Tag: nevin manimala

Discov Oncol. 2024 Oct 17;15(1):568. doi: 10.1007/s12672-024-01456-5.

ABSTRACT

OBJECTIVE: This study aims to investigate the causal relationship between cervical carcinoma in situ and antibody-mediated immune responses, providing a scientific basis for the prevention and treatment of cervical carcinoma in situ.

METHODS: A bidirectional Mendelian Randomization (MR) approach was utilized, leveraging two Genome-Wide Association Studies (GWAS) related to cervical carcinoma in situ and antibody-mediated immune responses to collect Single Nucleotide Polymorphism (SNP) data. Multiple statistical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, and weighted mode, were utilized. Antibody-mediated immune response-related SNPs were used as instrumental variables (IVs) for a forward MR analysis of cervical carcinoma in situ, while cervical carcinoma in situ-related SNPs served as IVs for a reverse MR analysis of antibody-mediated immune responses.

RESULTS: The forward MR analysis revealed significant causal associations between two SNPs, GCST90006901 (P = 0.012, OR (95%CI) = 1.167(1.034-1.317)) and GCST90006909 (P < 0.001, OR (95%CI) = 1.805(1.320-2.467)), within antibody-mediated immune responses and the occurrence of cervical carcinoma in situ. The reverse MR analysis demonstrated that cervical carcinoma in situ exerts influence on multiple SNPs associated with antibody-mediated immune responses. Specifically, GCST90006891 (P = 0.018, OR (95%CI) = 1.164(1.027-1.319)) and GCST90006894 (P = 0.048, OR (95%CI) = 1.074 (1.001-1.153)) showed positive effects, while GCST90006899 (P = 0.022, OR (95%CI) = 0.935(0.882-0.990)) and GCST90006911 (P = 0.0193, OR (95%CI) = 1.226(1.034-1.454)) exhibited distinct trends of influence.

CONCLUSION: The Mendelian Randomization analysis indicates a clear causal relationship between antibody-mediated immune responses and the prevalence of cervical carcinoma in situ, with cervical carcinoma in situ also exerting a certain degree of influence on antibody-mediated immune responses. This finding provides important insights into the interaction mechanism between the two and suggests avenues for developing effective prevention and control strategies.

PMID:39417906 | DOI:10.1007/s12672-024-01456-5

Arch Dermatol Res. 2024 Oct 17;316(10):697. doi: 10.1007/s00403-024-03434-x.

ABSTRACT

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32 ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216 ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17 A levels. Baseline levels of IL-17 A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated.

PMID:39417892 | DOI:10.1007/s00403-024-03434-x

Arch Dermatol Res. 2024 Oct 17;316(10):698. doi: 10.1007/s00403-024-03431-0.

ABSTRACT

Basal cell carcinoma (BCC) is a slowly progressive, locally aggressive and rarely metastasizing cancer, and although its mortality is low, its morbidity and cost of disease are high. While BCC is more common, cutaneous malignant melanoma (CMM) is significant due to its higher mortality rate. These patients can be treated, but recurrence, metastasis and mortality may occur in such patients. Various environmental, phenotypic and genotypic factors, especially ultraviolet (UV) radiations, play a role in the etiology of BCC and CMM. Histopathological examination continues to be the “gold standard” in their diagnosis. Spexin (SPX) and DARS2 are newly discovered proteins linked to many diseases, including cancer. These proteins may have an effect on the development and expression of skin cancers such as BCC and CMM. In this study, we evaluated the potential of SPX and DARS2 expressions as immunohistochemical biomarkers in the differential diagnosis of BCC and CMM. This study was conducted retrospectively using samples taken from the pathology laboratory. A total of 180 patient samples were used. The control group consisted of healthy skin tissues of the patients, and the other groups consisted of BCC and CMM tissues of the same patients. Tissue samples of all three groups were evaluated immunohistochemically with SPX and DARS2. The immunoreactivity of SPX was found to be higher in BCC and CMM tissue samples than in healthy skin tissues in the control group. DARS2 immunoreactivity was found to be higher in CMM tissues compared to the other two groups, and statistically significant in BCC tissues when compared with healthy control group tissues. SPX can be used as an immunohistochemical biomarker in the diagnosis of BCC and CMM. Since DARS2 expression is statistically more significant in CMM tissues than in BCC tissues, it can be used in differential diagnosis.

PMID:39417889 | DOI:10.1007/s00403-024-03431-0

Intensive Care Med. 2024 Oct 17. doi: 10.1007/s00134-024-07667-2. Online ahead of print.

ABSTRACT

PURPOSE: Antiseptic bathing has garnered attention in an effort to reduce hospital-acquired infections. Previous studies have shown the efficacy of antiseptic bathing in high-risk environments, such as intensive care units (ICUs), using chlorhexidine. In this study we aimed to evaluate the effectiveness of octenidine as a potential alternative due to its established popularity and widespread use in Europe.

METHODS: We compared the rates of ICU-acquired primary bacteremia and ICU-acquired multidrug-resistant organisms (MDROs) in a multicenter, cluster-randomized, double-blind, placebo-controlled, cross-over study using octenidine-impregnated and placebo washcloths. On 44 ICUs in 23 hospitals throughout Germany, we compared individual ICUs with themselves over two 12-month time periods. All data were obtained digitally via hospital information systems as individual ward-movement data and microbiological test results; both endpoints were algorithmically derived.

RESULTS: 104,039 ICU episodes from 93,438 patients with 712,784 microbiological test results were analyzed, thereby detecting 1508 cases of ICU-acquired primary bacteremia and 1871 cases of ICU-acquired MDRO. Bathing with octenidine-impregnated washcloths prevented ICU-acquired primary bacteremia; a risk reduction of 17% was seen homogeneously across all participating ICUs (adjusted hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.75; 0.92], p = 0.0003). This reduction affected predominantly coagulase-negative staphylococci (53%) and enterococci (17%). However, no intervention effect was seen for ICU-acquired MDROs (adjusted HR 0.98, 95% CI [0.83; 1.15]). Heterogeneity among intra-ICU intervention effects on MDRO acquisition was substantial.

CONCLUSIONS: Antiseptic bathing with octenidine may be effective in preventing ICU-acquired primary bacteremia, particularly due to Gram-positive bacteria and common skin commensals.

PMID:39417875 | DOI:10.1007/s00134-024-07667-2

Intensive Care Med. 2024 Oct 17. doi: 10.1007/s00134-024-07676-1. Online ahead of print.

ABSTRACT

PURPOSE: Net ultrafiltration (UF_NET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h^-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UF_NET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.

METHODS: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UF_NET ≥ 100 ml·h^-1, adjusted using a functional hemodynamic protocol (intervention), or a UF_NET ≤ 25 ml·h^-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.

RESULTS: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.

CONCLUSION: In patients with vasopressors, a UF_NET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

PMID:39417870 | DOI:10.1007/s00134-024-07676-1

Eur J Appl Physiol. 2024 Oct 17. doi: 10.1007/s00421-024-05629-6. Online ahead of print.

ABSTRACT

Gas exchange data acquired repeatedly under the same exercise conditions are assembled together to improve the kinetic parameters of breath-by-breath oxygen uptake. The latter are provided by the non-linear regression procedure, together with the corresponding estimators of the width of the Confidence Intervals (i.e., the Asymptotic Standard Errors; ASEs). We tested, for two different assembling procedures, whether the range of values identified by the ASE actually correspond to the 95% Confidence Interval. Ten O₂ uptake responses were acquired on 10 healthy volunteers performing a square-wave moderate-intensity exercise. Kinetic parameters were estimated running the non-linear regression with a mono-exponential model on an increasingly greater number of responses (Nr, from 1 to 10), assembled together using the “stacking” and the “1-s-bins” procedures. Kinetic values obtained assembling together the 10 repetitions were assumed as “true” values. The time constant was not affected by Nr or by the assembling procedure (ANOVA; p>0.54 and p>0.16, respectively). The corresponding ASE decreased according to Nr (ANOVA; p=0.000), being significantly smaller for the “1-s-bins” procedure compared to the “stacking” one (ANOVA; p<0.001). Excluding 20s at the start of the fitting window, the range of values identified with the ASE provided by the “1-s-bins” and the “stacking” procedures included the “true” value in 85% and in 95% of cases, respectively. The “stacking” procedure should be preferred since it yielded ASEs for the time constant that provided a range of values satisfying the statistical meaning of the width of the Confidence Intervals, at the given degree of probability.

