Category: Nevin Manimala

Graefes Arch Clin Exp Ophthalmol. 2021 Jun 14. doi: 10.1007/s00417-021-05257-2. Online ahead of print.

ABSTRACT

PURPOSE: To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the treatment of neovascular glaucoma.

METHODS: We performed a prospective, randomized, controlled clinical trial at Hiroshima University and Tsukazaki Hospital, Japan. Patients were randomized to Baerveldt glaucoma implantation (23 patients) or TLE (27 patients). The primary outcome measure was the rate of intraocular-pressure control. Secondary outcome measures included complications and interventions. We defined “failure” as intraocular pressure ≥ 22 mmHg or < 20% reduction from baseline pressure, on two consecutive follow-up visits; need for additional glaucoma surgery; vision-threatening complications; or loss of light perception. Kaplan-Meier analysis was used to determine surgical success rates. Postoperative complications and interventions were compared between the two groups with Pearson Chi-square tests.

RESULTS: There were no significant differences in demographic or ocular characteristics between the treatment groups at baseline. The postoperative follow-up was 26.6 ± 19.4 months in the Baerveldt group and 27.3 ± 20.1 months in the TLE group. There were no statistical differences (Mann-Whitney nonparametric tests with Bonferroni correction) in postoperative intraocular pressure measured at 6-month intervals. Success rates were 59.1 and 61.6% at 1-year after Baerveldt glaucoma implantation and TLE, respectively. Kaplan-Meier analysis showed no significant difference in success between groups (P = 0.71, log-rank test). Medication use, visual acuity, and interventions were similar between groups. Thirteen late postoperative complications developed in the Baerveldt glaucoma implantation group and four complications developed in the TLE group. Tube exposure was the most common late complication.

CONCLUSION: These two procedures produced similar surgical success, intraocular-pressure reductions, visual acuity, and number of medications at the last visit. The TLE group showed smaller numbers of late complications and patients who lost more than two lines of visual acuity. Therefore, TLE might be a safer and better way to treat patients with neovascular glaucoma.

PMID:34125289 | DOI:10.1007/s00417-021-05257-2

Arch Orthop Trauma Surg. 2021 Jun 14. doi: 10.1007/s00402-021-03991-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The risk factors for a second nonsimultaneous hip fracture are unclear, and in general, it is empirically assumed that they are similar to those associated with the first hip fracture. We aimed to determine the incidence of a second hip fracture and define the characteristics of the patients sustaining the event in a prospective cohort study in a Spanish population.

MATERIALS AND METHODS: We conducted a multicentric, prospective cohort study in a representative sample of 45 hospitals from 15 autonomic regions in Spain. In total, the study included 994 patients. One hundred and one patients presented a nonsimultaneous contralateral hip fracture, constituting the intervention group. The remaining 893 patients presenting with a hip fracture formed the control group. The main outcome measures of this study were sociodemographic characteristics of the patient, comorbid conditions, and baseline and postfracture clinical outcomes (inpatient complications and acute mortality).

RESULTS: The key fracture risk factors were a history of fragility fractures, the need for assistance when walking outdoors and a history of falls. There were no associations between the groups in any of the common fragility risk factors, including rheumatoid arthritis, secondary osteoporosis, or steroid consumption. The results showed that patients suffering a nonsimultaneous hip fracture had an increased risk of mortality after discharge compared with the control group.

CONCLUSION: A nonsimultaneous second hip fracture leads to a near-significant increase in four-month mortality. In our study, this fracture was associated with a history of falls, prior fragility fractures, and the need for a walking aid.

PMID:34125250 | DOI:10.1007/s00402-021-03991-0

J Neurol. 2021 Jun 14. doi: 10.1007/s00415-021-10635-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare disease characterized by rapid neuropathic progression. In pivotal studies of gene-silencing treatments, the modified Neuropathy Impairment Score + 7 tests (mNIS + 7) and Norfolk-Quality of Life (QOL)-Diabetic Neuropathy (DN) questionnaire assessed treatment impact on neuropathic progression. Establishing responder definition (RD) thresholds for these measures would enable evaluation of clinically meaningful treatment benefit.

