Iron-(Fe3+) dependent reactivation of telomerase drives colorectal cancers.

Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer (CRC) samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by re-activating the dormant human-reverse-transcriptase (hTERT) subunit of telomerase holoenzyme in an iron-(Fe3+)-dependent-manner and thereby drives CRCs. Chemical genetic screens combined with isothermal-dose response fingerprinting and mass-spectrometry identified a small molecule SP2509, that specifically inhibits Pirin-mediated hTERT reactivation in CRCs by competing with iron-(Fe3+) binding. Our findings, first to document how metal ions reactivate telomerase, provide a molecular mechanism for the well-known association between red meat, and increased incidence of CRCs. Small molecules like SP2509 represent a novel modality to target telomerase that acts as driver of 90% human cancers and is yet to be targeted in clinic.

Transvaginal versus transabdominal specimen extraction in minimally invasive surgery: a systematic review and meta-analysis.

AIM: Natural orifice specimen extraction (NOSE) is an alternative to conventional transabdominal retrieval. We aimed to compare outcomes following transvaginal specimen extraction (TVSE) and transabdominal specimen extraction (TASE) in minimally invasive abdominal surgery. METHODS: An electronic database search of PubMed, Embase and CENTRAL was performed from inception until March 2023. Comparative studies evaluating TVSE versus TASE in adult female patients were included. Studies involving transanal NOSE, endoluminal surgery, or TVSE with concomitant hysterectomy were excluded. Weighted mean differences (WMD) and odds ratio were estimated for continuous and dichotomous outcomes respectively. Primary outcomes were postoperative day 1 (POD1) pain and length of stay (LOS). Secondary outcomes were operative time, rescue analgesia, morbidity, and cosmesis. A review of sexual, oncological, and technical outcomes was performed. RESULTS: Thirteen studies (2 randomised trials, 11 retrospective cohort studies), involving 1094 patients (TASE 583, TVSE 511), were included in the analysis. Seven studies involved colorectal disease and six assessed gynaecological conditions. TVSE resulted in significantly decreased POD1 pain (WMD 1.08, 95% CI: 0.49, 1.68) and shorter LOS (WMD 1.18 days, 95% CI: 0.14, 2.22), compared to TASE. Operative time was similar between both groups, with fewer patients requiring postoperative rescue analgesia with TVSE. Overall morbidity rates, as well as both wound-related and non-wound related complication rates were better with TVSE, while anastomotic morbidity rates were comparable. Cosmetic scores were higher with TVSE. TVSE did not result in worse sexual or oncological outcomes. CONCLUSION: TVSE may be feasible and beneficial compared to TASE when performed by proficient laparoscopic operators, using appropriate selection criteria. Continued evaluation with prospective studies is warranted.

Postoperative outcomes after prehabilitation for colorectal cancer patients undergoing surgery: a systematic review and meta-analysis of randomized and nonrandomized studies.

PURPOSE: Prehabilitation (PH) is purported to improve patients' preoperative functional status. This systematic review and meta-analysis sought to compare short-term postoperative outcomes between patients who underwent a protocolized PH program and the existing standard of care among colorectal cancer patients awaiting surgery. METHODS: A search in MEDLINE/PubMed, the Cochrane Library, Embase, Scopus, and CINAHL was conducted to identify relevant articles. Repetitive and exhaustive combinations of MeSH search terms ("prehabilitation," "colorectal cancer," "colon cancer," and "rectal cancer") were used to identify randomized and nonrandomized studies comparing PH versus standard of care for colorectal cancer patients awaiting surgery. The primary outcomes included postoperative morbidity, length of hospital stay, and readmission rates. RESULTS: Seven studies including 1,042 colorectal cancer patients (PH, 382) were included. No significant differences were found in intraoperative outcomes. The postoperative complication rates were comparable between groups (Clavien-Dindo grades I and II: risk ratio, 0.82; 95% confidence interval, 0.62-1.07; P=0.15; Clavien-Dindo grades ≥III: risk ratio, 1.02; 95% confidence interval, 0.72-1.44; P=0.92). There were also no significant differences in length of hospital stay (P=0.21) or the risk of 30-day readmission (P=0.68). CONCLUSION: Although PH does not appear to improve short-term postoperative outcomes following colorectal cancer surgery, the quality of evidence is impaired by the limited trials and heterogeneity. Thus, further large-scale trials are warranted to draw definitive conclusions and establish the long-term effects of PH.

