A prevention protocol reduces spinal cord ischemia in patients undergoing branched/fenestrated endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication that is associated with thoracoabdominal aortic repair, with higher risk associated with increased aortic coverage length, making patients undergoing branched/fenestrated endovascular repair (B/FEVAR) particularly vulnerable. A bundled SCI prevention protocol was previously reported to reduce SCI rates when compared to a historic cohort in a single-center study. Therefore, this analysis aims to further validate and update outcomes associated with the protocol given the routine implementation of this strategy at two institutions (University of Florida and the University of Alabama at Birmingham) since inception. METHODS: Components of the SCI prevention protocol include selective cerebrospinal fluid drainage, specified blood pressure parameters, transfusion goals, and selective pharmacologic adjuncts (naloxone, steroids). This protocol was routinely implemented in May 2015. Patients undergoing B/FEVAR from May 2015 to December 2022 constituted the post-protocol cohort (n = 402) and were compared with the pre-protocol cohort (n = 160; January 2010-April 2015). The primary outcome was SCI incidence, and subgroup analysis was conducted among patients deemed to be high-risk (Crawford extent I-III thoracoabdominal aneurysm dissection-related disease, prior aortic repair, coverage proximal to zone 5). Survival analysis was performed using Kaplan-Meier methodology. RESULTS: The pre- and post-protocol cohorts were demographically similar, although more post-protocol patients were American Society of Anesthesiology class IV (86.1% vs 55.0%; P < .001). Thoracoabdominal aneurysm was the most common indication in both groups. Cerebrospinal fluid drain placement was more common in the post-protocol group, particularly among high-risk patients. SCI occurred in 15.9% of pre-protocol patients vs 3.0% of post-protocol patients (P < .001). In high-risk patients, the pre- and post-protocol cohort SCI incidence was 23.2% vs 5.0%, respectively (P < .001). Thirty-day mortality was decreased in the post-protocol cohort (6.3% vs 2.2%; P = .02). Although the post-protocol group had a trend toward improved 1-year survival, this was not statistically significant (84.4% vs 88.3%; log-rank P = .35). Among patients with SCI, 1-year mortality was 28% and 33.3% in the pre- and post-protocol groups, respectively (P = .46). CONCLUSIONS: Implementation of a bundled SCI prevention protocol significantly reduces SCI rates in patients undergoing B/FEVAR, which has now been validated at two institutions, with the most significant reductions occurring among high-risk patients. Although the overall 1-year mortality difference was not significantly different between the cohorts, the high mortality rates among patients with SCI highlights the importance of preventative measures.

Evaluation of the tolerability and safety of [225Ac]Ac-PSMA-I&T in patients with metastatic prostate cancer: a phase I dose escalation study.

BACKGROUND: Life expectancy of patients with metastatic castration-resistant prostate cancer (mCRPC) is still limited despite several systemic treatments. Within five years after diagnosis of primary prostate cancer, 10-20% of the patients have mCRPC and curation is not an option. Radionuclide therapy (RNT) targeted against prostate-specific membrane antigen (PSMA) emerged as a new treatment option and showed effective results in patients with mCRPC. Survival benefit after [177Lu]Lu-PSMA RNT has already been demonstrated in several clinical trials. However, [225Ac]Ac-PSMA (225Ac-PSMA) appears to be an even more promising radiopharmaceutical for the treatment of mCRPC. The use of alpha emitting radionuclides offers advantages over beta emitting radionuclides due to the high linear energy transfer effective for killing tumor cells and the limited range to reduce the radiation effects on the healthy tissue. However, these results are based on retrospective data and safety data of 225Ac-PSMA are still limited. Therefore, a prospective trial is needed to determine the optimal amount of activity that can be administered. METHODS: The 225Ac-PSMA-Imaging & Therapy (I&T) trial is an investigator-initiated phase I, single-center, open label, repeated dose-escalation and expansion trial. Patient with PSMA-positive mCRPC after at least one line of chemotherapy and/or one line of nonsteroidal antiandrogen will be treated with 225Ac-PSMA-I&T in increasing amount of activity per cycle. Dose-escalation following an accelerated 3 + 3 design which allows to open the next dose-level cohort in the absence of dose limiting toxicity while the previous one is still ongoing. Up to 4 treatment cohorts will be explored including up to 3 dose-escalation cohorts and one expansion cohort where patients will be administered with the recommended dose. A total of up to 30 patients will be enrolled in this trial. All patients will be evaluated for safety. Additionally, dosimetry was performed for the patients in the dose-escalation cohorts after the first 225Ac-PSMA-I&T administration. DISCUSSION: This trial will assess the safety and tolerability of 225Ac-PSMA-I&T in patients with mCRPC to recommend the optimal dose for the phase II trial. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT05902247). Retrospectively registered 13 June 2023.

