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Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis

Clin Exp Metastasis. 2024 Dec 16;42(1):3. doi: 10.1007/s10585-024-10322-1.

ABSTRACT

Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Overall Survival (OS) was measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). Our search resulted in the identification of 1429 potentially relevant reports, which were subsequently restricted to four following independent evaluation of three authors. The pooled HR for OS in RCC patients receiving early ToD versus late ToD dosing was 0.62 (95% Confidence Interval, 0.50-0.72; p < 0.001). According to our findings, a statistically significant improvement in terms of OS for mRCC patients receiving early ToD administration compared with late ToD dosing was observed, with a reduction of death by 38%. Well-designed, randomized clinical and translational trials are required to clarify this issue and to establish recommendations for personalized treatments according to ToD.

PMID:39680251 | DOI:10.1007/s10585-024-10322-1

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Direct anterior vs other surgical approaches in patients with lumbar stiffness undergoing total hip arthroplasty: a systematic review and meta-analysis

Arch Orthop Trauma Surg. 2024 Dec 16;145(1):48. doi: 10.1007/s00402-024-05682-y.

ABSTRACT

INTRODUCTION: The effectiveness of the direct anterior approach (DAA) compared to other surgical approaches for total hip arthroplasty (THA) in patients with lumbar spine stiffness remains unclear. This systematic review and meta-analysis aimed to compare clinical outcomes, including dislocation rates and other complications, between DAA and other surgical approaches for THA in patients with lumbar spine stiffness.

MATERIALS AND METHODS: We conducted a systematic review and meta-analysis to compare the DAA with other surgical approaches (anterolateral, direct lateral, posterolateral and direct superior) in patients with lumbar spine stiffness undergoing THA. We searched PubMed, Embase, and Cochrane Central databases for cohort studies and randomized controlled trials and calculated risk ratios (RRs) with 95% confidence intervals (CIs) to assess dislocation rates.

RESULTS: This analysis included 11 non-randomized studies comprising 2505 patients, of whom 738 patients (29.4%) underwent THA via DAA. The results demonstrated that the DAA group had significantly reduced dislocation rates (RR 0.31, 95% CI 0.14-0.67, P = 0.003, I2 = 0%) compared to other surgical approaches. Subgroup analysis showed significantly lower dislocation rates in DAA patients versus those undergoing the posterior approach (RR 0.22, 95% CI 0.10-0.52, P = 0.001, I2 = 0%). However, there was no statistically significant difference in dislocation rates between DAA and the lateral approach (RR 0.53, 95% CI 0.19-1.47, P = 0.22, I2 = 0%), although the rate was numerically lower.

CONCLUSION: The DAA was associated with lower dislocation rates compared to other surgical techniques in patients with lumbar spine stiffness undergoing THA.

PMID:39680248 | DOI:10.1007/s00402-024-05682-y

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Auditory processing deficits in subacute stroke

J Neurol. 2024 Dec 16;272(1):80. doi: 10.1007/s00415-024-12754-x.

ABSTRACT

BACKGROUND: Stroke is the second leading cause of disability worldwide. Stroke results in focal neurological deficit and often leads to auditory problems due to its impact on the auditory pathway. Altered connections in the auditory pathway, caused by stroke, can result in hearing difficulties ranging from impaired sound detection to altered auditory perception. A better understanding of how stroke affects these early sound processing mechanisms will provide valuable insights into stroke recovery and rehabilitation options.

METHODS: We recruited forty consecutive adult patients with stroke (30 males, 10 females) due to ischemic or intracerebral hemorrhage > 3 and up to 12 months after stroke (subacute stage). Brain MRIs were performed on all patients, and we calculated a central auditory nervous system stroke severity index (CANS SSI) according to number of CANS areas involved and an extended CANS definition of auditory responsive areas. All patients underwent cognitive screening assessment, basic audiological assessments, and a hierarchical central auditory processing assessment battery with the Queen Square Tests of Auditory Cognition (early perceptual processing, apperceptive processing, semantic Processing) and Gaps in Noise tests.

RESULTS: When comparing patients with auditory responsive cortical lesions and with versus without Heschl’s gyrus involvement (primary auditory cortex), patients with Heschl’s gyrus involvement exhibited worse early perceptual scores. The CANS SSI showed a significant negative correlation with early perceptual test scores.

CONCLUSION: This study demonstrates a correlation between stroke severity, characterized by a higher number of lesions involving auditory areas in patients with subacute stroke, and worse early perceptual scores. Heschl’s gyrus involvement is associated with poorer early perceptual score.

PMID:39680236 | DOI:10.1007/s00415-024-12754-x

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Assocıatıon between growth hormone gene polymorphısm and some growth traıts in Akkaraman and Anatolian Merino sheep

Mol Biol Rep. 2024 Dec 16;52(1):54. doi: 10.1007/s11033-024-10126-2.

ABSTRACT

BACKGROUND: There is a strong relationship between growth traits and genes. Identifying genotypes associated with superior phenotypic traits allows for targeted selection, facilitating the development of herds with desirable features. The growth hormone (GH) gene plays a crucial role in growth, development, and metabolism, making it a key focus for growth trait studies in livestock.

METHODS AND RESULTS: This study investigated the relationship between polymorphism in the GH gene and growth traits in 33 Akkaraman and 40 Anatolian Merino ewes. Traits such as birth weight (BW), weaning weight (WW), and 6-month weight (LW6), as well as body measurements (withers height (WH), rump height (RH), body length (BL), chest width (CW), chest circumference (CC)), were collected. Average daily weight gain (ADWG) and Kleiber ratios were calculated. Polymorphisms were detected through PCR-RFLP using the HaeIII enzyme, identifying three genotypes: AA, AB, and BB. Statistically significant differences were found between genotypes for WW, RH, WH, BL, CW, and CC (P < 0.05). Sheep with the AA genotype had higher averages, while AB individuals exhibited lower values for these traits. ADWG1 and KR1 values were higher in homozygous genotypes (AA and BB) than in heterozygous ones (AB), showing statistical significance (P < 0.05).

CONCLUSIONS: These results suggest that the GH gene may serve as a candidate for Marker-Assisted Selection (MAS) in Akkaraman and Anatolian Merino sheep, particularly for growth-related traits.

PMID:39680233 | DOI:10.1007/s11033-024-10126-2

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Leap in modelling human impact on climate may lead to early warning of climate disasters

Mathematicians have applied statistical mechanics to climate change detection and attribution for first time. They have shown how to separate the ‘signal’ of human-made climate change from the ‘noise’ of natural climate fluctuations. This allows for a dramatic improvement in the ability to detect climate change and early warnings of climatic tipping points.
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Correction: Ultrasound-guided supraclavicular block versus Bier block for emergency reduction of upper limb injuries: statistical analysis plan

Trials. 2024 Dec 14;25(1):815. doi: 10.1186/s13063-024-08697-3.

NO ABSTRACT

PMID:39674869 | DOI:10.1186/s13063-024-08697-3

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Outcomes and Trends in Axillary Management of Stage cN3b Breast Cancer Patients

Ann Surg Oncol. 2024 Dec 14. doi: 10.1245/s10434-024-16630-w. Online ahead of print.

ABSTRACT

BACKGROUND: There is limited data regarding sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for cN3b patients, who present with both axillary and ipsilateral internal mammary node involvement. We examined trends in the use of SLNB in cN3b patients and survival by axillary procedure for those with nodal pathologic complete response (nPCR).

METHODS: Adult women with nonmetastatic cN3b invasive breast carcinoma between 2012 and 2021 were selected from the National Cancer Database. These patients were compared based on type of axillary surgery, specifically SLNB, SLNB with axillary lymph node dissection (ALND), and ALND alone. Kaplan-Meier analysis was used to compare overall survival.

RESULTS: A total of 4,236 patients were included. In 2012, 8.5% of these patients underwent SLNB alone and 18.3% underwent SLNB+ALND. In 2021, this increased to 35.1% for SLNB alone and 23.0% for SLNB with subsequent ALND (p < 0.0001). For patients who received NAC, the rate of nPCR was overall found to be 24.9%. Overall survival of patients receiving SLNB or SLNB+ALND with nPCR was not statistically significantly different from the ALND only group with nPCR (p = 0.22 and 0.57, respectively).

CONCLUSIONS: There has been increasing use of the SLNB procedure for patients with cN3b breast cancer over the past decade. In patients with nPCR, SLNB was not associated with reduced survival. For well-selected cN3b patients with an excellent clinical response to NAC, including nPCR, axillary de-escalation strategies, such as SLNB with omission of completion axillary dissection, may be considered.

PMID:39674862 | DOI:10.1245/s10434-024-16630-w

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An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation

Metabolomics. 2024 Dec 14;21(1):5. doi: 10.1007/s11306-024-02200-4.

