bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-alcoholic steatohepatitis alters antigen-specific response against hepatocellular carcinoma in mice
Authors: Lacotte S , Slits F , Peloso A , Tihy M , Gex Q , Moeckli B , Toso C
Published: June 2022

Objective

Non-alcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). At time immunotherapy is used as first line treatment of advanced HCC, the impact of NASH on anti-cancer immunity remains unclear. We aim at assessing the tumor-specific T cell immune response in the presence of NASH in a mouse model of HCC recurrence.

Methods

We engineered an HCC cell line (RIL-175) with a cytoplasmic expression of ovalbumin (OVA) protein. C57BL/6N mice fed a high-fat (HFD) or a control diet (CD) for 35 weeks were injected in the portal vein with 1.5.105 RIL-175-LV-OVA-GFP cells.

Results

After 35 weeks of HFD, mice were obese and developed a massive steatosis with inflammation. In the liver of HFD-fed mice, we observed an increase of the CD8+ T cell subset corresponding to an expansion of the population of CD44+ CXCR6+ PD-1+ CD8+ T cells, known to promote NASH lesions. Fourteen days after injecting RIL-LV-OVA-GFP cells, HFD-fed mice developed a higher percentage of peripheral OVA-specific CD8 T cells than CD-fed mice (8.31 vs. 3.67%; p=0.010), but these cells were not able to prevent HCC growth, resulting in larger tumors in HFD-fed mice (620 vs. 1603mm3, p=0.051). In the liver, OVA-specific CD44+ CXCR6+ CD8+ cells were present in a similar manner in CD and HFD-fed mice, however with a higher expression of PD-1 in HFD-fed mice, suggesting a lower immune activity (MFI 12605 vs. 16083, p=0.0159). Using anti-CD122 antibody acting in decreasing the CXCR6+ PD-1+ cell subset, we were able to restore OVA-specific CD8 activity through a decrease in PD-1 expression (MFI 16406 vs. 10516, p=0.0571), and to decrease HCC growth compared to HFD mice non treated with anti-CD122 (p=0.0286).

Conclusion

The immune system is altered and fails to prevent HCC growth in HFD-fed mice. This effect is primarily linked to a higher representation of CD44+ CXCR6+ PD-1+ CD8+ T cells. Treatment with anti-CD122 act on these cells, and prevent HCC growth.
CD26-inhibition correlates with the absence of chronic lung allograft dysfunction and decreases fibroblast activity in vitro
Authors: Moneke I , Ögütür E , Chatterjee S , Haberecker M , Jang J H , Fähndrich S , Senbaklavaci Ö , Faccioli E , Opitz I , Passlick B , Diederichs S , Jungraithmayr W
Published: June 2022

Objective

Chronic lung allograft dysfunction (CLAD) limits the survival after lung transplantation (Tx). CLAD is characterized by progressive fibrosis of small airways and lung parenchyma. No effective therapy is available that reverses or prevents CLAD. CD26 is a molecule with enzymatic activity also playing a key role in the progression of fibrotic diseases. Here, we analyzed the inhibitory effect of CD26 on fibroblast activity in vitro and the role of CD26-inhibition on allograft rejection in lung transplant patients.

Methods

Profibrogenic mRNA and protein levels were analyzed in vitro on the CD26-expressing fibroblast cell line Wi-38 using RT-qPCR and Western blot. CD26 was inhibited by Vildagliptin. Migration and proliferation activity of activated fibroblasts were analyzed by Incucyte® and Celltiter-Glo®. Characteristics of patients undergoing lung Tx between 2004 and 2021 were reviewed. Lung biopsies were analyzed by immunohistochemistry (IHC) for CD26.

Results

In vitro, the expression of profibrogenic genes (αSMA, FAPα, IGFBP7, Collagen 3 and Fibronectin) was significantly reduced in activated lung fibroblasts by Vildagliptin treatment. Also, migration and proliferation activity were attenuated by Vildagliptin. In 221 patients analyzed, CLAD was absent in 34 patients treated with the CD26-inhibitor Sitagliptin vs. an incidence of 18% in patients without Sitagliptin intake (p=0.02). Five-year survival in patients on Sitagliptin was significantly improved vs. patients without CD26-inhibitor intake (80% vs. 58%, p=0.006). Likewise, the incidence of acute cellular rejection (ACR) was significantly reduced in patients on Sitagliptin (7% vs. 35%, p=0.01). IHC of patient lung biopsies showed expression of CD26 in perifibrotic areas of CLAD lesions. Additional clinical data from University Hospital Zurich and from University Hospital Padua confirmed the finding that Sitagliptin intake correlated with the absence of acute and chronic allograft rejection.

Conclusion

CD26-inhibition attenuates key pro-fibrotic mediators and fibroblast activity in vitro. Impressively, patients on CD26-inhibitor did not show any CLAD. Moreover, ACR was significantly reduced. Gliptins which are in routine clinical use for the treatment of type II diabetes therefore seem to have great potential to be repurposed for a novel clinical application against lung allograft rejection.
Finding the best available evidence in pancreatic surgery – the EVIglance randomised controlled trial
Authors: Probst P , Merz D , Joos M , Klotz R
Published: June 2022

Objective

Profound and thorough literature search is a vital element of evidence-based medicine. However, increasing number of publications and limited time make it hard to find the best available evidence. The objective of this randomised controlled trial (RCT) was to demonstrate the superiority of the ISGPS Evidence Map of Pancreatic Surgery (via EVIglance on www.evidencemap.surgery) compared to a conventional literature search via PubMed for answering clinically relevant questions in pancreatic surgery.