PMID:39417864 | DOI:10.1007/s00421-024-05629-6

Graefes Arch Clin Exp Ophthalmol. 2024 Oct 17. doi: 10.1007/s00417-024-06598-4. Online ahead of print.

ABSTRACT

PURPOSE: To assess the efficacy of adding Ahmed’s sub-flap mattress suture to deep sclerectomy (DS).

METHODS: Forty eyes with open angle glaucoma were assigned randomly into two groups: Group A: underwent DS with Ahmed’s sub-flap mattress suture. Group B: underwent conventional DS. Patients were followed up closely for 6 months with serial IOP measurements and ultrasound biomicroscopy (UBM) was used to assess the surgical site functionally and anatomically at the first and sixth month.

RESULTS: Adding Ahmed’s sub-flap mattress suture improved the IOP lowering effect of DS significantly from 43% in group B to 53% in group A at 6-month (p = 0.027). IOP in group A was at 1 week, 1 month and 6-month visits (7.9 ± 1.3, 11.7 ± 2.2 and 13.3 ± 1.9 mmHg respectively) compared to group B (10.1 ± 4.6, 14.1 ± 5.2 and 16.8 ± 4.1 mmHg respectively) (p = 0.025, 0.041 and 0.001 respectively). UBM parameters were significantly larger in group A at 1 and 6 months. Strong statistically significant negative correlations were established between IOP and all the UBM parameters apart from intrascleral lake height at the first and sixth month (p < 0.01 in all of them). Finally, significant correlations were found between IOP at 6 months and whole bleb anteroposterior length and height at 1 month (p = 0.001).

CONCLUSION: Adding Ahmed’s sub-flap mattress suture to routine DS is an effective economical addition that will enhance the IOP lowering effect of DS. Also, assessment of the bleb by UBM is useful in predicting the success of deep sclerectomy surgery.

PMID:39417853 | DOI:10.1007/s00417-024-06598-4

Acta Diabetol. 2024 Oct 17. doi: 10.1007/s00592-024-02374-2. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN) is a grave complication and the most common renal dysfunction of diabetes mellitus. Genetic factors, including Apolipoprotein E (APOE) isoforms, have been implicated in the pathogenesis of DN.

METHODS: A total of 577 type 2 Diabetes mellitus subjects were categorized into diabetes non-nephropathic (Controls: n = 321), diabetes nephropathic (DN: n = 256) groups. Demographic, clinical, and biochemical parameters including age, BMI, lipid profiles (TC, LDL-C, HDL-C, TG), glucose metabolism (plasma glucose, HbA1c, serum insulin), renal function (UACR, PCR), and blood pressure (SBP, DBP) were assessed. APOE variant frequencies were determined using restriction fragment length polymorphism (RFLP) analysis, validated against Hardy-Weinberg equilibrium (HWE), and statistically correlated with each clinical and biochemical parameter.

RESULTS: The DN group had an increased prevalence of hypertension, fatty liver, and dyslipidemia compared to the Control group. Biochemical analyses revealed elevated levels of TC (213.41 mg/dL vs. 189.32 mg/dL), LDL-C (134.46 mg/dL vs. 107.56 mg/dL), and reduced HDL-C (58.13 mg/dL vs. 65.32 mg/dL) in DN cases compared to Controls (all p < 0.0001). The APOE variants distribution showed a significant increase in E2 allele frequency (69.1% vs. 15.3%) and corresponding homozygous genotype (E2/2: 42.2% vs. 5.6%) in DN cohorts.

