HYENA detects oncogenes activated by distal enhancers in cancer.

Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm 'HYENA' to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking based on tumor whole-genome and transcriptome sequencing data. HYENA detects genes whose elevated expression is associated with somatic SVs by using a rank-based regression model. We systematically analyze 1146 tumors across 25 types of adult tumors and identify a total of 108 candidate oncogenes including many non-coding genes. A long non-coding RNA TOB1-AS1 is activated by various types of SVs in 10% of pancreatic cancers through altered 3-dimensional genome structure. We find that high expression of TOB1-AS1 can promote cell invasion and metastasis. Our study highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression.

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.

Mitochondrial metabolism is an attractive target for cancer therapy1,2. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC)1,3. Here we show that BTB and CNC homology1 (BACH1)4, a haem-binding transcription factor that is increased in expression in tumours from patients with TNBC, targets mitochondrial metabolism. BACH1 decreases glucose utilization in the tricarboxylic acid cycle and negatively regulates transcription of electron transport chain (ETC) genes. BACH1 depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin5,6, suppressing growth of both cell line and patient-derived tumour xenografts. Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7. Finally, BACH1 gene expression inversely correlates with ETC gene expression in tumours from patients with breast cancer and in other tumour types, which highlights the clinical relevance of our findings. This study demonstrates that mitochondrial metabolism can be exploited by targeting BACH1 to sensitize breast cancer and potentially other tumour tissues to mitochondrial inhibitors.

Cu/Cu2O/C nanoparticles and MXene based composite for non-enzymatic glucose sensors.

Copper/Cuprous oxide/Carbon nanoparticles decorated MXene composite was prepared and subsequently examined for its potential application as a non-enzymatic glucose sensor. To carry out this, initially the Cu MOF/MXene composite was synthesised by the hydrothermal method and was annealed in an unreacted environment at different time intervals. During this process, petal like Cu MOF on MXene loses the organic ligands to form a Cu/Cu2O/C based nanoparticles on MXene. Further, an electrode was fabricated with the developed material for understanding the sensing performance by cyclic voltammetry and chronoamperometry in 0.1 M NaOH solution. Results reveal that the highest weight percentage of copper oxide in the composite (15 min of annealed material) shows a higher electro catalytic activity for sensing glucose molecules due to more active sites with good electron transfer ability in the composite. The formed composite exhibits a wide linear range of 0.001-26.5 mM, with a sensitivity of 762.53µAmM-1cm-2(0.001-10.1 mM), and 397.18µAmM-1cm-2(11.2-26.9 mM) and the limit of detection was 0.103µM. In addition to this, the prepared electrode shows a good reusability, repeatability, selectivity with other interferences, stability (93.65% after 30 days of storage), and feasibility of measuring glucose in real samples. This finding reveals that the metal oxide derived from MOF based nanoparticle on the MXene surface will promote the use of non-enzymatic glucose sensors.

Predicting concrete strength early age using a combination of machine learning and electromechanical impedance with nano-enhanced sensors.

To ensure the structural integrity of concrete and prevent unanticipated fracturing, real-time monitoring of early-age concrete's strength development is essential, mainly through advanced techniques such as nano-enhanced sensors. The piezoelectric-based electro-mechanical impedance (EMI) method with nano-enhanced sensors is emerging as a practical solution for such monitoring requirements. This study presents a strength estimation method based on Non-Destructive Testing (NDT) Techniques and Long Short-Term Memory (LSTM) and artificial neural networks (ANNs) as hybrid (NDT-LSTMs-ANN), including several types of concrete strength-related agents. Input data includes water-to-cement rate, temperature, curing time, and maturity based on interior temperature, allowing experimentally monitoring the development of concrete strength from the early steps of hydration and casting to the last stages of hardening 28 days after the casting. The study investigated the impact of various factors on concrete strength development, utilizing a cutting-edge approach that combines traditional models with nano-enhanced piezoelectric sensors and NDT-LSTMs-ANN enhanced with nanotechnology. The results demonstrate that the hybrid provides highly accurate concrete strength estimation for construction safety and efficiency. Adopting the piezoelectric-based EMI technique with these advanced sensors offers a viable and effective monitoring solution, presenting a significant leap forward for the construction industry's structural health monitoring practices.

