Nevin Manimala

J Heart Lung Transplant. 2022 Aug 15:S1053-2498(22)02071-X. doi: 10.1016/j.healun.2022.08.006. Online ahead of print.

ABSTRACT

BACKGROUND: Risk scores integrate clinical variables emphasizing symptoms, exercise capacity, and measures of cardiac strain to predict clinical outcome better than any single value in pulmonary arterial hypertension (PAH). Risk scores have demonstrated prognostic utility for outcomes in registries, and recent studies have suggested that they are also therapy-responsive in controlled trials.

METHODS: FREEDOM-EV, a global, placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo. Clinical assessments were performed every 12 weeks to calculate the non-invasive French risk assessment (FRA), 4-strata COMPERA, REVEAL 2.0, and REVEAL Lite 2; median follow-up was 58 weeks. The Week 12 risk scores were used to predict time to clinical worsening (from Week 12) with Kaplan-Meier product-limit estimates. Log-rank test was used to calculate the statistical difference among risk categories, and mediation analysis tested the hypothesis that improvements in risk score contributed to reduced likelihood for clinical worsening. We assessed the previously proposed “net clinical benefit” (achievement of FRA low-risk status and absence of clinical worsening).

RESULTS: Both REVEAL scores, COMPERA, and FRA at Week 12 predicted subsequent clinical worsening better than baseline risk. Mediation analysis demonstrated that Week 12 risk score reduction explained part of TRE’s effect on clinical worsening, especially for those with higher baseline risk. TRE assigned participants were more likely to achieve the previously proposed “net clinical benefit” at Weeks 24 and beyond. Few participants who achieved ‘net clinical benefit’ had subsequent clinical worsening.

CONCLUSIONS: Contemporary risk scores were therapy responsive in FREEDOM-EV and early improvements predicted subsequent outcomes. This post hoc analysis suggests that risk scores may be a surrogate for clinical worsening.

PMID:36117055 | DOI:10.1016/j.healun.2022.08.006

J Foot Ankle Surg. 2022 Aug 9:S1067-2516(22)00229-0. doi: 10.1053/j.jfas.2022.07.008. Online ahead of print.

ABSTRACT

We examined outcomes following metatarsophalangeal joint cheilectomy with decompression osteotomy to evaluate the efficacy of this technique for treatment of hallux limitus/rigidus. At a minimum follow-up of 5 years, we identified 94 patients who fit the inclusion criteria. Chart review was performed to obtain range of motion (ROM) of the first metatarsophalangeal joint (MTPJ) preoperatively and at 6 weeks, 6 months, and 5 years postoperatively. Additionally, time to traditional shoe gear return, need for revision arthrodesis, radiographic findings, and postoperative visual analog scale (VAS) pain scores were reviewed. Statistical analysis was conducted by 1-way analysis of variance with post-hoc analysis and independent sample t-test. At an average follow-up of 6.3 ± 0.9 years, 42.3% (33/78) of females and 25.0% (4/16) of males reported limited ROM of the first MTPJ with 5 patients requiring first MTPJ arthrodesis. MTPJ ROM improved on average from 11.0° to 36.3° by 5-year minimum follow-up after surgery (p < .001). Analysis of variance revealed a significant difference of the preoperative ROM when compared to all postoperative time points (F[3,368] = 69.4, p < .001). Mean postoperative VAS pain scores after decompression osteotomy of the 5 patients who required MTPJ fusion were higher when compared to the rest of the patient cohort at final follow-up (7.4 ± 0.6 vs 1.5 ± 1.3; p < .001). Cheilectomy with decompression osteotomy for treatment of hallux limitus/rigidus leads to satisfactory long-term outcomes.

PMID:36117052 | DOI:10.1053/j.jfas.2022.07.008

Neurobiol Aging. 2022 Jul 11:S0197-4580(22)00146-4. doi: 10.1016/j.neurobiolaging.2022.07.002. Online ahead of print.

