Acoustic radiation force impulse (ARFI) shear wave elastography of the bowel wall in healthy volunteers and in ulcerative colitis

Background Acoustic radiation force impulse (ARFI) elastography is a non-invasive, ultrasound-based approach of evaluation of tissue elasticity. It has not yet been systematically applied to the bowel wall. Purpose To perform ARFI elastography of the bowel wall in healthy volunteers and patients with ulcerative colitis (UC). Material and Methods A high-frequency ultrasound (with bowel wall thickness and vascularization score) and an ARFI elastography of the bowel wall were performed in 20 patients with UC and 13 healthy volunteers. At least 10 ARFI measurements were obtained within the terminal ileum and the ascending, transverse, descending, and sigmoid colon and correlated with results of high-frequency ultrasound. Results The UC group had mostly moderate disease activity. All patients had signs of inflammation upon B-mode ultrasound. Eight patients showed an ulcerative (ileo)pancolitis. Overall, ARFI elastography values and wall thickness were higher in the UC group than in the group of healthy volunteers (P = 0.021 and P < 0.001, respectively). ARFI velocities of the separate segments were significantly higher in the transverse (P = 0.045) and sigmoid colon (P = 0.032) in case of UC. Conclusion ARFI elastography of the bowel wall of the colonic frame and the terminal ileum is feasible but shows high standard deviation. ARFI shear wave velocities appear to be slightly higher in patients with UC than in healthy volunteers, particularly in the sigmoid and transverse colon. Further studies are needed

Identification and functional characterization of a novel acetyl-CoA carboxylase mutation associated with ketoenol resistance in Bemisia tabaci

This is the final version. Available from Elsevier / Academic Press via the DOI in this record. Insecticides of the tetronic/tetramic acid family (cyclic ketoenols) are widely used to control sucking pests such as whiteflies, aphids and mites. They act as inhibitors of acetyl-CoA carboxylase (ACC), a key enzyme for lipid biosynthesis across taxa. While it is well documented that plant ACCs targeted by herbicides have developed resistance associated with mutations at the carboxyltransferase (CT) domain, resistance to ketoenols in invertebrate pests has been previously associated either with metabolic resistance or with non-validated candidate mutations in different ACC domains. A recent study revealed high levels of spiromesifen and spirotetramat resistance in Spanish field populations of the whitefly Bemisia tabaci that was not thought to be associated with metabolic resistance. We confirm the presence of high resistance levels (up to >640-fold) against ketoenol insecticides in both Spanish and Australian B. tabaci strains of the MED and MEAM1 species, respectively. RNAseq analysis revealed the presence of an ACC variant bearing a mutation that results in an amino acid substitution, A2083V, in a highly conserved region of the CT domain. F1 progeny resulting from reciprocal crosses between susceptible and resistant lines are almost fully resistant, suggesting an autosomal dominant mode of inheritance. In order to functionally investigate the contribution of this mutation and other candidate mutations previously reported in resistance phenotypes, we used CRISPR/Cas9 to generate genome modified Drosophila lines. Toxicity bioassays using multiple transgenic fly lines confirmed that A2083V causes high levels of resistance to commercial ketoenols. We therefore developed a pyrosequencing-based diagnostic assay to map the spread of the resistance alleles in field-collected samples from Spain. Our screening confirmed the presence of target-site resistance in numerous field-populations collected in Sevilla, Murcia and Almeria. This emphasizes the importance of implementing appropriate resistance management strategies to prevent or slow the spread of resistance through global whitefly populations.European Union Horizon 2020Australian cotton research and development corporatio

Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin’s disease developing resistance to pembrolizumab

Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin’s disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r/r Hodgkin’s disease. The benefit after pre-treatment with ICPi has not been studied, yet. Here, we report a patient with progressive Hodgkin’s disease on Pembrolizumab for the first time who achieved sustained complete remission (CR) after initiation of MEPED therapy. A 57-year-old patient was pre-treated with brentuximab vedotin for relapsed advanced Hodgkin’s disease and had received Pembrolizumab for progression from November 2020 to July 2022. Due to further progression, MEPED therapy was started in August 2022 and continued until May 2023. It consisted of a strictly oral daily (28-day cycle) application of low-dose treosulfan 250 mg, everolimus 15 mg, pioglitazone 45 mg, etoricoxib 60 mg, and dexamethasone 0.5 mg. Treatment response was evaluated by F-18 FDG-PET/CT (PET/CT). CR was defined by a negative Deauville score (DS) of 1-3. Already 3 months after starting MEPED, a CR (DS: 3) was confirmed by PET/CT in November 2022. The next follow-up in May 2023 continued to show CR (DS: 3). The therapy was very well tolerated. No hematological or other organ toxicity was observed. However, in May 2023 the patient presented with leg edema and weight gain, most likely due to pioglitazone and the PET/CT revealed suspected everolimus-induced pneumonitis, so MEPED was discontinued and diuretic therapy and treatment with prednisolone was started with gradual dose reduction. This resulted in a rapid complete resolution of the symptoms. The next PET-CT in July 2023 continued to show CR (DS: 3) without evidence of pneumonitis. Currently, therapy with MEPED has not been resumed. In conclusion, we demonstrate for the first time that MEPED therapy is highly effective in a patient with Hodgkin’s disease who has been refractory to ICPi. Sustained CR was achieved over 11 months after initiation of MEPED therapy. Further studies on a larger patient cohort should be performed

