Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats

Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P < 0.05) without altering minute volume (V_E). In combination to DZP, BUP/NLX significantly increased expiratory time (P < 0.01) and decreased f (P < 0.01), tidal volume (V_T, P < 0.001), and V_E (P < 0.001) while BUP only decreased V_T (P < 0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P < 0.001) and decreased f (P < 0.01) and V_E (P < 0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.     

胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗肝内胆管结石患者疗效研究*

目的 探讨采用胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢治疗肝内胆管结石(IHS)患者的临床疗效。方法 2018年9月～2021年6月我院诊治的71例IHS患者,其中33例(对照组)接受常规胆肠Roux-en-Y吻合术,另38例(观察组)接受胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗。采用ELISA法检测血清C反应蛋白(CRP)和白细胞介素-6(IL-6),使用全自动荧光免疫定量分析仪检测血清降钙素原(PCT)。结果 在术后1个月,观察组临床有效率为94.7%,显著高于对照组的75.8%(P<0.05);观察组血清GGT和ALT水平分别为(71.9±6.2)U/L和(38.7±5.9)U/L,显著低于对照组【分别为(95.8±6.9)U/L和(62.6±6.8)U/L,P<0.05】;观察组血清CRP和IL-6水平分别为(60.8±8.1)mg/L和(89.8±20.1)pg/mL,显著高于对照组【分别为(38.3±9.2)mg/L和(65.7±23.5)pg/mL,P<0.05】;观察组结石残留发生率为7.9%,显著低于对照组的21.2%(P<0.05)。结论 采用胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗HIS患者临床疗效较好,可提高结石清除率,防止术后返流性感染,同时也为复发结石、胆管狭窄或梗阻等提供了一条方便的进入肝内胆管的永久性胆道通路,是较为实用的治疗IHS的手术方法。     

An indissoluble knot: An unexpected troubleshooting during Micra implantation

Micra is a transcatheter leadless pacing system delivered percutaneously through femoral vein access into the right ventricle. We are going to describe an initially standard procedure, with an unexpected troubleshooting at the end: the impossibility to release the device and retract the delivery due to a knot in the tether.     

Efficacy and Tolerability of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Neurologic Diseases

PurposeIV immunoglobulin (Ig) therapy has been widely used for the treatment of neurologic disorders, autoimmune diseases, immunodeficiency-related diseases, blood system diseases, and cancers. In this review, we summarize the efficacy and tolerability of IVIg and SCIg therapy in neurologic diseases.MethodsWe summarized and analyzed the efficacy and tolerability of IVIg and SCIg in neurologic diseases, by analyzing the literature pertaining to the use of IVIg and SCIg to treat nervous system diseases.FindingsIn clinical neurology practice, IVIg has been shown to be useful for the treatment of new-onset or recurrent immune diseases and for long-term maintenance treatment of chronic diseases. Moreover, IVIg may have applications in the management of intractable autoimmune epilepsy, paraneoplastic syndrome, autoimmune encephalitis, and neuromyelitis optica. SCIg is emerging as an alternative to IVIg treatment. Although SCIg has a composition similar to that of IVIg, the applications of this therapy are different. Notably, the bioavailability of SCIg is lower than that of IVIg, but the homeostasis level is more stable. Current studies have shown that these 2 therapies have pharmacodynamic equivalence.ImplicationsIn this review, we explored the efficacy of IVIg in the treatment of various neurologic disorders. IVIg administration still faces many challenges. Thus, it will be necessary to standardize the use of IVIg in the clinical setting. SCIg administration is a novel and feasible treatment option for neurologic and immune-related diseases, such as chronic inflammatory demyelinating polyradiculoneuropathy and idiopathic inflammatory myopathies. As our understanding of the mechanisms of action of IVIg improve, potential next-generation biologics can being developed.     

Primary cutaneous mucormycosis in a lung transplant recipient: case report and concise review of the literature

Abstract: Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused by organisms of the class Zygomycetes. Immunocompromised individuals, including both solid organ and hematopoietic stem cell transplant recipients, are preferentially affected. Among solid organ transplant (SOT) recipients, the sinuses, with or without involvement of the orbits and cerebrum, are the most common sites of disease, although the pulmonary allograft appears to be targeted following lung transplantation. Here, we describe the unique case of a lung transplant recipient who developed multifocal cutaneous mucormycosis without involvement of the pulmonary allograft, and review the published literature regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis following SOT.     

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that C_peak, C_trough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.