Angiogenic markers and maternal echocardiographic indices in women with hypertensive disorders of pregnancy.

OBJECTIVE: The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). METHODS: In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth). Spearman's rank correlation was used to derive correlation coefficients between biomarkers and cardiac indices in the HDP and control populations. RESULTS: The HDP group included 61 (64.2%) pre-eclamptic patients and, among them, 42 (68.9%) delivered before 37 weeks' gestation. Twelve women with HDP (12.6%) underwent blood sampling and TTE after delivery, and, as they showed significantly lower levels of angiogenic markers, they were excluded from the analysis. There was a correlation between sFlt-1 and LV mass index (LVMI) (r = 0.246; P = 0.026) and early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') ratio (r = 0.272; P = 0.014) in the HDP group (n = 83), while in the controls, sFlt-1 showed a correlation with relative wall thickness (r = 0.409; P = 0.043), lateral e' (r = -0.562; P = 0.004) and E/e' ratio (r = 0.417; P = 0.042). PlGF correlated with LVMI (r = -0.238; P = 0.031) in HDP patients and with lateral e' (r = 0.466; P = 0.022) in controls. sFlt-1/PlGF ratio correlated with lateral e' (r = -0.568; P = 0.004) and E/e' ratio (r = 0.428; P = 0.037) in controls and with LVMI (r = 0.252; P = 0.022) and E/e' ratio (r = 0.269; P = 0.014) in HDP. CONCLUSIONS: Although the current data are not able to infer causality, they confirm the intimate relationship between the maternal cardiovascular system and angiogenic markers that are used both to diagnose and indicate the severity of HDP. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Catheter-associated bloodstream infection in patients with cancer: comparison of left- and right-sided insertions.

BACKGROUND: There is limited research on the relationship between side of insertion of central venous catheter (CVAD) and bloodstream infection risk in patients with cancer. AIM: To conduct an exploratory analysis of data from a randomized control trial (RCT) and data from a prospective cohort study to compare infection rates for right- and left-sided insertions. METHODS: The study populations were patients aged >14 years with cancer from two tertiary hospitals in Brisbane, Australia. The primary endpoint was catheter-associated bloodstream infection (CABSI) adjudicated by blinded assessors. For the RCT, randomized intention-to-treat comparisons were conducted between left- and right-side allocated insertion for early (≤14 days) and late (>14 days) infection using Cox proportional hazards regression. The RCT data were also combined with cohort study data collected from one of the hospitals prior to the RCT and non-randomized comparisons conducted between left- and right-sided insertions. FINDINGS: In 634 randomly allocated CVADs there were 141 CABSIs. Analysis showed strong evidence of right-side allocated insertions having an increased risk of early infection by 2.5 times (95% confidence interval (CI): 1.3-4.7); however, there was no evidence of increased risk for late infection (hazard ratio: 1.06; 95% CI: 0.71-1.59). Results from analysis of the RCT and cohort study data combined (2786 CVADs and 385 CABSIs) were similar. CONCLUSION: There appears to be an increased risk of CABSI in patients with cancer for CVAD inserted into the right-side for around two weeks after line insertion. The mechanism underpinning the increased risk is unknown.

Catheter-associated bloodstream infections in adults with cancer: a prospective randomized controlled trial.

BACKGROUND: A common complication of central venous access devices (CVADs) is catheter-associated bloodstream infection (CABSI). We previously demonstrated that insertion of CVADs on the right side was associated with increased risk of CABSI, and hypothesized that this related to the predominance of right-handedness in the patient population, resulting in greater movement and bacterial contamination. AIM: To perform a prospective randomized, controlled, non-blinded study to determine whether the side of CVAD insertion influenced the incidence of CABSI. METHODS: Adult cancer patients were randomly allocated to either dominant or non-dominant side CVAD insertion. The primary endpoint of the study was the number of line-days until CABSI, determined in a blinded fashion by two assessors. FINDINGS: In all, 640 CVADs were randomized to dominant (N = 322) or non-dominant (N = 318) side of insertion, 60% had haematological malignancies, and 40% solid tumours. CVADs were a peripherally inserted central catheter line (67%), tunnelled CVAD (23%), and non-tunnelled CVAD (10%). Twenty-two percent of CVADs were complicated by CABSI. The rate of CABSI per 1000 line-days was 3.49 vs 3.66 in the non-dominant vs dominant group (hazard ratio (HR): 0.91; 95% confidence interval (CI): 0.65-1.28). By multivariable analysis, the rate of CABSI was increased by: use of tunnelled CVADs compared to peripherally inserted central venous catheter lines (HR: 2.05; 95% CI: 1.45-2.91); having a haematological malignancy compared to non-gastrointestinal solid tumours (5.55; 2.47-12.5); but not dominant compared to non-dominant side of CVAD (0.97; 0.69-1.36). CONCLUSION: CABSI in adult patients with cancer was not impacted by whether CVAD insertion was on the dominant or non-dominant side.

Early removal of catheters in an Enhanced Recovery Pathway (ERP) with intrathecal opioid injection does not affect postoperative urinary outcomes.

BACKGROUND: Postoperative urinary retention (POUR) and catheter-associated urinary tract infections (CAUTI) are associated with significantly longer hospital length-of-stay and increased costs.1 This study investigates the effect of early removal of urinary catheters on POUR and CAUTI in patients undergoing an ERP with a preoperative intrathecal injection. METHODS: Retrospective cohort study of a prospectively maintained database of patients who underwent elective colorectal surgery in an Enhanced Recovery pathway was compared to historical National Surgical Quality Improvement Program cohort of patients. Primary outcomes measured are 30-day POUR and postoperative CAUTI rates. RESULTS: The overall POUR rate of ERP patients compared to non-ERP patients was significantly less (8% vs. 13%, p < 0.05). CAUTI rates were not significantly different between pre-ERP and ERP patients (1.2 vs 2.3%, p = 0.19). CONCLUSIONS: For patients undergoing ERP with a preoperative intrathecal opioid injection, early removal of urinary catheter significantly decreased POUR and did not significantly affect CAUTI rates. SUMMARY: The effect of early removal of urinary catheters on postoperative urinary retention and catheter-associated UTI rates in patients undergoing an ERP with a single preoperative intrathecal opioid injection was studied. Early urinary catheter removal after intrathecal injection was associated with decreased rates of POUR and equivalent CAUTI rates.

Costochondral grafting for paediatric temporomandibular joint reconstruction: 10-year outcomes in 55 cases.

Costochondral grafting (CCG) can be used for the reconstruction of ankylotic, hypoplastic, and resected temporomandibular joint (TMJ) defects. CCGs have previously been considered the gold standard in children due to their growth potential and autogenous origin, but the disadvantages are unpredictable growth and joint ankylosis. This was a retrospective study of all children who received CCGs for TMJ reconstruction from 1985 to 2004, to allow a 10-year follow-up. Fifty-five patients were included in this study, with 74 grafts being placed; their mean age was 7.9±4.2years. Infection-related ankylosis (18.2%) and craniofacial microsomia (16.4%) were the most common diagnoses. Overall, 58.2% of patients suffered one or more complications over the follow-up period, with ankylosis (32.7%) and overgrowth (16.4%) being most common. There was a significant correlation between those with infection-related ankylosis and subsequent complications (χ2=8.8, df=1, P<0.005), while ankylotic patients in general exhibited greater overall complication rates (χ2=9.0, df=1, P<0.005). Patients with congenital TMJ defects were more likely to be complication-free than those with acquired defects (χ2=4.0, df=1, P<0.05). Caution is advised when placing CCGs in paediatric patients with ankylosed TMJs, especially those with infection-related ankylosis.

Presentation of automated procedural guidance in surgical simulation: results of two randomised controlled trials.

