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1.
Respirol Case Rep ; 12(8): e01441, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39130088

RESUMO

Mediastinal diffuse large B-cell lymphoma (DLBC) may manifest in different presentations including systemic symptoms and local mass symptoms. We report two cases of diffuse large B-cell lymphoma presenting with pulmonary artery compression symptoms. The first case is of a 38-year-old Asian man which mimicked pulmonary embolism, and the second one is of a 27-year-old Asian woman who presented with fainting and respiratory symptoms due to local mass effect. Both cases were significantly improved after treatment. Local mass effect symptoms may be the first clinical presentation in DLBC lymphoma and should not be overlooked.

2.
Molecules ; 29(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38893546

RESUMO

Water scarcity poses a significant challenge for people living in arid areas. Despite the effectiveness of many bioinspired surfaces in promoting vapor condensation, their water-harvesting efficiency is insufficient. This is often exacerbated by overheating, which decreases the performance in terms of the micro-droplet concentration and movement on surfaces. In this study, we used a spotted amphiphilic surface to enhance the surfaces' water-harvesting efficiency while maintaining their heat emissivity. Through hydrophilic particle screening and hydrophobic groove modifying, the coalescence and sliding characteristics of droplets on the amphiphilic surfaces were improved. The incorporation of boron nitride (BN) nanoparticles further enhanced the surfaces' ability to harvest energy from condensation. To evaluate the water-harvesting performance of these amphiphilic surfaces, we utilized a real-time recording water-harvesting platform to identify microscopic weight changes on the surfaces. Our findings indicated that the inclusion of glass particles in hydrophobic grooves, combined with 1.0 wt.% BN nanoparticles, enhanced the water-harvesting efficiency of the amphiphilic surfaces by more than 20%.

3.
Ann Surg ; 280(2): 300-310, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557793

RESUMO

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.


Assuntos
Transplante de Fígado , Preservação de Órgãos , Perfusão , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Transplante de Fígado/economia , Pessoa de Meia-Idade , Perfusão/métodos , Preservação de Órgãos/métodos , Preservação de Órgãos/economia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Adulto , Idoso , Sobrevivência de Enxerto
4.
J Neurol Surg A Cent Eur Neurosurg ; 85(1): 32-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36693411

RESUMO

BACKGROUND: Postoperative shunt infection is a nightmare in neurosurgical practice with additional morbidity and mortality. A lot of protocols have contributed to the reduction of ventriculoperitoneal shunt (VPS) infections but not eradication. The aim of the study was to evaluate the rigid application of a modified Hydrocephalus Clinical Research Network (HCRN) protocol in the prevention of postoperative shunt infection. METHODS: We retrospectively evaluated children with congenital hydrocephalus who underwent VPS insertion, and in whom the protocol was applied from June 2019 to January 2020. Follow-up ranged from 11 to 24 months. RESULTS: Thirty-seven procedures were performed including 35 primary shunt insertions and two revision surgeries. The median age was 5 months (range, 1-30 months), and 25 patients were males. The most common cause for VPS placement was congenital hydrocephalus without identifiable cause in 28 cases (80%). The endoscope-assisted technique was used in the insertion of the proximal end in six cases (17%). The mean follow-up was 19.4 months (11-24 months). The rate of shunt infection was 0% till the last follow-up. CONCLUSION: The preliminary results showed an effective method for the prevention of postoperative shunt infections using the modified protocol. These initial findings need to be validated in a large prospective study before widespread application can be recommended.


Assuntos
Hidrocefalia , Criança , Masculino , Humanos , Lactente , Pré-Escolar , Feminino , Estudos Retrospectivos , Estudos Prospectivos , Hidrocefalia/cirurgia , Hidrocefalia/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia
5.
Case Rep Oncol ; 16(1): 728-733, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900826

RESUMO

Pembrolizumab is one of the approved treatments for many types of cancer including clear cell renal cell carcinoma (ccRCC). It has improved the prognosis of renal cell carcinoma, yet has many possible immune-related side effects. We discuss a rare case of rhabdomyolysis in an ccRCC patient treated with pembrolizumab. The case was complicated with acute kidney injury and severe hypothyroidism, which can be attributed to pembrolizumab.

6.
JHEP Rep ; 5(11): 100846, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37771368

RESUMO

The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.

