Tag: nevin manimala

JNCI Cancer Spectr. 2023 Apr 2:pkad022. doi: 10.1093/jncics/pkad022. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast cancer patients.

METHODS: Patients from the Tamoxifen and Exemestane Adjuvant Multinational trial received 5 years exemestane (exemestane group, n = 114) or 2.5 years tamoxifen followed by 2.5 years exemestane (sequential group, n = 92). Neuropsychological performance was assessed pre-endocrine therapy, after 1 year (ST follow-up) and at 5 years (LT follow-up). Controls (n = 120) were assessed with parallel intervals. With random effects modeling we evaluated cognitive changes from baseline to ST and LT follow-up. Statistical tests were 2-sided.

RESULTS: After controlling for age, intelligence quotient, attrition, menopausal symptoms, anxiety and/or depression, and/or fatigue, the sequential group showed ST and LT decline compared with controls on verbal memory (effect size [ES] = 0.26, P = .01; ES = 0.34, p = .003) and executive function (ES = 0.27, p = .007; ES = 0.38, p = .002). Compared with the exemestane group, the sequential group demonstrated ST decline on information processing speed (ES = 0.33; p = .01) and executive function (ES = 0.32; p = .01) and LT decline on verbal memory (ES = 0.33; p = .02). The exemestane group showed no cognitive decline compared with controls.

CONCLUSION(S): Cognitive adverse effects of tamoxifen alone and after switching to exemestane were observed, suggestive of a carryover effect of tamoxifen. Our results underline the need for well-controlled, prospective trials studying cognitive effects of endocrine therapy.

PMID:37004168 | DOI:10.1093/jncics/pkad022

Acta Otolaryngol. 2023 Apr 2:1-6. doi: 10.1080/00016489.2023.2191646. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Carcinomas of the minor salivary glands are rare with a heterogeneous pathology. This study explored the demographics, histology, treatment and survival in the Swedish population over 11 years.

MATERIAL AND METHODS: Cases of salivary gland carcinomas in the oral cavity were extracted from the ‘Swedish Head and Neck Cancer Register’ (2008-2018). Statistical analyses with cross tabulation, age grouping, chi-square, the Kaplan-Meier method and log-rank tests were performed.

RESULTS: Three hundred thirty cases were included (62% female; mean age 60 years; 83% were WHO Performance Status 0). The carcinomas were mostly stage I (57%), and the most common site was the palate with 165 tumours (50%). The most common histology was mucoepidermoid carcinoma (30%), followed by polymorphous low-grade adenocarcinoma (25%) and adenoid cystic carcinoma (24%). The distribution of histology differed between age groups. The five-year predicted overall survival rate was 83%. Most patients (89%) were treated with primary surgery.

CONCLUSION AND SIGNIFICANCE: The demographics, histology, and survival of minor salivary gland carcinomas in the oral cavity in the Swedish population correspond well with previously published material. The demographics and histology differ from carcinomas of the major salivary glands in the same population.

PMID:37004167 | DOI:10.1080/00016489.2023.2191646

Neurosurg Focus. 2023 Apr;54(4):E2. doi: 10.3171/2023.1.FOCUS22637.

ABSTRACT

OBJECTIVE: The management of excess CSF in patients with hydrocephalus typically requires using a shunt to divert CSF. Unfortunately, there is a high rate of shunt failure despite improvements in device components and insertion techniques. Reoperation is frequently necessary, which contributes to patient harm and increased healthcare costs. While factors affecting shunt failure are well defined in the pediatric population, information regarding adults is lacking. The authors undertook a systematic review and meta-analysis to determine how shunt failure in the adult population is reported and investigated the etiologies of shunt failure.

METHODS: This review is reported according to PRIMSA and utilized the MEDLINE, Embase, and Google Scholar databases. Abstracts were screened by two independent reviewers, and data were extracted in duplicate by two independent reviewers. Statistical analyses were performed using SPSS and Stata.

