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Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma

JAMA Dermatol. 2023 Aug 30. doi: 10.1001/jamadermatol.2023.2955. Online ahead of print.

ABSTRACT

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.

OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.

DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021.

MAIN OUTCOMES AND MEASURES: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups.

RESULTS: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.

CONCLUSIONS AND RELEVANCE: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

PMID:37647056 | DOI:10.1001/jamadermatol.2023.2955

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Longitudinal effects of FTO gene polymorphism on body composition, cardiorespiratory fitness, physical activity, inflammatory markers, and cardiovascular risk in children and adolescents. “The UP & DOWN study”

Scand J Med Sci Sports. 2023 Aug 30. doi: 10.1111/sms.14469. Online ahead of print.

ABSTRACT

The role of polymorphism rs9939609 of the FTO gene has been related with fat mass and cardiovascular risk in adults, but it remains unclear in children and adolescents. Hence, the main aim of this study was to determine the FTO polymorphism effects on body composition, cardiorespiratory fitness (CRF), physical activity (PA), inflammatory markers, and cardiovascular risk both in cross-sectional analysis and after two-years of follow-up in children and adolescents. A total of 2129 participants were included in this study. The rs9939609 polymorphism was genotyped. Body composition measurements, CRF, and moderate-to-vigorous PA (MVPA) were determined at baseline and after two-year of follow-up. Moreover, plasma leptin and adiponectin were also determined as inflammatory markers. Furthermore, an index of cardiovascular disease risk factors (CVDRF-I) was calculated. Codominant (TT vs. TA vs. AA) and dominant (AA+AT vs. TT) models were applied for statistical analysis. The results showed a main effect of the FTO genotype on body composition measures in both first and third year (p < 0.05), with lower adiposity in TT compared with AA or AA+AT group. These differences were maintained after accounting for pubertal maturity, sex, age, VO2 max, and MVPA. Moreover, lower leptin level was observed in TT compared to AA+AT group in the third year. An interaction in Gene*Time*Sex was found in height and neck circumference in dominant model (p = 0.047; p = 0.020, respectively). No differences were found in CRF, MVPA nor CVDRF-I between groups. Hence, homozygous TT allele could be a protective factor against weight gain from early childhood.

PMID:37647022 | DOI:10.1111/sms.14469

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Analysis of the prognostic value of uric acid on the efficacy of immunotherapy in patients with primary liver cancer

Clin Transl Oncol. 2023 Aug 30. doi: 10.1007/s12094-023-03314-2. Online ahead of print.

ABSTRACT

PURPOSE: Uric acid (UA) plays a dual role as an antioxidant and a prooxidant in patients with malignant tumors; however, the relationship between serum UA and malignancy is currently unclear. This study aims to investigate the prognostic value of serum uric acid level before immunotherapy on the efficacy of primary liver cancer (PLC) immunotherapy, which might provide a basis for optimizing the comprehensive treatment scheme.

METHODS: Patients with PLC who were admitted to the First Affiliated Hospital of Gannan Medical College from January 2019 to June 2022 and underwent immunotherapy were collected retrospectively. The difference between serum UA levels in patients with PLC, the correlation between serum UA levels, and the clinical characteristics of patients with PLC were analyzed using the chi-square test, and the survival was estimated using the Kaplan-Meier analysis. To further assess the prognostic significance of UA concentrations, univariate and multivariate Cox regression analyses were performed.

RESULTS: Ninety-nine patients were included in this study cohort. The median follow-up was 7 months (range: 1-29 months), and 76 (76.8%) of the 99 patients with PLC died as of December 31, 2022. Serum UA concentrations ranged from 105 to 670 μmol/l, with a median of 269 μmol/l. The results showed that the serum UA level of patients with PLC was higher than that of healthy subjects (P < 0.001). After subgroup analyses, only male patients with liver cancer had higher serum UA levels than healthy men (P = 0.001). The results of the Kaplan-Meier analysis showed that higher UA levels were associated with poor overall survival (OS) (P = 0.005). In univariate analysis, the OS rate of patients with elevated serum UA levels was significantly lower than the cut-off value (hazard ratio [HR]: 3.191, 95% confidence interval [CI]: 1.456-6.993, P = 0.004), with a median survival time of 151 and 312 days in the high and low serum UA groups, respectively. The results of multivariate analysis showed that the UA level was an independent prognostic factor for immunotherapy in patients with PLC (HR: 3.131, 95% CI: 1.766-5.553, P < 0.001).

CONCLUSIONS: The serum UA level is a reliable biomarker for predicting the prognosis of patients undergoing immunotherapy for PLC, and might provide a basis for the individualized treatment of these patients. Dynamic monitoring of the serum UA level may compensate for the deficiency of the current liver cancer staging system.