Transanal Total Mesorectal Excision With Delayed Coloanal Anastomosis (TaTME-DCAA) Versus Laparoscopic Total Mesorectal Excision (LTME) and Robotic Total Mesorectal Excision (RTME) for Low Rectal Cancer: A Propensity Score-Matched Analysis of Short-term Outcomes, Bowel Function, and Cost.

INTRODUCTION: Total mesorectal excision (TME) with delayed coloanal anastomosis (DCAA) is surgical option for low rectal cancer, replacing conventional immediate coloanal anastomosis (ICAA) with bowel diversion. This study aimed to assess the outcomes of transanal TME (TaTME) with DCAA versus laparoscopic TME (LTME) with ICAA versus robotic TME (RTME) with ICAA. METHODS: This was a retrospective propensity score-matched analysis of patients who underwent elective TaTME-DCAA between November 2021 and June 2022. Patients were propensity-score matched in a ratio of 1:3 to patients who underwent LTME-ICAA and RTME-ICAA from January 2019 to December 2020. Outcome measures were histopathologic results, postoperative morbidity, function, and inpatient costs. RESULTS: Twelve patients in the TaTME-DCAA group were compared with 36 patients in the LTME-ICAA and RTME-ICAA groups each after propensity score matching. Histopathologic results and postoperative morbidity rates were statistically similar. Overall stoma-related complication rates in the ICAA groups were 11%. Median total length of hospital stays for TME plus stoma reversal surgery was similar across all techniques (10 vs. 10 vs. 9 days; P =0.532). Despite a significantly shorter duration of follow-up, bowel function after TaTME-DCAA was comparable to that of LTME-ICAA and RTME-ICAA. Overall median inpatient costs of TaTME-DCAA were comparable to LTME-ICAA and significantly cheaper than RTME-ICAA ($31,087 vs. $29,927 vs. $36,750; P =0.002). CONCLUSIONS: TaTME with DCAA is a feasible and safe technique compared with other minimally invasive methods of TME, while avoiding bowel diversion and stoma-related complications, as well as comparing favorably in terms of overall hospitalization costs.

Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis.

Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.

Haemodynamic changes in visceral hybrid repairs of type III and type V thoracoabdominal aortic aneurysms.

The visceral hybrid procedure combining retrograde visceral bypass grafting and completion endovascular stent grafting is a feasible alternative to conventional open surgical or wholly endovascular repairs of thoracoabdominal aneurysms (TAAA). However, the wide variability in visceral hybrid configurations means that a priori prediction of surgical outcome based on haemodynamic flow profiles such as velocity pattern and wall shear stress post repair remain challenging. We sought to appraise the clinical relevance of computational fluid dynamics (CFD) analyses in the setting of visceral hybrid TAAA repairs. Two patients, one with a type III and the other with a type V TAAA, underwent successful elective and emergency visceral hybrid repairs, respectively. Flow patterns and haemodynamic parameters were analysed using reconstructed pre- and post-operative CT scans. Both type III and type V TAAAs showed highly disturbed flow patterns with varying helicity values preoperatively within their respective aneurysms. Low time-averaged wall shear stress (TAWSS) and high endothelial cell action potential (ECAP) and relative residence time (RRT) associated with thrombogenic susceptibility was observed in the posterior aspect of both TAAAs preoperatively. Despite differing bypass configurations in the elective and emergency repairs, both treatment options appear to improve haemodynamic performance compared to preoperative study. However, we observed reduced TAWSS in the right iliac artery (portending a theoretical risk of future graft and possibly limb thrombosis), after the elective type III visceral hybrid repair, but not the emergency type V repair. We surmise that this difference may be attributed to the higher neo-bifurcation of the aortic stent graft in the type III as compared to the type V repair. Our results demonstrate that CFD can be used in complicated visceral hybrid repair to yield potentially actionable predictive insights with implications on surveillance and enhanced post-operative management, even in patients with complicated geometrical bypass configurations.

Transvaginal Natural Orifice Specimen Extraction (NOSE) in Laparoscopic Colorectal Cancer Surgery With New Insights on Technique and Patient Selection.

