Circadian rhythm of markers of bone turnover in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) have a high risk of bone fractures. A circadian rhythmicity in turnover and mineralization of bone appears to be of importance for bone health. In CKD disturbances in the circadian rhythm of various functions has been demonstrated and indeed the circadian rhythm in the mineral metabolism is disturbed. The aim of the present study was to compare the circadian rhythm of bone turnover markers in ten patients with CKD to ten healthy controls. Bone turnover markers (C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase 5b, N-terminal propeptide of type I procollagen, bone alkaline phosphatase and osteocalcin) were measured every third hour for 24 h. All bone turnover markers displayed a significant circadian rhythm in both groups and there were no significant differences in the rhythmicity between the two groups (no group*time interaction). As expected, due to the reduced renal clearance, the overall level of C-terminal telopeptide of type I collagen and osteocalcin was higher in CKD compared to the healthy controls. The present study suggests that disturbances in the circadian rhythm of bone turnover do not explain the metabolic bone disease and increased risk of fractures in CKD.

Developmental stage and morphology of the competent blastocyst are associated with sex of the child but not with other obstetric outcomes: a multicenter cohort study.

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child? SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed. WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting. STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833). MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)). LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Surgical repair of parastomal bulging: a retrospective register-based study on prospectively collected data.

AIM: The aim of this work was to examine (1) the incidence of primary repair, (2) the incidence of recurrent repair and (3) the types of repair performed in patients with parastomal bulging. METHOD: Prospectively collected data on parastomal bulging from the Danish Stoma Database were linked to surgical data on repair of parastomal bulging from the Danish National Patient Register. Survival statistics provided cumulative incidences and time until primary and recurrent repair. RESULTS: In the study sample of 1016 patients with a permanent stoma and a parastomal bulge, 180 (18%) underwent surgical repair. The cumulative incidence of a primary repair was 9% [95% CI (8%; 11%)] within 1 year and 19% [95% CI (17%; 22%)] within 5 years after the occurrence of a parastomal bulge. We found a similar probability of undergoing primary repair in patients with ileostomy and colostomy. For recurrent repair, the 5-year cumulative incidence was 5% [95% CI (3%; 7%)]. In patients undergoing repair, the probability was 33% [95% CI (21%; 46%)] of having a recurrence requiring repair within 5 years. The main primary repair was open or laparoscopic repair with mesh (43%) followed by stoma revision (39%). Stoma revision and repair with mesh could precede or follow one another as primary and recurrent repair. Stoma reversal was performed in 17% of patients. CONCLUSION: Five years after the occurrence of a parastomal bulge the estimated probability of undergoing a repair was 19%. Having undergone a primary repair, the probability of recurrent repair was high. Stoma reversal was more common than expected.

Network meta-analysis of urinary retention and mortality after Lichtenstein repair of inguinal hernia under local, regional or general anaesthesia.

BACKGROUND: Urinary retention and mortality after open repair of inguinal hernia may depend on the type of anaesthesia. The aim of this study was to investigate possible differences in urinary retention and mortality in adults after Lichtenstein repair under different types of anaesthesia. METHODS: Systematic searches were conducted in the Cochrane, PubMed and Embase databases, with the last search on 1 August 2018. Eligible studies included adult patients having elective unilateral inguinal hernia repair by the Lichtenstein technique under local, regional or general anaesthesia. Outcomes were urinary retention and mortality, which were compared between the three types of anaesthesia using meta-analyses and a network meta-analysis. RESULTS: In total, 53 studies covering 11 683 patients were included. Crude rates of urinary retention were 0·1 (95 per cent c.i. 0 to 0·2) per cent for local anaesthesia, 8·6 (6·6 to 10·5) per cent for regional anaesthesia and 1·4 (0·6 to 2·2) per cent for general anaesthesia. No death related to the type of anaesthesia was reported. The network meta-analysis showed a higher risk of urinary retention after both regional (odds ratio (OR) 15·73, 95 per cent c.i. 5·85 to 42·32; P < 0·001) and general (OR 4·07, 1·07 to 15·48; P = 0·040) anaesthesia compared with local anaesthesia, and a higher risk after regional compared with general anaesthesia (OR 3·87, 1·10 to 13·60; P = 0·035). Meta-analyses showed a higher risk of urinary retention after regional compared with local anaesthesia (P < 0·001), but no difference between general and local anaesthesia (P = 0·08). CONCLUSION: Local or general anaesthesia had significantly lower risks of urinary retention than regional anaesthesia. Differences in mortality could not be assessed as there were no deaths after elective Lichtenstein repair. Registration number: CRD42018087115 ( https://www.crd.york.ac.uk/prospero).

