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1.
Vet Res Forum ; 15(4): 207-210, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770205

RESUMO

Genital tumours are rare among cattle, largely due to their relatively short lifespans. Leio-myoma, a smooth muscle tumour being more prevalent in dogs, appears only at a rate of 1.00 - 2.00% in cattle, affecting reproductive efficiency in cases of complete uterine obstruction. This case report involves an 8-year-old cow with repeated insemination attempts unveiled 5.00 cm intra-luminal uterine mass, obstructing the right uterine horn. Transrectal sonography (TRUS) revealed a highly vascularized mass with normal ovarian function. Confirmation of clinical condition, i.e., uterine leiomyoma, via uterine biopsy concluded the presence of neoplastic smooth muscle cells arranged in interlacing bundles showing mild pleomorphism, and special staining using Masson's trichrome revealed an unappreciable amount of connective tissue; subsequently right flank celiotomy was performed to remove the benign tumour. Forty-five days after celiotomy, TRUS examination confirmed an unobstructed uterine horn, and bilateral oviduct patency was adjudged with 2.50% methylene blue. Following treatment for chronic endometritis, artificial insemination led to conception nearly 90 days post-procedure. The TRUS aids preliminary diagnosis, while definitive identification demands necropsy and surgical methods. This case underscores the diagnostic significance of TRUS, histopathology and celiotomy for identifying and managing uterine leiomyoma in cattle.

2.
Indian J Pediatr ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710955

RESUMO

OBJECTIVES: To evaluate the risk of acquiring COVID-19 infection in patients who have undergone adeno-tonsillectomy (AT) as compared to their siblings. METHODS: In this bidirectional cohort control study, 36 cohorts, younger than 18 y, who underwent AT, and 27 controls (siblings of the enrolled cohorts, younger than 18 y) were recruited. Incidence of COVID-19 was analyzed by symptoms suggestive of COVID-19 infection, COVID-19 testing, and SARS-CoV-2 specific antibody measurement. RESULTS: In the cohort group, the overall COVID-19 positivity rate was 80.5% (n = 29/36) and symptomatic COVID-19 positivity rate was 68.9% (n = 20/29). Among the controls, the overall COVID-19 positivity rate was 44% (n = 12/27) and symptomatic COVID-19 positivity rate was 16% (n = 2/12). The cohorts had 1.8 times higher risk of contracting COVID-19 infection and the relative risk of symptomatic COVID-19 infections as compared to controls was 4.14. CONCLUSIONS: This pilot study indicates that adeno-tonsillectomy poses children at a significantly higher risk of COVID-19 infections and likely other viral upper respiratory tract infections.

3.
Indian J Urol ; 40(2): 112-120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725891

RESUMO

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

4.
BMJ Case Rep ; 17(5)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38782429

RESUMO

A girl in her middle childhood presented to the outpatient department (OPD) with a congenital melanocytic naevi (CMN) of the right nasal alar lobule. Her parents had aesthetic concerns and expressed their desire to get the lesion removed. The full-thickness excision of CMN was performed with the reconstruction of the defect using the nasolabial and dorsal nasal advancement flap with conchal cartilage to shape the contour of the ala.


Assuntos
Nevo Pigmentado , Neoplasias Nasais , Neoplasias Cutâneas , Retalhos Cirúrgicos , Humanos , Nevo Pigmentado/cirurgia , Nevo Pigmentado/congênito , Feminino , Neoplasias Nasais/cirurgia , Neoplasias Cutâneas/cirurgia , Criança , Nariz/cirurgia , Nariz/anormalidades , Procedimentos de Cirurgia Plástica/métodos , Rinoplastia/métodos
5.
NMR Biomed ; : e5144, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556777