ABSTRACT

Using exome sequencing, we analyzed 196 participants of the Cretan Aging Cohort (CAC; 95 with Alzheimer’s disease [AD], 20 with mild cognitive impairment [MCI], and 81 cognitively normal controls). The APOE ε4 allele was more common in AD patients (23.2%) than in controls (7.4%; p < 0.01) and the PSEN2 p.Arg29His and p.Cys391Arg variants were found in 3 AD and 1 MCI patient, respectively. Also, we found the frontotemporal dementia (FTD)-associated TARDBP gene p.Ile383Val variant in 2 elderly patients diagnosed with AD and in 2 patients, non CAC members, with the amyotrophic lateral sclerosis/FTD phenotype. Furthermore, the p.Ser498Ala variant in the positively selected GLUD2 gene was less frequent in AD patients (2.11%) than in controls (16%; p < 0.01), suggesting a possible protective effect. While the same trend was found in another local replication cohort (n = 406) and in section of the ADNI cohort (n = 808), this finding did not reach statistical significance and therefore it should be considered preliminary. Our results attest to the value of genetic testing to study aged adults with AD phenotype.

PMID:36117051 | DOI:10.1016/j.neurobiolaging.2022.07.002

Dent Traumatol. 2022 Sep 18. doi: 10.1111/edt.12790. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Evidence on the risk of injury at concerts is scant. The aim of this study was to collect data on general and dental injuries incurred by concertgoers in Switzerland and to investigate whether the frequency of accidents was related to music genre, gender and consumption of alcohol.

MATERIALS AND METHODS: A questionnaire-based, cross-sectional study comprising 451 concertgoers in Switzerland was conducted on the timeframe January 2019 to February 2021. The survey gathered data on general and dental injuries, alcohol consumption and drug use. The statistical analysis included Fisher’s exact tests, chi-squared tests, rank sum tests and logistic regressions (α = .05).

RESULTS: There were 28.8% of respondents who reported an injury incurred at a concert. Contusion was the most prevalent injury, accounting for 33.8% of all injuries. Legs were the most commonly injured body part (34.6%). Injuries to their mouth/lips/teeth were reported by 17.7% of respondents. Dental injuries, accounting for 4.6% of all reported injuries, comprised four tooth fractures, one lateral luxation and one avulsion. The risk of injury while attending punk rock concerts was 8.6 times higher than for pop concerts (p < .001). In comparison with pop concerts, metal and rock concerts had an increased risk of injury by factors of 5.1 and 2.3, respectively (p ≤ .029). Neither gender nor drug use had a significant effect on the injury risk (p ≥ .3). Heavy alcohol consumption (>5 standard glasses) increased the risk of injury by a factor of 2.3 (p = .028).

CONCLUSIONS: This study suggests that concert attendees at rock, metal and punk concerts face an increased risk of injury, which is likely due to the frequency of aggressive dance styles such as moshing. Heavy alcohol consumption leads to a greater risk of injury at concerts.

PMID:36116120 | DOI:10.1111/edt.12790

Chemistry. 2022 Sep 18. doi: 10.1002/chem.202200947. Online ahead of print.

ABSTRACT

Transmission electron microscopy (TEM) observations of negatively stained cell membrane (CM)-coated polymeric nanoparticles (NPs) reveal a characteristic core-shell structure. However, negative staining agents can create artifacts that complicate the determination of the actual NP structure. Herein, we demonstrate with various bare polymeric core NPs, such as poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) methyl ether-block-PLGA, and poly(caprolactone), that certain observed core-shell structures are actually artifacts caused by the staining process. To address this issue, we use fluorescence quenching to quantify the proportion of fully coated NPs and use statistical TEM analysis to identify and differentiate whether the observed core-shell structures of CM-coated PLGA (CM-PLGA) NPs are due to artifacts or to the CM coating. Integrated shells in TEM images of negatively stained CM-PLGA NPs are identified as artifacts. The present results challenge current understanding of the structure of CM-coated polymeric NPs and encourage researchers should use the proposed characterization approach to avoid misinterpretations.

PMID:36116117 | DOI:10.1002/chem.202200947

Exp Physiol. 2022 Sep 18. doi: 10.1113/EP090749. Online ahead of print.

ABSTRACT

NEW FINDINGS: What is the central question of this study? To determine whether the plasma concentration of Notch1 extracellular domain is altered in response to decreased and increased vascular wall shear stress in the forearm, in humans. What is the main finding and its importance? Notch1 extracellular domain is increased with acute increases in antegrade shear rate but does not change with 20 minutes of decreased shear rate caused by distal forearm occlusion. We in turn characterize a novel and integral endothelial mechanosensor in humans that can help explain vascular endothelial adjustments in response to increases in antegrade shear stress.

ABSTRACT: Notch1 has been proposed as a novel endothelial mechanosensor that is central for signalling adjustments in response to changes in vascular wall shear stress. However, there remains no controlled in vivo study in humans. Accordingly, we sought to address the question of whether plasma concentrations of Notch1 extracellular domain (ECD) is altered in response to transient changes in vascular wall shear stress. In 10 young healthy adults (6 M/4F), alterations in shear stress were induced by supra-systolic cuff inflation around the wrist. The opposite arm was treated as a time control with no wrist cuff inflation. Plasma was collected from an antecubital vein of both arms at baseline, 20-min of wrist cuff inflation (low shear), as well as 1-2 min (high shear) and 15-min following wrist cuff release (recovery). The Notch1 ECD was quantified using a commercially available ELISA. Duplex ultrasound was used to confirm alterations in shear stress. In the experimental arm, concentrations of Notch1 ECD remained statistically similar to baseline at all time points except for immediately following cuff release where it was elevated by ∼50% (P = 0.033), coinciding with the condition of high antegrade shear rate. Concentrations of Notch1 ECD remained unchanged in the control arm through all time points. These data indicate that Notch1 is a viable biomarker for quantifying mechanotransduction in response to increased shear stress in humans, and it may underlie the vascular adaptations or mal-adaptations associated with conditions that impact antegrade shear. This article is protected by copyright. All rights reserved.

PMID:36116111 | DOI:10.1113/EP090749

Dent Traumatol. 2022 Sep 18. doi: 10.1111/edt.12789. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: In case of crown fractures after traumatic dental injuries, the affected teeth can be restored either with reattachment of the fractured fragment or with a direct composite restoration. So far, longevity data for reattachments and direct composite restorations with regard to different failure types (pulp necrosis and infection, restoration loss) are scarce. Therefore, the aim of this retrospective study was to evaluate the restorative and biological survival of reattached fragments and composite restorations after crown fractures in permanent teeth.

MATERIAL AND METHODS: Dental records of patients treated between 2000 and 2018 were retrospectively analysed regarding the restoration (reattachment or direct composite restorations) of teeth with crown fractures. Survival (no further intervention) and restorative and/or biological failure of all restored teeth were recorded. Statistical analysis was performed using Kaplan-Meier statistics, and the mean annual failure rates for two and 5 years were calculated. Furthermore, the effect of potential risk factors on survival was assessed. Log-rank tests and univariate Cox regression models (likelihood ratio tests) were used to assess the univariate effect of all variables of interest. Variables with a p-value ≤.10 were included in a multivariate Cox regression model with shared frailty (p < .05).

RESULTS: Overall, 164 patients with 235 teeth (uncomplicated crown fracture: N = 201, complicated crown fracture: N = 34) were included (1.6 ± 2.5 years observation time). Of these, 59 teeth were restored with reattachment of the fragment and 176 with a composite restoration. Overall, composite restorations had a significantly higher survival rate than reattachments (p = .002). The cumulative survival after 2 years was 42.9% and 65.0% for teeth treated with a reattachment (mAFR = 34.5%) and a composite restoration (mAFR = 19.3%), respectively. When differentiating between failure types, restoration failure and pulp necrosis were significantly more frequently detected in reattached crown fractures compared to composite restorations (restorative failure: p = .001; biological failure: p = .036). In the multivariate Cox regression model, the variable jaw and luxation significantly influenced the survival when the tooth was restored with a composite restoration. The survival was not influenced by the fracture type.

CONCLUSIONS: Restorative and biological failures were more frequently detected when the tooth was restored with a reattached fragment compared to a direct composite restoration. Both, restoration failure and pulp necrosis with infection should be considered as frequent complications after restoration of crown-fractured teeth which emphasizes the necessity of regular and short follow-up intervals throughout the first 2 years.

