bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative stable states and hydrological regime shifts in a large intermittent river
Authors: Zipper Sam , Popescu Ilinca , Compare Kyle , Zhang Chi , Seybold Erin C
Published: June 2022

Non-perennial rivers and streams make up over half the global river network and are becoming more widespread. Transitions from perennial to non-perennial flow are a threshold-type change that can lead to alternative stable states in aquatic ecosystems, but it is unknown whether streamflow itself is stable in either wet (flowing) or dry (no-flow) conditions. Here, we investigated drivers and feedbacks associated with regime shifts between wet and dry conditions in an intermittent reach of the Arkansas River (USA) over the past 23 years. Multiple lines of evidence suggested that these regimes represent alternative stable states, including (a) significant jumps in discharge time series that were not accompanied by jumps in flow drivers such as precipitation and groundwater pumping; (b) a multi-modal state distribution with 92% of months experiencing no-flow conditions for <10% or >90% of days, despite unimodal distributions of precipitation and pumping; and (c) a hysteretic relationship between climate and flow state. Groundwater levels appear to be the primary control over the hydrological regime, as groundwater levels in the alluvial aquifer were higher than the stream stage during wet regimes and lower than the streambed during dry regimes. Groundwater level variation, in turn, was driven by processes occurring at both the regional scale (surface water inflows from upstream, groundwater pumping) and the reach scale (stream–aquifer exchange, diffuse recharge through the soil column). Historical regime shifts were associated with diverse pressures including network disconnection caused by upstream water use, increased flow stability potentially associated with reservoir operations, and anomalous wet and dry climate conditions. In sum, stabilizing feedbacks among upstream inflows, stream–aquifer interactions, climate, vegetation, and pumping appear to create alternative wet and dry stable states at this site. These stabilizing feedbacks suggest that widespread observed shifts from perennial to non-perennial flow will be difficult to reverse.
Recovery of Sobolev functions restricted to iid sampling
Authors: Krieg David , Novak Erich , Sonnleitner Mathias
Published: June 2022

We studyLqL_q-approximation and integration for functions from the Sobolev spaceWps(Ω)W^s_p(\Omega )and compare optimal randomized (Monte Carlo) algorithms with algorithms that can only use identically distributed (iid) sample points, uniformly distributed on the domain. The main result is that we obtain the same optimal rate of convergence if we restrict to iid sampling, a common assumption in learning and uncertainty quantification. The only exception is whenp=q=∞p=q=\infty, where a logarithmic loss cannot be avoided.
Symplectic structures with non-isomorphic primitive cohomology on open 4-manifolds
Authors: Gibson Matthew , Tseng Li-Sheng , Vidussi Stefano
Published: June 2022

We analyze four-dimensional symplectic manifolds of type

X
=

S
1

×

M
3

X=S^1 \times M^3

where

M
3

M^3

is an open

3
3

-manifold admitting inequivalent fibrations leading to inequivalent symplectic structures on

X
X

. For the case where

M
3

⊂

S
3

M^3 \subset S^3

is the complement of a

4
4

-component link constructed by McMullen-Taubes, we provide a general algorithm for computing the monodromy of the fibrations explicitly. We use this algorithm to show that certain inequivalent symplectic structures are distinguished by the dimensions of the primitive cohomologies of differential forms on

X
X

. We also calculate the primitive cohomologies on

X
X

for a class of open

3
3

-manifolds that are complements of a family of fibered graph links in

S
3

S^3

. In this case, we show that there exist pairs of symplectic forms on

X
X

, arising from either equivalent or inequivalent pairs of fibrations on the link complement, that have different dimensions of the primitive cohomologies.
Alien invasiveLeucaena leucocephalasuccessfully acquires nutrients by investing in below-ground biomass compared to nativeVachellia niloticain nutrient-amended soils in South Africa
Authors: Ndabankulu Khululwa , Tsvuura Zivanai , Magadlela Anathi
Published: June 2022

Soils in grasslands and savannas of southern Africa are acidic and nutrient-poor. Legume plants, such as Vachellia nilotica and alien invasive Leucaena leucocephala, are a major component of the vegetation there. Vachellia nilotica can establish in drought-prone environments, and is invasive in high rainfall areas. Leucaena leucocephala is an emerging invasive in South Africa and is ranked among the world’s 100 most invasive alien species. Alien plants can invade native habitats through their adaptability to low-resource soils, and thus can out-compete and displace native vegetation. We investigated the effects of phosphorus (P) deficiency and soil acidity on legume–microbe symbiosis, nitrogen (N) nutrition and carbon (C) growth costs of these two legumes in grassland soils. We used as inoculum and growth substrate soils collected from a long-term (>65 years) nutrient and lime-addition trial, the Veld Fertilizer Trial (VFT), located at Ukulinga Research Farm near Pietermaritzburg in South Africa. We used soils from three VFT treatments: soils fertilized with superphosphate (336 kg ha−1) applied once per year (+P), soils fertilized with superphosphate (336 kg ha−1) applied once per year with dolomitic lime (2250 kg ha−1) applied once every 5 years (P+L) and soils with no superphosphate and no dolomitic lime applications (Control). Seeds of V. nilotica and L. leucocephala were germinated and grown independently in these soils in green house conditions and harvested after 125 days for measurement of growth, legume–microbe symbiosis, N nutrition and C growth costs. Results showed that the two legumes had different growth adaptations. Vachellia nilotica grown in control soils and +P soils nodulated with various Burkholderia spp., while L. leucocephala did not nodulate in all soil treatments. Both legumes utilized for growth both atmospheric- and soil-derived N across all treatments thereby decreasing C growth costs. Vachellia nilotica grown in +P soils accumulated the most biomass and N nutrition. Leucaena leucocephala maximized specific N assimilation rates by investing in below-ground biomass accumulation in control soils. This shows that L. leucocephala possesses traits that are successful in acquiring nutrients by investing in below-ground biomass and relying on utilization of N from both the soil and the atmosphere.
Design, synthesis, and biological activity of a synthetically accessible analog of aplysiatoxin with an (R)-(−)-carvone-based conformation-controlling unit
Authors: Suzuki Yoshiyuki , Moritoki Keiichi , Kajiwara Mizuki , Yanagita Ryo C , Kawanami Yasuhiro , Hanaki Yusuke , Irie Kazuhiro
Published: June 2022

