bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperspectral evaluation of liver oxygenation in a murine model of metabolic associated liver disease and hepatocellular carcinoma
Authors: Peloso A , Lacotte S , Moeckli B , Oldani G , Tihy M , Rubbia-Brandt L , Toso C 
Published: June 2022

Abstract

Objective
Untreated MAFLD is a continuum of disease ranging from hepatic steatosis to cirrhosis and hepatocellular carcinoma (HCC). Throughout the disease progression, a change in hepatic hemodynamics occurs as portal hypertension. Hepatic arterial buffer response is a compensatory mechanism to maintain liver perfusion facing reduction of portal flow. These changes could also impair hepatic oxygenation homeostasis. The aim of this study is to test this hypothesis in mouse models and to shed light on the oxygenation of fatty, portal hypertensive liver and its impact on HCC carcinogenesis.

Methods
C57BL/6 mice were fed a HFD starting from 4 weeks of age, porto-systemic shunts (or sham) were created at 8 weeks, and monitored up to 40 weeks. ND-fed non-shunted mice were used as control group. Hyperspectral imaging (HSI) was utilized to quantify tissue oxygenation (StO2) of ND, HFD and HFD-shunted mice. In a second set of experiment, we explored the role of a common hepatic artery ligation in the studied DEN-induced HFD mouse model.

Results
HFD induced hepatic steatosis and portal pressure compared to ND. Porto-systemic shunt could deviate about 67% of the portal flow through the spleen to the systemic circulation, thus reducing portal pressure close-to-normal levels. Compared to control mice, HFD feeding increased liver oxygenation (p=0.0004), while shunting restored a close to normal level (p&lt;0.001). The oxygenation of small bowel is decreased in a similar manner in both HFD and HFD-shunted mice. In HFD-fed mice, artery ligation led to less carcinogenesis compared to mice without artery ligation (p=0.026). In addition, artery ligation was also associated with smaller HCCs (p=0.027).

Conclusion
Early stages of MAFLD alter hepatic oxygen homeostasis. Fatty liver, when associated to portal hypertension, express higher liver oxygenation levels, compared to control group. This could due to hepatocyte ballooning with a narrowing of portal system, thus bring portal hypertension state with a simultaneous arterial buffer response. Additionally, small bowel of portal hypertensive mice showed lower oxygen levels mirroring an intestinal venous congestion typical of portal hypertension. Oxygen deprivation, through artery ligation, decreases HCC carcinogenesis and reduces HCC nodules volume. Yet further research is needed but oxygen homeostasis seems play a role in MAFLD progression as well in HCC pathophysiology.
Primary infection by E. multilocularis induces distinct patterns of hepatic crosstalk between natural killer T and regulatory T cells in mice
Authors: Yarahmadov T , Wang J , Sanchez-Taltavull D , Brodie T , Büchi I , Stroka D , Keogh A , Alvarez C , Beldi G 
Published: June 2022

Abstract

Objective
The larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis (AE) in humans. Recently, opportunistic properties of the disease have been proposed based on the increased incidence in immunocompromised patients as well as on mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, little is known about how the local hepatic immune responses modulate the infection with E. multilocularis.

Methods
In a mouse model of oral infection that mimics the normal infection route in human patients, the adaptive immune response in the liver was assessed using single cell RNA sequencing of isolated hepatic CD3+ T cells at different infection stages.

Results
Single-cell RNA sequencing revealed specific temporal changes of natural killer T (NKT) cells and regulatory T (Treg) cells, indicating that these two cell types expand in the early phase and are subsequently inhibited in the late phase of infection. Receptor-ligand complex analysis via CellPhoneDB, consistently revealed high number of interactions between Tregs and NKT mainly at day 10 post infection. Relevant interactions between NKT and Treg cells at early phases include regulation of cell adhesion molecules such as integrins and selectins and TNF-dependent signalling. Immune suppressing interactions that include the checkpoint inhibitors (PD-1 and PD-L1), purinergic (ENTPD1, ADORA2A) and TGF-beta signalling are down regulated at early time points. String analysis supported these findings.

