Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING: 176 sites in 7 countries. PARTICIPANTS: 1085 insulin-naive adults with T2D. INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION: Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE: Novo Nordisk A/S.

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100.

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10-<15, ≥15-<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.

The role of non-invasive imaging techniques in detecting intra-abdominal adhesions: a systematic review.

BACKGROUND: Intra-abdominal adhesions after surgery are highly prevalent. Adhesions implicate complications during subsequent surgery and can cause chronic abdominal pain. The objective of this review was to investigate the usefulness of non-invasive diagnostic methods for detection of adhesions. METHODS: We searched the electronic databases: MEDLINE, Embase, and The Cochrane Central Register of Controlled Trials for studies investigating the use of non-invasive diagnostic imaging techniques for detecting adhesions. Main outcome was the sensitivity and specificity of each technique. We used the Quality Assessment of Diagnostic Accuracy studies tool to assess bias. RESULTS: In total, 25 studies were included: 18 using ultrasound (US), 5 using magnetic resonance imaging (MRI), 1 using computed tomography (CT), and 1 using both US and MRI. A total of 2195 patients were included. Overall accuracy ranged between 76 and 100% for US studies and between 79 and 90% for MRI and was 66% for CT. Sensitivity ranged between 21 and 100% for US and between 22 and 93% for MRI and was 61% for CT. Specificity was 32-100% for US, 25-93% for MRI, and 63% for CT. Bias analysis revealed that in most studies, investigators were blinded to the reference standard but not to the index test and 11 of 25 studies had a high risk of selection bias. CONCLUSIONS: Currently, abdominal US can be used to determine the presence of adhesions between bowel and the abdominal wall. MRI is also an accurate diagnostic modality and can in addition visualize adhesions between viscera, however, with a tendency to over diagnose adhesions. There is insufficient evidence to support CT as a diagnostic modality for adhesions.

A Comparative Study of Single-Port Laparoscopic Surgery Versus Robotic-Assisted Laparoscopic Surgery for Rectal Cancer.

INTRODUCTION: Conventional laparoscopic surgery is the treatment of choice for many abdominal procedures. To further reduce surgical trauma, new minimal invasive procedures such as single-port laparoscopic surgery (SPLS) and robotic assisted laparoscopic surgery (RALS) have emerged. The aim of this study was to compare the early results of SPLS versus RALS in the treatment of rectal cancer. METHODS: We performed a retrospective analysis of prospectively collected data on patients who had undergone SPLS (n = 36) or RALS (n = 56) in the period between 2010 and 2012. Operative and short-term oncological outcomes were compared. RESULTS: The RALS group had fewer patients with low rectal cancer and more patients with mid-rectal tumors (P = .017) and also a higher rate of intraoperative complications (14.3% vs 0%, P = .021). The rate of postoperative complications did not differ (P = .62). There were no differences in circumferential resection margins, distal resection margins, or completeness of the mesorectal fascia. The RALS group had a larger number of median harvested lymph nodes (27 vs 13, P = .001). The SPLS group had fewer late complications (P = .025). There were no locoregional recurrences in either of the groups. There was no difference in median follow-up time between groups (P = .58). CONCLUSION: Both SPLS and RALS may have a role in rectal surgery. The short-term oncological outcomes were similar, although RALS harvested more lymph nodes than the SPLS procedure. However, SPLS seems to be safer with regard to intraoperative and late postoperative complications.

Influence of intense neuromuscular blockade on surgical conditions during laparotomy: a pig model.

PURPOSE: Intense neuromuscular block may improve surgical conditions in ileus laparotomies; however, it is difficult to evaluate. The aim of this study was to investigate if neuromuscular block improved surgical conditions in pigs with artificial ileus laparotomy. METHODS: Six pigs were endotracheally intubated, mechanically ventilated, anesthetized with propofol and fentanyl, and randomized into two groups in a cross-over assessor-blinded design. Neuromuscular block was established with rocuronium. Artificial laparotomy for ileus was performed. We investigated the influence of intense neuromuscular block on surgical conditions with a subjective rating scale, force needed to close the fascia, incidences of abdominal contractions while suctioning the lungs, width of the wound diastase and operating time as outcome parameters. RESULTS: In all six pigs no abdominal contractions occurred while suctioning the lungs at intense neuromuscular block. Without neuromuscular block we detected abdominal contractions seen as hiccups and bucking. In all six pigs during intense neuromuscular block we found no visible electromyographic (EMG) activity in the abdominal muscles while suctioning the lungs. Without neuromuscular block suctioning the lungs elicited brief periods of abdominal EMG activity. No difference was found in the force needed to close the fascia when comparing no neuromuscular block with intense neuromuscular block. Furthermore, no significant differences were found in the width of the diastase, operating time and subjective ratings using a four-point rating scale when comparing no neuromuscular block with intense neuromuscular block. However, these outcomes were related to the order of the suturing round. CONCLUSION: Intense neuromuscular block prevented abdominal muscle contractions but did not influence the force needed to close the fascia.