Methods

A single-centre, blinded, cross-over RCT including medical students, residents and consultants as participants was performed. Participants conducted literature searches with two predefined PICO (Patient, Intervention, Control, Outcome) questions, one with PubMed and the other with EVIglance. The order of the search tools and the PICO questions were assigned by randomisation. Primary endpoint was time in minutes until a synopsis was made regarding the PICO question. The synopsis was characterised by the direction of the effect and the certainty of evidence. Three times 28 participants were needed to show a minimal difference of 3 minutes at a level of significance of alpha = 1.67%. Furthermore, the correct number of RCTs found by participants that were relevant to answer the PICO question was analysed.

Results

Each 28 medical students, residents and consultants were randomised and analysed. A synopsis for the PICO question was found with PubMed after 10.8 minutes and with EVIglance after 1.7 minutes (95%-CI for difference: 9.9 to 8.3 minutes; p<0.001). EVIglance answered the PICO significantly faster in all groups (medical students, residents and consultants) even after Bonferroni correction. Participants were able to guess both the direction of the effect (95% vs 48%; p<0.001) and the certainty of evidence (99% vs 30%; p<0.001) better with EVIglance than with PubMed. The correct number of relevant RCTs to answer the PICO question was found more often with EVIglance compared to PubMed (99% vs 15%; p<0.001).

Conclusion

Pancreatic surgeons find best available evidence faster via EVIglance on www.evidencemap.surgery. Furthermore, a synopsis made from EVIglance is more concise regarding direction of effect and certainty of evidence. Given the advantages of EVIglance it may be considered the new gold standard for finding best available evidence in pancreatic surgery.
Combined interdisciplinary treatment of metastatic bone lesions – embolization, biopsy, ablation, and surgery in one operative sitting
Authors: Haefeli P C , Fuchs B , Schelling G , Baumgärtner R , Möhl P , Lopez Benitez R , Link B-C
Published: June 2022

Objective

As a result of modern cancer treatment and thereby improved survival, many cancers spread to bone. Bone metastases may cause immobilizing pain and increase the risk of fracture even by inadequate or no trauma. Treatment of these patients should promptly address confirmation of the tumor entity, local control as well as adequate and lasting surgical stabilisation of the affected bone or joint. We present a setup to perform all the above in a single operative sitting.

Methods

Required imaging is completed before initial consultation. The treatment plan is discussed in an interdisciplinary team according to the primary tumor and thereof resulting survival estimation, the imaging evaluation and patient's expectations and needs.

In a single operative setup, the patients are treated by an interventional radiologist and an orthopaedic surgeon in a hybrid operating room. Thus, in one single setup the patient may undergo arteriogram to diagnose hypervascularity of the tumor followed by embolization if needed, CT-guided biopsy, percutaneous radiofrequency or cryotherapy ablation of the metastases for local tumor control and eventually surgical treatment with resection of the tumor, joint replacement or minimally-invasive stabilization as needed. Biopsy results may be discussed at inhouse tumor boards and adjuvant radio- or chemotherapy may be planned for the postoperative course.

Results

Five combined procedures were performed in 5 patients (3 female, 2 male patients; median age 65 years (range 61–77)) each in one single operative sitting since October 2021. Three patients suffered from metastases of renal cell carcinoma, one each from thyroid carcinoma and breast cancer respectively. Metastases were located in the femoral meta- and diaphysis in 3 cases and in the acetabulum in 2 cases. Median duration of this multidisciplinary intervention was 375 min (251–426). Median length of hospital stay was 5 days (3–10). Median time from referral to definitive treatment was 24 days (17–32). All patients were able to walk with crutches immediately after treatment. No complications occurred.

Conclusion

Combined multidisciplinary treatment of patients with metastatic bone disease is possible and may be favourable in respect of minimising the number of consultations, anaesthesias and interventions. This should lead to accelerated and pain-free mobilisation, thus maximising the patients’ quality of life.
Impact of gender on surgical site infections in abdominal surgery: A multi-center study
Authors: Zwicky S N , Gloor S , Tschan F , Candinas D , Demartines N , Weber M , Beldi G
Published: June 2022

Objective

Male sex is controversially discussed as a risk factor for surgical site infections (SSI). The aim of the present study was to evaluate the impact of gender on SSI in abdominal surgery under elimination of relevant confounders.

Methods

Clinicopathological data of 6603 patients undergoing abdominal surgery from a multi-center prospective database of four Swiss hospitals including patients between 2015 and 2018 were assessed. Patients were stratified according to postoperative SSI and risk factors for SSI were assessed using univariate and multivariate analysis.