7.
Reprod Sci ; 30(10): 3046-3054, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37191816

RESUMO

Does the late follicular phase progesterone (P4) and the P4-to-follicle-ratio affect the ploidy state of the biopsied embryos? A retrospective observational study conducted at ART Fertility Clinics Abu Dhabi and Muscat, including all stimulation cycles performed between January 2015 and December 2019. In total, 975 cycles were considered for this study. Inclusion criteria were ovarian stimulation due to primary/secondary infertility, patient's age between 18 and 45 years, ICSI as fertilization method, and patients undergoing preimplantation genetic testing for aneuploidies (PGT-A). Patients with testicular sperm extraction (TESE) and warmed oocytes were excluded. Our results have shown that progesterone had no effect on the euploid rate (p = 0.371). However, when adding the ratio of P4 to the number of follicles that were bigger than 10 mm in the last scan, a negative effect on the euploid rate (p < 0.05) was observed. This study was able to show that the use of only P4 is unable to predict ploidy outcomes. However, by including the number of follicles > 10 mm, a clear association was observed between P4/Foll ratio and euploid rate per cycle. The use of both parameters could aid clinicians in their decision to trigger a patient or continue stimulation. Further prospective studies are warranted to confirm those results.


Assuntos
Diagnóstico Pré-Implantação , Progesterona , Feminino , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Gravidez , Sêmen , Folículo Ovariano , Aneuploidia , Ploidias , Estudos Retrospectivos , Blastocisto/patologia , Fertilização in vitro/métodos , Taxa de Gravidez , Diagnóstico Pré-Implantação/métodos
8.
Int J Pharm Pract ; 31(2): 165-175, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-36595471

RESUMO

OBJECTIVE: This study aimed to analyse the patterns of the irrational use of medicines in Arab countries and to determine the factors contributing to these patterns. METHODS: A systematic literature review was conducted using two major databases: PubMed and Scopus. The systematic search targeted original studies conducted in Arab countries from 2000 to 2019. A conceptual framework was adopted from a previous study and was utilized to assess the irrational use of medicines and its influencing factors. RESULTS: A total of 136 studies from 16 Arab countries were included. Almost all were cross-sectional studies. Most focused on evaluating the irrational use of medicines rather than investigating the cause. The number of medications per encounter was 2.3 which is within the limits of developed countries (2.7). The percentage of antibiotics per 100 encounter was 50.1% and the percentage of injections prescribed per 100 encounter was 15.2%. The consumption of antibiotic and injections was much higher than that recommended by WHO. At the same time, the review identified that one fourth of all medications were unnecessarily prescribed. SUMMARY: The literature review revealed that the irrational use of medicine is prevalent in most Arab countries. Excessive use of antibiotics was the most commonly observed pattern. Therefore, there is a need to conduct further research to identify the factors that drive the irrational use of medicines in Arab countries and then to make recommendations to mitigate this issue.


Assuntos
Prescrições de Medicamentos , Padrões de Prática Médica , Humanos , Árabes , Antibacterianos/uso terapêutico , Organização Mundial da Saúde
9.
Surgery ; 173(3): 846-854, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36302699

RESUMO

BACKGROUND: The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation. METHODS: With the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion using our institutionally developed perfusion device. RESULTS: Expanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries. Perfusion duration ranged between 1 and 2 hours for the hypothermic oxygenated perfusion phase and between 4 and 9 hours for the normothermic machine perfusion phase. Three livers were judged to be untransplantable during normothermic machine perfusion based on perfusate lactate, bile production, and macro-appearance. One liver was not transplanted because of recipient issue after anesthesia induction and failed reallocation. Thirteen livers were transplanted, including 9 donors after cardiac death livers (donor warm ischemia time 16-25 minutes) and 4 from donors after brain death. All livers had the standardized lactate clearance >60% (perfusate lactate cleared to <4.0 mmol/L) within 3 hours of normothermic machine perfusion. Bile production rate was 0.2 to 10.7 mL/h for donors after brain death livers and 0.3 to 6.1 mL/h for donors after cardiac death livers. After transplantation, 5 cases had early allograft dysfunction (3 donors after cardiac death and 2 donors after brain death livers). No graft failure or patient death has occurred during follow-up time of 6 to 13 months. Two livers developed ischemic cholangiopathy. Compared with our previous normothermic machine perfusion study, the bile duct had fewer inflammatory cells in histology, but the post-transplant outcomes had no difference. CONCLUSION: Sequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.


