Nevin Manimala

Int J Clin Pract. 2021 Sep 6:e14810. doi: 10.1111/ijcp.14810. Online ahead of print.

ABSTRACT

BACKGROUND: Technetium-99m-dimercapto succinic acid (Tc-99m DMSA) scintigraphy is a commonly used imaging modality in children with urological abnormalities. The radiopharmaceuticals, which have the effects of ionizing radiation, are used in this method. This study aimed to investigate the impact of the Tc-99m DMSA scan on renal oxidative stress and mononuclear leukocyte (MNL) DNA damage.

METHODS: Children, who were followed up by pediatric nephrology at Bezmialem Vakif University and underwent Tc-99m DMSA scintigraphy between April 2015 and January 2016 with the indication of detection of renal scars, were included in this study. The exclusion criteria were nephrolithiasis, history of premature birth, and recent urinary tract infection six months prior to scintigraphy or antibiotic use in the last one month. Three ml heparinized blood samples were obtained just before, immediately after, and one week after the scintigraphy. MNL DNA damage, total antioxidant status (TAS), and total oxidant status (TOS) were measured in the blood samples. The oxidative stress index (OSI) was calculated. Spot urine samples were obtained from each patient before and within three days after performing the scintigraphy. TAS/Creatinine (TAS/Cr), TOS/Creatinine (TOS/Cr), and N-acetyl-glucosaminidase/creatinine (NAG/Cr) levels were measured in the urine samples.

RESULTS: Twenty-seven children were evaluated. The values between TAS, TOS and OSI levels in serum samples at baseline, immediately after, and one week after the scintigraphy (p=0.105, p=0.913, and p=0.721, respectively) showed no statistically significant difference. The levels of TAS/Cr, TOS/Cr, NAG/Cr ratios, and OSI, which were evaluated from urine samples before and within three days after the scintigraphy scan were also similar (p=0.391, p=0.543, p=0.819 and p=0.179 respectively). The levels of DNA damage only increased following scintigraphy scan and decreased a week later (p<0.05).

CONCLUSIONS: The effect of Tc-99m DMSA scintigraphy is insufficient to create oxidative damage, but it can cause DNA damage via the direct impact of ionizing radiation which can be repaired again in a short time.

PMID:34487588 | DOI:10.1111/ijcp.14810

Neuromodulation. 2021 Sep 6. doi: 10.1111/ner.13527. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the analgesic effect of high-voltage pulsed radiofrequency (HV-PRF) on the dorsal root ganglion (DRG) for neuropathic pain induced by spared nerve injury (SNI) in rats, especially the influence of this treatment on the DRG ultrastructure and voltage-gated sodium channel 1.7 (Nav1.7) level in the DRG.

MATERIALS AND METHODS: One hundred fifty adult male Sprague-Dawley rats were randomly divided into five groups: Sham, SNI, Free-PRF, standard-voltage PRF (SV-PRF), and HV-PRF. The 45V-PRF and 85V-PRF procedures applied to the left L5 DRG were performed in SV-PRF group and the HV-PRF group respectively on day 7 after SNI, whereas no PRF was concurrently delivered in Free-PRF group. The paw mechanical withdrawal threshold (PMWT) was detected before SNI (baseline) and on days 1, 3, 7, 8, 10, 14, and 21. The changes of left L5 DRG ultrastructure were analyzed with transmission electron microscopy on days 14 and 21. The expression levels of Nav1.7 in left L5 DRG were detected by immunofluorescence and Western blot.

RESULTS: Compared with the Free-PRF group, PMWT in the SV-PRF group and HV-PRF group were both significantly increased after PRF (all p < 0.05). Meanwhile, the PMWT was significantly higher in the HV-PRF group than that in the SV-PRF group on days 14 and 21 all (p < 0.05). There were statistically significant differences between the SV-PRF and Free-PRF groups (p < 0.05). Similarly, statistically significant difference was found between the HV-PRF and Free-PRF groups (p < 0.05). Especially, comparison of the SV-PRF group and the HV-PRF group revealed statistically significant difference (p < 0.05). The Nav1.7 levels were significantly down-regulated in the SV-PRF group and HV-PRF groups compared to that in the Free-PRF group (all p < 0.01). A significantly lower Nav1.7 level was also found in the HV-PRF group compared to that in the SV-PRF group (p < 0.05).

CONCLUSIONS: The HV-PRF produces a better analgesic effect than SV-PRF applied to the DRG in SNI rats. The underlying mechanisms may be associated with improving the histopathological prognosis and the downregulation of Nav1.7 levels in the DRG.

