Nevin Manimala

Eur Rev Med Pharmacol Sci. 2024 Feb;28(4):1314-1326. doi: 10.26355/eurrev_202402_35453.

ABSTRACT

OBJECTIVE: Pulmonary arterial hypertension (PAH) represents an important vascular complication of mixed connective tissue disease (MCTD) and systemic sclerosis (SSc). Microvascular involvement in these diseases can be investigated by means of nailfold capillaroscopy (NFC). Microvascular involvement detected in the nailfold bed is the mirror of the microvascular damage occurring in the entire body, further indicating the involvement of the target organs. The aim of this study was to evaluate the microvascular involvement in MCTD patients with or without PAH, compared to that found in SSc patients with or without PAH.

PATIENTS AND METHODS: This cross-sectional study was performed in the Department of Internal Medicine and Department of Rheumatology, Timișoara, Romania, during the time period between January 2017 and December 2022, on a group of 26 patients with MCTD and 26 SSc patients. Antinuclear antibodies, anti-U1-RNP, anti-Scl 70, anti-centromere, anti-cardiolipin antibodies (aCL) (IgM, IgG), anti-β2-glycoprotein I (aβ2GPI) (IgM, IgG) antibodies, and lupus anticoagulant (LAC) were determined in both the groups. PAH was evaluated through cardiac ultrasonography, determining the sPAP (systolic pulmonary artery pressure). Nailfold capillaroscopy was performed using a USB Digital Microscope and 2.0-megapixel digital camera recording capillaries density, giant capillaries, enlarged capillaries, capillaries hemorrhages, avascular areas, ramified/bushy capillaries scores. Data were recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student’s t-test, ANOVA test, and Pearson’s correlation. Differences were considered statistically significant if p-value < 0.05.

RESULTS: Among the MCTD patients, PAH was identified in 12 patients (46.15%), while among the SSc patients PAH was identified in 14 patients (53.84%). Development of PAH in MCTD patients was associated with lower capillaries density (p-value < 0.00001), higher scores of giant capillaries, ramified/bushy capillaries, and capillary hemorrhages (p-value < 0.00001, for each of them). Anti-U1-RNP, aCL, aβ2GPI antibodies and LAC were also found to be involved in PAH-associated MCTD development. Unlike MCTD patients, SSc patients with PAH presented with lower capillaries density and ramified/bushy capillaries scores (p-value < 0.05).

CONCLUSIONS: The MCTD patients who presented significant NFC abnormalities (especially active and late scleroderma-like capillaroscopic pattern) are prone to PAH development. Capillary density reduction is the most important factor associated with the occurrence of PAH. Differences in NFC findings (especially capillary density and ramified/bushy capillaries) were detected among patients with MCTD and SSc having PAH.

PMID:38436165 | DOI:10.26355/eurrev_202402_35453

Lasers Surg Med. 2024 Mar 4. doi: 10.1002/lsm.23775. Online ahead of print.

ABSTRACT

OBJECTIVES: Subcutaneous mastectomy is a crucial component of gender affirmation therapy for transgender men (TM), but the scars that result from this procedure can frequently impair their quality of life. This study aimed to assess the efficacy and safety of 1064-nm fractional picosecond laser (FxPico) treatment for hypertrophic and atrophic postmastectomy scars in TM.

METHODS: Twenty-two patients with a total of 35 pairs of bilateral symmetric mastectomy scars were enrolled. One of each pair of symmetric scars was randomly assigned to receive four FxPico treatments at 4-week intervals. All scars were evaluated using the modified Vancouver Scar Scale (mVSS) and three-dimensional imaging for scar roughness, melanin index, and hemoglobin index before each treatment session and at 1, 3, and 6 months following the last treatment. Additionally, participant-rated scar satisfaction (PSS) and scar improvement (Global Assessment Score, GAS), as well as adverse events were recorded.

RESULTS: During the 6-month follow-up period after the end of laser treatment sessions, the treated scars showed significant reductions in the mVSS compared to the untreated controls (p < 0.001), whereas the melanin index and hemoglobin index were not significantly different. Subgroup analysis of hypertrophic scars demonstrated statistically significant reductions in mVSS at 1 (p = 0.003) and 3 months (p = 0.041) after the end of laser treatments. PSS was significantly higher on the laser-treated scars than the controls (p = 0.008), and a participant-rated GAS of 2.95 ± 0.65 was found. There were no serious adverse events reported.

CONCLUSIONS: 1064-nm FxPico could be utilized to treat mastectomy scars among TM, particularly the hypertrophic type.

PMID:38436118 | DOI:10.1002/lsm.23775

Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241234790. doi: 10.1177/15330338241234790.