Conclusion
The data indicate that early interactions between NKT and Tregs potentially promote the formation of hepatic lesions and later also contribute to immunological suppression of the resolution of parasite-induced pathology. The obtained data provide a fresh insight on the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.
Phase Ib dose-escalation study of the hypoxia-modiﬁer myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
Authors: Schneider M , Linecker M , Fritsch R , Mühlematter U , Stocker D , Pestalozzi B , Samaras P , Jetter A , Kron P , Petrowsky H , Nicolau C , Lehn J-M , Humar B , Graf R , Clavien P-A , Limani P 
Published: June 2022

Abstract

Objective
Hypoxia is present in most solid tumors and acts as a driver of malignancy. Myo-inositol trispyrophosphate (ITPP) is a novel re-oxygenating compound without apparent toxicity. In preclinical models, it potentiates the efficacy of subsequent chemotherapy through vascular normalization. We sought to assess the safety, tolerability, and preliminary efficacy of ITPP.

Methods
In this monocentric, open-label, dose-escalation study following a 3+3 design, eligible patients with advanced primary and secondary hepatopancreatobiliary tumors received nine 8-h infusions of ITPP during 3 weeks across eight dose levels (1866–14,500 mg/m2/dose), followed by standard chemotherapy. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics and estimation of efficacy based on radiological responses and angiogenic serum markers. Registration number: NCT02528526.

Results
From April 2015 to July 2018, a total of 28 enrolled patients were assessed for the primary endpoints. ITPP was safe up to single doses of 12,390 mg/m2, and 32 ITPP-related adverse events occurred: 19 (67.8%) hypercalcemia, 5 (17.8%) hyponatremia, and 4 (14.2%) hypomagnesemia. Following ITPP monotherapy, 52% of patients displayed morphological disease stabilization. Following subsequent chemotherapy, 10% showed a partial response, and 60% had stable disease. Angiogenic markers were decreased in 60% after ITPP and tended to correlate with responses and survival after chemotherapy.

Conclusion
Administration of ITPP is safe up to 12,390 mg/m2 with favorable pharmacokinetics. Preliminary translational efficacy data show decreased angiogenic markers, which might indicate an anti-hypoxic effect and enhancement of chemotherapy through ITPP.
Robotic distal pancreatectomy, a novel standard of care? First benchmark values for surgical outcomes from 14 international expert centers
Authors: Müller P , Breuer E , Tschuor C , Saint-Marc O , Keck T , Coratti A , De Oliveira M , Allen P , Giulianotti P , Oberkofler C , Nickel F , Groot Koerkamp B , Martinie J , Yeo C , Hackert T , Petrowsky H , He J , Boggi U , Borel-Rinkes I H , Clavien P-A 
Published: June 2022

Abstract

Objective
Robotic distal pancreatectomy (DP) is emerging as the preferred treatment for body and tail tumors of the pancreas. To enable conclusive comparisons with the standard open or laparoscopic approaches and robotic surgery among centers, novel benchmark outcome values are urgently needed. Therefore, the aim of this study was to identify benchmark values from expert centers beyond the learning curve.

Methods
This multicenter study analyzed outcomes from consecutive patients undergoing robotic DP for resectable malignant or benign lesions from 14 international expert centers. After the learning curve, defined as the first 10 cases of robotic DP, all consecutive patients were included from the start of the program up to June 2020 with a minimum follow-up of 1 year. Benchmark patients were those without significant comorbidities including obesity (BMI &gt;35 kg/m2) cardiac disease, chronic pulmonary disease.
Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers.

Results
After reaching the learning curve, 289 (47%) of a total of 614 consecutive patients qualified as benchmark cases. The proportion of benchmark patients varied between 24%-64% per center. Benchmark cut-offs showed a low 6 month- postoperative mortality (&lt;0.6%), but high overall morbidity (&lt;58.3%). Benchmark cutoffs for operative time (&lt;300 min), conversion rate (&lt;3%), clinically relevant pancreatic fistulas (&lt;26.9%), CCI at 90-days (&lt;14.8), hospital stay (&lt;7 days) and readmission rate (&lt;22.9%). Benchmark cut-offs for complications remained unchanged after 3 months follow-up. For ductal adenocarcinoma benchmark cutoffs for number of lymph nodes were &gt; 19 with an R0 resection rate of &gt; 85%, and an overall survival of &gt;86% and &gt;52% after 1- and 5-years, respectively. Centers with a low cohort of benchmark patients (more difficult cases) had less clinically relevant pancreatic fistula (9% vs. 23%) and less overall complications (32% vs. 48%).

