Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Hiatus hernia repair with a new-generation biosynthetic mesh: a 4-year single-center experience.

BACKGROUND: Mesh augmentation is a highly controversial adjunct of hiatus hernia (HH) surgery. The current scientific evidence remains unclear and even experts disagree on indications and surgical techniques. With an aim to avoid the downsides of both non-resorbable synthetic and biological materials, biosynthetic long-term resorbable meshes (BSM) have recently been developed and are becoming increasingly popular. In this context, we aimed at assessing outcomes after HH repair with this new generation of mesh at our institution. METHODS: From a prospective database, we identified all consecutive patients that underwent HH repair with BSM augmentation. Data was extracted from electronic patient charts of our hospital information system. Endpoints of this analysis included perioperative morbidity, functional results and recurrence rates at follow-up. RESULTS: Between December 2017 and July 2022, 97 patients (elective primary cases n = 76, redo cases n = 13, emergency cases n = 8) underwent HH with BSM augmentation. Indications in elective and emergency cases were paraesophageal (Type II-IV) HH in 83%, and large Type I HH in 4%. There was no perioperative mortality, and overall (Clavien-Dindo ≥ 2) and severe (Clavien-Dindo ≥ 3b) postoperative morbidity was 15% and 3%, respectively. An outcome without postoperative complications was achieved in 85% of cases (elective primary surgery 88%, redo cases 100%, emergencies cases 25%). After a median (IQR) postoperative follow-up of 12 months, 69 patients (74%) were asymptomatic, 15 (16%) reported improvement, and 9 (10%) had clinical failure, of which 2 patients (2%) required revisional surgery. CONCLUSION: Our data suggest that HH repair with BSM augmentation is feasible and safe with low perioperative morbidity and acceptable postoperative failure rates at early to mid-term follow-up. BSM may be a useful alternative to non-resorbable materials in HH surgery.

Endoscopic vacuum therapy in the upper gastrointestinal tract: when and how to use it.

BACKGROUND: Endoscopic vacuum therapy (EVT) has emerged as a novel treatment option for upper gastrointestinal wall defects. The basic principle of action of EVT entails evacuation of secretions, removal of wound debris, and containment of the defect. Furthermore, there is increasing evidence that EVT reduces interstitial edema, increases oxygen saturation, and promotes tissue granulation and microcirculation. Various devices, such as macroporous polyurethane sponge systems or open-pore film drains, have been developed for specific indications. Depending on the individual situation, EVT devices can be placed in- or outside the intestinal lumen, as a stand-alone procedure, or in combination with surgical, radiological, and other endoscopic interventions. PURPOSE: The aim of this narrative review is to describe the current spectrum of EVT in the upper gastrointestinal tract and to assess and summarize the related scientific literature. CONCLUSIONS: There is growing evidence that the efficacy of EVT for upper GI leakages exceeds that of other interventional treatment modalities such as self-expanding metal stents, clips, or simple drainages. Owing to the promising results and the excellent risk profile, EVT has become the therapy of choice for perforations and anastomotic leakages of the upper gastrointestinal tract in many centers of expertise. In addition, recent clinical research suggests that preemptive use of EVT after high-risk upper gastrointestinal resections may play an important role in reducing postoperative morbidity.

Preemptive Endoluminal Vacuum Therapy to Reduce Morbidity After Minimally Invasive Ivor Lewis Esophagectomy: Including a Novel Grading System for Postoperative Endoscopic Assessment of GI-Anastomoses.