RESUMO

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

6.
Heliyon ; 10(7): e29079, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596136

RESUMO

The survival rate over a five-year period for rare pancreatic neuroendocrine tumors (PanNET) is notably lower compared to other neuroendocrine tumors due to late-stage detection, which is a consequence of the absence of suitable diagnostic markers; therefore, there exists a critical need for an early-stage biomarker-specific to PanNETs. This study introduces a novel approach, investigating the impact of small extracellular vesicles (sEV) in PanNET growth and metastasis. As proof of concept, this study shows a correlation between sEV concentration in controls and PanNET. Notably, higher sEV concentrations were observed in PanNETs than in controls (p < 0.0001) with a sensitivity of 100%. Further, apparent differences were observed in the sEV concentrations between controls and grades 1 PanNET (p = 0.005). The expression of sEV markers was confirmed using CD63, TSG101, CD9, Flotillin-1, and GAD65 antibodies. Additionally, the expression of cancer marker BIRC2/cIAP1 (p = 0.002) and autophagy marker Beclin-1 (p = 0.02) were observed in plasma-derived sEVs and PanNET tissue. This study represents the first to indicate the increased secretion of sEV in PanNET patients' blood plasma, proposing potential function of sEV as a new biomarker for early-stage PanNET detection.

7.
J Craniovertebr Junction Spine ; 15(1): 123-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38644911

RESUMO

Neurofibromatosis-1 (NF1) presents complex challenges due to its multisystemic effects, including kyphoscoliosis, dural ectasia, and arteriovenous fistulas (AVF). We present a case of a 31-year-old male with NF1 exhibiting severe cervical kyphoscoliosis, dural ectasia, a bisected cervical cord, and an arteriovenous fistula, highlighting the intricacies of managing such intricate cases. Rapid weakening in the patient's right arm and leg prompted imaging revealing severe cervical kyphotic deformity and a dural fold dividing the spinal cord. Surgical intervention addressed a high-flow arteriovenous fistula involving the right vertebral artery and an epidural vein, necessitating sacrifice of the artery. Posterior fusion and laminectomy were performed, resulting in stable neurological status postoperatively and significant improvement in sensory loss and weakness at three months. This case underscores the importance of a tailored posterior-only approach, involving dural fold release, to allow the spinal cord to relocate to a less tense position, thus demonstrating effective decompression in complex NF1 cases with concurrent kyphotic deformity and vertebral artery AVF.

8.
Nucl Med Mol Imaging ; 58(3): 150-151, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38633286

RESUMO

The prevalence of double primary prostate and bladder cancer is not uncommon. Though both share a common pathway of malignant transformation, they bear to differ in the case of 2-[18F]FDG PET/CT and [68Ga]Ga-PSMA uptake. We present a case of double primary cancer involving the bladder and prostate, where the prostatic primary showed intense [68Ga]Ga-PSMA uptake with non-avid skeletal and pulmonary metastases, which showed intense 2-[18F]FDG uptake, thus showing discordance due to different clonal origins.

9.
Methods Mol Biol ; 2788: 3-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656505

RESUMO

Carotenoids are the natural pigments available in nature and exhibit different colors such as yellow, red, and orange. These are a class of phytonutrients that have anti-cancer, anti-inflammatory, anti-oxidant, immune-modulatory, and anti-aging properties. These were used in food, pharmaceutical, nutraceutical, and cosmetic industries. They are divided into two classes: carotenes and xanthophylls. The carotenes are non-oxygenated derivatives and xanthophylls are oxygenated derivatives. The major source of carotenoids are vegetables, fruits, and tissues. Carotenoids also perform the roles of photoprotection and photosynthesis. In addition to the roles mentioned above, they are also involved and act as precursor molecules for the biosynthesis of phytohormones such as strigolactone and abscisic acid. This chapter briefly introduces carotenoids and their extraction method from plant tissue. Proposed protocol describes the extraction of carotenoid using solvents chloroform and dichloromethane. Reverse-phase HPLC can be performed with C30 columns using gradient elution. The column C30 is preferred to the C18 column because the C30 column has salient features, which include selective nature in the separation of structural isomers and hydrophobic, long-chain compounds, and shows the best compatibility with highly aqueous mobile phases. A complete pipeline for the extraction of carotenoids from plant tissue is given in the present protocol.


