Nevin Manimala

Kidney Res Clin Pract. 2025 Nov 17. doi: 10.23876/j.krcp.24.238. Online ahead of print.

ABSTRACT

BACKGROUND: Historically, human leukocyte antigen (HLA) matching has been a cornerstone of kidney transplantation (KT), with favorable outcomes. However, the survival benefit of KT with zero HLA mismatches appears to have decreased with the accumulation of transplantation experience and advancements in immunosuppressive therapies.

METHODS: This was a prospective observational cohort study based on data from the Korean Organ Transplantation Registry, including patients who underwent deceased donor KT from May 2014 to December 2022. A total of 3,350 KT patients were propensity score-matched at a 1:1 ratio and compared according to zero HLA mismatching (zero group) vs. non-zero HLA mismatching (non-zero group).

RESULTS: After matching, 276 patients in the zero group were compared to 276 patients in the non-zero group. Over a follow-up period of 38.4 ± 28.8 months, the use of immunosuppressants was similar between the two groups. Multivariable-adjusted hazard ratios of non-zero group vs. zero group were 1.63 (95% confidence interval [CI], 0.72-3.69; p = 0.24) for death censored graft failure, 1.62 (95% CI, 0.96-2.76; p = 0.07) for biopsy-proven rejection, 2.09 (95% CI, 0.87-5.00; p = 0.10) for death, 1.38 (95% CI, 1.02-1.86; p = 0.03) for posttransplant infection and 4.48 (95% CI, 1.52-13.25; p = 0.001) for antibody mediated rejection.

CONCLUSION: This study suggests that rigid adherence to HLA matching may be less critical than previously thought, particularly due to advancements in immunosuppressive therapies.

PMID:41342160 | DOI:10.23876/j.krcp.24.238

Kidney Res Clin Pract. 2025 Dec 4. doi: 10.23876/j.krcp.25.224. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a major global public health concern. However, a major challenge in addressing the AKI burden is the lack of global data on AKI-related mortality and its predictions, leaving significant limitations in understanding its trends over time. Therefore, we aimed to estimate AKI-related mortality rate trends and forecast future deaths.

METHODS: We evaluated the temporal trends in age-standardized AKI-related mortality from 1996 to 2021 across 43 countries using the World Health Organization Mortality Database, with future projections through to 2050. Temporal trends were assessed based on age-standardized mortality rates, and future projections up to 2050 were calculated using a predictive model that considered attributable risk factors from the Global Burden of Disease Study 2021.

RESULTS: Age-standardized AKI-related mortality rate per 1,000,000 people remained stable from 1996 to 2021 (10.47 [95% confidence interval (CI), 8.84-12.11] to 9.94 [95% CI, 8.32-11.57]). Although age-standardized mortality rates were lower in high-income countries (HICs) compared to low- and middle-income countries (LMICs), HICs exhibited a modest but statistically significant increasing trend (from 5.83 per 1,000,000 people [95% CI, 4.21-7.46] to 7.30 [95% CI, 5.66-8.95]), whereas LMICs showed a declining trend (from 19.66 [95% CI, 16.78-22.53] to 15.33 [95% CI, 12.37-18.29]). Projections indicate that mortality will rise to 11.36 per 1,000,000 population (95% CI, 10.65-12.07) by 2050, primarily attributable to population aging.

CONCLUSION: This global time-series modeling study highlights rising AKI-related mortality in HICs and/or aging populations. These findings underscore the need for targeted interventions to mitigate future AKI-related deaths.

PMID:41342156 | DOI:10.23876/j.krcp.25.224

Strabismus. 2025 Dec 4:1-9. doi: 10.1080/09273972.2025.2593528. Online ahead of print.

