Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents.

OBJECTIVES: Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking. METHODS: We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay. RESULTS: Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation. CONCLUSIONS: Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort.

Comparing a virtual reality head-mounted display to on-screen three-dimensional visualization and two-dimensional computed tomography data for training in decision making in hepatic surgery: a randomized controlled study.

OBJECTIVE: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. BACKGROUND: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. METHODS: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). RESULTS: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. CONCLUSIONS: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery.

Development and validity evidence of an objective structured assessment of technical skills score for minimally invasive linear-stapled, hand-sewn intestinal anastomoses: the A-OSATS score.

INTRODUCTION: The aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS). MATERIALS AND METHODS: The Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted. Video recordings were scored by two blinded raters assessing intrarater and interrater reliability and discriminative abilities between novices (n = 8), intermediates (n = 24), and experts (n = 8). RESULTS: The Delphi process included 18 international experts and was successfully completed after 4 rounds. A total of 4 relevant main steps as well as 15 substeps were identified and a definition of each substep was provided. A maximum of 75 points could be reached in the unweighted A-OSATS score and 170 points in the weighted A-OSATS score respectively. A total of 41 anastomoses were evaluated. Excellent intrarater (r = 0.807-0.988, p < 0.001) and interrater (intraclass correlation coefficient = 0.923-0.924, p < 0.001) reliability was demonstrated. Both versions of the A-OSATS correlated well with the general OSATS and discriminated between novices, intermediates, and experts defined by their OSATS global rating scale. CONCLUSION: With the weighted and unweighted A-OSATS score, we propose a new reliable standard to assess the creation of minimally invasive linear-stapled, hand-sewn anastomoses based on an international expert consensus. Validity evidence in live animal models is provided in this study. Future research should focus on assessing whether the weighted A-OSATS exceeds the predictive capabilities of patient outcomes of the unweighted A-OSATS and provide further validity evidence on using the score on different anastomotic techniques in humans.

Naturally occurring point mutation Cys460Trp located in the I-EGF1 domain of integrin ß3 alters the binding of some anti-HPA-1a antibodies.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets in the fetus or newborn by maternal platelet alloantibodies, mostly against human platelet antigen (HPA)-1a. Recent studies indicate that two anti-HPA subtypes exist: Type I reacts with epitopes residing on the plexin-semaphorin-integrin (PSI) and type II with plexin-semaphorin-integrin/integrin epidermal growth factor 1 (I-EGF1) domains of the ß3 integrin. Here, we evaluated whether a Cys460Trp mutation in the I-EGF1 domain found in a patient with Glanzmann thrombasthenia can alter the binding of anti-HPA-1a. METHODS: Stable HEK293 cell lines expressing wild-type and mutant αIIbß3 and αvß3 were generated to prove the reactivity of different antibodies against HPA-1a. RESULTS: Flow cytometry analysis of wild-type (Cys460) and mutant (Trp460) expressed on HEK293 cells showed equal surface expression of αIIbß3 and αvß3. When tested with mutant αIIbß3 cells, reduced binding was observed in Type II but not in Type I anti-HPA-1a. These results could be confirmed with platelets carrying Cys460Trp mutation. Interestingly, reduced binding of Type I antibodies was detected with mutant αvß3 cells. Both antibody types were found in maternal sera from FNAIT cases by an antigen-capture assay with use of HEK293 transfected cells. CONCLUSIONS: These observations confirm the existence of Type I and Type II anti-HPA-1a. Furthermore, this study underlines different immunogenicity of HPA-1a antigen(s) residing on either αIIbß3 or αvß3. Further analysis of FNAIT cases from mothers having a fetus with and without intracranial bleedings with use of such an approach may highlight the functional relevance of different anti-HPA-1a subtypes.

Platelet dysfunction caused by a novel thromboxane A2 receptor mutation and congenital thrombocytopenia in a case of mild bleeding.

