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Faecal microbiota composition is related to response to CDK4/6-inhibitors in metastatic breast cancer: A prospective cross-sectional exploratory study

Eur J Cancer. 2023 Jun 20;191:112948. doi: 10.1016/j.ejca.2023.112948. Online ahead of print.

ABSTRACT

BACKGROUND: Cyclin-dependent kinase (CDK)4/6-inhibitors with endocrine therapy represent the standard of treatment of hormone receptor-positive(HR+)/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Gut microbiota seems to predict treatment response in several tumour types, being directly implied in chemotherapy resistance and development of adverse effects. No evidence is available on gut microbiota impact on efficacy of HR+ breast cancer treatment.

PATIENTS AND METHODS: We assessed the potential association among faecal microbiota and therapeutic efficacy of CDK4/6-inhibitors on 14 MBC patients classified as responders (R) and non-responders (NR) according to progression-free survival. A stool sample was collected at baseline and V3-V4 16S targeted sequencing was employed to assess its bacterial composition. Statistical associations with R and NR were studied.

RESULTS: No significant differences were observed between R and NR in terms of α-/β-diversity at the phylum and species level. Machine-learning (ML) algorithms evidenced four bacterial species as a discriminant for R (Bifidobacterium longum, Ruminococcus callidus) and NR (Clostridium innocuum, Schaalia odontolytica), and an area under curve (AUC) of 0.946 after Random Forest modelling. Network analysis evidenced two major clusters of bacterial species, named Species Interacting Groups (SIG)1-2, with SIG1 harbouring 75% of NR-related bacterial species, and SIG2 regrouping 76% of R-related species (p < 0.001). Cross-correlations among several patients’ circulating immune cells or biomarkers and bacterial species’ relative abundances showed associations with potential prognostic implications.

CONCLUSIONS: Our results provide initial insights into the gut microbiota involvement in sensitivity and/or resistance to CDK4/6-inhibitors + endocrine therapy in MBC. If confirmed in larger trials, several microbiota manipulation strategies might be hypothesised to improve response to CDK4/6-inhibitors.

DATA AVAILABILITY STATEMENT: All raw data (fastq.gz files) and clinical metadata, complying with FAIR principles (https://www.go-fair.org/fair-principles/), are available at NCBI SRA portal under PRJNA946762 Bioproject.

PMID:37454444 | DOI:10.1016/j.ejca.2023.112948

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Direct-cortical visual evoked potential monitoring during brain tumor resection

J Clin Neurosci. 2023 Jul 14;115:1-7. doi: 10.1016/j.jocn.2023.06.014. Online ahead of print.

ABSTRACT

BACKGROUND: Visual evoked potential (VEP) recording is traditionally regarded as an unreliable evoked potential monitoring technique, precluding widespread use in intracranial neurosurgery. However, VEPs can serve as a useful intraoperative adjunct for real-time detection of mechanical damage to optic apparatuses. The low obtainability and prognostic utility of VEPs are associated with transcranial recording, which typically provides non-focal information and poor signal-to-noise ratio. Direct cortical VEP (DC-VEP) recordings may offer a solution.

METHODS: We evaluated the obtainability of DC-VEPs as well as their prognostic utility in predicting postoperative visual function deterioration in a series of brain tumor patients undergoing craniotomies for tumor resection. Patient records were retrospectively reviewed for all consecutive patients undergoing brain tumor resections with DC-VEP monitoring. Pre- and postoperative visual fields were characterized from patient charts and associated with the presence of intraoperative monitoring alerts to determine the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of DC-VEPs in detecting postoperative visual field deficits.

RESULTS: Twenty-two patients (9 male, 13 female) were included, with a median age of 60 years. DC-VEPs were reliably detected in 19 of 23 included surgeries (82.6%). The reported sensitivity, specificity, PPV, and NPV in detecting postoperative visual field deficits was 60%, 92.9%, 75%, and 86.7%, respectively. There was a statistically significant association between monitoring alerts and the presence of visual field deterioration by Fischer’s exact test (p = 0.0374).