ANTECEDENTES: La retención de orina y la mortalidad tras la reparación abierta de las hernias inguinales puede depender del tipo de anestesia. El objetivo de este estudio fue investigar posibles diferencias en la retención de orina y mortalidad en adultos tras reparación de Lichtenstein bajo diferentes métodos anestésicos. MÉTODOS: Se efectuaron búsquedas sistemáticas en las bases de datos Cochrane, PubMed y Embase con la última revisión el 1 de agosto de 2018. Los estudios elegibles incluyeron pacientes adultos sometidos a reparación electiva de hernia inguinal unilateral mediante la técnica de Lichtenstein bajo anestesia local, regional o general. Las variables de resultados fueron la retención de orina y la mortalidad, comparándose los tres tipos de anestesia con metaanálisis y un metaanálisis en red. RESULTADOS: En total se incluyeron 53 estudios con un total de 11.683 pacientes. Las tasas crudas de retención de orina fueron del 0,1% (i.c. del 95% 0,0-0,2%) para la anestesia local, del 8,6% (i.c. del 95% 6,6-10,5%) para la anestesia regional y del 1,4% (i.c. del 95% 0,6-2,2%) para la anestesia general. No se observó mortalidad relacionada con el tipo de anestesia. El metaanálisis en red mostró un riesgo más elevado de retención de orina tras la anestesia regional (razón de oportunidades, odds ratio, OR 15,73 (i.c. del 95% 5,85-42,32), P < 0,001) y anestesia general (OR 4,07 (i.c. del 95% 1,07-15,48), P = 0,040) en comparación con la anestesia local y un riesgo más alto tras la regional en comparación con la anestesia general (OR 3,87 (i.c. del 95% 1,10-13,60), P = 0,035). Los metaanálisis mostraron un riesgo más alto de retención de orina tras la anestesia regional en comparación con la anestesia local (P < 0,001), pero sin diferencias entre anestesia general y local (P = 0,08). CONCLUSIÓN: La anestesia local o general presentaba un riesgo significativo menor de retención urinaria en comparación con la anestesia regional. Las diferencias en mortalidad no pudieron ser evaluadas ya ningún paciente falleció tras la reparación electiva de Lichtenstein.

Use of Lactate ProTM2 for measurement of fetal scalp blood lactate during labor - proposing new cutoffs for normality, preacidemia and acidemia: a cross-sectional study.

OBJECTIVE: Measurement of fetal scalp blood lactate is a supplementary tool to cardiotocography in the case of a non-reassuring tracing. Several hand-held lactate meters have been launched, all with differentials in absolute values. Therefore, the reference intervals must be calculated for each device. The internationally accepted reference interval is based on measurement with Lactate ProTM with recently got out of production. The aim of this study was to propose cutoffs for normality, preacidemia, and acidemia in fetal scalp blood for Lactate ProTM2 based on the comparison of lactate values measured with Lactate ProTM and Lactate ProTM2. DESIGN: Seven hundred one fetal scalp blood samples were analyzed simultaneously. The conversion equations were retrieved from the linear regression model. On the basis of the cutoffs for Lactate ProTM cutoffs for Lactate ProTM2 were calculated. RESULTS: The conversion equations obtained were Lactate ProTM = -0.02 + 0.68 × Lactate ProTM2 (SD: -0.09-0.07 × Lactate ProTM2) and Lactate proTM2 (LP2) = 0.03 + 1.48 × Lactate ProTM (SD: 0.16 + 0.17 × Lactate ProTM). The correlation to umbilical arterial pH was identical for the two devices (r = -0.18), whereas the correlation to umbilical arterial lactate was better for Lactate ProTM than for Lactate ProTM2 (r = 0.38, respectively, r = 0.33). The correlation to umbilical arterial lactate was dependent on time from sampling to delivery. CONCLUSION: Proposed reference values for Lactate ProTM2: scalp lactate <6.3 mmol/L = normal, no indication for intervention; 6.3-7.1 mmol/L = preacidemia, repeated testing has to be considered; > 7.1 mmol/L = acidemia, expedite delivery.