Comparison of Postoperative Complications Between Laparoscopic Myomectomy and Total Laparoscopic Hysterectomy.

STUDY OBJECTIVE: To compare postoperative complications of laparoscopic myomectomy (LM) with total laparoscopic hysterectomy (TLH). A secondary outcome examined whether complications differ by age. DESIGN: A retrospective cohort study. SETTING: A multicenter academic healthcare system. PATIENTS: Individuals > 18 years old undergoing LM from 2011 to 2021 or TLH for benign indications from 2020 to 2021. INTERVENTIONS: LM or TLH. MEASUREMENTS AND MAIN RESULTS: There were 1178 patients in the LM group and 1304 in the TLH group. Patients who underwent LM were younger, more often premenopausal, nonsmokers, with lower body mass index, lower preoperative hemoglobin, larger uterine size, and lower American Society of Anesthesiologists class. LM had longer operative times (154.1 ± 74.5 vs 145.9 ± 70.5 min, p <.0001), higher use of intraoperative hemostatic agents (25% vs 9.1%, p <.0001), and higher estimated blood loss (222.7 ± 313.0 vs 87.4 ± 145.9 mL, p <.0001) than TLH. Postoperatively, LM was associated with fewer surgical site infections (3.1% vs 5.8%, p <.0001), readmissions within 30 days (2.0% vs 5.6%, p <.0001), or emergency department visits within 90 days (10.9% vs 14.4%, p = .008). LM were more likely to be admitted 24 hours postoperatively (5.9% vs 3.4%, p = .0023) or receive a blood transfusion within 30 days (4.0% vs 1.0%, p <.0001). Variables associated with increased risk of postoperative complications were tobacco use, American Society of Anesthesiologists class > 3, preoperative anemia, estimated blood loss ≥ 150 mL, and specimen weight > 250 g. Logistic regression demonstrated that operative time ≥185 minutes was most strongly associated with 24-hour admission postoperatively (odds ratio [OR] = 12.95; 95% confidence interval [CI], 3.71-45.27). In individuals ≤ 37 years of age, the LM group was less likely than the TLH group to experience surgical site infection (OR, 0.30; 95% CI, 0.14-0.62) or present to the emergency department (OR, 0.40; 95% CI, 0.26-0.63). CONCLUSION: In this large cohort of patients, both LM and TLH had low rates of postoperative complications, but the complications differed for each approach. In appropriate surgical candidates, either approach may be offered based upon patients' goals.

Association between skin ultrasound parameters and revision surgery after posterior spinal fusion.

PURPOSE: The literature is scarce in exploring the role of imaging parameters like ultrasound (US) as a biomarker for surgical outcomes. The purpose of this study is to investigate the associations between skin US parameters and revision surgery following spine lumbar fusion. METHODS: Posterior lumbar fusion patients with 2-years follow-up were assessed. Previous fusion or revision not due to adjacent segment disease (ASD) were excluded. Revisions were classified as cases and non-revision were classified as controls. US measurements conducted at two standardized locations on the lumbar back. Skin echogenicity of the average dermal (AD), upper 1/3 of the dermal (UD), lower 1/3 of the dermal (LD), and subcutaneous layer were measured. Echogenicity was calculated with the embedded echogenicity function of our institution's imaging platform (PACS). Statistical significance was set at p < 0.05. RESULTS: A total of 128 patients (51% female, age 62 [54-72] years) were included in the final analysis. 17 patients required revision surgery. AD, UD, and LD echogenicity showed significantly higher results among revision cases 124.5 [IQR = 115.75,131.63], 128.5 [IQR = 125,131.63] and 125.5 [IQR = 107.91,136.50] compared to the control group 114.3 [IQR = 98.83,124.8], 118.5 [IQR = 109.28,127.50], 114 [IQR = 94.20,126.75] respectively. CONCLUSION: The findings of this study demonstrate a significant association between higher echogenicity values in different layers of the dermis and requiring revision surgery. The results provide insights into the potential use of skin US parameters as predictors for revision surgery. These findings may reflect underlying alterations in collagen. Further research is warranted to elucidate the mechanisms driving these associations.