CONCLUSIONS: DC-VEPs can be reliably obtained and are useful for detecting mechanical injury to optic areas and tracts during tumor resection.

PMID:37454439 | DOI:10.1016/j.jocn.2023.06.014

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Perioperative factors influencing hospitalization duration for pediatric neck abscesses

Am J Otolaryngol. 2023 Jul 8;44(6):103967. doi: 10.1016/j.amjoto.2023.103967. Online ahead of print.

ABSTRACT

PURPOSE: Pediatric neck abscesses are a common pathology seen in an ambulatory setting. Although some pediatric neck abscesses are managed medically with antibiotics, surgical intervention is often required. Given the often non-emergent presentation of many abscesses, a variety of logistical and perioperative factors may delay time to care and subsequently prolong hospital stay. The objective of this study was to examine factors that influence the overall time to surgery (TTS) and hospital length of stay (LOS) in a pediatric population with neck abscesses who ultimately require surgical drainage.

MATERIALS AND METHODS: 161 pediatric patients who underwent incision and drainage of a neck abscess over a ten-year period at a tertiary referral children’s center were reviewed. Demographic information, radiographic studies, and surgical information were extracted from patient charts. Descriptive statistics, Mann-Whitney U tests, and multivariate analyses were performed.

RESULTS: The most common subcategory location was deep neck abscesses (33.1 %). Computed tomography (CT) was the most common pre-operative imaging modality (54.1 %) followed by ultrasound (US) (49.1 %) and magnetic resonance imaging (2.6 %). US and a combination of multiple preoperative imaging modalities were associated with increased LOS and TTS. Repeat surgery was associated with increased LOS. Pre-admission antibiotic use was associated with increased LOS and TTS. Younger patients were more likely to have a longer LOS.

CONCLUSIONS: A variety of factors can influence TTS, LOS, and time from surgery to discharge including patient age, abscess location, a non-optimized utilization of imaging modalities, the utilization of pre-admission antibiotics, and the need for repeat operations.

PMID:37454430 | DOI:10.1016/j.amjoto.2023.103967

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Institutional outbreaks of influenza-like illnesses in the state of São Paulo: an analysis of the epidemiological profile during the COVID-19 pandemic

Public Health. 2023 Jun 19;221:142-149. doi: 10.1016/j.puhe.2023.06.018. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to spatiotemporally analyze the profile of influenza-like illness (ILI) outbreaks in the state of São Paulo, Brazil, between 2020 and 2022.

STUDY DESIGN: This was a cross-sectional retrospective study.

METHODS: Outbreaks of ILI with final diagnoses of COVID-19, influenza, or other respiratory viruses (ORVs) recorded between January 2020 and November 2022, obtained from the Notifiable Diseases Information System (SINAN NET) Outbreak module, were analyzed. Kernel density estimates and Getis-Ord Gi∗ statistics were performed to identify spatial clusters.

RESULTS: A total of 13,314 ILI outbreaks were identified, involving 130,568 cases and 2649 deaths. Of these, 104,399 (80%) were confirmed as COVID-19, 15,861 (12%) were confirmed as ORV, and 10,308 (8%) were confirmed as influenza. The year 2021 had the highest number of outbreaks and cases. Schools recorded the most outbreaks and cases, followed by long-term care facilities for older adults (LTCs). The highest average number of cases per outbreak and the highest attack rates occurred at social gatherings and prisons. Prisoners were three times more likely to contract COVID-19 during outbreaks than people in other institutions. The highest hospitalization and mortality rates for all virus types occurred in the LTC group. The occurrence and intensity of outbreaks were highly heterogeneous among the different institutions after the introduction of new SARS-CoV-2 variants in the state.

CONCLUSIONS: ILI outbreaks were not randomly distributed; they clustered in specific areas. Transmissibility varied among different institutions with different responses to the COVID-19 pandemic. These results can be used as a basis for prioritizing actions and allocating resources during future pandemics.

PMID:37454404 | DOI:10.1016/j.puhe.2023.06.018

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Whole-body low-dose CT can be of value in prostate cancer decision-making: a retrospective study on 601 patients

Insights Imaging. 2023 Jul 16;14(1):124. doi: 10.1186/s13244-023-01475-w.

ABSTRACT

OBJECTIVES: To evaluate the diagnostic value of whole-body low-dose computed tomography (CT) to detect bone metastasis in prostate cancer (PCa) patients and its possible utility in therapeutic decision-making. Also, to determine the valuable CT features for lesion characterisation.

METHODS: This IRB-approved retrospective study reviewed PCa patients who underwent 68Ga-PSMA PET/CT in our centre from March 2017 to August 2022. Two board-certified radiologists and one nuclear medicine specialist reported all whole-body low-dose CT scans separately, unaware of the 68Ga-PSMA-PET results. The per-lesion and per-patient diagnostic performances were calculated. Also, the significance of CT features was evaluated. Moreover, the inter-observer agreement was analysed. A two-tailed p value < 0.05 was considered significant.

RESULTS: From 727 reviewed PCa patients, 601 (mean age = 68.7 ± 8.1) were found to be eligible, including 211 (35.1%) referrals for initial staging and 390 (64.9%) for evaluating the extent of the disease after biochemical recurrence. Per-patient diagnostic analysis for three reviewers showed 81.0-89.4% sensitivity and 96.6-98.5% specificity in detecting osteo-metastasis. It was able to correctly detect high-burden disease based on both CHAARTED and LATITUDE criteria. Regarding the value of underlying CT features, size > 1 cm, ill-defined borders, presence of soft-tissue component, and cortical destruction were statistically in favour of metastasis. Also, Hu > 900 was in favour of benign entities with 93% specificity.

CONCLUSIONS: Although not as accurate as 68Ga-PSMA PET/CT, whole-body low-dose CT might precisely classify PCa patients considering therapeutic decision-making. Additionally, we proposed diagnostic CT features that could help radiologists with better characterisation of the detected lesions.

CRITICAL RELEVANCE STATEMENT: The whole-body low-dose CT can be considered valuable in the clinical decision-making of prostate cancer patients. This modality may obviate performing multiple imaging sessions and high-cost scans in patients diagnosed with the high-burden disease.

PMID:37454388 | DOI:10.1186/s13244-023-01475-w

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Energy and air? The impact of energy efficiency improvement on air quality in China

Environ Sci Pollut Res Int. 2023 Jul 16. doi: 10.1007/s11356-023-28835-9. Online ahead of print.

ABSTRACT

The global economic growth is hindered by resources shortage, energy demand, air pollution and climate. Energy efficiency can reduce some pollutants while potentially increase others. This study refers to sulfur dioxide (SO2), nitrogen oxides (NOx), and dust and smoke (DS) as primary pollutants to distinguish it from secondary ones. The influence of energy efficiency, socioeconomic, and natural climatic factors on air quality is analyzed under the theory of STIRPAT. It is highly coupled between energy efficiency and the spatial distribution of air quality. Increased energy efficiency can improve air quality by reducing SO2 and NOx, but the impact on DS is insignificant. Air pollutants decrease by about 0.531% for every 1% increase in temperature and 0.105% for every 1% increase in precipitation. Consumption will reduce air pollution, and there is an inverted U-shaped relationship between population density, economic scale, urbanization, technology innovation, and air pollution. It is worth mentioning that this work adds temperature and precipitation to the STIRPAT as natural climatic factors, analyzing the impact of energy efficiency on air pollution under the two-factor restrictions of socioeconomic and natural climatic factors. Finally, management suggestions are made to improve air quality.

