Adult‐to‐adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end‐stage liver disease. Right‐lobe grafts have usually been preferred in view of the higher graft ...volume, which lowers the risk of a small‐for‐size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left‐liver graft procurement for calculated small‐for‐size A2ALDLT in four donors are presented. The graft‐to‐recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux‐en‐Y loop 4 months later in one donor. We show that LDH of the full‐left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.
This report of laparoscopic procurement of full‐left liver grafts for small‐for‐size adult‐to‐adult living donor liver transplants shows that this operation is technically feasible and has the potential to diminish donor morbidity. See editorial by Akoad and Pomfret on page 2243 and case reports on pages 2462 and 2467.
Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this ...STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US.
STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes vg/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed).
From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91–100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8–44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 67% of 33), upper respiratory infection (11 33%), and increased alanine aminotransferase (nine 27%). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study.
STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline.
Novartis Gene Therapies.
Iron–sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron–sulfur ...clusters are located in the mitochondria and in the cytosol. The mitochondrial iron–sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich’s ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron–sulfur cluster biosynthesis.
A 65-year-old patient developed an unexplained and ultimately lethal metabolic acidosis under prolonged treatment with tigecycline. Tigecycline is known to have a selective inhibitory effect on ...eukaryotic mitochondrial translation. The underlying molecular mechanisms of the metabolic acidosis in this patient were explored.
Oxidative phosphorylation system (OXPHOS) analysis, blue native polyacrylamide gel electrophoresis followed by in-gel activity staining in mitochondria, molecular analysis of mitochondrial DNA (mtDNA) for genomic rearrangements and sequencing of the rRNA genes was performed on the subject's skeletal muscle.
OXPHOS analysis revealed a combined deficiency of the complexes I, III, IV and V, with a preserved function of complex II (encoded by nuclear DNA), thus demonstrating a defective mtDNA translation. There were no known underlying mitochondrial genetic defects. The patient had a (m.1391T>A) variant within the 12SrRNA gene in heteroplasmy (50–60%).
This patient developed an ultimately lethal mitochondrial toxicity while receiving prolonged treatment with tigecycline, which was caused by a defective translation of the mtDNA. Tigecycline is known to suppress eukaryotic mitochondrial DNA translation, but until now this effect has been considered to be clinically insignificant. The observations in this patient suggest a clinically significant mitochondrial toxicity of tigecycline in this patient, and warrant further investigation.
The article “Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway”, written by A. V. Vanlander, R. Van Coster was originally published.
Purpose
To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers ...of the abdominal wall, and regarding possible materials to be used.
Methods
The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument.
Results
For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE.
Recommendations
When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.
Purpose
To evaluate the efficacy of negative pressure therapy for superficial and deep mesh infections after ventral and incisional hernia repair by a prospective monocentric observational study.
...Methods
During a 6-year period, 724 consecutive open ventral and incisional hernia repairs were performed. Pre- and intraoperative data as well as postoperative complications were prospectively recorded. In case of wound infection, negative pressure therapy (NPT) was our primary treatment.
Results
Sixty-three patients (8.7 %) were treated using negative pressure therapy after primary ventral and incisional hernia repair. Infectious complications needing NPT occurred in 54 patients in the retromuscular group (54/523; 10.3 %), none when laparoscopically treated and in 9 patients (9/143; 6.3 %) treated by an open intraperitoneal mesh technique. Considering outcome, all meshes were completely salvaged in the retromuscular mesh group after a median of 5 dressing changes (range, 2–9), while in the intraperitoneal mesh, group 3 meshes needed complete (
n
= 2) or partial (
n
= 1) excision. Mean duration to complete wound closure was 44 days (range, 26–63 days).
Conclusion
NPT is a useful adjunct for salvage of deep infected meshes, particularly when large pore monofilament mesh is used.
Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can ...occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.
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