The genetic architecture of a host shift: An adaptive walk protected an aphid and its endosymbiont from plant chemical defenses

This is the final version. Available from American Association for the Advancement of Science via the DOI in this record. The RNA and DNA sequence data generated in this study have been deposited with NCBI under accession number PRJNA574571. The sequence of RPS11/ADAMTS9 has been deposited under NCBI accession number MF1555663, and the accession numbers of other genes characterized in this study can be found in data file S1. All other data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.Host shifts can lead to ecological speciation and the emergence of new pests and pathogens. However, the mutational events that facilitate the exploitation of novel hosts are poorly understood. Here, we characterize an adaptive walk underpinning the host shift of the aphid Myzus persicae to tobacco, including evolution of mechanisms that overcame tobacco chemical defenses. A series of mutational events added as many as 1.5 million nucleotides to the genome of the tobacco-adapted subspecies, M. p. nicotianae, and yielded profound increases in expression of an enzyme that efficiently detoxifies nicotine, both in aphid gut tissue and in the bacteriocytes housing the obligate aphid symbiont Buchnera aphidicola. This dual evolutionary solution overcame the challenge of preserving fitness of a mutualistic symbiosis during adaptation to a toxic novel host. Our results reveal the intricate processes by which genetic novelty can arise and drive the evolution of key innovations required for ecological adaptation.European Union Horizon 2020Czech Science FoundationCzech Science FoundationEuropean Social Fund and the state budget of the Czech RepublicBiotechnology and Biological Sciences Research Council (BBSRC

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Partial retinal fenestration for optic disc pit maculopathy

The frequent side effect of maculopathy in the optic disc pit seems to be based on a pathogenetically incompletely comprehended fluid exchange between the optic disc and the macula. A surgical procedure using vitrectomy with the creation of a barrier between the macula and the optic disc pit, for example using an endolaser or a scleral flap, is possible. In addition, the partial retinal fenestration as described here in detail represents an alternative surgical procedure resulting in liquid being conducted from the optic disc pit into the vitreous cavity. Complete absorption of the subretinal and intraretinal fluid can be expected within the first postoperative year

Retrospective analysis of OCT parameters after intravitreal anti-VEGF inhibitors in neovascular AMD patients in a real-world setting

Purpose The aim of the present study was to evaluate changes of best corrected visual acuity (BCVA), retinal nerve fiber layer thickness (RNFL), total macular volume (TMV), intraocular pressure (IOP) and central retinal thickness (CRT) after intravitreal injection of ranibizumab, bevacizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD) in a clinical real world setting. Methods In a retrospective clinical study design, 120 patients (80 women and 40 men) were analyzed after being diagnosed with nAMD within 8 years (2010-2018). Every patient received at least 6 anti-VEGF injections in a Pro-Re-Nata or Treat-and-Extend regimen. OCT parameters (RNFL, TMV, CRT) and visual acuity (BCVA) were assessed at first diagnosis, at treatment day and during the course. Results Intraretinal fluid was reduced significantly in a magnitude of 88-64 mu m (CRT) and 0.75-0.55 mm(3) (TMV). Apart from a significant reduction immediately after the therapy start (post-3 injections) with ranibizumab (- 1.4 mu m, p = 0.03), RNFL thickness remained constant. A slight improvement in visual acuity of 0.06 logMAR could initially be observed. If further injections were required, only stabilization was achieved compared to baseline visual acuity. Conclusion The changes of OCT parameters CRT, TMV, and RNFL as well as the stabilization of functional results (BCVA) as illustrated in this study comparing effects of different anti-VEGF-agents provide evidence for the transferability of former results to a clinical real-world setting