Assuntos
Transplante de Fígado , Humanos , Morte Encefálica , Doadores Vivos , Perfusão , Lactatos , Preservação de Órgãos
10.
Int. arch. otorhinolaryngol. (Impr.) ; 26(4): 697-700, Oct.-Dec. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1421647

RESUMO

Abstract Introduction Chronic suppurative otitis media is one of the most common causes of reversible conductive hearing loss which can lead to necrosis of the ossicles. The incus, especially its long process, is the most common ossicle affected. Objectives The present study aims to assess the use of glass ionomer cement for the reconstruction of the long process of the incus. Methods The present study was conducted on 27 patients with chronic suppurative otitis media with central perforation with dry and quiescent ears with an eroded long process of the incus submitted to tympanoplasty. The audiological evaluations were done on all patients, including preoperative and postoperative evaluation of the airbone gap; the average pure tone threshold was done 6 months postoperatively. Results The average air pure tone threshold was 42.8 dB preoperatively and 22.5 dB postoperatively. The postoperative air pure tone thresholds were significantly smaller than the preoperative values (p < 0.01). The air-bone gap was 30.5 dB at 500 Hz, 31.6 dB at 1 KHz, and 24.1 dB at 2 kHz preoperatively, and 7.7 dB at 500 Hz, 7.2 dB at 1 KHz, and 7.1 dB at 2 kHz postoperatively at the end of 6 months of follow-up. There were significant hearing gains in the air-bone gap (p < 0.001). Conclusion Glass ionomer cement is a useful and effective material for bridging the defect of the long process of the incus.

12.
Cells ; 11(18)2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36139466

RESUMO

Autophagy eliminates excessive nutrients and maintains homeostasis. Obesity and metabolic syndrome (MetS) dysregulate autophagy, possibly partly due to mitochondria injury and inflammation. Elamipretide (ELAM) improves mitochondrial function. We hypothesized that MetS blunts kidney autophagy, which ELAM would restore. Domestic pigs were fed a control or MetS-inducing diet for 16 weeks. During the 4 last weeks, MetS pigs received subcutaneous injections of ELAM (0.1 mg/kg/day, MetS + ELAM) or vehicle (MetS), and kidneys were then harvested to measure protein expression of autophagy mediators and apoptosis. Systemic and renal venous levels of inflammatory cytokines were measured to calculate renal release. The function of isolated mitochondria was assessed by oxidative stress, energy production, and pro-apoptotic activity. MetS slightly downregulated renal expression of autophagy mediators including p62, ATG5-12, mTOR, and AMPK vs. control. Increased mitochondrial H2O2 production accompanied decreased ATP production, elevated apoptosis, and renal fibrosis. In MetS + ELAM, mito-protection restored autophagic protein expression, improved mitochondrial energetics, and blunted renal cytokine release and fibrosis. In vitro, mitoprotection restored mitochondrial membrane potential and reduced oxidative stress in injured proximal tubular epithelial cells. Our study suggests that swine MetS mildly affects renal autophagy, possibly secondary to mitochondrial damage, and may contribute to kidney structural damage in MetS.


Assuntos
Síndrome Metabólica , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Autofagia , Citocinas/metabolismo , Células Epiteliais/metabolismo , Fibrose , Peróxido de Hidrogênio/farmacologia , Rim/patologia , Síndrome Metabólica/metabolismo , Oligopeptídeos , Circulação Renal , Sus scrofa , Suínos , Serina-Treonina Quinases TOR/metabolismo
13.
Heliyon ; 8(9): e10595, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36132184

RESUMO

Procalcitonin (PCT) is a well-known biomarker that is directly connected to bacterial infection especially when it reaches significantly high levels. It is extremely rare to be witnessed in non-bacterial infections such as viral or parasitic. It may be elevated in other conditions such as trauma and autoimmune diseases. We present a rare case of a young gentleman, who had an extremely high PCT level that appeared to be a result of anaphylaxis due to worm infestation.

14.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 1): 724-729, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36032907

RESUMO

Eustachian tube (ET) is a tube connecting the middle ear cavity with the nasopharynx and has an important role in equalization of pressure around TM. Many studies investigated the role of ET function tests on the results of myringoplasty/tympanoplasty. Our aim is to assess the effect of successful myringoplasty on Eustachian tube function. A prospective study included 37 patients admitted to the E.N.T Department at Sohag University Hospital in the period between March 2018 and March 2019 suffering from dry central perforation necessitating myringoplasty. Pre-operative E.T function tests using tympanometry and methylene blue dye test were done. Post-operative follow-up tympanometry was done after 3 months for those with successful myringoplasty and compared to the preoperative assessment. Thirty-one (83%) patients had functioning ET, 6 (17%) had non-functioning ET and 32 patients (86.5%) had successful myringoplasty (taken healthy graft). According to the effect of myringoplasty on ET function test 3 months following surgery, (9%) were affected, either improved (3%) or worsen (6%), while (91%) were not affected by tympanometry in those with taken healthy graft cases. In our study, there was no significant effect of myringoplasty on E.T function. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-021-02534-8.