BACKGROUND: Following laparoscopic colorectal surgery, transabdominal specimen extraction requires a mini-laparotomy or Pfannenstiel incision, associated with increased postoperative pain and wound complications. The vagina has several unique properties that make natural orifice specimen extraction (NOSE) ideal. We report our experience with transvaginal NOSE for colorectal cancer surgery. MATERIALS AND METHODS: A transvaginal sizer allows the posterior vagina to be incised under tension. A transverse or cruciate incision is made, followed by the insertion of a double-ring wound protector. The external ring is opened against the perineum to shorten the length of the conduit for specimen delivery. Vaginotomy closure is performed via laparoscopy using a barbed suture. RESULTS: Seventeen consecutive female patients underwent elective colorectal cancer surgery with attempted transvaginal NOSE. Median age and body mass index was 67 (range: 50 to 82) years and 26.5 (range: 19.7 to 35.8) kg/m 2 , respectively. Fourteen patients (82%) underwent left-sided resections and 3 (18%) underwent right-sided resections. Median operating time, blood loss, and length of hospital stay was 245 (range: 155 to 360) minutes, 30 (range: 10 to 500) mL, and 3 (range: 2 to 9) days, respectively. Transvaginal extraction was unsuccessful in 1 (6%) patient. Two (12%) patients experienced early postoperative morbidity, neither attributable to the extraction procedure. Median tumor circumferential diameter was 3.3 (range: 2.2 to 7.0) cm. Median follow-up duration was 17 (range: 8 to 27) months. There was no instance of sexual dysfunction. CONCLUSIONS: Transvaginal NOSE for colorectal cancer surgery is feasible and safe in selected patients. Overall specimen diameter, inclusive of tumor and mesentery, relative to pelvic outlet and conduit diameter is the most important consideration for transvaginal NOSE.

Effect of preoperative oral antibiotics and mechanical bowel preparation on the prevention of surgical site infection in elective colorectal surgery, and does oral antibiotic regime matter? a bayesian network meta-analysis.

PURPOSE: Surgical site infection (SSI) impacts 5-20% of patients after elective colorectal surgery. There are varying reports on the effectiveness of oral antibiotics (OAB) with preoperative mechanical bowel preparation (MBP) in preventing SSI. We aim to determine the role of OAB and MBP in preventing SSI after elective colorectal surgery. We also determine if a specific OAB regimen will be more effective than others. METHODS: This study investigated the impact of OAB and MBP in patients undergoing elective colorectal surgery. PubMed, MEDLINE, Ovid, Cochrane Central Register of Controlled Trials, ACP Journal Club, and Embase databases were searched for randomized clinical trials (RCTs) published by June 2022. All RCTs comparing various preoperative bowel preparation regimens, including pairwise or multi-intervention comparisons, were included. To establish the role of OAB and MBP in preventing SSI, we conducted a Bayesian network meta-analysis on all RCTs. We further performed subgroup analysis to determine the most effective OAB regimen. RESULTS: Among included 46 studies with a total of 12690 patients, patients in the MBP + OAB group were less likely to have SSI than those having MBP-only (OR 0.55, 95% CrI 0.39-0.76), and without MBP and OAB (OR 0.52, 95% CrI 0.32-0.84). OAB regimen C (kanamycin + metronidazole) and A (neomycin + metronidazole) demonstrated a significantly reduced incidence of SSI, compared to regimen B (neomycin + erythromycin) with OR 0.24 (95% CrI 0.07-0.79) and 0.26 (95% CrI 0.07-0.99) respectively. CONCLUSIONS: OAB with MBP reduces the risk of SSI after elective colorectal surgery. Providing adequate aerobic and anaerobic coverage with OAB may confer better protection against SSI.

Laser hemorrhoidoplasty versus conventional hemorrhoidectomy for grade II/III hemorrhoids: a systematic review and meta-analysis.

PURPOSE: This study compared the short- and long-term clinical outcomes of laser hemorrhoidoplasty (LH) vs. conventional hemorrhoidectomy (CH) in patients with grade II/III hemorrhoids. METHODS: PubMed/Medline and the Cochrane Library were searched for randomized and nonrandomized studies comparing LH against CH in grade II/III hemorrhoids. The primary outcomes included postoperative use of analgesia, postoperative morbidity (bleeding, urinary retention, pain, thrombosis), and time of return to work/daily activities. RESULTS: Nine studies totaling 661 patients (LH, 336 and CH, 325) were included. The LH group had shorter operative time (P<0.001) and less intraoperative blood loss (P<0.001). Postoperative pain was lower in the LH group, with lower postoperative day 1 (mean difference [MD], -2.09; 95% confidence interval [CI], -3.44 to -0.75; P=0.002) and postoperative day 7 (MD, -3.94; 95% CI, -6.36 to -1.52; P=0.001) visual analogue scores and use of analgesia (risk ratio [RR], 0.59; 95% CI, 0.42-0.81; P=0.001). The risk of postoperative bleeding was also lower in the LH group (RR, 0.18; 95% CI, 0.12- 0.28; P<0.001), with a quicker return to work or daily activities (P=0.002). The 12-month risks of bleeding (P>0.999) and prolapse (P=0.240), and the likelihood of complete resolution at 12 months, were similar (P=0.240). CONCLUSION: LH offers more favorable short-term clinical outcomes than CH, with reduced morbidity and pain and earlier return to work or daily activities. Medium-term symptom recurrence at 12 months was similar. Our results should be verified in future well-designed trials with larger samples.

