Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates.

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39- CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells.

Systematic Review and Meta-analysis on Colorectal Cancer Findings on Colonic Evaluation After CT-Confirmed Acute Diverticulitis.

BACKGROUND: CT findings of acute diverticulitis can overlap with features of malignancy, and current guidelines recommend colonic evaluation after acute diverticulitis. However, the benefits of routine colonic evaluation have been questioned. OBJECTIVE: We review 30 studies, composed of 29,348 subjects, to evaluate the role of routine colonic evaluation after CT-proven acute diverticulitis. DATA SOURCES: Medline, EMBASE, and the Cochrane Library were searched for articles published up to July 2018 to identify all relevant articles. STUDY SELECTION: A combination of both Medical Subject Headings and non-Medical Subject Headings key terms using Boolean operators were used on Medline, including colonic neoplasms, colorectal cancer, colon cancer, colonic cancer, colonoscopy, and diverticulitis. Any randomized or nonrandomized, English-language article that specifically analyzed incidence of colorectal cancer after performing colonoscopy in patients with previous diverticulitis was included. MAIN OUTCOME MEASURES: The desired outcome was to evaluate for incidence of colonic malignancy in cases of acute colonic diverticulitis. Subgroup analyses for incidence of malignancy in uncomplicated and complicated diverticulitis, and Asian population studies were also performed. RESULTS: Findings of colonic malignancy occurred in 1.67% (95% CI, 1.24-2.14) of patients with CT-diagnosed diverticulitis. The risk of malignancy in cases with uncomplicated diverticulitis was 1.22% (95% CI, 0.63-1.97) as compared with 6.14% (95% CI, 3.20-9.82) in cases with complicated diverticulitis, with a relative risk of 5.033 (95% CI, 3.194-7.930; p < 0.001). LIMITATIONS: Significant variability in design and methodology of the individual studies contributed to the heterogeneity of this study, but these were addressed by using the random-effects model analysis. CONCLUSIONS: Colonic evaluation is worth considering for patients with diverticulitis because of the small but serious risk of underlying malignancy. The risk of malignancy is higher for patients of advanced age and with complicated diverticulitis.

The impact of postoperative complications on long-term quality of life after curative colorectal cancer surgery.

OBJECTIVE: To investigate the effect that complications have on patients' long-term quality of life (QoL) after curative colorectal cancer surgery. BACKGROUND: Colorectal cancer surgery is a high risk, with approximately 1 in 3 patients suffering a complication. The long-term consequences of postoperative complications are important but have poorly been documented. METHODS: The MRC-CLASICC trial (laparoscopic-assisted vs open surgery for colorectal cancer) included prospective evaluation of QoL using validated scoring questionnaires: EORTC QLQ-C30/CR38 and EQ5D. These were used to compare QoL at 3, 6, 18, and 36 months to baseline values for patients categorized into 2 groups: (i) those suffering any complication and (ii) those suffering any of 5 common complications (wound, chest, anastomotic leak, hemorrhage, and cardiac event). RESULTS: A total of 614 of 794 CLASICC patients were suitable for inclusion. Complications occurred in 215 (35.0%) patients, including: wound complications (61, 9.9%), chest infection (50, 8.1%), anastomotic leak (27, 4.4%), hemorrhage (14, 2.3%), and cardiac event (26, 4.2%). Significant long-term differences in QoL between patients with and without complications were found for Physical and Social Function, Role Functioning, and Body Image on EORTC QLQ-C30/QLQ-CR38 analysis and Mobility, Self-care, and Pain/Discomfort on EQ5D analysis. No significant differences were seen for emotional/cognitive functioning, global QoL, financial difficulties, or future perspectives. Risk factors of age, gender, ASA (American Society of Anesthesiologists) grade, and stoma moderated the impact of complications in the short- to medium-term QoL, but had less influence on long-term QoL. CONCLUSIONS: Postoperative complications have adverse effects on long-term QoL, particularly for Physical, Role and Social Functioning, and Body Image, as well as for Mobility, Self-care, and Pain/Discomfort. These findings should inform future preoperative counseling and health care planning.

Venous thromboembolism among Asian populations with localized colorectal cancer undergoing curative resection: is pharmacological thromboprophylaxis required? A systematic review and meta-analysis.