PMID:37646984 | DOI:10.1007/s12094-023-03314-2

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Palliative care for children with central nervous system tumors: results of a Spanish multicenter study

Clin Transl Oncol. 2023 Aug 30. doi: 10.1007/s12094-023-03301-7. Online ahead of print.

ABSTRACT

BACKGROUND: Brain tumors represent the most common cause of cancer-related death in children. Few studies concerning the palliative phase in children with brain tumors are available.

OBJECTIVES: (i) To describe the palliative phase in children with brain tumors; (ii) to determine whether the use of palliative sedation (PS) depends on the place of death, the age of the patient, or if they received specific palliative care (PC).

METHODS: Retrospective multicenter study between 2010 and 2021, including children from one month to 18 years, who had died of a brain tumor.

RESULTS: 228 patients (59.2% male) from 10 Spanish institutions were included. Median age at diagnosis was 5 years (IQR 2-9) and median age at death was 7 years (IQR 4-11). The most frequent tumors were medulloblastoma (25.4%) and diffuse intrinsic pontine glioma (DIPG) (24.1%). Median number of antineoplastic regimens were 2 (range 0-5 regimens). During palliative phase, 52.2% of the patients were attended by PC teams, while 47.8% were cared exclusively by pediatric oncology teams. Most common concerns included motor deficit (93.4%) and asthenia (87.5%) and communication disorders (89.8%). Most frequently prescribed supportive drugs were antiemetics (83.6%), opioids (81.6%), and dexamethasone (78.5%). PS was administered to 48.7% patients. Most of them died in the hospital (85.6%), while patients who died at home required PS less frequently (14.4%) (p = .01).

CONCLUSION: Children dying from CNS tumors have specific needs during palliative phase. The optimal indication of PS depended on the center experience although, in our series, it was also influenced by the place of death.

PMID:37646983 | DOI:10.1007/s12094-023-03301-7

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Mexicans vs Central Americans: Violented Migrants Crossing Mexico

J Racial Ethn Health Disparities. 2023 Aug 30. doi: 10.1007/s40615-023-01767-3. Online ahead of print.

ABSTRACT

INTRODUCTION: The World Health Organization considers that migrants who pass through the Mexico-US walkway suffer high levels of violence, compared to other regions of the world, mainly women. This study aims to identify the factors associated with the types of violence suffered by migrants in transit through Mexico to the USA.

DESIGN: A cross-sectional, exploratory, retrospective, and observational study was conducted. A questionnaire of 46 variables was applied, divided into four sections: sociodemographic background, leaving the home, transit, and stay at the border. Questions about different types of direct violence were included. The survey was applied to 612 Mexican and Central American migrants who were in the Chaparral customs office and in five shelters in Tijuana City, on the U.S.-Mexico border. The results were analyzed using descriptive techniques and multivariate analysis of main and inferential components, using the statistical program R.

RESULTS: The higher vulnerability of Central American migrants compared to Mexicans was documented, specially of women that proportionally were the most negatively affected victims including all types of violence, making it evident that one of each four was violented sexually and among them, only 50% asked for medical assistance. The multivariate analysis determined that the duration of the trip, and the type of transport can generate greater violence.

CONCLUSIONS: The results highlight the greater vulnerability of Central American migrants in their transit through Mexico, mainly women and, likewise, the lack of effective public policies that guarantee the protection of the health, safety, and human rights of migrants.

PMID:37646954 | DOI:10.1007/s40615-023-01767-3

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A comprehensive analysis of intraoperative factors associated with acute-on-chronic kidney injury in elderly trauma patients: blood loss as a key predictor

Aging Clin Exp Res. 2023 Aug 30. doi: 10.1007/s40520-023-02540-6. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative acute kidney injury (AKI) is a critical issue in geriatric patients with pre-existing chronic kidney disease (CKD) undergoing orthopedic trauma surgery. The goal of this study was to investigate modifiable intraoperative risk factors for AKI.

METHODS: A retrospective study was conducted on 206 geriatric patients with CKD, who underwent orthopedic trauma surgery. Several variables, including intraoperative blood loss, postoperative hypoalbuminemia, intraoperative blood pressure and long-term use of potentially nephrotoxic drugs, were analyzed.

RESULTS: Postoperative AKI (KIDGO) was observed in 25.2% of the patients. The 1-year mortality rate increased significantly from 26.7% to 30.8% in patients who developed AKI. Primary risk factors for AKI were blood loss (p < 0.001), postoperative hypoalbuminemia (p = 0.050), and potentially nephrotoxic drugs prior to admission (angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, diuretics, antibiotics, NSAIDs) (p = 0.003). Furthermore, the AKI stage negatively correlated with propofol dose per body weight (p = 0.001) and there was a significant association between AKI and the use of cement (p = 0.027). No significant association between intraoperative hypotension and AKI was observed in any statistical test. Femur fracture surgeries showed the greatest blood loss (524mL ± 357mL, p = 0.005), particularly intramedullary nailing at the proximal femur (598mL ± 395mL) and revision surgery (769mL ± 436mL).

CONCLUSION: In geriatric trauma patients with pre-existing CKD, intraoperative blood loss, postoperative hypoalbuminemia, and pre-admission use of potentially nephrotoxic drugs are associated with postoperative AKI. The findings highlight the necessity to mitigate intraoperative blood loss and promote ortho-geriatric co-management to reduce the incidence and subsequent mortality in this high-risk population.

PMID:37646924 | DOI:10.1007/s40520-023-02540-6

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A comparison of radiographic degeneration features of older Chinese women and older Italian Caucasian women with a focus on thoracic spine

Aging Clin Exp Res. 2023 Aug 30. doi: 10.1007/s40520-023-02537-1. Online ahead of print.

ABSTRACT

BACKGROUND: Compared with Caucasians, East Asians have a lower incident of back pain, lower prevalence and severity of osteoporotic vertebral fracture and lumbar spine degeneration.

AIM: This study compares radiographic spine degeneration features of older Chinese women (as an example of East Asians) and older Italian women (as an example of Caucasians) with a focus on the thoracic spine.

METHODS: From two population-based epidemiological studies conducted in Hong Kong, China and Rome, Italy, 297 pairs (mean age: 73.6 years) age-matched older community women’s lateral spine radiographs were sampled. Existence (or absence) of seven degeneration features were assessed including: (1) hyper-kyphosis, (2) disc space narrowing (T3/T4 ~ T11/T12), (3) osteoarthritic (OA) wedging (T4 ~ T12), (4) generalised osteophyte formation (T4 ~ T12); (5) acquired short vertebrae (T4 ~ T12), (6) Schmorl node (T4 – L5), (7) disc calcification (T4-L5).

RESULTS: Italian women were more likely to have hyper-kyphosis (53.4% vs 25.6%), disc space narrowing (34.4% vs. 17.2%), OA wedging (6.4% vs. 0.67%), Schmorl node (19.5% vs. 4.4%, all P < 0.001). However, there was no statistically significant difference in osteophyte formation (7.7% vs. 9.4%, P > 0.1) and acquired short vertebrae (8.0% vs. 10.4%, P > 0.1). Disc calcification was uncommon among both Chinese and Italians.

DISCUSSION AND CONCLUSION: For the first time, this study documented a lower prevalence of a number of thoracic spine degeneration features among Chinese. This study further affirms the concept of a generally healthier spine in older Chinese relative to older Caucasians. The observed differences may reflect a foundational background influence of genetic predisposition that represents an important line of future research.

PMID:37646923 | DOI:10.1007/s40520-023-02537-1

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Bioaccumulation of Chloropyrifos Organo-pesticide and Its Toxicogenic Association with Antioxidant GSTP1 in Pakistani Pest Control Workers

Appl Biochem Biotechnol. 2023 Aug 30. doi: 10.1007/s12010-023-04649-w. Online ahead of print.

ABSTRACT

Synthetic pesticides are employed to enhance agricultural production. Chronic exposure to organophosphate (OP) pesticides may be a source of health problems. The present study was designed to examine an association of GSTP1 (rs1695) polymorphism with OP pesticide chronic exposure. A case-control study was recruited with 250 subjects comprising exposed (n = 100) and controls (n = 150). A survey was conducted to determine the pesticide type to which workers had exposed. According to recorded survey assessment, two compounds of OP pesticides chloropyrifos and malathion were investigated in the blood samples of exposed study subjects using high-performance liquid chromatography (HPLC). For screening of genetic polymorphism in GSTP1 (rs1695) polymerase chain reaction, restriction length polymorphism (PCR-RFLP) and agarose gel electrophoresis were performed. Statistically, data were analyzed using SPSS v. 20.0 and MedCal© software. Total chrom© navigator programmer was used for detection of OP residues in serum and local pesticide solution. chloropyrifos-OP pesticide residues were detected in serum of estimated chronically exposed subjects at 206 nm HPLC optimal conditions. The pattern of GSTP1 (rs1695) genotypic frequencies depicted that heterozygous genotype was higher in Chloropyrifos exposed subjects (0.56) when compared with controls (0.44). Statistical outcomes showed an insignificant association with GSTP1 (rs1695) polymorphism and chloropyrifos-OP pesticide toxicity (Fisher’s exact test 1.0, p = 0.25). An insignificant allelic investigation reflected a protective effect of mutant allele G against chloropyrifos-OP pesticide toxicity in exposed subjects. Findings may be helpful in identifying bioaccumulated pesticide residues, but in studied Pakistani exposed workers, no significant association of GSTP1 (rs1695) variant with chloropyrifos-OPs was demonstrated.