ABSTRACT

INTRODUCTION: Inflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.

OBJECTIVE: This study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.

METHODS: We applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.

RESULTS: We identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.

CONCLUSION: MS imaging’s spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.

PMID:39674857 | DOI:10.1007/s11306-024-02200-4

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Biomolecule-functionalized polydiacetylene assembly for visual and on-site sensing of (E)-2-hexenal in fruits

J Food Sci. 2024 Dec 14. doi: 10.1111/1750-3841.17395. Online ahead of print.

ABSTRACT

(E)-2-Hexenal (E2H) is an important volatile organic compound (VOC) that can serve as a marker for fruit quality sensing and shelf-life evaluation. However, visual and portable sensors for E2H have not been reported mainly because of the difficulty in selective response to E2H while avoiding interference from other VOC, especially isomers. Herein, we developed a novel colorimetric sensor based on thiol-functionalized polydiacetylene assembly (PDA-SH/PDA) for the quantitative and selectivity of E2H. The mechanism was that E2H underwent a Michael addition reaction with sulfhydryl groups in PDA-SH/PDA. The Michael addition reaction destroyed the hydrogen bond and distorted the conjugated molecular system, resulting in colorimetric responses. Under optimal conditions, a good linear relationship was observed between E2H concentration and red colorimetric shift (R2 = 0.9679). The E2H sensor yields a high analytical sensitivity of 1.5203% and a limit of detection of 0.015 g L-1. Besides, the PDA-SH/PDA sensor can be used to visually distinguish E2H and its isomer (Z)-3-hexenal. The PDA-SH/PDA sensor yielded a statistically significant difference in red colorimetric shift (p < 0.01) between the pairs of isomers in the ripeness of fruits. At last, the sensor was utilized for detecting E2H in grapes from different shelf lives. We found that the E2H concentration increased from 66.16 ± 1.54 to 67.56 ± 1.30 µg L-1 as storage time was prolonged. The results of this research not only demonstrated the feasibility of visual and on-site detection of E2H but also provided potential promise for portable fruit quality sensing and shelf-life evaluation.

PMID:39674853 | DOI:10.1111/1750-3841.17395

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Application of modified Curie and SIOPEN skeleton scoring systems in 18F-AlF-NOTA-octreotide PET/CT for neuroblastoma

Ann Nucl Med. 2024 Dec 15. doi: 10.1007/s12149-024-02006-3. Online ahead of print.

ABSTRACT

OBJECTIVE: The study aimed to explore the role of fluorine-18-aluminum fluoride-1,4,7-triazacyclononane-1,4,7-triacetic acid-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT) in neuroblastoma (NB) and compared it with Iodine-123 labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy with single photon emission computed tomography/computed tomography (SPECT/CT), as well as to investigate the feasibility of the modified Curie scoring system and International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) skeleton scoring system applied in 18F-OC PET/CT.

METHODS: Patients with pathologically confirmed NB underwent 123I-MIBG scintigraphy with SPECT/CT and 18F-OC PET/CT according the standard imaging protocols. The interval between the two imaging techniques ranged from 0 to 22 days (median interval: 9 days). The number of lesions in modified Curie scoring system and SIOPEN skeleton scoring system applied on 123I-MIBG SPECT/CT and 18F-OC PET/CT was compared.

RESULTS: A total of 50 NB patients (male: female = 25:25) with a median age of 62-month-old were enrolled. 123I-MIBG and 18F-OC imaging were positive in 22 patients and negative in 27 patients. 1 patient had positive 18F-OC but negative 123I-MIBG results (p = 1.000). In lesion-based analysis, 18F-OC PET/CT revealed more positive lesions than 123I-MIBG scintigraphy with SPECT/CT (57 vs. 44, p < 0.001), regardless of bone/bone marrow lesions (43 vs. 37, p = 0.031) or soft tissue lesions (14 vs. 7, p = 0.016). The Curie scores of the two imaging techniques showed a significant difference (p = 0.047), whereas no statistic difference for SIOPEN scores (p = 0.688). The Curie and SIOPEN scores were significantly higher in patients with the presence of MYCN amplification or positive bone marrow puncture result (p < 0.05).

CONCLUSION: 18F-OC could be used in the evaluation of NB, and the modified Curie scoring system could be used to semi-quantify the disease extent of NB in 18F-OC PET/CT.

PMID:39674843 | DOI:10.1007/s12149-024-02006-3