PMID:34487572 | DOI:10.1111/ner.13527

Lasers Surg Med. 2021 Sep 6. doi: 10.1002/lsm.23459. Online ahead of print.

ABSTRACT

BACKGROUND: Various laser therapies have been introduced in scar management. However, pain during treatment has limited the application of laser therapy in pediatrics.

OBJECTIVES: To evaluate whether the use of the low-energy mode of a carbon dioxide (CO₂ ) laser improves hypertrophic scars in a pediatric population.

METHODS: This prospective, randomized, split-scar trial was designed to assess the safety and efficacy of low-energy CO₂ laser use. Patients aged <12 years with hypertrophic scars were enrolled. Each hypertrophic scar was equally divided into three parts: the two ends of each scar were randomly assigned to control and experimental groups, and the center portion was considered a transition zone and was not included in the analysis. A total of three laser treatments were performed at 1-month intervals. Scar scale scores 6 months after the final treatment was the primary outcome. Additionally, the Visual Analog Scale (VAS) was used to evaluate pain after each treatment.

RESULTS: Of the 23 patients enrolled, 20 completed the study. The total Patient and Observer Scar Assessment Scale (POSAS) score at the 6-month follow-up was significantly lower for the treated site (44.95 for the treated group vs. 64.85 for the control group, p < 0.0001). Both the patient and observer POSAS scores showed an obvious difference between the treated and control groups (19.95 vs. 29.95 for patient scores, respectively, p < 0.0001, and 26.00 vs. 34.90 for observer scores, respectively, p < 0.0001). All observer and patient scores describing pain, pruritus, color, stiffness, and thickness were statistically different and favored the treated site. No significant difference was found in patient score of irregularity. The average VAS therapeutic pain score was 3.5 ± 1.43 out of 10.

CONCLUSIONS: Low-energy CO₂ fractional laser therapy improved hypertrophic scars in a pediatric population. Therefore, for children with hypertrophic scar, low-energy CO₂ laser with less procedure pain may be more appropriate.

PMID:34487566 | DOI:10.1002/lsm.23459

Int Endod J. 2021 Sep 6. doi: 10.1111/iej.13628. Online ahead of print.

ABSTRACT

AIM: To investigate attitudes and approaches of UK primary care dentists to carrying out vital pulp treatment (VPT) after carious-exposure and with additional signs and symptoms indicative of irreversible pulpitis.

METHODOLOGY: An electronic questionnaire was openly distributed via publicly-funded (NHS) local dental committees, corporate dental service-providers, professional societies and social media. Principally NHS practitioners, and those from mixed and private practice were targeted, in addition to community and military dental officers, and dental therapists. Participants were asked questions relating to several clinical scenarios, with responses analysed using descriptive statistics. χ² tests with sequential Bonferroni correction were used to explore variables including the method of remuneration, practitioner type (dentist/therapist), postgraduate qualification(s), place of graduation and years since qualification. Variables with a relationship p≤0.2 were selected for backwards likelihood ratio logistic modelling.

RESULTS: In total, 648 primary care practitioners were included for analysis. Calcium hydroxide (CH) was most frequently used for direct pulp caps (DPCs) (398/600; 66.3%) with calcium-silicate cements (CSCs) less frequently used (119/600; 19.8%). Rubber dam was used by 222/599 (37.1%) practitioners. A definitive pulpotomy for the management of teeth with signs a symptoms indicative of irreversible pulpitis was selected by 65/613 (10.6%) dentists. The principal barrier for the provision of definitive pulpotomies was a lack of training (602/612; 98.4%). Regression analysis identified NHS practitioner’s as a good predictor for using CH for DPCs, having shorter emergency appointments, limited access to magnification and not using rubber dam. Non-UK graduates were more likely to select CSCs, appropriately control pulpal haemorrhage, undertake appropriate post-operative evaluation and use rubber dam.

CONCLUSIONS: Practitioners deviated from evidence-based guidelines in a number of aspects including material selection, asepsis and case selection. A number of other challenges exist in primary care in providing predictable VPTs, including lack of time and access to magnification. These were most evident in NHS practice, potentially exacerbating existing social health inequalities. Possible inconsistencies in the UK undergraduate curriculum were supported by a lack of association between years since qualification and technique employed as well as the fact that non-UK graduates and dentists with postgraduate qualifications adhered more to evidence-based VPT guidelines.

PMID:34487553 | DOI:10.1111/iej.13628

Clin Exp Immunol. 2021 Sep 6. doi: 10.1111/cei.13659. Online ahead of print.

ABSTRACT

Graft versus Host Disease (GvHD) is a major clinical problem with a significant unmet medical need. We examined the role of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) in a xenogenic GvHD (xeno-GvHD) model induced by injection of human peripheral mononuclear cells (hPBMC) into irradiated NSG mice. Targeting CTLA4 pathway by treatment with CTLA-4 Ig prevented xeno-GvHD, while anti-CTLA-4 antibody treatment exacerbated the lethality and morbidity associated with the GvHD. The xeno-GvHD is associated with infiltration of hPBMCs into the lungs, spleen, stomach, liver, and colon, and an increase in human pro-inflammatory cytokines including IFN-γ, TNFα and IL-5. Infiltration of donor cells and increases in cytokines were attenuated by treatment with CTLA-4 Ig but remained either unaffected or enhanced by anti-CTLA-4 antibody. Further, splenic human T cell phenotyping showed that CTLA-4 Ig treatment prevented the engraftment of human CD45+ cells while anti-CTLA-4 antibody enhanced donor T cell expansion, particularly CD4+ (CD45RO⁺ ) subsets including, Tbet⁺ CXCR3⁺ and CD25⁺ Foxp3 cells. Comprehensive analysis of transcriptional profiling of human cells isolated from mouse spleen identified a set of 417 differentially expressed genes (DEGs) by CTLA-4 Ig treatment and 13 DEGs by anti-CTLA4 antibody treatment. The CTLA-4 Ig regulated DEGs mapped to down regulated apoptosis, inflammasome, Th17 and Treg pathways, and enhanced TLR receptor signaling, TNF family signaling, complement system, and epigenetic and transcriptional regulation, where as anti-CTLA-4 antibody produced minimal to no impact on these gene pathways. Our results show an important role of co-inhibitory CTLA-4 signaling in xeno-GvHD and suggest therapeutic utility of other immune checkpoint co-inhibitory pathways in the treatment of immune-mediated diseases driven by hyperactive T-cells.

PMID:34487545 | DOI:10.1111/cei.13659

Carcinogenesis. 2021 Sep 6:bgab082. doi: 10.1093/carcin/bgab082. Online ahead of print.

ABSTRACT

Previous lung diseases (PLD) are known risk factors for lung cancer. However, it remains unclear how the association varies by lung cancer subtype and socio-demographic characteristics. We conducted a systematic literature search in three electronic databases from the inception of each database up until 13 January 2021. A total of 73 studies (18 cohort and 55 case-control studies) consisting of 97,322 cases and 7,761,702 controls were included. Heterogeneity was assessed using the I 2 statistic. Based on the heterogeneity, either the fixed-effects or random-effects model was used to estimate the pooled summary estimate (PSE) and 95% confidence interval (CI) for the association between PLD and lung cancer risk. A history of asthma, chronic bronchitis, emphysema, pneumonia, tuberculosis, and COPD was associated with higher lung cancer risk, with a history of COPD and emphysema having at least two-fold relative risk. A history of hay fever was associated with lower lung cancer risk (PSE= 0.66, 95% CI= 0.54-0.81), even among ever-smokers (PSE= 0.55, 95% CI= 0.41-0.73). Older individuals with a history of asthma, chronic bronchitis, emphysema, COPD, or tuberculosis were associated with higher lung cancer risk. Individuals with a diagnosis of asthma, emphysema, or pneumonia within 1 to 10 years prior to lung cancer diagnosis were associated with higher lung cancer risk. Among ever-smokers, a history of COPD or emphysema have at least two-fold relative risk of lung cancer. PLD was associated with higher risk of lung cancer. Individuals with PLD should be closely monitored and prioritised for lung cancer screening.

PMID:34487521 | DOI:10.1093/carcin/bgab082

Int J Qual Health Care. 2021 Sep 6:mzab130. doi: 10.1093/intqhc/mzab130. Online ahead of print.

ABSTRACT

BACKGROUND: Delays to the transfer of care from hospital to other settings represent a significant human and financial cost. This delay occurs when a patient is clinically ready to leave the inpatient setting but is unable to because other necessary care, support or accommodation is unavailable. The aim of this study was to interrogate administrative and clinical data routinely collected when a patient is admitted to hospital following attendance at the emergency department, to identify factors related to delayed transfer of care when the patient is discharged. We then used these factors to develop a predictive model for identifying patients at risk for delayed discharge of care.

