The BUSCOPAN study: a randomized-controlled non-inferiority trial of a continuous butylscopolamine infusion versus placebo in patients with a renal colic not responding to oral non-steroidal anti-inflammatory drugs

Purpose To investigate whether placebo is non-inferior to continuous infusion of butylscopolamine in patients with renal colic. Methods We conducted a placebo-controlled, multicenter, double-blind randomized clinical trial (RCT) including 128 patients with renal colic (confirmed by ultrasound or CT-scan). Patients were randomized to receive either continuous IV butylscopolamine 100 mg/24 h or placebo (saline). Primary outcome is the amount of opioid escape medication used, measured in doses administered. Secondary outcomes are pain measured on a Numeric Rating Scale (NRS), side effects, and time of drug administration. Non-inferiority was assessed using linear regression with robust standard errors, with non-inferiority limit set at 0.5 units of escape medication. Results Median number of doses of escape medication was one in both groups. The number of extra doses in the placebo group compared with the butylscopolamine group was 0.05, with a 95% robust confidence interval (CI) of 0.38-0.47. Upper limit of the CI remained below the non-inferiority limit of 0.5 (p = 0.04). No differences in secondary endpoints were seen between the groups. Conclusion Placebo is non-inferior to continuous IV butylscopolamine for pain relief in patients with renal colic. Based on this study and previous evidence, there is no role for continuous butylscopolamine IV in the treatment of renal colic. Trial NL7819Neuro-urology: functional disorders in male and female urogenital trac

Guest-Dependence on Spin Crossover and Thermal Expansion in Nanoporous Coordination Framework Materials

Coordination framework materials have attracted much interest in modern chemistry due to the plethora of properties that they may possess. The frameworks described in this thesis demonstrate the properties of spin crossover, anomalous thermal expansion, and nanoporosity, which enables guest-dependent studies into the material behaviour. The first frameworks described are the [Fe(bpac)M(CN)4]•x(bpac){guest} (M = Ni, Pd, Pt; bpac = 1,4-bis(4′-pyridyl)acetylene) family. The properties of the alcohol-solvated [Fe(bpac)Pd(CN)4]•x(bpac) (x = 0.4, 0.5) frameworks were studied, and the major guest influence on the resulting spin crossover behaviour was determined to be due to an internal pressure effect produced by the kinetic volume and compressibility of the guest. By obtaining a variety of EtOH adsorption isotherms and isobars, a Temperature-Pressure phase diagram of SCO was produced for the [Fe(bpac)Pd(CN)4]•0.4(bpac){EtOH} material. In addition to these frameworks, the behaviour of the [Fe(bpac)(Au(CN)2)2)]•{guest} framework material was also investigated. This framework demonstrated unprecedented multifunctional behaviour, with a synergistic interplay between the spin crossover, lattice structure and host–guest properties. The framework lattice was exceptionally flexible, and displayed a facile ‘scissor-type’ motion of the {Fe(Au(CN)2)2} (4,4) grids. Due to the extreme conformational flexibility of the {Fe(Au(CN)2)2} (4,4)-grids of this material, the [Fe(bpac)(Au(CN)2)2)]•{EtOH} sample displayed colossal uniaxial thermal expansion behaviour. Below the spin transition, the a parameter displayed a maximum thermal expansion coefficient of −1070 × 10−6 K−1, which is an order of magnitude greater than any yet reported for this quantity. Guest-dependent studies on this framework demonstrate the strong effect of guest properties on the conformation of the framework lattice and the spin transition behaviour

Limited diagnostic accuracy and clinical impact of single-operator peroral cholangioscopy for indeterminate biliary strictures

BACKGROUND: Single-operator peroral cholangioscopy (sPOCS) is considered a valuable diagnostic modality for indeterminate biliary strictures. Nevertheless, studies show large variation in its characteristics and measures of diagnostic accuracy. Our aim was to estimate the diagnostic accuracy of sPOCS visual assessment and targeted biopsies for indeterminate biliary strictures. Additional aims were: estimation of the clinical impact of sPOCS and comparison of diagnostic accuracy with brush cytology. METHODS: A retrospective single-center study of adult patients who underwent sPOCS for indeterminate biliary strictures was performed. Diagnostic accuracy was defined as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The clinical impact of sPOCS was assessed by review of medical records, and classified according to its influence on patient management. RESULTS: 80 patients were included, with 40 % having primary sclerosing cholangitis (PSC). Prior ERCP was performed in 88 %, with removal of a biliary stent prior to sPOCS in 55 %. The sensitivity, specificity, PPV, and NPV for sPOCS visual impression and targeted biopsies were 64 %, 62 %, 41 %, and 84 %, and 15 %, 65 %, 75 %, and 69 %, respectively. The clinical impact of sPOCS was limited; outcome changed management in 17 % of patients. Sequential brush cytology sensitivity, specificity, PPV, and NPV were 47 %, 95 %, 80 %, and 83 %. CONCLUSIONS: The diagnostic accuracy of sPOCS for indeterminate biliary strictures was found to be inferior to brush cytology, with a low impact on patient management. These findings are obtained from a select patient population with a high prevalence of PSC and plastic stents in situ prior to sPOCS