OBJECTIVE: Preemptive endoluminal vacuum therapy (pEVT) is a novel concept to reduce postoperative morbidity and has the potential to disrupt current treatment paradigms for patients undergoing esophagectomy. SUMMARY OF BACKGROUND DATA: Endoluminal vacuum therapy is an accepted treatment for AL after esophagectomy. METHODS: Retrospective analysis of patients undergoing minimally invasive Ivor Lewis esophagectomy with pEVT between 11/2017 and 10/2020. The sponge was removed endoscopically after 4-6 days, and anastomosis and gastric conduit were assessed according to a novel endoscopic grading system. Further management was customized according to endoscopic appearance and clinical course. Endpoints were postoperative morbidity and AL rate, defined according to the Clavien-Dindo (CD) and International Esodata Study Group classifications. RESULTS: PEVT was performed in 67 consecutive patients, 57 (85%) were high-risk patients with an ASA score >2, WHO/ECOG score >1, age >65 years, or BMI >29 kg/m2. Thirty patients experienced textbook outcome, and overall minor (≤CD IIIa) and major (≥CD IIIb) morbidity was 40.3% and 14.9% respectively. 30-day-mortality was 0%. Forty-nine patients (73%) had uneventful anastomotic healing after pEVT without further endoscopic treatment. The remaining 18 patients (27%) underwent prolonged EVT with uneventful anastomotic healing in 13 patients (19%), contained AL in 4 patients (6%), and 1 uncontained leakage (1.5%) in a case with proximal gastric conduit necrosis, resulting in an overall AL rate of 7.5%. CONCLUSIONS: PEVT is an innovative and safe procedure with a promising potential to reduce postoperative morbidity after minimally invasive Ivor Lewis esophagectomy and may be particularly valuable in highly comorbid cases.

Functional syndromes and symptom-orientated aftercare after esophagectomy.

BACKGROUND: Surgery is the cornerstone of esophageal cancer treatment but remains burdened with significant postoperative changes of gastrointestinal function and quality of life. PURPOSE: The aim of this narrative review is to assess and summarize the current knowledge on postoperative functional syndromes and quality of life after esophagectomy for cancer, and to provide orientation for the reader in the challenging field of functional aftercare. CONCLUSIONS: Post-esophagectomy syndromes include various conditions such as dysphagia, reflux, delayed gastric emptying, dumping syndrome, weight loss, and chronic diarrhea. Clinical pictures and individual expressions are highly variable and may be extremely distressing for those affected. Therefore, in addition to a mostly well-coordinated oncological follow-up, we strongly emphasize the need for regular monitoring of physical well-being and gastrointestinal function. The prerequisite for an effective functional aftercare covering the whole spectrum of postoperative syndromes is a comprehensive knowledge of the pathophysiological background. As functional conditions often require a complex diagnostic workup and long-term therapy, close interdisciplinary cooperation with radiologists, gastroenterologists, oncologists, and specialized nutritional counseling is imperative for successful management.

Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel-like-factor-6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data are yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid-X-receptor (FXR) signalling. METHODS: Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analysed in hepatocyte-specific Klf6-knockout mice following bile duct ligation (BDL). Chromatin-immunoprecipitation-assays (ChIP) and KLF6-overexpressing HepG2 cells were used to analyse the interaction of KLF6 and FXR target genes such as NR0B2. RESULTS: Based on IHC, PSC patients could be subdivided into two groups showing either low (<80%) or high (>80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan-Meier analysis. Klf6-knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region. CONCLUSION: Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2.

Strategies to prevent anastomotic leakage after esophagectomy and gastric conduit reconstruction.

BACKGROUND: Surgery remains the cornerstone of esophageal cancer treatment but is burdened with high procedure-related morbidity. Anastomotic leakage as the most important surgical complication after esophagectomy is a key indicator for quality in surgical outcome research. PURPOSE: The aim of this narrative review is to assess and summarize the current knowledge on prevention of anastomotic leakage after esophagectomy and to provide orientation for the reader in this challenging field of surgery. CONCLUSIONS: There are various strategies to reduce postoperative morbidity and to prevent anastomotic leakage after esophagectomy, including adequate patient selection and preparation, and many technical-surgical and anesthesiological details. The scientific evidence regarding those strategies is highly heterogeneous, ranging from expert's recommendations to randomized controlled trials. This review is intended to serve as an empirical guideline to improve the clinical management of patients undergoing esophagectomy with a special focus on anastomotic leakage prevention.

Endoscopic vacuum therapy (EVT) for early infradiaphragmal leakage after bariatric surgery-outcomes of six consecutive cases in a single institution.