No increased risk of perforation during colonoscopy in patients undergoing Nurse Administered Propofol Sedation.

OBJECTIVE: Nurse Administered Propofol Sedation (NAPS) contributes to a deeper sedation of the patients, making them unable to respond to pain and an increased incidence of perforations has been speculated. The objective of this study was to evaluate the risk of perforations during colonoscopies performed with either NAPS or conventional sedation regimes. MATERIAL AND METHODS: Data were retrospectively retracted from medical journals from 1 January 2007 to 31 December 2011. All journals were examined and cross-referenced to reveal any perforations. We analyzed all colonoscopies in regard to nature of the procedure (diagnostic vs therapeutic), experience of the endoscopist and ASA-classification of the patients. RESULTS: A total of 6371 colonoscopies were performed, of which 3155 were performed under propofol sedation. There were 16 perforations (0.25%); 10 of these performed during NAPS and 6 during conventional colonoscopy (p = 0.454, OR: 1.7 (95% CI: 0.6-5.7)). There were 4874 diagnostic and 1497 therapeutic colonoscopies, with a majority of the perforations (94%) occurring during a diagnostic procedure (p = 0.389). No statistically difference was found in the incidence of perforations caused by an experienced or less experienced endoscopist (p = 0.589). CONCLUSION: The risk of colonic perforations during colonoscopy was not found to be significantly higher in patients undergoing NAPS compared to patients undergoing conventional sedation, although a tendency may exist. Furthermore, we found no correlation to neither experience of the endoscopist, nature of the procedure nor sex of the patients. Larger and prospective studies are needed to further evaluate on this subject.

Intraperitoneal instillation of saline and local anesthesia for prevention of shoulder pain after laparoscopic cholecystectomy: a systematic review.

BACKGROUND: The laparoscopic technique has many advantages compared with open surgery for symptomatic cholecystolithiasis. Despite these advantages, many patients complain about shoulder pain (SP) after laparoscopic cholecystectomy. The purpose of this review was to evaluate intraperitoneal instillation (IPI) of saline and local anesthesia (LA) to minimize SP. METHODS: A search of the literature was conducted using PubMed and Excerpta Medica Database (EMBASE). Eligibility criteria were: randomized clinical trials (RCT) evaluating IPI of saline and/or LA to minimize incidence or severity of SP after laparoscopic cholecystectomy. Only papers published in English were included. Data extracted were year of publication, number of participants and allocation, timing of IPI, and nonsignificant or significant effect on incidence or severity of SP. RESULTS: A total of 24 RCTs were included in the review. Four RCTs reported results on IPI saline as intervention versus nothing as control. Seven RCTs reported results on IPI LA as intervention versus nothing as control. Sixteen RCTs reported results on IPI LA as intervention versus saline as control. IPI saline resulted in a significant reduction in SP severity compared with nothing. IPI LA was associated with an overall significant reduction of SP severity compared with nothing. Results regarding the effect IPI LA versus saline showed contradictory results in regards to both SP incidence and severity. CONCLUSIONS: Both IPI of saline and LA can be used to reduce SP severity after laparoscopic cholecystectomy. It is not possible to conclude whether the incidence of SP can be reduced with saline or LA, due to contradictive results.