Chronic hemorrhagic diathesis in patients showing normal levels of plasmatic clotting factors strongly suggests for congenital platelet disorders. We report on a pediatric patient (male, 3 years, D1) with mild bleeding. A sibling (D2), his mother (D3) and father (D4) were included for laboratory investigation. Platelet counts in D1, D2 and D4 indicated mild thrombocytopenia (100 Gpt/L). D1 and D3 platelets showed significantly diminished aggregation response on arachidonic acid and U46619 stimulation. Immunostaining for platelet proteins on blood smears of D1 and D2 indicated defects in ß1-tubulin. Exon sequencing of TBXA2R and TUBB1 revealed heterozygosity for the novel TBXA2R*c.908T>C (p.L303P) mutation in D1 and D3. TUBB1 was either wild type (D2, D3) or heterozygous (D1, D4) for the common polymorphism TUBB1*c.920G>A (rs6070697; p.R307H). In conclusion, the bleeding phenotype of the index patient can be explained by a diminished platelet function caused by the TBXA2R*c.908T>C mutation inherited from the mother and a mild thrombocytopenia with unknown molecular basis that is inherited from the father.

Does rating with a checklist improve the effect of E-learning for cognitive and practical skills in bariatric surgery? A rater-blinded, randomized-controlled trial.

BACKGROUND: Mental training of laparoscopic procedures with E-learning has been shown to translate to the operating room. The present study aims to explore whether the use of checklists during E-learning improves transfer of skills to the simulated OR on a Virtual Reality (VR) trainer for Roux-en-Y gastric bypass (RYGB). METHODS: Laparoscopy naive medical students (n = 80) were randomized in two groups. After an E-learning introduction to RYGB, checklist group rated RYGB videos using the validated Bariatric Objective Structured Assessment of Technical Skills (BOSATS) checklist while group without checklist only observed the videos. Participants then performed RYGB on a VR-trainer twice and were evaluated by a blinded expert rater using BOSATS. A multiple choice (MC) knowledge test on RYGB was performed. Suturing on a cadaveric porcine small bowel was evaluated using objective structured assessment of technical skill (OSATS). RESULTS: Checklist group was better in the knowledge test (A 8.3 ± 1.1 vs. B 7.1 ± 1.3; p ≤ 0.001) and there was a trend towards better VR RYGB performance (BOSATS) on the first try (85.9 ± 10.2 vs. 81.1 ± 11.5; p = 0.058), but not on the second try (92.0 ± 9.7 vs. 89.3 ± 10.5; p = 0.251). Suturing as measured by OSATS was not different (29.5 ± 3.0 vs. 29.0 ± 3.5; p = 0.472). CONCLUSION: This study presents evidence that the use of a BOSATS checklist during E-learning helps trainees to improve their knowledge acquisition with E-learning. The transfer from mental training to the simulated OR environment seems to be partially enhanced by use of the BOSATS checklist. However, more research is required to investigate potential benefits.

One or two trainees per workplace for laparoscopic surgery training courses: results from a randomized controlled trial.

BACKGROUND: There are no standards for optimal utilization of workplaces in laparoscopic training. This study aimed to define whether laparoscopy training should be done alone or in pairs (known as dyad training). METHODS: This was a three-arm randomized controlled trial with laparoscopically naïve medical students (n = 100). Intervention groups participated alone (n = 40) or as dyad (n = 40) in a multimodality training curriculum with e-learning, basic, and procedural skills training using box and VR trainers. The control group (n = 20) had no training. Post-performance of a cadaveric porcine laparoscopic cholecystectomy (LC) was measured as the primary outcome by blinded raters using the objective structured assessment of technical skills (OSATS). Global operative assessment of laparoscopic skills (GOALS), time for LC, and VR performances were secondary outcomes. RESULTS: There were no differences between groups for performance scores [OSATS: alone (40.2 ± 9.8) vs. dyad (39.8 ± 8.6), p = 0.995; alone vs. control (37.1 ± 7.4), p = 0.548; or dyad vs. control, p = 0.590; and GOALS score: alone (10.6 ± 3.0) vs. dyad (10.0 ± 2.7), p = 0.599; alone vs. control (10.1 ± 3.0), p = 0.748; or dyad vs. control, p = 0.998]. Dyad finished LC faster than control [median = 62.5 min (CI 58.0-73.0) vs. 76.5 min (CI 72.0-80+); p = 0.042], while there were no inter-group differences between alone vs. control [median = 69.0 min (CI 62.0-76.0) vs. control; p = 0.099] or alone vs. dyad (p = 0.840). Dyad and alone showed superior performance on the VR trainer vs. control for time, number of movements, and path length, but not for complications and application of cautery. CONCLUSIONS: The curriculum provided trainees with the laparoscopic skills needed to perform LC safely, irrespective of the number of trainees per workplace. Dyad training reduced the operation time needed for LC. Therefore, dyad training seems to be a promising alternative, especially if training time is limited and resources must be used as efficiently as possible. Trial registration German Clinical Trials Register: DRKS00004675.

Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study.

BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

Computer-assisted 3D bowel length measurement for quantitative laparoscopy.

BACKGROUND: This study aimed at developing and evaluating a tool for computer-assisted 3D bowel length measurement (BMS) to improve objective measurement in minimally invasive surgery. Standardization and quality of surgery as well as its documentation are currently limited by lack of objective intraoperative measurements. To solve this problem, we developed BMS as a clinical application of Quantitative Laparoscopy (QL). METHODS: BMS processes images from a conventional 3D laparoscope. Computer vision algorithms are used to measure the distance between laparoscopic instruments along a 3D reconstruction of the bowel surface. Preclinical evaluation was performed in phantom, ex vivo porcine, and in vivo porcine models. A bowel length of 70 cm was measured with BMS and compared to a manually obtained ground truth. Afterwards 70 cm of bowel (ground truth) was measured and compared to BMS. RESULTS: Ground truth was 66.1 ± 2.7 cm (relative error + 5.8%) in phantom, 65.8 ± 2.5 cm (relative error + 6.4%) in ex vivo, and 67.5 ± 6.6 cm (relative error + 3.7%) in in vivo porcine evaluation when 70 cm was measured with BMS. Using 70 cm of bowel, BMS measured 75.0 ± 2.9 cm (relative error + 7.2%) in phantom and 74.4 ± 2.8 cm (relative error + 6.3%) in ex vivo porcine evaluation. After thorough preclinical evaluation, BMS was successfully used in a patient undergoing laparoscopic Roux-en-Y gastric bypass for morbid obesity. CONCLUSIONS: QL using BMS was shown to be feasible and was successfully translated from studies on phantom, ex vivo, and in vivo porcine bowel to a clinical feasibility study.

Face validity of the pulsatile organ perfusion trainer for laparoscopic cholecystectomy.

BACKGROUND: The pulsatile organ perfusion (POP) trainer provides training of minimally invasive surgery (MIS) with real instruments and cadaveric organs. It provides training of full procedures with simulation of bleeding. Although widely used, the face validity has not yet been evaluated. This study aimed to establish face validity of the POP trainer for laparoscopic cholecystectomy (LC) and its usefulness compared with other training modalities. MATERIALS AND METHODS: During MIS courses, the participants (n = 52) used the POP trainer to perform LC. Face validity was assessed with questionnaires for realism and usefulness on a five-point Likert scale. Participants were divided into two groups: experts (n = 15) who had performed more than 50 laparoscopic procedures and novices (n = 37) with less than 50 procedures. Secondary aims included the ranking of training modalities, as well as exploration of their specific advantages and disadvantages. RESULTS: The POP trainer was found to be realistic (3.8 ± 0.9) and useful (4.6 ± 0.9). Differences between experts and novices were only found for "The training modality resembles reality" (3.1 ± 0.8 vs. 3.8 ± 0.7; p = 0.010), "The operation on the POP trainer is realistic" (3.4 ± 1.1 vs. 4.5 ± 0.8; p = 0.003), and "It would be desirable to have a POP trainer at my own hospital" (4.2 ± 1.1 vs. 4.8 ± 0.8; p = 0.040). In the ranking, the animal training (1.1 ± 0.3) placed first, the POP trainer (2.3 ± 0.9) second, and the VR trainer (2.8 ± 0.9) and box trainer (2.8 ± 1.1) third. The realistic simulation of animal training was named as an advantage most often, while the unrealistic simulation of the VR trainer was the most often named disadvantage. CONCLUSIONS: The POP trainer was rated a highly realistic and useful training modality with face validity for LC. Differences between experts and novices existed concerning realism and desirability. Future studies should evaluate the POP trainer for more advanced surgical procedures. The POP trainer widens the spectrum of modalities for training of MIS in a safe environment outside the operating room.