The Association between prior arthroplasty and Paraspinal Muscle Degeneration in patients undergoing elective lumbar surgery.

PURPOSE: Spinal and lower extremity degeneration often causes pain and disability. Lower extremity osteoarthritis, eventually leading to total knee- (TKA) and -hip arthroplasty (THA), can alter posture through compensatory mechanisms, potentially causing spinal misalignment and paraspinal muscle (PM) atrophy. This study aims to evaluate the association between prior THA or TKA and PM-degeneration in patients undergoing elective lumbar surgery for degenerative conditions. METHODS: A retrospective analysis of patients undergoing lumbar surgery for degenerative conditions was conducted. Patients were categorized based on prior THA, TKA, or both. Quantitative analysis of functional cross-sectional area (fCSA) and fat infiltration (FI) of psoas, multifidus (MF), and erector spinae (ES) muscles at L4-level was performed using T2-weighted MRI images. The association between the FI and fCSA of the PM and prior arthroplasty was investigated. Differences were assessed using ANOVA and multivariable linear regression. RESULTS: Overall, 584 patients (60% female, 64 ± 12 years) were included. 66 patients (11%) had prior TKA, 36 patients (6%) THA, and 15 patients (3%) both TKA and THA. Patients with arthroplasty were mostly female (57%) and notably older (p < 0.001). The FI of the MF and the ES was significantly higher in the arthroplasty-group (both p < 0.001). Patients with prior TKA showed significantly higher FI (Est = 4.3%, p = 0.013) and lower fCSA (Est=-0.9 cm2, p = 0.012) in the MF compared to the non-arthroplasty-group. CONCLUSION: This study demonstrates a significant lower fCSA and higher FI in the MF among individuals with prior TKA. This highlights the complex knee-spine relationship and how these structures interact with each other.

Abdominal aortic calcification is an independent predictor of perioperative blood loss in posterior spinal fusion surgery.

OBJECTIVE: Abdominal aortic calcification (AAC), often found incidentally on lateral lumbar radiographs, is increasingly recognized for its association with adverse outcomes in spine surgery. As a marker of advanced atherosclerosis affecting cardiovascular dynamics, this study evaluates AAC's impact on perioperative blood loss in posterior spinal fusion (PSF). METHODS: Patients undergoing PSF from March 2016 to July 2023 were included. Estimated blood loss (EBL) and total blood volume (TBV) were calculated. AAC was assessed on lateral lumbar radiographs according to the Kauppila classification. Predictors of the EBL-to-TBV ratio (%EBL/TBV) were examined via univariable and multivariable regression analyses, which adjusted for parameters such as hypertension and aspirin use. RESULTS: A total of 199 patients (47.2% female) were analyzed. AAC was present in 106 patients (53.3%). AAC independently predicted %EBL/TBV, accounting for an increase in blood loss of 4.46% of TBV (95% CI 1.17-7.74, p = 0.008). CONCLUSIONS: This is the first study to identify AAC as an independent predictor of perioperative blood loss in PSF. In addition to its link to degenerative spinal conditions and adverse postoperative outcomes, the relationship between AAC and increased blood loss warrants attention in patients undergoing PSF.

Association between lumbar intervertebral vacuum phenomenon severity and posterior paraspinal muscle atrophy in patients undergoing spine surgery.