Surgical techniques to minimize shoulder pain after laparoscopic cholecystectomy. A systematic review.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the treatment of choice for symptomatic cholecystolithiasis. Despite the many advantages over open surgery, many patients complain about referred pain to the shoulder during the postoperative course. The purpose of this review was to evaluate different intraoperative surgical methods to minimize shoulder pain (SP). METHODS: A search of the literature was conducted using PubMed, Excerpta Medica Database (EMBASE), and Cochrane database of systematic reviews. Eligibility criteria were: randomized clinical trials or meta-analysis evaluating intraoperative surgical methods applied to minimize incidence or severity of SP after LC. Only papers published in English were included. Data extracted were year of publication, number of participants and allocation, nonsignificant or significant effect on incidence or severity of SP. RESULTS: A total of 31 papers where included in the review. Seven, 8, and 12 papers investigated the effect of drains, abdominal wall lift (AWL), and low-pressure pneumoperitoneum respectively. Four papers investigated drain suction, active gas aspiration, low insufflation flow or N2O insufflation respectively. The interventions that overall showed a significant reduction on either the incidence or severity of SP were low-pressure pneumoperitoneum, low insufflation rate, and active gas aspiration. CONCLUSIONS: Drainage and AWL are not recommended to reduce SP after LC. Low-pressure pneumoperitoneum with carbon dioxide is the best documented intraoperative surgical method to minimize both the incidence and severity of SP after LC.

Oral chlorhexidine and microbial contamination during endoscopy: possible implications for transgastric surgery. A randomized, clinical trial.

BACKGROUND: One of the biggest concerns associated with transgastric surgery is contamination and risk of intra-abdominal infection with microbes introduced from the access route. The purpose of this study was to evaluate the effect of oral decontamination with chlorhexidine on microbial contamination of the endoscope. METHODS: In a prospective, randomized, single-blinded, clinical trial the effect of chlorhexidine mouth rinse was evaluated. As a surrogate for the risk of intra-abdominal contamination during transgastric surgery, microbial contamination of the endoscope during upper endoscopy was examined. Patients referred to upper endoscopy were assessed for eligibility and randomized to either chlorhexidine or no mouth rinse. Culture samples were collected from gastric aspirates and endoscopes. The primary outcome measure was colony forming units (CFU) in the endoscope samples. Secondary outcome measures were species specific effect of chlorhexidine on micro-organisms with abscess forming capabilities and the effect of proton pump inhibitor (PPI) treatment on CFU. RESULTS: Chlorhexidine mouth rinse resulted in a significant reduction of CFU in the endoscope samples (p = 0.001). There was no species specific effect and micro-organisms with abscess forming capabilities were equally present. PPI treatment was associated with significantly higher CFU counts in both the gastric (p = 0.004) and endoscope samples (p = 0.049). CONCLUSIONS: Chlorhexidine mouth rinse was effective in reducing microbial contamination of the endoscope, but micro-organisms with abscess forming capabilities were still present. PPI treatment significantly increased CFU and should be discontinued before transgastric surgery.

Correlation Between Time in Range and HbA1c in People with Type 2 Diabetes on Basal Insulin: Post Hoc Analysis of the SWITCH PRO Study.

INTRODUCTION: Use of continuous glucose monitoring (CGM) in people with diabetes may provide a more complete picture of glycemic control than glycated hemoglobin (HbA1c) measurements, which do not capture day-to-day fluctuations in blood glucose levels. The randomized, crossover, phase IV SWITCH PRO study assessed time in range (TIR), derived from CGM, following treatment with insulin degludec or insulin glargine U100 in patients with type 2 diabetes at risk for hypoglycemia. This post hoc analysis evaluated the relationship between TIR and HbA1c, following treatment intensification during the SWITCH PRO study. METHODS: Correlation between absolute values for TIR (assessed over 2-week intervals) and HbA1c, at baseline and at the end of maintenance period 1 (M1; week 18) or maintenance period 2 (M2; week 36), were assessed by linear regression and using the Spearman correlation coefficient (rs). These methods were also used to assess correlation between change in TIR and change in HbA1c from baseline to the end of M1, both in the full cohort and in subgroups stratified by baseline median HbA1c (≥ 7.5% [≥ 58.5 mmol/mol] or < 7.5% [< 58.5 mmol/mol]). RESULTS: A total of 419 participants were included in the analysis. A moderate inverse linear correlation was observed between TIR and HbA1c at baseline (rs -0.54), becoming stronger following treatment intensification during maintenance periods M1 (weeks 17-18: rs -0.59) and M2 (weeks 35-36: rs -0.60). Changes in TIR and HbA1c from baseline to end of M1 were also linearly inversely correlated in the full cohort (rs -0.40) and the subgroup with baseline HbA1c ≥ 7.5% (rs -0.43). This was less apparent in the subgroup with baseline HbA1c < 7.5% (rs -0.17) (p-interaction = 0.07). CONCLUSION: Results from this post hoc analysis of data from SWITCH PRO, one of the first large interventional clinical studies to use TIR as the primary outcome, further support TIR as a valid clinical indicator of glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03687827.