Results

In 649 of 6603 patients SSI was reported (9.8%). SSI was significantly associated with increased risk of reoperation (22.7% vs. 3.4%, p <0.001), higher mortality rate (4.6% vs. 0.9%, p <0.001) and higher rate of length of hospital stay > 75th percentile (57.0% vs. 17.9%, p <0.001). In univariate analysis male sex was a significant risk factor for SSI (p = 0.01). In multivariate analysis including multiple confounders’ such as comorbidities and perioperative factors there was no association between male sex and risk of SSI (OR 1.1 [CI 0.8–1.4]). BMI >= 30 kg/m2 (OR 1.8 [CI 1.3–2.3]), duration of surgery > 75th percentile (OR 2.3 [1.8–2.9]), high contamination level (OR 1.3 [1.0–1.6]), laparotomy (OR 1.3 [1.0–1.7]), previous laparotomy (OR 1.4 [1.1–1.7]), blood transfusion (OR 1.7 [1.2–2.4]), cancer (OR 1.3 [1.0–1.8]), malnutrition (OR 2.5 [1.8–3.4]) were independent risk factors for SSI in multivariate analysis.

Conclusion

Under elimination of relevant confounders there is no significant correlation between gender and risk of SSI after abdominal surgery. Independent risk factors for SSI as BMI >= 30 kg/m2, duration of surgery > 75th percentile, high contamination level, surgical approach or malnutrition should be considered during treatment.
Interdisciplinary combined sacrocolporectopexy: Results after one-year follow-up
Authors: Bauci G , Hülder T , Bischofberger S , Brunner W , Schmied B , Marti L
Published: June 2022

Objective

Multicompartmental pelvic floor descensus typically affects women after menopause, leading to a combination of faecal and urinary incontinence, dyspareunia, and evacuation disorders. The aim of this study was to access postoperative quality of life and complications as well as outcome after one-year follow-up after operation of multicompartmental pelvic floor prolapse (POP).

Methods

All Patients undergoing ventral mesh rectopexy by surgical department and anterior mesh sacrocolpopexy by gynecologists at the same time between 2015 and 2020 were enrolled. The study is a retrospective cohort study approved by the local Ethics committee. Follow-up was scheduled at 6 weeks, 6, and 12 months and consisted of clinical examination and questionnaires. Perioperative and long-time morbidity was assessed according to the Clavien-Dindo classification. Quality of life and patients’ satisfaction were evaluated at each consultation.

Results

Twenty-seven patients were included. All patients were seen at one-year follow-up.

Demographic and clinical features are reported in Table 1. Preoperatively, 22 patients (81.5%) were diagnosed with stage II-III (POP-Q) prolapse and severe multicompartment descensus detected on Magnetic Resonance (MR). Laparoscopic surgery was performed in 92.5% of cases and intraoperative conversion was necessary in 2 cases. In 15 cases (55%) a Dynamesh® Visible, in 11 cases (41%) a Gynamesh®, and in one (4%) case a Surgipro™ Mesh was used. No severe complications (Clavien-Dindo >=3) occurred postoperatively. 90-day mortality was 0%. Intraoperatively, a total of 1 vaginal, and 2 bladder lesions were corrected and healed without consequences. At 1 year, patients reported a high level of satisfaction and massive improvement of QoL (8.5 Pt. VAS Scale). During follow-up, one patient had to be reoperated because of incisional hernia and one to cover vaginal mesh exposure. A tension free vaginal tape (TVT) had to be inserted in 4 patients (15%) due to new onset of urinary incontinence. Symptomatic recurrence of prolapse did not occur.

Conclusion

Interdisciplinary combined sacrocolporectopexy is an effective therapy of multicompartmental pelvic floor descensus. It is a safe procedure with low perioperative morbidity and high patients’ satisfaction. Therefore, it might be the procedure of choice to correct multicompartmental POP.
3D-quantitated lung perfusion SPECT/CT: Impact on intended management compared to lung perfusion scan in marginal candidates for lung resection surgery
Authors: Mallaev M , Chirindel A-F , Nicolas G , Tamm M , Hojski A , Wiese M , Stolz D , Lardinois D
Published: June 2022

Objective

Based on previous studies, single-photon emission computed tomography/computed tomography (SPECT/CT) has been proven to be more accurate and reproducible than planar lung perfusion scintigraphy. We conducted a study to evaluate the impact of 3D-quantitated lung perfusion SPECT/CT on intended management in candidates for lung resection surgery.

Methods

Retrospective study including candidates for lung resection surgery with lung perfusion imaging. Patients underwent preoperative evaluation according to ERS/ESTS algorithm. The lobar contribution to the total lung perfusion was estimated using planar antero-posterior, posterior oblique and three-dimensional anatomical SPECT/CT method (CT Pulmo 3D and xSPECT- Quant, Siemens). The difference in lobar perfusion with resulting changes in the extent of lung resection were analyzed to reveal possible changes in operability.

Results

120 patients (46 females) with known lung cancer or pulmonary lesion considered for resection with available lung perfusion scintigraphy and SPECT/CT were enrolled. The mean age (±SD) of patients was 68 ±9 years, the target lesions were located in upper lobe in 57.7% and in lower lobe in 33.5%. The median [IQR] FEV1 was 70.5% [52–84] and median DLCO 56.6% [47.1–67.4]. The planar posterior oblique method, compared to 3D-quantitated SPECT/CT, underestimated the perfusion of upper lobes by a median difference of 5% (right [2–9; IQR]; left [2.5–8], p= < 0.0001), while it overestimated the both lower lobes (left by 4% [2–7]; right by 6% [2–9], p= < 0.0001). In contrast to the planar scintigraphy based evaluation, 4(3.3%) patients with upper lobe lesions were classified as inoperable when 3D-quantitated SPECT/CT was used for calculation of predicted postoperative lung function.