Assuntos
Carotenoides , Carotenoides/isolamento & purificação , Carotenoides/química , Carotenoides/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Plantas/química , Plantas/metabolismo , Extratos Vegetais/química
10.
Methods Mol Biol ; 2788: 19-37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656506

RESUMO

Metabolites are intermediate products formed during metabolism. Metabolites play different roles, including providing energy, supporting structure, transmitting signals, catalyzing reactions, enhancing defense, and interacting with other species. Plant metabolomics research aims to detect precisely all metabolites found within tissues of plants through GC-MS. This chapter primarily focuses on extracting metabolites using chemicals such as methanol, chloroform, ribitol, MSTFA, and TMCS. The metabolic analysis method is frequently used according to the specific kind of sample or matrix being investigated and the analysis objective. Chromatography (LC, GC, and CE) with mass spectrometry and NMR spectroscopy is used in modern metabolomics to analyze metabolites from plant samples. The most frequently used method for metabolites analysis is the GC-MS. It is a powerful technique that combines gas chromatography's separation capabilities with mass spectrometry, offering detailed information, including structural identification of each metabolite. This chapter contains an easy-to-follow guide to extract plant-based metabolites. The current protocol provides all the information needed for extracting metabolites from a plant, precautions, and troubleshooting.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Plantas , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Plantas/metabolismo , Plantas/química , Metaboloma , Extratos Vegetais/química , Extratos Vegetais/análise
11.
Indian J Otolaryngol Head Neck Surg ; 76(2): 1563-1568, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566628

RESUMO

The Objective of the study was to assess the ossicular status in chronic otitis media (COM)-mucosal and squamosal type and statistically evaluate the extent of ossicular destruction intraoperatively in COM patients. The findings of this study could help us to predict preoperatively the probability of having ossicular chain destruction in COM ears and thus patients could therefore be properly consented about these potential issues before surgery. The study was carried out in ENT department of tertiary health care hospital, between January 2019 to January 2020. All patients of all age groups and both genders, diagnosed with COM Mucosal and Squamosal Type with complaints of ear discharge and hearing loss with good cochlear reserve and requiring surgery were included in the study, after taking informed written consent in vernacular language. All the patients included in the study were evaluated with detailed history, clinical examination including otomicroscopy, tuning fork tests and pure tone audiometry. The patients were then posted for ear surgery and the middle ear status and ossicular chain status were assessed using a microscope intraoperatively. Out of 98 patients, 45(45.9%) had mucosal and 53 (54.08%) had squamosal disease. Ossicular chain was eroded in 69 cases (70.5%). 23 out of 45 (51.1%) mucosal cases and 46 out of 53 squamosal cases (86.7%) reported ossicular erosion. Most frequently involved was long process of incus > stapes > malleus. From our study, we concluded that there is a significant relationship between type of disease pathology in middle ear and ossicular erosion being higher in Squamosal type of COM, with malleus being the most resistant and incus being the most susceptible ossicle.

12.
Indian J Otolaryngol Head Neck Surg ; 76(2): 1503-1508, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566736

RESUMO

Objective: To assess the microvascular density (MVD) in juvenile nasopharyngeal angiofibroma (JNA) with CD34 immunostaining and evaluate its relationship with clinico-demographic features. Methods: This prospective study included patients with JNA undergoing endoscopic excision. The histopathological specimen was stained using CD-34 antibodies to calculate MVD. MVD and clinico-demographic features were correlated. Results: The study included 12 patients with a median age of 15.5 years. The mean MVD was 39 vessels/high power field (range 5 to 151 vessels). MVD was significantly associated only with the volume of tumour (r = 0.65, p = 0.02). The recurrence occurred in one patient with an MVD of 107. The median follow-up was 38 months. Conclusion: MVD is significantly associated with tumour volume in JNA, which implies a robust role of angiogenesis in the pathology of the tumour. Also, higher MVD may be a risk factor for recurrence.