PURPOSE: We compared the incidence of venous thromboembolism (VTE) among Asian populations with localized colorectal cancer undergoing curative resection with and without the use of pharmacological thromboprophylaxis (PTP). METHODS: A comprehensive literature search was undertaken to identify relevant studies published from January 1, 1980 to February 28, 2022. The inclusion criteria were patients who underwent primary tumor resection for localized nonmetastatic colorectal cancer; an Asian population or studies conducted in an Asian country; randomized controlled trials, case-control studies, or cohort studies; and the incidence of symptomatic VTE, deep vein thrombosis, and/or pulmonary embolism as the primary study outcomes. Data were pooled using a random-effects model. This study was registered in PROSPERO on October 11, 2020 (No. CRD42020206793). RESULTS: Seven studies (2 randomized controlled trials and 5 observational cohort studies) were included, encompassing 5,302 patients. The overall incidence of VTE was 1.4%. The use of PTP did not significantly reduce overall VTE incidence: 1.1% (95% confidence interval [CI], 0%-3.1%) versus 1.9% (95% CI, 0.3%-4.4%; P = 0.55). Similarly, PTP was not associated with significantly lower rates of symptomatic VTE, proximal deep vein thrombosis, or pulmonary embolism. CONCLUSION: The benefit of PTP in reducing VTE incidence among Asian patients undergoing curative resection for localized colorectal cancer has not been clearly established. The decision to administer PTP should be evaluated on a case-bycase basis and with consideration of associated bleeding risks.

Periprosthetic fracture as a late mode of failure of the Anatomique Benoist Girard II femoral prosthesis.

AIM: The Anatomique Benoist Girard (ABG) II femoral implant was a commonly used stem for primary total hip replacement (THR) at our institution (Launceston, Tasmania Australia). We identified peri-prosthetic fracture as the main cause of late failure. METHODS: The late periprosthetic fracture rate for ABG II implants was reviewed with national statistics, using Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) data. National revision rates for periprosthetic fracture were used to compare ABG II with all other cementless femoral stems. RESULT: ABG II stems accounted for 1% (2719 implants) of all femoral stem implants in Australia during the 12-year review period, compared to 23% (587 implants) in Launceston Hospitals. Although the Launceston cumulative percent revision rate for the ABG II stem was lower than the National rate at all time points, the reasons for revision were similar. The most common reason for revision of ABG II was fracture (56.8%), followed by loosening (15.3%). This differs from the reasons for revision in other cementless prostheses (loosening 23.9%, fracture 20.8%, dislocation 18.7%). Cumulative percent revision rates from late periprosthetic fracture, were higher for the ABG II stem than other cementless femoral prostheses. CONCLUSION: This review of the AOANJRR has confirmed a local and national higher revision rate of the ABG II stem due to late periprosthetic fracture compared with other cementless stems. Stem design must be considered to reduce the risk of late periprosthetic fracture.

The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial.

AIMS: Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. METHODS: A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. RESULTS: A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. CONCLUSION: There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663-671.

Effect of combined exercise training and behaviour change counselling versus usual care on physical activity in patients awaiting hip and knee arthroplasty: A randomised controlled trial.

Objective: This study aimed to determine if a novel intervention that combined individualised exercise training with behaviour change counselling based on Health Action Process Approach (HAPA) constructs could elicit long-term increase in physical activity (PA) and reduce comorbidity development among people requiring hip or knee arthroplasty. Method: A pre-registered two arm, parallel group, randomised controlled trial comparing the effect of a 12-week individualised exercise program combined with behavioural counselling delivered by accredited exercise physiologists, versus usual care to Osteoarthritis (OA) patients on public surgery waitlists. Participants were followed up at 6 months after baseline (pre-surgery) and again at 6 months post-surgery. Within and between group differences in post-surgery PA (as measured by ActivPal accelerometer), pain, function, quality of life, HAPA-based behavioural and psychological constructs, and health risk factors were analysed. Results: 63 participants (34 Female; Mean age â€‹= â€‹66.4 â€‹± â€‹7.2 â€‹yrs) consented to participate in this study. At 6 months post baseline and 6 months post-surgery there were significant improvements in PA, pain, function, and quality of life, however there were no significant differences in the between group responses. Significant between group changes were observed in several psychological constructs related to volition at 6 months post baseline; however, these had disappeared by 6 months post-surgery. Conclusions: An exercise program and HAPA guided counselling intervention can improve psychological constructs related to exercise behaviour; however, these did not result in significant between group changes in PA at the timepoints measured. Further research with larger sample size is required.Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN 12617000357358) Date of registration: 08/03/2017.

Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.

The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined 'IMF' classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).

A clinical predictive model for risk stratification of patients with severe acute lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common presentation of surgical admissions, imposing a significant burden on healthcare costs and resources. There is a paucity of standardised clinical predictive tools available for the initial assessment and risk stratification of patients with LGIB. We propose a simple clinical scoring model to prognosticate patients at risk of severe LGIB and an algorithm to guide management of such patients. METHODS: A retrospective cohort study was conducted, identifying consecutive patients admitted to our institution for LGIB over a 1-year period. Baseline demographics, clinical parameters at initial presentation and treatment interventions were recorded. Multivariate logistic regression was performed to identify factors predictive of severe LGIB. A clinical management algorithm was developed to discriminate between patients requiring admission, and to guide endoscopic, angiographic and/or surgical intervention. RESULTS: 226/649 (34.8%) patients had severe LGIB. Six variables were entered into a clinical predictive model for risk stratification of LGIB: Tachycardia (HR ≥ 100), hypotension (SBP < 90 mmHg), anaemia (Hb < 9 g/dL), metabolic acidosis, use of antiplatelet/anticoagulants, and active per-rectal bleeding. The optimum cut-off score of ≥ 1 had a sensitivity of 91.9%, specificity of 39.8%, and positive and negative predictive Values of 45% and 90.2%, respectively, for predicting severe LGIB. The area under curve (AUC) was 0.77. CONCLUSION: Early diagnosis and management of severe LGIB remains a challenge for the acute care surgeon. The predictive model described comprises objective clinical parameters routinely obtained at initial triage to guide risk stratification, disposition and inpatient management of patients.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Obstructing Colorectal Cancer Treated by Endoscopic Stenting as a Bridge to Surgery.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict adverse survival outcomes among patients with colorectal cancer (CRC). This study evaluates the prognostic value of NLR among patients with obstructing CRC who successfully underwent stenting before curative surgery. METHODS: We retrospectively reviewed patients who underwent stenting before surgery. Patient demographics, tumor characteristics, perioperative outcomes, recurrence-free survival (RFS), and overall survival (OS) were analyzed. NLR was calculated from the differential white blood cell counts at least 4 days after successful stenting, before elective surgery. Optimal cutoff to dichotomize NLR was obtained by maximizing log-rank test statistic with recursive partitioning of KaplanMeier RFS and OS curves. The optimal cutoff for high NLR was ≥ 5 at presentation before stenting, and ≥ 4 after stenting. RESULTS: Fifty-seven patients with localized obstructing CRC underwent successful endoscopic stenting before curative surgery. High NLR was associated with lymphovascular invasion (P = 0.006) and apical lymph node involvement (P = 0.034). Major perioperative complication(s) (hazard ratio [HR], 11.34; 95% confidence interval [CI], 2.49 to 51.56; P < 0.01) and high NLR (HR, 3.69; 95% CI, 1.46 to 9.35; P < 0.01) negatively impacted OS on univariate and multivariate analyses. High NLR negatively impacted RFS on univariate analysis (HR, 2.91; 95% CI, 1.29 to 6.60; P = 0.01). CONCLUSION: NLR of ≥ 4 after stenting is an independent prognostic factor among patients with obstructing localized CRC who are successfully decompressed by endoscopic stenting before curative surgery.

Stenting as a bridge to surgery for obstructed stage IV colorectal cancers - long-term outcomes of a 10-year study.

INTRODUCTION: Successful stenting of an obstructing colorectal tumor can avert upfront emergency surgery in malnourished obstructed patients with metastatic disease and poor physiological condition. This study aims to evaluate the outcomes of stenting followed by primary colorectal tumor resection among patients with obstructed stage IV colorectal cancer at presentation, over a 10-year period. METHODS: From 2007 to 2016, a cohort comprising 25 consecutive patients were retrospectively reviewed from a prospectively collected database. The durability of palliation of bowel obstruction, oncological outcomes and factors influencing overall survival were analyzed. RESULTS: No re-interventions were required for bowel obstruction during the study period. The overall perioperative morbidity rate was 16%, with no postoperative 90-day mortality. Laparoscopic resection rate was 52% and stoma formation rate was 8%. The median overall survival was 24 months for the entire cohort, and the 1-, 3- and 5-year survival rates were 80%, 35% and 23.33% respectively. More than one site of distant metastases, peritoneal involvement, and elevated carcinoembryonic antigen levels were significantly associated with poorer survival outcomes. Patients with peritoneal-only metastasis had worse outcomes, with a median survival of 7 months and no patients surviving beyond 18 months. CONCLUSION: Stenting followed by resection of the primary obstructing colorectal cancer provides durable palliation among patients with stage IV disease, with low perioperative morbidity and stoma formation rates. Superior survival was observed among patients with single-site, non-peritoneal distant metastases.

Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer.

Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy in human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look for evidence of bacterial antigen recognition in human colon, lung, and kidney carcinomas. Using mass cytometry and single-cell mRNA sequencing, we identify a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 and observe high expression of CD39 on MAIT cells from colorectal cancer (CRC) only, which we show in vitro to be expressed specifically after TCR stimulation. We further reveal that these cells are phenotypically and functionally exhausted. Sequencing data show high bacterial infiltration in CRC tumors and highlight an enriched species, Fusobacteria nucleatum, with capability to activate MAIT cells in a TCR-dependent way. Our results provide evidence of a MAIT cell response to microbial antigens in CRC and could pave the way for manipulating MAIT cells or the microbiome for cancer therapy.

Topical haemostatic powder as a novel endoscopic therapy for severe colonic diverticular bleeding.

BACKGROUND: Although most diverticular bleeding resolve spontaneously, up to 30% can bleed torrentially, necessitating angioembolization, endoscopic or surgical intervention. Non-contact endoscopic therapies, such as topical haemostatic powders, do not require precise targeting and are attractive because identification of specific culprit diverticulum is difficult. While their use in non-variceal upper gastrointestinal bleeding is well established, its role in lower gastrointestinal bleeding remains unclear. We used topical Hemospray in a novel setting of severe diverticular bleeding, evaluating its efficacy in achieving haemostasis, reducing re-bleeding and the need for re-intervention. METHODS: Consecutive patients from a tertiary colorectal unit who underwent colonoscopy and Hemospray for severe diverticular bleeding from November 2016 to October 2017 were included. Hemospray was endoscopically applied to colonic segments with major stigmata of recent haemorrhage. RESULTS: Ten patients had a median time to colonoscopy of 22 h (range: 8-54) from admission. Median of 3.5 units (range: 0-10) of packed cells were transfused pre-endoscopy. All achieved immediate haemostasis without further haemodynamic instability or re-bleeding. No endoscopic, radiological or surgical re-intervention was required. Patients were fit for discharge within a median of 3 days (range: 2-7) following Hemospray. There were no morbidities, mortalities or readmissions for diverticular bleeding after a median follow-up of 9.5 months (range: 3-16). CONCLUSION: This feasibility study shows that topical haemostatic powders can offer a safe and effective therapeutic endoscopic option in severe diverticular bleeding with high haemostatic rate. Prospective controlled trials are required to establish its efficacy compared to conventional therapy.

Appendiceal diverticulosis: a harbinger of underlying primary appendiceal adenocarcinoma?

Diagnosis of primary appendiceal adenocarcinoma (PAA) is hindered by its rarity and largely asymptomatic nature. Appendiceal diverticulosis (AD) is equally rare. We report an unusual case of PAA presenting with perforated appendiceal diverticulitis, and discuss a review of the literature about its association, and its surgical and pathological implications. A middle-aged man was admitted with right iliac fossa (RIF) pain and a corresponding tender abdominal mass for 5 days. Computerised tomography (CT) scan demonstrated a thickened appendix with 3 cm abscess at its base. During laparoscopic appendicectomy, the appendiceal phlegmon was adhered to the surrounding bowel. Histology showed a perforated diverticulum near the appendiceal tip, and a primary appendiceal well-differentiated adenocarcinoma located proximal to it with clear margins. Up to 48% of ADs are associated with appendiceal neoplasms, but its coexistence with PAA is reported in fewer than ten instances worldwide. Obstructing appendiceal tumours, by raising intraluminal pressure, can predispose to AD formation. Intestinal-type PAA is often managed like its colorectal counterpart, although controversies about management of PAA in a perforated AD remain. Recognition of the association of AD and PAA is critical to ensure meticulous oncological resection and histological examination.

A Prospective Randomised Controlled Trial of a Single Intravenous Infusion of Ferric Carboxymaltose vs Single Intravenous Iron Polymaltose or Daily Oral Ferrous Sulphate in the Treatment of Iron Deficiency Anaemia in Pregnancy.

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: -2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: -23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms. In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.