Simplified analogs of aplysiatoxin (ATX) such as 10-Me-aplog-1 exhibit potent antiproliferative activity toward human cancer cell lines by activating protein kinase C (PKC). However, the synthesis of 10-Me-aplog-1 involved a 23-step longest linear sequence (LLS). Therefore, we have been working toward the development of a more synthetically accessible analog of ATX. In this study, we designed a new analog of ATX wherein a cyclic ketal moiety derived from (R)-(−)-carvone replaced the spiroketal moiety in 18-deoxy-aplog-1. The new analog's synthesis proceeded in an eight-step LLS. Although the configuration at position 3 of the cyclic ketal in the (R)-(−)-carvone-based analog was opposite to those of ATX and 18-deoxy-aplog-1, the antiproliferative activity toward human cancer cell lines of the carvone-based analog was comparable to that of 18-deoxy-aplog-1. The obtained results indicate the potential of the carvone-based analog as a basis for discovering PKC-targeting molecules requiring a decreased number of synthetic steps.
COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning
Authors: Huffman Anthony , Ong Edison , Hur Junguk , D’Mello Adonis , Tettelin Hervé , He Yongqun
Published: June 2022

Rational vaccine design, especially vaccine antigen identification and optimization, is critical to successful and efficient vaccine development against various infectious diseases including coronavirus disease 2019 (COVID-19). In general, computational vaccine design includes three major stages: (i) identification and annotation of experimentally verified gold standard protective antigens through literature mining, (ii) rational vaccine design using reverse vaccinology (RV) and structural vaccinology (SV) and (iii) post-licensure vaccine success and adverse event surveillance and its usage for vaccine design. Protegen is a database of experimentally verified protective antigens, which can be used as gold standard data for rational vaccine design. RV predicts protective antigen targets primarily from genome sequence analysis. SV refines antigens through structural engineering. Recently, RV and SV approaches, with the support of various machine learning methods, have been applied to COVID-19 vaccine design. The analysis of post-licensure vaccine adverse event report data also provides valuable results in terms of vaccine safety and how vaccines should be used or paused. Ontology standardizes and incorporates heterogeneous data and knowledge in a human- and computer-interpretable manner, further supporting machine learning and vaccine design. Future directions on rational vaccine design are discussed.
Endoscopic surveillance after bariatric surgery: Results from a large, single-institution cohort
Authors: Lazaridis I , Kraljevic M , Thomas K , Gätzi D , Stöcklin P , Zingg U , Delko T
Published: June 2022

Objective

Sleeve gastrectomy (SG) and Roux-en-Y-gastric bypass (RYGB) are associated with long- term abnormalities, including erosive esophagitis (EE), hiatal hernia (HH), gastritis, Barrett`s esophagus and ulcers. The aim of this study is to assess the prevalence of abnormal endoscopic and histologic findings after SG and RYGB in a large cohort.

Methods

This is a retrospective analysis of 720 consecutive patients who underwent esophagogastroduodenoscopy (EGD) after primary SG or RYGB. Patients were invited for a control EGD after two years of follow-up. EGD was also performed in order to evaluate postoperative symptoms, such as nausea, vomiting or reflux. If revisional surgery was planned, an EGD was included in the prerevisional work up.

Results

304 post-SG patients (64.1% female) and 416 post-RYGB patients (85% female) were included. The mean age at the time of operation was 43.9 years (95% confidence intervals (CI) 42.5–43.3 years) for the post-SG group and 40.5 years (95% CI 39.4–41.6 years) for the post-RYGB group (p<0.001). The mean preoperative body mass index (BMI) was 44.2 kg/m2 (95%CI 43.4–44.9) and 41.1 kg/m2 (95%CI 40.7–41.5) for the post-SG and the post-RYGB group respectively (p<0.001). EE, gastritis and HH were more prevalent after SG than RYGB (38.8% vs 8.9%, 62.5% vs 27.6% and 28% vs 2.6% respectively, p<0.001). RYGB was associated with more postoperative ulcers than SG (14.4% vs 0.7%, p<0.001). The incidence of anastomotic strictures requiring anastomotic dilatation after RYGB was 4.6%. No significant difference was found in the prevalence of Barrett`s esophagus (4.3% post SG vs. 4.1 post RYGB, p=1.000) and Helicobacter pylori (3.3% post SG vs. 1.2% post RYGB, p=0.065) between the two groups.