PURPOSE: Anastomotic leakages or staple line defects after Roux-en-Y gastric bypass (RYGB) and primary laparoscopic sleeve gastrectomy (LSG), respectively, with consecutive bariatric revisional surgery are associated with relevant morbidity and mortality rates. Endoscopic vacuum therapy (EVT) with or without stent-over-sponge (SOS) has been shown to be a promising therapy in foregut wall defects of various etiologies and may therefore be applied in the treatment of postbariatric leaks. METHODS: We report the results of six consecutive patients treated with EVT (83% in combination with SOS) for early postoperative leakages in close proximity to the esophagogastric junction (EGJ) after LSG (n = 2) and RYGB (n = 4) from May 2016 to May2018. RESULTS: All patients (2/6 male, median age 51 years, median BMI 44.2 kg/m2) were treated successfully without further signs of persisting leakage at the last gastroscopy. The lesions' size ranged from 0.5 cm2 to 9 cm2, and the leaks were connected to large (max. 225 cm2) abscess cavities in 80% of the cases. Median duration of treatment (= EVT in situ) was 23.5 days (range, 7-89). The number of endoscopic interventions ranged from 1 to 24 (median, n = 7), with a median duration between vacuum sponge replacements of 4 days. CONCLUSION: EVT is an effective and safe treatment for staple line defects or anastomotic leakage after bariatric surgeries and can therefore be adopted for the treatment of midgut wall defects. Further studies with a greater number of patients comparing surgical drainage alone or in combination with EVT versus EVT alone are needed.

18FDG-PET-CT identifies histopathological non-responders after neoadjuvant chemotherapy in locally advanced gastric and cardia cancer: cohort study.

BACKGROUND: Pathologic response to neoadjuvant chemotherapy (neoCTX) is a prognostic factor in many cancer types, and early prediction would help to modify treatment. In patients with gastric and esophagogastric junction (AEG) cancer, the accuracy of FDG PET-CT to predict early pathologic response after neoadjuvant chemotherapy (neoCTX) is currently not known. METHODS: From a consecutive cohort of 72 patients, 44 patients with resectable, locally-advanced gastric cancer or AEG Siewert type II and III received neoCTX after primary staging with endoscopic ultrasound, PET-CT and laparoscopy. Overall, 14 patients did not show FDG uptake, and the remaining 30 were restaged by PET-CT 14 days after the first cycle of neoCTX. Metabolic response was defined as decrease of tumor standardized uptake value (SUV) by ≥35%. Major pathologic regression was defined as less than 10% residual tumor cells. RESULTS: Metabolic response after neoCTX was detected in 20/30 (66.7%), and non-response in 10/30 (33.3%) patients. Among metabolic responders, n = 10 (50%) showed major and n = 10 (50%) minor pathologic regression. In non-responders, n = 9 (90%) had minor and 1 (10%) a major pathologic regression. This resulted in a sensitivity of 90.9%, specificity 47.3%, positive predictive value 50%, negative predictive value 90% and accuracy of 63.3%. CONCLUSION: Response PET-CT after the first cycle of neoCTX does not accurately predict overall pathologic response. However, PET-CT reliably detects non-responders, and identifies patients who should either immediately proceed to resection or receive a modified multimodality therapy. TRIAL REGISTRATION: The trial was registered and approved by local ethics committee PB_2016-00769.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial.

Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. Objective: To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. Interventions: Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). Main Outcomes and Measures: The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. Results: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and Relevance: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. Trial Registration: clinicaltrials.gov Identifier: NCT00356213.

The Comprehensive Complication Index (CCI®): Added Value and Clinical Perspectives 3 Years "Down the Line".