PMID:37454380 | DOI:10.1007/s11356-023-28835-9

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Clinical impact of a celiac axis stenosis in patients undergoing hepatobiliary surgery

Langenbecks Arch Surg. 2023 Jul 16;408(1):279. doi: 10.1007/s00423-023-03003-2.

ABSTRACT

BACKGROUND: Celiac axis stenosis (CAS) often is an incidental finding in terms of diagnostic for hepatobiliary surgery since most cases remain asymptomatic. It remains unclear whether CAS is a risk factor for postoperative complications after hepatobiliary surgery. Therefore, the aim of this study was to evaluate the impact of an asymptomatic CAS on the postoperative morbidity and survival of patients undergoing hepatobiliary surgery.

METHODS: We retrospectively analyzed CT scans and clinicopathological data of 250 consecutive patients undergoing hepatobiliary surgery between 2011 and 2018 in our tertiary center. We compared the postoperative course between patients with and without an incidental CAS as well as their overall survival.

RESULTS: CAS was caused by atherosclerotic stenosis in 16 (64%) patients, by ligamentous stenosis in 4 (16%) and by combined conditions in 5 cases (20%). Mean age of patients in the CAS group was significantly higher in comparison to patients of the non-CAS group (71.0 vs. 59.1 years, p < 0.001). Major hepatectomy was conducted in 40% of the CAS patients and 19.6% of non-CAS patients, respectively (p = 0.036). Interestingly, no statistically significant differences in postoperative morbidity (40 vs. 46.2%, p = 0.673) or in overall survival between the groups (41.3 vs. 51.9 months, p = 0.611) were observed.

CONCLUSION: Our analysis found no correlation between an asymptomatic celiac axis stenosis and postoperative complications or overall survival after hepatobiliary surgery. Which impact the incidental CAS may have in highly complex cases remains unclear. Further studies are needed to identify patients who benefit from CAS treatment before hepatobiliary surgery.

PMID:37454337 | DOI:10.1007/s00423-023-03003-2

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Evaluating the geometric and dosimetric impact of applying anisotropic CTV to PTV margins in image-guided post-prostatectomy radiation therapy

J Med Imaging Radiat Oncol. 2023 Jul 16. doi: 10.1111/1754-9485.13563. Online ahead of print.

ABSTRACT

INTRODUCTION: Guidelines for clinical target volume (CTV) to planning target volume (PTV) margins in post-prostatectomy radiation therapy (PPRT) are varied and often not clearly defined. Assessment of appropriateness of margins is commonly measured on prevalence of geographic miss.

METHODS: Cone-beam CT (CBCT) images (n = 92) for 10 PPRT patients were incorporated to provide on-treatment information on the appropriateness of six different CTV expansion margins in terms of geographic miss and change in dose-volume statistics for CTV, rectum and bladder. Uniform margins included 10 mm, 5 mm, 10 mm + 5 mm posteriorly and 5 mm + 3 mm posteriorly. In addition, two anisotropic margins were evaluated by separating the superior and inferior portions of the CTV before expansion. Treatment plans were created for each PTV retrospectively.

RESULTS: The frequency of geographic miss was the smallest for the large uniform expansions but resulted in the highest organ-at-risk (OAR) doses. Geographic miss in the smaller uniform and anisotropic PTVs was more prevalent but commonly to a small volume < 1% of CTV. When averaged over all CBCT fractions, V95% dose for all CTV margins remained > 99%. The anisotropic expansions generated smaller irradiated target volumes and consequently saw up to 7.3% reduction in bladder dose when compared with similar uniform expansion margins.

CONCLUSION: Supplementing the incidence of geographic miss with dosimetric information on target coverage and OAR doses provides more informed assessment of the appropriateness of different CTV expansion margins. Our study extends the evaluation of anisotropic margins for PPRT.

