Requirements for Rehabilitation Services for Children after Severe Acquired Brain Injury.

Aim Acquired brain injury (ABI) is a common cause of acquired disability in children. Rehabilitation services are known to be underdeveloped in Ireland. We aimed to estimate the incidence of severe ABI in young people in Ireland. Methods The National Quality Assurance and Information System (NQAIS) database was analysed to identify patients aged 1-16 years who had suffered a "probable severe acquired brain injury requiring rehabilitation" (PSABIR) from 2016 - 2019. PSABIR is defined as the co-occurrence of a medical condition likely to cause ABI with a length of hospital admission longer than 28 days. Results 187 young people in Ireland had PSABIRs from 2016-2019, accounting for 21.4% of all prolonged admissions (incidence 4.55 per 100,000 per year). Median length of stay was 46 days (IQR 35- 80 days). Two children (1%) were discharged directly to specialist rehabilitation; 132 (70.6%) were discharged directly home. Conclusion Severe ABI accounts for a significant proportion of prolonged paediatric admissions, with an average of 47 such events per year. Most young people spend the acute and subacute phases of recovery in a tertiary acute hospital, before being discharged directly home. Rehabilitation services need to be developed in all settings to address unmet need.

Older age and comorbidity are independent mortality predictors in a large cohort of 1305 COVID-19 patients in Michigan, United States.

INTRODUCTION: Higher comorbidity and older age have been reported as correlates of poor outcomes in COVID-19 patients worldwide; however, US data are scarce. We evaluated mortality predictors of COVID-19 in a large cohort of hospitalized patients in the United States. DESIGN: Retrospective, multicenter cohort of inpatients diagnosed with COVID-19 by RT-PCR from 1 March to 17 April 2020 was performed, and outcome data evaluated from 1 March to 17 April 2020. Measures included demographics, comorbidities, clinical presentation, laboratory values and imaging on admission. Primary outcome was mortality. Secondary outcomes included length of stay, time to death and development of acute kidney injury in the first 48-h. RESULTS: The 1305 patients were hospitalized during the evaluation period. Mean age was 61.0 ± 16.3, 53.8% were male and 66.1% African American. Mean BMI was 33.2 ± 8.8 kg m-2 . Median Charlson Comorbidity Index (CCI) was 2 (1-4), and 72.6% of patients had at least one comorbidity, with hypertension (56.2%) and diabetes mellitus (30.1%) being the most prevalent. ACE-I/ARB use and NSAIDs use were widely prevalent (43.3% and 35.7%, respectively). Mortality occurred in 200 (15.3%) of patients with median time of 10 (6-14) days. Age > 60 (aOR: 1.93, 95% CI: 1.26-2.94) and CCI > 3 (aOR: 2.71, 95% CI: 1.85-3.97) were independently associated with mortality by multivariate analyses. NSAIDs and ACE-I/ARB use had no significant effects on renal failure in the first 48 h. CONCLUSION: Advanced age and an increasing number of comorbidities are independent predictors of in-hospital mortality for COVID-19 patients. NSAIDs and ACE-I/ARB use prior to admission is not associated with renal failure or increased mortality.

Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Live surgery: highly educational or harmful?

PURPOSE: Live surgery (LS) is considered a useful teaching opportunity. The benefits must be balanced with patient safety concerns. To evaluate the rate of complications of a series of urologic LS performed by experts during the Congress Challenge in Laparoscopy and Robotics (CILR). METHODS: We present a large, multi-institution, multi-surgeon database that derives from 12 CILR events, from 2004 to 2015 with a total of 224 cases. Radical prostatectomy (RP) was the most common procedure and a selection of complex cases was noted. The primary measure was postoperative complications and use of a Postoperative Morbidity Index (PMI) to allow quantitative weighing of postoperative complications. RESULTS: From 12 events, the number of cases increased from 11 in 2004 to 27 in 2015 and a total of 27 surgeons. Of 224 cases (164 laparoscopic and 60 robotic), there were 26 (11.6%) complications: 5 grade I, 5 grade II, 3 grade IIIa, 12 grade IIIb and 1 grade V, the latter from laparoscopic cystectomy. Analysis of PMI was 23 times higher from cystectomy compared to RP. CONCLUSIONS: In the setting of live surgery, the overall rate of complications is low considering the complexity of surgeries. The PMI is not higher in more complex procedures, whereas RP seems very safe.

Robotic uterine-sparing vesicovaginal fistula repair.