ABSTRACT

Purpose: The aim of the study was to compare the amplitudes of negative and positive fusional vergences in exophoria and esophoria using a synoptophore and prism bar. Methods: A prospective study was conducted from May to July 2024 among university students. In participants with mild to moderate heterophoria, horizontal fusional vergence amplitudes (blur, break and recovery points) were assessed for distance using prism bar and synoptophore. Consistent testing conditions and standardized procedures were maintained. Data were analyzed using SPSS v26 with the Wilcoxon signed-rank test. p values less than 0.05 were considered as statistically significant. To assess the level of difference between values from synoptophore and prism bar, descriptive statistics was used across heterophoria grades. Results: A total of 60 participants were divided into mild (<10 PD) and moderate (>10-20 PD) exophoria and esophoria groups (n = 15 each). The values obtained from synoptophore yielded consistently higher fusional vergences than prism bar. In mild exophoria, the synoptophore had small, but statistically significant higher negative fusional vergence break point (11.8 ± 1.15 PD) than the prism bar (10.53 ± 1.55 PD, p < .05), as with the positive fusional vergence break (17.27 ± 1.75 PD vs. 15.4 ± 1.71 PD, p < .05). In mild esophoria, the synoptophore had a greater positive fusional vergence break (23.33 ± 1.05 PD) compared to the prism bar (22.33 ± 1.05 PD, p < .05). For moderate deviations, higher values for blur, break and recovery points were seen with the values obtained from synoptophore in both positive and negative fusional vergence. Conclusion: The negative and positive fusional vergences were higher when measured with the synoptophore than the prism bar in both mild and moderate deviations, consistent with earlier research and reinforcing the need for further studies to establish clinical relevance.

PMID:41342148 | DOI:10.1080/09273972.2025.2593528

JMIR Bioinform Biotechnol. 2025 Jul 11;6:e69298. doi: 10.2196/69298.

ABSTRACT

BACKGROUND: Despite being an important life-saving medical device to ensure smooth breathing in critically ill patients, the tracheal tube causes damage to the oral mucosa of patients during use, which increases not only the pain but also the risk of infection.

OBJECTIVE: This study aimed to establish finite element models for different fixation positions of tracheal catheters in the oral cavity to identify the optimal fixation position that minimizes the risk of oral mucosal pressure injury.

METHODS: Computed tomography data of the head and face from healthy male subjects were selected, and a 3D finite element model was created using Mimics 21 and Geomagic Wrap 2021 software. A pressure sensor was used to measure the actual pressure exerted by the oral soft tissue on the upper and lower lips, as well as the left and right mouth corners of the tracheal catheter. The generated model was imported into Ansys Workbench 22.0 software, where all materials were assigned appropriate values, and boundary conditions were established. Vertical loads of 2.6 N and 3.43 N were applied to the upper and lower lips, while horizontal loads of 1.76 N and 1.82 N were applied to the left and right corners of the mouth, respectively, to observe the stress distribution characteristics of the skin, mucosa, and muscle tissue in four fixation areas.

RESULTS: The mean (SD) equivalent stress and shear stress of the skin and mucosal tissues were the lowest in the left mouth corner (28.42 [0.65] kPa and 6.58 [0.16] kPa, respectively) and progressively increased in the right mouth corner (30.72 [0.98] kPa and 7.05 [0.32] kPa, respectively), upper lip (35.20 [0.99] kPa and 7.70 [0.17] kPa, respectively), and lower lip (41.79 [0.48] kPa and 10.02 [0.44] kPa, respectively; P<.001 for both stresses). The equivalent stress and shear stress of the muscle tissue were the lowest in the right mouth angle (34.35 [0.52] kPa and 5.69 [0.29] kPa, respectively) and progressively increased in the left mouth corner (35.64 [1.18] kPa and 5.74 [0.30] kPa, respectively), upper lip (43.17 [0.58] kPa and 8.91 [0.55] kPa, respectively), and lower lip (43.17 [0.58] kPa and 11.96 [0.50] kPa, respectively; P<.001 for both stresses). The equivalent stress and shear stress of muscle tissues were significantly greater than those of skin and mucosal tissues in the four fixed positions, and the difference was statistically significant (P<.05).

CONCLUSIONS: Fixation of the tracheal catheter at the left and right oral corners results in the lowest equivalent and shear stresses, while the lower lip exhibited the highest stresses. We recommend minimizing the contact time and area of the lower lip during tracheal catheter fixation, and to alternately replace the contact area at the left and right oral corners to prevent oral mucosal pressure injuries.

PMID:41342147 | DOI:10.2196/69298

J Antimicrob Chemother. 2025 Dec 4:dkaf435. doi: 10.1093/jac/dkaf435. Online ahead of print.

ABSTRACT

BACKGROUND: Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity.

OBJECTIVE: To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010-2020).

METHODS: A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin).

RESULTS: Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance.

CONCLUSIONS: Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections.

PMID:41342135 | DOI:10.1093/jac/dkaf435

Eur J Neurol. 2025 Dec;32(12):e70440. doi: 10.1111/ene.70440.