Use of a hydrophilic coating wire reduces significantly the rate of central vein punctures and the incidence of pneumothorax in totally implantable access port (TIAP) surgery.

BACKGROUND: Insertion of a Totally Implantable Access Port (TIAP) can be performed either via Central Vein Puncture (CVP) or Brachiocephalic Vein Cut-down (venous section-VS). The primary success rate of TIAP implantation using VS rarely ever achieves 100%. The objective of this study was to describe a modified VS approach using a hydrophilic coated wire (TVS). METHODS: From 01.01.2015 to 31.12.2015, all patients receiving TIAP implantations were screened. During this time, all patients in whom the primary VS procedure was found to be unsuccessful were analysed. RESULTS: In 2015, 1152 patients had TIAP implantations performed by 24 different surgeons. Of these, 277 patients needed a second line rescue strategy either by CVP (n = 69) or TVS (n = 208). There were no statistically significant differences regarding demographics or indication for TIAP implantation between CVP and TVS. The operation time and the qualification of the operating surgeon between CVP and TVS did not differ significantly. After the introduction of the guidewire with a hydrophilic coated wire, the need for CVP decreased significantly from 12.7% to 8.8% (p < 0.0001). In patients receiving CVP as a second line rescue strategy, the incidence of pneumothorax (n = 3 patients (4.3%)) was significantly higher compared to patients with TVS as a second line rescue strategy (n = 1 patient (0.48%), p = 0.02). CONCLUSION: The use of a hydrophilic coated wire significantly decreased the number of CVP and the incidence of pneumothorax. TVS is a safe and successful second-line rescue strategy.

Sequential learning of psychomotor and visuospatial skills for laparoscopic suturing and knot tying-a randomized controlled trial "The Shoebox Study" DRKS00008668.

PURPOSE: Learning curves for minimally invasive surgery are prolonged since psychomotor skills and visuospatial orientation differ from open surgery and must be learned. This study explored potential advantages of sequential learning of psychomotor and visuospatial skills for laparoscopic suturing and knot tying compared to simultaneous learning. METHODS: Laparoscopy-naïve medical students were randomized into a sequential learning group (SEQ) or a simultaneous learning group (SIM). SEQ (n = 28) trained on a shoebox with direct 3D view before proceeding on a box trainer with 2D laparoscopic view. SIM (n = 25) trained solely on a box trainer with 2D laparoscopic view. Training time and number of attempts needed were recorded until a clearly defined proficiency level was reached. RESULTS: Groups were not different in total training time (SEQ 5868.7 ± 2857.2 s; SIM 5647.1 ± 2244.8 s; p = 0.754) and number of attempts to achieve proficiency in their training (SEQ 44.0 ± 17.7; SIM 36.8 ± 15.6; p = 0.123). SEQ needed less training time on the box trainer with 2D laparoscopic view than did SIM (SEQ 4170.9 ± 2350.8 s; SIM 5647.1 ± 2244.8 s; p = 0.024), while the number of attempts here was not different (SEQ 29.9 ± 14.1; SIM 36.8 ± 15.6; p = 0.097). SEQ was faster in the first attempts on the shoebox (281.9 ± 113.1 s) and box trainer (270.4 ± 133.1 s) compared to the first attempt of SIM on the box trainer (579.4 ± 323.8 s) (p < 0.001). CONCLUSION: In the present study, SEQ was faster than SIM at the beginning of the learning curve. SEQ did not reduce the total training time needed to reach an ambitious proficiency level. However, SEQ needed less training on the box trainer; thus, laparoscopic experience can be gained to a certain extent with a simple shoebox.