Conclusion

SG is associated with higher rates of EE, gastritis and HH, while the prevalence of ulcers is higher post RYGB. There is a low risk of anastomotic stricture post RYGB. The incidence of Barrett`s oesophagus is low after both procedures. Routine use of EGD after bariatric surgery should be evaluated.
Long-term quality of life after gastric band removal and concomitant conversion to gastric bypass: A single center cohort study
Authors: Pfister M , Teuben M P J , Teuber H , Nocito A , Probst P , Müller M K
Published: June 2022

Objective

To report long-term quality of life and determine predictors for improved quality of life after gastric band removal and concomitant conversion to Roux-en-Y gastric bypass.

Methods

Clinical data of all patients who underwent conversion surgery from 2011 to 2017 were extracted from a prospectively maintained bariatric database and retrospectively analysed. During scheduled follow-up visits at 1, 6, 12, 24, 36, 48, and 60 months after surgery, physical and laboratory data as well as quality of life questionnaires were obtained. The primary outcome was change in postoperative Moorehead-Ardelt Quality of Life Questionnaire II Score (Moorehead Score). Secondary outcomes included common efficacy and safety outcomes utilized in bariatric surgery. Mixed ANOVA analysis, Chi Square test and Fisher's exact test were used.

Results

Overall, 108 patients who underwent conversion surgery were included. Mean duration of banding until conversion was 11.3 ± 4.3 years. The reason for conversion surgery was band failure in 45.4% (n=49) and band intolerance in 33.3% (n=36) of patients. In the remaining 21.3% (n=23) of cases a combination of both failure and intolerance was present. Mean follow-up time was 53 months. Postoperative mean Moorehead Score increased significantly after one (1.6 ± 0.9, p<0.01) and after five years (1.6 ± 0.8, p<0.01) compared to baseline values (0.7 ± 1.1). Mixed ANOVA analysis showed a significantly superior increase in Moorehead Score in males (p=0.024). No other significant predictors were identified. Neither the reason for conversion, nor preoperative parameters or long-term postoperative outcome parameters including postoperative weight loss or safety outcomes significantly affected postoperative quality of life improvement. Lasting BMI reduction (-4.6 kg/m2, p<0.01) to 33.0 ± 6.7 kg/m2 and weight loss (-12.9%, p<0.01) five years after conversion surgery were present. Internal hernia was the most common early postoperative complication, occurring in 14.8% (n=16) of cases.

Conclusion

Band removal with concomitant gastric bypass in patients with failed gastric banding improves long-term quality of life and may be the rescue procedure of choice in this setting.
Does the change from conventional circular to linear stapling in proximal gastric bypass surgery affect long-term quality of life?
Authors: Teixeira H , Teuben M P J , Teuber H , Hauswirth F , Probst P , Müller M K
Published: June 2022

Objective

The continuous desire to improve bariatric surgery outcomes, and therefore patient satisfaction, leads to a constant search for new surgical approaches. Every change in a well-established protocol needs to undergo evaluation and its benefit for patients must be demonstrated. With respect to technical changes in bariatric surgery, long-term effects on quality of life have not yet been studied. We analyzed quality of life scores and clinical outcomes at a single bariatric center transitioning from circular to a linear bypass protocol.

Methods

Between June 2012 and March 2016, 235 patients were included in this retrospective study from a prospectively collected database. Two groups were compared. Group CBP included those patients treated with a circular stapling bypass protocol (n=117). This protocol was primarily used in 2012. Between 2013 and 2015 a transition period occurred. Thereafter, the linear stapling bypass protocol (Group LBP, n=118) was primarily utilized. Quality of life (QoL) was assessed with the Moorehead-Ardelt QoL score, which was gathered preoperatively, and at 1, 2, and 5 years after surgery.

Results

Quality of life scores improved significantly after intervention in both study groups. The most prominent improvement was seen within the first year after surgery. There were no statistically significant differences between the groups. During the first two years, quality of life score improvement occurred independently of achieved weight loss, whereas a correlation between QoL-improvement and reported weight loss was identified between 24 and 60 months postoperatively (r2 0.112, p<0.001). Further, complications had no impact on change in QoL scores.

Conclusion

Quality of life scores assessed by the Moorehead-Ardelt QoL questionnaire were, independent of operative technique and postoperative weight loss, significantly improved in the first two years after gastric bypass surgery. Thereafter, QoL scores showed lasting improvement in correlation with further weight loss.
Comparison of single- versus double-anastomosis duodenal switch: A single-center experience with 2-year follow-up
Authors: Iranmanesh P , Boudreau V , Gmora S , Hong D , Anvari M
Published: June 2022

Objective

Single-anastomosis duodenal switch (SADS) has emerged in recent years as an alternative to the standard double-anastomosis duodenal switch (DADS). The objective of this study was to compare short- and medium-term outcomes between SADS and DADS.

Methods

Data collected in the Ontario Bariatric Registry between 2010 and 2019 were used for this retrospective study to determine outcomes of patients undergoing primary laparoscopic SADS versus DADS at a Canadian tertiary hospital and bariatric center of excellence. The primary outcome was weight loss at 1 and 2 years after surgery. Short-term secondary outcomes included operative times, intra- and early postoperative complications, hospital length of stay (LOS), and 30-day readmissions. Medium-term secondary outcomes included late postoperative complications as well as nutritional deficiencies and persistent diarrhea at 1 and 2 years after surgery. Subgroup analyses were performed to compare patients undergoing one- and two-stage procedures.