ABSTRACT

BACKGROUND: Insurance data allow insights into dispensations of medications. This retrospective study over 49 months examined dispensations of monoclonal antibodies against calcitonin gene-related peptide (CGRP-mAbs).

METHODS: Using nationwide insurance data, we examined dispensations of erenumab, fremanezumab, or galcanezumab from September 1, 2018 to September 30, 2022. We examined the duration of treatment and breaks (Kaplan-Meier curves, medians, quartiles), persistence (proportion of days covered), and switches, acute medications, and other preventatives.

RESULTS: Of 8.8 million persons, 8934 were at least once dispensed a CGRP-mAb (83.5% women, median age 45 years). Median individual follow-up time was 710 days, median duration of treatment with any CGRP-mAb was 297 days, 42.9% had CGRP-mAbs for at least 1 year. Median duration of treatment with the first-ever CGRP-mAb was 327 days; 63.4% experienced a therapy break. Within 1 year after stopping, 53.5% resumed the same CGRP-mAb, 16.9% another CGRP-mAb, 29.6% did not resume any CGRP-mAb; 13.7% started a second CGRP-mAb and 1.7% a third. 22% definitively stopped therapy within their follow-up. Dispensation of triptans decreased during and after therapy with CGRP-mAbs; dispensation of other acute prescription medications was low without change. 11.4% had other preventatives before and 2.4% during CGRP-mAb therapy. The proportion of days covered was 96%.

CONCLUSIONS: In this nationwide study persistence with CGRP-mAbs was excellent; dispensations of triptans and other preventatives decreased during CGRP-mAb therapy. Therapy breaks were common, but the majority resumed CGRP-mAbs, which indicates the need for long-term prophylaxis.

PMID:41342133 | DOI:10.1111/ene.70440

Lung Cancer. 2025 Nov 21;211:108851. doi: 10.1016/j.lungcan.2025.108851. Online ahead of print.

ABSTRACT

BACKGROUND: In an integrated analysis of phase I/II trials (STARTRK-2, STARTRK-1, ALKA-372-001), entrectinib induced responses in global populations with advanced ROS1-fusion positive (ROS1-fp) non-small cell lung cancer (NSCLC). This study reports updated efficacy and safety data in Asian patients from the integrated analysis (cutoff: 16 July 2023).

METHODS: Asian patients with ROS1 tyrosine kinase inhibitor-naïve locally advanced/metastatic ROS1-fp NSCLC, with/without central nervous system (CNS) metastasis were included. The primary endpoints were overall response rate (ORR) and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, IC-DoR, and safety. An exploratory subgroup analysis of patients naïve to systemic therapy in the metastatic setting (1L) was also investigated.

RESULTS: The efficacy-evaluable population included 99 patients. Median (range) age was 53 (20, 86) years; 32.3 % of patients had baseline CNS metastases. Confirmed ORR was 68.7 % (95 % confidence interval [CI] 58.6 %-77.6 %); median DoR was 18.6 months (95 % CI 11.1-38.5). Confirmed IC-ORR was 34.8 % (95 % CI 16.4 %-57.3 %); median IC-DoR was 9.4 months (95 % CI 6.8-not evaluable). Median time to CNS progression was 28.9 months (95 % CI 15.7-41.4). In the 1L population (n = 40), confirmed ORR was 67.5 % (95 % CI 50.9 %-81.4 %); median DoR was 38.5 months (95 % CI 11.1-not evaluable). The most frequent treatment-related adverse events were weight increased (45.9 %), constipation (40.4 %), and dysgeusia (39.4 %).

CONCLUSION: This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

PMID:41337800 | DOI:10.1016/j.lungcan.2025.108851

Hum Immunol. 2025 Dec 2;87(1):111618. doi: 10.1016/j.humimm.2025.111618. Online ahead of print.

ABSTRACT

Autoimmune thyroid disease (AITD) is among the most common autoimmune diseases, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), but their pathophysiological mechanism isn’t fully understood with multiple involved genetic factors. Programmed cell death-1 (PD-1) boosts the suppression of regulatory T cells. The promoter region polymorphism rs36084323 affected PD-1 gene transcription and activation in many cancer and autoimmune diseases. Genetic correlation between this polymorphism and AITD pathogenesis was evaluated in Egyptian patients & included: Group 1; fifty-five GD patients & forty five HT patients, Group 2; one hundred fifty controls by PCR-RFLP technique. GD patients showed significantly higher AG, AA, and A allele frequencies of the PD-1 rs36084323 gene than the control group with no significant disparities between HT patients and controls for any genotype or allele. When analyzing all AITD patients compared to control group, only the A allele showed higher frequency approaching statistical significance (p = 0.057). AA genotype and elevated free T4 were significant risk factors for GD, while elevated TSH was a significant protective factor for GD and a significant risk factor for HT. PD-1 rs36084323 polymorphism differs between GD and HT and is associated with higher risk of GD in Egyptian patients.