Acceptance of texture-modified in-between-meals among old adults with dysphagia.

BACKGROUND AND AIMS: Old adults suffering from dysphagia have difficulties swallowing, chewing and/or eating, and are therefore at high risk of undernutrition. In-between-meals that are texture modified are of particular importance for people suffering from dysphagia. To meet their adequate daily amount of food intake they are recommended to eat 3-5 in-between-meals daily. The aim of the current pilot study was to identify the most liked in-between-meals for old adults based on flavour and describe the basic sensory properties of these in-between-meals. Following, the equality between flavour and appearance-based preferences was investigated. METHODS: From three nursing homes 30 old adults aged 70 years or older suffering from dysphagia were recruited. They were assessing 20 texture modified in-between-meals based on their flavour and appearance on a 3 point hedonic scale. RESULTS: When participants were asked to assign liking based on flavour, the most liked in-between-meals were frozen, cold and sweet (vanilla ice cream, strawberry parfait and panna cotta). These meals were among the in-between-meals richest in fat and energy. Liking based on flavour and appearance was equal in 18 out of 20 samples. Furthermore, nutritional and sensory characteristics of the preferred meals were described. CONCLUSION: Flavour and sensory-based ranking of in-between-meals opens the possibility to design new in-between-meals to old adults with dysphagia, by choosing the most liked in-between-meals to offer the target group.

Radioactive seed localisation of non-palpable lymph nodes - A feasibility study.

BACKGROUND: Radioactive seed localisation (RSL) is a preoperative localisation method using a small titanium seed containing iodine-125. The method is increasingly applied for localising non-palpable lesions in the treatment of breast cancer. We believe that RSL has the potential to be used in various surgical specialties. The aim of this feasibility study was to test RSL as a preoperative localisation of non-palpable lymph nodes. METHODS: Between November 24, 2015 and October 26, 2016, 15 patients with suspicious lymph nodes on imaging were included in the study. The lymph nodes were located in the axillary region (n = 9), the head and neck region (n = 5) and the inguinal region (n = 1). The seeds were placed in the centre of the lymph node, in the capsule or just outside the capsule guided by ultrasound. During surgery, incision and localisation of the lymph nodes were performed based on the auditory signal of the gamma probe. After excision, lymph nodes including iodine seeds were sent for pathologic examination and the seeds were returned to the Department of Nuclear Medicine. RESULTS: The non-palpable lymph nodes were all successfully marked using ultrasound. The lymph nodes were successfully localised and excised during surgery, and the procedure was performed without complications in the majority of the cases. CONCLUSION: Localisation of suspicious non-palpable lymph nodes using RSL is feasible. RSL may ease the surgical procedure, minimise trauma to the surrounding tissue and ultimately benefit the patient. Future prospective studies are necessary to determine the further use of RSL within different surgical specialties.

Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

Staging with computed tomography of patients with colon cancer.

PURPOSE: Accurate staging of colonic cancer is important for patient stratification. We aimed to correlate the diagnostic accuracy of preoperative computed tomography (CT) with final histopathology as reference standard. METHODS: Data was collected retrospectively on 615 consecutive patients operated for colonic cancer. Evaluation was based upon T-stage. Patients were stratified into high-risk and low-risk groups, based on the extent of tumor invasion beyond the proper muscle layer of more or less than 5 mm. The Kendall tau correlation coefficient was used to calculate concordance between radiological (r)T-stage obtained at CT imaging and pathological (p)T-stage from the final pathology. RESULTS: In total, 501 patients were included. We found no significant differences in the Kendall tau values for diagnostic measures between the groups at the 95% confidence interval (CI) level: 49% (95% CI, 43-55) for all individuals, 48% (95% CI, 40-56) for screened individuals, and 47% (95% CI, 37-56) for non-screened individuals. The overall sensitivity and specificity for all individuals in identifying high-risk tumors on CT was 65% (95% CI, 56-73) and 89% (95% CI, 85-92). The risk of ending up in the high-risk group due to overstaging among all individuals was calculated as the number needed to harm 11.7 (95% CI, 9-16). CONCLUSIONS: There is basis for improvement of CT-based preoperative staging of patients with colorectal cancer. Supplementary modalities may be needed for correct staging of patients preoperatively, especially in relation to stratification of patients into neoadjuvant treatments or tailored therapy in patients with early cancers.