OBJECTIVE: To explore the added value of the comprehensive complication index (CCI) to standard assessment of postoperative morbidity, and to clarify potential controversies for its application. BACKGROUND: The CCI was introduced about 3 years ago as a novel metric of postoperative morbidity, integrating in a single formula all complications by severity, ranging from 0 (uneventful course) to 100 (death). It remains unclear, how often the CCI adds to standard reporting of complications and how to apply it in complex postoperative courses. METHODS: CCI data were prospectively collected over a 1-year period at our institution. The proportion of patients with more than 1 complication and the severity of those complications were assessed to determine the additional value of the CCI compared to the Clavien-Dindo classification. Complex and controversial cases were presented to 90 surgeons worldwide to achieve consensus in weighing each postoperative event. Descriptive statistics were used to evaluate agreement among surgeons and to suggest solutions for consistent use of the CCI. RESULTS: Complications were identified in 24% (290/1212) of the general surgical population. Of those, 44% (127/290) developed more than 1 complication by the time of discharge, and thereby CCI added information to the standard grading system of complications. Information gained by the CCI increased with the complexity of surgery and observation time. CONCLUSIONS: The CCI adds information on postoperative morbidity in almost half of the patients developing complications, with particular value following extensive surgery and longer postoperative observation up to 3 months. Each single complication, independently of their inter-connection, should be included in the CCI calculation to best mirror the patients' postoperative morbidity.

Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity-3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS).

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS). METHODS: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ±â€Š11 kg/m, mean age was 43 ±â€Š5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications. RESULTS: Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ±â€Š21.9% vs. 76.6 ±â€Š20.9%, P = 0.139; 2 years: 74.7 ±â€Š29.8% vs. 77.7 ±â€Š30%, P = 0.513; 3 years: 70.9 ±â€Š23.8% vs. 73.8 ±â€Š23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively. CONCLUSIONS: In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB.

Planned secondary wound closure at the circular stapler insertion site after laparoscopic gastric bypass reduces postoperative morbidity, costs, and hospital stay.

PURPOSE: The aims of the present study were to assess whether planned secondary wound closure at the insertion site of the circular stapler reduces wound infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric bypass (RYGB) and to identify independent predictive factors increasing the risk for wound infections after RYGB. METHODS: This paper is a retrospective single-center analysis of a prospectively collected database of 1400 patients undergoing RYGB surgery in circular technique between June 2000 and June 2016. Planned secondary wound closure at the circular stapler introduction site was performed at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a historical control of 1109 (79.2%) consecutive patients with primary wound closure. Independent predictive factors for wound infection were assessed by multivariable analysis. RESULTS: Secondary wound closure significantly decreased wound infection rate from 9.3% (103/1109) to 1% (3/291) (p < 0.001) leading to a shorter hospital stay (mean 9 (SD8) vs. 7 days (SD2), p < 0.001), lower costs (p = 0.039), and reduced postoperative morbidity (mean 90-day Comprehensive Complication Index (CCI) 7.4 (SD14.0) vs. 5.1 (SD11.1) p = 0.008) when compared to primary wound closure. Primary wound closure, dyslipidemia, and preoperative gastritis were independent predictive risk factors for developing wound infections both in the univariate (p < 0.001; p = 0.048; p = 0.003) and multivariable analysis (p < 0.001; p = 0.040; p = 0.012). Further, on multivariable analysis, the female gender was a predictive factor (p = 0.034) for wound infection development. CONCLUSIONS: Secondary wound closure at the circular stapler introduction site in laparoscopic RYGB significantly reduces the overall wound infection rate as well as postoperative morbidity, costs, and hospital stay when compared to primary wound closure.

Rapid and body weight-independent improvement of endothelial and high-density lipoprotein function after Roux-en-Y gastric bypass: role of glucagon-like peptide-1.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces body weight and cardiovascular mortality in morbidly obese patients. Glucagon-like peptide-1 (GLP-1) seems to mediate the metabolic benefits of RYGB partly in a weight loss-independent manner. The present study investigated in rats and patients whether obesity-induced endothelial and high-density lipoprotein (HDL) dysfunction is rapidly improved after RYGB via a GLP-1-dependent mechanism. METHODS AND RESULTS: Eight days after RYGB in diet-induced obese rats, higher plasma levels of bile acids and GLP-1 were associated with improved endothelium-dependent relaxation compared with sham-operated controls fed ad libitum and sham-operated rats that were weight matched to those undergoing RYGB. Compared with the sham-operated rats, RYGB improved nitric oxide (NO) bioavailability resulting from higher endothelial Akt/NO synthase activation, reduced c-Jun amino terminal kinase phosphorylation, and decreased oxidative stress. The protective effects of RYGB were prevented by the GLP-1 receptor antagonist exendin9-39 (10 µg·kg(-1)·h(-1)). Furthermore, in patients and rats, RYGB rapidly reversed HDL dysfunction and restored the endothelium-protective properties of the lipoprotein, including endothelial NO synthase activation, NO production, and anti-inflammatory, antiapoptotic, and antioxidant effects. Finally, RYGB restored HDL-mediated cholesterol efflux capacity. To demonstrate the role of increased GLP-1 signaling, sham-operated control rats were treated for 8 days with the GLP-1 analog liraglutide (0.2 mg/kg twice daily), which restored NO bioavailability and improved endothelium-dependent relaxations and HDL endothelium-protective properties, mimicking the effects of RYGB. CONCLUSIONS: RYGB rapidly reverses obesity-induced endothelial dysfunction and restores the endothelium-protective properties of HDL via a GLP-1-mediated mechanism. The present translational findings in rats and patients unmask novel, weight-independent mechanisms of cardiovascular protection in morbid obesity.

