An inflammatory myofibroblastic tumour (IMT) is a rare neoplasm of mesenchymal origin, defined by myofibroblastic spindle cells accompanied by inflammatory cells, lymphocytes and eosinophils. Its symptomatology depends on the involved site and tends to mimic a malignant tumour clinically and radiologically. The head and neck region accounts for 5% of all IMTs. Here, we report a case of a 35-year-old woman, with no medical history, who presented with a mouth-opening limitation of 8 mm evolving for three years and occurring six months after of a wisdom tooth extraction. She also experienced a recent occurrence of left eye ptosis and a converging strabismus. On examination, the patient had a body temperature at 37°C, with hypoesthaesia of the left chin and infraorbital area, without any other abnormality. Laboratory examinations did not reveal a biological inflammatory syndrome or rhabdomyolysis. The infectious investigations were all negative, as well as the immunological tests, in particular negative for anti-AChR and anti-MuSK antibodies. On the facial computed tomography (CT) scan, we noted an active reshuffle in the left mandible ascending branch with a thickening of the ipsilateral pterygoid muscles and the left temporal meningeal tissue. After corticosteroid therapy 0.7 mg/kg/j, we obtained an improvement in the patient\'s mouth-opening, thus a biopsy of the lesion was performed under local anaesthesia, revealing IMT. The patient continued the corticosteroids therapy with a progressive tapering resulting in a marked clinical improvement of the mouth-opening limitation and her ptosis.
CONCLUSIONS: An inflammatory myofibroblastic tumour (IMT) is a challenging disease.Given the variable clinical and radiological presentation of the disease, it is of paramount importance to know it, to be swiftly recognised so diagnosis can be promptly made.The adapted treatment should be immediately started to prevent possible life-threatening outcomes.

The implementation of biocatalytic steroid hydroxylation processes plays a crucial role in the pharmaceutical industry due to a plethora of medicative effects of hydroxylated steroid derivatives and their crucial role in drug approval processes. Cytochrome P450 monooxygenases (CYP450s) typically constitute the key enzymes catalyzing these reactions, but commonly entail drawbacks such as poor catalytic rates and the dependency on additional redox proteins for electron transfer from NAD(P)H to the active site. Recently, these bottlenecks were overcome by equipping Escherichia coli cells with highly active variants of the self-sufficient single-component CYP450 BM3 together with hydrophobic outer membrane proteins facilitating cellular steroid uptake. The combination of the BM3 variant KSA14m and the outer membrane pore AlkL enabled exceptionally high testosterone hydroxylation rates of up to 45 U gCDW-1 for resting (i.e., living but non-growing) cells. However, a rapid loss of specific activity heavily compromised final product titers and overall space-time yields. In this study, several stabilization strategies were evaluated on enzyme-, cell-, and reaction level. However, neither changes in biocatalyst configuration nor variation of cultivation media, expression systems, or inducer concentrations led to considerable improvement. This qualified the so-far used genetic construct pETM11-ksa14m-alkL, M9 medium, and the resting-cell state as the best options enabling comparatively efficient activity along with fast growth prior to biotransformation. In summary, we report several approaches not enabling a stabilization of the high testosterone hydroxylation rates, providing vital guidance for researchers tackling similar CYP450 stability issues. A comparison with more stable natively steroid-hydroxylating CYP106A2 and CYP154C5 in equivalent setups further highlighted the high potential of the investigated CYP450 BM3-based whole-cell biocatalysts. The immense and continuously developing repertoire of enzyme engineering strategies provides promising options to stabilize the highly active biocatalysts.