15.
Appl Radiat Isot ; 188: 110413, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35994917

RESUMO

The present work aims to study gamma rays emitted by radionuclides such as 238U, 232Th and 40K from acidic Monqul volcanics. The studied volcanics are represented by a thick stratified lava flows interbanded with their pyroclastics. They are composed of thick lava flows of andesite and, to a lesser extent of basalt, and acidic volcanics including rhyolite and dacite. The average values of 238U, 232Th and 40K are (46 ± 24 Bq kg-1), (62 ± 11 Bq kg-1) and (1227 ± 318 Bq kg-1) in the rhyolite-dacite samples are greater than the worldwide average. The variation of radioactive bearing minerals observed inside granite faults produced the great amounts of radioactivity perceived in the samples. Calculating radiological risks is used to assess the public's radioactive risk from radionuclides revealed in the studied Rhyolite-dacite samples. The acceptable limit for excess lifetime cancer (ELCR) evaluations has been exceeded. As a result, Rhyolite-dacite are inappropriate for apply in building materials.


Assuntos
Monitoramento de Radiação , Radioatividade , Rádio (Elemento) , Poluentes Radioativos do Solo , Egito , Radioisótopos de Potássio/análise , Monitoramento de Radiação/métodos , Radioisótopos/análise , Rádio (Elemento)/análise , Medição de Risco , Poluentes Radioativos do Solo/análise , Tório/análise
16.
Medicine (Baltimore) ; 101(23): e29236, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687772

RESUMO

INTRODUCTION: Although it usually involves extranodal sites such as the gastrointestinal tract in more than 80% of cases, mantle cell lymphoma is considered a rare cause of gastrointestinal bleeding, especially severe and life-threatening bleeding. PATIENT CONCERN: A 60-year-old man with peptic ulcer disease, who presented with severe upper gastrointestinal (GI) bleeding and large gastric ulcer. DIAGNOSIS: Primary gastric mantle cell lymphoma. INTERVENTIONS: He was treated conservatively with blood transfusion and started on Traneximic acid for 3 days. Then, the patient underwent urgent hemostatic radiotherapy. OUTCOMES: The patient became stable and kept in the hospital for monitoring with a definite diagnosis of stage IV Mantle cell lymphoma is made. CONCLUSION: Mantle cell lymphoma should be kept in mind when assessing massive upper GI bleeding, as an unusual cause of bleeding gastric ulcer, given that bleeding is an uncommon presenting feature of GI lymphoma.


Assuntos
Linfoma de Célula do Manto , Úlcera Péptica , Úlcera Gástrica , Adulto , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/complicações , Úlcera Péptica Hemorrágica/complicações , Úlcera Gástrica/complicações , Úlcera Gástrica/diagnóstico
17.
Materials (Basel) ; 15(12)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35744366

RESUMO

The present work is concerned with assessing the cancer risk contributed by the studied granite types including valuable metals, such as Cu, Au, and Ba mineralization, as well as radioactive-bearing mineralization, such as monazite and zircon, in south Monqul at Wadi Makhrag El Ebel, north Eastern Desert, Egypt. The mineralization analyses illustrated that copper mineralization containing chrysocolla and tenorite minerals were restricted to the alteration zone, especially (argillic, phyllic, and propylitic) in monzogranite. However, barite veinlets had an ENE-WSW trend, while gold mineralization was confined to quartz veins having NE-SW trends. Monazite and zircon are radioactive-bearing minerals recorded in monzogranite causing high radioactive zones in south Monqul. The radionuclide activity concentrations were detected in the studied monzogranites. The mean values of AU (103 ± 91 Bq kg-1), ATh (78 ± 19 Bq kg-1), and AK (1484 ± 334 Bq kg-1) in the monzogranite samples were higher than the recommended worldwide average. The change in radioactive-transporting minerals found inside granite faults caused the high amounts of radioactivity seen in the samples. Due to the monzogranites being applied in building materials, the radiological hazards were assessed by calculating risk indices such as annual effective dose (AED) and excess lifetime cancer risk (ELCR). The acceptable limit for the ELCR readings was surpassed. As a result, the investigated monzogranite samples are not suitable for use in infrastructure materials.

