Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies

BACKGROUND: <br/> Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.<br/> METHODOLOGY:<br/> Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.<br/> PRINCIPLE FINDINGS:<br/> IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.<br/> CONCLUSION:<br/> Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh

Carbon-fibre plates for traumatic and (impending) pathological fracture fixation: where do we stand? A systematic review

BackgroundCarbon-fibre (CF) plates are increasingly used for fracture fixation. This systematic review evaluated complications associated with CF plate fixation. It also compared outcomes of patients treated with CF plates versus metal plates, aiming to determine if CF plates offered comparable results. The study hypothesized that CF plates display similar complication rates and clinical outcomes as metal plates for fracture fixation.MethodsThe study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were searched from database inception until June 2023: PubMed, MEDLINE, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar. Studies reporting on clinical and radiological outcomes of patients treated with CF plates for traumatic fractures and (impending) pathological fractures were included. Study quality was assessed, and complications were documented as number and percentage per anatomic region.ResultsA total of 27 studies of moderate to very low quality of evidence were included. Of these, 22 studies (800 patients, median follow-up 12 months) focused on traumatic fractures, and 5 studies (102 patients, median follow-up 12 months) on (impending) pathological fractures. A total of 11 studies (497 patients, median follow-up 16 months) compared CF plates with metal plates. Regarding traumatic fractures, the following complications were mostly reported: soft tissue complications (52 out of 391; 13%) for the humerus, structural complications (6 out of 291; 2%) for the distal radius, nonunion and structural complication (1 out of 34; 3%) for the femur, and infection (4 out of 104; 4%) for the ankle. For (impending) pathological fractures, the most frequently reported complications were infections (2 out of 14; 14%) for the humerus and structural complication (6 out of 86; 7%) for the femur/tibia. Comparative studies reported mixed results, although the majority (7 out of 11; 64%) reported no significant differences in clinical or radiological outcomes between patients treated with CF or metal plates.ConclusionThis systematic review did not reveal a concerning number of complications related to CF plate fixation. Comparative studies showed no significant differences between CF plates and metal plates for traumatic fracture fixation. Therefore, CF plates appear to be a viable alternative to metal plates. However, high-quality randomized controlled trials (RCTs) with long-term follow-up are strongly recommended to provide additional evidence supporting the use of CF plates.Level of evidence: III, systematic review.Orthopaedics, Trauma Surgery and Rehabilitatio

Introducing fluorescence-guided surgery for pediatric Ewing, osteo-, and Rhabdomyosarcomas: a literature review

Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.Experimentele farmacotherapi

Candidate biomarkers for specific intraoperative near-infrared imaging of soft tissue sarcomas: a systematic review

Simple SummaryNear-infrared imaging of tumors during surgery facilitates the oncologic surgeon to distinguish malignant from healthy tissue. The technique is based on fluorescent tracers binding to tumor biomarkers on malignant cells. Currently, there are no clinically available fluorescent tracers that specifically target soft tissue sarcomas. This review searched the literature to find candidate biomarkers for soft tissue sarcomas, based on clinically used therapeutic antibodies. The search revealed 7 biomarkers: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFR alpha, and CD40. These biomarkers are abundantly present on soft tissue sarcoma tumor cells and are already being targeted with humanized monoclonal antibodies. The conjugation of these antibodies with a fluorescent dye will yield in specific tracers for image-guided surgery of soft tissue sarcomas to improve the success rates of tumor resections.Surgery is the mainstay of treatment for localized soft tissue sarcomas (STS). The curative treatment highly depends on complete tumor resection, as positive margins are associated with local recurrence (LR) and prognosis. However, determining the tumor margin during surgery is challenging. Real-time tumor-specific imaging can facilitate complete resection by visualizing tumor tissue during surgery. Unfortunately, STS specific tracers are presently not clinically available. In this review, STS-associated cell surface-expressed biomarkers, which are currently already clinically targeted with monoclonal antibodies for therapeutic purposes, are evaluated for their use in near-infrared fluorescence (NIRF) imaging of STS. Clinically targeted biomarkers in STS were extracted from clinical trial registers and a PubMed search was performed. Data on biomarker characteristics, sample size, percentage of biomarker-positive STS samples, pattern of biomarker expression, biomarker internalization features, and previous applications of the biomarker in imaging were extracted. The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFR alpha, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFR alpha for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.Surgical oncolog

Evaluation of potential targets for fluorescence-guided surgery in pediatric Ewing sarcoma: a preclinical proof-of-concept study

Simple Summary The only cure for children with Ewing sarcoma (ES) is surgery. Unfortunately, surgeons are often not able to differentiate healthy from malignant tissue. Fluorescent imaging during the operation will facilitate recognition of malignant cells, but unfortunately there are no ES specific tracers available yet. We searched for proteins on ES cells that could be used as a target against which specific tracers could be developed. The most promising proteins, CD99, CD117, and GD2, were found in paraffin-embedded tissue samples collected from ES patients. Tracers against CD99 and CD117, consisting of monoclonal antibodies attached with a fluorescent dye, showed positive signals on cultured ES cells. In a proof-of-concept study, these tracers were topically applied on fresh ES tissue, showing a signal in the tumor. Our results indicate the applicability for fluorescence-guided surgery of ES-based tracers, but these data have to be confirmed in a larger cohort of pediatric ES patients. Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients.Orthopaedics, Trauma Surgery and Rehabilitatio

