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Biomedical subjects

Amit Agrawal

Publications and source records attributed to Amit Agrawal.

At least 19 recordsLinked to original sources

Diagnostic and Predictive Value of Circulating and Exosomal microRNAs in Ferroptosis-Associated Neurological Conditions: A Systematic Review and Meta-analysis.

Circulating microRNAs (miRNAs) have emerged as potential non-invasive markers for intracranial pathology, yet their diagnostic accuracy and relationship with ferroptosis-mediated neuronal damage remain poorly defined. The primary objective of this study was to evaluate the diagnostic and predictive potential of circulating and exosomal miRNAs across ferroptosis-associated neurological conditions and to explore their associations with ferroptosis-related pathways. Following PRISMA-DTA guidelines, a systematic literature search was conducted across PubMed, Scopus, Cochrane, and ScienceDirect, identifying 205 records. After screening for human clinical cohort validation, 7 studies were included in the qualitative synthesis and 5 in the quantitative meta-analysis. Pooled Area-under-the-Curve (AUC) was calculated using a random-effects inverse-variance model, while prognostic correlation coefficients (r) were synthesized using Fisher's Z-transformation. Methodological quality was assessed via QUADAS-2. Analysis of 7 clinical cohorts provided heterogeneous evidence on the diagnostic and prognostic potential of miRNAs. Random-effects pooling of the two eligible diagnostic AUC estimates yielded an exploratory pooled AUC of 0.87 (95% CI, 0.79-0.94; I2 .90%). Prognostic synthesis of Group 2 identified an exploratory association between miRNA levels and clinical severity scales (exploratory pooled correlation coefficient of 0.67 (95% CI: 0.56-0.76; I2 .714.4%). Selected miRNAs were mapped to ferroptosis-associated regulators, including SLC7A11, ABCB8, and SLC40A1. Exosomal miRNAs hold potential to indicate disease-associated molecular information, although comparative clinical evidence remains yet to be explored. Circulating and exosomal miRNAs show promising diagnostic and prognostic potential across selected neurological conditions. These findings highlight a potential mechanistic association between miRNA expression and ferroptosis-mediated neuronal injury.

Humans↗

Extracranial meningioma in the vicinity of the temporal bone: a difficult preoperative diagnosis.

BACKGROUND: Extracranial meningioma is a rare tumor, and most of the time only after histopathologic examination is diagnosis possible. CASE DESCRIPTION: A 40-year-old right-handed woman presented with progressive swelling over the right side of the forehead and temporal region associated with proptosis and visual loss. Incisional biopsy of the lesion was reported as spindle cell tumor. Computed tomography scan showed large enhancing predominantly extracranial lesion located in the right anterior frontotemporal region extending into the infratemporal fossa and a relatively thin sheet of tumor on the intracranial aspect of the thickened temporal. Intraoperative impression was malignant tumor involving the temporalis muscle, and a near total excision of the lesion was performed. Histopathologic features were suggestive of meningothelial meningioma arising from the temporal bone with predominant extracranial extension. CONCLUSION: Preoperative suspicion of a meningioma in this patient would have resulted in a more aggressive surgical approach as these lesions are relatively benign with indolent course.

Adult↗

Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals: dual-function microcarriers for optical encoding and magnetic separation.

Mesoporous beads are promising materials for embedding functional nanoparticles because of their nanometer-sized pores and large surface areas. Here we report the development of silica microbeads embedded with both semiconductor quantum dots (QD) and iron oxide (Fe3O4) nanocrystals as a new class of dual-function carriers for optical encoding and magnetic separation. The embedding (doping) process is carried out by either simultaneous or sequential addition of quantum dots and iron oxide (Fe3O4) nanocrystals in solution. The doping process is fast and quantitative, but the incorporated iron oxide strongly attenuates the signal intensity of QD fluorescence. We find that this attenuation is not due to conventional fluorescence quenching but is caused by the broad optical absorption spectrum of mixed-valence Fe3O4. For improved biocompatibility and reduced nonspecific binding, the encoded beads are further coated with amphiphilic polymers such as octylamine poly(acrylic acid). The results indicate that the polymer-coated beads are well suited for target capturing and enrichment, yielding magnetic separation efficiencies higher than 99%. By combining the multiplexing capability of QDs with the superparamagnetic properties of iron oxide nanocrystals, this class of encoded beads is expected to find broad applications in high-throughput and multiplexed biomolecular assays.

Ferric Compounds↗

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.

BACKGROUND: High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. PATIENTS AND METHODS: According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. RESULTS: Twelve patients with a median age of 75.1 years (49.1-85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3rd to 7th line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for > or = 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7-36) months. The time to treatment failure was 4 (0.5-36) months. CONCLUSION: Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy.

Journal Article↗

"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer.

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1st line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line), 46.1% (on 3rd line) and 20% (on 4th line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64 (28.7%) patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line) and 22.2% (on 3rd line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

Journal Article↗

Neuromuscular disorders in critical illness.

Neuromuscular disorders in the background of critical illness are under diagnosed. Standardized screening for weakness in the intensive care unit (ICU) setting is uncommon and persistent weakness as a sequel of critical illness is usually not recognized by physicians in the ICU for whom survival from acute illness is the primary outcome. The spectrum of illness ranges from isolated nerve entrapment with focal pain or weakness, to disuse muscle atrophy with mild weakness, and to severe myopathy or neuropathy with associated severe, prolonged weakness. This update focuses on neuromuscular disorders occurring in the critical care set up associated with diffuse and severe weakness.

Critical Illness↗

Counting single native biomolecules and intact viruses with color-coded nanoparticles.

Nanometer-sized particles such as semiconductor quantum dots and energy-transfer nanoparticles have novel optical properties such as tunable light emission, signal brightness, and multicolor excitation that are not available from traditional organic dyes and fluorescent proteins. Here we report the use of color-coded nanoparticles and dual-color fluorescence coincidence for real-time detection of single native biomolecules and viruses in a microfluidic channel. Using green and red nanoparticles to simultaneously recognize two binding sites on a single target, we demonstrate that individual molecules of genes, proteins, and intact viruses can be detected and identified in complex mixtures without target amplification or probe/target separation. Real-time coincidence analysis of single-photon events allows rapid detection of bound targets and efficient discrimination of excess unbound probes. Quantitative studies indicate that the counting results are remarkably precise when the total numbers of counted molecules are more than 10. The use of bioconjugated nanoparticle probes for single-molecule detection is expected to have important applications in ultrasensitive molecular diagnostics, bioterrorism agent detection, and real-time imaging and tracking of single-molecule processes inside living cells.

Base Sequence↗

Intensification regimen for advanced-stage resectable hypopharyngeal carcinoma.

OBJECTIVE: To determine feasibility, compliance, long-term survival, and disease control rates in the intensification regimen for advanced resectable hypopharyngeal carcinoma. DESIGN: Prospective, nonrandomized, controlled phase 2 trial with a median follow-up period of 89 months (range, 3.4-140.0 months). SETTING: Cancer center at a state university. PATIENTS: Thirty-two patients (age range, 44-79 years; median age, 59 years) with advanced (69% stage IV, 31% stage III) resectable hypopharyngeal carcinoma. INTERVENTIONS: Combination of surgery, radiation therapy, and chemotherapy (cisplatin and paclitaxel) along with intraoperative radiation therapy. MAIN OUTCOME MEASURES: Compliance, long-term survival, and locoregional and systemic disease control rates and functional outcome. RESULTS: The protocol compliance rate was 62% (20 of 32 patients), and the overall 5-year survival rate was 56%. Local recurrence occurred in 3 patients (9%). The systemic disease control rate was 91% (29 of 32 patients). Total laryngectomy was required in 15 patients (47%); preservation of the larynx was possible in 17 patients (53%). Only 3 (13%) of 6 patients were percutaneous endoscopic gastrostomy tube dependent in the long-term follow-up. CONCLUSIONS: The intensification regimen described in this study accomplished excellent long-term survival and disease control rates in patients with advanced resectable hypopharyngeal carcinoma. The future plan is to proceed with a phase 3 trial if the single-institutional experience at The Ohio State University can be duplicated in a multi-institutional phase 2 study.

Adult↗

Clinical relevance of the nutcracker esophagus: suggested revision of criteria for diagnosis.

BACKGROUND: Nutcracker esophagus (NE) is a manometric finding defined by peristaltic contractions with a mean distal esophageal amplitude (DEA) >180 mm Hg. This threshold has been selected as it exceeds the average DEA in healthy volunteers by 2 SDs. Since its introduction the clinical significance of this finding has been challenged, as many patients with NE are asymptomatic. AIM: To evaluate whether defining NE based on a different DEA threshold would be clinically more meaningful. METHODS: Retrospective review of prospectively collected manometry data between October 2001 and December 2003. Using previously published normal DEA values (mean and SD) patients with NE were stratified into 3 groups: group A (2 to 3 SD above mean): DEA 180 to 220 mm Hg; group B (3 to 4 SD above mean): DEA 220 to 260 mm Hg; and group C (>4 SD above mean): DEA >260 mm Hg. Symptoms, esophageal acid exposure, bolus transit data, and lower esophageal sphincter data were reviewed. RESULTS: The stratification of 56 NE patients into groups A, B, and C were 31, 16, and 9, respectively. The proportion of patients presenting with chest pain increased from 23% in group A to 69% in group B and 100% in group C. Patients in group C had significantly (P<0.05) higher mean lower esophageal sphincter pressure, shorter bolus transit time, and lower frequency of abnormal reflux. CONCLUSIONS: A revised definition of NE to include patients with a DEA >260 mm Hg, and possibly those with >220 may have greater clinical relevance.

Adolescent↗

Long-term results of a multimodal intensification regimen for previously untreated advanced resectable squamous cell cancer of the oral cavity, oropharynx, or hypopharynx.

BACKGROUND: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed. METHODS: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery. RESULTS: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%. CONCLUSIONS: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.

Adult↗

Robust ego-motion estimation and 3-D model refinement using surface parallax.

We present an iterative algorithm for robustly estimating the ego-motion and refining and updating a coarse depth map using parametric surface parallax models and brightness derivatives extracted from an image pair. Given a coarse depth map acquired by a range-finder or extracted from a digital elevation map (DEM), ego-motion is estimated by combining a global ego-motion constraint and a local brightness constancy constraint. Using the estimated camera motion and the available depth estimate, motion of the three-dimensional (3-D) points is compensated. We utilize the fact that the resulting surface parallax field is an epipolar field, and knowing its direction from the previous motion estimates, estimate its magnitude and use it to refine the depth map estimate. The parallax magnitude is estimated using a constant parallax model (CPM) which assumes a smooth parallax field and a depth based parallax model (DBPM), which models the parallax magnitude using the given depth map. We obtain confidence measures for determining the accuracy of the estimated depth values which are used to remove regions with potentially incorrect depth estimates for robustly estimating ego-motion in subsequent iterations. Experimental results using both synthetic and real data (both indoor and outdoor sequences) illustrate the effectiveness of the proposed algorithm.

Algorithms↗

Concepts of seroma formation and prevention in breast cancer surgery.

BACKGROUND: Seroma formation is the commonest early sequel to breast cancer surgery especially when axillary dissection is undertaken. It is associated with significant morbidity and financial burden. The main pathophysiology of seroma is still poorly understood and remains controversial. The optimal ways to reduce the incidence of seroma formation are unknown. The aim of this paper is to review the concepts of pathophysiology of seroma formation following mastectomy and breast-conserving surgery for cancer. The various techniques in practice to reduce its incidence and treatment are outlined. METHOD: MEDLINE search of published work on the subject with respect to its pathophysiology, prevention and treatment was carried out. Manual retrieval of relevant articles in the reference lists of the original papers from the MEDLINE was then carried out. RESULT: The pathophysiology and mechanism of seroma formation in breast cancer surgery remains controversial and not fully understood. Methods of prevention and treatment of seroma remain varied and inconclusive. CONCLUSION: Evidence suggests an increase in the incidence of seroma because of thermal trauma from electrocautery dissection, but this is indispensable for surgical haemostasis. Obliteration of dead space by various flap apposition techniques has been shown to be advantageous in reducing incidence and volume of seroma. Low-pressure suction drainage reduces seroma volume and duration of drainage leading to earlier drain removal. Preventive measures have to be tailored according to individual patient and operative factors.

Antineoplastic Agents, Hormonal↗

Symptom and function heterogenicity among patients with distal esophageal spasm: studies using combined impedance-manometry.

