Toxicity outcome of endorectal brachytherapy boost in medically inoperable patients.

AIM: This communication reviews results and toxicity of image-guided high-dose-rate endorectal brachytherapy (HDREBT) boost after external beam radiotherapy (ERT) in medically inoperable patients with rectal cancer. MATERIALS AND METHODS: A total of 18 patients with rectal cancer and clinical stage T2-4N0­2 treated with HDREBT boost after ERT were retrospectively reviewed. RESULTS: Following treatment with a median total dose (EQD2, α/ß = 10) of 66 Gy (range 48-92 Gy), the incidence of early and late rectal grade 3 toxicity was 11% and 19%, respectively. There was no correlation between the occurrence of acute and late toxicity. CONCLUSION: With proper technique, a combined approach using EBRT and HDREBT was associated with acceptable toxicity in medically inoperable rectal cancer patients.

Exploring the burden of X-linked hypophosphatemia: a European multi-country qualitative study.

INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare, lifelong, progressive disease characterised by renal phosphate wasting and abnormal bone mineralisation. Symptoms begin in early childhood, with the development of rickets and related skeletal deformities and reduced growth, progressing to long-term complications, including pseudofractures and fractures, as well as pain, stiffness and fatigue. The present study was designed to explore the patient experience of pain, stiffness and fatigue and the psychosocial impact of XLH in detail. METHODS: A cross-sectional qualitative study was conducted in the United Kingdom (18), Finland (6), France (4), Germany (1) and Luxembourg (1) with XLH patients aged 26 and over. Interview discussion guides were developed in consultation with clinical experts and patient associations. Data were analysed thematically. RESULTS: Participants (N = 30) described pain, stiffness and fatigue as frequently experienced symptoms with a significant impact on physical functioning and activities of daily living (ADLs). Some also described the symptoms as impacting their mood/mental health, relationships, social life and leisure activities. Participants described how common symptoms could interact or aggravate other symptoms. Symptoms had often worsened over time, and for many, were associated with concern about the future. Most participants were worried or felt guilty about having children with XLH. The findings confirmed and extended the existing model of the burden of XLH. CONCLUSION: The present study is the first to provide an in-depth analysis of pain, stiffness and fatigue, their impact and the interrelatedness of these symptoms among adults with XLH. The study also described the psychosocial impact of XLH as a hereditary, lifelong progressive disease.

Feasibility of a guided participation discharge program for very preterm infants in a neonatal intensive care unit: a randomized controlled trial.

BACKGROUND: Previous studies showed that parents of very preterm infants expressed feelings of incompetence and experienced high levels of stress upon the discharge of their infants. We conducted a systematic review of seven studies and observed potential benefits for parental outcomes when using discharge interventions that adopted guided participation (GP). More evidence is needed on the effective doses of discharge interventions underpinned by the principles of GP. AIM: To investigate the feasibility and preliminarily estimate the effects on parental competence and stress outcomes of a newly developed, nurse-led, GP discharge program for mothers of very preterm infants. METHODS: A two-arm randomized controlled trial was conducted in a neonatal intensive care unit (NICU). Mothers of infants with gestational ages of ≤32 weeks who had no congenital malformations and did not need to undergo major surgeries were recruited. All mothers were the primary caregivers to their infants. The intervention group received a nurse-led GP discharge intervention (three structured 30- to 60-min GP sessions and one follow-up phone call). The control group received usual care. The parental outcomes were measured using the Parenting Sense of Competence Scale (C-PSOC) and Perceived Stress Scale (C-PSS) at baseline (T0), on the day of discharge (T1), after the follow-up phone call (within 72 h after discharge) (T2), and 1 month after discharge (T3). The outcomes were analyzed using generalized estimating equations based on intention-to-treat principles. RESULTS: Thirty infant-mother dyads were recruited. Greater improvements in the C-PSOC score were observed in the intervention group than in the control group at T1 and T2, although these differences were statistically insignificant. The intervention group exhibited greater improvements than the control group in the C-PSS scores at T1, T2, and T3, although these differences were also not statistically significant. CONCLUSIONS: The findings suggest that a GP discharge intervention could improve parenting competence and stress among mothers with very preterm infants. The absence of adverse events suggests that the GP discharge intervention could be feasibly implemented in NICU settings. This feasibility study was not powered to determine the effectiveness of the intervention but is anticipated to lay the foundation for a future full-scale study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03668912. Date of registration: 13 September 2018 (retrospectively registered).