Conclusion

In selected patients with upper lobe lesions, 3D-quantitated SPECT/CT would have changed the treatment strategy from operable to inoperable. Importantly, post-operative mortality in this particular subgroup was disproportionally high. 3D-quantitated SPECT/CT shall be further evaluated as it might improve preoperative risk stratification in marginal lung resection candidates.
Surgical and non-operative management of displaced scapular fractures and long-term outcomes
Authors: Graafland M , van de Wall B , van Veelen N , van Leeuwen R , Hoepelman R , Knobe M , Link B-C , Babst R , Beeres F
Published: June 2022

Objective

To compare the long-term functional outcome of surgically and non-operatively managed patients with displaced intra- and extra-articular scapular fractures.

Methods

This study included patients with intra- and extra-articular scapula fractures, treated between 2010 and 2020 in a Swiss level 1 trauma centre. The decision to operate was based on standardized criteria for fracture displacement. Patients with isolated Bankart lesions (Ideberg 1) and process fractures (AO type 14-A) were excluded. Primary outcomes were functional patient reported measures (DASH score) and quality of life (EQ5D score). Secondary outcomes were complications, radiological union, satisfaction with treatment, pain and range of motion.

Results

Out of 486 cases, 74 patients had displaced scapula fractures. Forty patients were treated surgically and 34 were treated conservatively. Significantly more patients with intra-articular fractures and high-energy trauma were treated surgically. Fifty percent returned the questionnaires after a mean follow-up of 47 months (± SD 36). The mean DASH score of this group was 12 (SD 15.6), with a mean of 14.7 (SD 15.9) in the surgery group and 9.8 (SD 14.6) in the non-operative group (p = 0.7). Multivariate analysis did not show statistically significant correlating factors. No significant differences in quality of life were observed. Patients rated their treatment with a mean of 8.6/10 (SD 1.8). Among surgically treated patients, 19 underwent a deltoid sparing procedure with significant shorter time to union than those that underwent deltoid release (23 vs. 49 weeks, p<0.01). Complications occurred in 3/28 surgically treated patients and all three required a reoperation.

Conclusion

Functional results after conservative and surgical treatment were similar, despite more complex fractures and more intra-articular fractures being treated surgically. Osteosynthesis of both intra- and extra-articular scapula fractures is safe and leads to good functional results, furthermore, new minimal invasive techniques may lead to faster bone healing and return to work and sports.
Low-profile dual mini-fragment plating of diaphyseal clavicle fractures. A biomechanical comparative analysis
Authors: Pastor T , Knobe M , van de Wall B J M , Rompen I F , Zderic I , Visscher L , Link B-C , Babst R , Gueorguiev B , Beeres F J P
Published: June 2022

Objective

Implant removal rates after clavicle plating are high. Recently, low-proﬁle dual mini-fragment plate constructs have proven safe for the ﬁxation of diaphyseal clavicle fractures. Therefore, the aims of this study was to investigate: (1) the biomechanical competence of different dual plate designs in terms of stiffness and cycles to failure, and (2) to compare them against 3.5 mm single superoanterior plating.

Methods

12 artificial clavicles were assigned to 2 groups and instrumented with titanium matrix mandible plates as follows: group 1 (2.5 mm anterior+2.0 mm superior) and group 2 (2.0 mm anterior+2.0 mm superior). An unstable clavicle shaft fracture (AO/OTA15.2C) was simulated. Specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with torsion around the shaft axis and compared to previous published data of 6 locked superoanterior plates tested under the same conditions (group 3)

Results

Displacement (mm) after 5000 cycles was highest in group 3 (10.7±0.8) followed by group 2 (8.5±1.0) and group 1 (7.5±1.0), respectively. Both outcomes were significantly higher in group 3 as compared to both groups 1 and 2 (p≤0.027). Cycles to failure were highest in group 3 (19536±3586) followed by group 1 (15834±3492) and group 2 (11104±3177), being significantly higher in group 3 as compared to group 2 (p=0.004).

Conclusion

Low-profile 2.0/2.0 dual plates demonstrated similar initial stiffness compared to 3.5 mm single plates, however, they revealed significantly lower endurance to failure. Moreover, low-profile 2.5/2.0 dual plates showed significant higher initial stiffness and similar resistance to failure compared to 3.5 mm single locked plates and can therefore be considered as a useful alternative for diaphyseal clavicle fracture fixation. These results complement the promising results of several clinical studies.
Brain metastasis incidence in gastro-esophageal cancer: A meta-analysis
Authors: Sleiman M-J , Abbassi Z , Jung M , Toso C , Chevallay M , Mönig S
Published: June 2022

Objective

Upper gastrointestinal cancers (UGC) are a leading cause of cancer related deaths. Brain metastases (BM) from gastric and esophageal cancer are rare and associated with a poor survival time. The precise incidence of BM for UGC is lacking.