METHODS: mNIS + 7 and Norfolk-QOL-DN were administered at baseline and week 65 to 165 adults with ATTRv-PN receiving inotersen (n = 106) or placebo (n = 59) in the NEURO-TTR study. Anchor-based approaches for estimating RD thresholds were used for Norfolk QOL-DN, while distribution-based approaches were used for both measures. Responders were patients with a score change < RD, indicating improvement or stabilization (i.e., no clinically meaningful progression). Odds ratios (ORs) and Fisher’s exact tests compared proportions of responders by treatment.

RESULTS: The mean RD estimates were 12.2 points and 8.8 points for mNIS + 7 and Norfolk QOL-DN, respectively. The proportions of patients whose change in score indicated improvement or stabilization were statistically significantly larger for inotersen than placebo for all estimated RD thresholds for mNIS + 7 (64-86% responders for inotersen vs. 27-46% for placebo, ORs = 3.8-7.2, ps < 0.001) and Norfolk QOL-DN (66-81% vs. 35-56%, ORs = 2.4-3.6, ps < 0.05).

DISCUSSION: Establishing RD thresholds for these instruments enables evaluation of clinically relevant and individual-level treatment benefit on neuropathic progression. Across RDs estimated using multiple methods, a higher proportion of patients receiving inotersen than placebo showed improved or stabilized neuropathic progression at week 65.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01737398; Date of registration: November 29, 2012.

PMID:34125267 | DOI:10.1007/s00415-021-10635-1

Eur Arch Otorhinolaryngol. 2021 Jun 14. doi: 10.1007/s00405-021-06937-9. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the changes in voice nasality after septoplasty and turbinate hypertrophy reduction and to evaluate the effect of these changes on patients’ voice-related quality of life.

METHODS: Sixty patients with nasal obstruction symptoms caused by septal deviation and inferior turbinate hypertrophy who underwent septoplasty and inferior turbinate hypertrophy reduction and 25 healthy controls were included. Active anterior rhinomanometry and acoustic rhinometry were utilized for the evaluation of nasal patency and nasometry was used for quantitative assessment of nasalance. All participants completed validated questionnaires for assessing nasal obstruction symptom severity, psychological status and the impact of voice performance on their quality of life preoperatively and 6 months after septoplasty.

RESULTS: Patients presented preoperatively statistically significantly lower nasalance scores and higher VHI scores than controls (p < 0.05). Septoplasty and inferior turbinate hypertrophy reduction led to improvement of nasalance for the nasal text and the physical subscale of the VHI scores. Postoperatively, there were no statistically significant differences in nasalance and VHI scores between patients and controls. Significant correlations were found only for the baseline and the postoperative nasalance scores for the nasal text and the total nasal cavity volume (p < 0.05). Postoperatively, patients who presented significant improvement of nasal obstruction symptoms and resolution of stress levels were more likely to positively evaluate the impact of their voice quality on their daily life (OR: 2.32, 95% CI 1.08-5.15, p = 0.041 and OR: 3.06, 95% CI 1.15-7.04, p = 0.038, respectively).

CONCLUSION: Septoplasty and inferior turbinate hypertrophy reduction may increase the nasal resonance, but in the long term, this change appears not to be significant enough. The severity of nasal obstruction symptoms and psychological status mainly affect the patients’ perceptual assessment regarding the effect of voice performance on their quality of life.

PMID:34125283 | DOI:10.1007/s00405-021-06937-9

HNO. 2021 Jun 14. doi: 10.1007/s00106-021-01066-5. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic ear surgery (EES) is increasingly used internationally instead of microscopic ear surgery (MES), but has not yet become established as a routine procedure everywhere in Germany.

OBJECTIVE: The incision-suture time and practicability of EES in the setting of a German clinic were investigated.