Conclusion
This benchmark analysis sets novel reference values for robotic DP, indicating favorable outcomes as compared to laparoscopic and open DP. These references values may serve for quality control of surgery in centers embarking in robotic DP, and include the procedure in the standard of care.
Compliance to infection-preventing measures in colorectal surgery – a word of caution
Authors: Deslarzes P , Jurt J , Hübner M , Demartines N , Grass F 
Published: June 2022

Abstract

Objective
The success of a colorectal surgical site infection (SSI) preventing bundle is dependent on compliance to individual infection-preventing measures. The present study aimed to assess whether challenging circumstances may affect bundle compliance.

Methods
Retrospective analysis including consecutive patients undergoing colorectal surgery and appendectomy between November 2018 and October 2020, after implementation of an evidence-based SSI-preventing care bundle. Bundle items were antibiotic administration, disinfection, core temperature control, glove change, intra-abdominal lavage and drain placement according to pre-defined standards. Compliance to each item was assessed according to surgical duration, patient age and time of surgery.

Results
Over the study period, 463 patients underwent appendectomy, 458 patients colonic surgery and 98 patients rectal resections. Compliance to intraabdominal lavage standards decreased significantly with surgical duration of colonic resections (88% for surgeries lasting &lt;90 minutes vs. 56% for surgeries lasting &gt; 180 minutes), while similar decreasing compliance patterns were observed regarding intraabdominal drain placement (86% vs. 68%) and core temperature control (64% vs. 57%, all p&gt;0.05) with long lasting procedures. Compliance to antibiotic timing and glove change recommendations was higher in patients undergoing day-time colectomies (08 h and 16 h) compared to patients operated on during night shifts (0h-08 h, 93% vs. 69% and 87% vs. 58%, respectively, both p&lt;0.05). Specific compliance patterns were not observed in patients undergoing appendectomy or rectal surgery. Furthermore, patient age had no impact on bundle compliance.

Conclusion
The present study revealed decreasing compliance to several infection-preventing bundle items with increasing surgical duration and during night shifts. This may contribute to worse outcomes in these challenging settings but may be a point of attention that can be corrected.
A multifactorial intervention to reduce use of antibiotics in acute uncomplicated diverticulitis – a single centre feasibility study
Authors: Galli R , Mitas D , Molteni P , Burri E , Lamm S , Rosenberg R 
Published: June 2022

Abstract

Objective
Standard treatment for uncomplicated diverticulitis in our institution consists of antibiotics. However, current evidence suggests that bacterial infection has a less predominant role than previously thought, and that uncomplicated acute diverticulitis may be a self-limiting condition in which inflammation can be managed without antibiotics. With the support of a multidisciplinary team we developed an intervention in order to reduce the use of antibiotics for patients with uncomplicated diverticular disease.

Methods
Standard practice and knowledge of current evidence were investigated with a structured survey sent to general practitioners and gastroenterologists with private practice in the area. A clinical process model for treatment of uncomplicated left-sided diverticulitis was created and exclusion criteria were selected in order to define patients with a high risk of developing complications. An educational intervention based on current evidence and the new treatment pathway was conducted on hospital staff as well as primary care physicians in the area in order to raise awareness about the possibility of avoiding antibiotics in uncomplicated diverticulitis. Patients were also involved and received an informative sheet about the rationale of the new treatment, the planned follow up and warning signs warranting further investigations and referral in case of outpatient treatment. All patients from May 2021 to December 2021 with a computed tomography-verified left-sided acute uncomplicated diverticulitis were included in the study and evaluated prospectively.

Results
Of 60 patients with acute uncomplicated diverticulitis, 23 (38%) were eligible for treatment without antibiotics. High inflammatory markers on presentation were the main reason (84%) for giving antibiotics. Adherence to the new policy was 74%. None of the 17 patients initially managed without antibiotics failed conservative treatment.

Conclusion
This project confirmed that treatment of uncomplicated diverticulitis without antibiotics can successfully be offered to a selected group of patients without altering the course of the disease. Further efforts are needed in order to overcome existing barriers to rational antimicrobial use such as lack of trust in new guidelines, general uncertainty and risk avoidance, patients’ expectations for antibiotic treatment, and fear of legal consequences.
Swiss pilot low-dose computed tomography lung cancer screening study
Authors: Jungblut L M , Walter J E , Zellweger C , Patella M , Franzen D , Schneiter D , Matter A , Frauenfelder T , Opitz I 
Published: June 2022

Abstract

Objective
Low-dose computed tomography (LDCT) lung cancer screening is endorsed by US guidelines and has recently been shown effective in a large European randomized controlled trial. Nevertheless, actual realization of a lung cancer screening program is challenging and depends on country-specific factors. This pilot study aimed to evaluate implementation, execution, and performance of LDCT lung cancer screening in Switzerland.