Intact interferon signaling in peripheral blood leukocytes of high-grade osteosarcoma patients

High-grade osteosarcoma has a poor prognosis with an overall survival rate of about 60 percent. The recently closed European and American Osteosarcoma Study Group (EURAMOS)-1 trial investigates the efficacy of adjuvant chemotherapy with or without interferon-α. It is however unknown whether the interferon-signaling pathways in immune cells of osteosarcoma patients are functional. We studied the molecular and functional effects of interferon treatment on peripheral blood lymphocytes and monocytes of osteosarcoma patients, both in vivo and ex vivo. In contrast to other tumor types, in osteosarcoma, interferon signaling as determined by the phosphorylation of signal transducer and activator of transcription (STAT)1 at residue 701 was intact in immune cell subsets of 33 osteosarcoma patients as compared to 19 healthy controls. Also, cytolytic activity of interferon-α stimulated natural killer cells against allogeneic (n = 7 patients) and autologous target cells (n = 3 patients) was not impaired. Longitudinal monitoring of three osteosarcoma patients on interferon-α monotherapy revealed a relative increase in the CD16-positive subpopulation of monocytes during treatment. Since interferon signaling is intact in immune cells of osteosarcoma patients, there is a potential for indirect immunological effects of interferon-α treatment in osteosarcoma

Abdominal Compartment Syndrome and Intra-abdominal Ischemia in Patients with Severe Acute Pancreatitis

Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia. The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS. Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra-abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group. This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU

Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture

Background: In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults.Methods: To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling.Results: Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9).Conclusions: This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture

Simultaneous transurethral resection of the prostate and cystolithotripsy: a urological dilemma examined

Introduction: Controversy exists over whether transurethral resection of the prostate (TURP) in men with bladder stones prevents recurrence of stone formation and facilitates stone discharge. We sought to evaluate whether TURP in patients who underwent cystolithotripsy led to a lower recurrence of bladder stones for which a re-cystolithotripsy was necessary.Methods: Patients (n=127) who underwent transurethral cystolithotripsy with (n=38) or without simultaneous TURP (n=89) between January 2009 and December 2013 were retrospectively included in five centers in the Netherlands. Median followup was 48 months. The primary endpoint was to compare the relative risk between both groups for re-cystolithotripsy due to recurrent bladder stones. Secondary outcomes were the relative risk of urinary retention, the need for a (re-)TURP and the average time until recurrence.Results: Patients who underwent a cystolithotripsy with a simultaneous TURP had a lower need for re-cystolithotripsy, resulting in a risk reduction of 72%. (relative risk [RR] 0.28 [0.07-1.13], p=0.06, number needed to treat [NNT]=7). The length of in hospital stay (3.4 vs. 1.6 days, p=0.04) and operative time (58 vs. 33 minutes, p<0.01) was longer when a TURP was performed. There was no significant difference in complication rate, occurrence of urinary retention, reTURP, and re-admission. Eighty-one percent of patients who did not undergo a TURP remained free of bladder stone recurrence. Due to the retrospective nature of the study, essential data concerning prostate volume and micturition analysis was lacking.Conclusions: A simultaneous TURP in patients who underwent a cystolithotripsy showed a trend towards a protective effect on the need for re-cystolithotripsy.Neuro-urology: functional disorders in male and female urogenital trac

Safety Measures During Cholecystectomy: Results of a Nationwide Survey

BACKGROUND: This study aimed to identify safety measures practiced by Dutch surgeons during laparoscopic cholecystectomy. METHOD: An electronic questionnaire was sent to all members of the Dutch Society of Surgery with a registered e-mail address. RESULTS: The response rate was 40.4% and 453 responses were analyzed. The distribution of the respondents with regard to type of hospital was similar to that in the general population of Dutch surgeons. The critical view of safety (CVS) technique is used by 97.6% of the surgeons. It is documented by 92.6%, mostly in the operation report (80.0%), but often augmented by photography (42.7%) or video (30.2%). If the CVS is not obtained, 50.9% of surgeons convert to the open approach, 39.1% continue laparoscopically, and 10.0% perform additional imaging studies. Of Dutch surgeons, 53.2% never perform intraoperative cholangiography (IOC), 41.3% perform it incidentally, and only 2.6% perform it routinely. A total of 105 bile duct injuries (BDIs) were reported in 14,387 cholecystectomies (0.73%). The self-reported major BDI rate (involving the common bile duct) was 0.13%, but these figures need to be confirmed in other studies. CONCLUSION: The CVS approach in laparoscopic cholecystectomy is embraced by virtually all Dutch surgeons. The course of action when CVS is not obtained varies. IOC seems to be an endangered skill as over half the Dutch surgeons never perform it and the rest perform it only incidentally

Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells

High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma