Tag: pubmed

Stat Methods Med Res. 2021 Sep 14:9622802211037071. doi: 10.1177/09622802211037071. Online ahead of print.

ABSTRACT

Ultrahigh-dimensional gene features are often collected in modern cancer studies in which the number of gene features $p$ is extremely larger than sample size $n$. While gene expression patterns have been shown to be related to patients’ survival in microarray-based gene expression studies, one has to deal with the challenges of ultrahigh-dimensional genetic predictors for survival predicting and genetic understanding of the disease in precision medicine. The problem becomes more complicated when two types of survival endpoints, distant metastasis-free survival and overall survival, are of interest in the study and outcome data can be subject to semi-competing risks due to the fact that distant metastasis-free survival is possibly censored by overall survival but not vice versa. Our focus in this paper is to extract important features, which have great impacts on both distant metastasis-free survival and overall survival jointly, from massive gene expression data in the semi-competing risks setting. We propose a model-free screening method based on the ranking of the correlation between gene features and the joint survival function of two endpoints. The method accounts for the relationship between two endpoints in a simply defined utility measure that is easy to understand and calculate. We show its favorable theoretical properties such as the sure screening and ranking consistency, and evaluate its finite sample performance through extensive simulation studies. Finally, an application to classifying breast cancer data clearly demonstrates the utility of the proposed method in practice.

PMID:34519231 | DOI:10.1177/09622802211037071

Urologia. 2021 Sep 14:3915603211046161. doi: 10.1177/03915603211046161. Online ahead of print.

ABSTRACT

AIMS: Ureteropelvic junction obstruction (UPJO) may originate from extrinsic or intrinsic causes in children. The aim of this study is to present preoperative and postoperative data of our patients operated for UPJO.

METHODS: A total of 64 patients who underwent open pyeloplasty were investigated retrospectively. They were evaluated in terms of demographically, clinics, hydronephrosis, differential renal functions (DRFs), half-time tracer clearance (½TC), and histopathologic results. Patients’ numerical results were stated as mean ± standard deviation (SD).

RESULTS: Male gender was more prevalent (n = 47, 73.4%) and mean age at surgery was 46.87 months. UPJO was located at the left side in 56.3% (n = 36), and at the right side in 39.1% (n = 25) of patients. It was bilateral in 4.7% (n = 3). Hydronephrosis was found antenatally in 68.8% (n = 44) of patients. The mean preoperative DRF was 49.7% (21-78%) and mean postoperative DRF was 49.2% (20-56%). Mean renal scintigraphic t_1/2 was >20 min for all patients. The mean AP diameter was 21.58 mm (10-62 mm). Muscular hypertrophy was the most common pathological finding, mean length of excised segment was 10.26 mm (3-40 mm). Crossing vessel (CV) was detected in 17.18% (n = 11). The CV was statistically associated with increased age of operation, left side, and female gender. Statistically significant hydronephrosis was found in non-CV patients. Re-operation was required in seven patients (7.8%).

CONCLUSIONS: Intrinsic pathologies are more seen in the etiology of UPJO patients with antenatal diagnosis and this group needs operation at an earlier age. However, CV is found more commonly in patients who are diagnosed and operated at older ages.

PMID:34519240 | DOI:10.1177/03915603211046161

Turk J Med Sci. 2021 Sep 14. doi: 10.3906/sag-2104-138. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between the activation of the renin-angiotensin system and the increase in erythropoiesis has been shown in many studies. In addition, the use of angiotensin converting enzyme inhibitors or angiotensin-receptor blockers has been reported to reduce hemoglobin levels in various patient groups at risk for secondary erythrocytosis/polycythemia.

AIMS: To investigate whether there is any change in hemoglobin levels after starting ACEI or ARB in patients who have not previously used them.

METHODS: 351 patients who were started on RAAS blockers were evaluated retrospectively. None of the patients had anemia before starting RAAS blockers. A median of 6 (4-12) months after the start of the drug, complete blood count and kidney function tests were evaluated. Hemoglobin values before and after the start of the drug were compared statistically.

RESULTS: A statistically significant decrease in mean Hb value was found after starting ACEI or ARB (14.39±1.29 g/dl vs. 13.98±1.36 g/dl, p<0.001). The decrease in control Hb values was higher in the ARB group than in the ACEI group (-0.53±0.06 g/dl vs -0.29±0.06 g/dl, p<0.001).

CONCLUSIONS: A significant decrease in mean Hb level was detected in the first year following the first administration of ACEIs or ARBs.

PMID:34519192 | DOI:10.3906/sag-2104-138

Drug Deliv. 2021 Dec;28(1):1877-1889. doi: 10.1080/10717544.2021.1974608.