Methods
Since October 2018, asymptomatic participants aged 55–74 years with more than 30 pack-years smoking history were enrolled at a tertiary hospital in Switzerland. Participants with history of lung cancer, major (palliative) health problems or those that had a thorax CT scan 18 months prior to enrollment were excluded. First, we evaluated lung cancer risk according to NLST guidelines. Second, we estimated lung cancer risk using the PLCOm2012 model risk calculator with threshold of 5%. Lung nodules were assessed according to Lung-RADS (Version 1.1. 2019). Participants were recruited through flyers, a newspaper article and pulmonary specialists. Screening consisted of one LDCT-scan, follow-up was recommended for suspicious nodules only. LDCT assessment was performed by two radiologists, one of them a board certified chest radiologist. Enrollment and follow-up are currently ongoing.

Results
To date, 75 participants (25 (33%) females) with a median age of 62 years (interquartile range [IQR] 56–67 years) were included. Median number of pack years smoked was 49 (IQR 41–58 pack years). Median PLCOm2012 6-year lung cancer probability was 2.7% (IQR 2.6–2.9%), 19 (26%) participants had stopped smoking before enrollment. 6 participants required follow up imaging of suspect nodules, resulting in a recall rate of 8%. At baseline, lung cancer was found in 2 (2.7%, one squamous cell (stage IIIA) and one adenocarcinoma (stage IV)) participants.

Conclusion
In this Swiss LDCT lung cancer screening pilot study using modified inclusion criteria, 2.7% were diagnosed with lung cancer to date.
Local control and short-term outcomes after VATS segmentectomy vs lobectomy for pT1c pN0 NSCLC (2–3 cm)
Authors: Forster C , Abdelnour-Berchtold E , Bédat B , Perentes J Y , Sauvain M-O , Christodoulou M , Triponez F , Karenovics W , Krueger T , Gonzalez M 
Published: June 2022

Abstract

Objective
Pulmonary segmentectomy has shown comparable oncological results to lobectomy for non-small cell lung cancers (NSCLC) of less than 2 cm. However, controversy remains for tumors of larger size. The aim of this study was to compare short-term outcomes and local control in pT1c pN0 NSCLC that were intentionally treated by VATS segmentectomy or lobectomy.

Methods
Multicenter retrospective study from January 2014 to October 2021 of 162 consecutive patients undergoing complete (R0) anatomical resections for pT1c pN0 NSCLC. Two groups, VATS lobectomy (VL) or VATS segmentectomy (VS) were defined according to the extension of the resection. Patients’ characteristics, postoperative outcomes and survival were compared.

Results
In total, 162 patients underwent VL (n=81) or VS (n=81). Except for age (median of 68 vs 71 years, p=0.034) and past medical history of cancer (32% vs 48%, p=0.038), there was no difference between VL and VS in terms of demographics and comorbidities (table1). Segmentectomies were performed in upper lobes in 68% and single segments represented 46% of all cases. Conversion thoracotomy rate was 5% in both groups. Morbidity were similar in both groups (34% vs 30%, p=0.5). The median time for chest tube removal (3 vs 2 days, p=0.002) and median LOS (6 vs 5 days, p=0.039) were in favor of the VS group. Significantly larger tumor (25 mm vs 23.5 mm p=0.001) and an increased number of lymph nodes removal (median 14 vs 10, p&lt;0.001) were found in the VL group. During the follow-up (median: 31 months), no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.2%) (p=0.414). Overall survival was comparable in-between both groups (p=0.166).

Conclusion
Despite a short follow-up, our preliminary data shows that local control is comparable for VATS lobectomy and VATS segmentectomy. Further prospective randomized trials are needed to corroborate these results.
The Prembion® pre-biotic improves the impact of anti-CTLA4 immune checkpoint inhibitor in a murine model of malignant pleural mesothelioma
Authors: Gattlen C , Chriqui L-E , Hao Y , Gonzalez M , Krueger T , Siankevich S , Dyson P , Cavin S , Perentes J-Y 
Published: June 2022

Abstract

Objective
Immune checkpoint inhibition (ICI) therapy has revolutionized the outcome of certain cancers such as malignant pleural mesothelioma (MPM). However, patient responsiveness to this treatment remains unpredictable. Recently, a role for the gut microbiota composition has emerged for patients to generate a robust immune response against their tumors, following immunotherapy. Here, we studied the impact of Prembion®, a pre-biotic and modulator of the gut microbiota, on tumor control and lymphocyte infiltration in a murine MPM model treated by ICI.