The distance of insertion points from wound margins in interrupted and vertical mattress sutures influences the tensile load capacity: An in vitro experimental study.

AIM: To determine the tensile load capacity (TLC) and the tearing characteristics for interrupted and vertical mattress sutures with different insertion points from the wound margin, and the effect of the bite size when using vertical mattress sutures. MATERIALS AND METHODS: A total of 120 gingiva and lining mucosa samples obtained from pig jaws were divided into groups according to the suturing technique (interrupted and vertical mattress sutures), distance of the insertion points from the wound margin (margin, 1, 3, and 5 mm) and bite size (1, 3, and 5 mm). The TLC of the suture and the tearing characteristics were evaluated using a tensile tester device. RESULTS: The TLC was significantly higher for vertical mattress sutures than for interrupted sutures regardless of the distance of the insertion points from the wound margin (intergroup p < .001). This distance significantly influenced the TLC for vertical mattress sutures (p < .05) but not for interrupted sutures (p > .05). Testing the tearing characteristics revealed that no tissue tearing occurred in groups when the insertion points were more than 3 mm from the wound margin. CONCLUSION: The TLC is higher for vertical mattress sutures than for interrupted sutures, and it increases when the insertion points are farther from the wound margin.

Effectiveness of call system implementation for postpartum hemorrhage in a tertiary emergency medical center: a retrospective cohort study.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal death and severe maternal morbidity worldwide. Previous studies have reported the importance of multidisciplinary treatment approaches for postpartum hemorrhage; however, only a few studies have shown a clear improvement in maternal outcomes. Therefore, this study aimed to investigate the efficacy of a call system for postpartum hemorrhage in a tertiary emergency facility for rapid multidisciplinary treatment and its effect on maternal outcomes. METHODS: This single-center retrospective cohort study included patients transferred to our hospital due to postpartum hemorrhage between April 1, 2013, and March 31, 2019. The primary outcome was mortality, and the secondary outcomes were morbidity (duration of hospital stay, duration of intensive care unit stay, admission to the intensive care unit, respirator use, duration of ventilator support, acute kidney injury, transfusion-associated circulatory overload/transfusion-related acute lung injury, hysterectomy, composite adverse events, blood transfusion initiation time, blood transfusion volume, and treatment for postpartum hemorrhage). An in-hospital call system implementation commenced on April 1, 2016. The study outcomes were compared 3 years before and after implementing the call system. RESULTS: The blood transfusion initiation time and duration of hospital stay were significantly shortened after implementing the call system for postpartum hemorrhage. No maternal deaths were observed after implementing the system. CONCLUSIONS: Implementing call systems specialized for postpartum hemorrhage in tertiary emergency facilities may improve maternal outcomes.

Methodology for implementing early recovery after surgery protocols in colorectal surgery.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols in colorectal surgery leads to improved quality of care and more efficient resource utilization. Despite these positive outcomes, the penetration of ERAS protocols in the Czech Republic is low. The aim of this study is to present a general methodology for implementing an ERAS protocol in colorectal surgery. METHODS: The methodology is based on the authors' extensive experience in implementing clinical protocols at various institutions in the Czech Republic, as well as published international experiences. This methodology is described in detail and supplemented with data obtained during implementation of an ERAS program at the author's institution. RESULTS: The preparatory phase includes in-depth quality of care audits and preparation of an ERAS protocol. The purpose of the audits is to identify areas of care where standardization or targeted changes in clinical practice are desirable. The implementation phase involves staff training, technical implementation support, protocol dissemination, adherence monitoring, and evaluation of a pilot phase with subsequent protocol adjustments. The evaluation phase involves data collection, maintaining a prospective database, and regular assessments. CONCLUSION: The presented methodology describes the individual steps in the process of implementing a clinical protocol into practice. This text can serve as a manual for implementing an ERAS protocol in colorectal surgery at any institution.

Prognostic effects of treatment protocols for febrile convulsive status epilepticus in children.

BACKGROUND: Febrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence. METHODS: This was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002-December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007-February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013-April 2016), BCT was indicated for FCSE resistant to fPHT or PB. RESULTS: The rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40). CONCLUSIONS: While the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.

Influence of Postponed Follow-Up after Cochlear Implant Activation during the COVID-19 Pandemic on Aided Sound Field Detection and Speech Recognition.

INTRODUCTION: The objective of this study was to assess the influence of postponing the first post-activation follow-up due to the COVID-19 pandemic on the aided sound field detection thresholds and speech recognition of cochlear implant (CI) users. METHODS: A retrospective review was performed at a tertiary referral center. Two groups of adult CI recipients were evaluated: (1) patients whose first post-activation follow-up was postponed due to COVID-19 closures (postponed group; n = 10) and (2) a control group that attended recommended post-activation follow-ups prior to the COVID-19 pandemic (control group; n = 18). For both groups, electric thresholds were estimated at initial activation based on comfort levels and were measured behaviorally at subsequent post-activation follow-ups. For the control group, behavioral thresholds were measured at the 1-month follow-up. For the postponed group, behavioral thresholds were not measured until 3 months post-activation since the 1-month follow-up was postponed. The aided pure-tone average (PTA) and word recognition results were compared between groups at the 3-month follow-up and at an interim visit 2-9 weeks later. RESULTS: At the 3-month follow-up, the postponed group had significantly poorer word recognition (23 vs. 42%, p = 0.027) and aided PTA (42 vs. 37 dB HL, p = 0.041) than the control group. No significant differences were observed between 3-month data from the control group and interim data from the postponed group. CONCLUSIONS: The postponed follow-up after CI activation was associated with poorer outcomes, both in terms of speech recognition and aided audibility. However, these detrimental effects were reversed following provision of an individualized map, with behaviorally measured electric threshold and comfort levels. While adult CI recipients demonstrate an improvement in speech recognition with estimated electric thresholds, the present results suggest that behavioral mapping within the initial weeks of device use may support optimal outcomes.

Evidence-based protocol for diagnosis and treatment of hepatorenal syndrome is independently associated with lower mortality.

BACKGROUND: Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients. METHODS: An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis. RESULTS: The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27mg to 22mg and from 236g to 144g, respectively, after the institution of the protocol. This was not associated with higher mortality. CONCLUSION: The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.

Combination of gemcitabine, nab-paclitaxel, and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma: study protocol for an open-label, single-arm phase I study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is still a highly fatal malignancy among the most common cancers. More powerful treatments are expecting to bring hope for patients. Biweekly gemcitabine/nab-paclitaxel/S-1 (GAS) was proved safe and effective for patients with locally advanced pancreatic cancer in Japan. The objective of this study is to evaluate the feasibility and toxicity of GAS (repeated every 3 weeks) in the treatment of locally advanced or advanced pancreatic cancer and determine the recommended dose of S-1 in this combination. METHODS: This is an open-label, single-arm, and single-center phase I trial. Patients who have been diagnosed with locally advanced or advanced PDAC pathologically without previous systemic treatments will be enrolled and be treated with GAS chemotherapy every 3 weeks (nab-paclitaxel 125 mg/m 2, ivgtt, day1, 8; gemcitabine 1000 mg/m2, day1, 8; different doses of S-1 within a dose escalation scheme) until the presence of disease progression (PD), intolerable adverse events (AEs), or requirement of patients and researchers. The primary endpoints are maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). The secondary endpoints include safety, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). DISCUSSION: This trial will adjust the administration of GAS to make it more effective for Chinese patients, while exploring the toxicity and feasibility of this adjustment. TRIAL REGISTRATION: ChiCTR, ( ChiCTR1900027833 ). Registered 30 November 2019.