Survival outcomes of salvage surgery in the watch-and-wait approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis compared the outcomes of the watch-and-wait (WW) approach versus radical surgery (RS) in rectal cancers with clinical complete response (cCR) after neoadjuvant chemoradiotherapy. METHODS: This study followed the PRISMA guidelines. Major databases were searched to identify relevant articles. WW and RS were compared through meta-analyses of pooled proportions. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis rates. Pooled salvage surgery rates and outcomes were also collected. The Newcastle-Ottawa scale was employed to assess the risk of bias. RESULTS: Eleven studies including 1,112 rectal cancer patients showing cCR after neoadjuvant chemoradiation were included. Of these patients, 378 were treated nonoperatively with WW, 663 underwent RS, and 71 underwent local excision. The 2-year OS (risk ratio [RR], 0.95; P = 0.94), 5-year OS (RR, 2.59; P = 0.25), and distant metastasis rates (RR, 1.05; P = 0.80) showed no significant differences between WW and RS. Local recurrence was more frequent in the WW group (RR, 6.93; P < 0.001), and 78.4% of patients later underwent salvage surgery (R0 resection rate, 97.5%). The 2-year DFS (RR, 1.58; P = 0.05) and 5-year DFS (RR, 2.07; P = 0.02) were higher among RS cases. However, after adjustment for R0 salvage surgery, DFS showed no significant between-group difference (RR, 0.82; P = 0.41). CONCLUSION: Local recurrence rates are higher for WW than RS, but complete salvage surgery is often possible with similar long-term outcomes. WW is a viable strategy for rectal cancer with cCR after neoadjuvant chemoradiation, but further research is required to improve patient selection.

Surgery for chronic arthropathy in people with haemophilia.

BACKGROUND: Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the absence or deficiency of a clotting factor protein. Staging classifications, such as the Arnold-Hilgartner classification for haemophilic arthropathy of the knee, radiologically reflect the extent of knee joint destruction with underlying chronic synovitis. Management of this highly morbid disease process involves intensive prophylactic measures, and chemical or radioisotope synovectomy in its early stages. However, failure of non-surgical therapy in people with progression of chronic arthropathy often prompts surgical management, including synovectomy, joint debridement, arthrodesis, and arthroplasty, depending on the type of joint and extent of the damage. To date, management of people with mild to moderate chronic arthropathy from haemophilia remains controversial; there is no agreed standard treatment. Thus, the benefits and disadvantages of non-surgical and surgical management of mild to moderate chronic arthropathy in people with haemophilia needs to be systematically reviewed.  OBJECTIVES: To assess the efficacy and safety of surgery for mild to moderate chronic arthropathy in people with haemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, and two trial registers to August 2022. We also handsearched relevant journals and conference abstract books. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing surgery and non-surgical interventions, for any joint with chronic arthropathy, in people with haemophilia, who were at least 12 years old. DATA COLLECTION AND ANALYSIS: The review authors did not identify any trials to include in this review. MAIN RESULTS: The review authors did not identify any trials to include in this review. AUTHORS' CONCLUSIONS: The review authors did not identify any trials to include in this review. Due to a lack of research in this particular area, we plan to update the literature search every two years, and will update review if any new evidence is reported. There is a need for a well-designed RCT that assesses the safety and efficacy of surgical versus non-surgical interventions for chronic arthropathy in people with haemophilia.

Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System.

Objective: We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour. Methods: This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7). Results: A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03-2.08) and B2-S (HR 1.65, 95% CI 1.25-2.18). Conclusion: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.

Frailty scoring in vascular and endovascular surgery: A systematic review.