Predictors of repeat participation in the NHS bowel cancer screening programme.

OBJECTIVES: Most types of population-based cancer screening require repeat participation to be effective. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). METHODS: The BCSP in England offers biennial colorectal cancer screening using a guaiac fecal occult blood test (gFOBt) from age 60-74 years. This analysis included 62,081 individuals aged 60-64 years at the time of the first invitation (R1). The main outcome was repeat participation at their second (R2) or third (R3) invitation. Behavioural measures derived from screening records included late return of the gFOBt kit, compliance with follow-up investigations and previous screening participation. Other potential predictors of repeat participation included results of individual test kit analysis (normal, weak positive, strong positive, spoilt) and the definitive result of the gFOBt screening episode (normal or abnormal). Age, sex and socioeconomic deprivation were also recorded. RESULTS: Overall repeat uptake was 86.6% in R2 and 88.6% in R3. Late return of the test kit was consistently associated with lower uptake (R2: 82.3% vs 88.6%, P<0.001; R3: 84.5% vs 90.5%, P<0.001). A definitive abnormal gFOBt result in the previous screening episode was a negative predictor of repeat uptake (R2: 61.4% vs 86.8%, P<0.001; R3: 65.7% vs 88.8%, P<0.001). Weak positive (R2: 76.9% vs 86.8%, P<0.001; R3: 81.7% vs 88.8%, P<0.05) and spoilt test kits (R2: 79.0% vs 86.6%, NS; R3: 84.2% vs 92.2%, P<0.05) were associated with lower repeat uptake, but were not consistently independent predictors in all invitation rounds or subgroups. Among those with a definitive abnormal gFOBt result, noncompliance with follow-up in a previous screening episode was also associated with lower repeat uptake (R2: 24.3% vs 67.1%, P<0.001; R3: 43.2% vs 69.9%, P<0.001). CONCLUSIONS: Behavioural markers and test results from previous screening episodes have been implicated in subsequent gFOBt uptake.

Is it feasible to discuss an advance directive with a Chinese patient with advanced malignancy? A prospective cohort study.

OBJECTIVES: Advance directives have been implemented for years in western countries, but the concept is new to Asian cultures. According to traditional Chinese culture, family members usually play a decisive role in a patient's treatment plan. Thus it may be hard to implement an advance directive despite its importance to the treatment of patients. The objectives of this study were to assess the feasibility of advance directive engagement and to explore significant contributing factors to achieving such a goal. DESIGN: Prospective cohort study. SETTING: Palliative Care Unit of Clinical Oncology, Tuen Mun Hospital, Hong Kong. PATIENTS: The subjects of the investigation were adult patients diagnosed to have advanced malignancy and newly referred to the hospice service from 24 April 2009 to 30 July 2009. Data were collected from nursing assessment forms, locally designed advance directive forms, a checklist completed by oncologists, and details available in the electronic hospital record. RESULTS: Of the 191 eligible patients, 120 (63%) had the advance directive, whereas 71 (37%) did not. In the Cox regression model, the patient having insight of a poor prognosis was the most significant factor facilitating advance directive engagement (P=0.001). Any family objection in the discussion of advance directives was also an important factor, though it did not reach statistical significance (P=0.082). Other factors like age, gender, education, religion, financial status, living environment, understanding the diagnosis, bereavement experience, type of cancer, nature of illness, courses of chemotherapy or radiotherapy received, main caregiver, in-house supporter, nurse-led clinic attendance, clinical psychologist consultation, and in-patient hospice nurse coordinator interview were all statistically insignificant. CONCLUSIONS: Our study demonstrated that it was feasible to discuss an advance directive with Chinese patients with advanced malignancy. When patients have insight about their poor prognosis and family members have no objection, it may be appropriate to discuss an advance directive.

