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High Grade B Cell Lymphoma, NOS, and High Grade B Cell Lymphoma with Dual Hit or Triple Hit have been recently recategorized in the 2016 revision of the WHO classification of lymphoid neoplasms. In this study we have characterized the genetic, histopathological, and clinical features of a series of this type of lymphoid neoplasia (17 HGBCL NOS and 53 HGBCL DH/TH).HGBCL NOS showed better response to first line treatment than HGBCL with DH/TH but no significant differences in PFS or OS were found between the two categories. Survival analysis in the whole cohort of cases found that only the presence of BCL2 translocation was significantly associated with PFS. Other clinical features such as IPI, LDH or stage were equivalent in both categories. Furthermore, both high grade and DLBCL morphological patterns showed equivalent PFS and OS in this set of High grade BCL NOS/DH/TH.Key points BCL2 translocation in High Grade B Cell Lymphoma NOS and High Grade B Cell Lymphoma with DH/TH is associated with reduced progression free survival.Both high grade and DLBCL morphological patterns showed equivalent outcome regarding PFS and OS in HGBCL.

Objective: This study assessed changes in anxiety during different phases of childbirth in a sample of women demanding epidural anesthesia., Design: Prospective, longitudinal case series., Sample: A total of 133 women who demanded epidural anesthesia for childbirth answered the questionnaires., Methods: Anxiety state was measured using the State Trait Anxiety Inventory (STAI) questionnaire. The STAI-S (anxiety state) was administered in three phases during childbirth: Phase 1 was before applying epidural anesthesia, Phase 2 was 45 min after the application of epidural anesthesia and Phase 3 was at less than 24 h after delivery. Data were collected in two general hospitals: a third-level public hospital and a well-recognized private hospital., Main Outcome Measures: STAI scores., Results: Anxiety state decreases significantly after applying the epidural anesthesia (Phase 2) compared to before anesthesia (Phase 1), and it remains low levels 24 h after childbirth (Phase 3). There were statistically significant differences in STAI scores between the different phases administrated (Phases 1 and 2: p < 0.001; effect size, d = 1.40; Phases 1 and 3: p < 0.001; effect size, d = 1.39). In Phase 3, women with cesarean section birth had significant differences in STAI scores relative to those with spontaneous birth (p = 0.037; d = 0.44). The type of health-care setting (public or private), the educational level and the numbers of previous births does not affect the level of anxiety state in women in any of the three phases., Conclusions: Women's anxiety decreases significantly after applying epidural anesthesia, and it remains low 24 h after delivery. Anxiety against childbirth was not influenced by the health system used by women, by the condition of primiparous or multiparous, or by the educational level. Women who received an epidural anesthesia with a cesarean section reported higher rates of anxiety state after birth.

Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system). Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types.

Background: The involvement of voltage-dependent calcium channels and reactive oxygen species in the pathophysiology of neuropathic pain might justify the preventative administration of antioxidant enzymes, at low doses, in combination with gabapentin (GaP) to maximize its analgesic effect in an experimental model of neuropathic pain in rats., Methods: This work investigated the analgesic effects of these drugs, alone or in combination, by intraperitoneal administration for three consecutive days before (Series I) or after (Series II) a peripheral neuropathy induced by left sciatic nerve ligation. A prospective randomized study was conducted using 96 Wistar rats (50 males and 46 females). Mechanical hypersensitivity was measured with a dynamic plantar anesthesiometer. A hot plate analgesia meter calculated the thermal sensitivity. Side effect profiles for drug combinations were evaluated with a conventional scale to assess levels of sedation interfering with postural control and righting reflexes., Results: Preinjury administration (Series I) of GaP alone prevented the development of mechanical hypersensitivity at the nerve-damage hind paw. When GaP was administered concurrently with superoxide dismutase and catalase, its preventive analgesic effect did not increase. Antioxidants administered alone were completely ineffective at modulating the mechanical or thermal hypersensitivity. When treatments were only delivered following surgery (Series II), only the group receiving combined GaP and antioxidants treatment prior to nerve injury showed higher thermal thresholds from postsurgery days 7-30., Conclusions: These results suggest that preventive antioxidants in combination with GaP provided a synergistic suppression of thermal hypersensitivity that GaP alone cannot produce.

Purpose: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-κB activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas., Experimental Design: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability., Results: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and reduced expression of several prosurvival and antiapoptotic factors., Conclusions: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies., (©2013 AACR.)

Activities of enzymes involved in muscle damage [creatine kinase (CK) and aspartate aminotransferase (AST)] and levels of malondialdehyde (MDA) as a marker of oxidative stress were monitored in the plasma of 27 members of an America's Cup yachting crew. The preventive benefits of allopurinol on muscle damage were also tested. In racing period A, the crew was divided into two groups according to their tasks on board. Blood samples from all 27 sailors were obtained before the start of a 5-day fleet race, after the last race, and after the ten match races. In period B, crew members were divided at random into two groups. One group (13 participants) received 300 mg/day of allopurinol 3 h before racing. The other ten members received placebo. Blood samples were collected just before and after the second round of the Louis Vuitton Cup. All participants showed increased CK and AST activities after the racing period A. The increase in CK activity was highest in sailors involved in strenuous physical work. At the end of period A, plasma MDA levels were higher in all participants as compared with non-participant athletes. In period B, a significant decrease in CK activity, but not in AST, appeared among participants receiving allopurinol. Plasma MDA decreased in sailors treated with allopurinol, but this reduction did not reach statistical significance. America's Cup is a sailing sport with high physical demands, as shown by the increase in muscle-damage markers. Treatment with allopurinol appeared to decrease the levels of muscle damage markers.

Background: To compare the analgesic efficacy of epidural infusions of levobupivacaine, bupivacaine and ropivacaine in labor., Methods: 102 nulliparous parturients in early labor were enrolled in this randomized, double-blind clinical trial. They were randomly assigned to receive one of three continuous epidural infusion regimens: levobupivacaine 0.125%, bupivacaine 0.125% or ropivacaine 0.2%, all with fentanyl 1 microg/mL at 8 mL/h. Supplementary analgesia was provided with an 8-mL epidural bolus of the study solution if visual analogue scale (VAS) score for pain was 40 (0-100 mm). Pain and motor and sensory block were measured at 0, 15 and 30 min, 1, 2, 3 and 4h and full cervical dilatation., Results: Analgesia was satisfactory in all three groups, with VAS score <40 mm at all measurements. VAS scores were greater in those receiving levobupivacaine (P<0.005). Motor block was greater with bupivacaine than levobupivacaine (P<0.01). There were no differences in motor block between levobupivacaine and ropivacaine. There were no other differences between groups., Conclusion: All three regimens were effective during first stage of labor although pain scores were higher in those receiving levobupivacaine. Motor block was greater with bupivacaine than with levobupivacaine.

Block of the sciatic nerve at the midfemoral level is usually performed using nerve stimulation techniques. We investigated the efficacy of ultrasound, combined with nerve stimulation, to locate and block the sciatic nerve at the lateral midfemoral level compared to nerve stimulation alone. Sixty-one patients scheduled for foot and ankle surgery were enrolled in this prospective, randomized study. Thirty patients underwent a lateral block of the sciatic nerve at the midfemoral level guided by ultrasound (group US) and 31 patients received the block without ultrasound (group ES). Once an adequate motor response was obtained using nerve stimulation, 35 mL of ropivacaine 0.5% was administered. The main end-points of the study were: number of attempts to obtain an adequate motor response, success rate of nerve location at the first attempt, quality and duration of both sensory and motor blocks, and anesthetic distribution. The success of sciatic nerve location at the first attempt was significantly more frequent in the US group than in the ES group (76.6% versus 41.9%; P < 0.001). The quality of the sensory block and the tolerance to the pneumatic tourniquet were also significantly better in the US group (P < 0.01). We conclude that ultrasound combined with nerve stimulation improved the quality of the sensory block and the tolerance to the pneumatic tourniquet, reducing the number of attempts to perform sciatic nerve block at the midfemoral level.

