Internal evaluation of risk stratification tool using serial procalcitonin and clinical risk factors in pediatric febrile neutropenia: The non-interventional, single institution experience prior to clinical implementation.

Risk stratification of pediatric febrile neutropenia (FN) is an established concept, yet clinical risk tools misclassify nearly 5% of clinical standard-risk episodes with severe outcomes. The internal evaluation of a clinical risk tool before implementation has not been well-described. In this noninterventional cohort study, we evaluated a study decision rules (SDR) tool; a clinical risk tool with serial procalcitonin. The study standard-risk (SSR) group met clinical standard-risk criteria with two serial procalcitonin <0.4 ng/mL. The study high-risk (SHR) group met clinical high-risk criteria or clinical standard-risk with a procalcitonin ≥0.4 ng/mL. Descriptive and bivariate statistics compared the groups and outcomes. Clinical criteria alone identified 39.1% (238/608) standard-risk episodes; 5.9% (14/238) had severe events. Prospectively using the SDR, the SHR group encompassed 76.6% (92/120) of episodes; severe events occurred in 20% (3/15) of standard-risk episodes included due to elevated procalcitonin ≥0.4 ng/mL. The SHR group had more blood stream infections [21.7% (20/92) vs. 0% (0/28); P = 0.007] and intensive care admissions [13% (12/92) vs. 3.6% (1/28); P = 0.158]. In conclusion, the SDR with serial procalcitonin aided in identifying severe events in clinical standard-risk episodes, but analysis was limited. Institutions may consider similar internal evaluation methodology before FN episode risk stratification.

Characterization and clinicopathological significance of circulating tumour cells in patients with oral squamous cell carcinoma.

Circulating tumour cells (CTCs) are cancer cells released by cancer into the peripheral circulation. Haematogenous tumour spread is a hallmark of metastatic malignancy and a key factor in cancer recurrence and prognosis. CTCs have diagnostic and prognostic significance for a number of adenocarcinomas and melanoma. A review of the published peer-reviewed literature was performed to determine the clinical relevance of CTCs as a biomarker in the management of oral squamous cell carcinoma (OSCC). Fourteen studies met the eligibility criteria. With regard to patients with OSCC, this review found the following: (1) CTCs have been detected using multiple techniques; (2) the presence of CTCs does not appear to be related to tumour differentiation or size; (3) CTCs may be detected without lymph node involvement; (4) the detection of CTCs may be prognostic for both disease-free survival and overall survival; (5) quantification of CTCs may reflect the efficacy of therapy; (6) CTCs may be of value for ongoing patient monitoring. Preliminary evidence suggests that CTCs have diagnostic and prognostic potential as a biomarker for oral cancer management and warrant further investigation to determine their appropriate place in the management of OSCC patients.

The incidence and effect of resternotomy following cardiac surgery on morbidity and mortality: a 1-year national audit on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care.

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.

Complications related to peri-operative transoesophageal echocardiography - a one-year prospective national audit by the Association of Cardiothoracic Anaesthesia and Critical Care.

Previous studies on the safety of peri-operative transoesophageal echocardiography seem to suggest a low rate of associated morbidity and mortality. That said, there has been a paucity of prospective multicentre studies in this important area of clinical practice. We carried out a one-year prospective study in 2017, co-ordinated by the Association of Cardiothoracic Anaesthesia and Critical Care, to determine the rate and severity of complications associated with peri-operative transoesophageal echocardiography in anaesthetised cardiology and cardiac surgical patients. With the help of clinicians from 28 centres across the UK and Ireland, we recorded the total number of examinations conducted in anaesthetised patients during the study period. All major complications at each centre were prospectively reported and recorded. Of the 22,314 examinations, there were 17 patients diagnosed with a major complication which caused either palatal injury or gastro-oesophageal disruption. This corresponds to an incidence of 0.08% (95%CI 0.05-0.13%) or approximately 1:1300 examinations. There were seven deaths reported during the study period which were directly attributed to these complications, corresponding to an incidence of 0.03% (95%CI 0.01-0.07%) or approximately 1:3000. These figures are higher than previously reported and suggest a high probability of death following the development of a complication (~40%). Most complications occurred in patients without known risk factors for transoesophageal echocardiography associated gastro-oesophageal injury. We suggest clinicians and departments review their procedural guidelines, especially in relation to probe insertion techniques, together with the information communicated to patients when the risks and benefits of such examinations are discussed.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Using the cavitation collapse time to indicate the extent of histotripsy-induced tissue fractionation.

Histotripsy is an ultrasonic tissue ablation method based on acoustic cavitation. It has been shown that cavitation dynamics change depending on the mechanical properties of the host medium. During histotripsy treatment, the target-tissue is gradually fractionated and eventually liquefied to acellular homogenate. In this study, the change in the collapse time (t col) of the cavitation bubble cloud over the course of histotripsy treatment is investigated as an indicator for progression of the tissue fractionation process throughout treatment. A 500 kHz histotripsy transducer is used to generate single-location lesions within tissue-mimicking agar phantoms of varying stiffness levels as well as ex vivo bovine liver samples. Cavitation collapse signals are acquired with broadband hydrophones, and cavitation is imaged optically using a high-speed camera in transparent tissue-mimicking phantoms. The high-speed-camera-acquired measurements of t col validate the acoustic hydrophone measurements. Increases in t col are observed both with decreasing phantom stiffness and throughout histotripsy treatment with increasing number of pulses applied. The increasing trend of t col throughout the histotripsy treatment correlates well with the progression of lesion formation generated in tissue-mimicking phantoms (R 2 = 0.87). Finally, the increasing trend of t col over the histotripsy treatment is validated in ex vivo bovine liver.

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

A qualitative exploration of the informed consent process in hematopoietic cell transplantation clinical research and opportunities for improvement.

Informed consent (IC) struggles to meet the ethical principles it strives to embody in the context of hematopoietic cell transplantation (HCT). Patients often participate in multiple clinical trials making it difficult to effectively inform the participants and fulfill complex regulations. The recent Notice of Proposed Rule Making would make major changes to federal requirements, providing a timely opportunity to evaluate existing practice. Twenty health care professionals within a Midwest Academic Medical Center involved in obtaining IC in the HCT clinic or involved in patient care during or after the IC process were interviewed to understand: (1) how they approached the IC process; (2) how they described a 'successful' IC process; and (3) opportunities for innovation. Narrative and discourse analyses of interviews indicate that providers understand IC to be a collaborative process requiring engagement and participation of providers, patients and caregivers. 'Markers of success' were identified including cognitive, affective and procedural markers focusing on patient understanding and comfort with the decision to participate. Opportunities for innovating the process included use of decision aids and tablet-based technology, and better use of patient portals. Our findings suggest specific interventions for the IC process that could support the process of consent for providers, patients and caregivers.

Ureteral Complications in Kidney Transplantation: Analysis and Management of 853 Consecutive Laparoscopic Living-Donor Nephrectomies in a Single Center.

BACKGROUND: We report the incidence and nature of ureteral and surgical complications in our series of 853 consecutive living-donor renal transplants after laparoscopic living-donor nephrectomy. The aim of this study was to analyze the therapeutic approaches to ureteral complications in kidney transplantations and their relationship with recipient outcome. METHODS: The medical records of patients who underwent kidney transplantation from 2000 to 2014 were reviewed retrospectively. After the donor nephrectomies were performed with the use of laparoscopic, hand-assisted laparoscopic, and vesico-ureteral anastomosis, the recipient's ureteral complications were classified according to the mechanism and site of urinary tract involvement: anastomosis stricture, anastomosis leakage, vesico-ureteral reflux, and urolithiasis. RESULTS: Among the 853 cases of kidney transplantation, ureteral complications occurred in 66 patients (7.73%). The most common complication was urinary tract infection caused by vesico-ureteral reflux (n = 24, 2.81%), which was managed with by means of sub-ureteral polydimethylsiloxane injection. The second most common complication was the anastomosis site stricture (n = 23, 2.69%), which was treated by means of ureteral re-implantation or percutaneous nephrostomy. Anastomosis site leakage occurred in 11 patients (1.28%) and was managed by percutaneous nephrostomy with double-J stenting and drainage or ureteral re-implantation. Urolithiasis occurred in 8 patients (0.93%). CONCLUSIONS: There was an 8% rate of recipient ureteral complications at our institution. Of the 66 patients, 46 (5.4%) required surgical repair. The remaining 20 patients with ureteral complications were treated with conservative care or minimally invasive procedures. The keys to successful management of these problems are early diagnosis and prompt reconstruction whenever possible. Most ureteral complications are easily managed with a successful outcome with early intervention.