ABSTRACT

Vulvovaginal candidiasis is a pervasive gynecological condition among women worldwide due to infection recurrence and resistance to conventional drugs. This calls for a novel formulation of alternative medication and with enhanced efficacy. This study aimed to fabricate mixed-lipid nanoconstructs (MLNCs) of voriconazole (VCZ) with a low concentration of lipids applying high shear homogenization and ultrasonication to form a semisolid formulation. Tefose 63 and Gelot 64 were employed as emulsifiers that are specified for vaginal preparations; as per their mucoadhesive properties and their texture enhancing characters, although usually used as lipids in different lipid carriers. A 2⁴ factorial design was established and the optimized formulation was prepared using 10% total lipids, in which solid lipids (Sterotex NF: Glyceryl monostearate) ratio was 1.92:1 and the oils percentage was 30% (Maisine: Glyceryl monooleate, in the ratio of 1:1), and the emulsifiers mixture (Tefose 63: Gelot 64) ratio was 1:1, as 10% of total formulation weight. The optimized formulation with a viscosity of 964.49 ± 57.99 cp showed spherical nanoparticles (322.72 ± 15.11 nm) that entrapped 67.16 ± 3.45% of VCZ and exhibited release of 70.08 ± 2.87% in 8 h. The optimized formulation with high bioadhesive potentials significantly reduced the fungal burden in female Wistar rats infected with vaginal candidiasis, compared to the aqueous VCZ suspension (p < .05). Furthermore, in vivo histopathological findings proved the effectiveness and the safety of the optimized MLNCs formulation after vaginal application. Inclusively, MLNCs formulation could be a promising vaginal delivery system of VCZ for the treatment of vulvovaginal candidiasis.

PMID:34519230 | DOI:10.1080/10717544.2021.1974608

Eur J Neurol. 2021 Sep 14. doi: 10.1111/ene.15103. Online ahead of print.

ABSTRACT

AIM: Many migraine patients rely on over-the-counter (OTC) analgesics for the treatment of migraine attacks. Fixed-dose combinations of aspirin, paracetamol and caffeine (APC) are used for treating migraine in many countries for a long time. We performed a meta-analysis for the comparison of APC vs placebo, which has not been done so far.

METHODS: Randomised, blinded, placebo-controlled, parallel-group studies using APC to treat a migraine attack were included in a meta-analysis. We calculated relative rates (RR) for APC compared with placebo.

RESULTS: Seven studies were included, with 3,306 participants (2,147 with APC and 1,159 with placebo). For the primary efficacy outcome pain-free at 2 h, APC was superior to placebo (19.6% vs. 9.0%, and RR = 2.2; 95%-confidence interval (CI): 1.4-3.3). For the co-primary efficacy outcome pain relief at 2 h, APC was superior to placebo (54.3% vs. 31.2%, and RR = 1.7; 95% CI: 1.6-1.9). Adverse event (AE) rates were more frequent for APC than for placebo (10.9% vs. 7.8%, and RR = 1.7, 95%-CI: 1.3-2.2).

CONCLUSIONS: APC is superior to placebo in the treatment of acute migraine attacks. The efficacy for a pain-free response and for pain relief at 2 h is clinically relevant.

PMID:34519136 | DOI:10.1111/ene.15103

Pain Pract. 2021 Sep 14. doi: 10.1111/papr.13076. Online ahead of print.

ABSTRACT

BACKGROUND: As a new technology, electronic wrist-ankle acupuncture (E-WAA) combines the advantages of wrist-ankle acupuncture and transcutaneous electrical nerve stimulation, but the analgesic effect and mechanism need to be clarified. The purpose of this study was to identify the pain modulation caused by electronic wrist-ankle acupuncture by evaluating the response of prefrontal cortex (PFC) from the perspective of neurophysiology.

METHODS: 50 male volunteers (age 25.00±1.05 years) with trapezius myofascial pain syndrome were randomly allocated into intervention group (E-WAA treatment)or sham control group at a 1:1 ratio. An outcome evaluation system was used to induce tenderness on the Jianjing point and record the pain value. A multichannel functional near-infrared spectroscope was used to detect the prefrontal cortex activation during tenderness before and after treatment to demonstrate the neuromodulation mechanism. A general linear model and t-test (p<0.05) were used to analyze the difference in the oxyhemoglobin (HbO) concentration and pain value.

RESULTS: In the intervention group, the pain value of volunteers decreased significantly (p=0.017) after E-WAA treatment, while there was no statistical difference(p=0.082) in the sham group. Before treatment, the frontopolar (FP) and dorsolateral prefrontal cortex (DLPFC)were the activation areas of the PFC. The E-WAA treatment then suppressed the activation of the two areas. The HbO concentration of the FP and DLPFC changed from a sharp rise during tenderness to not changing with tenderness stimulation.

CONCLUSION: The results demonstrated that the E-WAA have a great analgesic effect. The FP and DLPFC were relative to the analgesia neuromodulation induced by the E-WAA.

PMID:34519161 | DOI:10.1111/papr.13076

Head Neck. 2021 Sep 14. doi: 10.1002/hed.26872. Online ahead of print.

ABSTRACT

BACKGROUND: The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis.

METHODS: Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed.

RESULTS: Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient’s habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions.

CONCLUSIONS: Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.

PMID:34519124 | DOI:10.1002/hed.26872

Eur J Neurol. 2021 Sep 14. doi: 10.1111/ene.15102. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long-term rhythm monitoring. There is an unmet need for a pre-selection of CS patients benefiting from such work-up. We therefore developed a clinical risk score for the prediction of AF after CS and evaluated its performance over one year of follow-up.