Direct Observation versus Endoscopic Video Recording-Based Rating with the Objective Structured Assessment of Technical Skills for Training of Laparoscopic Cholecystectomy.

PURPOSE: The validated Objective Structured Assessment of Technical Skills (OSATS) score is used for evaluating laparoscopic surgical performance. It consists of two subscores, a Global Rating Scale (GRS) and a Specific Technical Skills (STS) scale. The OSATS has accepted construct validity for direct observation ratings by experts to discriminate between trainees' levels of experience. Expert time is scarce. Endoscopic video recordings would facilitate assessment with the OSATS. We aimed to compare video OSATS with direct OSATS. METHODS: We included 79 participants with different levels of experience [58 medical students, 15 junior residents (novices), and 6 experts]. Performance of a cadaveric porcine laparoscopic cholecystectomy (LC) was evaluated with OSATS by blinded expert raters by direct observation and then as an endoscopic video recording. Operative time was recorded. RESULTS: Direct OSATS rating and video OSATS rating correlated significantly (x03C1; = 0.33, p = 0.005). Significant construct validity was found for direct OSATS in distinguishing between students or novices and experts. Students and novices were not different in direct OSATS or video OSATS. Mean operative times varied for students (73.4 ± 9.0 min), novices (65.2 ± 22.3 min), and experts (46.8 ± 19.9 min). Internal consistency was high between the GRS and STS subscores for both direct and video OSATS with Cronbach's α of 0.76 and 0.86, respectively. Video OSATS and operative time in combination was a better predictor of direct OSATS than each single parameter. CONCLUSION: Direct OSATS rating was better than endoscopic video rating for differentiating between students or novices and experts for LC and should remain the standard approach for the discrimination of experience levels. However, in the absence of experts for direct rating, video OSATS supplemented with operative time should be used instead of single parameters for predicting direct OSATS scores.

Laparoscopic Mesh-augmented Hiatoplasty With Cardiophrenicopexy Versus Laparoscopic Nissen Fundoplication for the Treatment of Gastroesophageal Reflux Disease: A Double-center Randomized Controlled Trial.

OBJECTIVE: Laparoscopic mesh-augmented hiatoplasty with cardiophrenicopexy (LMAH-C) might represent an alternative treatment of gastroesophageal reflux disease (GERD) and may provide durable reflux control without fundoplication. The expected benefit is the prevention of fundoplication-related side effects. Aim of the present trial was to compare LMAH-C with laparoscopic Nissen fundoplication (LNF) in patients with GERD. METHODS: In a double-center randomized controlled trial (RCT) patients with proven GERD were eligible and assigned by central randomization to either LMAH-C (n = 46) or LNF (n = 44). The indigestion subscore of the Gastrointestinal Symptom Rating Scale questionnaire (GSRS) indicating gas-related symptoms as possible side effects of LNF was the primary endpoint. Secondary endpoints comprised pH testing and endoscopy and other symptoms measured by the GSRS, dysphagia, and the Gastrointestinal Quality of Life Index. The follow-up period was 36 months. RESULTS: Indigestion subscore (LMAH-C 2.9 ±â€Š1.5 vs LNF 3.7 ±â€Š1.6; P = 0.031) but not dysphagia (2.8 ±â€Š1.9 vs 2.3 ±â€Š1.7; P = 0.302) and quality of life (106.9 ±â€Š25.5 vs 105.8 ±â€Š24.9; P = 0.838) differed between the groups at 36 months postoperatively. Although the reflux subscore improved in both groups, it was worse in LMAH-C patients (2.5 ±â€Š1.6 vs 1.6 ±â€Š1.0; P = 0.004) corresponding to a treatment failure of 77.3% in LMAH-C patients and of 34.1% in LNF patients (P < 0.001). CONCLUSIONS: LNF is more effective in the treatment of GERD than LMAH-C. Procedure-related side effects seem to exist but do not affect the quality of life. Laparoscopic fundoplication therefore remains the standard surgical treatment for GERD.