UNASSIGNED: Determine the efficacy, effectiveness, and safety of fluoroscopically- or ultrasound-guided caudal epidural steroid injections (ESIs) with or without catheter placement for the treatment of chronic low back (CLBP), radicular pain, and/or chronic post-surgical back pain (CPSBP).
UNASSIGNED: Systematic review.
UNASSIGNED: Adults ≥18 years with CLBP, radicular pain, or CPSBP ≥3 months.
UNASSIGNED: Fluoroscopically- or ultrasound-guided caudal ESI with or without a catheter including epidural neuroplasty.
UNASSIGNED: Sham, placebo procedure, active standard care treatment, or none.
UNASSIGNED: The primary outcome was the proportion of individuals with reduction of pain by ​≥ ​50%. Secondary outcomes included functional improvement, analgesic use, subsequent spinal surgery, healthcare utilization, and mean improvement in pain. Reported adverse events were also cataloged.
UNASSIGNED: Four reviewers independently assessed publications before January 2, 2022 in PubMed, Ovid MEDLINE, and Scopus. Quality of evidence was evaluated using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework.
UNASSIGNED: Of 364 records screened, 23 publications met inclusion criteria. The success rates for the primary outcome could only be extrapolated from one study. Another study used a composite improvement scale that included pain and functional outcomes. The reported success rates in these two studies ranged from 40 to 58% at three months, 25%-67% at six months, and 58%-61% at one year. Data on secondary outcomes were limited; however, rates of functional improvement as measured by mean improvement in Oswestry Disability Index (ODI) ranged from 2% to 55%.
UNASSIGNED: There is moderate-quality evidence that caudal ESIs using an in-dwelling catheter for two days is an effective treatment for pain and dysfunction associated with disc herniation with radicular pain and for CPSBP at three, six, and 12 months. There is low-quality evidence supporting the effectiveness of other caudal ESI techniques for pain and dysfunction associated with central lumbar spinal stenosis with neurogenic claudication, discogenic CLBP, and CLBP without disc herniation or radiculitis.

UNASSIGNED: The efficacy of ultrasonography-guided intra-flexor retinaculum corticosteroid injection is compared to within-carpal tunnel steroid injection, for the treatment of elderly patients with carpal tunnel syndrome (CTS).
UNASSIGNED: In this prospective, double-blind, randomized trial, the elderly patients with CTS are allocated 1:1 into the two treatment groups. Subjects and assessors remained blinded to group allocation throughout the trial. All patients received 40 ​mg triamcinolone (1 ​mL) plus 1 ​mL of 2% lidocaine, either fenestrated in the flexor retinaculum (group 1) or injected within the carpal tunnel between the flexor retinaculum and median nerve (group 2). Patients were instructed to use a wrist splint for two weeks post-treatment. Symptom severity, grip, electrodiagnostic indices, and ultrasonographic features were measured at baseline and 6-weeks thereafter. The primary outcomes were median nerve distal motor and sensory latencies, and those secondary outcomes were Boston Carpal Tunnel Questionnaire (BCTQ) scores, visual analog scale (VAS) pain scores, and the median nerve inlet cross-sectional area (CSA).
UNASSIGNED: Of 92 individuals screened, 50 eligible participants were randomized, all of whom completed the study and were included in the analysis. Patients receiving the intra-flexor retinaculum injection demonstrated significantly greater improvements in their total BCTQ score (p ​= ​0.023), VAS score (p ​= ​0.026), and inlet CSA (p ​= ​0.004), while the electrodiagnostic indices and the grip scale did not differ between groups.
UNASSIGNED: The intra-flexor retinaculum corticosteroid injection can provide better functional recovery and symptom reduction for elderly patients with CTS, compared to the within-carpal tunnel corticosteroid injection.

UNASSIGNED: To determine the diagnostic potential of neutrophil-to-lymphocyte ratio (NLR) as a POC marker to discriminate tuberculous from non-tuberculous CAP and identify limitations if any at a tertiary care centre in Uttarakhand, India.
UNASSIGNED: 225 patients presenting with respiratory complaints were recruited from the General Medicine clinics and investigated. NLR was noted at onset and correlated with final diagnosis.
UNASSIGNED: NLR from both groups did not exhibit a statistically significant difference. The area under curve (AUC) exhibited an accuracy of 49.1% in differentiating tuberculous from non-tubercular CAP, and an anomalous effect of prior steroid exposure on NLR was noted as a limitation.
UNASSIGNED: The disparity of our results from previous studies warranted a review of literature which rendered a significant limitation of NLR. The NLR is affected by catecholamines, which makes the marker unreliable in patients with exogenous steroid exposure. This was not noted in the previous studies. We presume indiscriminate steroid usage in the pandemic confounded our findings. We propose that this limitation be accounted for in future studies so that NLR\'s true utility may be identified.

