Nevin Manimala

J Adv Periodontol Implant Dent. 2025 Apr 21;17(2):65-70. doi: 10.34172/japid.025.2292. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Excess cement is one of the most prevalent problems with cement-retained implant-supported prostheses. The excess cement may be considered an important source of inflammation during implant application. Optimizing the design procedure for reducing excess cement is necessary for successful and safe implant applications.

METHODS: This study assessed the effect of two confounding factors, i.e., emergence profile and space gap size, on the level of excess cement. Three types of emergence profiles (concave, convex, and straight) and three different gap sizes (30, 60, and 90 µm) were considered for implant design, and the level of excess cement was measured for each design.

RESULTS: Statistical analyses using one-way ANOVA followed by post hoc P value correction revealed that the best emergence profile with the lowest excess cement was the straight profile, with statistically lower excess cement compared with concave and convex profiles (P<0.05) and no significant difference between concave and convex profiles. Furthermore, analyses showed that lower gap size was associated with lower excess cement, even though increasing the gap size from a threshold (>60 µm) made the difference significant. Interaction analysis using two-way ANOVA also indicated the interaction between the emergence profile and space gap size.

CONCLUSION: The results emphasized that a straight profile with a smaller gap size should be considered to reduce the excess cement. However, due to the small sample size of the study, further analyses with different types of materials, angles of deformation, and gap sizes are required to reveal the exact relationship between excess cement and the design specifications.

PMID:40673117 | PMC:PMC12261064 | DOI:10.34172/japid.025.2292

Transl Lung Cancer Res. 2025 Jun 30;14(6):1914-1928. doi: 10.21037/tlcr-2024-1092. Epub 2025 Jun 24.

ABSTRACT

BACKGROUND: Although Kirsten rat sarcoma virus (KRAS) mutations represent the most frequent oncogenic driver alterations in Caucasian lung adenocarcinoma (LADC) patients, their impact on immune phenotype and tumor morphology is largely unexplored. Here, we investigated the associations between KRAS mutation subtypes, immune landscape, and tumor heterogeneity in surgically treated LADC, with a particular focus on specific tumor growth patterns.

METHODS: This study included 87 surgically treated patients with histologically confirmed early-stage LADC. Three tumorous and one non-tumorous tissue microarray (TMA) cores were collected from each patient. KRAS genotyping was performed using polymerase chain reaction (PCR)-based assays. We assessed the immune landscape by evaluating the NLRP3 inflammasome, CD3, CD163, and PD-L1 expression.

RESULTS: The mutational landscape concerning the type of KRAS mutation was mostly homogenous across TMA cores, with KRASG12C being the most frequently detected alteration. Notably, in 19 cases, the dominant mutational subtype differed between the tumor punctures originating from the same tumor. Although KRASG12A mutation was not detected in LADC samples with a lepidic growth pattern and micropapillary LADCs lacked wild-type KRAS gene, no statistically significant association was found between the KRAS mutation subtype and LADC growth pattern. NLRP3 expression significantly correlated with CD3 and CD163 expressions (P<0.001), and elevated NLRP3 levels were characteristic of LADCs with solid growth pattern (P=0.001). Tumor samples with solid morphology expressed significantly higher levels of PD-L1 than acinar- or lepidic-pattern LADCs (P=0.007 and P=0.002, respectively).

CONCLUSIONS: KRAS mutation subtypes may have a heterogeneous distribution across different tumor regions, contributing to cases with concomitant mutation subtypes that create significant diagnostic challenges. The growth pattern-specificity of NLRP3 and PD-L1 offers additional guidance for the future development of alternative immunotherapeutic approaches.

PMID:40673097 | PMC:PMC12261357 | DOI:10.21037/tlcr-2024-1092

Transl Lung Cancer Res. 2025 Jun 30;14(6):2197-2209. doi: 10.21037/tlcr-2025-505. Epub 2025 Jun 26.

ABSTRACT

BACKGROUND: Treatment of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) remains an unmet need. Among these patients, the efficacy of immunotherapy has not been thoroughly investigated. The purpose of our study was to evaluate the efficacy of immunotherapy in patients with ALK-TKI-resistant NSCLC, stratified by programmed cell death ligand-1 (PD-L1) expression.

METHODS: We retrospectively collected the data of advanced NSCLC patients with ALK-rearrangement, who were treated with immunotherapy or chemotherapy after the development of ALK-TKI resistance at the Shanghai Chest Hospital. Progression-free survival (PFS) was used to evaluate the outcomes.