Effects of environmental cleaning bundles on reducing healthcare-associated Clostridioides difficile infection: a systematic review and meta-analysis.

Environmental contamination with Clostridioides difficile plays an important role in the transmission of C. difficile infection (CDI) in healthcare and long-term care facilities, which results in prolonged length of stay, higher risk of mortality and increased healthcare costs. Environmental cleaning bundles are introduced to improve environmental cleanliness. This study aimed to evaluate whether environmental cleaning bundles applied in hospital, community and long-term care settings reduce the incidence of healthcare-associated CDI compared with conventional cleaning practices. Relevant databases, websites and trial registration platforms were searched. Two reviewers conducted study screening and selection, data collection, risk of bias assessment and evidence quality assessment independently. Meta-analyses were conducted using Review Manager 5.3. Ten eligible studies [one randomized controlled trial (RCT) and nine non-RCTs] were included. No significant effect of environmental cleaning bundles on the CDI incidence rate was found [risk ratio (RR)=0.96, 95% confidence interval (CI) 0.71-1.29; studies=2; I2=49%; very low quality]. However, the removal of surface markers was improved significantly (RR=1.55, 95% CI 1.30-1.84; studies=3; I2=98%; very low quality), and the percentage of CDI rooms with positive cultures of C. difficile (RR=0.16, 95% CI 0.08-0.31; studies=4; I2=7%; moderate quality) was reduced significantly after the implementation of environmental cleaning bundles. Environmental cleaning bundles may consequently be helpful in improving the thoroughness of cleaning of environmental surfaces in hospital and long-term care settings. More well-conducted RCTs are expected to provide stronger evidence.

Progressive kidney degeneration in mice lacking tensin.

Tensin is a focal adhesion phosphoprotein that binds to F-actin and contains a functional Src homology 2 domain. To explore the biological functions of tensin, we cloned the mouse tensin gene, determined its program of expression, and used gene targeting to generate mice lacking tensin. Even though tensin is expressed in many different tissues during embryogenesis, tensin null mice developed normally and appeared healthy postnatally for at least several months. Over time, -/- mice became frail because of abnormalities in their kidneys, an organ that expresses high levels of tensin. Mice with overt signs of weakness exhibited signs of renal failure and possessed multiple large cysts in the proximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent. Ultrastructurally, noncystic areas showed typical cell-matrix junctions that readily labeled with antibodies against other focal adhesion molecules. In abnormal regions, cell-matrix junctions were disrupted and tubule cells lacked polarity. Taken together, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion. All other tissues appeared normal, suggesting that, in most cases, tensin's diverse functions are redundant and may be compensated for by other focal adhesion proteins.

Interactions of tensin with actin and identification of its three distinct actin-binding domains.

Tensin, a 200-kD phosphoprotein of focal contacts, contains sequence homologies to Src (SH2 domain), and several actin-binding proteins. These features suggest that tensin may link the cell membrane to the cytoskeleton and respond directly to tyrosine kinase signalling pathways. Here we identify three distinct actin-binding domains within tensin. Recombinant tensin purified after overexpression by a baculovirus system binds to actin filaments with Kd = 0.1 microM, cross-links actin filaments at a molar ratio of 1:10 (tensin/actin), and retards actin assembly by barbed end capping with Kd = 20 nM. Tensin fragments were constructed and expressed as fusion proteins to map domains having these activities. Three regions from tensin interact with actin: two regions composed of amino acids 1 to 263 and 263 to 463, cosediment with F-actin but do not alter the kinetics of actin assembly; a region composed of amino acids 888-989, with sequence homology to insertin, retards actin polymerization. A claw-shaped tensin dimer would have six potential actin-binding sites and could embrace the ends of two actin filaments at focal contacts.