13.
Pestic Biochem Physiol ; 200: 105844, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582571

RESUMO

Enzymes have attracted considerable scientific attention for their crucial role in detoxifying a wide range of harmful compounds. In today's global context, the extensive use of insecticides has emerged as a significant threat to the environment, sparking substantial concern. Insects, including economically important pests like Helicoverpa armigera, have developed resistance to conventional pest control methods through enzymes like carboxyl/cholinesterases. This study specifically focuses on a notable carboxyl/cholinesterase enzyme from Helicoverpa armigera (Ha006a), with the goal of harnessing its potential to combat environmental toxins. A total of six insecticides belonging to two different classes displayed varying inhibitory responses towards Ha006a, thereby rendering it effective in detoxifying a broader spectrum of insecticides. The significance of this research lies in discovering the bioremediation property of Ha006a, as it hydrolyzes synthetic pyrethroids (fenvalerate, λ-cyhalothrin and deltamethrin) and sequesters organophosphate (paraoxon ethyl, profenofos, and chlorpyrifos) insecticides. Additionally, the interaction studies between organophosphate insecticides and Ha006a helped in the fabrication of a novel electroanalytical sensor using a modified carbon paste electrode (MCPE). This sensor boasts impressive sensitivity, with detection limits of 0.019 µM, 0.15 µM, and 0.025 µM for paraoxon ethyl, profenofos, and chlorpyrifos, respectively. This study provides a comprehensive biochemical and biophysical characterization of the purified esterase Ha006a, showcasing its potential to remediate different classes of insecticides.


Assuntos
Clorpirifos , Inseticidas , Mariposas , Organotiofosfatos , Paraoxon/análogos & derivados , Piretrinas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Carboxilesterase/metabolismo , Helicoverpa armigera , Piretrinas/farmacologia , Piretrinas/metabolismo , Colinesterases , Resistência a Inseticidas
14.
Ann Geriatr Med Res ; 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509825

RESUMO

Introduction: Older patients are particularly vulnerable to age-related respiratory changes. This prospective randomized controlled trial studied the effects of high and low fractions of inspired oxygen (FiO2) with the recruitment maneuver (RM) during extubation on lung atelectasis post-operatively in older patients undergoing major abdominal surgery. Methods: We randomized a total of 132 patients aged >60 years who underwent both elective and emergency major abdominal surgeries and met the inclusion criteria into three groups (H, HR, and LR) using computer-generated block randomization. Group H received high FiO2 (1), Group HR received high FiO2 (1) with RM followed by a positive end-expiratory pressure of 5 cm H2O, and Group LR received low FiO2 (0.4) with RM followed by a positive end-expiratory pressure of 5 cm H2O 10 min before extubation. Oxygenation and atelectasis were measured using the arterial partial pressure of oxygen (PaO2)/FiO2 ratios and lung ultrasound score. Postoperative pulmonary complications were recorded up to 24 h postoperatively. Results: The mean PaO2/FiO2 at 30 min post-extubation was significantly higher in Groups LR and HR compared to that in Group H (390.71 ± 29.55, 381.97 ± 24.97, and 355.37 ± 31.7, p <0.001). In the immediate postoperative period, the median lung ultrasound score was higher in Group H than that in Groups LR and HR (6 [5-7]), 3 [3-5], and 3.5 [2.25-4.75], p <0.001). The incidence of oxygen desaturation and oxygen requirements was higher in Group H during the postoperative period. Conclusion: The RM before extubation is beneficial in reducing atelectasis and postoperative pulmonary complications, irrespective of the FiO2 concentration used in older adults undergoing major abdominal surgeries.

15.
Eur J Obstet Gynecol Reprod Biol X ; 22: 100295, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38496380

RESUMO

Background: With ever increasing rates of emergency caesarean deliveries (CD),incorporating the ERAS protocol might provide a perfect window of opportunity to increase maternal comfort during the postsurgical period, but also improve outcomes and facilitate optimal return of physiological function. Objective: To determine whether an ERAS pathway at emergency caesarean birth would permit a reduction in postoperative length of stay and improve postoperative patient satisfaction. Material & methods: Patients undergoing emergent caesarean delivery at ≥ 34 weeks of gestation were randomized to ERAS or conventional care. The primary outcome was to compare postoperative length of hospital stay. Secondary outcome variables included first oral intake, passage of flatus/defecation, first ambulation, first urination after catheter removal and postoperative pain scores in both groups. Results: We randomized 142 women (71 each in ERAS versus Conventional arm) undergoing emergency cesarean delivery. Incorporation of ERAS protocol resulted in shorter length of hospital stay (73.92 ± 8.96 in conventional arm vs 53.87 ± 15.02 in ERAS arm; p value <.0001). Significant difference was seen in visual analogue scoring during initial ambulation and rest on day 0 and day 1 between ERAS and conventional arms with mean scores being lower in ERAS arm compared to Conventional arm (p value <.05). In terms of quality of life, ERAS arm had better quality of life compared to conventional arm. Conclusion: Incorporation of ERAS protocol in emergency caesarean definitely improves patient outcome in terms of early resumption of activities with better quality of life.