RESULTS: The pooled rates of shunt failure were 10% (95% CI 5%-15%) in studies with a mean follow-up time of less than 1 year, 12% (95% CI 8%-14%) with a follow-up time between 1 and 2 years, and 32% in studies with a follow-up time of 2 years or greater (95% CI 19%-43%). The pooled rate of failure was 17% across all studies. The most common cause of shunt failure was obstruction at 3.0% (95% CI 2%-4%), accounting for 23.2% of shunt failures. Infection was the second most common at 2.8% (95% CI 2%-3%), accounting for 22.5% of shunt failures. The most common location of shunt failure was the distal catheter, with a failure rate of 4.0% (95% CI 3%-5%), accounting for 33.4% of shunt failures. The definition of shunt failure was heterogeneous and varied depending on institutional practices. The combination of symptoms with either CT or MRI was the most frequently reported method for assessing shunt failure.

CONCLUSIONS: Important variation regarding how to define, investigate, and report shunt failure was identified. The overall shunt failure rate in adults is at least 32% after 2 years, which, while lower than that typically reported in the pediatric population, is significant. The most common causes of shunt failure in adults are infection and obstruction. The most common site of failure occurred at the distal catheter, highlighting the need to develop strategies to both report and mitigate distal shunt failure in adult shunt patients.

PMID:37004137 | DOI:10.3171/2023.1.FOCUS22637

Neurosurg Focus. 2023 Apr;54(4):E6. doi: 10.3171/2023.1.FOCUS22640.

ABSTRACT

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH.

METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement.

RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase).

CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

PMID:37004136 | DOI:10.3171/2023.1.FOCUS22640

Neurosurg Focus. 2023 Apr;54(4):E8. doi: 10.3171/2023.1.FOCUS22642.

ABSTRACT

OBJECTIVE: Long-standing overt ventriculomegaly in adults (LOVA) is a form of chronic hydrocephalus and its pathophysiology and treatment remain debated. An analysis of CSF dynamics in this condition has rarely been reported. The aim of this study was to analyze hydrodynamic characteristics of patients with suspected LOVA to discuss its pathophysiological mechanisms and the importance of CSF dynamics analysis for diagnosis and treatment of these patients.

METHODS: This retrospective cohort study, conducted between May 2018 and October 2022, included adult patients aged > 18 years investigated in a department of neurosurgery through a lumbar infusion study for suspicion of LOVA (n = 23). These patients were then compared with a control cohort explored for suspicion of idiopathic normal pressure hydrocephalus (iNPH; n = 30). Clinical symptoms, radiological findings, and hydrodynamic parameters were analyzed. The authors specifically compared two hydrodynamic parameters: resistance to CSF outflow, or Rout, which relies on CSF resorption, and pressure-volume index (PVI), which reflect overall craniospinal compliance. The lumbar infusion study was considered pathological (confirming the diagnosis of chronic hydrocephalus) when at least one of these two parameters was altered.

RESULTS: Rout was significantly less frequently increased (cutoff ≥ 12 mm Hg/ml/min) in patients with LOVA (52%) than in those with iNPH (97%; p < 0.001). In contrast, PVI was impaired (cutoff ≤ 25 ml) in both cohorts, i.e., in 61% of patients with LOVA and in 83% of patients with iNPH. Overall, the rate of pathological lumbar infusion study in LOVA (87%) was not statistically different than in iNPH (100%). However, PVI was the only impaired parameter most frequently found in those with LOVA (35%) compared with those with iNPH (3%; p = 0.002).

CONCLUSIONS: This study suggests that there is a differential CSF dynamics pattern when comparing patients with LOVA versus those with iNPH. A higher proportion of patients with LOVA showed isolated compliance impairment. These findings highlight the utility of CSF dynamics analysis for the evaluation of patients with suspected chronic obstructive hydrocephalus such as LOVA. Future research with larger case series may help define diagnosis and treatment algorithms of chronic obstructive hydrocephalus based on CSF dynamics analysis, in addition to clinical and radiological criteria.

PMID:37004133 | DOI:10.3171/2023.1.FOCUS22642

Chin Neurosurg J. 2023 Apr 1;9(1):8. doi: 10.1186/s41016-023-00322-7.

ABSTRACT

INTRODUCTION: In the present letter we share the results of an analysis of more than 140,000 non traumatic arterial subarachnoid hemorrhages whereas the majority of them is expected to be after aneurysm rupture, in which we investigate a possible correlation of climatic changes and emotional bursts as correlating factors for such a rupture.

METHODS: We obtained the daily number of SAH from 2006 to 2018 for males and females from the German National statistics agency. The ICD codes provided to us were I60.1-I60.7, which are SAHs originating from intracranial arteries and excluding traumatic SAH and other not specified SAH.

RESULTS: An increase of mean SAH per day could be seen in winter compared to summer and family events seemed to have a protective effect against aneurysmal SAH. Additionally 6.55 more women per day suffer an SAH compared to men.

CONCLUSION: There is a statistical significant higher risk of aneurysm ruptures in winter and in females, and a statistical lower number in Mother’s day.

PMID:37004110 | DOI:10.1186/s41016-023-00322-7

Biol Sex Differ. 2023 Mar 31;14(1):15. doi: 10.1186/s13293-023-00501-2.

ABSTRACT

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus.

METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 μL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 μL of 10^-2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO^-2); and hydrogen peroxide (H₂O₂) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO^-2, and H₂O₂. The HPBMs were then removed for the analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05.

RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO^-2, and H₂O₂ when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO^-2, and H₂O₂. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs.

CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

PMID:37004108 | DOI:10.1186/s13293-023-00501-2

Eye Vis (Lond). 2023 Apr 1;10(1):14. doi: 10.1186/s40662-023-00331-8.

ABSTRACT

BACKGROUND: Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME.

METHODS: Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways.

RESULTS: The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME.

CONCLUSIONS: Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.

PMID:37004107 | DOI:10.1186/s40662-023-00331-8

AIDS Res Ther. 2023 Mar 31;20(1):20. doi: 10.1186/s12981-023-00514-2.

ABSTRACT

BACKGROUND: We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum.

METHODS: This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes.

RESULTS: Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size.

CONCLUSIONS: There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study.

PMID:37004096 | DOI:10.1186/s12981-023-00514-2

Arthroplasty. 2023 Apr 2;5(1):18. doi: 10.1186/s42836-023-00175-6.

ABSTRACT

INTRODUCTION: Primary total knee arthroplasty (TKA) is a preferred treatment for end-stage knee osteoarthritis. In the setting of a failed TKA, revision total knee arthroplasty (rTKA) acts as a salvage procedure and carries a higher risk compared to primary TKA. Given increased interest in postoperative outcomes from these procedures, a thorough understanding of the demographics, comorbidities, and inpatient outcomes is warranted. This study aimed to report the epidemiological data of demographics, comorbidity profiles and outcomes of patients undergoing TKA and rTKA.

METHODS: A retrospective review of NIS registry discharge data from 2006 to 2015 third quarter was performed. This study included adults aged 40 and older who underwent TKA or rTKA. A total of 5,901,057 TKA patients and 465,968 rTKA patients were included in this study. Simple descriptive statistics were used to present variables on demographics, medical comorbidities, and postoperative complications.

RESULTS: A total of 5,901,057 TKA and 465,968 rTKA discharges were included in this study, with an average age of 66.30 and 66.56 years, and the major payor being Medicare, accounting for 55.34% and 59.88% of TKA and rTKA cases, respectively. Infection (24.62%) was the most frequent reason for rTKA, and was followed by mechanical complications (18.62%) and dislocation (7.67%). The most common medical comorbidities for both groups were hypertension, obesity, and diabetes. All types of inpatient complications were reported in 22.21% TKA and 28.78% of rTKA cases. Postoperative anemia was the most common complication in both groups (20.34% vs. 25.05%).

CONCLUSIONS: Our data demonstrated a 41.9% increase in patients receiving TKA and 28.8% increase in rTKA from the years 2006 to 2014. The data showed a 22.21% and a 28.78% “complication” rate with TKA and rTKA, with postoperative anemia being the most common complication. The top 3 medical comorbidities were hypertension, obesity, and diabetes for both groups and with increased focus on perioperative optimization, future analyses into preoperative medical optimization, and improved primary arthroplasty protocol may result in improved postoperative outcomes.

PMID:37004093 | DOI:10.1186/s42836-023-00175-6