Study protocol for an open-label, single-arm, phase Ib/II study of combination of toripalimab, nab-paclitaxel, and gemcitabine as the first-line treatment for patients with unresectable pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a dismal response to single-use of immune checkpoint inhibitors (ICIs). ICIs combined with systemic therapy has shown efficacy and safety in various solid tumors. Nab-paclitaxel and gemcitabine (AG), as the standard first-line treatment for advanced PDAC, has been widely used in recent years. The combination of ICIs and AG chemotherapy appears to be a promising option in the treatment of PDAC. METHODS: This is an open-label, single-arm, and single-center phase Ib/II trial. The enrolled subjects are the unresectable (locally advanced or metastatic) PDAC patients without previous systemic treatments. All subjects receive an intravenous injection of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on day 1 and day 8, along with toripalimab 240 mg at day 1 every 3 weeks. The subjects may discontinue the treatment because of progression disease (PD), intolerable toxicities, requirements of patients or researchers. For local advanced patients who are evaluated as partial response (PR), surgeons need to assess the surgical possibility. The primary objective of this trial is to evaluate the safety and overall survival (OS) of this combination therapy; and the secondary objective is related to the assessment of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and the rate of resection or R0 resection after receiving toripalimab plus AG treatment. Besides, we expect to identify the predictive biomarkers (such as MMR protein and PD-L1 expression, the number of TILs, the small RNA of EBV and so on) and explore the correlation between these biomarkers and tumor response to this combined regimen. DISCUSSION: This trial is the first attempt to evaluate the efficacy and safety of the combination of toripalimab plus AG chemotherapy as a first-line treatment for unresectable PDAC patients. The results of this phase Ib/II study will provide preliminary evidence for further assessment of this combined therapeutic regimen for unresectable PDAC patients. TRIAL REGISTRATION: Trial registration: ChiCTR ( ChiCTR2000032293 ). Registered 25 April 2020 - Retrospectively registered.

Opium-Related Lead Toxicity: An Integrative Review and Case Series.

BACKGROUND: Restrictive regulations and the increased price of opioids have resulted in the addition of impurities to illicit opioids by drug dealers. Among the adulterants, lead salts are optimal agents to make packages heavier. Consequently, lead toxicity has emerged in the opioid-user population. OBJECTIVES: Our goal was to review the related literature and describe patients with common presentations of opioid-related lead poisoning to provide a basis to prepare optimal management. METHODS: A narrative review was performed aiming to study opioid lead poisoning. PubMed and Google Scholar databases were explored with two Medical Subject Heading terms, lead poisoning and substance-related disorders to find a broad but relevant spectrum of articles. Then, the reference lists within those articles were checked to upgrade our literature pool on this issue. RESULTS: Ultimately, among English-language articles, 16 were case series and case reports of patients with lead intoxication after opioid consumption. Data pertaining to disease characteristics, diagnosis, and treatment protocols were extracted. CONCLUSIONS: The clinical presentation of opioid lead intoxication can vary from rather asymptomatic to severely debilitating gastrointestinal or neurologic symptoms. The diagnosis is made by checking lead blood levels after obviating other critical diagnoses and should be considered in each drug user in endemic regions of opioid addiction, such as the Middle East. Management protocols are suggested to cover both features of opioid-related complications and lead toxicity.

[Course of Revision of the Diagnosis and Treatment Protocol for COVID-19 and the Forensic Contribution].

ABSTRACT: From January 15 to March 3, 2020, seven editions of the guidelines for the diagnosis and treatment of COVID-19 have been issued successively by the National Health Commission of the People's Republic of China, and the guidelines' name was changed from Guidelines for Diagnosis and Treatment of Novel Coronavirus Pneumonia to Diagnosis and Treatment for COVID-19. It optimized and perfected the etiology, clinical manifestations and types, diagnostic procedures and specific treatment measures of the disease, so that the clinical management of the cases was more scientific. In the revision process of guidelines for diagnosis and treatment, forensic medicine experts have also made some positive suggestions on clinical diagnosis and treatment. Especially regarding the pathological changes of COVID-19, they have repeatedly called for rapid autopsy at different levels. With the support, understanding and cooperation of all parties, pathological examination of more than ten cases of the remains were carried out, which made an important contribution to the understanding of the clinical characteristics and pathological characteristics of the disease and the improvement of treatment plans.

Regulation of programmed death-ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine.

Anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy, which is one of the most promising cancer therapies, is licensed for treating various tumors. Programmed death-ligand 1, which is expressed on the surface of cancer cells, leads to the inhibition of T lymphocyte activation and immune evasion if it binds to the receptor PD-1 on CTLs. Anti-PD-1/PD-L1 Abs inhibit interactions between PD-1 and PD-L1 to restore antitumor immunity. Although certain patients achieve effective responses to anti-PD-1/PD-L1 therapy, the efficacy of treatment is highly variable. Clinical trials of anti-PD-1/PD-L1 therapy combined with radiotherapy/chemotherapy are underway with suggestive evidence of favorable outcome; however, the molecular mechanism is largely unknown. Among several molecular targets that can influence the efficacy of anti-PD-1/PD-L1 therapy, PD-L1 expression in tumors is considered to be a critical biomarker because there is a positive correlation between the efficacy of combined treatment protocols and PD-L1 expression levels. Therefore, understanding the mechanisms underlying the regulation of PD-L1 expression in cancer cells, particularly the mechanism of PD-L1 expression following DNA damage, is important. In this review, we consider recent findings on the regulation of PD-L1 expression in response to DNA damage signaling in cancer cells.