18.
Front Vet Sci ; 9: 800237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372531

RESUMO

The objective is to propose a modified FCI scoring protocol of the canine hip joint via: (1) providing morphometric criteria of each score; (2) quantifying the extent of lateral and dorsal acetabular femoral head (AFH) coverage; (3) evaluating the steepness of cranial acetabular edge (acetabular index angle) and inclination angle (IA) in normal and dysplastic coxofemoral joints of Labrador Retrievers. The long-term goal is to achieve a selective breeding protocol using parental phenotypically healthy coxofemoral joints based on the standard extended-leg VD radiograph to help reduce the prevalence of CHD among offspring. Investigated populations were classified into normal (grade A) and dysplastic coxofemoral joints (grades B to E) based on the morphometric criteria previously established by the conventional FCI scoring system. Center-edge (CE) angle, Norberg angle (NA), indices of dorsal AFH coverage width and area, acetabular index angle, and inclination angle were determined for each group. Variables were compared between groups using ANOVA. Spearman correlation coefficient was used to determine the linear relationship between selected variables. Overall, all radiographic measurements differed significantly (P < 0.0001) among the five tested groups using ANOVA test. Dorsal AFH coverage area index was the only measure that differed significantly (P ≤ 0.007) between every two consecutive groups using Tukey's test. Significant correlations were identified between the Norberg and CE angles (r s = 0.95, P < 0.0001), the width and area of dorsal AFH coverage (r s = 0.96, P < 0.0001), and the radiographic techniques utilized to assess lateral vs. dorsal AFH coverage (r s ≥ 0.80, P < 0.0001). Evaluation of CE-angle, dorsal AFH coverage area index and acetabular index angle is recommended during selective breeding to include parents with radiographically healthy joints and reduce the incidence of hip dysplasia among offspring. Dogs with CE-angle <27°, dorsal AFH coverage area index <53%, and/or acetabular index angle >9° may be consistent with hip dysplasia and are recommended to be excluded from potential breeding groups. Re-evaluation of coxofemoral joints with borderline values located between near-normal and mildly dysplastic coxofemoral joints is strongly recommended to be performed after 6 months.

19.
Cureus ; 13(12): e20439, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35047276

RESUMO

Pleural effusion can rarely present as an initial manifestation of Ewing sarcoma. We illustrate a case of a young male adult who was admitted with pleural effusion that led to the diagnosis of Ewing sarcoma.

20.
Front Immunol ; 11: 832, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457754

RESUMO

Inhibitors that block the programmed cell death-1 (PD-1) pathway can potentiate endogenous antitumor immunity and have markedly improved cancer survival rates across a broad range of indications. However, these treatments work for only a minority of patients. The efficacy of anti-PD-1 inhibitors may be extended by cytokines, however, the incorporation of cytokines into therapeutic regimens has significant challenges. In their natural form when administered as recombinant proteins, cytokine treatments are often associated with low response rates. Most cytokines have a short half-life which limits their exposure and efficacy. In addition, cytokines can activate counterregulatory pathways, in the case of immune-potentiating cytokines this can lead to immune suppression and thereby diminish their potential efficacy. Improving the drug-like properties of natural cytokines using protein engineering can yield synthetic cytokines with improved bioavailability and tissue targeting, allowing for enhanced efficacy and reduced off-target effects. Using structure guided engineering we have designed a novel class of antibody-cytokine fusion proteins consisting of a PD-1 targeting antibody fused together with an interleukin-21 (IL-21) cytokine mutein. Our bifunctional fusion proteins can block PD-1/programmed death-ligand 1 (PD-L1) interaction whilst simultaneously delivering IL-21 cytokine to PD-1 expressing T cells. Targeted delivery of IL-21 can improve T cell function in a manner that is superior to anti-PD-1 monotherapy. Fusion of engineered IL-21 variants to anti-PD1 antibodies can improve the drug-like properties of IL-21 cytokine leading to improved cytokine serum half-life allowing for less frequent dosing. In addition, we show that targeted delivery of IL-21 can minimize any potential detrimental effect on local antigen-presenting cells. A highly attenuated IL-21 mutein variant (R9E:R76A) fused to a PD-1 antibody provides protection in a humanized mouse model of cancer that is refractory to anti-PD-1 monotherapy. Collectively, our preclinical data demonstrate that this approach may improve upon and extend the utility of anti-PD-1 therapeutics currently in the clinic.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Interleucinas/uso terapêutico , Neoplasias/terapia , Animais , Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Neoplasias/imunologia , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico
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