Results

Data of 107 patients who underwent SADS (n = 25) or DADS (n = 82) were included in the study. Follow-up data were available for 59/107 (55.1%) patients at 1 year and 47/107 (43.9%) at 2 years after surgery. Patients in the SADS and DADS groups had similar %TBWL at 1 year (23.6 versus 26.2, P = 0.617) and 2 years (24.8 versus 30.2, P = 0.116) after surgery. Short- and medium-term outcomes were similar between groups. There was no difference between patients undergoing one- versus two-stage procedures.

Conclusion

This study showed that patients undergoing SADS and DADS had similar weight loss at 1 and 2 years. Early and late postoperative morbidity, operative times, early readmissions, and LOS were also similar between groups. Further studies with longer follow-up are required to confirm these results.
Long-term outcomes of ruptured hepatocellular carcinoma: An international multicentric propensity score-matched study
Authors: Joliat G-R , de Man R , Rijckborst V , Cimino M , Torzilli G , Choi G H , Lee H S , Goh B , Kokudo T , Shirata C , Hasegawa K , Nishioka Y , Vauthey J-N , Baimas-George M , Vrochides D , Demartines N , Halkic N , Labgaa I
Published: June 2022

Objective

Long-term outcomes of patients with ruptured hepatocellular carcinoma (rHCC) remain scant. This study aimed to assess disease-free survival (DFS) and overall survival (OS) after surgical resection of rHCC compared to non-ruptured HCC (nrHCC).

Methods

Patients with rHCC and nrHCC were collected from 8 centers in Europe, Asia, and North America. Resected rHCC patients were matched 1:1 to patients undergoing surgery for nrHCC using propensity score and nearest-neighbor method (matching criteria: age, tumor size, cirrhosis, Child-Pugh score, Barcelona Clinic Liver Cancer stage, resection status, grade, and microvascular invasion). Survival rates were calculated using Kaplan-Meier method.

Results

A total of 2033 patients were included: 226 rHCC patients (172 operated: 68 with upfront surgery and 104 after embolization) and 1807 nrHCC patients. Median DFS and OS of rHCC patients (all treatments confounded) were 10 months (95% CI 7–13) and 22 months (95% CI 13–31). Prognostic factors for worse OS among rHCC patients were absence of preoperative arterial embolization (HR 2.3, 95% CI 1.2–4.6, p=0.016), cirrhosis Child B/C (HR 2.4, 95% CI 1.1–5.4, p=0.040), and R1/R2 margins (HR 2, 95% CI 1–5, p=0.049). Survivals were similar between Western and Eastern rHCC patients.

After propensity score matching, 106 rHCC patients and 106 nrHCC patients displayed similar characteristics. Patients with rHCC had shorter median DFS (12 months, 95% CI 7–17 vs. 22 months, 95% CI 12–32, p=0.011), but similar median OS compared to nrHCC patients (43 months, 95% CI 21–65 vs. 63 months, 95% CI 21–105, p=0.060).

Conclusion

In this large dataset including Eastern and Western patients, rHCC was associated with shorter DFS compared to nrHCC, while OS was similar.
Inhibition of SUMOylation modulates the immunosuppressive microenvironment of pancreatic cancer
Authors: Erdem S , Narayanan J S , Mohottige Don N , Worni M , White R R , Chen Y
Published: June 2022

Objective

Pancreatic cancer (PC) is a highly aggressive disease that is poorly responsive to available immunotherapy approaches, such as checkpoint inhibitors. Post-translational protein modification (PTM) by small ubiquitin-like modifier (SUMO) is upregulated in cancer, and high expression of SUMOylation-related factors correlates with poor survival in PC. TAK-981 is a novel inhibitor of SUMOylation that has demonstrated induction of anti-tumor immune responses in preclinical models. Our hypothesis is that TAK-981 will decrease SUMOylated proteins and subsequently modulate the tumor microenvironment to increase anti-tumor immunity.

Methods

In order to recapitulate the microenvironment of human PC, a 3-dimensional organoid cell line derived from a genetically-engineered “KPC” mouse was used. Organoids were injected orthotopically into the head of the pancreas via laparotomy. Once tumors reached 5–7 mm in diameter on ultrasound imaging, mice were randomized to one of two treatment groups: Control/Vehicle versus TAK-981 (15 mg/kg) delivered daily via intraperitoneal injection. Tumors were harvested on day 14 for gene expression analysis by quantitative real time PCR (RT-qPCR).

Results

Tumor growth (Fig. 1) in the TAK-981 15 mg/KG daily group (mean + SD volume = 207 + 109 mm3) was significantly inhibited compared to the vehicle group (595 + 141 mm3, p < 0.01). Immunohistochemical staining for CD 31 (Fig. 2) and Caspase 3 indicated a reduction of angiogenesis and increased apoptosis of tumor cells, consistent with the well-established roles of SUMOylation in angiogenesis and tumorigenesis. Gene expression analysis of tumor lysates showed a 26-fold increase in expression of Interferon beta (p<0.05), and an almost 2-fold increase in expression of genes related to dendritic cell activation, including CD80 (p<0.05) and CD86 (p=0.14) in the TAK-981 group, suggesting a modulation of the immune microenvironment.

Conclusion

Our results suggest that the inhibition of SUMOylation with TAK-981 is associated with improved local tumor control and changes in the immunosuppressive tumor microenvironment. We expect that TAK-981 will improve PC responsiveness to immunotherapy, such as with checkpoint inhibitors.
Systematic review on the use and management of drainages in pancreatic surgery
Authors: Pietrogiovanna L , Canovi S , Probst P , Hauswirth F , Müller M K , Renzulli P
Published: June 2022

Objective

The use of drains in pancreatic surgery, both in distal pancreatectomy (DP) and partial pancreaticoduodenectomy (PD) is controversial. The aim of this meta-analysis was to assess the potential benefit of drainage use in pancreatic surgery on postoperative outcomes.

Methods

A systematic literature search was performed in MEDLINE, Web of Science and CENTRAL. All RCTs investigating the use and management of any drainage in patients undergoing pancreatectomy were included. Data on mortality, postoperative complications and length of hospital stay (LOS) were analysed. A random-effects model for Mantel-Haenzsel and inverse variance analysis was used. Cochrane RoB 2.0 tool and GRADE approach was used for assessment of risk of bias and certainty of evidence.

Results

Ten RCTs investigating drainage vs no drainage, timing of drainage removal or type of drainage in PD such as DP with a total of 2004 patients were included. Drainage vs no drainage: Three RCTs (two with PD and DP, one with PD only). Neither mortality (OR 1.57, 95%-CI: 0.62 to 3.93 p=0.34) nor overall complications (OR 0.88, 95%-CI: 0.71 to 1.08, p=0.21) differed between both groups (certainty of evidence: low). However, one trial was stopped prematurely because of higher 90-day mortality in the no drainage group. Early vs late drainage removal: Four RCTs (two with PD and DP, two with PD only). Early drain removal resulted in both a significant reduction of chyle leak (OR 0.22, 95%-CI: 0.06 to 0.59, p<0.01) as well as a shortening of LOS (mean difference -2.64 days, 95%CI: -4.63 to -0.65, p<0.01). For both outcomes the certainty of evidence was moderate. Mortality, postoperative pancreatic fistula and hemorrhage showed no difference between early vs late drainage removal (certainty of evidence: low). Active vs passive drainage: Three RCTs (one with PD and DP, two with PD only). None of the studies found any significant difference in outcome with regard to the type of drainage.

Conclusion

There is no evidence that drainages after pancreatic surgery should be standard of care. However, there is also no evidence that placing a drain leads to worse outcomes. If a drainage is used it should be removed early to avoid chyle leak and accelerate hospital discharge.
Prevention and management of anastomotic leakage after colorectal surgery: A Swiss national consensus
Authors: Lázaro-Fontanet E , Clerc D , Girardin T , Martin D , Hübner M , Hahnloser D
Published: June 2022

Objective

Anastomotic leakage (AL) is one of the most feared complications of colorectal surgery. Despite surgical improvements, AL incidence remains significant and guidance on its prevention and management is lacking. The aim of the study was to achieve a Swiss nationwide consensus on clinical prevention and management of AL.

Methods

A three-step Delphi consensus meeting was performed in 2020 involving 78 Swiss surgeons from 40 centers. A steering-group drafted the questions, gathered best available evidence which was discussed in meetings prior answering the questions. Consensus was defined as ≥70% of agreement.

Results

The three consensus meetings were attended by 66, 57 and 37 surgeons, respectively. Surgeons’ median experience was 14 years, with 47% performing >50 colorectal resections yearly. Consensus was reached on routine use of preoperative nutritional screening (100%) using nutritional scores (88%) and >10% weight loss (95%). but not low BMI (63%) or low albumin (64%). Consensus was reached for no bowel preparation (BP) prior to right colectomy (RC) (76%) and for mechanical BP with oral antibiotics prior anterior resections (AR) (70%). No consensus was found on BP prior left colectomy (LC). Respondents favored a side-to-side anastomosis (76%) after RC, with extra-corporeal confection (70%), without consensus on the anastomosis being stapled or hand-sewn; an end-to-end (73%), stapled (80%) anastomosis after LC and a stapled anastomosis (86%) after AR, irrespective of the anastomosis configuration type. Anastomotic control with transanal leak-test was supported by 92%, while ICG control did not reached consensus (67%). After TME, routine diversion was favored (73%), irrespective of neoadjuvant therapy (94%) or not (70%). Consensus was reached on routine postoperative CRP monitoring (94%). CT-scan with rectal contrast enema was the preferred investigation for suspected AL after RC or LC (82%) and AR (76%). Conservative management of AL, provided appropriate clinical state, was an acceptable option after LC (72%), AR with stoma (95%), but not after RC (59%) or AR without stoma (53%).

Conclusion

Consensus was reached on several clinical aspects for prevention and management of AL among Swiss colorectal surgeons, providing national guidance. Further data is required on intraoperative aspects of anastomosis confection and control to ensure broader consensus.
Combined expression of fascin-1 and MAP17 in colorectal cancer: A group of patients in high risk
Authors: Tampaki E C , Nonni A , von Flüe M , Felekouras E , Nikiteas N , Tampakis A
Published: June 2022

Objective

Fascin and MAP17 are two well-known stem cell markers that have been previously shown to be associated with aggresive clinical features in cancer. This study aimed to assess their expression patterns and clinical significance in colorectal cancer.

Methods

Immunohistochemistry was used to assess the expression of fascin-1 and MAP17 in 111 specimens from patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data.

Results

Fascin-1 and MAP17 expression levels were associated with progressive anatomic disease extent (p=0.005), higher T classification (p=0.033), lymph node metastasis (p=0.002), high grade tumors (p=0.002), and vascular invasion (p=0.021). All patients with combined high fascin-1 and MAP17 expression died within 46 months after surgery, whereas patients with low fascin-1 and MAP17 expression had an excellent 5-year overall survival rate of 92.8% (95% CI: 83–98). Concerning 3-year PFS, only 14.3% (95%CI: 11–30) of patients with combined high expression of both biomarkers did not experience recurrence or death within 30 months of surgery.