Interleukin-15 receptor α on hepatic stellate cells regulates hepatic fibrogenesis in mice.

BACKGROUND & AIMS: Interleukin-15 (IL-15) and its high affinity receptor interleukin-15 receptor alpha (IL-15Rα) are widely expressed in immune cells and hepatic resident cells. IL-15 signaling has important functions in homeostasis of natural killer (NK), natural killer T (NKT) and cytotoxic T (CD8(+) T) cells, and in liver regeneration. We hypothesized that IL-15 has a protective role in liver fibrosis progression by maintaining NK cell homeostasis. METHODS: Fibrosis was induced using two mechanistically distinct models. Congenic bone marrow transplantation was used to evaluate the contribution of IL-15 signaling from various compartments to NK, CD8(+) T and NKT cell homeostasis and fibrogenesis. The gene expression profile of hepatic stellate cell (HSC) from IL-15Rα knockout (IL-15RαKO) mice and wild-type mice were captured using microarray analysis and validated in isolated HSC. Quantitative real-time PCR was used to assess repressors of collagen transcription. RESULTS: IL-15RαKO mice exhibited more fibrosis in both models. IL-15 signaling from specific types of hepatic cells had divergent roles in maintaining liver NK, CD8(+) T and NKT cells, with a direct and protective role on radio-resistant non-parenchymal cells beyond the control of NK homeostasis. HSCs isolated from IL-15RαKO mice demonstrated upregulation of collagen production. Finally, IL-15RαKO HSC with or without transforming growth factor beta (TGF-ß) stimulation exhibited increased expression of fibrosis markers and decreased collagen transcription repressors expression. CONCLUSIONS: IL-15Rα signaling has a direct anti-fibrotic effect independent of preserving NK homeostasis. These findings establish a rationale to further explore the anti-fibrotic potential of enhancing IL-15 signaling in HSCs. LAY SUMMARY: We investigated how a cellular protein, Interleukin-15 (IL-15), decreases the amount of scar tissue that is formed upon liver injury. We found that IL-15 and its receptor decrease the amount of scar tissue that is created by specialized liver cells (called stellate cells) and increase the number of a specific subgroup of immune cells (natural killer cells) that are known to eliminate stellate cells. TRANSCRIPT PROFILING ACCESSION NUMBER: GSE45612, GSE 68001 and GSE 25097.

Long-term follow-up of lung transplant recipients supports non-operative treatment of uncomplicated diverticulitis.