Effects of intra-operative maintenance of general anaesthesia with propofol on postoperative pain outcomes - a systematic review and meta-analysis.

Propofol is used both for induction and maintenance of anaesthesia. Recent evidence shows that propofol has analgesic properties. This meta-analysis evaluated differences in postoperative analgesia between general anaesthetic maintenance with intravenous propofol and inhalational anaesthetics. Fourteen trials met inclusion criteria and were included. Our outcomes were pain scores 2 and 24 h after surgery. No significant difference in pain scores was found at 2 h after surgery (Hedge's g (95% CI) -0.120 (-0.415-0.175) (p = 0.425). Propofol was associated with a statistically significant, albeit marginal, reduction in pain scores 24 h after surgery (Hedge's g (95% CI) -0.134 (-0.248 to -0.021) (p = 0.021). Data were insufficient to allow a meaningful analysis regarding 24-h morphine-equivalent consumption. Propofol was associated with reduced postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304-0.656) (p < 0.0001). In conclusion, this meta-analysis suggests that propofol improves postoperative analgesia compared with inhalational anaesthesia 24 h after surgery, with a lower incidence of nausea and vomiting.

Beneficial Effects of Necrosis Modulator, Indole Derivative NecroX-7, on Renal Ischemia-Reperfusion Injury in Rats.

Renal ischemia-reperfusion injury (IRI) is involved in multiple diseases, such as kidney transplantation or contrast-induced nephropathy, and leads to acute kidney injury. However, there are no pharmacological agents available to prevent IRI. In this study, we investigated the effects of necroX-7 against renal IRI in a rat model. Seven-week-old male Sprague-Dawley rats were divided into four groups: saline-treated sham or IRI group, necroX-7-treated sham or IRI group. All animals had right nephrectomy and IRI was followed by reperfusion after clamping the left renal vessels for 35 minutes. NecroX-7 or saline was intravenously injected at 5 minutes before reperfusion. The effects of necroX-7 on IRI were evaluated using biochemical, histological, and molecular markers. The serum creatinine level was increased after IRI compared with sham. The necroX-7 significantly decreased creatinine level compared with the saline in IRI (1.36 ± 0.11 vs 2.35 ± 0.42 mg/dL; P < .05). An immunohistochemical study revealed that necroX-7 improved renal tubular injury, and attenuated 8-OHdG-positive cells (P < .001) and high-mobility group Box 1 protein (HMGB1) expression compared with saline treatment in IRI (P < .001). NecroX-7 significantly reduced monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in IRI (necroX-7-treated IRI vs saline-treated IRI rats; 1.73 ± 0.42 vs 7.23 ± 0.54-fold for MCP-1, P < .05; 0.79 ± 0.59 vs 3.72 ± 0.37-fold for TNF-α, P < .05; 0.50 ± 0.36 vs 2.43 ± 0.41-fold for IL-1ß, P < .001). In conclusion, necroX-7 improved renal dysfunction after IRI. These effects of necroX-7 occurred with the suppression of reactive oxygen species, HMGB1, and inflammatory responses. We suggest that necroX-7 has potential therapeutic benefits in renal IRI.

Baseline body mass index among children and adults undergoing allogeneic hematopoietic cell transplantation: clinical characteristics and outcomes.

Obesity is an important public health problem that may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic hematopoietic SCTs between 2004 and 2012. Pretransplant body mass index (BMI) was classified as underweight, normal weight, overweight or obese using the WHO classification or age-adjusted BMI percentiles for children. The study population was predominantly Caucasian, and the median age was 51 years (5 months-73 years). The cumulative 3-year incidence of nonrelapse mortality (NRM) in underweight, normal weight, overweight and obese patients was 20%, 19%, 20% and 33%, respectively. Major causes of NRM were acute and chronic GVHD. The corresponding incidence of relapse was 30%, 41%, 37% and 30%, respectively. Three-year OS was 59%, 48%, 47% and 43%, respectively. Multivariate analysis showed that obesity was associated with higher NRM (hazard ratio (HR) 1.43, P=0.04) and lower relapse (HR 0.65, P=0.002). Pretransplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese compared with normal weight patients (P=0.04 and P=0.05, respectively). The increase in NRM observed in obese patients was partially offset by a lower incidence of relapse with no difference in OS.

The expression of vascular endothelial growth factor and Syndecan-4 in cartilage from osteoarthritic knees.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren-Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

The effects of intra-operative dexmedetomidine on postoperative pain, side-effects and recovery in colorectal surgery.

In this double-blind, randomised study, 100 patients undergoing open or conventional laparoscopic colorectal surgery received an intra-operative loading dose of dexmedetomidine 1 µg.kg(-1) followed by an infusion of 0.5 µg.kg(-1) .h(-1) , or a bolus and infusion of saline 0.9% of equivalent volume. Forty-six patients in the dexmedetomidine group and 50 in the saline group completed the study. The area under the curve of numerical rating scores for pain at rest for 1-48 h postoperatively was significantly lower in the patients receiving dexmedetomidine (p = 0.041). There was no difference in morphine consumption, duration of recovery ward or hospital stay. From the data obtained in this study, we calculated a number needed to treat for effective pain relief of 4. Intra-operative dexmedetomidine in colorectal surgery resulted in a reduction in resting pain scores, but there was no morphine-sparing effect or improvement in patients' recovery outcome measures.

Trends in the incidence of and survival rates for oral cavity cancer in the Korean population.

OBJECTIVE: This study assessed trends in the incidence of and survival rates for oral cavity cancer in the Korean population. MATERIALS AND METHODS: Data from the Korea Central Cancer Registry were extracted for 10,282 patients diagnosed with oral cavity cancer (C01-C06) between 1999 and 2010 to evaluate the age-standardised incidence rate, annual percentage change (APC) and 5-year relative survival rate (RSR) according to gender and age. RESULTS: In males, the incidence rate slightly decreased [APC of -0.2% (P = 0.6427)]; in females, the incidence rate increased [APC of 3.1% (P < 0.05)]. In males and females, the incidence of oral tongue cancer (C02) significantly increased [APC of 2.2% and 4.1%, respectively (P < 0.05)]. This increase in oral tongue cancer incidence was most prominent in the younger age group (<40 years, APC = 6.1%, P < 0.05). The incidence of buccal cheek cancer increased only among males [APC of 4.8% (P < 0.05)]. The 5-year RSR improved from 42.7% (1993-1995) to 59.5% (2006-2010), corresponding to an increase of 16.8% from 1993 to 2010 (P < 0.05). CONCLUSION: The incidence of oral cavity cancer in females increased, whereas it stabilised or decreased in males. However, the incidence of oral tongue cancer increased in both males and females, especially in the younger age group.

Comparison of cell proliferation and epigenetic modification of gene expression patterns in canine foetal fibroblasts and adipose tissue-derived mesenchymal stem cells.

OBJECTIVES: This study compared rate of cell proliferation, viability, cell size, expression patterns of genes related to pluripotency and epigenetic modification between canine foetal fibroblasts (cFF) and canine adipose tissue-derived mesenchymal stem cells (cAd-MSC). MATERIALS AND METHODS: Proliferation pattern, cell viability as well as cell size at each passage of cFF and cAd-MSC were measured when cultures reached confluence. In addition, real-time PCR was performed to investigate expression of Dnmt1, HDAC1, OCT4, SOX2, BAX, BCL2 genes with reference to ß-actin gene expression as an endogenous control in both cell lines. RESULTS: cFF and cAd-MSC differed in number of generations, but not in doubling times, at all passages. Mean cell size of cAd-MSC was significantly smaller than that of cFF. Cell viability was significantly lower in cFFs and apoptotic level was significantly lower in cAd-MSC compared to passage-matched cFF. In the expression of genes related to pluripotency and epigenetic modification, level of HDAC1 in cAd-MSC was significantly higher than in cFF, but expression of Dnmt1 did not differ between the two groups. OCT4 and SOX2 were significantly more highly expressed in cAd-MSC compared to cFF. CONCLUSIONS: cAd-MSC have higher stem-cell potential than cFF in terms of proliferation patterns, epigenetic modification and pluripotency, thus cAd-MSC could be more appropriate than cFF as donors of nuclei in somatic cell nuclear transfer for transgenesis.