Tag: pubmed

Audiol Neurootol. 2022 Mar 28:1-8. doi: 10.1159/000522566. Online ahead of print.

ABSTRACT

INTRODUCTION: The rates of cochlear nerve abnormalities and cochlear malformations in pediatric unilateral hearing loss (UHL) are conflicting in the literature, with important implications on management. The aim of this study was to investigate the incidence of cochlear nerve deficiency (CND) in pediatric subjects with UHL or asymmetric hearing loss (AHL).

METHODS: A retrospective chart review of pediatric subjects <18 years of age evaluated for UHL or AHL with fine-cut heavily T2-weighted magnetic resonance imaging (MRI) between January 2014 and October 2019 (n = 291) at a tertiary referral center was conducted. MRI brain and computed tomography temporal bone were reviewed for the presence of inner ear malformations and/or CND. Status of the ipsilateral cochlear nerve and inner ear was evaluated. Pure tone average (PTA) at 500, 1,000 and 2,000 Hz was assessed.

RESULTS: 204 subjects with UHL and 87 subjects with AHL were included. CND (aplasia or hypoplasia) was demonstrated in 61 pediatric subjects with UHL (29.9%) and 10 with AHL (11.5%). Ipsilateral cochlear malformations were noted in 25 subjects with UHL (12.3%) and 11 with AHL (12.6%), and ipsilateral vestibular malformations in 23 (11.3%) and 12 (13.8%) ears, respectively. Median PTA was statistically significantly higher in ears with CND (98.33) than ears with normal nerves (90.84).

DISCUSSION/CONCLUSION: Imaging demonstrated a high incidence of inner ear malformations, particularly CND, in pediatric subjects with UHL. Auditory findings indicated CND cannot be ruled out by thresholds alone as some CND ears did demonstrate measurable hearing. Radiologic evaluation by MRI should be performed in all patients within this population to guide counseling and management of hearing loss based on etiology, with implications on candidacy for cochlear implantation.

PMID:35344959 | DOI:10.1159/000522566

Oncology. 2022 Mar 28. doi: 10.1159/000524340. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with hormone receptor positive metastatic breast cancer, Palbociclib has been shown to improve overall survival and progression-free survival (PFS) when combined with endocrine therapy. Dose modification of palbociclib is effective in the management of adverse events. Despite variable clinical response, no predictive biomarkers of efficacy to palbociclib have been identified in metastatic breast cancer. In our study, we aimed to assess the PFS of metastatic breast cancer patients who received dose-reduced palbociclib and compare the results in the non-dose reduced group. We also evaluated the clinical significance of progesterone receptor (PR) and Ki67 as predictive biomarkers of palbociclib.

METHODS: Seventy-six palbociclib-treated metastatic breast cancer patients were included in our study. PFS was compared between dose reduced and non-dose reduced groups. PR expression and Ki67 status were assessed by immunohistochemistry (IHC). Kaplan-Meier method and log-rank test were used to analyze PFS.

RESULTS: Of the 76 patients, 40 (52.6%) experienced dose reduction. Statistical analysis of the results revealed that there were no statistically significant differences observed between dose-reduced (16.5 months) vs non-dose reduced (17.7 months) patients in PFS (p=0.5493). For patients with Ki67 ≥ 14%, PFS was 15.2 months (95% CI: 10.2 to 22.2 months; p= 0.3024). In patients with PR ≥ 20%, median PFS was 25.0 months (lower 95% CI: 16.8 months; p=0.0069).

CONCLUSION: Our study indicated that dose reduction of palbociclib is frequently required but does not appear to affect PFS. PR expression was suggested to be a significant predictive factor for palbociclib responsiveness.

PMID:35344965 | DOI:10.1159/000524340

Tuberculosis (Edinb). 2022 Mar 18;134:102198. doi: 10.1016/j.tube.2022.102198. Online ahead of print.

ABSTRACT

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, ‘heals the host; ‘ but does not ‘kill the bug.’

PMID:35344918 | DOI:10.1016/j.tube.2022.102198

Eur J Radiol. 2022 Mar 9;150:110227. doi: 10.1016/j.ejrad.2022.110227. Online ahead of print.

ABSTRACT

PURPOSE: To determine the normal thickness and MRI appearance of the Tibialis Posterior Tendon near the navicular insertion in normal volunteers.