METHODS: Our proposed risk score ranges from 0 to 16 points and comprises variables known to be associated with occult AF in CS patients including age, NT-proBNP, electro- and echocardiographic features (supraventricular premature beats, atrial runs, atrial enlargement, left ventricular ejection fraction) and brain imaging markers (multi-territory/prior cortical infarction). We prospectively followed all CS patients admitted to our Stroke Unit between March 2018 to August 2019 for AF detection over one year after discharge.

RESULTS: During the one-year follow-up, we diagnosed 24 (16%) out of 150 CS patients with AF (detected via ECG-controls, n=18; loop recorder-monitoring, n=6). Our predefined AF risk score (cutoff ≥4 points; highest Youden’s Index) had a sensitivity of 92% and a specificity of 67% for one-year prediction of AF. Notably, only two CS patients with <4 score points were diagnosed with AF later on (negative predictive value: 98%).

CONCLUSIONS: We here present a clinical risk score for one-year prediction of AF in CS with high sensitivity, reasonable specificity, and excellent negative predictive value. Generalizability of our score needs to be tested in external cohorts with continuous cardiac rhythm monitoring.

PMID:34519135 | DOI:10.1111/ene.15102

Histopathology. 2021 Sep 14. doi: 10.1111/his.14566. Online ahead of print.

ABSTRACT

AIMS: Emerging data support that submucosa-invasive (pT1b) esophageal adenocarcinomas are cured via endoscopic resection provided that invasion measures ≤500 microns (μm), they lack other histologic features predictive of nodal metastasis, and have negative margins. Hence, pathologists’ measurement of depth of submucosal invasion in endoscopic resections may dictate further management (i.e. endoscopic follow-up vs. esophagectomy). In this study, we assessed the interobserver agreement in measuring the depth of submucosal invasion in esophageal endoscopic resections.

METHODS AND RESULTS: Six subspecialized gastrointestinal (GI) pathologists from 5 academic centers independently measured the depth of submucosal invasion in μm from the deepest muscularis mucosae on 37 esophageal endoscopic resection slides (Round 1 scoring). A consensus meeting with a systematic approach for measuring and discussion of pitfalls was undertaken and re-measuring (Round 2 scoring) was done. Interobserver agreement was assessed by the `intraclass correlation coefficient (ICC) and Cohen’s kappa statistics. A lack of agreement was seen amongst the six reviewers with a poor ICC for both rounds: 1 [0.40, 95% CI 0.26-0.56]; 2 [ 0.49 ,95%CI 0.34-0.63]. When measurements were categorized as < or >500 μm, the overall agreement amongst the 6 reviewers was only fair for both rounds: 1[Kappa 0.37, 95% CI 0.22-0.53]; 2 [Kappa 0.29, 95%CI 0.12- 0.46].

CONCLUSIONS: Our study shows a lack of agreement among GI pathologists in measuring depth of submucosal invasion in esophageal endoscopic resections despite formulating a consensus approach for scoring. If important management decisions continue to be based upon this parameter, more reproducible and concrete guidelines are needed.

PMID:34519098 | DOI:10.1111/his.14566

Vet Dermatol. 2021 Sep 14. doi: 10.1111/vde.13022. Online ahead of print.

ABSTRACT

BACKGROUND: The pathogenesis of feline allergic dermatitis (FAD) is unclear, with several differences from allergic dermatitis in dogs and humans.

HYPOTHESIS/OBJECTIVES: To survey cytokine expression levels in healthy cats and cats affected with allergic dermatitis or asthma.

ANIMALS: Formalin-fixed, paraffin-embedded skin biopsies from 22 cats with allergic dermatitis and 21 cats without allergic dermatitis were used for cutaneous assays. Serum was obtained from 17 healthy cats, 18 cats with allergic dermatitis, and 18 cats with a presumptive diagnosis of asthma.

METHODS AND MATERIALS: Cutaneous mRNA expression was evaluated with quantitative PCR [interleukin (IL)-31 and IL-31 Receptor A] and RNA in situ hybridisation (ISH) [IL-5, IL-31, IL-31RA, IL-33 and Oncostatin M receptor (OSMR)-β]. IL-31 protein concentrations were evaluated in serum with an enzyme-linked immunosorbent assay. Serum levels of 19 additional cytokines were evaluated using a Luminex panel.

RESULTS: IL-31, IL-31RA, IL-5 and IL-33 mRNA expression were either expressed in low quantities or undetectable in most samples. By contrast, OSMR-β expression was significantly higher in the skin of allergic versus healthy cats (P < 0.0001). Although serum IL-31 was detected in a larger number of cats with allergic dermatitis than healthy cats, and concentrations appeared to be higher in cats with allergies, this difference was not statistically significant. Cats affected by asthma also exhibited insignificantly higher concentrations of IL-31 in the serum.

CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that feline allergic diseases may exhibit different pathomechanisms from allergic diseases affecting other species. These findings are useful in guiding further therapeutic development toward targets that may have a role in the pathogenesis of feline allergic skin disease.

PMID:34519120 | DOI:10.1111/vde.13022