16.
Biochem Pharmacol ; 223: 116126, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490521

RESUMO

Anastasis cascade including induction of Epithelial to Mesenchymal Transition (EMT), DNA repair, and stimulation of pro-survival mediators collectively exaggerate therapy resistance in cancer prognosis. The extensive implications of DNA-damaging agents are clinically proven futile for the rapid development of disease recurrence during treatment regime. Herein we report a glycosidic derivative of Δ9-tetrahydrocannabinol (THC-9-OG) abrogates sub-toxic doses of 5-Fluorouracil (5FU) induced EMT in colon cancer cells nullifying DNA repairing mechanism. Our in vitro and in vivo data strongly proclaims that THC-9-OG could not only abrogate 5FU mediated background EMT activation through stalling matrix degradation as well as murine 4T1 lung metastasis but also vigorously diminished Rad-51 repairing mediator along with stimulation of γ-H2AX foci formation. The combinatorial treatment (5FU + THC-9-OG) in Apc knockout colorectal carcinoma model conferred remission of the crypt progenitor phenotype which was prominently identified in 5FU treatment. Mechanistically, we demonstrated that 5FU plus THC-9-OG significantly attenuated major EMT inducer Vimentin via extensive ROS generation along with autophagy induction via LC3B I-II conversion and p62 degradation in a p-ATM dependent manner. Additionally, Cannabinoid receptor CB1 was responsible for abrogation of Vimentin since we found increase in the expression of γH2AX and decrease in vimentin expression in CB1 agonist (ACEA) plus 5FU treated cells. Nutshell, our results unveil a new direction of Cannabinoid based combinatorial approach to control background EMT along with robust enhancing of DNA damage potential of sub-toxic concentration of 5FU resulting immense inhibition of distant metastasis coupled with triggering cell death in vitro and in vivo.


Assuntos
Canabinoides , Humanos , Animais , Camundongos , Fluoruracila/farmacologia , Transição Epitelial-Mesenquimal , Vimentina/genética , Vimentina/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia , Autofagia , DNA
17.
Indian J Surg Oncol ; 15(1): 1-7, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511023

RESUMO

Breast cancer is the most common cancer affecting women globally, with an increasing incidence of breast cancer in young women in India and worldwide. Despite medical advancements, the lifetime risk of developing breast cancer is still high. The emergence of breast cancer in young women is now acknowledged as a distinct entity characterized by unique clinical and biological features and an overall poor prognosis. This article discusses the changing landscape of breast cancer in young women in India and globally, potential examples of the underlying reasons, and possible strategies to start reversing the current upward trend.

18.
Cancer Immunol Immunother ; 73(4): 72, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430405

RESUMO

BACKGROUND: Inhibition of the adenosine 2A receptor (A2AR) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A2AR antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer. METHODS: Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab). Primary endpoints were objective response rate per RECIST v1.1 and prostate-specific antigen (PSA) response rate. Secondary endpoints included radiological progression-free survival (rPFS), overall survival, safety, and pharmacokinetics. RESULTS: Fifty-nine patients were treated (Module 1, n = 29; Module 2, n = 30). Median number of prior therapies was 4. One confirmed complete response by RECIST (Module 1) and 2 confirmed PSA responses (1 per module) were observed. The most frequent adverse events (AEs) possibly related to AZD4635 were nausea (37.9%), fatigue (20.7%), and decreased appetite (17.2%) in Module 1; nausea (50%), fatigue (30%), and vomiting (23.3%) in Module 2. No dose-limiting toxicities or treatment-related serious AEs were observed. In Module 1, AZD4635 geometric mean trough concentration was 124.9 ng/mL (geometric CV% 69.84; n = 22); exposures were similar in Module 2. In Modules 1 and 2, median (95% CI) rPFS was 2.3 (1.6 -3.8) and 1.5 (1.3- 4.0) months, respectively. Median PFS was 1.7 versus 2.3 months for patients with high versus low blood-based adenosine signature. CONCLUSION: In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile. CLINICAL TRIAL: gov identifier: NCT04089553.