MATERIALS AND METHODS: In a retrospective study, 60 consecutive MES patients from 2015 were compared with 60 consecutive EES patients from 2018. Hearing results, tympanic membrane findings after 3 weeks, and incision-suture times were compared.

RESULTS: In EES, access was mostly transmeatal and bone of the anterior auditory canal wall had to be removed less often than in MES. There was no statistically significant difference in surgery times between the two groups. Perforation closure was achieved in 57/60 and 59/60 ears in the MES and EES groups, respectively. Hearing was improved in both groups. There was no statistical difference in hearing improvement between the two groups.

CONCLUSION: EES is a time efficient and minimally invasive method which represents a viable alternative to MES with comparable results.

PMID:34125238 | DOI:10.1007/s00106-021-01066-5

Acta Neuropathol. 2021 Jun 14. doi: 10.1007/s00401-021-02325-z. Online ahead of print.

ABSTRACT

Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson’s disease (PD) albeit with incomplete and age-dependent penetrance. All pathogenic LRRK2 mutations reside within the two catalytic domains of LRRK2-either in its kinase domain (e.g. G2019S) with modest effect or its ROC-COR GTPase domain (e.g. R1441G/H) with large effect on LRRK2 kinase activity. We have previously reported assays to interrogate LRRK2 kinase pathway activity in human bio-samples measuring phosphorylation of its endogenous substrate Rab10, that mirrors LRRK2 kinase activation status. Here, we isolated neutrophils from fresh peripheral blood from 101 participants including 42 LRRK2 mutation carriers (21 with the G2019S and 21 with the R1441G mutations), 27 patients with idiopathic PD, and 32 controls. Using a dual approach, LRRK2 dependent Rab10 phosphorylation at Threonine 73 (pRab10^Thr73) was measured by quantitative multiplexed immunoblotting for pRab10^Thr73/total Rab10 as well as targeted mass-spectrometry for absolute pRab10^Thr73 occupancy. We found a significant over fourfold increase in pRab10^Thr73 phosphorylation in carriers of the LRRK2 R1441G mutation irrespective of clinical disease status. The effect of the LRRK2 G2019S mutation did not reach statistical significance. Furthermore, we show that LRRK2 phosphorylation at Serine 935 is not a marker for LRRK2 kinase activity in human neutrophils. When analysing pRab10^Thr73 phosphorylation in post-mortem brain samples, we observed overall high variability irrespective of clinical and LRRK2 mutation status and attributed this mainly to the adverse effect of the peri- and post-mortem period on the stability of posttranslational modifications such as protein phosphorylation. Overall, in vivo LRRK2 dependent pRab10^Thr73 phosphorylation in human peripheral blood neutrophils is a specific, robust and promising biomarker for significant LRRK2 kinase hyperactivation, as with the LRRK2 R1441G mutation. Additional readouts and/or assays may be needed to increase sensitivity to detect modest LRRK2 kinase activation, as with the LRRK2 G2019S mutation. Our assays could be useful for patient stratification and target engagement studies for LRRK2 kinase inhibitors.

PMID:34125248 | DOI:10.1007/s00401-021-02325-z

HNO. 2021 Jun 14. doi: 10.1007/s00106-021-01063-8. Online ahead of print.

ABSTRACT

BACKGROUND: Perpendicular vascular changes (PVC) are markers of tumor-induced neoangiogenesis at the vocal folds. Contact endoscopy with narrow-band imaging (CE-NBI) allows a detailed analysis of such vascular changes.

OBJECTIVE: This work intends to evaluate the potential of CE-NBI for diagnosis of benign, dysplastic, and malignant lesions of the vocal folds. In addition, it should be determined whether CE-NBI offers an additional benefit in detecting PVC compared to white-light endoscopy (WLE) and NBI alone.

