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Background: The wrist is a complex joint that plays a role in several everyday tasks. Various radiological indices have been created to assess the alignment and structure of the wrist using standard X-ray images. Nevertheless, these indicators may differ based on variables such as age, gender, ethnicity, handedness, and wrist position. This research aimed to assess the radiological indices of the wrist in a group of healthy people from Jordan and investigate the impact of age and gender on these indices. Methods: We obtained data from a sample of 385 patients who presented at our hospital with minor non-specific wrist pain and satisfied the specified criteria for inclusion. We conducted measurements of radial inclination, radial height, volar tilt, ulnar variance, and carpal height ratio using both anteroposterior and lateral views of the wrist. We used linear regression and independent sample t-test to examine the correlation between age, gender, and radiological indicators. The reliability of the measurements was assessed using the intraclass correlation coefficient (ICC). Results: Our study revealed a negative correlation between age and carpal height ratio (r = -0.13, p = 0.03). However, no significant gender differences were seen in any of the radiological indices (p > 0.05). Our findings indicate that ulnar variance had the greatest level of reliability across observers, with an intra-observer intraclass correlation coefficient (ICC) of 0.95 and an inter-observer ICC of 0.8. Conversely, volar tilt exhibited the lowest inter-observer reliability, with an ICC of 0.1.Our results provide a valuable point of reference for the wrist morphology and alignment in the Jordanian population. Our suggestion is that the carpal height ratio might indicate alterations in the wrist joint due to aging, whereas ulnar variation may serve as a dependable indicator of wrist alignment. We suggest doing more research to investigate the biological and anatomical factors behind these results and to compare them with other demographic groups.
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Modern visual perception techniques often rely on multiple heterogeneous sensors to achieve accurate and robust estimates. Knowledge of their relative positions is a mandatory prerequisite to accomplish sensor fusion. Typically, this result is obtained through a calibration procedure that correlates the sensors' measurements. In this context, we focus on LiDAR and RGB sensors that exhibit complementary capabilities. Given the sparsity of LiDAR measurements, current state-of-the-art calibration techniques often rely on complex or large calibration targets to resolve the relative pose estimation. As such, the geometric properties of the targets may hinder the calibration procedure in those cases where an ad hoc environment cannot be guaranteed. This paper addresses the problem of LiDAR-RGB calibration using common calibration patterns (i.e., A3 chessboard) with minimal human intervention. Our approach exploits the flatness of the target to find associations between the sensors' measurements, leading to robust features and retrieval of the solution through nonlinear optimization. The results of quantitative and comparative experiments with other state-of-the-art approaches show that our simple schema performs on par or better than existing methods that rely on complex calibration targets.
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BACKGROUND: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors. METHODS: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate. RESULTS: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality. CONCLUSION: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.
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COVID-19 , Choque Séptico , Infecciones Estreptocócicas , Adulto , Niño , Humanos , Estudios Retrospectivos , Pandemias , Estudios de Cohortes , Infecciones Estreptocócicas/epidemiología , COVID-19/epidemiología , Unidades de Cuidados Intensivos , Streptococcus pyogenes , Choque Séptico/epidemiologíaRESUMEN
Proximal humerus fractures (PHFs) are a common type of fracture in adults. Although PHFs are common, bilateral presentation is extremely rare. Most PHFs are treated conservatively. In this report, we describe a 69-year-old right-hand-dominant male patient who was involved in a high-impact motor vehicle accident (MVA). The patient's upper limbs were in a fully extended position while he was holding the driving wheel, where he sustained a side impaction to the car by a hard object that caused bilateral four-part PHF with dislocation, which was confirmed on radiological investigations. The orthopedic surgery team believed that surgical treatment was necessary and ideal for these bilateral fracture dislocations, specifically bilateral reverse total shoulder arthroplasty (RTSA). This is due to multiple factors, including the risk of humeral head avascular necrosis (AVN), the patient's advanced age, low demand, poor bone stock, osteoporosis, and a non-fixable fracture pattern. The patient underwent a single-stage bilateral RTSA procedure, which was well tolerated. He was optimized postoperatively. The post-operative X-ray showed good and satisfactory implant positions and orientation. Functional assessment using the Constant-Murley Score (CMS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were calculated at three-months follow-up (right-left: 50-60 and 41-14, respectively), at five-months follow-up (right-left: 34-66 and 38-14, respectively), and at eight-months follow-up (right-left: 40-68 and 24-7.5, respectively). Follow-up X-rays revealed good tuberosities healing, and no loosening or scapular notching. In addition, pain was assessed on a numerical rating scale (NRS), which demonstrated fast pain relief. Short-term follow-up with the patient demonstrated that he was satisfied with the surgery, especially the left side with a pain score on the NRS of one. We selected to share our experience of this complex case with our peers in the field of orthopedic surgery worldwide so that such a procedure could be implemented in similar cases to ensure satisfactory outcomes following bilateral four-part PHF with dislocation.
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Acute popliteal arterial thrombotic occlusion following total knee arthroplasty is a rare but serious complication, most of which happens due to blunt trauma during surgery in patients with preexisting peripheral vascular disease. Historically, popliteal artery thrombosis has been approached only by open surgery. In this report, we describe a case of acute thrombotic occlusion of the popliteal artery occurring immediately after total knee arthroplasty in a patient who was presumed healthy and found to have antiphospholipid syndrome and was successfully managed by mechanical endovascular thrombectomy.
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PURPOSE: T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden-related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness. EXPERIMENTAL DESIGN: We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis. RESULTS: ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2-STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell-like CD44+ Tim-3hi TCF1- CD127- KLRG1+ differentiation. CONCLUSIONS: Tumor burden-induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.
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BACKGROUND: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU). METHODS: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors. RESULTS: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors. CONCLUSIONS: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03335995.
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Respiración Artificial , Accidente Cerebrovascular , Humanos , Anciano , Estudios de Cohortes , Estudios Prospectivos , Respiración Artificial/métodos , Actividades Cotidianas , Calidad de Vida , Accidente Cerebrovascular/etiología , Unidades de Cuidados IntensivosRESUMEN
The Hippo signalling pathway is a master regulator of cell growth, proliferation, and cancer. The transcriptional coregulators of the Hippo pathway, YAP and TAZ, are central in various cancers. However, how YAP and TAZ get activated in most types of cancers is not well understood. Here, we show that androgens activate YAP/TAZ via the androgen receptor (AR) in prostate cancer (PCa), and that this activation is differential. AR regulates YAP translation while inducing transcription of the TAZ encoding gene, WWTR1 Furthermore, we show that AR-mediated YAP/TAZ activation is regulated by the RhoA GTPases transcriptional mediator, serum response factor (SRF). Importantly, in prostate cancer patients, SRF expression positively correlates with TAZ and the YAP/TAZ target genes CYR61 and CTGF We demonstrate that YAP/TAZ are not essential for sustaining AR activity, however, targeting YAP/TAZ or SRF sensitize PCa cells to AR inhibition in anchorage-independent growth conditions. Our findings dissect the cellular roles of YAP, TAZ, and SRF in prostate cancer cells. Our data emphasize the interplay between these transcriptional regulators and their roles in prostate tumorigenesis and highlight how these insights might be exploited therapeutically.
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Neoplasias de la Próstata , Receptores Androgénicos , Humanos , Masculino , Andrógenos , Carcinogénesis , Próstata , Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismoRESUMEN
PURPOSE: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. METHODS: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. RESULTS: Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective. CONCLUSION: Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.