RESULTS: The final analysis included 89 patients between June 1, 2018, and December 31, 2022, who met the selection criteria. The entire cohort had a median follow-up time of 33.4 months. The patients who received immunotherapy had better PFS than those who received non-immunotherapy (median PFS: 5.3 vs. 2.5 months; P=0.009). The PD-L1-positive patients who received immunotherapy had a median PFS of 7.1 months, while those who received non-immunotherapy had a median PFS of 2.5 months (P=0.02). No such statistically significant difference was observed in the PD-L1-negative patients (median PFS for with immunotherapy vs. without immunotherapy: 1.5 vs. 2.9 months; P=0.68). The PD-L1-positive patients who underwent re-biopsy after the development of TKI resistance and who received immunotherapy had a PFS of 7.8 months, while those who received non-immunotherapy had a PFS of 2.7 months (P=0.002).

CONCLUSIONS: This was the first real-world retrospective study to show that some patients with positive PD-L1 expression may benefit from immune-based therapy after the development of ALK-TKI resistance. However, we still recommend biopsy for patients who develop ALK-TKI resistance to provide further treatment guidance.

PMID:40673075 | PMC:PMC12261234 | DOI:10.21037/tlcr-2025-505

Mathematica (N Y). 2025 Mar;4(1):66-83. doi: 10.1007/s44007-024-00144-8. Epub 2024 Dec 23.

ABSTRACT

Primary open angle glaucoma (POAG) is a leading cause of irreversible blindness with risk factors including elevated intraocular pressure (IOP), and both high and low blood pressure (BP). This study investigates the joint influence of IOP and BP on retinal hemodynamics, emphasizing venous circulation. A synthetic dataset comprising 2500 eyes with varied IOP [5-45] mmHg, systolic BP (SBP) [90-200] mmHg and diastolic BP (DBP) [40-120] mmHg was created. Mean pressure $\left(\bar{P}\right)$ , mean flow $\left(\bar{Q}\right)$ , and mean resistance $\left(\bar{R}\right)$ , were estimated using a validated mathematical model. The values of these hemodynamic output variables were then analyzed in relation to different values of IOP and mean arterial pressure (MAP; MAP = 1/3 SBP + 2/3 DBP). Clinical data from a population-based Greek study were similarly analyzed. Differences in the simulated hemodynamic output variables and clinical markers between healthy and POAG eyes were then measured. Synthetic dataset analysis revealed that $\bar{R}$ and $\bar{P}$ vary significantly depending on different IOP-MAP combinations. Notably, eyes with low MAP and high IOP demonstrated a drastic increase in $\bar{R}$ in the venules accompanied with a dramatic decrease in $\bar{P}$ in the central retinal vein (CRV). Clinical data indicated that venules in POAG eyes had significantly higher $\bar{R}$ than healthy eyes (p < 0.01), along with decreased $\bar{P}$ in the CRV of POAG eyes compared to healthy eyes (p = 0.01). The study highlights the increased susceptibility to venous collapse in POAG eyes and the importance of considering the venous side of retinal circulation in the combined impact of risk factors in POAG.

PMID:40673059 | PMC:PMC12263117 | DOI:10.1007/s44007-024-00144-8

J Assoc Med Microbiol Infect Dis Can. 2025 May 29;10(2):171-178. doi: 10.3138/jammi-2024-0038. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The rates of HIV and syphilis in Saskatchewan (SK) have been rising rapidly in recent years. The syndemic has raised concern for neurosyphilis, a complication that can occur at any stage of syphilis and is more common in people living with HIV (PLWH). Criteria published by the Public Health Agency of Canada recommends considering a lumbar puncture (LP) in patients with concomitant HIV and syphilis infection whose rapid plasma reagin (RPR) titre is ≥1:32 or whose CD4+ count is ≤350. We assessed whether this recommendation was met at 2 comparable clinical sites.

METHODS: In this retrospective analysis, we compare rates of LP and corresponding syphilis treatment success at two clinics in Saskatoon, SK: a community-based primary care clinic and a tertiary care hospital-based infectious disease clinic.

RESULTS: Of 193 syphilis cases across both sites, 128 cases met laboratory criteria for lumbar puncture. Rates of LP (9% primary care clinic and 19% infectious disease clinic) and syphilis treatment success (87% primary care clinic and 89% infectious disease clinic) were comparable between groups. When RPR titre was controlled for, clinic type did not statistically significantly affect the rates of lumbar puncture (p = 0.104) or syphilis treatment success (p = 0.068). A RPR titre ≥1:32 was positively associated with both treatment success (OR 2.596) and lumbar puncture (OR 4.495).

CONCLUSION: Results suggest that there is no difference in either the community or hospital-based clinic type for syphilis treatment success and that rates of lumbar puncture of patients meeting serologic criteria are low across diverse HIV patient groups and clinical settings.