Presence of an SH2 domain in the actin-binding protein tensin.

The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

The implementation of an end-of-life integrated care pathway in a Chinese population.

The integrated care pathway is used in end-of-life care to improve quality of care; the Liverpool Care Pathway (LCP) has been used in Europe and North America. Tuen Mun Hospital is a regional hospital in Hong Kong, China. The End-of-life Care Pathway (ECP) based on the concepts used in the Liverpool Care Pathway, was developed, with modification to suit the local condition. Criteria for entry onto the ECP were that the multidisciplinary team agreed the patient was dying, and was at least two of the following: bedbound; semi-comatose; only able to take sips of fluid; no longer able to take tablets. The ECP template replaced all other inpatient documents. The ECP was implemented in the palliative care unit for terminal cancer patients. An audit was performed to review the result. Fifty-one Chinese patients were included in the audit with mean age 64. The median duration of ECP use was 24 hours. All patients had current medication assessed and non-essential drugs were discontinued. The audit result suggested integrated care pathway in end-of-life care could be implemented successfully in an Oriental culture. The acceptance of using the ECP as a standard clinical practice takes time and education. Appropriate template design and supervision are the keys to success.

Is skeletal stability after bimaxillary surgery for skeletal class III deformity related to surgical occlusal contact?

A stable occlusion at the time of surgery is considered important for post-surgical stability after orthognathic surgery. The aim of this study was to determine whether skeletal stability after bimaxillary surgery using a surgery-first approach for skeletal class III deformity is related to the surgical occlusal contact or surgical change. Forty-two adult patients with a skeletal class III deformity corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy with a surgery-first approach were studied. Dental models were set and used to measure the surgical occlusal contact, including contact distribution, contact number, and contact area. Cone beam computed tomography was used to measure the surgical change (amount and rotation) and post-surgical skeletal stability. The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated. No relationship was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant relationship was found between maxillary and mandibular stability and the amount and rotation of surgical change. The results suggest that in the surgical-orthodontic correction of skeletal class III deformity with a surgery-first approach, the post-surgical skeletal stability is not related to the surgical occlusal contact but is related to the surgical change.

Integrators of epidermal growth and differentiation: distinct functions for beta 1 and beta 4 integrins.

Mammalian epithelia are critically dependent on interactions with components in the underlying basal lamina for proper morphogenesis and function. Substratum attachment is essential for survival, proliferation, movement, and differentiation; detachment compromises the cell's ability to perform these functions, often resulting in human disease. Interactions with the extracellular matrix are mediated through transmembrane integrin receptors that transmit signals to the cytoskeleton and to signaling molecules within the proliferating cells of the epithelium. In the past year, novel insights have emerged regarding the specific role of integrins in their attachment to extracellular matrix and in their signal transduction pathways within the epidermis.

Intercostal nerve blockade for cancer pain: effectiveness and selection of patients.