Surgical versus medical treatment of type 2 diabetes mellitus in nonseverely obese patients: a systematic review and meta-analysis.

OBJECTIVE: To compare surgical versus medical treatment of type 2 diabetes mellitus (T2DM) remission and comorbidities in patients with a body mass index (BMI) less than 35 kg/m2. BACKGROUND: Obesity surgery can achieve remission of T2DM and its comorbidities. Metabolic surgery has been proposed as a treatment option for diabetic patients with BMI less than 35 kg/m2 but the efficacy of metabolic surgery has not been conclusively determined. METHODS: A systematic literature search identified randomized (RCT) and nonrandomized comparative observational clinical studies (OCS) evaluating surgical versus medical T2DM treatment in patients with BMI less than 35 kg/m2. The primary outcome was T2DM remission. Additional analyses comprised glycemic control, BMI, HbA1c level, remission of comorbidities, and safety. Random effects meta-analyses were calculated and presented as weighted odds ratio (OR) or mean difference (MD) with 95% confidence intervals (95% CI). RESULTS: Five RCTs and 6 OCSs (706 total T2DM patients) were included. Follow-up ranged from 12 to 36 months. Metabolic surgery was associated with a higher T2DM remission rate (OR: 14.1, 95% CI: 6.7-29.9, P < 0.001), higher rate of glycemic control (OR: 8.0, 95% CI: 4.2-15.2, P < 0.001) and lower HbA1c level (MD: -1.4%, 95% CI -1.9% to -0.9%, P < 0.001) than medical treatment. BMI (MD: -5.5 kg/m2, 95% CI: -6.7 to -4.3 kg/m2, P < 0.001), rate of arterial hypertension (OR: 0.25, 95% CI: 0.12-0.50, P < 0.001) and dyslipidemia (OR: 0.21, 95% CI: 0.10-0.44, P < 0.001) were lower after surgery. CONCLUSION: Metabolic surgery is superior to medical treatment for short-term remission of T2DM and comorbidities. Further RCTs should address the long-term effects on T2DM complications and mortality.

Stathmin in pancreatic neuroendocrine neoplasms: a marker of proliferation and PI3K signaling.

Chromosome 1p35-36, which encodes tumor suppressors and mitotic checkpoint control genes, is commonly altered in human malignancies. One gene at this locus, stathmin 1 (STMN1), is involved in cell cycle progression and metastasis. We hypothesized that increased STMN1 expression may play a role in pancreatic neuroendocrine neoplasm (pNEN) malignancy. We investigated stathmin copy number variation, mRNA, and protein expression using PCR-Taqman Copy Number Assays, Q-PCR, Western blot, and immunohistochemistry. A mechanistic role for stathmin in proliferation was assessed in the BON cell line under growth-restrictive conditions and siRNA silencing. Furthermore, its role in PI3K signaling pathway activation was evaluated using pharmacological inhibitors. mRNA (p = 0.0001) and protein (p < 0.05) were overexpressed in pNENs. Expression was associated with pNEN tumor extension (p < 0.05), size (p < 0.01), and Ki67 expression (p < 0.01). Serum depletion decreased Ki67 expression (p < 0.01) as well as Ser38 phosphorylation (p < 0.05) in BON cells. STMN1 knockdown (siRNA) decreased proliferation (p < 0.05), and PI3K inhibitors directly inhibited proliferation via stathmin inactivation (dephosphorylation p < 0.01). We identified that stathmin was overexpressed and associated with pathological parameters in pancreatic NENs. We postulate that STMN1 overexpression and phosphorylation result in a loss of cell cycle mitotic checkpoint control and may render tumors amenable to PI3K inhibitory therapy.