METHODS: This is a single centre, retrospective, cross-sectional study of patients admitted to an English National Health Service university hospital following attendance at the emergency department between January 2018 and December 2020. Clinical information (e.g., NEWS scores), as well as administrative data that had significant associations with admissions that resulted in delayed transfers of care, were used to develop a predictive model using a mixed-effects logistic model. Detailed model diagnostics and statistical significance, including receiver operating characteristic analysis, were performed.

RESULTS: Three-year (2018-20) data were used; a total of 92,444 admissions (70%) were used for model development and 39,877 (30%) admissions for model validation. Age, gender, ethnicity, National Early Warning Score, Glasgow admission prediction score (GAPS), Index of Multiple Deprivation decile, arrival by ambulance and admission within the last year were found to have a statistically significant association with delayed transfers of care. The proposed eight-variable predictive model showed good discrimination with 79% sensitivity (95% confidence intervals: 79%, 81%), 69% specificity (95% CI: 68%, 69%) and 70% (95% confidence intervals: 69%, 70%) overall accuracy of identifying patients who experienced a delayed transfer of care.

CONCLUSION: Several demographic, socio-economic and clinical factors were found to be significantly associated with whether a patient experiences a delayed transfer of care or not following an admission via the emergency department. An eight-variable model has been proposed, which is capable of identifying patients who experience delayed transfers of care with 70% accuracy. The eight-variable predictive tool calculates the probability of a patient experiencing a delayed transfer accurately at the time of admission.

PMID:34487520 | DOI:10.1093/intqhc/mzab130

Brain Inj. 2021 Sep 6:1-8. doi: 10.1080/02699052.2021.1972451. Online ahead of print.

ABSTRACT

OBJECTIVE: Clinical practice guidelines (CPGs) synthesize research evidence for health professionals and improve consistency of clinical care. However, it is unclear if concussion clinicians use them in their practice. We aimed to describe which CPGs New Zealand clinicians used and facilitators and barriers to uptake of these resources.

MATERIALS AND METHODS: We used snowballing recruitment methods to survey New Zealand concussion clinicians. Descriptive statistics and qualitative description were used to evaluate survey responses.

RESULTS: Ninety-six clinicians took part in the survey. A majority (70%) indicated they were aware of and had used at least one concussion CPG. Facilitators and barriers to using CPGs related to clinician experience, nature of the CPG, the work context, characteristics of clients and whether strategies were provided to encourage their use.

CONCLUSIONS: Participants viewed concussion CPGs as helpful tools for informing clinical practice. That less experienced clinicians were less likely to use concussion CPGs than more experienced clinicians suggests there is an opportunity to develop strategies to improve the uptake of CPGs among newer clinicians. This and other areas of further research include how well CPGs capture relevant cultural factors and the role of case complexity in clinicians’ willingness to use concussion CPGs.

PMID:34487457 | DOI:10.1080/02699052.2021.1972451

J Eur Acad Dermatol Venereol. 2021 Sep 6. doi: 10.1111/jdv.17643. Online ahead of print.

ABSTRACT

Alopecia areata (ΑΑ) is an inflammatory disease of the hair follicle unit characterised by non-scarring hair loss. The complex interplay and communication between cells of the immune system and the microenvironment around the hair follicle ensure a homeostasis which is compromised in AA.

PMID:34487410 | DOI:10.1111/jdv.17643

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2021 Jul;29(4):977-983. doi: 10.32687/0869-866X-2021-29-4-977-983.

ABSTRACT

The inclusion of public health and health care measures in labor functions of professional standards of medical specialists increased significance of mastering of these standards by students during specialty training, since on this depends their successful completion of primary accreditation of specialists and implementation of job descriptions in the course of daily activities. The purpose of the study was to analyze factors determining qualitative of mastering the discipline “Public health and Health Care” by students of medical educational organizations. The analytical, logical, statistical, questionnaire survey and direct ranking methods were applied. The sampling of 316 students of the Sechenov University was involved in survey using questionnaire of 17 closed questions. The study established that the determining factors effecting quality of mastering by students the discipline “Public health and Health Care” are the need to use by physicians this knowledge in the course of their daily activities; the need of students to pass profile exam; the determination of up to 40% of trainees to work as heads of structural units or professionals of health care and public health; the dedication of student; organization of educational process at the Chair; the professionalism of faculty; the application of active learning methods in classroom; organization of career guidance among students.

PMID:34486869 | DOI:10.32687/0869-866X-2021-29-4-977-983