Diagnostic accuracy of third-generation dual-source dual-energy CT: a prospective trial and protocol for clinical implementation.

PURPOSE: Uric acid (UA) calculi can be referred to chemolitholysis rather than invasive treatment. Dual-energy computed tomography (DECT) may be able to distinguish between UA and non-UA (NUA) calculi. The aim of this study was to evaluate the validity of third-generation DECT for the first time and to investigate whether combining DECT with clinical parameters can increase its predictive accuracy. MATERIALS AND METHODS: All patients who presented to our emergency department between January 2015 and March 2017 with urinary stones were prospectively included in this observational study and underwent DECT with subsequent interventional stone removal. Stone composition was analyzed using infrared spectrometry as the gold standard. Predictive accuracy of DECT and clinical covariates was computed by assessing univariate and multivariate areas under the curve (AUCs). RESULTS: Of 84 patients with 144 urinary stones, 10 (11.9%) patients had UA stones according to infrared spectrometry, and the remaining stones were NUA or mixed stones. DECT had a positive predictive value of 100% and a negative predictive value of 98.5% for UA stones. The AUC for urine pH alone was 0.71 and 0.97 for DECT plus urine pH. No UA stones were found in patients with a urine pH above > 5.5. Mean DLP was 225.15 ± 128.60 mGy*cm and mean effective dose was 3.38 ± 1.93 mSv. CONCLUSIONS: DECT is a safe method for assigning patients to oral chemolitholysis. Clinical preselection of patients based on urinary pH (< 6.0) leads to a more liable use of DECT. Third-generation DECT needs significant lower radiation doses compared to previous generations.

Safety and outcomes of 177 Lu-DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia.

BACKGROUND: Peptide receptor radionuclide therapy with 177 Lu-DOTATATE is a promising treatment for inoperable or metastatic neuroendocrine tumours (NET). In 2015, the NSW Ministry of Health provided funding for 177 Lu-DOTATATE treatment of NET under an evaluation framework. AIMS: To examine the safety and outcomes of NET patients treated with 177 Lu-DOTATATE under the evaluation framework and assess the statewide implementation of the NSW Lutate therapy referral and protocol for neuroendocrine cancer patients. METHODS: A quality of care clinical audit was conducted on all NET patients treated with 177 Lu-DOTATATE from October 2010 to October 2015 at St George Hospital, and from August 2013 to March 2017 at Royal North Shore Hospital. Percentage of patients who met protocol selection criteria was calculated. Survival was estimated using the Kaplan-Meier method. Adjusted regression analyses assessed associations between key clinical factors and outcomes. RESULTS: A total of 279 patients was treated. Statewide protocol implementation led to an increase from 60.5 to 83.8% in patients meeting selection criteria. Estimated median overall survival was significantly longer for patients who met selection criteria compared with those who did not (50.7 vs 34.2 months) (P = 0.018). This was driven by the significantly worse overall survival in patients who failed exclusion criteria (P < 0.001). 177 Lu-DOTATATE was well tolerated with haematological, renal and hepatic treatment-related serious adverse events experienced by 9.7, 0.4 and 0.4% of patients respectively. CONCLUSIONS: 177 Lu-DOTATATE is a promising treatment for advanced NET. Superior survival in patients who met selection criteria emphasise the importance of protocol adherence.

Introduction to contrast-enhanced ultrasound of the brain in neonates and infants: current understanding and future potential.

Contrast-enhanced ultrasound (CEUS) is a valuable bedside imaging technique that enables both qualitative and quantitative assessment of cerebral perfusion. In neonates and infants whose fontanelles remain open, the technique is particularly useful as it delineates cerebral pathology with high soft-tissue contrast. The technique has the potential to be a valuable alternative to computed tomography (CT) or magnetic resonance imaging (MRI) in critically ill neonates and infants in need of bedside imaging. While further studies are needed to validate the technique, preliminary data in this regard appear promising. This review introduces the current understanding and future potential of brain CEUS.

Surveying the management of Achilles tendon ruptures in the Netherlands: lack of consensus and need for treatment guidelines.

