Nevin Manimala

J Radiat Res. 2022 Nov 19:rrac074. doi: 10.1093/jrr/rrac074. Online ahead of print.

ABSTRACT

We compared the dose distributions of carbon-ion pencil beam scanning (C-PBS), proton pencil beam scanning (P-PBS) and Volumetric Modulated Arc Therapy (VMAT) for locally recurrent rectal cancer. The C-PBS treatment planning computed tomography (CT) data sets of 10 locally recurrent rectal cancer cases were randomly selected. Three treatment plans were created using identical prescribed doses. The beam angles for C-PBS and P-PBS were identical. Dosimetry, including the dose received by 95% of the planning target volume (PTV) (D95%), dose to the 2 cc receiving the maximum dose (D2cc), organ at risk (OAR) volume receiving > 15Gy (V15) and > 30Gy (V30), was evaluated. Statistical significance was assessed using the Wilcoxon signed-rank test. Mean PTV-D95% values were > 95% of the volume for P-PBS and C-PBS, whereas that for VMAT was 94.3%. However, PTV-D95% values in P-PBS and VMAT were < 95% in five and two cases, respectively, due to the OAR dose reduction. V30 and V15 to the rectum/intestine for C-PBS (V30 = 4.2 ± 3.2 cc, V15 = 13.8 ± 10.6 cc) and P-PBS (V30 = 7.3 ± 5.6 cc, V15 = 21.3 ± 13.5 cc) were significantly lower than those for VMAT (V30 = 17.1 ± 10.6 cc, V15 = 55.2 ± 28.6 cc). Bladder-V30 values with P-PBS/C-PBS (3.9 ± 4.8 Gy(RBE)/3.0 ± 4.0 Gy(RBE)) were significantly lower than those with VMAT (7.9 ± 8.1 Gy). C-PBS provided superior dose conformation and lower OAR doses compared with P-PBS and VMAT. C-PBS may be the best choice for cases in which VMAT and P-PBS cannot satisfy dose constraints. C-PBS could be another choice for cases in which VMAT and P-PBS cannot satisfy dose constraints, thereby avoiding surgical resection.

PMID:36403118 | DOI:10.1093/jrr/rrac074

Int Endod J. 2022 Nov 20. doi: 10.1111/iej.13871. Online ahead of print.

ABSTRACT

AIM: Selective root canal retreatment is when the treatment is limited to root(s) with radiographic evidence of periapical pathosis. The goals of this retrospective study were as follows: i) evaluate the clinical and radiographic (periapical radiographs (PR) or cone beam computerised tomographs (CBCT)) outcome of selective root canal retreatment after ≥ 12 months follow-up; ii) evaluate the periapical status of the unretreated roots; iii) assess tooth survival.

METHODS: A retrospective study (January 2018 to April 2021) was conducted to identify permanent multirooted teeth that underwent selective root canal retreatment. Clinical records, PR and CBCT were examined to ascertain variables of interest. Outcomes (per root and per tooth) were classified into “favourable” or “unfavourable” using well-established clinical and radiographic healing criteria. Treatment outcomes for the whole tooth and per root were compared as well as bivariate associations between the treatment outcome of the retreated roots and the treatment-related parameters (quality of root filling, sealer extrusion, iatrogenic mishaps, type of restoration) were analysed using Fisher’s exact test (α = 0.05). Survival was recorded in months.

RESULTS: A total of 75 teeth (195 roots) in 75 subjects were available for outcome analysis. The favourable outcome per tooth was 86.7%. At follow-up, 92.6% of the retreated roots had a favourable outcome. From the unretreated roots, 3.5% showed radiographic signs of an emerging periapical lesion. No statistical difference was shown between the outcomes per root and per tooth between both groups. None of the treatment-related parameters had a direct influence on the outcome of the retreated roots. The survival rate at 12-48 months after retreatment was 91.5%.

CONCLUSIONS: Selective root canal retreatment is associated with a favourable outcome in a majority of cases. Untreated roots rarely developed radiographic signs of a new periapical lesion at follow-up. Future high-quality clinical trials with larger sample sizes and longer follow-up periods are required to confirm these findings.

PMID:36403111 | DOI:10.1111/iej.13871

Aging Cell. 2022 Nov 19:e13739. doi: 10.1111/acel.13739. Online ahead of print.

ABSTRACT

Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti-adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine- and cysteine-titrated diets, we demonstrate that the anti-adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. In mice, the magnitude of SAAR-induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age-at-onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. Controlled feeding of low-SAA, high-polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia.

PMID:36403077 | DOI:10.1111/acel.13739

J Orthop Surg Res. 2022 Nov 19;17(1):502. doi: 10.1186/s13018-022-03402-z.

ABSTRACT

BACKGROUND: Anatomic repair of anterior talofibular ligament (ATFL) is used to manage chronic lateral ankle instability (CLAI). However, the optimal suture configuration used to repair the ATFL is not yet determined. It remains unclear whether suture configuration affects clinical outcomes in such patients.

PURPOSE: To compare the functional outcomes of all-inside arthroscopic ATFL repair using either a loop suture and or a free-edge suture configuration in CLAI patients.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: This retrospective cohort study included 71 patients with CLAI who had undergone an all-inside arthroscopic ATFL repair procedure with either loop suture (n = 36) or free-edge suture (n = 35) from February 2016 to July 2018. Comparable pre-operatively, the Visual analogy score (VAS), American Orthopedic Foot and Ankle Society scoring system (AOFAS), Karlsson Ankle Functional Score (KAFS) scoring system, Anterior Talar Translation (ATT) and Active Joint Position Sense (AJPS) were used to evaluate postoperative ankle function.

RESULTS: There were no postoperative wound complications, implant reactions, or neurological or vascular injuries. Postoperative hospitalization, VAS, AOFAS, KAFS, AJPS and the time of return to sport were similar between the loop suture group and free-edge suture group. Requiring a longer procedure time, patients with loop suture configuration achieved better ATT.

CONCLUSION: All-inside arthroscopic ATFL repair procedure for CLAI treatment provides better ATT and comparable functional outcomes when a loop suture configuration is used instead of a free-edge suture configuration. A statistical difference in ATT was observed. Given the relatively short follow-up, it is questionable whether this will have any clinical relevance.

PMID:36403066 | DOI:10.1186/s13018-022-03402-z

Hum Genomics. 2022 Nov 19;16(1):60. doi: 10.1186/s40246-022-00434-8.

ABSTRACT

BACKGROUND: The interferon-induced transmembrane-protein 3 (IFITM3) is a vital component of the immune system’s defense against viral infection. Variants in the IFITM3 gene have been linked to changes in expression and the risk of severe Coronavirus disease 2019 (COVID-19). This study aimed to investigate whether IFITM3 rs6598045, quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) values, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are associated with an increased mortality rate of COVID-19.

METHODS: The genotyping of IFITM3 rs6598045 polymorphism was analyzed using the amplification refractory mutation system-polymerase chain reaction in 1342 recovered and 1149 deceased patients positive for SARS-CoV-2.

RESULTS: In this study, IFITM3 rs6598045 G allele as minor allele frequency was significantly more common in the deceased patients than in the recovered ones. Furthermore, the highest mortality rates were observed in Delta variant and lowest qPCR Ct values. COVID-19 mortality was associated with IFITM3 rs6598045 GG and AG in Delta variant and IFITM3 rs6598045 AG in Alpha variant. A statistically significant difference was observed in the qPCR Ct values between individuals with GG and AG genotypes and those with an AA genotype.

CONCLUSION: A possible correlation was observed between the mortality rate of COVID-19, the G allele of IFITM3 rs6598045, and SARS-CoV-2 variants. However, large-scale research is still required to validate our results.

PMID:36403064 | DOI:10.1186/s40246-022-00434-8

Syst Rev. 2022 Nov 19;11(1):248. doi: 10.1186/s13643-022-02120-1.

ABSTRACT

BACKGROUND: Core outcome sets (COSs) aim to reduce outcome heterogeneity in clinical practice and research by suggesting a minimum number of agreed-upon outcomes in clinical trials. Most COSs in the musculoskeletal field are developed for specific conditions. We propose that there are likely to be common core domains within existing musculoskeletal COSs that may be used as a starting point in the development of future COSs. We aim to identify common core domains from existing COSs and to facilitate the development of new COSs for musculoskeletal conditions. As a secondary aim, we will assess the development quality of these COSs.

METHODS: A systematic review including musculoskeletal COSs. We will search Core Outcome Measures in Effectiveness Trials (COMET) database, MEDLINE, EMBASE, Scopus, Cochrane Methodology Register and International Consortium for Health Outcome Measurement (ICHOM). Studies will be included if related to the development of a COS in adults with musculoskeletal conditions and for any type of intervention. Quality will be assessed using the Core Outcome Set-Standards for Development (COS-STAD) recommendations. Data extracted will include scope of the COS, health condition, interventions and outcome domains. Primary outcomes will be all core domains recommended within each COS. We define a common core outcome domain as one present in at least 67% of all COSs. All findings will be summarized and presented using descriptive statistics.

DISCUSSION: This systematic review of COSs will describe the core domains recommended within each musculoskeletal COS. Common domains found may be used in the initial stages of development of future musculoskeletal COSs.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021239141.

PMID:36403060 | DOI:10.1186/s13643-022-02120-1

Respir Res. 2022 Nov 19;23(1):319. doi: 10.1186/s12931-022-02242-z.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation. The present study reported the burden of COPD, and its attributable risk factors, in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex and socio-demographic index (SDI).

METHODS: Data from the Global Burden of Disease (GBD) 2019 study were used to report the burden of COPD in the MENA countries. The prevalence, deaths, and disability-adjusted life-years (DALYs) were presented as counts and age-standardised rates per 100,000 population, with their associated 95% uncertainty intervals (UIs).