Systematic review and network meta-analysis of methods of mesh fixation during laparoscopic ventral hernia repair.

BACKGROUND: Ventral hernia repairs are common and have high recurrence rates. They are usually repaired laparoscopically with an intraperitoneal mesh, which can be fixed in various ways. The aim was to evaluate the recurrence rates for the different fixation techniques. METHODS: This systematic review included studies with human adults with a ventral hernia repaired with an intraperitoneal onlay mesh. The outcome was recurrence at least 6 months after operation. Cohort studies with 50 or more participants and all RCTs were included. PubMed, Embase and the Cochrane Library were searched on 22 September 2016. RCTs were assessed with the Cochrane risk-of-bias assessment tool and cohort studies with the Newcastle-Ottawa scale. Studies comparing fixation techniques were included in a network meta-analysis, which allowed comparison of more than two fixation techniques. RESULTS: Fifty-one studies with a total of 6553 participants were included. The overall crude recurrence rates with the various fixation techniques were: absorbable tacks, 17·5 per cent (2 treatment groups); absorbable tacks with sutures, 0·7 per cent (3); permanent tacks, 7·7 per cent (20); permanent tacks with sutures, 6·0 per cent (25); and sutures, 1·5 per cent (6). Six studies were included in a network meta-analysis, which favoured fixation with sutures. Although statistical significance was not achieved, there was a 93 per cent chance of sutures being better than one of the other methods. CONCLUSION: Both crude recurrence rates and the network meta-analysis favoured fixation with sutures during laparoscopic ventral hernia repair.

Incidence and risk factors for parastomal bulging in patients with ileostomy or colostomy: a register-based study using data from the Danish Stoma Database Capital Region.

AIM: The aim was to investigate the incidence and risk factors for parastomal bulging, a clinically important complication, in patients with an ileostomy or colostomy. METHOD: The Danish Stoma Database Capital Region prospectively collects data on patients with a stoma up to a year after surgery. Stoma care nurses clinically assessed the main outcome, parastomal bulging. We linked data from the Stoma Database to data from the Danish Anaesthesia Database. Cumulative incidence of parastomal bulging over the first year was calculated with death and stoma reversal as competing risks. Risk factors were investigated using an exploratory approach. RESULTS: In a study population of 5019, the cumulative incidence (with competing risks) of parastomal bulging was 36.2% at 400 days after surgery. Age, colostomy, male gender, alcohol consumption and laparoscopy were associated with an increased risk of parastomal bulging. Compared with cancer, inflammatory bowel disease was associated with a lower risk of parastomal bulging, and diverticulitis was associated with a higher risk. Peristomal mesh and stomas placed through a separate incision were associated with a reduction in risk. There was neither increased nor decreased risk of parastomal bulging for body mass index, American Society of Anesthesiologists score, smoking status, emergency surgery and preoperative stoma site marking. CONCLUSION: Parastomal bulging is a common complication affecting one in three patients within 1 year of surgery. Along with previous findings, there is now considerable evidence for age and colostomy as being risk factors for parastomal bulging.

Endoscopic ultrasonography and computed tomography scanning for preoperative staging of colonic cancer.

PURPOSE: With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post-operative histology as gold standard. METHODS: A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014-January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated for "low risk" (T1+T2+T3 with ≤5 mm extramural invasion) and "high risk" (T3 with >5 mm of extramural spread + T4) colonic cancer. RESULTS: Sensitivity and specificity in "low risk" colonic cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT 0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or N+ disease. CONCLUSIONS: The sensitivity of EUS and CT were good and comparable regarding T-stage evaluation, while EUS had a significantly higher specificity in the evaluation of "low risk" tumours. The results obtained for "high risk" colonic cancer were difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future. TRIAL REGISTRATION: NCT02324023.