Methods

We searched: “Gastric cancer OR Oesophageal Cancer AND Cerebral Metastasis” in Pubmed, EMBASE, Cochrane Library. Inclusion criteria were all studies with an incidence rate of BM from UGC cancer patients cohort. When the inclusion criteria were met, we extracted the following endpoints: year of publication, country of population, tumor localization, histology, number of brain lesion, synchronous or metachronous brain metastases, stage of the primary tumor, other localization of metastases, surgical treatment of the primary tumor, brain metastasis treatment (surgery, steatosic radiosurgery, whole brain radiation, gamma knife surgery), survival and follow-up.

Results

52 studies were included. The total number of patients with oesophageal tumor were described in 30 studies with 41636 patients from which 1234 patients (2.9%) had BM. 526 patients (63%) had an adenocarcinoma, 287 (34%) had a SCC and 17 (3%) other histology. BM was unique in 288 patients (50%) and multiples in 282 patients (50%). A combined radiotherapy and surgery was performed in 129 patients (17.9%). Surgical metastasectomy was performed in 172 patients (24.25%). Stereotaxic radiotherapy was delivered in 60 patients. (8.5%) A whole brain radiotherapy was performed in 265 patients (35.9%). Gamma knife surgery was performed in 43 patients (5.9%). Chemotherapy in 10 patients (1.6%) and no treatment in 43 patients. (5.9%). The median survival was reported from 3 month to 24 months. We identified 12 articles which matched the research criteria for gastric cancer with a total of 73.781 primary gastric tumors where 645 presented brain metastasis (0.87%). 159 patients had single BM (42.3%) compared to 217 patients with multiple BM (57.7%). We identified 434 adenocarcinoma which represent 81.1% of the brain metastasis. Median survival for patients with brain metastasis from gastric cancer was described from 1.3 month to 27 months.

Conclusion

Brain metastases from UGI cancer are rare and associated with a low survival. Multimodal treatment is the most described treatment strategy. More studies are required to assess the role of brain imaging in the initial staging of UGI cancer.
Design of the OptiSurg trial: Multicenter open-label randomized controlled trial of time restricted feeding (TRF) vs regular dietary advices in patient undergoing femoral endarterectomy
Authors: Kiesworo K , Longchamp J , Brusa J , Côté E , Agius T , Macarthur M , Mitchell S , Deslarzes C , Corpataux J-M , Allagnat F , Collet T-H , Ozaki C-K , Déglise S , Longchamp A
Published: June 2022

Objective

Vascular patients suffer some of the highest complications rates. Surprisingly, there is no uniformly accepted medical therapy to reduce complications in these patients. Time restricted feeding (TRF) is an approach that emphasizes energy intake limited to certain windows of time within the 24-hour cycle, without restrictions on any calories or macronutrients. In healthy young human, TRF improves cardio-metabolic fitness. However, there is a lack of research on TRF in patient undergoing surgery, and suffering from cardiovascular diseases. This study aims to investigate the feasibility and efficacy of a pre-operative 2-week, 10-hour TRF in patient undergoing vascular surgery.

Methods

The OptiSurg Study is a randomized open-label clinical trial, that plan to enroll 40 patients, undergoing elective femoral endarterectomy. Only Fontaine stage II peripheral artery disease, and a BMI ≥ 20 kg/m2 are included. Patients are randomized with a 1:1 ratio to either the control or intervention group. The control group receives diet nutritional counselling (standard of care, SOC). The intervention group receives the same SOC and a self-selected 10-hour TRE window. After the surgery, patients will be on SOC only, and followed every 3 months up to 1 year. Primary endpoint is a composite of death, myocardial infarction, stroke, and surgical re-intervention at 1 month post-operative. Blood glucose, body weight, body composition, biomarkers (neuroendocrine, inflammatory and metabolic), sleep and quality of life will also be examined. Temporal calorie intake is monitored with the smartphone application myCircadianClock preoperatively. VascuQoL-6 is used to monitor quality of life.

Results

9 participants were enrolled since the start of the recruitment in February 2021, 4 were randomized in the 8 hours TRF intervention, and 5 to SOC. They all completed the study: 7 men and 2 women, age 73, 53–87 (median, min-max) years. Using the myCircadianClock app, adherence to the TRF was >90% (Figure 1).

Conclusion

Our preliminary experience seems to demonstrate that a 2-week TRF regimen before vascular surgery is feasible. The complete results will be disseminated through future peer-reviewed manuscripts, reports and presentations.
Learning to read may help promote attention by increasing the volume of the left middle frontal gyrus and enhancing its connectivity to the ventral attention network
Authors: Wang Yanpei , Guan Haoran , Ma Leilei , Luo Jie , Chu Congying , Hu Mingming , Zhao Gai , Men Weiwei , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , He Yong , Dong Qi , Tao Sha
Published: June 2022

