Nevin Manimala

Clin Exp Med. 2025 Jan 3;25(1):28. doi: 10.1007/s10238-024-01545-3.

ABSTRACT

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach. We enrolled three matched cohorts: 37 sepsis patients with hepatic dysfunction (S-HD), 37 sepsis patients without hepatic dysfunction (S-CON), and 18 healthy controls (HC). We measured five proposed biomarkers of hepatic dysfunction-ARG1, MDH1, GSTα, 5-NT, and SDH-using multiplex immunoassays. These biomarkers were compared to traditional markers of hepatic dysfunction, including albumin, bilirubin, ALT, AST, and GGT, across the cohorts using both conventional statistical methods and machine learning techniques. The median age of participants was comparable across cohorts: S-HD (65.0 years, IQR 49.5-82.5), S-CON (65.0 years, IQR 48.0-81.5), and HC (62.5 years, IQR 53.0-65.0; P = 0.794). Patients with hepatic dysfunction (S-HD) exhibited higher illness severity scores compared to those without hepatic dysfunction (S-CON): MODS scores were median 7.0 (IQR 4.0-10.0) in S-HD versus median 4.0 (IQR 2.0-7.0) in S-CON (P = 0.005), and SOFA scores were median 7.0 (IQR 4.0-11.0) in S-HD versus median 3.0 (IQR 2.0-6.0) in S-CON (P < 0.001). Hemoglobin and platelet counts were lower, while creatinine levels were higher in S-HD compared to S-CON (P < 0.05). On ICU Day 1, bilirubin, ALT, AST, GGT, and INR were significantly elevated in S-HD relative to S-CON (P ≤ 0.001), and albumin levels were lower (P < 0.05). Additionally, ARG1, GSTα, 5-NT, and SDH were significantly higher in S-HD patients on ICU Day 1 compared to S-CON (P < 0.05). ARG1, MDH1, and SDH showed positive correlations with AST, ALT, and MODS (P < 0.01). From ICU Day 1 to Day 7, ARG1, GSTα, SDH, and AST levels significantly decreased in S-HD patients (P < 0.05), whereas MDH1 and 5-NT levels did not. Among the proposed biomarkers, GSTα and 5-NT did not correlate with traditional hepatic dysfunction markers but were significant in identifying S-HD patients (feature importance 0.131 and 0.097, respectively) in a random forest classification model. This comprehensive model demonstrated excellent performance in distinguishing sepsis patients with hepatic injury, with sensitivity 0.93, specificity 0.94, NPV 0.94, PPV 0.94, and AUC 0.94. The biomarkers ARG1, MDH1, GSTα, 5-NT, and SDH show promise as novel indicators of hepatic dysfunction associated with sepsis. This study provides a foundational basis for subsequent research aimed at characterizing and clinically validating these markers. Future investigations should focus on integrating these potential biomarkers into routine laboratory assessments for sepsis and related hepatic injury.

PMID:39751971 | DOI:10.1007/s10238-024-01545-3

Lasers Med Sci. 2025 Jan 3;40(1):6. doi: 10.1007/s10103-024-04275-w.

ABSTRACT

To assess and compare two techniques of low-level laser application-transgingival (TLLLT) and intrasulcular (ILLLT)-used in photobiomodulation as an adjunct to basic periodontal therapy (BPT) in patients with periodontitis. A randomized, split-mouth, double-blind clinical trial was conducted, selecting three diseased periodontal sites from different quadrants in each patient. These sites were assigned to one of three treatment groups: SRP (control), SRP + TLLLT (test 1), and SRP + ILLLT (test 2). Low-level laser therapy in the test groups was applied at 48 h, 7 days, and 14 days after full-mouth SRP. Clinical parameters such as probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Standardized periapical radiographs were used to assess radiographic bone density (RBD) 6 months post-treatment. Statistical analyses included repeated measures ANOVA for continuous variables and chi-square tests for categorical variables, with significance set at p < 0.05 and a 95% confidence interval. Significant reductions in PD (p < 0.001) and CAL (p < 0.001) were observed across all groups at 3 and 6 months, with no significant differences between groups. There were also no significant changes in BOP and RBD between groups at the follow-up intervals. Adjunctive photobiomodulation did not provide additional clinical or radiographic benefits over SRP alone, regardless of the laser application technique employed.

PMID:39751964 | DOI:10.1007/s10103-024-04275-w

Oral Maxillofac Surg. 2025 Jan 3;29(1):23. doi: 10.1007/s10006-024-01319-x.

ABSTRACT

PURPOSE: This study aimed to evaluate the dental and skeletal stability one year after Miniscrew-Assisted Rapid Palatal Expansion (MARPE) by using 3D image data.