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Encefalitis , Meningoencefalitis , Humanos , Adulto , Persona de Mediana Edad , Estudios de Cohortes , Estudios Prospectivos , Cuidados Críticos , Unidades de Cuidados IntensivosRESUMEN
Carbon nanotubes (CNTs) are nanometer-sized structures that can be used to reinforce cement matrices. The extent to which the mechanical properties are improved depends on the interfacial characteristics of the resulting materials, that is, on the interactions established between the CNTs and the cement. The experimental characterization of these interfaces is still impeded by technical limitations. The use of simulation methods has a great potential to give information about systems lacking experimental information. In this work, molecular dynamics (MD) and molecular mechanics (MM) were used in conjunction with finite element simulations to study the interfacial shear strength (ISS) of a structure formed by a pristine single-walled CNT (SWCNT) inserted in a tobermorite crystal. The results show that, for a constant SWCNT length, ISS values increase when the SWCNT radius increases, while for a constant SWCNT radius, shorter lengths enhance ISS values.
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The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest-scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell-line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ-dependent anchorage-independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.
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Mesotelioma , Factores de Transcripción , Humanos , Vía de Señalización Hippo , Mesotelioma/genética , Mesotelioma/metabolismo , Mesotelioma/patología , Mutación/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Proteínas Señalizadoras YAPRESUMEN
Immunogenic cell death (ICD) can switch immunologically "cold" tumors "hot", making them sensitive to immune checkpoint inhibitor (ICI) therapy. Many therapeutic platforms combine multiple modalities such as oncolytic viruses (OVs) and low-dose chemotherapy to induce ICD and improve prognostic outcomes. We previously detailed many unique properties of oncolytic bovine herpesvirus type 1 (oBHV) that suggest widespread clinical utility. Here, we show for the first time, the ability of oBHV monotherapy to induce bona fide ICD and tumor-specific activation of circulating CD8+ T cells in a syngeneic murine model of melanoma. The addition of low-dose mitomycin C (MMC) was necessary to fully synergize with ICI through early recruitment of CD8+ T cells and reduced infiltration of highly suppressive PD-1+ Tregs. Cytokine and gene expression analyses within treated tumors suggest that the addition of MMC to oBHV therapy shifts the immune response from predominantly anti-viral, as evidenced by a high level of interferon-stimulated genes, to one that stimulates myeloid cells, antigen presentation and adaptive processes. Collectively, these data provide mechanistic insights into how oBHV-mediated therapy modalities overcome immune suppressive tumor microenvironments to enable the efficacy of ICI therapy.
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Introduction: Acute kidney injury (AKI) is frequently observed in patients with COVID-19 admitted to intensive care units (ICUs). Observational studies suggest that cardiovascular comorbidities and mechanical ventilation (MV) are the most important risk factors for AKI. However, no studies have investigated the renal impact of longitudinal covariates such as drug treatments, biological variations, and/or MV parameters. Methods: We performed a monocentric, prospective, longitudinal analysis to identify the dynamic risk factors for AKI in ICU patients with severe COVID-19. Results: Seventy-seven patients were included in our study (median age: 63 [interquartile range, IQR: 53-73] years; 58 (75%) men). Acute kidney injury was detected in 28 (36.3%) patients and occurred at a median time of 3 [IQR: 2-6] days after ICU admission. Multivariate Cox cause-specific time-dependent analysis identified a history of hypertension (cause-specific hazard (CSH) = 2.46 [95% confidence interval, CI: 1.04-5.84]; P = .04), a high hemodynamic Sequential Organ Failure Assessment score (CSH = 1.63 [95% CI: 1.23-2.16]; P < .001), and elevated Paco2 (CSH = 1.2 [95%CI: 1.04-1.39] per 5 mm Hg increase in Pco2; P = .02) as independent risk factors for AKI. Concerning the MV parameters, positive end-expiratory pressure (CSH = 1.11 [95% CI: 1.01-1.23] per 1 cm H2O increase; P = .04) and the use of neuromuscular blockade (CSH = 2.96 [95% CI: 1.22-7.18]; P = .02) were associated with renal outcome only in univariate analysis but not after adjustment. Conclusion: Acute kidney injury is frequent in patients with severe COVID-19 and is associated with a history of hypertension, the presence of hemodynamic failure, and increased Pco2. Further studies are necessary to evaluate the impact of hypercapnia on increasing the effects of ischemia, particularly in the most at-risk vascular situations.