OBJECTIVE: To investigate the effectiveness and usability of automated procedural guidance during virtual temporal bone surgery. METHODS: Two randomised controlled trials were performed to evaluate the effectiveness, for medical students, of two presentation modalities of automated real-time procedural guidance in virtual reality simulation: full and step-by-step visual presentation of drillable areas. Presentation modality effectiveness was determined through a comparison of participants' dissection quality, evaluated by a blinded otologist, using a validated assessment scale. RESULTS: While the provision of automated guidance on procedure improved performance (full presentation, p = 0.03; step-by-step presentation, p < 0.001), usage of the two different presentation modalities was vastly different (full presentation, 3.73 per cent; step-by-step presentation, 60.40 per cent). CONCLUSION: Automated procedural guidance in virtual temporal bone surgery is effective in improving trainee performance. Step-by-step presentation of procedural guidance was engaging, and therefore more likely to be used by the participants.

Post-transplant lymphoproliferative disorder in paediatric patients: the Irish perspective-a single centre experience.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a serious complication of both solid organ and haematopoietic stem cell transplantation in children. Its incidence has increased over the last decade as a result of more potent immunosuppressive regimens. Many treatments have been explored however optimal therapy remains controversial. AIMS: We report on the diagnosis, treatment and outcome of ten patients who were diagnosed with PTLD in Our Lady's Hospital for Sick Children in Dublin between 2004 and 2015 inclusive. METHODS: Data were collected by retrospective review of patient medical records. RESULTS: 9 out of ten of our patients are alive and disease free following treatment for PTLD with rituximab alone or in combination with chemotherapy. CONCLUSION: The outcome of paediatric patients treated for PTLD at our institution is at least comparable to published international series and supports the use of rituximab ± low dose chemotherapy in the treatment of this malignancy.

Effects of anatomical variation on trainee performance in a virtual reality temporal bone surgery simulator.

OBJECTIVE: To investigate the importance of anatomical variation in acquiring skills in virtual reality cochlear implant surgery. METHODS: Eleven otolaryngology residents participated in this study. They were randomly allocated to practice cochlear implant surgery on the same specimen or on different specimens for four weeks. They were then tested on two new specimens, one standard and one challenging. Videos of their performance were de-identified and reviewed independently, by two blinded consultant otolaryngologists, using a validated assessment scale. The scores were compared between groups. RESULTS: On the standard specimen, the round window preparation score was 2.7 ± 0.4 for the experimental group and 1.7 ± 0.6 for the control group (p = 0.01). On the challenging specimen, instrument handling and facial nerve preservation scores of the experimental group were 3.0 ± 0.4 and 3.5 ± 0.7 respectively, while the control group received scores of 2.1 ± 0.8 and 2.4 ± 0.9 respectively (p < 0.05). CONCLUSION: Training on temporal bones with differing anatomies is beneficial in the development of expertise.

Treatment of aplastic anaemia with lower-dose anti-thymocyte globulin produces similar response rates and survival as per standard dose anti-thymocyte globulin schedules.

BACKGROUND: Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. AIMS: Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA. We aimed to review the outcome of AA patients treated with these protocols and compare them to the published literature. METHODS: We conducted a retrospective study of 31 adults who received first-line ATGAM for AA and compared response rates and survival between cohorts who received standard (40 mg/kg/day D1-4) versus lower-dose (15 mg/kg/day D1-5) ATGAM schedules. RESULTS: There were similar rates of response (64 vs 71%, P = 1.0), relapse (33 vs 33%, P = 1.0), transformation (14 vs 24%, P = 0.66) or infection (43 vs 47%, P = 1.0), respectively, between standard and lower-dose cohorts. At a median follow up of 24 months, there was no statistical difference between standard and lower-dose cohorts in either event-free (42.2 vs 64.7%, P = 0.91) or overall survival (73.1 vs 88.2%, P = 0.75). CONCLUSION: Our experience suggests that lower-dose ATGAM at 15 mg/kg/day D1-5 as treatment of AA produces similar responses and outcomes as per standard-dose ATGAM schedules. Prospective trials comparing ATGAM dose schedules in AA are warranted.

Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome--a randomised controlled trial.

BACKGROUND AND AIMS: Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. METHODS AND RESULTS: Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). CONCLUSION: High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. TRIAL REGISTRATION: www.controlled-trials.com, ISRCTN59927814.

A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma.

BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.

Immunotherapy following relapse of acute leukaemia after T-cell-replete allogeneic peripheral blood progenitor cell transplantation: importance of new onset chronic graft-versus-host disease.

INTRODUCTION: To further define the relative impact of immunotherapy and subsequent development of graft-versus-host disease (GVHD) on survival in patients with relapsed acute leukaemia postallogeneic hematopoietic stem cell transplant (SCT), we performed a single-centre retrospective analysis of 32 actively treated patients between 2003 and 2011. METHODS: A total of 13 patients were identified who were treated actively with cessation of immunosuppression ± Fludarabine, Cytarabine, G-CSF (FLAG) induction, but no donor leucocyte infusion (DLI) (non-DLI group) and 19 patients received the same step-wise therapy plus G-CSF mobilized DLI (G-DLI group). RESULTS: Groups were not statistically different with regards to baseline characteristics; however, the G-DLI group contained more sibling donors as opposed to unrelated donors than the non-DLI group. With a median follow-up of 47 months, the median overall survival (OS) of the non-DLI and G-DLI groups was not statistically different (8 months vs. 9 months, respectively, P = 0.5). Survival at 3 years was <10% in both groups. Univariate analysis identified response to FLAG, and new onset chronic GVHD as the only factors associated with improved OS. CONCLUSION: Second donor stem cell infusions are unwarranted in the treatment of relapse after allogeneic SCT and therapeutic strategies should focus on cytoreduction followed by immune modulation with the aim of invoking chronic GVHD.

Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients.

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

Oral ribavirin for treatment of respiratory syncitial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell transplantation.

The prognosis for patients with respiratory syncytial virus (RSV) or parainfluenza virus type 3 (PIV3) respiratory tract infection post allogeneic haematopoietic progenitor cell transplant (HPCT) is historically poor. The use of oral ribavirin (RBV) has not been widely studied in this patient population. We examined the outcomes of 15 consecutive patients (RSV, n=13 and PIV3, n=2) treated with oral RBV post HPCT. Oral RBV was commenced at a starting dose of 10 mg/kg/day, increasing to a maximum dose of 60 mg/kg/day depending on response and tolerance. At diagnosis, seven patients had upper respiratory tract infection (URTI) and eight had lower respiratory tract infection (LRTI). The starting RBV dose of 10 mg/kg/day did not prevent the progression of URTI to LRTI in any patient. However, with dose escalation, six of the seven patients responded to RBV therapy and survived their infective episode. Of the eight patients presenting with LRTI, six patients survived their infection, again after dose escalation of RBV. There was no dose-limiting toxicity seen in any patient. Our results indicate that oral RBV has clinical efficacy in the treatment of RSV/PIV3 infection post HPCT. However, a starting dose of 10 mg/kg/day appears ineffective; we recommend a starting dose of 20 mg/kg/day in this patient group.

Genome size and ploidy of Thysanoptera.

Flow cytometry was used to study the genome sizes and ploidy levels for four thrips species: Franklinothrips orizabensis Johansen (Thysanoptera: Aeolothripidae), Frankliniella occidentalis Pergande, Frankliniella fusca Hinds, and Thrips tabaci Lindeman (Thysanoptera: Thripidae). F. orizabensis males and females had 1C genome sizes of 426 Mb and 422 Mb, respectively. Male and female F. fusca had 1C genome sizes of 392 Mb and 409 Mb, whereas F. occidentalis males and females had smaller 1C genomes that were 345 Mb and 337 Mb, respectively. Male F. orizabensis, F. occidentalis and F. fusca were haploid and females diploid. Five isofemale lines of T. tabaci, initiated from parthenogenetic, thelytokous females and collected from different locations in North Carolina, were included in this study; no males were available. One isofemale line was diploid with a genome size of 1C = 310 Mb, and the other four had a mean genome size of 1C = 482 Mb, which is consistent with evidence from microsatellite data of diploidy and polyploidy, respectively, in these same five thelytokous lines. This is the first study to produce genome size estimates for thysanopteran species, and report polyploidy in T. tabaci populations.