Methods
Prembion® (diluted into drinking water) was administrated to BALBc mice for 14 days. These animals were then inoculated orthotopically with a syngeneic MPM cell line (AB12-luc cells injected in the pleura) and followed by bioluminescence imaging. We determined the tumor growth and mouse survival in different groups: untreated control, Prembion®, IgG control, anti-PDL-1, anti-CTLA4, Prembion®+anti-PDL-1 and Prembion®+anti-CTLA4. A correlation between tumor response/animal survival and MPM infiltration with CD8+ lymphocytes was also performed by immunohistochemistry.

Results
Prembion® was well tolerated and did not affect animal weight or activity. Interestingly, Prembion® was as effective as anti-PDL1 and anti-CTLA4 monotherapy on tumor control, prolonging survival by 4.0 ± 1.1 days compared to controls (p&lt;0.05). Moreover Prembion® potentiated anti-CTLA4 efficacy with a significant improvement in mouse survival of the Prembion®+anti-CTLA4 compared to controls (3.6 ± 1.1 days, p&lt;0.05). Additionally, this finding correlated with enhanced MPM infiltration by CD8+ lymphocytes compared to controls (p&lt;0.05).

Conclusion
Prembion® positively regulated the adaptive immune response against MPM and helped to improve the impact of anti-CTLA4 ICI on MPM. Further work focusing on the gut microbiome changes induced by Prembion® are ongoing to better understand the mechanisms involved.
Minimally invasive plate osteosynthesis for clavicle shaft fractures
Authors: Burkhard M D , Michelitsch C , Stillhard P F , Müller T , Sommer C 
Published: June 2022

Abstract

Objective
Whereas open reduction and internal fixation remains the surgical standard for displaced clavicle shaft fractures, the minimally invasive plate osteosynthesis (MIPO) technique has been introduced for multifragmentary, non-antomically reducible fractures, and unstable fractures with significant soft tissue injuries. Its advantages lie in the preservation of the vascular supply of the fracture zone and the preservation of the supraclavicular nerve. The aim of this study was to prove feasibility and share our experiences with this technique.

Methods
In this single center retrospective case series, we analyzed all patients that underwent MIPO for displaced clavicular shaft fractures from 2001–2021. Patient history, fracture morphology and perioperative data were documented. Outcomes were assessed based on clinical and radiographic follow-up reports.

Results
In total, 1128 clavicle osteosyntheses were performed, of which 908 (80.5%) were treated with a plate and 220 (19.5%) with titanium elastic nail (TEN). Of the 908 plate osteosyntheses, 43 (4.7%) were performed with the MIPO approach. Mean age was 44 ± 15 years, 83.3% were males and 79.1% were sports injuries. The fractures were categorized as AO/OTA type C injuries (n=26) in most patients, followed by A (n=9) and B (n=8). Two open (Gustilo I) and 41 closed fractures were noted (Tscherne 0=26; I=13, II=2). In seven patients (16.7%), the clavicle fractures were part of a severe polytrauma. Concomitant serial rib fractures and scapular fractures were found in 19 (45.2%) and 10 patients (23.8%), respectively. Length of surgery was 63 ± 28 min, and hospitalization was 4 ± 3 days (excl. polytraumas). 27 of the 43 fractures (62.8%) were clinically and radiographically followed up in our outpatient clinic, of which 26 (96.3%) healed with noticeable callus formation. In one case, a pseudoarthrosis was found two years after fracture treatment. Otherwise, all patients followed a remarkable postoperative course, were pain-free and able to return to work, most within five weeks.

Conclusion
In this retrospective analysis, 96.3% of the clavicle shaft fractures treated with MIPO healed in a timely manner. The MIPO technique is feasible and plausibly advantageous for distinct fracture and injury patterns (i.e. multifragmentary fractures or unstable fractures with soft tissue injuries). Future comparative studies are warranted to clarify our observations.