CONCLUSION: The study found a higher frequency of E2 allele in the DN group compared to Controls, though no statistically significant risk of DN was linked to this allele. The results suggest a potential association for APOE polymorphisms, requiring broader studies to clarify the role of APOE polymorphisms in DN susceptibility.

PMID:39417844 | DOI:10.1007/s00592-024-02374-2

Addiction. 2024 Oct 17. doi: 10.1111/add.16688. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: In 2018, the country of Georgia legalized cannabis for recreational use and decriminalized limited possession. This study aimed to assess whether cannabis use increased among young adults (ages 18-29 years) in Georgia after national policy changes and to evaluate whether perceived access became easier after legalization and current risk factors of young adult cannabis use.

METHODS: We used data from the Georgian nationally representative survey administered in 2015 (n = 1308) and 2022 (n = 758), before and after decriminalization. We performed appropriate bivariate analyses and multivariable linear and logistic regressions to assess the following: legalization’s impact on cannabis use; perceived difficulty to obtain cannabis; age of first use; differences in use between females and males; and factors associated with current use.

FINDINGS: Among young adults lifetime prevalence of cannabis use was similar in 2015 (17.3%) and 2022 (18.1%) [Odds Ratio (95% confidence interval) = 1.1 [0.7, 1.6], P = 0.726). Annual prevalence (7% in 2015 vs 7.7% in 2022) was also similar (1.1 [0.7, 2.0], P = 0.650). In 2022 it was less difficult to obtain cannabis than in 2015 (0.5 [0.4, 0.8], P = 0.021). The age of first use increased statistically significantly (18.1 years in 2015 vs 19.1 in 2022, P = 0.003). In 2022, annual prevalence of use was lower among females (1.9% vs 13.1%; OR = 0.1 [0.0, 0.3], P < 0.0001) and higher among those who gambled (11.7% vs 4.4%; OR = 3.2 [1.5, 6.8], P < 0.003). Males initiated cannabis use at an earlier age (19.1 years vs 20.6 for females, P = 0.03), and could obtain cannabis easier than females (P < 0.0001).

CONCLUSION: There was a minimal shift of cannabis use in young adults following implementation of recreational cannabis use legalization in Georgia. Males and people who gambled were at higher risk of cannabis use.

PMID:39417804 | DOI:10.1111/add.16688

Knee. 2024 Oct 15;51:258-267. doi: 10.1016/j.knee.2024.09.013. Online ahead of print.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a globally prevalent condition leading to joint pain and disabilities. Surgical interventions such as opening-wedge high tibial osteotomy (OWHTO) and opening-wedge distal tuberosity osteotomy (OWDTO) aim to alleviate symptoms and delay disease progression. Quadriceps strength, crucial for knee function, may decline postoperatively, affecting patient outcomes. However, little is known about quadriceps strength variation after OWHTO and OWDTO. This study investigated changes in quadriceps strength before and after OWHTO and OWDTO.

METHODS: This retrospective study included patients who underwent OWHTO or OWDTO between 2016 and 2022. Quadriceps strength and demographic and surgical data were collected preoperatively and at 6 and 12 months postoperatively. Statistical analyses were performed to compare changes in quadriceps strength over time.

RESULTS: Of 120 knees, 52 (OWHTO, 27; OWDTO, 25) were included in this study. Quadriceps strength increased over 12 months post-OWHTO, significantly improving at 12 months compared to the preoperative and 6-month values. In OWDTO, the strength improved but not significantly.

CONCLUSIONS: Quadriceps strength improved following OWHTO and OWDTO, with OWHTO showing significant enhancements. Future studies should investigate the relationship between quadriceps strength and functional outcomes and guide rehabilitation strategies for improved postoperative recovery.

PMID:39413454 | DOI:10.1016/j.knee.2024.09.013