Attention and reading are essential skills for successful schooling and in adult life. While previous studies have documented that attention development supports reading acquisition, whether and how learning to read may improve attention among school-age children and the brain structural and functional development that may be involved remain unknown. In this prospective longitudinal study, we examined bidirectional and longitudinal predictions between attention and reading development and the neural mediators of attention and reading development among school-age children using cross-lagged panel modeling. The results showed that better baseline reading performance significantly predicted better attention performance one year later after controlling for baseline attention performance. In contrast, after controlling for baseline reading performance, attention did not significantly predict reading performance one year later, while more attention problems also significantly predicted worse reading performance. Both the increasing gray matter volume of the left middle frontal gyrus and the increasing connectivity between the left middle frontal gyrus and the ventral attention network mediated the above significant longitudinal predictions. This study, directly revealed that reading skills may predict the development of important cognitive functions, such as attention, in school-age children. Therefore, learning to read is not only a challenge for school-age children but is also an important way to optimize attention and brain development.
Maternal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination During Pregnancy: Impact on Infant Anti-Pertussis Antibody Concentrations by Maternal Pertussis Priming Series
Authors: Havers Fiona P , Skoff Tami H , Rench Marcia A , Epperson Monica , Rajam Gowrisankar , Schiffer Jarad , Hariri Susan , Swaim Laurie S , Baker Carol J , Healy C Mary
Published: June 2022

Background

Acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccines for the US childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy may be impacted.

Methods

Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMCs) of pertussis-specific immunoglobulin G antibodies (international units per milliliter) in cord blood of infants born to women born after 1997 (aP-primed) were compared with those born to women born before 1992 (wP-primed).

Results

253 and 506 infants born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger, more likely to be Hispanic or non-Hispanic Black, and had lower-birthweight infants (P < .01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed vs wP-primed women (PT, 17.3 vs 36.4; GMC ratio, .475; 95% confidence interval [CI], .408–.552 and FHA, 104.6 vs 121.4; GMC ratio, 0.861; 95% CI, .776–.958). No differences were observed for anti-fimbriae or anti-pertactin antibodies.

Conclusions

Transplacental anti-pertussis antibody concentrations in infants of women vaccinated with Tdap during pregnancy differed by type of childhood vaccine the women received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP-primed vs wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in infants born to aP-primed vs those born to wP-primed women.
Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California
Authors: Bruxvoort Katia J , Lewnard Joseph A , Chen Lie H , Tseng Hung Fu , Chang Jennifer , Veltman Jennifer , Marrazzo Jeanne , Qian Lei
Published: June 2022

Background

Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea.

Methods

We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non–OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome.

Results

The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3–2.8) for recipients of 4CMenB and 5.2 (4.6–5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34–.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82–1.17).

Conclusions

These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.
Laparoscopic total fundoplication is superior to medical treatment for reducing the cancer risk in Barrett’s esophagus: a long-term analysis
Authors: Szachnowicz S , Duarte A F , Nasi A , da Rocha J R M , Seguro F B , Bianchi E T , Tustumi F , de Moura E G H , Sallum R A A , Cecconello I
Published: June 2022

The present study aims to compare the effectiveness of surgical and medical therapy in reducing the risk of cancer in Barrett’s esophagus in a long-term evaluation. A prospective cohort was designed that compared Barrett’s esophagus patients submitted to medical treatment with omeprazole or laparoscopic Nissen fundoplication. The groups were compared using propensity score matching paired by Barrett’s esophagus length. A total of 398 patients met inclusion criteria. There were 207 patients in the omeprazole group (Group A) and 191 in the total fundoplication group (Group B). After applying the propensity score matching paired by Barrett’s esophagus length, the groups were 180 (Group A) and 190 (Group B). Median follow-up was 80 months. Group B was significantly superior for controlling GERD symptoms. Group B was more efficient than Group A in promoting Barrett’s esophagus regression or blocking its progression. Group B was more efficient than Group A in preventing the development of dysplasia and cancer. Logistic regression was performed for the outcomes of adenocarcinoma and dysplasia. Age and body mass index were used as covariates in the logistic regression models. Even after regression analysis, Group B was still superior to Group A to prevent esophageal adenocarcinoma or dysplasia transformation (odds ratio [OR]: 0.51; 95% confidence interval [CI]: 0.27–0.97, for adenocarcinoma or any dysplasia; and OR: 0.26; 95% CI: 0.08–0.81, for adenocarcinoma or high-grade dysplasia). Surgical treatment is superior to medical management, allowing for better symptom control, less need for reflux medication use, higher regression rate of the columnar epithelium and intestinal metaplasia, and lower risk for progression to dysplasia and cancer.
Safety and efficacy of neoadjuvant treatment with immune checkpoint inhibitors in esophageal cancer: real-world multicenter retrospective study in China
Authors: Yang Yang , Tan Lijie , Hu Jian , Li Yin , Mao Yousheng , Tian Ziqiang , Zhang Baihua , Ma Jianqun , Li Hecheng , Chen Chun , Chen Keneng , Han Yongtao , Chen Longqi , Liu Junfeng , Yu Bentong , Yu Zhentao , Li Zhigang ,   the Esophageal Cancer Committee of Chinese Anti-Cancer Association
Published: June 2022

Immune checkpoint inhibitors (ICIs) have shown a powerful benefit in the neoadjuvant therapy for esophageal cancer, but evidence for its safety and efficacy is limited and may not reflect real-world practice. We retrospectively reviewed the database of treatment-naive patients from 15 esophageal cancer centers in China who received ICIs as neoadjuvant treatment for locally advanced esophageal cancer from May 2019 to December 2020. The primary endpoints were rate and severity of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs). Secondary endpoints included pathologically complete response (pCR) rate, R0 resection rate, mortality and morbidity. Among the 370 patients, 311 (84.1%) were male with a median age of 63 (range: 30–81) years and stage III or IVa disease accounted for 84.1% of these patients. A total of 299 (80.8%) patients were treated with ICIs and chemotherapy. TRAEs were observed in 199 (53.8%) patients with low severity (grade 1-2, 39.2%; grade 3-4, 13.2%; grade 5, 1.4%), and irAEs occurred in 24.3% of patients and were mostly of grade 1-2 severity (21.1%). A total of 341 (92.2%) patients had received surgery and R0 resection was achieved in 333 (97.7%) patients. The local pCR rate in primary tumor was 34.6%, including 25.8% of ypT0N0 and 8.8% of ypT0N+. The rate of postoperative complications was 41.4% and grade 3 or higher complications occurred in 35 (10.3%) patients. No death was observed within 30 days after surgery, and three patients (0.9%) died within 90 days postoperatively. This study shows acceptable toxicity of neoadjuvant immunotherapy for locally advanced esophageal cancer in real-world data. Long-term survival results are pending for further investigations.
Double machine learning-based programme evaluation under unconfoundedness
Authors: Knaus Michael C
Published: June 2022

This paper reviews, applies, and extends recently proposed methods based on double machine learning (DML) with a focus on programme evaluation under unconfoundedness. DML-based methods leverage flexible prediction models to adjust for confounding variables in the estimation of (a) standard average effects, (b) different forms of heterogeneous effects, and (c) optimal treatment assignment rules. An evaluation of multiple programmes of the Swiss Active Labour Market Policy illustrates how DML-based methods enable a comprehensive programme evaluation. Motivated by extreme individualised treatment effect estimates of the DR-learner, we propose the normalised DR-learner (NDR-learner) to address this issue. The NDR-learner acknowledges that individualised effect estimates can be stabilised by an individualised normalisation of inverse probability weights.
The impact of prenatal and early-life arsenic exposure on epigenetic age acceleration among adults in Northern Chile
Authors: Bozack Anne K , Boileau Philippe , Hubbard Alan E , Sillé Fenna C M , Ferreccio Catterina , Steinmaus Craig M , Smith Martyn T , Cardenas Andres
Published: June 2022

Exposure to arsenic affects millions of people globally. Changes in the epigenome may be involved in pathways linking arsenic to health or serve as biomarkers of exposure. This study investigated associations between prenatal and early-life arsenic exposure and epigenetic age acceleration (EAA) in adults, a biomarker of morbidity and mortality. DNA methylation was measured in peripheral blood mononuclear cells (PBMCs) and buccal cells from 40 adults (median age = 49 years) in Chile with and without high prenatal and early-life arsenic exposure. EAA was calculated using the Horvath, Hannum, PhenoAge, skin and blood, GrimAge, and DNA methylation telomere length clocks. We evaluated associations between arsenic exposure and EAA using robust linear models. Participants classified as with and without arsenic exposure had a median drinking water arsenic concentration at birth of 555 and 2 μg/l, respectively. In PBMCs, adjusting for sex and smoking, exposure was associated with a 6-year PhenoAge acceleration [B (95% CI) = 6.01 (2.60, 9.42)]. After adjusting for cell-type composition, we found positive associations with Hannum EAA [B (95% CI) = 3.11 (0.13, 6.10)], skin and blood EAA [B (95% CI) = 1.77 (0.51, 3.03)], and extrinsic EAA [B (95% CI) = 4.90 (1.22, 8.57)]. The association with PhenoAge acceleration in buccal cells was positive but not statistically significant [B (95% CI) = 4.88 (−1.60, 11.36)]. Arsenic exposure limited to early-life stages may be associated with biological aging in adulthood. Future research may provide information on how EAA programmed in early life is related to health.
Thymectomy for treatment of anti-NMDA receptor encephalitis
Authors: Palleiko Benjamin A , Salamatbad Gidon , Bludevich Bryce M , Maxfield Mark W
Published: June 2022

In this case report, we present a 25-year-old woman who was diagnosed with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis and subsequently was found to have thymic hyperplasia. She underwent robotic bilateral access thymectomy for treatment of her anti-NMDA receptor encephalitis and has remained asymptomatic after her operation without any medication. This is only the second reported case of thymectomy for treatment of this condition. This case may further suggest thymic tissue is involved in the development of anti-NMDA receptor encephalitis and that thymectomy is an appropriate treatment for a subset of patients with this disease.
Successful repair of an outflow graft twisting of Heartmate II left ventricular assist device: a case report
Authors: Berger Rafal , Radwan Medhat , Werner Sebastian , Schlensak Christian
Published: June 2022

An outflow graft obstruction impairing the blood flow is a complication of a left ventricular assist device therapy due to thrombosis as the most common cause. We describe a rare case of a patient who presented with a new low-flow alarm after 7 years of uneventful left ventricular assist device support with Heartmate II device. Computed tomography and surgical exploration revealed an obstruction caused by a twist of the outflow graft. A successful surgical repair without the use of cardiopulmonary bypass could be performed and resulted in immediate relief of symptoms.
Thermal sensitivity and seasonal change in the gut microbiome of a desert ant, Cephalotes rohweri
Authors: McMunn Marshall S , Hudson Asher I , Zemenick Ash T , Egerer Monika , Bennett Lucas , Philpott Stacy M , Vannette Rachel L
Published: June 2022

Microorganisms within ectotherms must withstand the variable body temperatures of their hosts. Shifts in host body temperature resulting from climate change have the potential to shape ectotherm microbiome composition. Microbiome compositional changes occurring in response to temperature in nature have not been frequently examined, restricting our ability to predict microbe-mediated ectotherm responses to climate change. In a set of field-based observations, we characterized gut bacterial communities and thermal exposure across a population of desert arboreal ants (Cephalotes rohweri). In a paired growth chamber experiment, we exposed ant colonies to variable temperature regimes differing by 5°C for three months. We found that the abundance and composition of ant-associated bacteria were sensitive to elevated temperatures in both field and laboratory experiments. We observed a subset of taxa that responded similarly to temperature in the experimental and observational study, suggesting a role of seasonal temperature and local temperature differences amongst nests in shaping microbiomes within the ant population. Bacterial mutualists in the genus Cephaloticoccus (Opitutales: Opitutaceae) were especially sensitive to change in temperature—decreasing in abundance in naturally warm summer nests and warm growth chambers. We also report the discovery of a member of the Candidate Phlya Radiation (Phylum: Gracilibacteria), a suspected epibiont, found in low abundance within the guts of this ant species.
Desulfolunaspp. form a cosmopolitan group of anaerobic dehalogenating bacteria widely distributed in marine sponges
Authors: Horna-Gray Isabel , Lopez Nora A , Ahn Youngbeom , Saks Brandon , Girer Nathaniel , Hentschel Ute , McCarthy Peter J , Kerkhof Lee J , Häggblom Max M
Published: June 2022

Host-specific microbial communities thrive within sponge tissues and this association between sponge and associated microbiota may be driven by the organohalogen chemistry of the sponge animal. Several sponge species produce diverse organobromine secondary metabolites (e.g. brominated phenolics, indoles, and pyrroles) that may function as a chemical defense against microbial fouling, infection or predation. In this study, anaerobic cultures prepared from marine sponges were amended with 2,6-dibromophenol as the electron acceptor and short chain organic acids as electron donors. We observed reductive dehalogenation from diverse sponge species collected at disparate temperate and tropical waters suggesting that biogenic organohalides appear to enrich for populations of dehalogenating microorganisms in the sponge animal. Further enrichment by successive transfers with 2,6-dibromophenol as the sole electron acceptor demonstrated the presence of dehalogenating bacteria in over 20 sponge species collected from temperate and tropical ecoregions in the Atlantic and Pacific Oceans and the Mediterranean Sea. The enriched dehalogenating strains were closely related to Desulfoluna spongiiphila and Desulfoluna butyratoxydans, suggesting a cosmopolitan association between Desulfoluna spp. and various marine sponges. In vivo reductive dehalogenation in intact sponges was also demonstrated. Organobromide-rich sponges may thus provide a specialized habitat for organohalide-respiring microbes and D. spongiiphila and/or its close relatives are responsible for reductive dehalogenation in geographically widely distributed sponge species.
Clay chips and beads capture in situ barley root microbiota and facilitate in vitro long-term preservation of microbial strains
Authors: Abdelfadil Mohamed R , Taha Manar H , El-Hadidi Mohamed , Hamza Mervat A , Youssef Hanan H , Khalil Mohab , Henawy Ahmed R , Nemr Rahma A , Elsawey Hend , Tchuisseu Tchakounte Gylaine Vanissa , Abbas Mohamed , Youssef Gehan H , Witzel Katja , Shawky Mohamed Essam , Fayez Mohamed , Kolb Steffen , Hegazi Nabil A , Ruppel Silke
Published: June 2022

Capturing the diverse microbiota from healthy and/or stress resilient plants for further preservation and transfer to unproductive and pathogen overloaded soils, might be a tool to restore disturbed plant–microbe interactions. Here, we introduce Aswan Pink Clay as a low-cost technology for capturing and storing the living root microbiota. Clay chips were incorporated into the growth milieu of barley plants and developed under gnotobiotic conditions, to capture and host the rhizospheric microbiota. Afterward, it was tested by both a culture-independent (16S rRNA gene metabarcoding) and -dependent approach. Both methods revealed no significant differences between roots and adjacent clay chips in regard total abundance and structure of the present microbiota. Clay shaped as beads adequately supported the long-term preservation of viable pure isolates of typical rhizospheric microbes, i.e. Bacillus circulans, Klebsiella oxytoca, Sinorhizobium meliloti, and Saccharomyces sp., up to 11 months stored at −20°C, 4°C, and ambient temperature. The used clay chips and beads have the capacity to capture the root microbiota and to long-term preserve pure isolates. Hence, the developed approach is qualified to build on it a comprehensive strategy to transfer and store complex and living environmental microbiota of rhizosphere toward biotechnological application in sustainable plant production and environmental rehabilitation.