MATERIALS AND METHODS: By using a 3T MRI system 41 ankles were imaged, and PD weighted images with fat saturation were acquired in the three orthogonal planes. Symptoms of tendon pathology and history of trauma or surgery of the tendon were used as volunteer exclusion criteria. Two different measurement points were determined to evaluate hyperintensity and thickness. Two radiologists assessed the internal signal of the Tibialis Posterior Tendon independently by using axial and coronal images. Tendon hyperintensity was classified from homogenously dark to different degrees of hyperintense signal, where 0 means no internal hyperintensity, 1 – minimal hyperintensity, 2 – moderate and 3 – marked. Correlations between the two observers were obtained by Cohen’s kappa. Descriptive statistics were also obtained.

RESULTS: Eight men and 13 women (total 21) volunteers, age range 19-43(average 24.7)years were included in the study. At measurement point-1 on the coronal images, observer-1 and observer-2 evaluated hyperintensity (mostly minimal) respectively in 90.5% and 95.3% of tendons with a Cohen’s kappa coefficient of 0.701 (moderate agreement) for the right foot and in 60% and 70% of tendons with a Cohen’s kappa coefficient of 0.624 (moderate agreement) for the left foot. On axial images both observers assessed hyperintensity (mostly marked) in 100% of the tendons with a coefficient of 0.763 (moderate agreement) for the right foot, and in 95% of tendons with a coefficient of 0.839 (strong agreement) for the left foot. At measurement point-2 on coronal images, both observers rated any degree of hyperintensity in 33.3% of tendons with a coefficient of 1.00 (perfect agreement) for the right foot, in 38.9% of tendons with a coefficient of 0.766 (moderate agreement) for the left foot. On axial images both observers evaluated hyperintensity (mostly minimal) in 100% of tendons with a kappa coefficient of 0.702 (moderate agreement) for the right foot, in 95% of tendons with a coefficient of 0.790 (moderate- to strong agreement) for the left foot.

CONCLUSION: The Tibialis Posterior Tendon, near the navicular insertion (navicular tendon and tarsometatarsal tendon), exhibits an apparent thickening and most importantly hyperintensity which should be regarded as a normal finding, and not lead to an erroneous diagnosis of tendinopathy. This observation was almost always the case for the navicular insertion and less so for the tarsometatarsal tendon.

PMID:35344915 | DOI:10.1016/j.ejrad.2022.110227

Mult Scler Relat Disord. 2022 Mar 15;61:103743. doi: 10.1016/j.msard.2022.103743. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple Sclerosis (MS) is a chronic debilitating neurological disease affecting young adults. The disease involves immune-mediated demyelination of nerve fibers and neurons that leads to disruption of brain-body communication, leading to permanent nerve damage. MS-associated retrovirus envelope protein (MSRV-Env) has been detected in the blood and lesions of MS patients, and its role is suggested in the pathogenesis of MS. Temelimab is a humanized IgG4 monoclonal antibody (mAb) that targets the MSRV-Env protein and neutralizes its action. Several clinical trials have been conducted to evaluate the effectiveness of the drug in MS.

MATERIALS AND METHODS: A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 11th sept 2021. All statistical analysis was conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. Those studies were selected which compared Temelimab therapy to inactive control. The primary outcome of interest was drug safety and efficacy; information about immunogenicity was also included. Random-effect model was used to pool the studies, and the result was reported in the risk ratio (RR) with corresponding 95% Confidence interval (CI).

RESULTS: Phase I, Phase II-a and Phase II-b trials demonstrate the safety and effectiveness of Temelimab. Our analysis showed statistically non-significant Risk Ratio (RR) of Adverse events in Temelimab group than that in placebo group (1.01 [0.70,1.46]; p-value = 0.94; I² = 0%) . Considering the effect of Temelimab on brain lesions, pooled result showed statistically significant Risk Ratio (RR) of brain lesions in placebo group than that in Temelimab group (0.75 [0.69,0.81), p-value < 0.00001, I² = 0% CONCLUSION: Qualitative and quantitative analysis of the trials assessing the safety and efficacy of Temelimab demonstrate that the drug is safe as well as favourable for use in MS patients.

PMID:35344907 | DOI:10.1016/j.msard.2022.103743

Mult Scler Relat Disord. 2022 Mar 5;61:103726. doi: 10.1016/j.msard.2022.103726. Online ahead of print.

ABSTRACT

BACKGROUND: Rehabilitation treatment may alleviate the disease severity of patients with NMOSD. The reports of rehabilitation exercise for NMOSD during acute phase are rare.