PMID:40673055 | PMC:PMC12253935 | DOI:10.3138/jammi-2024-0038

J Assoc Med Microbiol Infect Dis Can. 2025 May 29;10(2):146-159. doi: 10.3138/jammi-2024-0017. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The impact of the COVID-19 pandemic on antimicrobial use in Canadian hospitals is not well characterized. We explored the relationship between the COVID-19 pandemic and Canadian hospital antimicrobial purchasing (AMP)-a proxy for consumption.

METHODS: Hospital-level AMP data were obtained from IQVIA, a health analytics company, and matched with inpatient patient-day denominator data from 28 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Monthly AMP was measured using defined daily doses (DDDs) per 1,000 patient-days. Segmented linear regression with hospital-level clustering assessed for step and slope changes in AMP between pre-pandemic (January 1, 2018 – February 29, 2020) and pandemic (March 1, 2020 – December 31, 2021) periods.

RESULTS: Although we found an initial increase in AMP with the onset of the pandemic (+42 DDDs/1,000 patient-days [pd]) followed by a decreasing trend in AMP during the pandemic (-5 DDDs/1,000 pd per month), neither was statistically significant. Changes in trends varied across antimicrobial classes/subclasses, with decreases in broad-spectrum penicillins (-2 DDDs/1,000 pd per month, p < .001) and macrolides/lincosamides (-2 DDDs/1,000 pd per month, p < .001) and an increase in carbapenems (1 DDD/1,000 pd per month, p < .001). These results coincided with decreases in piperacillin/tazobactam (p = .003) and azithromycin (p = .001) and an increase in meropenem (p < .001).

CONCLUSIONS: We observed a transient increase in overall AMP with the onset of the pandemic (March 2020) in this exploratory analysis of a sample of 28 hospitals. Changes in trends varied by antimicrobial class/subclass and individual agent. Further work is needed to discern contributors to these trends, such as changes in inpatient characteristics and treatment guidelines.

PMID:40673051 | PMC:PMC12253941 | DOI:10.3138/jammi-2024-0017

Trauma Surg Acute Care Open. 2025 Jul 15;10(3):e001698. doi: 10.1136/tsaco-2024-001698. eCollection 2025.

ABSTRACT

BACKGROUND: In 2003, Georgia’s trauma mortality rate was 16% above the national average. By 2020, mortality had decreased to 6% below the national average, translating to 1,803 fewer lives lost than might have been expected if 2003 trends had continued. The purpose of this study is to assess the state-wide economic impact of reduced mortality and disability measured in the amount of lifetime personal income and state tax revenue preserved.

METHODS: Using the Centers for Disease Control and Prevention’s Web-Based Injury Statistics Query and Reporting System database, state/national trauma mortality rates for 2020 were compared with 2003. Years of potential life lost (YPLL) for trauma victims up to 65 were calculated for the same time period. Rates of severe disability were calculated based on the average results of four studies (1992-2022) and used to estimate additional YPLL. The per-capita personal income for Georgia and the average percent of personal income paid in state taxes were calculated using federal and state data. These numbers were then multiplied by state YPLL rates to calculate lifetime personal income and state tax revenue lost due to trauma.

RESULTS: $4.3 billion in lifetime personal income preserved (averted death $1.3 billion and averted disability $2.9 billion). $508 million in lifetime tax revenue preserved (averted death $158 million and averted disability $349 million).

CONCLUSIONS: Reduced state trauma mortality and disability substantially benefitted lifetime potential personal income and lifetime potential state and local tax revenue. This study provides states with a template to evaluate the economic impact of reducing trauma mortality. While the causes of reduced mortality are manifold, anything that can be done to reduce trauma mortality is a worthwhile investment. Accordingly, state trauma system funding should be considered an investment, not a cost.

LEVEL OF EVIDENCE: Economic and value-based evaluations, Level III.

PMID:40673040 | PMC:PMC12265832 | DOI:10.1136/tsaco-2024-001698

Rev Bras Ginecol Obstet. 2025 Jul 15;47:e-rbgo55. doi: 10.61622/rbgo/2025rbgo55. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to evaluate the clinical and functional implications of cesarean section (CS) skin scars on women’s lives, emphasizing the relationship between scar characteristics and quality of life.

METHODS: In this cross-sectional study, women older than 18 years old who had undergone CS with a Pfannenstiel incision within the past 6-36 months were evaluated. The Patient Scar Assessment Questionnaire (PSAQ) and the Patient and Observer Scar Assessment Scale (POSAS) were used to assess clinical scar parameters. Functionality was appraised using eight questions derived from the International Classification of Functionality, Disability, and Health (ICF). The association between scar appearance scores and functionality questions was analyzed statistically.