Environmentally Persistent Free Radicals (EPFRs). 3. Free versus Bound Hydroxyl Radicals in EPFR Aqueous Solutions

Additional experimental evidence is presented for in vitro generation of hydroxyl radicals because of redox cycling of environmentally persistent free radicals (EPFRs) produced after adsorption of 2-monochlorophenol at 230 °C (2-MCP-230) on copper oxide supported by silica, 5% Cu(II)O/silica (3.9% Cu). A chemical spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), in conjunction with electron paramagnetic resonance (EPR) spectroscopy was employed. Experiments in spiked O17 water have shown that ∼15% of hydroxyl radicals formed as a result of redox cycling. This amount of hydroxyl radicals arises from an exogenous Fenton reaction and may stay either partially trapped on the surface of particulate matter (physisorbed or chemisorbed) or transferred into solution as free OH. Computational work confirms the highly stable nature of the DMPO–OH adduct, as an intermediate produced by interaction of DMPO with physisorbed/chemisorbed OH (at the interface of solid catalyst/solution). All reaction pathways have been supported by ab initio calculations

Corannulene and its complex with water: A tiny cup of water

Contains fulltext : 174624.pdf (publisher's version ) (Open Access) Contains fulltext : 174624_suppl.pdf (publisher's version ) (Open Access

Is the Anterior Injection Approach Without Ultrasound Guidance Superior to the Posterior Approach for Adhesive Capsulitis of the Shoulder? A Sequential, Prospective Trial

Background Shoulder injections for conditions such as adhesive capsulitis are commonly performed and can be administered through image-based or landmark-based injection approaches. Ultrasound-guided injections are widely used and accurate because ultrasound allows real-time visualization of the needle and injected contrast. Landmark-based injections would be advantageous, if they were accurate, because they would save the time and expense associated with ultrasound. However, few prospective studies have compared well-described landmark-based shoulder injection techniques without ultrasound. Question/purpose Using anatomic landmarks, and without using ultrasound, is the accuracy of glenohumeral injection for adhesive capsulitis greater via the posterior approach or via a new anterior approach? Methods Between 2018 and 2020, we treated 108 patients potentially eligible for adhesive capsulitis treatment. These patients had clinical symptoms of aggravating shoulder pain with a duration of less than 4 months and passively impaired, painful glenohumeral ROM. Due to the exclusion of patients with other shoulder conditions (full-thickness rotator cuff ruptures and posttraumatic stiffness), 95 patients received an injection in this sequential, prospective, comparative study. Between 2018 and 2019, 41 patients (17 males and 24 females; mean age 52 +/- 5 years; mean BMI 24 +/- 3 kg/m(2)) were injected through the posterior approach, with the acromion as the anatomical landmark, during the first part of the study period. After that, between 2019 and 2020, 54 patients (20 males and 34 females; mean age 54 +/- 4 years; mean BMI 23 +/- 3 kg/m(2)) received an injection through a new anterior approach, with the acromioclavicular joint as the anatomic landmark, during the second part of the study period. Injections via both approaches were administered by two experienced shoulder specialists (both with more than 10 years of experience). Both specialists had experience with the posterior approach before this study, and neither had previous training with the new anterior approach. Injections contained a corticosteroid, local anaesthetic, and contrast medium. Radiographs were taken within 20 minutes after the injection, and a radiologist blinded to the technique determined accuracy. Accurate injections were defined as having contrast fluid limited to the glenohumeral joint, while inaccurate injections displayed leakage of contrast fluid into the soft tissue or subacromial space. All of the enrolled patients were analyzed. Results In the group with the posterior approach, the accuracy was 78% (32 of 41) in contrast to 94% (51 of 54, odds ratio 0.21 [95% CI 0.05 to 0.83]; p = 0.03) in patients with the new anterior approach. Conclusion The new anterior approach without the use of ultrasound was more accurate than the posterior approach. In fact, it was nearly as accurate as previously published ultrasound-guided approaches. We recommend using the new anterior approach for intraarticular glenohumeral injections instead of ultrasound-guided injections because it will save time and costs associated with ultrasound. Still, the clinical effects (anxiety, pain, functional outcome, and adverse events) of the new anterior approach should be compared with ultrasound-guided injections in a randomized study.Orthopaedics, Trauma Surgery and Rehabilitatio

Structure of 2,4-Diaminopyrimidine-Theobromine Alternate Base Pairs

We report the structure of dusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine cytosine. We have found the four lowest energy structures, which include the Watson Crick base pairing motif. This Watson Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs

Structure of 2,4-Diaminopyrimidine-Theobromine Alternate Base Pairs

We report the structure of dusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine cytosine. We have found the four lowest energy structures, which include the Watson Crick base pairing motif. This Watson Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs