Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

The height of the operating table affects the performance of residents in combined spinal and epidural anesthesia training by affecting the vision of the puncture needle: a randomized controlled trial.

BACKGROUND: The present study aimed to evaluate whether the operating table height affected the success rate and incidences of complications of combined spinal-epidural anesthesia administered by residents during training. METHODS: One-hundred-and-eighty patients were randomly allocated according to landmarks on the resident's body: umbilicus (group U), lowest rib margin (R), and xiphoid process (X). The success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma were recorded. RESULTS: There were no differences between the three groups in the success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma. However, paresthesia during epidural catheter advancement was more common on the left side (66.7%) than the right side (33.3%) (P = 0.03). In group R, the success rate of epidural anesthesia was higher during the residents' third time (100%) than their first time (50%; P = 0.01). Most residents (83%) preferred the table height at which the needle insertion point was at the level of their lowest rib margin. CONCLUSIONS: Neither the success nor the complication of combined spinal-epidural anesthesia in lateral decubitus position during residents' training affected by the operating table height. However, paresthesia was more likely to occur on the left side when a stiff catheter was inserted into the epidural space. It may be better to keep the table height at residents' lowest rib margin. It was not just preferred by most of residents but also better for their training of performing epidural anesthesia. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at Chinese Clinical Trial Registry (NCT: ChiCTR1800016078, Principal investigator: Juan Gu, Date of registration: 9 May 2018). Registry URL http://www.chictr.org.cn.

Effects of dexmedetomidine on cognitive function in elderly patients after laparoscopic cholecystectomy: A protocol for systematic review and meta-analysis.

BACKGROUND: Although many studies have reported the effects of dexmedetomidine on cognitive function (CF) in elderly patients after laparoscopic cholecystectomy (LCT), to this date, its effects are still not well understood. The aim of this study is to produce a qualitative synthesis of assessing the effects of dexmedetomidine on CF in elderly patients after LCT. METHODS: We will conduct a comprehensive search in Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, VIP Database, WANGFANG Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the commencement to March 31, 2020 without restrictions of language and publication status. In addition, we will also search grey literature, including conference abstracts, dissertations, reference lists of included studies and relevant reviews. All potential studies will be identified independently by 2 authors to determine their inclusion against previously defined eligibility criteria. The quality of selected papers will be assessed using Cochrane risk of bias tool. All statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will provide a synthesis of the current available data on assessing the effects of dexmedetomidine on CF in elderly patients after LCT. CONCLUSIONS: Its findings will provide qualitative evidence to better understand the effects of dexmedetomidine on CF in elderly patients after LCT.INPLASY Registration Number: INPLASY202040030.

NOX2 is involved in CB2-mediated protection against lung ischemia-reperfusion injury in mice.

Lung ischemia-reperfusion injury (LIRI) can occur in many clinical scenarios. Activation of the cannabinoid 2 (CB2) receptor limits tissue injury in some ischemia-reperfusion (I/R) models. However, whether and how CB2 receptor activation alleviates lung injury induced by I/R remain unclear. In this study, we sought to determine whether JWH133, a selective CB2 receptor agonist, could alleviate lung injury induced by I/R and to examine the role of NOX2 in this process. Here, an I/R model was established using male C57BL/6 mice, by blocking the left pulmonary hilum for 1 h, followed by reperfusion for 2 h. Results showed that pretreatment with JWH133 significantly attenuated I/R-induced lung injury (decreased lung injury scores and wet-to-dry weight ratio and increased oxygenation index), alleviated oxidative stress (increased superoxide dismutase (SOD), and decreased Malondialdehyde (MDA) levels). It also significantly increased CB2 receptor mRNA expression and protein levels and significantly reduced NOX2 mRNA and protein expression. Further, the CB2 receptor antagonist AM630 eliminated these effects mediated by JWH133. Pretreatment with the NOX2 inhibitor, gp91 ds-tat, reduced NOX2 expression, but did not affect CB2 receptor expression and failed to alleviate lung injury and oxidative stress after additional JWH133 treatment. Our study suggests that CB2 receptor activation alleviates LIRI by inhibiting oxidative stress and that NOX2 is involved in CB2-mediated protection against LIRI in mice.

