An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications

To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.     

Low serum adiponectin is independently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis

BACKGROUND: We aimed at investigating serum adiponectin in patients with the metabolic syndrome (MetS), in patients with angiographically diagnosed coronary artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We enrolled 687 consecutive patients undergoing coronary angiography for the evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD- subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001) and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons). In analysis of covariance the MetS and significant CAD proved associated with serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum adiponectin is independently associated with both the MetS and coronary atherosclerosis.     

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant – a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO₂/FiO₂ ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.     

An acceleromyographic train-of-four ratio of 1.0 reliably excludes respiratory muscle weakness after major abdominal surgery: a randomized double-blind study

Purpose

This randomized double-blind study was designed to determine if respiratory muscle weakness – measured by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and forced expiratory volume in one second (FEV₁) – persists even if an acceleromyographic train-of-four ratio (TOFR) of 1.0 is reached after major abdominal surgery.

Methods

Twenty patients underwent respiratory function tests before induction of anesthesia. Rocuronium was given, and the tests were repeated after extubation when the TOFR reached 1.0. The patients were then randomized to receive sugammadex 1 mg·kg^-1 or placebo, and the same tests were repeated five and 20 min later. Between-group comparisons were carried out with a mixed-model analysis of variance analysis.

Results

After anesthesia and adequate epidural analgesia, MIP and MEP decreased by 60% in both groups. In the placebo group, MIP decreased from a pre-induction value (median [range]) of 61.8 [31.3-96.1] to 19.6 [8.3-58.3] cm H₂O after extubation without significant variation five and 20 min after placebo. In the sugammadex group, MIP decreased from a pre-induction value of 57.8 [13.0-96.4] to 20.5 [6.4-67.3] cm H₂O after extubation. No differences were recorded after sugammadex administration (P = 0.246 between groups). In the placebo group, MEP decreased from 88.8 [65.1-120.3] before induction to 37.6 [13.4-70.6] cm H₂O after extubation. In the sugammadex group, MEP decreased from 85.5 [58.6-132.7] to 30.8 [10.5-60.5] cm H₂O, with no improvement five and 20 min after either placebo or sugammadex administration (P = 0.648). Similarly, the FCV and FEV₁ decreased 30-40% after extubation in both study groups.

Conclusion

Acceleromyographic TOFR of 1.0 excludes residual neuromuscular paralysis. However, major respiratory dysfunction is observed after abdominal surgery. This trial was registered at ClinicalTrials.gov: NCT01503840.     

Impact of tutorial assistance in laparoscopic sigmoidectomy for acute recurrent diverticulitis

Purpose

Adequate training and close supervision by an experienced surgeon are crucial to assure the patient safety during laparoscopic training. This study evaluated the impact of tutorial assistance on the duration of surgery and postoperative complications after laparoscopic sigmoidectomy.

Methods

The data from 235 patients undergoing laparoscopic sigmoidectomy were collected. Operating surgeons were classified as either residents/registrars (group A, tutorial assistance) or consultants operating autonomously (group B). Groups were compared concerning the duration of surgery and in-hospital complications using a multivariable regression model accounting for the most relevant confounders.

Results

The median duration of the operation in group A (n = 75) was 221 min, and that in group B (n = 160) 189 min (p < 0.001). The risk of developing any in-hospital complication (Clavien–Dindo classification I–V) was 36.0 % in Group A and 32.5 % in group B (95 % CI ?16.6, 9.6 %). The risk of developing moderate to severe surgical complications (Clavien–Dindo classification II-V) was 16.0 % in group A and 12.5 % in group B (95 % CI ?13.3, 6.3 %).

Conclusions

We were unable to demonstrate a clear impact of tutorial assistance on the risk of postoperative complications. Although associated with a longer duration of surgery, laparoscopic sigmoidectomy for acute recurrent sigmoid diverticulitis conducted by a junior supervised surgeon appears to be a safe surgical modality.     

Micro- and Nano-CT for the Study of Bone Ultrastructure

Micro-computed tomography (micro-CT)—a version of X-ray CT operating at high spatial resolution—has had a considerable success for the investigation of trabecular bone micro-architecture. Currently, there is a lot of interest in exploiting CT techniques at even higher spatial resolutions to assess bone tissue at the cellular scale. After recalling the basic principles of micro-CT, we review the different existing system, based on either standard X-ray tubes or synchrotron sources. Then, we present recent applications of micro- and nano-CT for the analysis of osteocyte lacunae and the lacunar-canalicular network. We also address the question of the quantification of bone ultrastructure to go beyond the sole visualization.     

Clinical inertia in patients with type 2 diabetes treated with oral antidiabetic drugs: Results from a Japanese cohort study (JDDM53)

Aims/IntroductionTreatment intensification is commonly delayed in people with type 2 diabetes, resulting in poor glycemic control for an unacceptable length of time and increased risk of complications.Materials and MethodsThis retrospective study investigated clinical inertia in 33,320 Japanese adults with type 2 diabetes treated with oral antidiabetic drugs (OADs) between 2009 and 2018, using data from the Computerized Diabetes Care (CoDiC^®) database.ResultsThe median time from first reported glycated hemoglobin (HbA1c) ≥7.0% (≥53 mmol/mol) to treatment intensification was considerably longer and HbA1c levels were higher the more OADs the patient was exposed to. For patients receiving three OADs, the median times from HbA1c ≥7.0% (53 mmol/mol) to intensification with OAD, glucagon‐like peptide‐1 receptor agonist or insulin were 8.1, 9.1 and 6.7 months, with a mean HbA1c level at the time of intensification of 8.4%, 8.9% and 9.3%, respectively. The cumulative incidence for time since the first reported HbA1c ≥7.0% (≥53 mmol/mol) to intensification confirmed the existence of clinical inertia, identifying patients whose treatment was not intensified despite poor glycemic control. HbA1c levels ≥7.0% (≥53 mmol/mol) after ≥6 months on one, two or three OADs were observed in 42%, 51% and 58% of patients, respectively, showing that approximately 50% of patients are above HbA1c target regardless of how many OADs they take.ConclusionsReal‐world data here show clinical inertia in Japanese adults with type 2 diabetes from early diabetes stages when they are receiving OADs, and illustrate a need for earlier, more effective OADs or injectable treatment intensification and better communication around the existence of clinical inertia.