Transgastric pure-NOTES peritoneoscopy and endoscopic ultrasonography for staging of gastrointestinal cancers: a survival and feasibility study.

BACKGROUND: Human natural orifice transluminal endoscopic surgery (NOTES) has mainly been based on simultaneous laparoscopic assistance (hybrid NOTES), forgoing the theoretical benefits of the NOTES technique. This is due to a lack of NOTES-specific instruments and endoscopes, making pure-NOTES procedures difficult and time consuming. An area where pure NOTES could be adopted at its present stage of development is minimally invasive staging of gastrointestinal (GI) cancer. The aim of this study is to evaluate the feasibility of combining transgastric (TG) pure-NOTES peritoneoscopy and intraperitoneal endoscopic ultrasonography (ip-EUS) with intraluminal EUS (il-EUS) for peritoneal evaluation. METHODS: This was a feasibility and survival study where il-EUS followed by ip-EUS and peritoneoscopy was performed in 10 pigs subjected to TG pure NOTES. A score was given with regard to achieved visualisation of predefined anatomical structures. Survival was assessed at postoperative day (POD) 14. RESULTS: All animals survived until POD 14. Median total procedural time was 94 min (range 74-130 min). Median time for il-EUS, ip-EUS and peritoneoscopy was 11 min (range 7-14 min), 13 min (range 8-20 min) and 10 min (range 6-23 min). Il-EUS, ip-EUS and peritoneoscopy resulted in a score of 15/15 points (range 14-15 points), 6/9 points (range 1-8 points) and 12/13 points (range 8-13 points). CONCLUSIONS: TG pure-NOTES peritoneoscopy and ip-EUS combined with il-EUS is feasible and provides sufficient peritoneal evaluation. The technique could have potential for minimally invasive staging of GI cancers.

Pure natural orifice transluminal endoscopic surgery (NOTES) with ultrasonography-guided transgastric access and over-the-scope-clip closure: a porcine feasibility and survival study.

BACKGROUND: Most natural orifice transluminal endoscopic surgery (NOTES) procedures to date rely on the hybrid technique with simultaneous laparoscopic access to protect against access-related complications and to achieve adequate triangulation for dissection. This is done at the cost of the potential benefits of this new minimally invasive technique. This study aimed to evaluate the feasibility and safety of a transgastric (TG) pure-NOTES procedure in a diagnostic setting. METHODS: A TG pure-NOTES procedure with endoscopic ultrasonograpy (EUS)-guided access and over-the-scope-clip (OTSC) closure was performed for 10 pigs in a survival and feasibility study. A full macroscopic necropsy with subsequent histologic evaluation was performed on postoperative day (POD) 14. The outcome parameters were uncomplicated follow-up assessment, survival, intraoperative complications, intraabdominal pathology, macroscopic full-thickness closure, and histology-proven full-thickness healing of the gastrotomy. RESULTS: An uncomplicated postoperative course was reported for 9 of the 10 pigs, and survival was reported for all 10 pigs. For all the pigs, EUS-guided access was performed successfully with a median duration of 25 min (range, 12-62 min) and without intraoperative complications or access-related lesions at necropsy. An OTSC closure was achieved with a median duration of 11 min (range, 3-28 min). The OTSC provided immediate closure, but according to the authors' definition of a full-thickness healing evaluated by histologic examination, this was not achieved in any of the cases. Although all the animals survived until POD 14, intraabdominal chronic abscesses were present in 3 of the 10 pigs at necropsy. CONCLUSIONS: The EUS-guided TG access proved to be feasible without access-related complications. Although OTSC provided an immediate closure, the histopathology raised concerns regarding the risk of perforation. Together with the high risk of intraabdominal infection, TG pure-NOTES is not yet ready for routine clinical practice.

[Transvaginal hybrid natural orifice transluminal endoscopic surgery cholecystectomy]. / Hybrid transvaginal natural orifice transluminal endoscopic surgerykolecystektomi.

Natural orifice transluminal endoscopic surgery (NOTES) is a minimally invasive surgical technique where access to the abdominal cavity is achieved through one of the natural orifices of the body. Based on experience from gynaecology, transvaginal access has been the easiest NOTES technique to implement in clinical practice. As was the case with laparoscopy, transvaginal NOTES has primarily been evaluated for cholecystectomy. Although the evidence is limited, the data support a safety profile comparable to that of laparoscopy. As for potential benefits, further research needs to be conducted.