Effects of monoacylglycerol lipase inhibitor URB602 on lung ischemia-reperfusion injury in mice.

Lung ischemia-reperfusion injury (LIRI) is a common and severe postoperative pathologic complication that often occurs when the oxygen supply disrupted to the lung tissue fallowed by reperfusion period, in most cases after lung transplantation and cardiopulmonary bypass. Endocannabinoids such as 2-arachidonoylglycerol (2-AG) have very important role as regulators of inflammation. Monoacylglycerol lipase (MAGL) is the main 2-AG-degrading enzyme, and the downstream metabolites of 2-AG play a role in the inflammation. Ischemia reperfusion (IR) was induced by clamping the left pulmonary hilum for 60 min, followed by 120 min of reperfusion in male C57BL/6 mice. Effects of URB602, a MAGL inhibitor, were evaluated in a preventive or therapeutic regimen (5 min before ischemia or reperfusion, respectively). Oxygenation index, wet-to-dry weight ratio and lung injury score were analyzed. Endocannabinoids including 2-AG, anandamide (AEA) and arachidonic acid (AA) levels, metabolites such as Prostaglandin I2 (PGI2), Thromboxane B2 (TXB2) and Leukotrienes B4 (LTB4) and inflammatory markers (Interleukin 6 (IL-6) andTumor necrosis factor-α (TNF-α)) in lung tissues were measured by using mass spectrometry or ELISA analyses. We found that IR increased the wet-to-dry weight ratio of lung and lung injury score and decreased oxygenation index as compared to the sham group. Moreover, treatment with URB602 in preventive or therapeutic regimen reduced the wet-to-dry weight ratio and lung injury score while increased oxygenation index when compared with the IR group, with a more improvement in the preventive regimen group. In addition, treatment with URB602 before ischemia increased 2-AG level but decreased metabolites (AA, PGI2, TXB2, LTB4) and inflammatory markers (IL-6, TNF-α). Thus, our study demonstrated that a pretreatment with URB602 significantly reduced IR-induced lung injury and inflammation. URB602 inhibited LIRI and inflammation by increasing 2-AG level and reducing downstream metabolites from AA to PGI2, TXB2 and LTB4 in lung tissues.

[Effect of Epidural Volume Extension on Combined Spinal-anesthesia of Parturients in Women Undergoing Cesarean Delivery].

OBJECTIVE: To evaluate the blocking characteristics of epidural volume extension on combined spinal-anesthesia of parturients undergoing cesarean delivery. METHODS: Eighty parturients were randomly allocated to one of four groups, receiving 0, 5, 10 or 15 mL normal saline, respectively, through epidural catheter at a rate of 0.5 mL/s (n = 20 in each group) after combined spinal-anesthesia with 11 mg intrathecally isobaric bupivacaine. Peak sensory block height, time for sensory block to sixth thoracicdermatome level, time for highest modified Bromage motor score, time for sensory regression to tenth thoracicdermatome level, and motor block recovery to Modified Bromage 0 were recorded. RESULTS: The groups with 10 mL and 15 mL epidural extension had a higher level of peak sensory and shorter time for the sensory block to sixth thoracicdermatome level compared with the control group (P< 0.05). There were no significant group differences in the time for sensory regression to tenth thoracicdermatome level (P > 0.05). The saline epidural extension groups had significant shorter time for highest modified Bromage motor score and motor block recovery to Modified Bromage 0 compared with the control group (P < 0.05). The use of phenylephrine was significantly higher in the 15 mL treatment group (P < 0.05). CONCLUSION: 10 mL of epidural saline volume extension is optimal for combined spinal-epidural anaesthesia of parturients undergoing caesarean delivery.

