The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis

ObjectiveTo systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients.MethodsPubMed, EMBASE and the Cochrane Library were searched up to March 1^st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses.ResultsEHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01).ConclusionEHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.     

Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Atypical Abnormal Pulmonary Vein Drainage with Atrial Septal Defect: Surgical Treatment

Sinus venosus atrial septal defect (SV‐ASD) usually coexists with partial anomalous pulmonary vein connection (PAPVC). It is a difficult diagnosis in transthoracic echocardiography (TTE) due to eccentric position of defects. We present a rare case of atypical anatomical variation in PAPVC, which was never described before. Two right pulmonary veins drained into superior vena cava, which overrode SV‐ASD and interatrial septum, a third pulmonary vein into the right atrium. Complete diagnosis could not be set after TTE, nor transesophageal echocardiography, whereas angio‐CT was finally conclusive. This diagnostic approach allowed the surgical planning.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

足趾移植长手指全形再造术的临床应用

目的探讨足趾移植长手指全形再造手术的临床疗效。方法自2015年6月至2019年6月,对16例因外伤致手指缺损患者采用足趾移植长手指全形再造术,术后评估供区及受区的感觉功能、运动功能及外观形态,分析指甲畸形及增生性瘢痕的发生情况,并记录术后发生感染、血肿、皮片坏死及供区愈合不良等情况;通过调查问卷的方式分析患者的满意度。结果所有患者术后获随访1~12个月,其中2例受区发生感染,1例受区皮片边缘发生坏死,经换药后予以缓解;其余患者的供、受区均未出现长时间的痛疼感觉,受区感觉功能恢复达87.50%,受区运动功能恢复均较满意,手指外形基本满意。供区感觉受影响者2例,运动功能受限者1例,外形一般者2例。所有患者无指甲畸形及增生性瘢痕发生;满意者1例,基本满意者14例,不满意者1例。结论采用足趾移植长手指全形再造手术,基本可以满足患者及医师对于缺损手指进行完美修复的目标。     

普通变异型免疫缺陷病合并肝硬化1例并文献复习

目的:讨论普通变异型免疫缺陷病(common variable immunodeficiency disease,CVID)的发病机制、临床表现及治疗方法。方法:报道1例普通变异型免疫缺陷病合并肝硬化患者并复习相关文献。结果:普通变异型免疫缺陷病是临床少见病,易误诊,病因不清,临床表现复杂,部分患者病程中可出现肝功能异常,甚至并发肝硬化。结论:临床反复感染的患者应考虑CVID的可能,须进一步作血浆免疫球蛋白的检测确诊。对已经确诊患者定期补充静脉丙种球蛋白,同时还应定期检查肝功能。     

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

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??Objective    To investigate the effect of tooth movement at different time after the repair of alveolar bone defects. Methods    Defective alveolar bone model was established on one side in forty white rabbits??which were filled with bone meal and attached with Bio-Gide membrane as experiment sides. The other side was performed routine tooth extraction as control. Track the mandibular second molar in both sides respectively in 1 week??1 month??2 months and 3 months after operation. One month later??the distance between the mandibular second molar and third molar was measured with electronic vernier caliper in the experiment side and control side. The mandibular tissue was made paraffin section and hematoxylin eosin staining. Three views of the periodontal ligament in a third place of the mesial roots of the second molar was randomly chosen to count the total number of osteoclasts. Paired-t test analysis was made to evaluate the displacement of the mandibular second molar in experiment and control side??and to evaluate the number of osteoclasts in two side. Results    In Group 1w and Group 1 m??the displacement of the mandibular second molar in experiment group was smaller than that in the control side??P??0.05??. There was no statistical significance in Group 2 m and Group 3 m. The number of osteoclasts in the experiment side was less than the control group in Group 1 w and Group1 m??P??0.05??. No statistical significance in Group 2 m and Group 3 m was found. Conclusion    Orthodontic treatment can be performed two months after the repair of alveolar bone defects.