Deep dissecting hematoma (DDH) is a disease in which minor trauma leads to the formation of an extensive hematoma. If left untreated, this can result in significant skin necrosis. Therefore, early treatment following a precise diagnosis is essential. However, the complexity of the disease may require differentiating it from soft tissue infections. A 58-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia developed skin complications such as purpura and blisters on his right upper extremity while undergoing veno-venous extracorporeal membrane oxygenation (VV-ECMO). We initially suspected a soft tissue infection or venous perfusion defect caused by the VV-ECMO cannula; however, these conditions were not observed. After making an exploratory incision, we diagnosed the patient with DDH and performed hematoma removal and skin grafting. The initial symptoms of DDH include erythema, swelling, and pain. It is important to differentiate DDH from soft tissue infections, especially necrotizing fasciitis, which is a more urgent condition. Because a surgical incision is necessary for the diagnosis and treatment of DDH, we do not hesitate to perform an exploratory incision to prevent skin necrosis, thereby contributing to early healing.

BACKGROUND: Acute liver failure (ALF) may be the first and most dramatic presentation of Wilson\'s disease (WD). ALF due to WD (WD-ALF) is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation. There is no firm recommendation on specific and supportive medical treatment for this condition.
OBJECTIVE: To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.
METHODS: A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.
RESULTS: During the study period, 16 children (9 males) received a diagnosis of WD and 2 of them presented with ALF. The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids, and survived without liver transplant. The second, exclusively treated with supportive therapy, needed a hepatotransplant to overcome ALF.
CONCLUSIONS: Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition, which is currently only treated with liver transplantation.

UNASSIGNED: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.
UNASSIGNED: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).
UNASSIGNED: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.
UNASSIGNED: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Background and Objectives: Inflammatory bowel disease (IBD), which includes Crohn\'s disease (CD) and ulcerative colitis (UC), often necessitates long-term treatment and hospitalizations and also may require surgery. The macrophage-stimulating 1 (MST1) rs3197999 polymorphism is strongly associated with the risk of IBD but its exact clinical correlates remain under investigation. We aimed to characterize the relationships between the MST1 rs3197999 genotype and the clinical characteristics in children and adolescents with IBD within a multi-center cross-sectional study. Materials and Methods: Clinical data included serum C-reactive protein (CRP), albumin, activity indices (PUCAI, PCDAI), anthropometric data, pharmacotherapy details, surgery, and disease severity. Genotyping for rs3197999 was carried out using TaqMan hydrolysis probes. Results: The study included 367 pediatric patients, 197 with Crohn\'s disease (CD) (40.6% female; a median age of 15.2 years [interquartile range 13.2-17.0]) and 170 with ulcerative colitis (UC) (45.8% female; a median age of 15.1 years [11.6-16.8]). No significant relationships were found between MST1 genotypes and age upon first biologic use, time from diagnosis to biological therapy introduction, PUCAI, PCDAI, or hospitalizations for IBD flares. However, in IBD, the height Z-score at the worst flare was negatively associated with the CC genotype (p = 0.016; CC: -0.4 [-1.2-0.4], CT: -0.1 [-0.7-0.8], TT: 0.0 [-1.2-0.7)]). The TT genotype was associated with higher C-reactive protein upon diagnosis (p = 0.023; CC: 4.3 mg/dL [0.7-21.8], CT 5.3 mg/dL [1.3-17.9], TT 12.2 mg/dL [3.0-32.9]). Conclusions: This study identified links between MST1 rs3197999 and the clinical characteristics of pediatric IBD: height Z-score and CRP. Further studies of the associations between genetics and the course of IBD are still warranted, with a focus on more extensive phenotyping.

Cytochrome P450 (P450) enzymes dominate steroid metabolism. In general, the simple C-hydroxylation reactions are mechanistically straightforward and are generally agreed to involve a perferryl oxygen species (formally FeO3+). Several of the steroid transformations are more complex and involve C-C bond scission. We initiated mechanistic studies with several of these (i.e., 11A1, 17A1, 19A1, and 51A1) and have now established that the dominant modes of catalysis for P450s 19A1 and 51A1 involve a ferric peroxide anion (i.e., Fe3+O2¯) instead of a perferryl ion complex (FeO3+), as demonstrated with 18O incorporation studies. P450 17A1 is less clear. The indicated P450 reactions all involve sequential oxidations, and we have explored the processivity of these multi-step reactions. P450 19A1 is distributive, i.e., intermediate products dissociate and reassociate, but P450s 11A1 and 51A1 are highly processive. P450 17A1 shows intermediate processivity, as expected from the release of 17-hydroxysteroids for the biosynthesis of key molecules, and P450 19A1 is very distributive. P450 11B2 catalyzes a processive multi-step oxidation process with the complexity of a chemical closure of an intermediate to a locked lactol form.