Introduction: L'insuffisance rénale aiguë (IRA) est fréquemment observée chez les patients atteints de COVID-19 admis dans les unités de soins intensifs (USI). Des études observationnelles suggèrent que les comorbidités cardiovasculaires et la ventilation mécanique (VM) seraient les plus importants facteurs de risque de l'IRA. Aucune étude n'a cependant examiné l'impact sur la fonction rénale de covariables longitudinales telles que les traitements médicamenteux, les variations biologiques et/ou les paramètres de la VM. Méthodologie: Nous avons procédé à une analyse prospective et longitudinale dans un seul centre hospitalier afin d'identifier les facteurs de risque dynamiques de l'IRA chez les patients hospitalisés aux USI en raison d'une forme grave de la COVID-19. Résultats: Soixante-dix-sept patients ont été inclus dans notre étude (75 % d'hommes [n=58]; âge médian: 63 ans [ÉIQ: 53-73]). L'IRA a été détectée chez 28 patients (36,3 %) et est survenue dans un délai médian de 3 jours (ÉIQ: 2-6 jours) après l'admission à l'USI. Une analyse de Cox multivariée, spécifique à la cause et tenant compte du temps, a permis de dégager les éléments suivants comme étant des facteurs de risque indépendants pour l'IRA: des antécédents d'hypertension (probabilité par cause [PPC]=2,46 [IC 95 %: 1,04-5,84]; p=0,04), un score SOFA hémodynamique élevé (PPC=1,63 [IC 95 %: 1,23-2,16]; p<0,001) et une concentration élevée de PaCO2 (PPC=1,2 [IC 95 %: 1,04-1,39] pour chaque augmentation de 5 mmHg de pCO2; p = 0,02). En ce qui concerne les paramètres de la VM, une pression expiratoire positive (PPC=1,11 [IC 95 %: 1,01-1,23] pour chaque augmentation de 1 cm H2O; p = 0,04) et l'utilisation d'un bloc neuromusculaire (PPC=2,96 [IC 95 %: 1,22-7,18]; p=0,02) ont été associés à l'IRA dans l'analyse univariée seulement, et non après ajustement. Conclusion: L'IRA est fréquente chez les patients atteints d'une forme grave de COVID-19 et elle est associé à des antécédents d'hypertension, à la présence d'une instabilité hémodynamique et à une augmentation de la pCO2. D'autres études sont nécessaires pour évaluer l'impact de l'hypercapnie sur l'augmentation des effets de l'ischémie, en particulier dans les situations vasculaires les plus à risque.
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Concrete is well known for its compression resistance, making it suitable for any kind of construction. Several research studies show that the addition of carbon nanostructures to concrete allows for construction materials with both a higher resistance and durability, while having less porosity. Among the mentioned nanostructures are carbon nanotubes (CNTs), which consist of long cylindrical molecules with a nanoscale diameter. In this work, molecular dynamics (MD) simulations have been carried out, to study the effect of pristine or carboxyl functionalized CNTs inserted into a tobermorite crystal on the mechanical properties (elastic modulus and interfacial shear strength) of the resulting composites. The results show that the addition of the nanostructure to the tobermorite crystal increases the elastic modulus and the interfacial shear strength, observing a positive relation between the mechanical properties and the atomic interactions established between the tobermorite crystal and the CNT surface. In addition, functionalized CNTs present enhanced mechanical properties.
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Malignant TS-GCT is an extremely rare and aggressive tumor with only few cases published in the literature, due to the small number of cases is not completely understood and is diagnostically challenging. Although surgical treatment is the primary treatment modality, there is no consensus regarding adjuvant treatment. Regardless of mode of treatment, the tumor still caries unfavorable prognosis. In this paper, we reviewed the literature for cases of malignant TS-GCT. We also would like to present an additional case of malignant TS-GCT that was found in an unusual location in subcutaneous tissue of the midthigh.