One in 10 independently living adults aged 65 years old and older is considered frail, and frailty is associated with poor postoperative outcomes. This systematic review aimed to examine the association between frailty assessments and postoperative outcomes in patients with vascular disease. Electronic databases - MEDLINE, Embase, and the Cochrane Library - were searched from inception until January 2022, resulting in 648 articles reviewed for potential inclusion and 16 studies selected. Demographic data, surgery type, frailty measure, and postoperative outcomes predicted by frailty were extracted from the selected studies. The risk of bias was assessed using the Newcastle-Ottawa Scale. The selected studies (mean age: 56.1-76.3 years) had low-to-moderate risk of bias and included 16 vascular (elective and nonelective) surgeries and eight frailty measures. Significant associations (p < 0.05) were established between mortality (30-day, 90-day, 1-year, 5-year), 30-day morbidity, nonhome discharge, adverse events, failure to rescue, patient requiring care after discharge, and amputation following critical limb ischaemia. The strongest evidence was found between 30-day mortality and frailty. Composite 30-day morbidity and mortality, functional status at discharge, length of stay, spinal cord deficit, and access site complications were found to be nonsignificantly associated with frailty. With frailty being significantly associated with several adverse postoperative outcomes, preoperative frailty assessments can potentially be clinically useful in helping practitioners predict and guide the pre-, peri-, and postoperative management of frail with vascular disease.

Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes.

Ensuring high vaccination and even booster vaccination coverage is critical in preventing severe Coronavirus Disease 2019 (COVID-19). Among the various COVID-19 vaccines currently in use, the mRNA vaccines have shown remarkable effectiveness. However, systemic adverse events (AEs), such as postvaccination fatigue, are prevalent following mRNA vaccination, and the underpinnings of which are not understood. Herein, we found that higher baseline expression of genes related to T and NK cell exhaustion and suppression were positively correlated with the development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased expression of genes associated with T and NK cell exhaustion and suppression reacted to vaccination were associated with greater levels of innate immune activation at 1 day postvaccination. We further found, in a mouse model, that altering the route of vaccination from intramuscular (i.m.) to subcutaneous (s.c.) could lessen the pro-inflammatory response and correspondingly the extent of systemic AEs; the humoral immune response to BNT162b2 vaccination was not compromised. Instead, it is possible that the s.c. route could improve cytotoxic CD8 T-cell responses to BNT162b2 vaccination. Our findings thus provide a glimpse of the molecular basis of postvaccination fatigue from mRNA vaccination and suggest a readily translatable solution to minimize systemic AEs.

Candida glabrata chorioamnionitis in a twin pregnancy following in vitro fertilisation: a rare cause of septic miscarriage.

Candida glabrata chorioamnionitis is uncommon and associated with poor fetal outcomes. We present a case of C. glabrata chorioamnionitis of a dichorionic diamniotic pregnancy conceived by fresh embryo transfer. Despite antifungal therapy with amphotericin B, spontaneous miscarriage of both twins occurred. The mother otherwise recovered uneventfully. Our case highlights the high fetal mortality associated with C. glabrata chorioamnionitis and the challenges of antifungal treatment in pregnancy. We recommend a low threshold of suspicion for Candida infection in pregnancy, notably those involving transvaginal uterine instrumentation such as in vitro fertilisation.

The detection of delirium in admitted oncology patients: a scoping review.

PURPOSE: Delirium leads to poor outcomes for patients and careers and has negative impacts on staff and service provision. Cancer rates in elderly populations are increasing and frequently, cancer diagnoses are a co-morbidity in the context of frailty. Data relating to the epidemiology of delirium in hospitalised cancer patients are limited. With the overarching purpose of improving delirium detection and reducing the morbidity and mortality of delirium in cancer patients, we reviewed the epidemiological data and approach to delirium detection in hospitalised, adult oncology patients. METHODS: MEDLINE, EMBASE, CINAHL, PsycINFO, and SCOPUS databases were searched from January 1996 to August 2017. Key concepts were delirium, cancer, inpatient oncology and delirium screening/detection. RESULTS: Of 896 unique studies identified; 91 met full-text review criteria. Of 12 eligible studies, four applied recommended case ascertainment methods to all patients, three used delirium screening tools alone or with case ascertainment tools sub-optimally applied, four used tools not recommended for delirium screening or case ascertainment, one used the Confusion Assessment Method with insufficient information to determine if it met case ascertainment status. Two studies presented delirium incidence rates: 7.8%, and 17% respectively. Prevalence rates ranged from 18-33% for general medical or oncology wards; 42-58% for Acute Palliative Care Units (APCU); and for older cancer patients: 22% and 57%. Three studies reported reversibility; 26% and 49% respectively (APCUs) and 30% (older patients with cancer). Six studies had a low risk of bias according to QUADAS-2 criteria; all studies in the APCU setting were rated at higher risk of bias. Tool selection, study flow and recruitment bias reduced study quality. CONCLUSION: The knowledge base for improved interventions and clinical care for adults with cancer and delirium is limited by the low number of studies. A clear distinction between screening tools and diagnostic tools is required to provide an improved understanding of the rates of delirium and its reversibility in this population.