OBJECTIVES: To review treatment results of intercostal nerve blockade at our centre and those reported in the literature, and to determine which patients benefit most from this procedure. DESIGN: Retrospective study. SETTING: Regional palliative care centre in a regional hospital in Hong Kong. PATIENTS: Oncology patients who had intercostal nerve blockade at Tuen Mun Hospital from 1995 to 2005 were divided into three groups: (1) those who appeared not to tolerate opioids; (2) those deemed to have inadequate pain control, despite high doses of analgesics; and (3) those referred to avoid early use of high-dose opioids and tolerance. MAIN OUTCOME MEASURES: The effectiveness and complications of intercostal nerve blockade, and the extent of benefit derived from intercostal nerve blockade in different patient groups. RESULTS: This study found that 80% of the 25 patients noted optimal local pain control and 56% experienced reduction in analgesic use after intercostal nerve blockade. About 32% did not notice recurrence of the targeted pain till the end of their lives. None of the patients developed pneumothorax. Most benefit from intercostal nerve blocks were derived by group 2 patients, 90% of whom obtained optimal local pain control (P=0.23) and enjoyed a significant reduction in analgesics use (P=0.019), and in 40% their target pain was controlled till the end of life. Only about one third of group 3 patients had subsequent reduction in use of analgesics, mainly because they had co-existing pain other than at the target selected for treatment. Half (50%) of group 1 patients achieved optimal pain control. CONCLUSION: Our treatment results from intercostal nerve blockade are comparable to those reported in the literature. The procedure is safe if closely monitored. Good selection of cases is important for optimising the therapeutic gain. The largest benefit is obtained in patients who have inadequate pain control after high-dose morphine.

Percutaneous replacement of a right jugular dialysis catheter via a stenosed superior vena cava.

A female patient with end-stage renal failure, who was maintained on haemodialysis via multiple central dialysis catheters, developed chronic occlusion of the left brachiocephalic vein. Subsequently, the right jugular dual lumen PermCath became dysfunctional because of marked superior vena cava stenosis. Angioplasty of the superior vena cava stenosis was performed but failed to restore adequate catheter function. The patient was referred for possible salvage of her central venous access and re-insertion of a new PermCath. During surgery, the right jugular PermCath was removed, the superior vena cava was stented to establish venous patency, and a new PermCath was re-inserted via the existing right jugular puncture site. The technique helps reduce cost and time, and avoids another jugular puncture. In addition, this procedure saves a central venous access which is important in patients on long-term haemodialysis.

Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL.

The BCR/ABL oncogene causes chronic myelogenous leukemia (CML) in humans and induces growth factor independence of hematopoietic cell lines in tissue culture. p210BCR/ABL is localized at least in part to the cytoskeleton, and has been shown to interact directly with actin filaments through an actin binding domain located in the C-terminus of ABL. CML cells have reduced adhesion to some extracellular matrix components but the mechanism of this phenomenon is unknown. In this study we examined tyrosine phosphorylation of focal adhesion proteins in cells expressing p210BCR/ABL. An interleukin-3 (IL-3)-dependent cell line, 32Dc13, was transformed with a BCR/ABL cDNA, and the patterns of localization, expression, and tyrosine phosphorylation of focal adhesion proteins were compared among untransformed 32Dc13 cells with and without IL-3 stimulation and BCR/ABL-transformed 32Dc13 cells. Of the focal adhesion proteins examined, only paxillin exhibited tyrosine phosphorylation in response to IL-3; while in cells transformed by p210BCR/ABL, paxillin, vinculin, p125FAK, talin and tensin were constitutively tyrosine phosphorylated. IL-3 induced a transient association between paxillin and vinculin, while in BCR/ABL-transformed cells, several proteins coimmunoprecipitated with paxillin, including vinculin, p125FAK, talin and tensin. Pseudopodia enriched in focal adhesion proteins were transiently detected in 32Dc13 cells in response to IL-3, but constitutively detected in cells expressing p210BCR/ABL. p210BCR/ABL protein was also found concentrated in punctate structures adjacent to the cell membrane in myeloid cell lines, which often contained vinculin and paxillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Probabilistic prediction of unknown metabolic and signal-transduction networks.

Regulatory networks provide control over complex cell behavior in all kingdoms of life. Here we describe a statistical model, based on representing proteins as collections of domains or motifs, which predicts unknown molecular interactions within these biological networks. Using known protein-protein interactions of Saccharomyces cerevisiae as training data, we were able to predict the links within this network with only 7% false-negative and 10% false-positive error rates. We also use Markov chain Monte Carlo simulation for the prediction of networks with maximum probability under our model. This model can be applied across species, where interaction data from one (or several) species can be used to infer interactions in another. In addition, the model is extensible and can be analogously applied to other molecular data (e.g., DNA sequences).