Are assisted reproduction technologies associated with categorical or dimensional aspects of psychopathology in childhood, adolescence or early adulthood? Results from a Danish prospective nationwide cohort study.

An increasing number of children are conceived using assisted reproduction technologies (ART), but little is known about the long-term risk in terms of mental health outcomes. All twin and singleton children conceived via ART and born in 1995 were sampled from the Danish in vitro fertilization registry and matched to four spontaneously conceived (SC) children. The children were followed-up at the age of 3, 7, 14 and 18 years in the Danish Psychiatric Central Research Registry, to estimate the prevalence of all possible psychiatric diagnoses; dimensional aspects of psychopathology were assessed at the age of 14 years, using the Child Behavior Checklist (CBCL). The study included 858 ART children and 3436 SC children. ART and SC children were not clinically distinguishable on either the categorical measures of psychopathology at the age of 3, 7, 14 and 18 years, or on CBCL scale scores at the age of 14 years. The findings remained nonsignificant after controlling for sample differences. This large, prospective, nationwide cohort study provides evidence to support that ART exposure does not increase the risk of adverse mental health outcomes considered as a whole, while power was limited to discard an effect of ART on specific mental health disorders.

An investigation into between-meal food desires among hospitalised haematological cancer patients.

BACKGROUND & AIMS: Hospitalised haematological cancer patients often suffer from reduced appetite and food intake, which negatively influences the patients' well-being and nutritional status. The aim of this study was to identify specific between-meal food desires in a patient group, in order to increase food intake. The study was conducted using a picture-aided questionnaire, and relating the preferences to factors that could easily be implemented in the hospital menu, such as time of the day and texture. Moreover, the results of the questionnaire were verified by acceptance tests on six selected food items. METHODS: A structured 42 items food questionnaire was developed and used to quantify appetitive food desires in patients during morning (11 am) and afternoon (3 pm) sessions. Food items were scored according to patients' preferences and immediate desire to eat. A total of 112 hospitalised haematological cancer patients, screened for nutrition-related symptoms, participated. Univariate statistical models were used to investigate the influence of time-of-day and food texture on between-meal desires. RESULTS: Fresh fruit, ice cream, cheese and mashed potatoes with bacon were the most desired food items. Patients showed significant higher desire to eat in the morning as opposed to the afternoon. Moreover, texture had an influence on food desire, where liquid food was more desired than food with soft or coarse texture. CONCLUSION: Ranking of food desires among hospitalised cancer patients showed inclination for fresh fruit, ice cream, mashed potatoes with bacon, and cheese. Time of the day (morning) and texture (liquid) had the greatest and most positive impact on food desires. The findings may be easily implemented in hospital food service routines for cancer patients, and might positively contribute to patients' well-being and nutrition.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.

The identification of a volume-regulated anion channel: an amazing Odyssey.

The volume-regulated anion channel (VRAC) plays a pivotal role in cell volume regulation in essentially all cell types studied. Additionally, VRAC appears to contribute importantly to a wide range of other cellular functions and pathological events, including cell motility, cell proliferation, apoptosis and excitotoxic glutamate release in stroke. Although biophysically, pharmacologically and functionally thoroughly described, VRAC has until very recently remained a genetic orphan. The search for the molecular identity of VRAC has been long and has yielded multiple potential candidates, all of which eventually turned out to have properties not fully compatible with those of VRAC. Recently, two groups have independently identified the protein leucine-rich repeats containing 8A (LRRC8A), belonging to family of proteins (LRRC8A-E) distantly related to pannexins, as the likely pore-forming subunit of VRAC. In this brief review, we summarize the history of the discovery of VRAC, outline its basic biophysical and pharmacological properties, link these to several cellular functions in which VRAC appears to play important roles, and sketch the amazing search for the molecular identity of this channel. Finally, we describe properties of the LRRC8 proteins, highlight some features of the LRRC8A knockout mouse and discuss the impact of the discovery of LRRC8 as VRAC on future research.

Measuring the impact of a restrictive transfusion guideline in patients with acute myeloid leukaemia.