PURPOSE: Intervertebral vacuum phenomenon (IVP) and paraspinal muscular atrophy are age-related changes in the lumbar spine. The relationship between both parameters has not been investigated. We aimed to analyze the correlation between IVP and paraspinal muscular atrophy in addition to describing the lumbar vacuum severity (LVS) scale, a new parameter to estimate lumbar degeneration. METHODS: We analyzed patients undergoing spine surgery between 2014 and 2016. IVP severity was assessed utilizing CT scans. The combination of vacuum severity on each lumbar level was used to define the LVS scale, which was classified into mild, moderate and severe. MRIs were used to evaluate paraspinal muscular fatty infiltration of the multifidus and erector spinae. The association of fatty infiltration with the severity of IVP at each lumbar level was assessed with a univariable and multivariable ordinal regression model. RESULTS: Two hundred and sixty-seven patients were included in our study (128 females and 139 males) with a mean age of 62.6 years (55.1-71.2). Multivariate analysis adjusted for age, BMI and sex showed positive correlations between LVS-scale severity and fatty infiltration in the multifidus and erector spinae, whereas no correlation was observed in the psoas muscle. CONCLUSION: IVP severity is positively correlated with paraspinal muscular fatty infiltration. This correlation was stronger for the multifidus than the erector spinae. No correlations were observed in the psoas muscle. The lumbar vacuum severity scale was significantly correlated with advanced disc degeneration with vacuum phenomenon.

Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis.

Type 2 diabetes (T2D) is implicated in the injury of several organs, including the brain resulting in neuronal damage, which may lead to cognitive impairment and dementia. Additionally, it is linked to inflammation, cytokine release, apoptosis and various degenerative conditions. Astrocytes and microglia might have a role in mediating these processes. Caffeine, a psychoactive beverage, has been shown to reduce the risk of cognitive and memory impairment. This study proposes anti-inflammatory and anti-apoptotic role of caffeine, which can be mediated via microglia/astrocyte activation and overexpression of pro-inflammatory molecules. T2D was induced in rats by feeding with high fat high sugar diet and injecting a single low dose streptozotocin (STZ) intraperitoneally. Other diabetic rats were given caffeine orally (in two doses) for 5 weeks, starting 1 week before STZ injection. Measurement of plasma cytokines, TNFα and IL6, was performed using enzyme-linked immunosorbent assay (ELISA) technique. After sacrificing animals, brains were obtained and processed for histological evaluation. Immunohistochemistry was also performed using the following primary antibodies, anti-astrocyte marker GFAP, anti-microglia marker CD11b and apoptotic marker (anti-cleaved caspase-3). There was upregulation of IL6 and TNF-α in diabetic rats. Additionally, histological evaluation of the hippocampus of diabetic rats revealed cellular degeneration. There was increased immunostaining of GFAP, CD11b and cleaved caspase-3 in diabetic rats. Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner. In conclusion, caffeine had an ameliorative role in enhancing hippocampal degenerative changes in T2D.

Revascularization Options for Left Main Disease: What Clinicians Need to Know.

PURPOSE OF REVIEW: Left main disease represents the highest-risk lesion subset of coronary artery disease and is associated with adverse cardiovascular events. Accordingly, we aim to understand how the significance of left main disease is assessed by different modalities, followed by a review of management options in current era. RECENT FINDINGS: Invasive coronary angiogram remains the gold standard for assessment of left main disease, but intracoronary imaging or physiological testing is indicated for angiographically equivocal disease. Revascularization by either coronary artery bypass surgery or percutaneous coronary intervention is strongly recommended, which have been compared by six randomized trials, as well as recent meta-analyses. Surgical revascularization remains the preferred mode of revascularization, especially in patients with high lesion complexity and left ventricular dysfunction. Randomized studies are needed to understand if current-generation stents with the use of intracoronary imaging and improved medical therapy could match outcomes with surgical revascularization.

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway.

A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids VIc, VIf, VIg, VIi, and VIk have the highest antiproliferative activity. Compounds VIc, VIf, VIg, VIi, and VIk inhibited EGFR with IC50 values ranging from 96 to 127 nM. Compounds VIf and VIk had the most potent inhibitory activity as BRAFV600E (IC50 = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI50 = 44 and 35 nM against four cancer cell lines, respectively). Compound VIk, the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC50 value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, VIc, VIf, and VIk have a high capacity to inhibit LOX-IMVI cell line survival.

Abdominal aortic calcification is independently associated with lumbar endplate degeneration.

BACKGROUND: Abdominal aortic calcification (AAC) is associated with lower back pain, reduced bone mineral density of the spine. Vascular changes could also affect the already sparsely perfused intervertebral endplate and intervertebral disc. METHODS: Lumbar MRIs and lateral radiographs of patients with lower back pain were retrospectively analyzed. AAC was assessed on lateral lumbar radiographs according to the Kauppila score, with a maximum score of 24. Patients were grouped into no (AAC = 0), moderate (AAC 1 to ≤ 4), and severe AAC (AAC ≥ 5). Endplate and disc degeneration were classified according to the total endplate score (TEPS) and Pfirrmann classification. The associations between AAC and degenerative changes was analyzed with a generalized mixed model and was adjusted for age, sex, body mass index as well as diabetes mellitus, and smoking status. RESULTS: A total of 217 patients (47.9% female) were included in the analysis, totaling 1085 intervertebral levels. Of those, 45 (20.7%) patients had moderate, and 39 (18%) had severe AAC. The results of the generalized mixed model showed no significant association between AAC and disc degeneration (p > 0.05). In contrast, a significant positive association between AAC and the severity of TEPS (ß: 0.51, 95% CI: 1.92-2.12, p = 0.004) was observed in the multivariable analysis. CONCLUSIONS: This study demonstrates an independent association between AAC and endplate degeneration. These findings expand our knowledge about the degenerative cascade of the lumbar spine and suggest that AAC might be a modifiable risk factor for endplate changes.

New strategies for targeting kinase networks in cancer.

Targeted strategies against specific driver molecules of cancer have brought about many advances in cancer treatment since the early success of the first small-molecule inhibitor Gleevec. Today, there are a multitude of targeted therapies approved by the Food and Drug Administration for the treatment of cancer. However, the initial efficacy of virtually every targeted treatment is often reversed by tumor resistance to the inhibitor through acquisition of new mutations in the target molecule, or reprogramming of the epigenome, transcriptome, or kinome of the tumor cells. At the core of this clinical problem lies the assumption that targeted treatments will only be efficacious if the inhibitors are used at their maximum tolerated doses. Such aggressive regimens create strong selective pressure on the evolutionary progression of the tumor, resulting in resistant cells. High-dose single agent treatments activate alternative mechanisms that bypass the inhibitor, while high-dose combinatorial treatments suffer from increased toxicity resulting in treatment cessation. Although there is an arsenal of targeted agents being tested clinically and preclinically, identifying the most effective combination treatment plan remains a challenge. In this review, we discuss novel targeted strategies with an emphasis on the recent cross-disciplinary studies demonstrating that it is possible to achieve antitumor efficacy without increasing toxicity by adopting low-dose multitarget approaches to treatment of cancer and metastasis.

Scalable Synthesis and Characterization of Multilayer γ-Graphyne, New Carbon Crystals with a Small Direct Band Gap.

γ-Graphyne is the most symmetric sp2/sp1 allotrope of carbon, which can be viewed as graphene uniformly expanded through the insertion of two-carbon acetylenic units between all the aromatic rings. To date, synthesis of bulk γ-graphyne has remained a challenge. We here report the synthesis of multilayer γ-graphyne through crystallization-assisted irreversible cross-coupling polymerization. A comprehensive characterization of this new carbon phase is described, including synchrotron powder X-ray diffraction, electron diffraction, lateral force microscopy, Raman spectroscopy, infrared spectroscopy, and cyclic voltammetry. Experiments indicate that γ-graphyne is a 0.48 eV band gap semiconductor, with a hexagonal a-axis spacing of 6.88 Å and an interlayer spacing of 3.48 Å, which is consistent with theoretical predictions. The observed crystal structure has an aperiodic sheet stacking. The material is thermally stable up to 240 °C but undergoes transformation at higher temperatures. While conventional 2D polymerization and reticular chemistry rely on error correction through reversibility, we demonstrate that a periodic covalent lattice can be synthesized under purely kinetic control. The reported methodology is scalable and inspires extension to other allotropes of the graphyne family.

Targeting Natural Plant Metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular Docking, Molecular Dynamics, and Physicochemical Properties Study.