Background and Objective: To evaluate the efficacy of 0.1% ropivacaine with fentanyl 2 microg mL(-1) via epidural for analgesia in labour., Methods: In a randomized study, 80 nulliparous parturients in labour had epidural analgesia initiated with 0.2% ropivacaine and fentanyl and were then randomized to receive either 0.1% ropivacaine with fentanyl 2 microg mL(-1) at 10mL h(-1) (Group R1, n = 38) or 0.2% ropivacaine with fentanyl 2 microg mL(-1) at 8 ml h(-1) (Group R2, n = 39) as epidural infusions. Supplementary analgesia was provided on request with ropivacaine 0.2% 5 mL as an epidural bolus., Results: There were no significant differences between the visual analogue pain scores either with respect to motor block or sensory block. The amount of local anaesthetic used was lower in the 0.1% ropivacaine group than in the 0.2% ropivacaine group (P = 0.001). Side-effects, patient satisfaction, labour outcome and neonatal outcomes were similar in both groups., Conclusions: An epidural infusion of 0.1% ropivacaine with fentanyl 2 microg mL(-1) at 10 mL h(-1) provided adequate analgesia in the first stage of labour. The level of analgesia was similar to that obtained using 0.2% ropivacaine with fentanyl 2 microg mL(-1) and with no differences with regard to motor or sensory block.

Background and Objectives: The midfemoral approach to the sciatic nerve (MF) is a new technique that has been used for postoperative analgesia after knee surgery. The aim of the present study was to compare efficacy, performance time, and patient acceptance of the midfemoral approach to that of the lateral approach at the level of the popliteal fossa (popliteal block [PB])., Methods: Sixty-three patients were enrolled in this prospective, randomized study. Thirty-two patients received a lateral sciatic nerve block (group PB) and 31 patients a midfemoral block (group MF). Ropivacaine 0.5% (30 mL) was used in both groups., Results: The quality of nerve blockade was comparable in both groups. Onset of sensory block for peroneal and tibial nerves was significantly shorter in group MF than in group PB, 5 (1-20) minutes and 5 (1-20) minutes versus 10 (1-40) minutes and 10 (1-45) minutes, respectively. Onset of motor block in both territories was also shorter in group MF compared with PB, 6 (2-35) minutes and 5 (2-55) minutes versus 15 (2-60) minutes and 15 (2-60) minutes, respectively (P <.05). There was no difference in duration of sensory and motor blockade, 16 (7-32) hours versus 16 (6-43) hours and 16 (8-32) hours versus 16 (6-25) hours. There was no significant difference between both groups with respect to difficulty of nerve block performance. Patient discomfort during needle puncture was also similar., Conclusions: The midfemoral approach to the sciatic nerve for ankle and foot surgery resulted in a reliable anesthetic, comparable to that of the lateral popliteal approach. This technique is simple, safe, and provides postoperative analgesia as effective as that obtained with the lateral approach.

Objective: To evaluate the cardiovascular effects of ketamine, midazolam, thiopentone and propofol in acutely hypovolemic pigs and to determine whether the association of ketamine and midazolam offers any advantage., Patients and Methods: Twenty-two Landrace-Large-White pigs. After monitoring was begun, acute hypovolemia was induced by means of rapid exsanguination of 30% of calculated volume. Hemodynamic variables were measured: a) at baseline; b) after exsanguination; c) 2 min after anesthetic induction; d) 10 min after anesthetic induction, and e) after reinfusion of the exsanguinated volume., Results: All pressures, cardiac output, cardiac index, and mixed venous oxygen saturation fell significantly with the induction of hypovolemia. Heart rate, systemic vascular resistances and arteriovenous oxygen differential increased. Ten min after anesthetic induction, heart rate in the midazolam group was significantly lower than in the ketamine-midazolam group. Arterial pressures decreased significantly after anesthetic induction with all drugs. The decrease in systolic arterial pressure was smaller in thiopenthal-anesthetized pigs than in pigs receiving either midazolam or propofol at the 10 min recording. The decrease in mean arterial and diastolic pressure after 10 min was smaller with thiopental than with any other drug. The decrease in mean arterial pressure was less in the thiopental and ketamine-midazolam groups than in the others after reinfusion. Diastolic arterial pressure at 10 min and after reinfusion had decreased less in the thiopental and ketamine-midazolam groups than in the propofol group. After anesthetic induction, the post-hypovolemic figures for cardiac output and cardiac index held steady or changes were slightly accentuated, with no statistically significant differences among the groups., Conclusions: The intravenous anesthetics evaluated were detrimental to cardiovascular function in acute hypovolemic pigs. Low-dose thiopental and ketamine plus midazolam may be the anesthetics of choice in this setting. Propofol caused the greatest degree of hemodynamic instability.