Interventions to change physician transfusion behavior are often evaluated by examining the amount of red blood cell (RBC) units transfused or the proportion of patients transfused before and after the intervention. The pre-transfusion haemoglobin concentration is a sensitive measure of transfusion practice, but has not been used to evaluate behavioral interventions. We examined the effect of a Danish National Board of Health December 2007 transfusion guideline on the behavior of clinicians treating acute myeloid leukaemia (AML). We compared the effect of the guideline on pre-transfusion haemoglobin concentrations with other measures of transfusion behavior, including use of RBC units and proportion of patients transfused. No change in transfusion behavior could be demonstrated by examining amount of RBC units transfused and proportion of patients transfused. Conversely, the pre-transfusion haemoglobin concentration fell significantly. Pre-transfusion haemoglobin determination is a sensitive measure of the effect of an intervention to change physician transfusion behaviour.

A 24-h a la carte food service as support for patients at nutritional risk: a pilot study.

BACKGROUND: Undernutrition and insufficient energy and protein intake is a common problem in hospitalised patients. The aim of this pilot study was to investigate whether a novel hospital menu would be an effective strategy for increasing nutritional intake in patients at nutritional risk. METHODS: A historically controlled intervention pilot study was conducted. Forty patients at nutritional risk were offered a novel hospital menu as a supplement to the ordinary hospital menu. The menu consisted of 36 naturally energy-enriched small dishes served on demand 24 h a day. Energy and protein intake were calculated as the mean over a period of 3 days. RESULTS: No significant difference in energy and protein intake was observed between the groups; however, a significant (P = 0.001) time gradient in total energy intake was observed in the intervention group. Moreover, a significant (P = 0.03) time gradient in energy intake received from the novel menu was observed. The dishes from the novel menu were mainly ordered from 11.00 h to 14.00 h and from 17.00 h to 18.00 h. CONCLUSIONS: No overall significant differences in energy and protein intake between the groups were found. However, the present pilot study revealed a significant time gradient in total energy intake (P = 0.001) and in energy intake from the novel menu (P = 0.03). This indicates the need to include a run-in period when investigating novel hospital menus as a support for patients at nutritional risk. Additionally, food service, available 24 h a day, appears to be unnecessary.

On the role of TRPC1 in control of Ca2+ influx, cell volume, and cell cycle.

Ca(+) signaling plays a crucial role in control of cell cycle progression, but the understanding of the dynamics of Ca(2+) influx and release of Ca(2+) from intracellular stores during the cell cycle is far from complete. The aim of the present study was to investigate the role of the free extracellular Ca(2+) concentration ([Ca(2+)](o)) in cell proliferation, the pattern of changes in the free intracellular Ca(2+) concentration ([Ca(2+)](i)) during cell cycle progression, and the role of the transient receptor potential (TRP)C1 in these changes as well as in cell cycle progression and cell volume regulation. In Ehrlich Lettré Ascites (ELA) cells, [Ca(2+)](i) decreased significantly, and the thapsigargin-releasable Ca(2+) pool in the intracellular stores increased in G(1) as compared with G(0). Store-depletion-operated Ca(2+) entry (SOCE) and TRPC1 protein expression level were both higher in G(1) than in G(0) and S phase, in parallel with a more effective volume regulation after swelling [regulatory volume decrease (RVD)] in G(1) as compared with S phase. Furthermore, reduction of [Ca(2+)](o), as well as two unspecific SOCE inhibitors, 2-APB (2-aminoethyldiphenyl borinate) and SKF96365 (1-(ß-[3-(4-methoxy-phenyl)propoxyl-4-methoxyphenethyl)1H-imidazole-hydrochloride), inhibited ELA cell proliferation. Finally, Madin-Darby canine kidney cells in which TRPC1 was stably silenced [TRPC1 knockdown (TRPC1-KD) MDCK] exhibited reduced SOCE, slower RVD, and reduced cell proliferation compared with mock controls. In conclusion, in ELA cells, SOCE and TRPC1 both seem to be upregulated in G(1) as compared with S phase, concomitant with an increased rate of RVD. Furthermore, TRPC1-KD MDCK cells exhibit decreased SOCE, decreased RVD, and decreased proliferation, suggesting that, at least in certain cell types, TRPC1 is regulated during cell cycle progression and is involved in SOCE, RVD, and cell proliferation.