Laparoscopic colorectal resection for polyps not suitable for colonoscopic removal.

BACKGROUND: Endoscopic removal of large sessile polyps is sometimes technically difficult and is associated with an increased risk of complications. Moreover, the incidence of invasive carcinoma within these polyps is not negligible. Laparoscopic colorectal resection has been recommended in the treatment of these large polyps. This study aimed to evaluate the outcomes of laparoscopic colorectal resection for polyps that were not suitable for colonoscopic removal. METHODS: Forty-five patients (28 men and 17 women) who underwent laparoscopic colorectal resection with the preoperative diagnosis of colorectal polyps were analyzed. The reasons for surgical resection were large sessile polyps (n = 34), difficult position (n = 2), recurrence after transanal endoscopic microsurgery (n = 1), and the presence of intramucosal malignancy on histology after colonoscopic polypectomy (n = 8). RESULTS: The mean age of the patients was 66.7 years (range, 33-89). Previous abdominal operation had been performed in 12 patients (26.7%). Two patients underwent subtotal colectomy because of multiple polyps (14 and 19, respectively). Synchronous resection of other organs was performed in two patients (a right salpingo-oophorectomy and a right adrenalectomy). Intraoperative complications occurred in two patients, and two patients (4.5%) required conversion because of perforation of the colon during dissection and dense adhesions, respectively. There was no postoperative mortality. Complications occurred in seven patients (15.6%), and they included postoperative ileus (n = 4), anastomotic leakage (n = 1), urinary retention (n = 1), and urinary tract infection (n = 1). Reoperation was required in one patient for anastomotic leakage. The median hospital stay was 6 days. The histopathology of colorectal polyps showed tubular (n = 12), tubulovillous (n = 13), and villous adenoma (n = 12); mixed adenomatous/hyperolastic polyps (n = 2); inflammatory polyp (n = 1); and colonic lipoma (n = 1). Four patients, who had previous polypectoray with intramucosal malignancy, had no residual pathology. The median size was 3.0 cm. Invasive carcinoma was found in 16 patients (35.6%). The median number of lymph node sampling was six, and two patients had lymph node metastases. CONCLUSIONS: Colonic polyps that were not amendable for colonoscopic removal were associated with a high incidence of malignant invasion. Laparoscopic colectomy offers safe and effective management of these polyps with the benefits of early postoperative recovery.

Raising harmonic variation of arterial pulse in dying rats.

Our previous study revealed that the coefficient of variation of harmonic magnitude (HCV) of radial arterial pulse was significantly raised before the death of cancer patients. In this study, we recorded the caudate arterial pulse of 24 Sprague-Dawley rats that had a fatal dose of urethane injected into their abdomens. Twenty rats were dead within 3 hours after the injection and four survived. We defined the last 100 minutes of each rat's life as the dying process. During the dying process, we found that both the systolic blood pressure and diastolic blood pressure dropped steeply during the last 5 minutes. However, all HCVs, except HCV1, climbed steeply before the last 5 minutes. The HCV1 of the dying rats was significantly higher than that of rats that survived, starting from the first minute (P < 0.01). The HCV2 of the dying rats was significantly higher than that of the survived rats starting from the 52nd minute (P < 0.05). The HCV3 and HCV4 of the dying rats were significantly higher than those of the survived rats until the 70th minute and the 80th minute, respectively (P < 0.05). Furthermore, HCV2-HCV4 proceeded with the dying process and increased gradually. We concluded that HCVs, which failed first in the high-frequency components and then in the low-frequency components, could provide physicians with earlier information to prevent the coming failure of circulatory system, and could reflect quantitatively pathological severity and predict patient outcome. The specific Fourier components in the pulse provide more physiological information than systolic and diastolic blood pressures.