METHODS: Patients with transverse maxillary deficiency from the age of 16 onwards were enrolled consecutively in this prospective longitudinal cohort study. The MARPE appliance was digitally and individually designed and fabricated. Cone-beam computed tomography (CBCT) scans and intra-oral scans (IOS) were acquired before the start of MARPE treatment (T0), immediately after active expansion (T1) and one-year post-expansion (T2). Nasal floor width (NFW), palatal alveolar width at the first molar (M1) and first premolar (P1) (PAW), nasal cavity width (NCW), intermolar width (IMW) and interpremolar width (IPW) were measured to assess the immediate (ΔT0-T1) and net (ΔT0-T2) skeletal and dentoalveolar expansion and relapse (ΔT1-T2). Potential correlations with age, sex and midpalatal suture maturation (MSM) stage were also investigated.

RESULTS: Thirty-one patients (6 men, 25 women, mean age: 26.2 years) were included. The mean follow-up time (T0-T2) was 12.2 months. The initial NFW increase demonstrated a relapse of 0.6 ± 1.2 mm, or 11.6% of the initial expansion (p < 0.01). Expansion at the alveolar level remained stable during the follow-up. IPW also remained stable during the follow-up (4.2 ± 1.3 mm at T1; 4.4 ± 2.6 mm at T2). IMW exhibited a relapse of 3.8 ± 2.1 mm, or 60.2% of the initial expansion (p < 0.001) during T1-T2. There was no statistically significant correlation between stability and age, sex and MSM stage.

CONCLUSIONS: MARPE is an effective therapy for the correction of transverse maxillary discrepancy in late adolescents and adults, achieving a clinically stable skeletal outcome one year after expansion.

PMID:39751963 | DOI:10.1007/s10006-024-01319-x

Mol Genet Genomics. 2025 Jan 3;300(1):12. doi: 10.1007/s00438-024-02221-7.

ABSTRACT

Precursors of microRNAs (pre-miRNAs) are less used in silico to mine miRNAs. This study developed PmiR-Select^® based on covariance models (CMs) to identify new pre-miRNAs, detecting conserved secondary structural features across RNA sequences and eliminating the redundancy. The pipeline preceded PmiR-Select^® filtered 20% plant pre-miRNAs (from 38589 to 8677) from miRBase. The second filter reduced pre-miRNAs by 7% (from 8677 to 8045) through length limit to pre-miRNAs (70-300 nt) and miRNAs (20-24 nt). The 80% redundancy threshold was statistically the best, eliminating 55% pre-miRNAs (from 8045 to 3608). Angiosperms retained the highest number of pre-miRNAs and their families (2981 and 2202), followed by gymnosperms (362 and 271), bryophytes (183 and 119), and algae (82 and 78). Thirty-seven conserved pre-miRNA families happened among plant land clades, but none with algae. The PmiR-Select^® was applied to the rice genome, producing 8536 pre-miRNAs from 36 families. The 80% redundancy threshold retained 3% pre-miRNAs (n = 264) from 36 families, valuable experimental and computational research resources. 14% (n = 1216) of 8536 were new pre-miRNAs from 19 new families in rice. Only 16 new sequences from six families overlapped (39 to 54% identities) with rice pre-miRNAs and five species on miRBase. The validation against mature miRNAs identified 8086 pre-miRNAs from 13 families. Eleven ones have already been recorded, but two new and abundant pre-miRNAs [miR437 (n = 296) and miR1435 (n = 725)] scattered in all 12-rice chromosomes. PmiR-Select^® identified pre-miRNAs, decreased the redundancy, and discovered new miRNAs. These findings pave the way to delineating benchtop and computational experiments.

PMID:39751956 | DOI:10.1007/s00438-024-02221-7

Daru. 2025 Jan 3;33(1):11. doi: 10.1007/s40199-024-00554-7.

ABSTRACT

BACKGROUND: The inappropriate use of antibiotics increases the costs of treatment, antibiotic resistance, increased disease length and duration of hospital stay.

OBJECTIVES: The aim of this study was investigating the pattern of use and effectiveness of the Linezolid in COVID-19 hospitalized patients.

METHODS: In this retrospective cross-sectional analytical study was carried out from February 2020 (from the beginning of the pandemic in Iran) to the end of September 2020, 32 COVID-19 patients that used Linezolid were included. The data retrieved from medical document’s unit and analysis was performed by SPSS statistical software version 20.

RESULTS: According to the three elements of the 1- culture of resistant bacteria 2-the correct daily dose and 3-adequate duration of the drug, consumption pattern of Linezolid was irrational in 24 (75%) COVID-19 patients and it was rational only in 8 (25%) patients. Twenty-three (71.9%) patients received sufficient doses of the drug and 9 (28.1%) patients did not receive the required minimum dose. Four (50%) patients who rationally received Linezolid improved and the remaining 4 died. Leukopenia occurred in 1 patient (3.1%), anemia appeared in 24 individuals (75%), and 15 patients (46.9%) developed thrombocytopenia.