The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.

Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysisattempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstrated statistically increased odds of aortic dissection (OR, 2.38; 95% CI, 1.71-3.32) aortic aneurysm (OR, 1.98; 95% CI, 1.59-2.48), and aortic aneurysm or dissection (OR, 1.47; 95% CI, 1.13-1.89; I2 = 72%) with current use of fluoroquinolones compared to their nonuser counterparts. Based on the "number needed-to-harm" analysis, 7246 (95% CI: 4329 to 14,085) patients would need to be treated with fluoroquinolones for a duration of at least three days in order for one additional patient to be harmed, assuming a population baseline incidence of aortic dissection and aneurysm rupture to be 10 per 100,000 patient-years. With strong statistical association, these findings suggest a causal relationship, warranting future research to elucidate the pathophysiological and mechanistic plausibility of this association. These findings however, should not cease prescription of fluoroquinolones, especially when clinically indicated.

Computer-Navigated versus Conventional Total Knee Arthroplasty: A Meta-Analysis of Functional Outcomes from Level I and II Randomized Controlled Trials.

The main purpose of this article is to provide an up-to-date systematic review and meta-analysis comparing functional outcomes of total knee arthroplasty using either computer navigation (NAV-TKA) or conventional methods (CON-TKA) from the latest assemblage of evidence. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. All Level I and II randomized controlled trials (RCTs) in PubMed, EMBASE, and Cochrane that compared functional outcomes after NAV- and CON-TKA were included in the review. Selected end points for random effects, pairwise meta-analysis included Knee Society Knee Score (KSKS), KS Function Score (KSFS), KS Total Score (KSTS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion at three arbitrary follow-up times. A total of 24 prospective RCTs comprising 3,778 knees were included from the initial search. At long-term follow-up (>5 years), NAV-TKA exhibited significantly better raw KSKS (p = 0.001) (low-quality evidence), contrary to CON-TKA, which reflected significantly better raw KSTS (p = 0.004) (high-quality evidence). While change scores (KSKS, WOMAC) from preoperative values favor CON-TKA at short-term (<6 months) and medium-term follow-up (6-60 months), long-term follow-up change scores in KSKS suggest the superiority of NAV-TKA over CON-TKA (p = 0.02) (very low-quality evidence). Overall, sizeable dispersion of nonstatistically significant functional outcomes in the medium term was observed to eventually converge in the long term, with less differences in functional outcome scores between the two treatment methods in short- and long-term follow-up. While raw functional outcome scores reflect no differences between NAV and CON-TKA, long-term follow-up change scores in KSKS suggest superiority of NAV-TKA over its conventional counterpart. Prospective studies with larger power are required to support the pattern of diminishing differences in functional outcome scores from medium- to long-term follow-up between the two modalities.

Robotic ICG guided anatomical liver resection in a multi-centre cohort: an evolution from "positive staining" into "negative staining" method.

BACKGROUND: Laparoscopic major anatomical liver resection is challenging. The robotic liver resection (RLR) approach, with Firefly indocyanine green (ICG) imaging, was proposed to overcome the limitations of laparoscopy. The aim of this multi-centre international study was to evaluate the use of Firefly ICG imaging in anatomical RLR. METHODS: A retrospective study of consecutive patients undergoing RLR anatomical resection with intra-operative ICG administration from January 2015 to July 2018 were enrolled. Patients who underwent simultaneous or en-bloc resections of other organs were excluded. RESULTS: A total of 52 patients were recruited of which 32 patients were healthy donors, 17 with malignancy and 3 for benign conditions. 12 patients had cirrhosis. 28 patients underwent a right hepatectomy (53.8%) with left hepatectomy performed with 18 patients. 40 patients underwent negative staining and 12 patients via direct portal vein injection for positive staining. ICG demarcation line was visualized in 43 patients and was clearer than the ischaemic demarcation line in 29 patients. All resections for malignancy had clear margins. There were no 30-day/inpatient mortalities. CONCLUSION: Robotic ICG guided hepatectomy technique for anatomical liver resection is safe, feasible and has the benefit for improved visualization in healthy donors and cirrhotic patients.