ABSTRACT

Background: Hepatocellular carcinoma is frequently diagnosed in advanced stages, leading to a poorer prognosis. Therefore, early diagnosis and identification of biomarkers may significantly improve outcomes. Methods: This cross-sectional study enrolled 486 participants distributed among 3 groups: F1 to F3 = 184, F4 = 183, and hepatocellular carcinoma = 119. Liver fibrosis staging was performed using FibroScan, while imaging features were used for hepatocellular carcinoma detection. Epithelial membrane antigen and cytokeratin-1 levels in serum were quantified through Western blot and ELISA, respectively. Results: Patients diagnosed with hepatocellular carcinoma exhibited significantly elevated levels of epithelial membrane antigen and cytokeratin-1 compared to non-hepatocellular carcinoma patients, with a highly significant statistical difference (P < .0001). Epithelial membrane antigen demonstrated diagnostic performance with an area under the curve of 0.75, a sensitivity of 69.0%, and a specificity of 68.5%. Cytokeratin-1 for the identification of hepatocellular carcinoma showed a sensitivity of 79.0% and a specificity of 81.4%, resulting in an area under the curve of 0.87. The developed HCC-Check, which incorporates epithelial membrane antigen, cytokeratin-1, albumin, and alpha-fetoprotein, displayed a higher area under the curve of 0.95 to identify hepatocellular carcinoma, with a sensitivity of 89.8% and a specificity of 83.9%. Notably, HCC-Check values exceeding 2.57 substantially increased the likelihood of hepatocellular carcinoma, with an estimated odds ratio of 50.65, indicating a higher susceptibility to hepatocellular carcinoma development than those with lower values. The HCC-Check diagnostic test exhibited high precision in identifying patients with hepatocellular carcinoma, particularly those with small tumor sizes (<5 cm) and a single nodule, as reflected in area under the curve values of 0.92 and 0.85, respectively. HCC-Check was then applied to the validation study to test its accuracy and reproducibility, showing superior area under the curves for identifying different stages of hepatocellular carcinoma. These outcomes underscore the effectiveness of the test in the early detection of hepatocellular carcinoma. Conclusion: The HCC-Check test presents a highly accurate diagnostic method for detecting hepatocellular carcinoma in its early stages.

PMID:38436112 | DOI:10.1177/15330338241234790

Disabil Rehabil Assist Technol. 2024 Mar 4:1-11. doi: 10.1080/17483107.2024.2323698. Online ahead of print.

ABSTRACT

Assistive technology (AT) represents one way to improve access and participation in the school and home environments of people with disabilities (PWDs). This study analyzed the obstacles to AT acquisition, knowledge, use, recommendation, and training in special needs centers in the United Arab Emirates (UAE) from the perspective of professionals (teachers and therapists). A questionnaire was developed and its validity and reliability were confirmed. The questionnaire was distributed to all special-needs centers in the UAE via Survey Monkey, and 78 responses were received. The results indicate the nature of obstacles to AT use in special education centers in the UAE, with obstacles related to parents having the highest mean. The results also indicated a statistically significant difference in professionals’ perception of obstacles to using AT based on experience level, center location, and level of education. Implications for further research and recommendations for policy and practice are provided.

PMID:38436086 | DOI:10.1080/17483107.2024.2323698

Circ Cardiovasc Interv. 2024 Mar 4:e013581. doi: 10.1161/CIRCINTERVENTIONS.123.013581. Online ahead of print.

ABSTRACT

BACKGROUND: Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers.

METHODS: We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25-49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg).

RESULTS: The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (P<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (P=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (P=0.141) or adjusted (P=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (P=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (P=0.017) or adjusted (P=0.015) analysis.

CONCLUSIONS: TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.

PMID:38436084 | DOI:10.1161/CIRCINTERVENTIONS.123.013581

Pediatr Hematol Oncol. 2024 Mar 4:1-14. doi: 10.1080/08880018.2024.2324394. Online ahead of print.

ABSTRACT

To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10-23 days), and for platelets, it was 15 days (range: 11-28 days). Acute GVHD of Grade I-II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4-140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.

PMID:38436082 | DOI:10.1080/08880018.2024.2324394

Expert Rev Anticancer Ther. 2024 Mar 4:1-13. doi: 10.1080/14737140.2024.2325404. Online ahead of print.

ABSTRACT

OBJECTIVES: Neoadjuvant immunotherapy has emerged as a prominent research focus recently. For potentially operable patients, neoadjuvant therapy serves as a primary method to reduce tumor load and facilitate surgical interventions.

METHODS: We retrieved articles from PubMed, Embase, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology websites from inception to December 2023. Statistical analyses were performed using the R software. Primary outcomes assessed included major pathological response (MPR), pathological complete response (pCR), and treatment-related adverse events (trAEs).

RESULTS: 29 studies encompassing 1163 patients were included. The MPR rate of neoadjuvant combination immunotherapy was 38% (95% confidence interval [CI]: 25%-52%), and the pCR rate was 33% (95%CI: 25%-42%). These values were significantly higher than those obtained with single agent immunotherapy (p < 0.001). The pooled incidence of overall trAEs was 83% (95%CI: 73%-92%), and grade (G) 3-4 trAEs was 22% (95%CI: 15%-29%), both significantly higher than those observed with single agent immunotherapy (p < 0.05).