PURPOSE: This study aimed to describe and analyse usual care of Achilles tendon ruptures (ATRs) by orthopaedic surgeons and trauma surgeons in the Netherlands. METHODS: A nationwide online survey of ATR management was sent to all consultant orthopaedic and trauma surgeons in the Netherlands, requesting participation of those involved in ATR management. Data on individual characteristics and the entire ATR management (from diagnosis to rehabilitation) were gathered. Consensus was defined as ≥ 70% agreement on an answer. RESULTS: A total of 91 responses (70 orthopaedic surgeons and 21 trauma surgeons) were analysed. There was consensus on the importance of the physical examination in terms of diagnosis (> 90%) and a lack of consensus on diagnostic imaging (ultrasound/MRI). There was consensus that non-surgical treatment is preferred for sedentary and systemically diseased patients and surgery for patients who are younger and athletic and present with larger tendon gap sizes. There was consensus on most of the non-surgical methods used: initial immobilisation in plaster cast with the foot in equinus position (90%) and its gradual regression (82%) every 2 weeks (85%). Only length of immobilisation lacked consensus. Surgery was generally preferred, but there was a lack of consensus on the entire followed protocol. Orthopaedic and trauma surgeons differed significantly on their surgical (p = 0.001) and suturing techniques (p = 0.002) and methods of postoperative immobilisation (p < 0.001). Orthopaedic surgeons employed open repair and Bunnell sutures more often, whereas trauma surgeons used minimally invasive approaches and bone anchors. Rehabilitation methods and advised time until weight-bearing and return to sport varied. Orthopaedic surgeons advised a significantly longer time until return to sport after both non-surgical treatment (p = 0.001) and surgery (p = 0.002) than trauma surgeons. CONCLUSION: This is the first study to describe the entire ATR management. The results show a lack of consensus and wide variation in management of ATRs in the Netherlands. This study shows that especially the methods of the perioperative and rehabilitation phases were inconclusive and differed between orthopaedic and trauma surgeons. Further research into optimal ATR management regimens is recommended. In addition, to achieve uniformity in management more multidisciplinary collaboration between Dutch and international surgeons treating ATRs is needed. LEVEL OF EVIDENCE: Cross-sectional survey, Level V.

A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol.

BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy. METHODS: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug. DISCUSSION: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

A new prescription model for regional citrate anticoagulation in therapeutic plasma exchanges.

BACKGROUND: Regional citrate anticoagulation (RCA) is proposed for various extracorporeal purification techniques to overcome the risk of bleeding that might result from systemic anticoagulation. Yet, no individualized treatment protocol has been proposed for therapeutic plasma exchange (TPE) so far. The objective of this study was to assess the determinants of blood citrate concentration needed and to develop an individualized RCA protocol useful for clinical practice. METHODS: The study population included 14 patients who underwent a total of 47 TPE sessions. Citrate was infused pre-plasmafilter. Post-plasmafilter and systemic plasma ionized calcium concentrations were measured at standardized time intervals. An algorithm was proposed for the supplementation of calcium. During the discovery phase, citrate was infused at a fixed starting rate, and adapted accordingly to obtained post-plasmafilter ionized calcium levels. Using a mathematical approach, an algorithm was thereafter developed for individualized prescriptions of citrate. RESULTS: Pre-treatment values of hematocrit and plasma ionized calcium were the main determinants of the required rate of citrate infusion. These can be integrated into a final equation enabling to individualize the prescription. A prefilter ionized calcium concentration between 0.24 and 0.33 mmol/l prevented coagulation of the extracorporeal circuit. Significant hypocalcemia occurred in 8.5% of treatments. There were no significant acid-base disturbances. CONCLUSION: We propose a new protocol, which enables for the first time to individualize the prescription of regional citrate anticoagulation during TPE, in an efficient manner. The immediately obtained regional anticoagulation protects against both the risk of coagulation of the membrane and the exposure to an excess of citrate.

Induction of labour practices in New South Wales hospitals: Before and after a statewide policy.

Midwifery Unit Managers completed surveys in 2008 and 2014 to determine methods of induction of labour. There was an increase in balloon catheter use for cervical ripening (rate difference 37%, P = 0.007). Currently, all respondent hospitals have an oxytocin protocol; district hospitals had a significant increase in use of post-maturity protocols (rate difference = 40%, P = 0.01) but there was no change in use of prostaglandin protocols.