PMID:36116107 | DOI:10.1111/edt.12789

Aust Endod J. 2022 Sep 18. doi: 10.1111/aej.12691. Online ahead of print.

ABSTRACT

Successful root canal treatment requires effective irrigation of the entire root canal system. While chelating agents support irrigation, they can also alter physicochemical properties of the root dentin structure. The aim of this study is to evaluate the effect of different chelation agents on root dentin roughness. Twenty-five extracted maxillary incisors were used in this study. Samples were separated longitudinally and divided into five groups: distilled water, NaOCl, ethylenediaminetetraacetic acid (EDTA), phytic acid and citric acid (CA). Atomic force microscope and energy dispersive X-ray spectroscopy analyses were used for analysing. One-way analysis of variance and Turkey tests were used in the statistical analysis of the study. EDTA, CA and phytic acid solutions increased the roughness and phytic acid and CA solutions decreased the Ca/P ratio in dentin tissue. No statistical difference was observed in the other groups. The decrease of Ca/P ratio should be taken under consideration during irrigation. The increase in surface roughness may provide clinical benefit by supporting the adhesion of the root canal filling materials to the dentin surface.

PMID:36116094 | DOI:10.1111/aej.12691

Updates Surg. 2022 Sep 18. doi: 10.1007/s13304-022-01376-5. Online ahead of print.

ABSTRACT

To evaluate the short- and long-term survival of hyperthermic intraperitoneal chemotherapy (HIPEC) in the patients with advanced gastric cancer (AGC) through randomized controlled trials (RCTs). We analyzed the endpoints of AGC patients including 1-, 2-, 3-, and 5-year overall survival (OS), intestinal anastomotic leakage, myelosuppression, nausea and vomiting from included studies. And we retrieved RCTs from medical literature databases. Risk ratios (RR) was used to calculated the endpoints. Totally, we retrieved 13 articles (14 trial comparisons) which contained 1091 patients. They were randomized to HIPEC group and control group. The results showed that there was no significant differences in survival rates between HIPEC group and control group at 1-, 2- and 3-year follow-up, while a statistical significant overall survival effect was found at the 5-year follow-up [RR: 1.20, 95% CI 1.01 to 1.43, I² = 0.0%]. And there is no significant difference in the risk of intestinal anastomotic leakage, myelosuppression and nausea and vomiting. Compared with the control group, HIPEC could improve the long-term OS without increasing the risk of adverse effect in AGC patients with/without peritoneal carcinomatosis, but there was no benefit at short-term OS.

PMID:36116077 | DOI:10.1007/s13304-022-01376-5

Cancer Causes Control. 2022 Sep 18. doi: 10.1007/s10552-022-01626-2. Online ahead of print.

ABSTRACT

PURPOSE: Neighborhood environments may influence cancer risk. Average population effect estimates might mask differential effects by socioeconomic position. Improving neighborhood environments could inadvertently widen health inequalities if important differences are overlooked.

METHODS: Using linked records of hospital admissions in UK Biobank, we assessed associations between admission with a primary diagnosis of cancer (any/breast/colorectal), and exposure to neighborhood greenspace, physical activity facilities, and takeaway food stores, and whether household income and area deprivation modify these associations. We used adjusted Cox proportional hazards models, and estimated relative excess risks due to interaction (RERI) to assess effect modification.

RESULTS: Associations between neighborhood exposures and cancer-related hospitalizations were weak to null overall, but with some evidence of effect modification. Most notably, more greenspace near home was associated with 16% lower hazard of cancer-related hospital admission in deprived areas (95% CI 2-29%). This was further pronounced for people in low-income households in deprived areas, and for breast cancer.

CONCLUSION: In deprived neighborhoods, increasing the amount of greenspace may help reduce cancer-related hospitalizations. Examining effect modification by multiple socioeconomic indicators can yield greater insight into how social and environmental factors interact to influence cancer incidence. This may help avoid perpetuating cancer inequalities when designing neighborhood environment interventions.

PMID:36116076 | DOI:10.1007/s10552-022-01626-2