Assuntos
Anticorpos Monoclonais , Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antígeno Prostático Específico , Antineoplásicos/uso terapêutico , Fadiga , Adenosina , Náusea/tratamento farmacológico
19.
Indian J Anaesth ; 68(3): 254-260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476554

RESUMO

Background and Aims: There is limited literature wherein the hypotensive drugs have been compared to know the cerebral effects by monitoring regional cerebral oxygen saturation (rScO2). This study aimed to compare the effects of dexmedetomidine and nitroglycerin on rScO2 during controlled hypotensive anaesthesia using near-infrared spectroscopy (NIRS). The primary objective was to evaluate the non-inferiority of dexmedetomidine versus nitroglycerin in the occurrence of cerebral desaturation events (CDEs) during hypotensive anaesthesia. Methods: Adult patients scheduled to undergo head and neck surgery under general anaesthesia randomised to receive either dexmedetomidine or nitroglycerin infusion for controlled hypotensive anaesthesia. Cerebral oximetry was monitored with NIRS, and data regarding CDEs, bilateral rScO2, and peri-operative haemodynamics were collected. Continuous data were analysed using unpaired Student's t-tests except for intra-group analyses, which were analysed using paired t-tests. Categorical data were analysed using the Chi-square test. For comparison of time to CDEs, Kaplan-Meier survival analysis with log-rank test was performed. Results: Of the 82 patients in both groups, CDEs were observed in 15 patients each. A decrease from baseline by 20% was observed in three patients: one in Group N and two in Group D. Statistically, there was an equal risk of getting CDEs in the groups. The time to CDE was comparable (P > 0.05). The difference in heart rate was statistically significant (P < 0.001). Conclusion: Dexmedetomidine is non-inferior to nitroglycerin in terms of the occurrence of cerebral desaturation events when used for controlled hypotensive anaesthesia in head and neck surgeries.

20.
J Biochem Mol Toxicol ; 38(3): e23672, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462741

RESUMO

Adhesion G protein-coupled receptor G4 (ADGRG4) is a G protein-coupled receptor (GPCR) that belongs to the adhesion family. Participation of ADGRG4 in cell adhesion and migration, signaling pathway activation, influence on angiogenesis, and modulation of immune responses are some of the possible ways through which it may contribute to oncogenesis. Conducting extensive omics studies poses budgetary challenges to small labs in peripheral areas, primarily due to restricted research funding and resource limitations. Here we propose a low-budget model for biomarker screening. A total of 11 ovarian cancer samples were sent for exome sequencing. Among various genes, ADGRG4 variants were present in all 11 samples and thus were chosen as a potential biomarker in the present population. However, the precise role of ADGRG4 in cancer is not fully understood. The present study aims to look at the association between the ADGRG4 gene variants and their risk of ovarian cancer in the North Indian region of Jammu and Kashmir, India. Overall, 235 individuals (115 cases and 120 healthy controls) were genotyped for the selected biomarker using Sanger sequencing. Logistic regression was used to assess the relationship between the variant and ovarian cancer. A statistically significant association was identified between the ADGRG4 variant rs5930932 polymorphism and the incidence of ovarian cancer among the study population. When corrected for age and BMI, the dominating OR of variant rs5930932 was 1.035 (1.003-1.069) under HWE patients (0.95) and controls (0.18), with a p-value of (0.03). According to the findings of the current investigation, the ADGRG4 gene variant rs5930932 increases the chance of developing ovarian cancer in the studied population.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Humanos , Feminino , Biomarcadores Tumorais/genética , Sequenciamento do Exoma , Genótipo , Neoplasias Ovarianas/genética , Receptores Acoplados a Proteínas G/genética , Índia/epidemiologia
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