RESULTS: Ninety-six women were assessed, revealing that appearance and satisfaction with appearance had the worst scores on the PSAQ. Scar irregularity was the most frequently reported scar characteristic on the POSAS. On the ICF-derived questionnaire, the “self-care” domain was the most affected, with women reporting problems on activities such as choosing swimwear and lingeries. There was a significant correlation (p < 0,05) between the women dissatisfaction with the scar appearance and impairment in ‘interpersonal interactions and relationships’ and ‘self-care’, as the “domestic life” domain wasn’t affected.

CONCLUSIONS: Cesarean section skin scars can lead to dissatisfaction and functional impairments, affecting women’s quality of life. These findings underscore the necessity for multidisciplinary care and thorough discussions about delivery methods to improve post-surgical outcomes.

PMID:40673039 | PMC:PMC12266858 | DOI:10.61622/rbgo/2025rbgo55

Rev Bras Ginecol Obstet. 2025 Jul 15;47:e-rbgo54. doi: 10.61622/rbgo/2025rbgo54. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to compare the plasma protein profiles between 7 preeclampsia patients with severe features (PE+) and 7 preeclampsia patients without severe features (PE-) and 10 healthy pregnancies (HP); identify differentially expressed proteins among these groups and explore the altered signaling pathways and their association with the severity of this cardiovascular condition.

METHODS: Plasma proteins were quantified using mass spectrometry, followed by comprehensive bioinformatics and statistical analyses. Protein identification and annotation were performed using UniProt and PatternLab for Proteomics. Multivariate statistical analyses, including PLS-DA and sPLS-DA, as well as VIP score evaluation and Volcano plot visualization, were conducted with MetaboAnalyst to assess group separation and identify key discriminative features. Functional enrichment and pathway analyses were carried out using Metascape.

RESULTS: Using a fold change and volcano plot validation of 1.2, comparisons between HP and PE+ revealed that proteins such as AMBP (inter-alpha trypsin inhibitor light chain), VTN (vitronectin), CLU (clusterin), F2 (prothrombin), and PZP (pregnancy zone protein) were upregulated in PE+. Conversely, ITIH4 (inter-alpha trypsin inhibitor heavy chain H4), APOL1 (apolipoprotein 1) and SERPIND1 (heparin cofactor II) were downregulated in PE+ relative to HP. When comparing HP with PE-, SERPINA3 (alpha-1-antichymotrypsin) and HBB (hemoglobin subunit beta) were downregulated in PE-. Between PE- and PE+, APCS (serum amyloid P component) and HBB were upregulated in PE+; whereas SERPINC1 (antithrombin), PSG1 (pregnancy-specific beta-1-glycoprotein 1), ITIH4, and C5 (complement C5) were downregulated in PE+ compared to PE-.

CONCLUSION: These findings offer valuable insights into the different pathophysiological mechanisms underlying the two subgroups of PE. The upregulated proteins in PE+ (AMBP, VTN, CLU, F2, PZP, APCS, and HBB) play key roles in regulating blood pressure, modulating the extracellular matrix and influencing immune responses. Overall, this research deepens our understanding of the complexity and clinical significance of PE.

PMID:40673030 | PMC:PMC12266872 | DOI:10.61622/rbgo/2025rbgo54

Rev Bras Ginecol Obstet. 2025 Jul 15;47:e-rbgo50. doi: 10.61622/rbgo/2025rbgo50. eCollection 2025.

ABSTRACT

OBJECTIVE: To evaluate the impact of São Paulo State Law n° 17.137/2019 on the cesarean section rate at a public secondary-level maternity hospital and to analyze predictive factors and complications associated with cesarean under request. This law was enacted to allow pregnant women in São Paulo to request a cesarean section without medical indication.

METHODS: This retrospective study analyzed medical records of pregnant women ≥ 39 weeks gestation attended at the Ribeirão Preto Women’s Health Reference Center (CRSMRP-Mater). Two groups were evaluated: 1,999 patients before the law (July 2018-July 2019) and 3,207 after its implementation (August 2019-July 2021, excluding the suspension period). Descriptive and analytical statistical methods were applied.

RESULTS: The overall cesarean rates increased significantly from 23.6% to 27.7% (p < 0.01), with 15,1% of cesareans during the law period being under maternal request (134 patients). A previous cesarean was the only factor significantly associated with electing a new cesarean. Hospital length of stay was significantly longer in the law period (p < 0.01), possibly reflecting the increased cesarean rate. No significant differences were observed in maternal or neonatal complications between cesareans under request and those conducted for medical reasons.

CONCLUSION: São Paulo State Law n°. 17.137/2019 was associated with an increased cesarean rate in CRSMRP-Mater. The findings highlight the need for robust educational approaches and evidence-based obstetric practices to reduce unnecessary elective cesareans.

PMID:40673026 | PMC:PMC12266855 | DOI:10.61622/rbgo/2025rbgo50