[Detection of a myxofibrosarcoma during surgery for inguinal hernia]. / Fund af myksofibrosarkom under operation for ingvinalhernie.

Myxofibrosarcoma is a sarcoma commonly seen in the extremities of elderly patients. We present a case of a 66-year-old man planned for surgery for inguinal hernia based on a physical examination and ultrasonography. However, no inguinal hernia was found during surgery. Instead, a myxofibrosarcoma was found in the inguinal canal. Myxofibrosarcoma located in the groin has only been reported a few times in the literature. It is discussed how to differentiate between hernia and other pathology in the groin.

Gastrotomy Healing After Transgastric Peritoneoscopy: A Randomized Study in a Pig Model.

INTRODUCTION: Reliable closure and infection prevention are the main barriers for implementation of pure transgastric peritoneoscopy. The primary aim of this study was to assess healing of over the scope clip (OTSC) closed gastrotomies. MATERIALS AND METHODS: Pure transgastric peritoneoscopy was performed in 7 pigs. The pigs were randomized to 14 or 28 postoperative days (POD) of follow-up. Decontamination of the access route was performed before instrumentation. A full necropsy was performed. Closure was evaluated with histopathological examination of excised gastrorrhaphies. RESULTS: Three pigs were allowed 14 POD of follow-up, and 4 pigs were allowed 28 POD of follow-up. Survival was achieved in 6 of the 7 animals; 1 pig was euthanized due to diffuse peritonitis. Based on our definition, full-thickness healing had only been achieved in a single pig allowed 28 POD. With respect to clinical relevancy, full-thickness healing was deemed achieved in 4 of 6 pigs completing follow-up and in all pigs allowed and surviving 28 POD. Access required repeated punctures and the use of several endoscopic instruments. CONCLUSIONS: Full-thickness healing of the gastrotomy was only found in a single case when adhering to the per protocol definition. Endoscopic ultrasonography-guided access was difficult. It lacks reproducibility and needs refinement. Despite a combined decontamination regimen, infectious complications still occurred.

Assessing transgastric Natural Orifice Transluminal Endoscopic Surgery prior to clinical implementation.

The objective was to investigate whether transgastric Natural Orifice Transluminal Endoscopic Surgery (NOTES) could be implemented safely in clinical practice. The experimental studies proved ultrasonography guided access through the stomach to be feasible and safe without iatrogenic complications. Although the technique was safe, further development is needed to increase reproducibility and reduce the procedural time used for gaining access. Closing the gastrotomy after the procedure can be performed easily by application of an endoscopic clip (Over-The-Scope-Clip). Microscopic evaluation of excised gastrorrhaphies revealed that sufficient healing had been achieved after long-term follow-up. A fundamental problem with TG peritoneoscopy is the lack of NOTES specific endoscopes. With the combination of intraluminal EUS and peritoneoscopy with extraluminal EUS, it was possible to achieve sufficient visualisation of anatomical structures of interest in the diagnostics and staging of upper gastrointestinal cancers. Another problem with TG NOTES is the risk of intra-abdominal infections. Using a multimodal decontamination regimen reduced the rate of intra-abdominal pathology, but the risk of intra-abdominal abscess formation as a result of contamination from the access route was still present. To reduce this contamination, mouthwash with chlorhexidine was effective in a human randomised study. The same study also found significant higher bacterial load in the stomach of patients using proton pump inhibitor, emphasising the need to pause PPI prior to future TG interventions. Whether the risk of infectious complications after TG NOTES is comparable between animals and humans is debatable. Despite this, the subject of infectious complications and the safety profile of the TG technique require further research. Based on the evidence available in the literature and current experience, clinical implementation to the benefit of patients does not seem justifiable at present time.

[Natural Orifice Transluminal Endoscopic Surgery--the next step in minimal invasive surgery]. / NOTES-kirurgi er det naeste udviklingstrin inden for minimalt invasiv kirurgi.

Natural Orifice Transluminal Endoscopic Surgery (NOTES) is a recently introduced minimal invasive surgical technique using the natural openings of the human body. The Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) has identified a number of areas that require further investigation before NOTES can be implemented in daily clinical practice. The past years have shown extensive progress within research and development of NOTES, but randomized controlled trials are still lacking. These are essential to determine whether NOTES will benefit patients and the health care sector in general.