CONCLUSION: We suggest that the prescription of Linezolid is in accordance with the standard instructions and the stewardship antibiotic program to reduce the medication costs, drug side effects, and the prevalence of antibiotic resistance.

PMID:39751953 | DOI:10.1007/s40199-024-00554-7

Clin Oral Investig. 2025 Jan 3;29(1):43. doi: 10.1007/s00784-024-06125-z.

ABSTRACT

AIMS: Our goal is to perform a meta-analysis to investigate the risk of periodontitis associated with specific dietary patterns.

METHODS: We employed the PRISMA methodology in a meta-analysis to examine the correlation between dietary patterns and the risk of periodontitis. We systematically searched three online databases from inception to November 2024 to identify relevant studies. Summary estimates with 95%CI were calculated to assess the relationship between specific dietary patterns and the risk of periodontitis. Cumulative estimates were synthesized using random-effects or fixed-effects models. Heterogeneity among studies was evaluated using Cochran’s Q and I² statistics.

RESULTS: In total, we included 19 articles that analyzed 5 dietary patterns The study showed that a diet high in inflammation-promoting foods significantly raised the likelihood of periodontitis (OR = 1.39, 95% CI, 1.09-1.77), in contrast, dietary patterns like the mediterranean diet (OR = 0.96, 95% CI, 0.94-0.98), plant-based diet (OR = 0.92, 95% CI, 0.86-0.98), or dairy-rich diet (OR = 0.76, 95% CI, 0.66-0.87) lowered the risk of periodontitis. The analysis revealed no statistically significant association between a western diet (OR = 1.07; 95% CI, 0.86-1.33) and the risk of periodontitis.

CONCLUSIONS: As dietary diversity and complexity continue to expand, there has been a concomitant increase in the prevalence of periodontal disease. This study has identified specific dietary patterns associated with the risk of periodontitis, particularly highlighting the heightened risk linked to pro-inflammatory diets. These findings emphasize the importance of implementing targeted dietary practices to reduce the incidence of this condition.

PMID:39751926 | DOI:10.1007/s00784-024-06125-z

Cancer Immunol Immunother. 2025 Jan 3;74(2):72. doi: 10.1007/s00262-024-03905-0.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) show optimal treatment effects on recurrent or metastatic nasopharyngeal carcinoma(R/M NPC). Nonetheless, whether metastatic sites impact ICIs efficacy remains unclear.

METHODS: We performed a secondary analysis of R/M NPC patients treated with KL-A167, a programmed cell death-ligand 1(PD-L1) inhibitor, based on a multicenter, single-arm, phase II study from China between 2019 and 2021 years, which represents the first and most comprehensive analysis of the effectiveness of a PD-L1 inhibitor in patients who have been previously treated. The Cox proportional hazard model was utilized to evaluate the association between sites and PFS and OS. Sensitivity analysis and subgroup analysis were carried out to confirm the reliability of our findings.

RESULTS: A total of 153 R/M NPC patients were included. The mean age was 47 years and 81% of patients were males. All patients in our study had distant metastasis, with a majority (n = 69) presenting with more than 2 sites of distant metastasis upon admission. The collected sites of metastasis included liver, lung, lymph and bone. Among the 153 patients, 37.9% (58 patients) received anti-PD-L1 treatment for a minimum of 6 months, and 17.6% (27 patients) were treated for at least 12 months. By conducting multivariate analysis, R/M NPC patients with non-liver metastases presented significantly longer progress-free survival (PFS, HR:1.67, CI:1.09-0.2.55, p = 0.018) and overall survival (OS, HR:2.52, CI:1.49-4.28, p < 0.001) compared with those with liver metastasis. The median PFS (72 vs. 144 days, p < 0.0001) and OS (730 vs. 305 days, p < 0.0001) were significantly longer for patients with non-liver metastases. However, lung, bone and lymph node metastasis had no statistical significance on PFS and OS (p > 0.005). Our sensitive analysis showed liver metastases patients with less other site metastases (0 or 1) had shorter OS compared to non-liver metastases patients with more other metastases(≥ 2). Furthermore, subgroup analysis indicated the robustness evidence liver metastasis indeed a valuable prognostic factor for survival.

CONCLUSIONS: Compared to patients with other metastatic sites, R/M NPC patients with liver metastasis have poor survival patterns when receiving anti-PD-L1 therapy. Our study provides rational evidence for the urgent need to explore more efficacy treatment modalities for NPC patients with liver metastasis.

PMID:39751901 | DOI:10.1007/s00262-024-03905-0

Int J Colorectal Dis. 2025 Jan 3;40(1):5. doi: 10.1007/s00384-024-04781-x.