Conclusion

Conclusions; Combined high expression of fascin-1 and MAP17 identifies a group of patiens with poor early overall survival, indicating therefore targeted therapy's necessity.
A pilot, prospective, observational study to investigate the value of NGS liquid biopsies to predict tumor response after neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer: The LiBReCa study
Authors: Roesel R , Epistolio S , Saletti P , De Dosso S , Valli M , Franzetti-Pellanda A , Deantonio L , Bigioggero M , Spina P , Popeskou S G , Mongelli F , Frattini M , Christoforidis D
Published: June 2022

Objective

Circulating tumor DNA (ctDNA) has been shown to correlate with therapy response in different types of cancer.Little is known about the value of liquid biospies in locally advanced rectal cancer (LARC) to select patients for non-operative management. Our aim was to explore the value of serial liquid biopsies for response monitoring after neo-adiuvant chemoradiation therapy (nCRT) in LARC.

Methods

Twenty-five consecutive LARC patients undergoing long course nCRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded tissue (diagnostic biopsy and surgical specimen)and from plasma ctDNA collected at different time points: on the first and last day of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, at the day of surgery (Top) prior to resection, and 3–7 days after surgery (Tpost-op). At the day of surgery a mesenteric vein sample was also collected (Timv). The relationship between the ctDNA at those time-points and the Tumor Regression Grade (TRG) of the surgical specimen was statistically explored.

Results

ctDNA was detected in 87% of samples at baseline but only in 13%, 10%, 25% and 17% at T4, T7, Top and Tpost-op respectively. Pathological complete response (TRG1) was not statistically associated with gradual negativization of ctDNA mutations in plasma samples obtained in the aforementioned time points compared to tissue biopsy. However a positive liquid biopsy at Top was significantly associated to no response to nCRT (TRG 4) .

Conclusion

ctDNA evaluation by NGS technology was not a good marker for defining LARC patients that are more prone to develop complete response to nCRT, however persistence of ctDNA molecular alterations after this treatment could be a marker of poor-response.
Impact of gut microbiota and immune contexture on effectiveness of neo-adjuvant chemo-radiotherapy in locally advanced rectal cancer (LARC)
Authors: Roesel R , Basso C , Epistolio S , Djordjevic J , Sorrenti E , Terzaghi L , Galafassi J , Spina P , Popeskou S G , Mongelli F , Frattini M , Iezzi G , Christoforidis D
Published: June 2022

Objective

Among patients affected by Locally Advanced Rectal Cancer (LARC), 15–20% ultimately reveal a complete pathological response to the neo-adjuvant chemo-radiotherapy nCRT), which might render the surgical resection no longer necessary. However, the possibility to adopt alternative management options, such as a “wait and see” strategy, is hampered by the lack of reliable indicators of complete responsiveness to nCRT. Our hypothesis is that the composition of LARC-associated microbiome and immune contexture may predict the responsiveness to nCRT. We therefore proceed to a quantitative and qualitative evaluation of gut microbiome composition and immune contexture in LARC bioptic tissues and we then comparatively evaluated those markers in complete responders (Tumor regression grade, TRG,1) versus others (TRG2-3-4).

Methods

FFPE (Formalin Fixed Paraffin Embedded) LARC tissues from diagnostic biopsies and corresponding resections from patients treated at our hospital from 2012 to December 2019 were collected. Following sample deparaffinization, n. 71 genomic DNA (gDNA) and total cellular RNA were extracted. DNA used for microbiome analysis, upon amplification and sequencing of the hypervariable V3-V4 region of 16S gene. Expression of immune cell genes was evaluated by the Nanostring PanCancer Immune profiling panel on extracted RNA.

Results

Regarding the Microbiome profile we found no difference in terms of biodiversity between complete responders and others. However, we found some species significantly disregulated, in particular an over-expression of Alloprevotella Rava and down-expression of Porphyromonas Asaccharolytica, Turicibacter Sanguinis, Leptotrichia Trevisanii, Fusobacterium Nucleatum. The immune contexture analysis revealead a significant disregulation of 41 genes.

Conclusion

FFPE tissues from diagnostic biopsies proved suitable for the analysis of LARC-associated microbiome and immune contexture.

A specific microbiome signature appears to be associated with responsiveness to neo-adjuvant chemoradiotherapy. Defined immune related genes, in particular those associated with IFN-gamma response, are up-regulated in tumors exhibiting complete response. A possible associations between the bacterial species significantly disregulated and this favorable immune contexture is currently under investigation.
Risk factors for chronic postsurgical pain in visceral surgery: A matched case-control analysis
Authors: Perrodin S , Trinh W-H , Streitberger K , Di Pietro Martinelli C , Holzgang M , Candinas D , Beldi G
Published: June 2022

Objective

Chronic postsurgical pain (CPSP) is defined as new and persisting pain three months after a surgical procedure, whereby other causes of pain have been excluded. Although CPSP following orthopedic or gynecological surgery has been well investigated, we are lacking data for patients undergoing abdominal visceral surgery. We aim to identify the risk factors for CPSP in this patient population.

Methods

We performed a retrospective case-control matched analysis including all patients diagnosed with CPSP after abdominal visceral surgery between 2016 and 2019, matched to a control group of patients who did not develop CPSP. Excluded were patients for whom no follow-up was available 3 months or more after surgery. Two-to-one case-control matching was based on operation category (hepato-pancreatico-biliary, upper gastrointestinal, colorectal, transplantation, bariatric and others) and date of surgery. The influence of personal, surgical and pain management factors were explored and multivariate logistic regression analysis was performed.

Results

176 patients were diagnosed with CPSP during the study period. They were matched to a sample of 394 control patients extracted from the cohort of 3554 patients without CPSP. The incidence proportion of CPSP was 4.7%. Multivariate logistic regression analysis showed that age under 65 years (OR 2.22, CI 1.34-3.69, p=0.002), preexisting chronic pain of any origin (OR 3.39, CI 2.04-5.62, p=0.000), previous abdominal surgery (OR 1.71, CI 1.07-2.71, p=0.024), acute postoperative pain (2.62, CI 1.55-4.42, p=0.000) and length of stay over three days (OR 2.11, CI 1.26-3.53, p=0.004) were independent risk factors for CPSP. Preoperative Pregabalin intake was protective (OR 0.04, CI 0.01-0.33, p=0.003).

Conclusion

The identification of these risk factors allows for a preventive and personalized health care approach to our at-risk patients, for whom the optimization of postoperative acute pain management and an additional follow-up consultation 3 months after surgery might be indicated to avoid a delay in diagnosing CPSP. A possible explanation for the protective effect of Pregabalin is that in these patients, preexisting chronic pain might be better controlled in the preoperative phase, and they might have additional follow-up in the postoperative phase, be it from a pain specialist or their general practitioner.
Low-energy fractures of the pelvis in the elderly and mortality
Authors: Ramser M
Published: June 2022

Objective

While the prognostic impact of hip fractures in the elderly is widely accepted, the risk and excess mortality associated with pelvic fragility fractures is still underestimated and receives considerably less attention. Morbidity and mortality might thereby be related to fracture morphology and/or patient characteristics. The aim of this project is to investigate the prognostic value of specific fracture characteristics with respect to overall survival and to compare it with an established classification system.

Methods

Retrospective analysis of patients ≥60 years, treated conservatively for a CT-scan verified, low-energy pelvic ring fracture diagnosed between August 2006 and December 2018. Survival data was available from patients’ charts and cantonal or national registries.

The prognostic value of fracture characteristic describing the anterior and posterior involvement of the pelvic ring was investigated. This analysis was repeated after patients were stratified into a high-risk vs a low-risk group according to patient characteristic (age, gender, comorbidities, mobility, living situation). This allowed to assess the impact of the different fracture morphologies on mortality in fit vs. frail senior patients separately

Results

Overall, 428 patients (83.4% female) with a mean age of 83.7 years were included. Two thirds of patients were still living in their home and mobile without walking aid at baseline. In-hospital mortality was 0.7%, overall, one-year mortality 16.9%. An independent and significant association of age, gender and comorbidities to overall survival was found. Further, the occurrence of a horizontal sacral fracture as well as a ventral comminution or dislocation was associated with an increased mortality. The effect of a horizontal sacral fracture was more accentuated in low-risk patients while the ventral fracture components showed a larger effect on survival in high-risk patients. No association of the FFP classification with survival was observed.

Conclusion

Specific fracture characteristics such as horizontal sacral fracture, comminuted and dislocated ventral fractures may indicate a higher mortality risk of patients with a pelvic fragility fracture. Hence, they should be taken into account in future treatment algorithms and decisions on patient management.
Time to treatment initiation: An analysis of sarcoma patients treated at Multidisciplinary-Team/Sarcoma-Board (MDT/SB's) over a four-year period
Authors: Schärer M , Heesen P , Theus-Steinemann C , Bode B , Fuchs B
Published: June 2022

Objective

It is hypothesized that in the treatment of patients with soft tissue sarcomas (STS) the interval from establishing the diagnosis until initiation of treatment is relevant for the overall survival. Therefore, time to treatment initiation (TTI) was defined as a quality indicator for monitoring the treatment standard. The primary objective of this study was to find out how long (in days) it takes from establishing the sarcoma diagnosis through biopsy until initiation of treatment in patients suffering from STS. Secondary objectives were defined as the comparison between the different dignities, the different institutions and how the Swiss Sarcoma Network (SSN) cohort compares to the international standard.

Methods

This is a retrospective analysis of prospectively collected data from the SSN. All patients being presented to the MDT/SB within a four-year period from 2018 to 2022 were included in this study. TTI and secondary objectives were determined using non-parametric summary statistics and presented as median and interquartile range. Ethic approval was granted for this study.

Results

In total 383 patients were recorded in the respective time period in the SSN. In this study 278 patients with a malignant or intermediate STS according to WHO2020 were included. There were 66% (n=185) with a malignant and 44% (n=93) with an intermediate STS. The median TTI was 23 (8-52) days. In the malignant group, the median TTI was 21 (5-43) days and in the intermediate group 32 (11-59) days. In the different institutions the median TTI's were 10 (-6-30), 28 (12-78), 24 (10-58), 24 (10-53) and 12 (-12-54) days.