OBJECTIVE: To explore the efficacy and safety of rehabilitation exercise in patients with NMOSD during acute phase.

METHODS: This is a prospective cohort study of 36 patients (rehabilitation exercise group, RG) and 37 patients (control group, CG) in whom acute attack of NMOSD involved the spinal cord with EDSS≥4.5 were included. EDSS, American Spinal Injury Association Impairment Scale (AIS) grade, total motor score (TMS), light touch score (LTS), pin prick score (PPS), Berg balance scale (BBS), and Barthel index (BI) were used as outcome measures.

RESULTS: During hospitalization, EDSS scores of both groups decreased significantly (P<0.05). After treatment, the decline in EDSS was more significant in RG than in CG (P<0.05). The change reaching minimal clinically important difference (MCID) was observed in 90% (9/10) of patients in RG and in 27.78% (5/18) of patients in CG in the subgroup with EDSS 4.5-6.0 (MCID, 1.0), which was statistically significant between the groups (P<0.05). In the subgroup with EDSS 6.5-10.0 (MCID, 0.5), the proportion of patients with the change that reached MCID was significantly different between CG and RG (P<0.05). BBS, TMS, and BI score significantly improved after treatment (P<0.001). The improvement ranges of BBS, TMS, and BI scores were more significant in RG than CG (P<0.05). AIS grade improvement in RG was significantly higher than in CG. There were no significant changes in LTS and PPS after treatment in either of the groups. In RG, two mild adverse events were recorded.

CONCLUSION: Rehabilitation exercise may improve nervous system function, balance function, and activities of daily living in patients with acute NMOSD, with few adverse reactions.

PMID:35344908 | DOI:10.1016/j.msard.2022.103726

Leg Med (Tokyo). 2022 Mar 23;57:102057. doi: 10.1016/j.legalmed.2022.102057. Online ahead of print.

ABSTRACT

We analyzed 400 deaths that occurred in the bathtub during a 10-year period in the central area of Kanagawa prefecture in Japan. There were 72 (18%) medico-legal autopsy cases. The average age at death was 76.4 ± 11.9 years. Drowning (n = 21, 70.8%) was the most common cause of death in the 72 autopsy cases. The study examined the bodies of 40 cases within a postmortem interval of 3 days. The mean age of the 40 cases of sudden death during bathing was 68.6 ± 12.5 years. Results revealed cardiac hypertrophy in 12 cases (30%), lipofuscin deposition in 39 cases (97.5%), basophilic degeneration in 12 cases (30%), anisocytosis of the nucleus of myocardial cells in 18 cases (45%), perivascular fibrosis in 17 cases (42.5%), amyloid deposits in 1 case, and aortic valve calcification in 1 case. The hearts of control subjects who had lived to 20-99 years were also examined; the frequency of each change was higher in people older than 70 years. There was no statistically significant difference in age-related cardio-pathological changes between cases of sudden death during bathing in people in their 70s and controls in their 70s. It can be concluded that this age-related histopathological index is not related to sudden death during bathing. A large number of elderly people, including those without heart disease, have died during bathing. Preventive measures against sudden death during bathing are strongly recommended, e.g., elderly people should not be left totally unsupervised while they bathe.

PMID:35344880 | DOI:10.1016/j.legalmed.2022.102057

J Clin Neurosci. 2022 Mar 25;99:336-341. doi: 10.1016/j.jocn.2022.03.012. Online ahead of print.

ABSTRACT

Central nervous system tumours are the leading oncology cause of paediatric mortality. The aim of this research was to identify stages within the diagnostic process of a primary paediatric brain tumour that could be improved resulting in better outcomes.

METHODS: The electronic medical records of Queensland Children’s Hospital patients with central nervous system tumours between the 17/12/2014 till 11/12/2019 were retrospectively accessed. Time intervals of symptom onset to first medical review,location, time till medical imaging,subspecialty or neurosurgical review, timing of surgery, diagnosis and mortality status were recorded then analysed.

RESULTS: A total of 168 patients were included. Mean age to 7.5, 65% male, with pilocytic astrocytoma representing 31%. 71.4% of the population were from a major city as determined by Remoteness Area classification, ABS, with 19% inner regional and 9.5% being outer regional and remote. The average time from first medical review to diagnostic imaging was significantly different when comparing remoteness classification (p = 0.044). There was also a statistically significant difference in the duration of time from medical imaging to specialist review comparing major city and outer regional/remote (p = 0.016) and inner regional versus outer regional/remote areas (p = 0.026).