BACKGROUND: Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a clinically available tool that assesses the functional defect of various manometric abnormalities. The aim of our study was to evaluate esophageal bolus transit in patients with manometrically defined distal esophageal spasm (DES). METHODS: Patients referred for esophageal function testing underwent combined MII-EM studies including 10 liquid and 10 viscous swallows. Individual swallows were classified using previously published manometric and impedance criteria. DES is traditionally defined as > or =20% simultaneous contractions in the distal esophagus. Diagnosis of esophageal transit abnormalities was defined by the presence of > or =30% incomplete liquid or > or =40% incomplete viscous swallows. RESULTS: Data from 71 patients (43 female, mean age 57 yr, range 16-85) with a manometric diagnosis of DES were analyzed. During liquid swallows, patients with chest pain had higher (p < 0.05) distal esophageal amplitudes (202.3 +/- 34.5 mmHg) and a higher (p < 0.05) percentage of swallows with complete bolus transit (89%+/- 3%) compared to patients presenting with dysphagia (amplitude 117.8 +/- 8.7 mmHg; percentage of complete transit 69%+/- 5%) and patients with reflux symptoms (amplitude 116.4 +/- 12.7 mmHg; percentage of complete transit 74%+/- 5%). Fifty-one percent of the DES patients had a normal bolus transit for liquid and viscous, 24% abnormal bolus transit for one substance, and 25% abnormal bolus transit for liquid and viscous. CONCLUSION: Pressure and bolus transit information in patients with manometrically defined DES points toward heterogenicity of this group of patients. Outcomes data are warranted to evaluate whether stratifying DES patients based on pressure and bolus transit information may improve the clinical approach.

Adolescent↗

Intramedullary endometriosis of the conus medullaris: case report.

OBJECTIVE: Intraspinal endometriosis is an extremely rare condition with characteristic symptoms, including lower back pain that increases in severity during each menstrual cycle. METHODS: Here, we report a case of endometriosis involving the conus cauda region. This patient presented with acute deterioration secondary to hemorrhage. We also review the relevant literature. RESULTS: Magnetic resonance imaging scans of the dorsolumbar region showed a mass lesion within the spinal canal at the L1-L2 level with evidence of acute hemorrhage. The patient underwent an emergency D12-L2 laminectomy and microdecompression of the lesion. The histological and immunohistochemical features were characteristic of intraspinal endometriosis. CONCLUSION: Intraspinal endometriosis must be recognized as a potential cause of periodic neurological signs and symptoms in young and middle-aged women.

Acute Disease↗

Nonacid reflux in patients with chronic cough on acid-suppressive therapy.

BACKGROUND: It is generally accepted that extraesophageal gastroesophageal reflux disease (GERD) symptoms and their persistence despite acid-suppressive therapy are poor prognostic factors for antireflux surgery. Recent studies indicating that cough can be temporally associated with reflux episodes of pH 4 to 7 (ie, nonacid reflux) reinvigorates the need for a more careful workup in patients with cough suspected to be due to GERD. AIM: To evaluate the frequency of chronic cough associated with nonacid reflux and the response of these patients to laparoscopic Nissen fundoplication. METHODS: We retrospectively reviewed data from patients with persistent cough despite twice-daily proton pump inhibitor (PPI) with or without the use of nighttime regimens of histamine-2 receptor antagonist (H2RA), who had undergone combined multichannel intraluminal impedance and pH monitoring. The association of cough and reflux was evaluated by calculating the symptom index (SI) [positive if > or = 50%]. A subset of patients with positive SI values for impedance-detected reflux with therapy was referred for laparoscopic Nissen fundoplication. RESULTS: Of 50 patients (38 female patients; mean age, 43 years; age range, 6 months to 84 years) who were monitored while receiving therapy, 13 patients (26%) had a positive SI for cough. The SI-positive group had a lower percentage of female patients and patients of younger age compared to the SI-negative group. Laparoscopic Nissen fundoplication was performed in six SI-positive patients who became asymptomatic and stopped receiving acid-suppressive therapy during follow-up evaluations (median time, 17 months; range, 12 to 27 months). CONCLUSION: Impedance pH monitoring should be performed while receiving therapy in patients with persistent symptoms who are receiving PPI therapy. A positive SI for nonacid reflux may be helpful in selecting patients who will benefit from antireflux surgery.

Adolescent↗

Post-traumatic epilepsy: an overview.

Post-traumatic epilepsy (PTE) is a recurrent seizure disorder secondary to brain injury following head trauma. PTE is not a homogeneous condition and can appear several years after the head injury. The mechanism by which trauma to the brain tissue leads to recurrent seizures is unknown. Cortical lesions seem important in the genesis of the epileptic activity, and early seizures are likely to have a different pathogenesis than late seizures. Anti-epileptic drugs available for treatment are phenytoin, sodium valproate, and carbamazepine. Newer anti-epileptics are helpful, particularly in patients with associated post-traumatic stress disorders; however, no randomized controlled studies are available to prove that one of these drugs is better than the other. Current evidence is that the treatment of early post-traumatic seizures does not influence the incidence of post-traumatic epilepsy. Routine preventive anticonvulsants are not indicated for patients with head injuries, and treatment in the acute phase does not reduce death or disability rates.

Anticonvulsants↗