CONCLUSION: This study demonstrated the efficacy of neoadjuvant combination immunotherapy. Given that the majority of the included trials were phase II with small sample sizes, further multicenter phase III randomized controlled trials should be conducted to validate the findings of the review.

PMID:38436076 | DOI:10.1080/14737140.2024.2325404

Coron Artery Dis. 2024 Mar 4. doi: 10.1097/MCA.0000000000001352. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse cardiac events are common in older patients with non-ST elevation acute coronary syndrome (NSTEACS), yet prognostic predictors are still lacking. This study investigated the long-term prognostic significance of non-invasive measures including endothelial function, carotid intima-media thickness (CIMT), and vascular stiffness in older NSTEACS patients referred for invasive treatment.

METHODS: NSTEACS patients aged 75 years and older recruited to a multicentre cohort study (NCT01933581) were assessed for baseline endothelial function using endoPAT logarithm of reactive hyperemia index (LnRHI), CIMT using B-mode ultrasound, and vascular stiffness using carotid-femoral pulse wave velocity (cfPWV). Long-term outcomes included major adverse cardiovascular events (MACE), a composite of death, reinfarction, urgent revascularization, stroke/transient ischemic attack, and significant bleeding.

RESULTS: Recruitment resulted in 214 patients assessed for LnRHI, 190 patients assessed for CIMT and 245 patients assessed for cfPWV. For LnRHI group (median follow-up 4.73 years [IQR: 1.41-5.00]), Cox regression analysis revealed a trend towards increased risk of MACE (HR: 1.24 [95% CI: 0.80-1.93]; P = 0.328) and mortality (HR: 1.49 [95% CI: 0.86-2.59]; P = 0.157), but no significance was reached. No difference for other components of MACE was found. For CIMT group (median follow up 4.74 years [IQR: 1.55-5.00]), no statistically significant difference in MACE was found (HR: 0.92 [95% CI: 0.53-1.59]; P = 0.754). Similarly, for cfPWV group (median follow-up 4.96 years [IQR: 1.55-5.00]), results did not support prognostic significance (for MACE, HR: 0.95 [95% CI: 0.65-1.39]; P = 0.794).

CONCLUSION: Endothelial function, CIMT and vascular stiffness were proven unsuitable as strong prognostic predictors in older patients with NSTEACS.

CLINICAL TRIAL REGISTRATION: NCT01933581.

PMID:38436050 | DOI:10.1097/MCA.0000000000001352

Sports Health. 2024 Mar 4:19417381241230612. doi: 10.1177/19417381241230612. Online ahead of print.

ABSTRACT

BACKGROUND: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex.

HYPOTHESIS: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients.

STUDY DESIGN: Cross-sectional study.

LEVEL OF EVIDENCE: Level 4.

METHODS: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest.

RESULTS: The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups.

CONCLUSION: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients.

CLINICAL RELEVANCE: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.

PMID:38436049 | DOI:10.1177/19417381241230612

PeerJ. 2024 Feb 28;12:e17034. doi: 10.7717/peerj.17034. eCollection 2024.

ABSTRACT

The use of pesticides to control pests, weeds, and diseases or to regulate plant growth is indispensable in agricultural production. However, the excessive use of these chemicals has led to significant concern about their potential negative impacts on health and the environment. Phosmet is one such pesticide that is commonly used on plants and animals against cold moth, aphids, mites, suckers, and fruit flies. Here, we investigated the effects of phosmet on a model organism, Daphnia magna using acute and chronic toxicity endpoints such as lethality, mobility, genotoxicity, reproduction, and gene expression. We performed survival experiments in six-well plates at seven different concentrations (0.01, 0.1, 1, 10, 25, 50, 100 μM) as well as the control in three replicates. We observed statistically significant mortality rates at 25 µM and above upon 24 h of exposure, and at 1 µM and above following 48 h of exposure. Genotoxicity analysis, reproduction assay and qPCR analysis were carried out at concentrations of 0.01 and 0.1 μM phosmet as these concentrations did not show any lethality. Comet assay showed that exposure to phosmet resulted in significant DNA damage in the cells. Interestingly, 0.1 μM phosmet produced more offspring per adult compared to the control group indicating a hormetic response. Gene expression profiles demonstrated several genes involved in different physiological pathways, including oxidative stress, detoxification, immune system, hypoxia and iron homeostasis. Taken together, our results indicate that phosmet has negative effects on Daphnia magna in a dose- and time-dependent manner and could also induce lethal and physiological toxicities to other aquatic organisms.

PMID:38436013 | PMC:PMC10908259 | DOI:10.7717/peerj.17034