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than -9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of -49.02, -48.07, and -67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.

Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker?

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.

Pediatric EBV Positive Mucocutaneous Ulceration in Stomach a Rare Entity.

Epstein Barr virus (EBV) related lymphoproliferative diseases may occur in immunocompromised patients or patients with a history of drug use causing immunodeficiency. EBV positive mucocutaneous ulceration in the new classification of lymphoproliferative diseases in 2016 is very rare in children. Involvement occurs in the skin, oral mucosa, and gastrointestinal system. Gastric involvement is very rare in the literature. There is no case of gastric involvement in children. There are no specified modalities in the treatment of EBV positive mucocutaneous ulceration. We presented our pediatric patient with ataxia telangiectasia who presented with abdominal pain and difficulty swallowing and diagnosed with EBV positive mucocutaneous ulceration in the stomach. We started brentuximab vedotin during the treatment process, and complete remission was achieved after 6 cures of treatment. Our patient is the first case of EBV positive mucocutaneous ulceration in the pediatric case series.

Whipple's disease - a rare and challenging complication in a patient with Crohn's disease.

INTRODUCTION: Whipple's disease (WD) is a rare and infectious condition leading to multi-organ impairment caused by Tropheryma whipplei (TW), a ubiquitously occurring bacterium. TW can be detected in tissues by histological detection of PAS ("periodic acid-ship reaction")-positive macrophages and by polymerase-chain-reaction (PCR). Clinically, WD is often characterized by diarrhea, abdominal pain, and weight loss. These symptoms are also typical for a flare in Crohn's disease (CD) and, therefore, can lead to fatal misdiagnosis and wrong treatment by using biologics (e.g., anti-TNF-α). CASE REPORT: We here report a young male patient with pre-existing CD. The patient's symptoms were misinterpreted as a flare of CD and illustrate the multifaceted nature of WD. After intensifying immunosuppressive therapy, the patient developed therapy-refractory diarrhea with several opportunistic infections with a final, fatal outcome. CONCLUSION: Patients with inflammatory bowel disease (IBD) are not only at risk from infectious complications known with clostridium difficile or cytomegalovirus (CMV); infection with WD should also be ruled out by endoscopy and biopsy before the escalation of the immunosuppressive regime.

Relation of the Sural Nerve and Medial Neurovascular Bundle With the Achilles Tendon in Children With Cerebral Palsy Treated by Percutaneous Achilles Tendon Lengthening.

BACKGROUND: One of the most common treatment options for a short Achilles tendon (AT) in cerebral palsy is percutaneous AT lengthening using 3 hemisections. Because of proximity of neurovascular structures around the tendon, iatrogenic injury to them have been a concern about this technique. The sural nerve (SN) is under risk of injury at the site of the lateral incomplete cut, especially if it is done proximally. The medial neurovascular bundle is under injury risk at medial cuts. The aim of the article was to study the anatomical relations of the SN and medial neurovascular bundle to the AT, and define dangerous levels for injury with the help of magnetic resonance imaging (MRI). METHODS: Patients operated for percutaneous Achilles lengthening were called for MRI investigation of the SN and medial neruvascular bundle integrity and their anatomical relation with the AT. The distance of 5 mm was taken as the threshold for increased risk of injury. Measurements were done on MRI at each cm from the insertion of the tendon on both medial and lateral sides, and at the level of the middle cut. RESULTS: Thirty ankles operated and followed at least 1 year were included to the study. On the medial side, the tibial nerve, and the posterior tibial artery lied more than 5 mm away from the tendon at all levels in all patient. On the lateral side, the first 4 cm were relatively safe for the middle lateral cut, while increased risk of SN damage was detected in more proximal levels. Overall, 6 of 30 ankles had radiographically detectable SN injury. CONCLUSIONS: The first 4 cm of the AT on the lateral side was detected to be safe for the middle lateral directed cut, while whole tendon length were found to be safe for the first and the third cuts of the percutaneous Achilles lengthening surgery using 3 hemisections in children with cerebral palsy. LEVEL OF EVIDENCE: Level III.