INTRODUCTION AND HYPOTHESIS: The objective was to describe a technique for the robotic repair of complex vesicovaginal fistula (VVF) with uterine preservation. METHODS: From 2015 to 2017, two patients underwent the procedure. Following placement of the patient in the lithotomy position, catheterization of the fistulous tract and laparoscopic omental harvesting is performed. Then, the robotic system is docked. A transverse incision was made in the peritoneum above the uterus was made to provide access to the bladder, the uterus is mobilized, and a cystotomy is performed to identify the structures. Subsequently, the cystotomy is extended toward the fistulous tract, the plane between the organs is dissected to proceed with the vaginal closure, the vagina is closed, the omental flap is interposed, and the bladder is closed. RESULTS: Mean operative time (OT) was 219 min. Mean estimated blood loss (EBL) was 75 ml. One of the patients had an intraoperative cervix canal injury that was identified and repaired. The postoperative course was uneventful, and the mean length of hospital stay (LOS) was 1 day. A mean follow-up of 17 (±9.89) months showed no recurrence at cystoscopy or imaging evaluation. CONCLUSIONS: Uterine-sparing VVF repair is feasible and safe. More studies are needed to assess equivalence compared with other procedures.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.

Out of sight, out of mind? A national survey of paediatricians in Ireland regarding Fetal Alcohol Spectrum Disorders.

Fetal Alcohol Spectrum Disorders (FASDs) are one of the major causes of preventable developmental delay. There is no register of children with FASDs in Ireland. Up to 81% of Irish women report drinking alcohol during the periconceptual period or pregnancy. We aimed to evaluate self-reported knowledge and practice of doctors working in paediatrics in Ireland with regards to FASDs and alcohol consumption during pregnancy. We circulated a survey to all paediatric doctors in Ireland, either enrolled in specialist training or registered as trainers. Fifty-six respondents (31.3%) were unaware of the existence of FASDs. Sixty-two (34.6%) believed most patients with FASDs have dysmorphic features. Seventy-three respondents (40.8%) routinely ask about maternal alcohol consumption during pregnancy in the context of developmental delay. Thirty-one respondents (17.3%) stated that mild alcohol intake in the third trimester of pregnancy is safe. Our survey suggests prenatal alcohol exposure may not be routinely considered in the evaluation of children with developmental delay by paediatric doctors in Ireland.

[Interest using 3D ultrasound and MRI fusion biopsy for prostate cancer detection]. / Quel est l'intérêt de l'échographie 3D et fusion d'image IRM pour la détection du cancer de la prostate ?

INTRODUCTION: The strategic therapy for prostate cancer depends on histo-pronostics data, which could be upgraded by obtaining targeted biopsies (TB) with MRI (magnetic resonance imagery) fusion 3D ultrasound. OBJECTIVES: To compare diagnostic yield of image fusion guided prostate biopsy using image fusion of multi-parametric MRI (mpMRI) with 3D-TRUS. MATERIALS AND METHODS: Between January 2010 and April 2013, 179 consecutive patients underwent outpatient TRUS biopsy using the real-time 3D TRUS tracking system (Urostation™). These patients underwent MRI-TRUS fusion targeted biopsies (TB) with 3D volume data of the MRI elastically fused with 3D TRUS at the time of biopsy. RESULTS: A hundred and seventy-three patients had TBs with fusion. Mean biopsy core per patient were 11.1 (6-14) for SB and 2.4 (1-6) for TB. SBs were positive in 11% compared to 56% for TB (P<0.001). TB outperformed systematic biopsy(SB) in overall any cancer detection rate, detection of clinically significant cancer (58% vs. 36%), cancer core length (6.8mm vs. 2.8mm), and cancer rate per core (P<0.001). In multivariable logistic regression, with TB we have more chance to find a clinically significant cancer (OR:3.72 [2-6.95]). When both TRUS and MRI are positive, there is 2.73 more chance to find a clinically significant cancer. CONCLUSION: MR/TRUS elastic fusion-guided biopsies outperform systematic random biopsies in diagnosing clinically significant cancer. Ability of interpretation of real-time TRUS is essential to perform the higher level of MR/US fusion and should be use for active surveillance. LEVEL OF PROOF: 4.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma.

BACKGROUND: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). METHODS: Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft. RESULTS: We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis. CONCLUSIONS: Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.

Neonatal referrals to the coroner service: a short survey on current practice.

In Ireland, coroners are required by law to ascertain the details of potentially unexplained deaths. The Coroner's Acts (1962 and 2005) detail deaths which must be notified to the coroner. We surveyed current practice regarding the notification of the Coroner Service following neonatal deaths by telephone interview of senior clinical nurse managers of paediatric units with neonatal inpatients. Five of 21 units (23.8%) reported that all neonatal deaths would prompt contact with the Coroner Service, with four more units (19%) reporting that unexpected neonatal deaths would be referred. Nine units (42.9%) reported that referral was at the discretion of the consultant involved while three units (14.3%) do not refer neonatal deaths to the coroner.

The relationship between vitamin D and chemotherapy-induced toxicity - a pilot study.

BACKGROUND: There are anecdotal data that lower levels of vitamin D may be associated with increased levels of toxicity in individuals receiving chemotherapy; we therefore wished to investigate this further. METHODS: From a cohort of over 11 000 individuals, we included those who had vitamin D levels (serum 1,25(OH)(2)D3) measured before and during chemotherapy. They were analysed for side effects correlating Chemotherapy Toxicity Criteria with vitamin D levels, normalising data for general markers of patient health including C-reactive protein and albumin. RESULTS: A total of 241 (2% of the total cohort) individuals entered the toxicity analysis. We found no overall difference in toxicity effects experienced by patients depending on whether they were vitamin D depleted or had sufficient levels (P=0.78). CONCLUSION: This pilot study suggests routine vitamin D measurement during treatment does not appear to be necessary in the management of chemotherapy-induced toxicity.

Dystonia in children with acquired brain injury.

AIM: To quantify the proportion of children who develop dystonia after acquired brain injury (ABI) admitted to a tertiary paediatric intensive care unit (PICU) and analyse the trajectory of dystonia over a 6 month period. METHODS: Children's Health Ireland at Temple Street PICU electronic database was searched for key terms related to ABI from January 1, 2016 to March 14, 2021. Individuals meeting inclusion criteria were analysed, and clinical data pertinent to ABI, dystonia, treatment and outcomes were reviewed. RESULTS: Six-hundred and forty-three PICU episodes (580 patients) met search criteria for ABI, with 379 included in the final analysis. Twelve patients developed dystonia following ABI, giving an incidence of 3.2%. The incidence was higher in the hypoxia/anoxia and TBI cohort at 8.3% and 6.2%, respectively. All patients developed dystonia within the first month following ABI (50% by a week). Patients who developed dystonia compared to non-dystonia cohort had a median lower GCS on admission (4.5 versus 7.0, p value 0.032), longer median length of PICU stay (14.0 versus 3.0 days, p value < 0.001) and were older (median age 9.08 versus 4.68 years, p value 0.06). Dystonia persisted in the majority at 6 months (10/11), requiring on-going medical therapies. CONCLUSION: In our retrospective study, the estimated incidence of dystonia following ABI admitted to the PICU was 3.2%, highest in the hypoxia/anoxia (8.3%) and TBI (6.2%) cohorts. Dystonia emerged early and persisted at 6 months in the majority. This is the first review of dystonia, clinical trajectory and outcomes conducted post-PICU admission for ABI. Future prospective studies are required to determine the true prevalence and burden of disease in the PICU setting.

Clinical utility of temozolomide in the treatment of malignant paraganglioma: a preliminary report.

We report on the efficacy and safety of short-term administration of temozolomide, an inhibitor of nucleoside incorporation, in a 60-year-old woman with widespread hepatic metastases from a malignant paraganglioma. Temozolomide was orally administered in daily doses of 250 mg on days 1 to 5 and repeated every 28 days for five cycles. Clinical improvement was immediate and associated with weight gain, and further reduction in blood pressure without ortho-static intolerance. In addition, abnormal hepatic function was normalized and catecholamine production was significantly reduced. Except for mild nausea, adverse effects were virtually absent. Bone marrow function, renal function, and serum electrolytes remained normal; hemoglobin remained above 9 g/dl through treatment. The platelet count decreased but not to clinically meaningful levels. These responses allowed for a surgical debulking procedure to be performed safely without complications. The results suggest that temozolomide may be useful in presurgical preparation of patients with pheochromocytoma especially in those with widespread metastatic disease and poor physical condition. However, the present findings need confirmation in a larger study and the role of temozolomide in the long-term treatment of malignant paraganglioma/pheochromocytoma remains to be established.