PMID:37646887 | DOI:10.1007/s12010-023-04649-w

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Clinical characterization of patients with HLA-B27-associated uveitis and evaluation of the impact of systemic treatment on the recurrence rate: a cross-sectional study

J Ophthalmic Inflamm Infect. 2023 Aug 30;13(1):38. doi: 10.1186/s12348-023-00352-3.

ABSTRACT

INTRODUCTION: Despite HLA-B27-associated uveitis is one of the most frequent etiologies of uveitis worldwide, there are scarce studies on the clinical spectrum of this disease and the implications of therapeutic strategies used in the Latin-American population, with none conducted in Colombia. Thus, this study aimed to describe the clinical characteristics of a cohort of patients with positive HLA-B27-associated uveitis in Colombia and evaluate the impact of systemic treatment on the recurrence rate.

METHODS: We retrospectively reviewed 490 clinical charts of patients with uveitis, searching for those with positive HLA-B27-associated uveitis over eight years in a referral center in Bogotá, Colombia. We used descriptive statistics to summarize demographic and clinical characteristics and conducted a Chi-square test, Fisher Exact test, Spearman correlation, and Mann-Whitney test to assess associations between treatment strategies and the recurrences rate.

RESULTS: We analyzed 39 patients (59% females) with positive HLA-B27-associated uveitis, with a median age at the first consultation of 44.5 years (Range: 2-80) and a mean follow-up time of 86.4 weeks (1.65 years). Most patients had unilateral uveitis (53.8%) and an anterior anatomical diagnosis (76.6%); two had anterior chamber fibrinous reaction, and only one had hypopyon. Most patients did not show associated systemic symptoms (66.7%). Topical corticosteroids, NSAIDs, methotrexate, mydriatics, and adalimumab were the most used treatments. The most common complications included cataracts, posterior synechiae, and macular edema. We identified that the rate of recurrences decreases over time (r = -0.6361, P = 0.002571), and this decrease seems to be associated with the initiation of disease-modifying antirheumatic drugs (DMARDs) in chronic and recurrent cases.

CONCLUSION: The clinical spectrum of HLA-B27-associated uveitis in Colombian patients is distinct from other latitudes. Notably, we found a female predominance, older age at presentation, higher frequency of bilateral and vitreous involvement, and lower frequency of concomitant systemic diseases. Additionally, our results suggest that DMARDs such as methotrexate and biologic agents are good therapeutic options to avoid recurrences in chronic and recurrent cases.

PMID:37646883 | DOI:10.1186/s12348-023-00352-3

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Heavyweight versus non-heavyweight mesh in ventral hernia repair: a systematic review and meta-analysis

Hernia. 2023 Aug 30. doi: 10.1007/s10029-023-02865-1. Online ahead of print.

ABSTRACT

PURPOSE: There is considerable variability among surgeons regarding the type of mesh used in ventral hernia repair. There has been an increasing incidence of mesh fractures with lightweight (LW) and mediumweight (MW) meshes. However, HW mesh has been associated with a greater foreign body sensation and chronic pain. This meta-analysis aims to compare the outcomes of HW and non-heavyweight (NHW) meshes in ventral hernia repair.

METHODS: We systematically reviewed the PubMed, Embase, Cochrane, and Scopus databases to identify studies comparing HW with NHW meshes in hernia repair. Outcomes analyzed included hernia recurrence, seroma, hematoma, foreign body sensation, postoperative pain, and wound infection. We performed two subgroup analyses focusing on randomized controlled trials and open retromuscular repairs. Statistical analysis was performed using RevMan 5.4.

RESULTS: We screened 1704 studies. Nine studies were finally included in this meta-analysis and comprised 3001 patients from 4 RCTs and 5 non-randomized. The majority of patients (57.1%) underwent open retromuscular repair. HW mesh was significantly associated with increased in foreign body sensation (OR 3.71; 95% CI 1.40-9.84; p = 0.008), but there was no difference in other outcomes. In RCTs analysis, there was no difference between meshes. In open retromuscular repairs, HW mesh was associated with more seromas (OR 1.48; 95% CI 1.01-2.17; p = 0.05).

CONCLUSION: Our study found that HW mesh was associated with more foreign body sensation. Also, open retromuscular repairs analysis showed that HW was associated with more seromas. Further randomized studies are needed to understand better the role of HW mesh in ventral hernia repair.

PMID:37646880 | DOI:10.1007/s10029-023-02865-1