Conclusion

In the SSN cohort the overall median TTI was 23 days. In the literature, a TTI delay of more than 42 days led to a slightly reduced overall survival. Compared to the international standard, we conclude that within the SSN network, patients face an adequate waiting time until treatment initiation with no potential restrictions to overall survival.
Electrocautery smoke exposure and smoke evacuation in thoracic surgery: A prospective randomized study
Authors: Kocher G J , Dorn P , Hutterli M , Koss A
Published: June 2022

Objective

Worldwide, health care professionals working in operating rooms (ORs) are exposed to electrocautery smoke on a daily basis.

Aims of this study were to determine the composition and concentrations of electrocautery smoke in the OR using mass spectrometry and investigate whether smoke evacuation systems, operative technique and distance to the cautery source are effective in reducing exposure.

Methods

Single-center study at our thoracic surgical unit including 122 surgical procedures. Besides room air measurements away from the operating table (n=35) and direct breath analysis (n=3), 84 minimally invasive and open procedures were in each group 1:1 computer randomized to smoke evacuation system (SES) versus no SES use and hazardous compounds were measured at the height of the operating surgeons respiratory tract.

Results

Irritating, toxic, carcinogenic and mutagenic volaticle organic compounds (VOCs) were observed in OR air, with some exceeding permissible exposure limits (OSHA/NIOSH). Mean total concentration of harmful compounds at surgeon height without SES was 273ppb (±189ppb) with a maximum total concentration of harmful substances of 8991ppb .

Maximum total VOC concentrations were 1.6±1.2 ppm (minimally-invasive surgery) and 2.1±1.5 ppm (open surgery), and total maximum VOC concentrations were 1.8±1.3 ppm at the OR table and 1.4±1.0 ppm in OR air in general. Neither difference was statistically significant.

In open surgery, SES significantly reduced maximum concentrations of specific VOCs at surgeon height, including aromatics and aldehydes.

Conclusion

Our data indicate relevant exposure of health care professionals to volatile organic compounds in the OR. Surgical technique and distance to cautery devices did not significantly reduce exposure. SES reduced exposure to specific harmful VOC's during open surgery.
Conservative treatment versus reversed shoulder prothesis for proximal humerus fractures in the elderly: A meta-analysis of observational studies and randomised clinical trials
Authors: Ferree S , Beeres F , Rompen I , Link B , Babst R , van de Wall B
Published: June 2022

Objective

The treatment of complex proximal humerus fractures in elderly patients is not yet fully eluci-dated. Of all treatment options reverse shoulder arthroplasty (RSA) and non operative treat-ment (NOT) appear to provide the best results. Evidence to guide the choice between the two is sparse. Therefore, this review provides an overview of the available evidence on RSA versus non-operative treatment.

Methods

Studies comparing RSA and NOT were included for direct comparison by systematic re-view and pooled analysis for patient rated outcome and range of motion. Additionally, indirect comparison of case-series and non-comparative studies on either treatment modalities was performed separately.

Results

Comparative: Reverse shoulder arthroplasty resulted in better patient rated outcome scores and better range of motion. Pain and treatment satisfaction scores were better after RSA. Non comparative studies reported similar patient rated and range of motion scores for both RSA and after NOT.

Conclusion

The functional and range of motion outcomes after RSA seem satisfactory and potentially superior to NOT in elderly patients. The complication rate is acceptably low and an overall revision rate of 5% was found. These results should however be viewed in light of distinct differences in patient characteristics between treatment groups.
Outcome oriented clinical research and quality measurement in fracture care
Authors: Bilici M , Reinhardt J , Morgenstern M , Müller A M , Rikli D
Published: June 2022

Objective

The paradigm shift according to the principles of Value-Based Healthcare is receiving growing attention. In Orthopedic Trauma care, there are no defined standards to provide an incentive system to recompensate for quality instead of quantity. The definitions of quality from the patient's view have to be validated and included in the reimbursement cycle. In our Department, we now have fully standardized and structured documentation and outcome measurement workflow from the clinical point of view.

Methods

We set up a Fracture Registry with a REDCap® Database to document every patient with surgical treatment. Included are all surgically treated fractures of the extremities, excluding the hand. Furthermore pelvic, acetabular, and periprosthetic fractures, joint dislocations, and tendon ruptures. With interfaces to our Clinical Documentation Systems, the administrative effort became very efficient. The interfaces provide a possibility to identify every patient with inclusion criteria and implement reminder feedback for Surgeons. We collect PROMs with the heartbeat-Software, and document CROMs with REDCap®. We merged these data using the software ‘R’. The documentation of each patient is completed with a database for Adverse Events.

Results

Data-entry rates were less than 50% in 2018 and have reached 99.1% for 2020 and 99.5% for 2021 for surgically treated fracture patients. Until the submission of this abstract, 2382 surgical procedures have been performed at our Department on 2073 hospitalized patients. 972 patients were included in the Fracture Registry (47%). In a feasibility study, we have merged clinical data with the PROMs of patients treated for distal radius (DR) and proximal humerus (PH) fractures. The baseline values for DR of the quality-of-life questionnaire EQ5D was 0.83 (n=144), after 3months 0.9 (n=58) and 0.97 one year after treatment (n=6). Although not more than a trend, we realized the same pattern for PH-patients with an EQ5D-Baseline of 0.75 (n=63), three months values of 0.75 (n=58), and one-year results of 0.87 (n=6).

Conclusion

Collecting structured data allows combining routine clinical data with PROMs and CROMs. This information is of inestimable value to define the quality of care for Orthopedic Trauma Surgery. Our combination of Databases to collect diagnosis, subjective and objective outcome measures has been proven feasible and showed high data quality.