PMID:41337788 | DOI:10.1016/j.humimm.2025.111618

Am J Hosp Palliat Care. 2025 Dec 3:10499091251405385. doi: 10.1177/10499091251405385. Online ahead of print.

ABSTRACT

BackgroundPalliative care (PC) has the potential to alleviate symptom burden and enhance quality of life, yet use of PC among American Indians lags significantly behind whites.MethodsThis randomized clinical trial employed a randomized, complete block, posttest-only control group design to evaluate the efficacy of a culture-centric narrative video message to increase knowledge of and communication about PC among AI adults residing in three Great Plains Reservations compared to a general PC message or no message. Measures included participants’ knowledge of and intentions to discuss PC using a posttest survey.ResultsN = 320 individuals completed the survey. Both the culture-centric and general messages demonstrated statistically significant results for increasing participants’ PC knowledge compared to the no message group. The culture-centric message participants had greater odds of feeling the emotions and agreeing with the characters compared to the general message; however, there were no differences noted in intentions to discuss PC.ConclusionsThis study demonstrates the importance of messaging to improve PC knowledge and reduce misperceptions among populations with a history of mistrust of healthcare institutions. Embedding the culture’s values and ways of understanding serious illness care can serve to break down barriers in PC acceptance and provide opportunities for improving quality of life for AIs with serious illness.

PMID:41337781 | DOI:10.1177/10499091251405385

Pain Physician. 2025 Nov;28(6):E657-E665.

ABSTRACT

BACKGROUND: Low dose ketamine infusions (LDKI) may provide adequate adjuvant analgesia while reducing postoperative opioid consumption in specific populations, such as patients with opioid tolerance or high intensity postoperative pain. However, there is currently limited data on the incidence of central nervous system adverse effects such as delirium, hallucinations, agitation, sedation, or nightmares using LDKI in treating postoperative pain.

OBJECTIVES: We aimed to compare the incidence of central nervous system adverse effects in patients receiving an LDKI compared with patients not receiving an LDKI for the first postoperative 48 hours.

STUDY DESIGN: Unicentric prospective cohort comparative study.

SETTING: An academic university hospital.

METHODS: Patients older than 18 who underwent major orthopedic, abdominal, or thoracic surgery were grouped into those who received an LDKI (LDKI group, n = 101), and patients who did not receive ketamine (non-K group, n = 138) based on the responsible anesthesiologist decision. The LDKI group received a 0.1 mg/kg/h ketamine infusion as part of a multimodal analgesic plan. The primary outcome was a composite of postoperative LDKI-related central nervous system adverse effects (delirium, hallucinations, or nightmares) within the first 48 hours after exposure compared with the non-K group. The secondary outcomes were pain intensity and cardiovascular variables (blood pressure and heart rate).

RESULTS: There were no differences in cognitive dysfunction (delirium), agitation or sedation between groups (P > 0.05). The primary composite objective of central nervous system symptoms occurred in 12.9% of the LDKI group compared with 2.2% in the non-K group. The adjusted risk of psychomimetic symptoms using propensity score matching was an odds ratio of 4.84 (95% CI, 1.33 – 17.76) with a P value < 0.016. The cumulative incidence of nightmares (8.9% vs 0.72%, P = 0.001) and hallucinations (6.8% vs 2.2%, P = 0.071) were both higher in the LDKI group.Hemodynamic variables were not statistically different between groups. Pain level was significantly lower in the LDKI group (P = 0.03), however, both groups presented a mean Visual Analog Scale score below 4 mm.

LIMITATIONS: Our study is limited by its observational method, since no intervention was assigned by the investigator.

CONCLUSIONS: An LDKI (0.1 mg/kg/h) for postoperative pain is associated with a low incidence of minor central nervous system effects, i.e., nightmares and hallucinations. There is no significant association with major central nervous system adverse effects, such as delirium, sedation, or agitation, supporting its safety as an adjuvant in multimodal analgesia.

PMID:41337769