interbody fusion (ALIF) allows for comprehensive discectomy, less trauma to spinal nerves and paraspinal muscles and avoidance of the disadvantages of repeat posterior approaches. However, ALIF has also been associated with risk of vascular injury and retrograde ejaculation. This current systematic review and meta-analysis aims to assess the viability of ALIF as a surgical treatment for recurrent disc herniations. METHODS: Seven studies were identified from six electronic databases and secondary reference lists. Pre-defined endpoints were extracted from the included studies and meta-analyzed. RESULTS: For the 181 patients from included studies, ALIF resulted in significant average improvements in Oswestry Disability Index (ODI) scores (50.49%, P<0.001), Visual Analogue Scale (VAS) back pain scores (47.85%, P<0.001) and VAS leg pain scores (37.00%, P<0.001). Average blood loss was acceptable at 122 mL (P<0.001) and average operation duration was 89 minutes (P<0.001). Average hospital stay was 5.28 days (P<0.001). Only 22 perioperative complications were reported, with subsidence the most commonly reported complication. CONCLUSIONS: Pooled evidence suggests that ALIF is a feasible approach for the treatment of recurrent disc herniations, demonstrating significant improvements in back and leg pain and minimal complications. These findings warrant further investigation in large prospective registries and multi-center studies.

Focal hypermobility observed in cervical arthroplasty with Mobi-C.

In recent decades cervical arthroplasty, or cervical disc replacement, has been steadily increasing in popularity as a procedure for the treatment of degenerative pathologies of the cervical spine. This is based on an evolving body of literature that documents superior outcomes in cervical disc replacement over fusion, for both single and double level pathologies, in well selected patients. One of the more recent and popular implants currently on the market is the Mobi-C cervical artificial disc (LDR Medical; Troyes, France). In this paper we report on two cases where focal hypermobility was observed following total disc replacement using the Mobi-C cervical artificial disc. This is followed by a discussion as to potential contributing factors to this hypermobility in relation to both implant design, and operative technique, suggesting potential changes that might prevent this in future patients.

Management of patients following detection of unsuspected colon lesions by PET imaging.

Positron emission tomography (PET) is a well-established and integral component of multimodality imaging in oncology. However, the expanded use of PET in oncological and also non-oncological imaging (such as in assessing inflammatory conditions) has identified more lesions or tumors at unsuspected locations, such as in the large bowel during examination of patients not known to have colorectal disease. We review the clinical significance of colon lesions that were discovered incidentally by PET imaging and management strategies for gastroenterologists.

Use of endoscopic mucosal clips in radiotherapy planning for oesophageal carcinoma: a series of three cases.

This paper describes the technique of placing endoscopic mucosal clips to localize oesophageal carcinoma and hence facilitate radiotherapy planning. This technique has been used on three patients in our centre. One was treated radically with external beam radiotherapy and two were treated palliatively (retreatment) with intraluminal brachytherapy. Mucosal hemoclips were placed at the time of endoscopy to indicate the superior and inferior extent of the tumour. The clips provided a radiologically-recognisable marker of the tumour extent and were visible on simulation films or planning CT scans. The radiation portal included the tumour as demarcated by the clips with an adequate margin. There were no complications related to the placement of the clips. All patients completed the radiotherapy course as planned.