PMID:37454334 | DOI:10.1111/1754-9485.13563

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Application of the lateral preputial fascial island flap in hypospadias reoperation

Zhonghua Nan Ke Xue. 2021 Dec;27(12):1098-1102.

ABSTRACT

OBJECTIVE: To evaluate the application and effect of the lateral preputial fascial island flap (LPFIF) in hypospadias reoperation.

METHODS: We retrospectively analyzed the clinical data on the children patients undergoing hypospadias reoperation with LPFIF in our Department of Urology from December 2016 to June 2019.

RESULTS: A total of 85 cases were included in this study, including 18 cases of LPFIF, 19 cases of Duplay technique, 25 cases of tubularized incised plate urethroplasty (TIP) and 23 cases of Mathieu urethroplasty. The patients were aged from 18 months to 12 years and 8 months, averaging 4.6 years. Postoperatively, all the children were followed up for ≥ 6 months, which found satisfactory appearance of the penis body and glans, the urethral orifice in the normal position of the glans, and the external orifice of the urethra fissured. Urethral fistula occurred in 2 cases and glans dehiscence in 1 after LPFIF; 5 of the patients presented urethral fistula after Duplay; 3 developed urethral fistula and 1 urethral stricture after TIP; 6 showed urethral fistula and 2 glans dehiscence after Mathieu urethroplasty. No postoperative urethral stricture, urethral diverticulum or flap necrosis occurred in any of the cases. Hypospadias reoperation succeeded in 83.3% (15/18) of the cases after LPFIF. The urine flow curve of the LPFIF cases was bell-shaped or high flat-shaped, with a maximum urinary flow rate of 8.56 ± 3.99 ml/s and an average urinary flow rate of 5.23 ± 2.32 ml/s, not significantly different from those of the TIP and Duplay cases.

CONCLUSIONS: There is no statistically significant difference in the success rate of hypospadias reoperation between TIP and LPFIF. Urethroplasty with LPFIF can be used as one of the surgical options for hypospadias reoperation.

PMID:37454319

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Dual mediating effects of positive and negative emotions on fertility stress and fertility quality of life among infertile men in China

Zhonghua Nan Ke Xue. 2021 Dec;27(12):1092-1097.

ABSTRACT

OBJECTIVE: To explore the effects of fertility stress on the quality of life (QOL) of infertile men and the dual mediating roles of positive and negative emotions in fertility stress and fertility QOL.

METHODS: Using the Fertility Problem Inventory, Fertility Quality of Life Questionnaire and Positive and Negative Affect Scale, we conducted a cross-sectional survey among 304 infertile men. We established a structural equation model for analysis of the relationship between the four variables of fertility stress, fertility QOL, positive emotion and negative emotion.

RESULTS: The scores of the patients in fertility stress, fertility QOL, positive emotion and negative emotion were (158.42 ± 21.725), (60.72 ± 10.926), (32.15 ± 6.294) and (19.48 ± 6.378), respectively. The root mean square error approximation (RMSEA) of the direct effect model, positive emotion separate mediation model and negative emotion separate mediation model was >0.08, and the dual mediation model showed optimum fit indexes, with χ2 / df = 1.959, goodness of fit index (GFI) = 0.950, adjusted GFI (AGFI) = 0.919, normed fit index (NFI) = 0.899, incremental fit index (IFI) = 0.948, Tucker-Lewis index (TLI) = 0.926, comparative fit index (CFI) = 0.947, and RMSEA = 0.056. The results of bootstrap test indicated that the positive and negative emotions had significant mediating effects, both incomplete, on fertility stress and fertility QOL. Moreover, the separate mediation of positive emotion exhibited no statistically significant difference from that of negative emotion (95% CI: -0.063 to 0.028).

CONCLUSIONS: Positive emotion and negative emotions are part of the intermediary in fertility stress and fertility QOL. Fertility stress can affect fertility QOL through the dual mediating effect of positive emotion and negative emotions in infertile men.

PMID:37454318