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Lipoma arborescens (villous lipomatous proliferation of the synovial membrane) is a rare, benign articular lesion characterized by diffuse villous proliferation of the synovium with mature fat substitution of the sub-synovial connective tissue. The etiology of this condition still remains unknown. It represents part of differential diagnosis for a progressive swollen knee with chronic pain secondary to synovial proliferative disorders with or without associations with osteoarthritis. We report an intraoperative finding of lipoma arborescence in a patient who underwent bilateral primary total knee replacement secondary to advanced osteoarthritis.
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Rotating hinged knee replacements are used to restore knee stability when intrinsic stability is lost in the form of soft tissue compression. With medical engineering advancements and improvements in arthroplasty, intrinsic stability can be achieved by an implant post system. We present the case of a 44-year-old female who presented with post-traumatic right knee multi-ligamentous instability and advanced secondary osteoarthritis following a traumatic knee dislocation two years ago. The patient initially underwent a hinged total knee replacement. After five years, she got dislocation of hinged total knee replacement that affected her condition and necessitated emergency admission for open reduction and revision. Most reported cases of rotating hinge prosthesis dislocation occurred during the first year of follow-up. However, our case dislocated after five years of follow-up due to dislodgement from the tibial tray with the polyethylene channel in the form of fatigue failure of the anti-dislocation mechanism.
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Immune checkpoint therapy has shown great promise in the treatment of cancers with a high mutational burden, such as mismatch repair-deficient colorectal carcinoma (dMMR CRC). However, many patients fail to respond to immune checkpoint therapy. Using a mouse model of dMMR CRC, we demonstrated that tumors can be further sensitized to immune checkpoint therapy by using a combination of low-dose chemotherapy and oncolytic HSV-1. This combination induced the infiltration of CD8+ and CD4+ T cells into the tumor and the upregulation of gene signatures associated with the chemoattraction of myeloid cell subsets. When combined with immune checkpoint therapy, the combination promoted the infiltration of activated type 1 conventional dendritic cells (cDC1s) into the tumor. Furthermore, we found this combination strategy to be dependent on cDC1s, and its therapeutic efficacy to be abrogated in cDC1-deficient Batf3-/- mice. Thus, we demonstrated that the adjuvanticity of dMMR CRCs can be improved by combining low-dose chemotherapy and oncolytic HSV-1 in a cDC1-dependent manner.
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Adenocarcinoma/terapia , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/terapia , Células Dendríticas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Viroterapia Oncolítica , Adenocarcinoma/patología , Animales , Antineoplásicos/farmacología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Terapia Combinada , Células Dendríticas/efectos de los fármacos , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Ratones Endogámicos C57BL , Mitomicina/farmacología , Mitomicina/uso terapéutico , Proteínas Represoras/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Transcriptoma/genéticaRESUMEN
Immunofluorescence microscopy is routinely used to visualise the spatial distribution of proteins that dictates their cellular function. However, unspecific antibody binding often results in high cytosolic background signals, decreasing the image contrast of a target structure. Recently, convolutional neural networks (CNNs) were successfully employed for image restoration in immunofluorescence microscopy, but current methods cannot correct for those background signals. We report a new method that trains a CNN to reduce unspecific signals in immunofluorescence images; we name this method label2label (L2L). In L2L, a CNN is trained with image pairs of two non-identical labels that target the same cellular structure. We show that after L2L training a network predicts images with significantly increased contrast of a target structure, which is further improved after implementing a multiscale structural similarity loss function. Here, our results suggest that sample differences in the training data decrease hallucination effects that are observed with other methods. We further assess the performance of a cycle generative adversarial network, and show that a CNN can be trained to separate structures in superposed immunofluorescence images of two targets.