Low-dose spinal-epidural anesthesia for Cesarean section in a parturient with uncontrolled hyperthyroidism and thyrotoxic heart disease.

A 29-year-old woman at 34 weeks' gestation with uncontrolled hyperthyroidism and thyrotoxic heart disease was admitted to urgency Cesarean section. After preoperative sedation and good communication, low-dose spinal anesthesia (7.5 mg 0.5 % bupivacaine) combined with epidural anesthesia (6 ml 2 % lidocaine) was performed through L3-4 inter-vertebral. Opioids were given intravenously to the mother for sedation after delivery of the baby. Satisfactory anesthesia and sedation was provided during surgery. The mother and the neonate were safe and no special complication was found after surgery. Our case demonstrated that low-dose spinal anesthesia combined with epidural anesthesia with intravenous opioids can provide satisfactory anesthesia and sedation, and reduce the risk of heart failure and thyroid storm.

[ED50 of Intrathecal Isobaric Bupivacaine with Epidural Volume Extension for Cesarean Delivery].

OBJECTIVE: To determine the 50% effective dose (ED50) of intrathecal isobaric bupivacaine in combined spinal-epidural anaesthesia with epidural volume extension for caesarean surgery. METHODS: Eighty-four women undergoing elective caesarean sections were randomly assigned to seven groups, receiving intrathecally isobaric bupivacaine in a dosage of 6, 7, 8, 9, 10, 11 or 12 mg (n=12 per group), respectively. Ten mL normal saline was injected through an epidural catheter at a rate of 0.5 mL/s. Successful induction was defined as Hollmen pinprick block grade 2 at a height equal to or higher than T6. Success (surgery) was defined as success (induction) plus no requirement for epidural supplementation throughout surgery. The ED50 values were determined using a logistic regression model. RESULTS: The EDs for success (induction) and success (surgery) were 8.121 mg (95% confidence interval: 7.421-8.821) and 9.012 mg (95% confidence interval: 7.747-10.280), respectively. With increase in amount of intrathecal bupivacaine, time to success (induction) was shortened (P<0.05), resulting in increased successful numbers for both induction and surgery. No differences were found in the use of phenylephrine, haemodynamic stability and the occurrence of nausea and vomiting among groups. CONCLUSION: When combined with epidural volume extension, intrathecal bupivacaine has an ED50 of 8.121 mg and 9.012 mg for success (induction) and success (surgery), respectively, in women undergoing caesarean sections.

[Appling the color Doppler in abdominal aortic balloon occlusion for pelvic and sacral surgery].

OBJECTIVE: To apply the color Doppler in abdominal aortic balloon occlusion for pelvic or sacral surgery, and to evaluate its effectiveness in controlling blood loss. METHODS: A Philips 4500 color Doppler was used to place abdominal aortic balloons in 20 patients with pelvic or sacral tumors who underwent surgery. The temporary abdominal aortic balloons were used for controlling blood loss in the surgery. Transesophageal echocardiography was performed to detect the renal blood flow. RESULTS: Abdominal aortic balloons were successfully placed to the 20 patients, with a water injection rate of 10-18 (13.8 +/- 2.6) mL and a total of 45-180 min occlusion during the 70-450 (265 +/- 102) min surgery. The intraoperative blood loss ranged from 250 to 4000 (1357 +/- 997) mL. The water injection rate of abdominal aortic-balloons (Y) was correlated with the diameter of abdominal aorta (X): Y = 7.1602X + 2. 9968 (R2 = 0.7371, P < 0.05). Renal blood flow was not affected. The patients stayed in hospital for 7-13 (9.8 +/- 11.9) days after operation. One patient developed complications. The one year recurrence rate of tumors was 10%. CONCLUSION: The color Doppler provides a simple and accurate instrument for abdominal aortic-balloon occlusion, with reliable blood loss control.