CONCLUSIONS: Delays in imaging in outer regional and remote Queensland are contributing to a delay in diagnosis and intervention in paediatric brain tumours. Service provision for neurosurgery in outer regional and remote Queensland is currently on par with inner regional and city areas. Suspicion of paediatric brain tumours is needed with clear referral pathways for general practitioners to access diagnostic imaging.

PMID:35344871 | DOI:10.1016/j.jocn.2022.03.012

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Mar 21;275:121175. doi: 10.1016/j.saa.2022.121175. Online ahead of print.

ABSTRACT

The ending of estrogen production in the ovaries after menopause results in a series of important physiologic changes, including hair texture and growth. In this study we demonstrate that Raman spectroscopy can be used successfully as a tool to probe menopause-induced changes on hair, in particular when coupled with suitable chemometrics approaches. The detailed analysis of the average Raman spectra (in particular of the Amide I and νS-S stretching spectral regions) of the hair samples of women pre- and post-menopause allowed to estimate that absence of estrogen in post-menopause women leads to an average reduction of ∼12% in the thickness of the hair cuticle, compared to that of pre-menopause women, and revealed the strong prevalence of disulphide bonds in the most stable gauche-gauche-gauche conformation in the hair cuticle. From the analysis of the νS-S stretching spectral region it could also be concluded that the amount of α-helix keratin is slightly higher for post-menopause than for pre-menopause women. A series of statistical models were developed in order to classify the hair samples. Outperforming the traditional PCA-LDA (principal component analysis – linear discriminant analysis) approach, in the present study a GA-LDA (genetic algorithm – linear discriminant analysis) strategy was used for variable reduction/selection and samples’ classification. This strategy allowed to develop of a statistical model (L16), which has exceptional prediction capability (total accuracy of 96.6%, with excellent sensitivity and selectivity) and can be used as an efficient instrument for the hair samples’ classification. In addition, a new chemometrics approach is here presented, which allows to overcome the intrinsic limitations of the GA algorithm and that can be used to develop statistical models that use GA as the variable reduction/selection method, but superseding its stochastic nature. Three suitable models for classification of the hair samples according to the menopause status of the women were developed using this novel approach (LV17, BLV20 and PLS7 models), which are based on the Fisher’s and Bayers’ LDA approaches and the PLS-DA method. The followed new chemometrics approach uses the results of a large set of GA-LDA runs over the full data matrix for the selection of the reduced data matrices. The criterion for the selection of the variables is their statistical significance in terms of number of occurrences as solutions of the whole set of GA-LDA runs.

PMID:35344858 | DOI:10.1016/j.saa.2022.121175

Comput Biol Med. 2022 Mar 23;145:105439. doi: 10.1016/j.compbiomed.2022.105439. Online ahead of print.

ABSTRACT

Acetyl-CoA carboxylase (ACC) is crucial for polyketides biosynthesis and acts as an essential metabolic checkpoint. It is also an attractive drug target against obesity, cancer, microbial infections, and diabetes. However, the lack of knowledge, particularly sequence-structure function relationship to narrate ligand-enzyme binding, has hindered the progress of ACC-specific therapeutics and unnatural “natural” polyketides. Structural characterization of such enzymes will boost the opportunity to understand the substrate binding, designing new inhibitors and information regarding the molecular rules which control the substrate specificity of ACCs. To understand the substrate specificity, we determined the crystal structure of AccB (Carboxyl-transferase, CT) from Streptomyces antibioticus with a resolution of 2.3 Å and molecular modeling approaches were employed to unveil the molecular mechanism of acetyl-CoA recognition and processing. The CT domain of S. antibioticus shares a similar structural organization with the previous structures and the two steps reaction was confirmed by enzymatic assay. Furthermore, to reveal the key hotspots required for the substrate recognition and processing, in silico mutagenesis validated only three key residues (V223, Q346, and Q514) that help in the fixation of the substrate. Moreover, we also presented atomic level knowledge on the mechanism of the substrate binding, which unveiled the terminal loop (500-514) function as an opening and closing switch and pushes the substrate inside the cavity for stable binding. A significant decline in the hydrogen bonding half-life was observed upon the alanine substitution. Consequently, the presented structural data highlighted the potential key interacting residues for substrate recognition and will also help to re-design ACCs active site for proficient substrate specificity to produce diverse polyketides.

PMID:35344865 | DOI:10.1016/j.compbiomed.2022.105439