MATERIALS AND METHODS: Three examiners evaluated histologically verified cases of benign, dysplastic, and malignant lesions of the larynx in WLE, NBI, and CE-NBI (n = 60). In each mode, they examined the lesion for PVC and assessed the lesion’s dignity. The proportion of lesions with detected PVC, the statistical measures of performance in detecting high-grade dysplasia and carcinoma, and the interrater variability for each mode were calculated.

RESULTS: CE-NBI proved superior to the other investigated diagnostic methods in terms of detecting PVC and in terms of sensitivity and accuracy in the diagnosis of high-grade dysplasia and carcinoma. A clear association of such pathologies with PVC was seen.

CONCLUSION: CE-NBI detects PVC more frequently and reliably than the other methods investigated. The association of these vascular patterns to high-grade dysplasia and vocal fold carcinomas could be confirmed. Compared to WLE and NBI endoscopy, the diagnostic quality for detecting high-grade dysplasia and carcinoma is increased. Thus, CE-NBI can improve endoscopic differentiation between benign and malignant lesions of the vocal folds by enhancing the detection of PVC.

PMID:34125236 | DOI:10.1007/s00106-021-01063-8

Infect Agent Cancer. 2021 Jun 13;16(1):42. doi: 10.1186/s13027-021-00382-3.

ABSTRACT

BACKGROUND: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.

METHODS: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.

RESULTS: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36).

CONCLUSIONS: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

PMID:34120615 | DOI:10.1186/s13027-021-00382-3

BMC Public Health. 2021 Jun 14;21(1):1135. doi: 10.1186/s12889-021-11154-4.

ABSTRACT

BACKGROUND: Antenatal care (ANC) played a crucial role in ensuring maternal and child safety and reducing the risk of complications, disability, and death in mothers and their infants. The objective of this study was to evaluate the current status of ANC emphasizing the number, timing, and content of examinations on a national scale.

METHODS: The data was collected from maternal and newborn’s health monitoring system at 8 provinces in China. After ethical approval, all pregnant women registered in the system at their first prenatal care visit, we included 49,084 pregnant women who had delivered between January 1, 2018 and December 31, 2018. Descriptive statistics of all study variables were calculated proportions and chi-square for categorical variables.

RESULTS: Of the 49,084 women included in this study, the mean number of ANC visits was 6.95 ± 3.45. By percentage, 78.79% women received ANC examinations at least five times, 39.93% of the women received ANC examinations at least eight times and 16.66% of the women received ANC examinations at least 11 times. The proportion of first ANC examination in first trimester was 61.87%. The percentage of normative ANC examinations and the percentage of qualified ANC examinations were 30.98 and 8.03% respectively. Only 49.40% of the total women received all six kinds of examination items in first ANC examination: 91.47% received a blood test, 91.62% received a urine test, 81.56% received a liver function examination, 80.52% received a renal function examination, 79.07% received a blood glucose test, and 86.66% received a HIV/HBV/syphilis tests. 50.85% women received the first ANC examination in maternal and child health care (MCH) institutions, 14.07% in a general hospital, 18.83% in a township hospital, 13.15% in a community health services center, and 3.08% in an unspecified place. The proportion of women who received each of the ANC examination items in community health services center was the highest, but that in the MCH institutions was the lowest.

CONCLUSIONS: There is a big difference between the results of this study and the data in official reports, this study found the current status of antenatal care is not optimal in China, findings from this study suggest that the systematization, continuity and quality of ANC examinations need to be improved.

PMID:34120600 | DOI:10.1186/s12889-021-11154-4

BMC Med Educ. 2021 Jun 13;21(1):342. doi: 10.1186/s12909-021-02759-9.

ABSTRACT

BACKGROUND: Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the “shows how” level of Miller’s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents.

METHODS: In this retrospective study, eight different conventional methods of assessment including residents’ attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches.

RESULTS: Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents’ average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value < 0.05). The overall correlation between conventional and electronic methods was significant (P-value = 0.017).

CONCLUSION: In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment.

PMID:34120607 | DOI:10.1186/s12909-021-02759-9