ABSTRACT

PURPOSE: The role of adjuvant chemotherapy in rectal cancer patients downstaged to ypT0-2 N0 after neoadjuvant chemoradiotherapy (CRT), and surgery is still debated. This study investigates the impact of adjuvant chemotherapy on survival outcomes in this patient population.

METHODS: This retrospective study analyzed hospital records of rectal cancer cases from Shefa Al Orman Cancer Hospital between January 2016 and December 2020, focusing on patients downstaged to ypT0-2 N0 after neoadjuvant CRT and surgery. Patients were divided into two groups based on whether they received adjuvant chemotherapy. Baseline characteristics, DFS, and OS were compared, and survival factors were analyzed using univariate and multivariate Cox regression.

RESULTS: Eighty-five patients met the inclusion criteria; 55 received adjuvant chemotherapy, and 30 did not. The median age was 52, but those receiving adjuvant therapy were younger (47 vs. 60 years, P = 0.006). No significant differences were observed in sex, tumor location, or pathology between groups. Although adjuvant chemotherapy showed a trend toward better 3-year DFS (89.5% vs. 81.9%, P = 0.153) and OS (88.1% vs. 84.6%, P = 0.654), these differences were not statistically significant. Univariate and multivariate analyses confirmed no significant effect of adjuvant chemotherapy on DFS or OS, nor were any other variables significantly associated with survival.

CONCLUSION: Adjuvant chemotherapy did not significantly improve DFS or OS in rectal cancer patients downstaged to ypT0-2 N0 following neoadjuvant CRT and surgery. Further studies are needed to define the role of adjuvant therapy in this group.

PMID:39751895 | DOI:10.1007/s00384-024-04781-x

Calcif Tissue Int. 2025 Jan 3;116(1):15. doi: 10.1007/s00223-024-01311-3.

ABSTRACT

Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI. A Danish nationwide register-based cohort study utilizing data from the Danish National Patient Register and the Danish National Prescription Register. All individuals registered with an OI diagnosis in Denmark from 1995 through 2018, along with a reference population matched 1:5 based on sex, birth year, and month. Sub-hazard ratios (SHR) for peptic ulcer disease, diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, constipation, abdominal wall hernia, and other reasons for abdominal discomfort. The study included 864 individuals with OI (472 women) and 4,276 in the reference population (2,332 women). The SHR was significantly increased for ulcer (3.28 [95% CI 2.21-4.28]), constipation (2.67 [1.91-3.74]), and hernia (among women: 1.85 [1.22-2.80]). Higher SHRs were also observed for inflammatory bowel disease, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain. SHRs were not statistically significantly increased for diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, kidney stones or hemorrhoid disease. Individuals with OI have a higher risk of peptic ulcer disease, constipation, hernia among women, inflammatory bowel diseases, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain, compared with the general population.

PMID:39751887 | DOI:10.1007/s00223-024-01311-3

Aging Dis. 2024 Dec 18. doi: 10.14336/AD.2024.1174. Online ahead of print.

ABSTRACT

Neuroinflammation plays a critical role in Alzheimer’s (AD) and Parkinson’s diseases (PD) onset, pathophysiology, and progression. The aim of our meta-analysis was to review the available literature to assess the role of neuroinflammation in the pathogenesis of the two most common neurological diseases: Parkinson’s disease and Alzheimer’s disease. Two medical databases were searched: Web of Science and PubMed in the period from 2009-2023, where a total of 37 publications that met the inclusion criteria were selected for further evaluation. Both patients with AD and with PD showed statistically significantly higher levels of interleukin IL-6 compared to the control group: p-value of 0.0034 for AD (SMD, 1.17; 95% CI, 0.39-1.96) and p-value of 0.0487 for PD (SMD 0.29 95% Cl 0.00-0.59). In AD patients, statistical significance (for random effect) was also observed for IL-1β, where higher values of this cytokine were recorded in patients compared to controls (p-value <0.001). In turn, in patients with PD, apart from IL-6, statistical significance was also observed for tumor necrosis factor-α (TNF-α) (p= 0.0431, SMD 0.52 95%Cl 0.02-1.02). Significant heterogeneity was also recorded (Q =85.48; P < 0.01; I² = 87%). In both study groups, significant differences in common effect were observed for the anti-inflammatory cytokine IL-10, which could suggest a protective effect of this cytokine in patients with neurodegenerative diseases. The obtained results reinforce the existing clinical evidence that Alzheimer’s and Parkinson’s diseases are accompanied by an inflammatory response, with considerably higher blood levels observed for pro-inflammatory cytokines: IL-6, TNF-α and IL-1β.

PMID:39751856 | DOI:10.14336/AD.2024.1174