BACKGROUND: We aim to assess the incidence, current treatment, and outcome of diverticulitis in highly immunosuppressed lung transplant recipients. METHODS: Retrospective analysis of a prospective database of 403 lung transplant recipients transplanted between 1992 and 2013 with a mean follow-up of 100 months (SD 58.0). RESULTS: 4.46% of lung transplant recipients (n=18) developed diverticulitis. Eight lung transplant recipients developed uncomplicated diverticulitis, which were all treated successfully with antibiotics. Three patients (37.5%) underwent elective sigmoid resection with severe Grade 3b complications after two of five (40%) surgical procedures. Diverticulitis recurrence occurred in five patients (60%). In total, 10 lung transplant recipients presented with 11 episodes of perforated diverticulitis with a 30-day mortality rate of 9.1%. Hartmann procedure was performed in eight lung transplant recipients. Sigmoid resection with primary anastomosis and protective ileostomy was performed in three patients with Hinchey I. Two of these patients developed anastomotic leakage with a secondary Hartmann procedure. CONCLUSION: Due to high leakage rate after resection with primary anastomosis and protective ileostomy in our cohort of lung transplant recipients with perforated diverticulitis, the Hartmann procedure seems to be the safer option. In contrast, in uncomplicated diverticulitis, non-operative treatment can be considered as a safe and highly successful treatment option, even for recurrences.

Effects of Art on Surgical Patients: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of the study was to assess the effect of art including ambient features such as music, interior design including visual art, and architectural features on health outcomes in surgical patients. BACKGROUND: Healing environments can have a positive influence on many patients, but data focusing on art in surgical patients remain scarce. METHODS: We conducted a systematic search following the PRISMA guidelines from January 2000 to October 2014 on art in surgical patients. For music interventions, we pooled controlled studies measuring health outcomes (eg, pain, anxiety, blood pressure, and heart rate) in a meta-analysis. For other art forms (ambient and architectural features and interior design), we did a narrative review, also including nonsurgical patients, and looked for examples covering 3 countries. RESULTS: Our search identified 1101 hits with 48 studies focusing on art in surgical patients: 47 studies on musical intervention and 1 on sunlight. The meta-analysis of these studies disclosed significant effects for music on pain after surgery, anxiety, systolic blood pressure, and heart rate, when compared with control groups without music. Effects of music were larger with self-selected music, and lower in surgical interventions performed under general anesthesia. Interior design features such as nature images and more spacious rooms, and architectural features providing more sunlight had positive effects on anxiety and postoperative pain. CONCLUSIONS: Self-selected music for surgical patients is an effective and low-cost intervention to enhance well being and possibly faster recovery. Although potentially very important, the impact of environmental features and spacious architecture with wide access to sunlight remains poorly explored in surgery. Further experimental research is needed to better assess the magnitude of the impact and cost effectiveness.

Lower Rates of Hypocalcemia Following Near-Infrared Autofluorescence Use in Thyroidectomy: A Meta-Analysis of RCTs.

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy. OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy. METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included. RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant. CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

Analysis of different outcome parameters and quality of life after different techniques of free vascularized lymph node transfer.

OBJECTIVE: Vascularized lymph node transfer (VLNT) has become an important surgical technique in the treatment of lymphedema. Considering the different available regions available for flap harvest, we aimed to analyze different donor sites for VLNT with respect to donor-site morbidity, impact on limb volume and patient-reported outcome measurements (PROMs). METHODS: A single-center prospective study on all patients receiving VLNT at the Department of Plastic Surgery and Hand Surgery of the University Hospital Zurich between September 2016 and 2023 was conducted. Lymph nodes were harvested either from the omentum (GE-VLNT), the lateral thoracic wall (LTW) or the superficial inguinal region (SI-VLNT). Volume measurements and PROMs were assessed preoperatively and at different postoperative intervals. RESULTS: Overall, 70 patients with upper limb lymphedema (21%) or lower limb lymphedema (79%) with different lymphedema stages were included. 49 patients received GE-VLNT, followed by LTW-VLNT (n = 16) and SI-VLNT (n = 5). Lymph node harvest from the superficial inguinal region was associated with a significantly higher frequency of seroma development. Average percentage volume loss related in comparison to the preoperative volume of the affected limb was 9% after GE-VLNT, 10% after LTW-VLNT and 5% after SI-VLNT without a significant difference between the groups. PROMs revealed significant improvements for physical functioning, symptoms and psychological well-being, with no difference between VLNT techniques. CONCLUSIONS: VLNT leads to a significant improvement of quality of life and can effectively reduce limb volume, regardless of the selection of donor-site. GE-VLNT has become our flap of choice due to its low donor-site morbidity and its properties that allow a double transplantation while avoiding a second donor-site.