RESULTS: In 2019, the regional age-standardised point prevalence and rates of death due to COPD were 2333.9 (2230.1, 2443.6) and 26.1 (22.2, 29.5) per 100,000, which represent a 30.6% (28.2%, 33.0%) increase and an 18.0% (2.8%, 30.9%) decrease, respectively, since 1990. The regional age-standardised DALY rate in 2019 was 649.1 (574.6, 717.7) per 100,000, which had decreased by 11.8% (0.9%, 21.1%) since 1990. Turkey had the highest age-standardised point prevalence in 2019 [3287.1 (3187.4, 3380.3)], while Afghanistan had the highest age-standardised death [40.4 (24.2, 52.6)] and DALY [964.5 (681.8, 1203.2)] rates. The regional age-standardised point prevalence, death and DALY rates in 2019 increased with advancing age and were higher in males in almost all age groups. There was a U-shaped association between SDI and the burden of COPD over the period 1990 to 2019. Moreover, in 2019 smoking (43.7%), ambient particulate matter pollution (22.8%) and occupational particulate matter (11.4%) had the largest proportion of attributable DALYs for both sexes.

CONCLUSIONS: COPD is one of the leading causes of death and disability in the MENA region, although the age-standardised burden has decreased over the last 30 years. Nevertheless, COPD accounted for a substantial number of deaths and DALYs, especially among the elderly. Programs targeting risk factors, like smoking, should be taken into consideration.

PMID:36403049 | DOI:10.1186/s12931-022-02242-z

Health Qual Life Outcomes. 2022 Nov 19;20(1):152. doi: 10.1186/s12955-022-02062-1.

ABSTRACT

OBJECTIVES: To explore through a systematic review, the convergent validity of EQ-5D (EQ-5D-3L and EQ-5D-5L (total score and dimensions)) with core outcomes in dementia and investigate how this may be impacted by rater-type; with the aim of informing researchers when choosing measures to use in dementia trials.

METHODS: To identify articles relevant to the convergent validity of EQ-5D with core dementia outcomes, three databases were electronically searched to September 2022. Studies were considered eligible for inclusion within the review if they included individual level data from people with dementia of any type, collected self and/or proxy reported EQ-5D and collected at least one core dementia outcome measure. Relevant data such as study sample size, stage of dementia and administration of EQ-5D was extracted, and a narrative synthesis was adopted.

RESULTS: The search strategy retrieved 271 unique records, of which 30 met the inclusion criteria for the review. Twelve different core outcome measures were used to capture dementia outcomes: cognition, function, and behaviour/mood across the studies. Most studies used EQ-5D-3L (n = 27). Evidence related to the relationship between EQ-5D and measures of function and behaviour/mood was the most robust, with unanimous directions of associations, and more statistically significant findings. EQ-5D dimensions exhibited associations with corresponding clinical outcomes, whereby relationships were stronger with proxy-EQ-5D (than self-report).

CONCLUSION: Measuring health-rated quality of life in dementia populations is a complex issue, particularly when considering balancing the challenges associated with both self and proxy report. Published evidence indicates that EQ-5D shows evidence of convergent validity with the key dementia outcomes, therefore capturing these relevant dementia outcomes. The degree of associations with clinical measures was stronger when considering proxy-reported EQ-5D and differed by EQ-5D dimension type. This review has revealed that, despite the limited targeted psychometric evidence pool and reliance on clinical and observational studies, EQ-5D exhibits convergent validity with other dementia outcome measures.

PMID:36403046 | DOI:10.1186/s12955-022-02062-1

BMC Pediatr. 2022 Nov 19;22(1):668. doi: 10.1186/s12887-022-03733-0.

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the effect of family integrated care (FICare) on the prognosis of children hospitalized with preterm infants.

METHODS: Two hundred thirty preterm infants admitted to our hospital from January 2019 to April 2021 were enrolled in a prospective randomized study and divided into 115 cases in the intervention group and 115 cases in the control group according to the random number table method, and given the FICare and the conventional care, respectively. The duration of nasogastric tube retention, time to achieve total enteral nutrition, rate of weight gain, exclusive breastfeeding rate, length of hospital stay, growth and development, readmission rate, parental self-efficacy, family functioning and complications related to prematurity were compared between the two groups.

RESULTS: Compared with the control group, the intervention group had shorter nasogastric tube retention time, shorter time to achieve total enteral nutrition, higher exclusive breastfeeding rate, shorter time of hospital stay and better growth rate. Before the intervention, there was no difference in parental self-efficacy and family functioning between the two groups; after the intervention, the intervention group had higher parental self-efficacy and higher ratings of family functioning, and the difference was statistically significant. Compared with the control group, the intervention group had a lower readmission rate and significantly lower incidence of infection and choking.

CONCLUSION: The FICare can shorten the time of nasogastric tube retention, shorten time to achieve total enteral nutrition and hospital stay, increase the rate of exclusive breastfeeding and the rate of weight gain, finally improve the prognosis of preterm infants and have a positive effect on parents.

PMID:36403036 | DOI:10.1186/s12887-022-03733-0

BMC Cancer. 2022 Nov 19;22(1):1195. doi: 10.1186/s12885-022-10275-2.

ABSTRACT

BACKGROUND: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa.

METHODS: CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0.

RESULTS: CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 – 95.5%), a specificity of 92.5% (95% CI: 85.7 – 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 – 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa.

CONCLUSIONS: In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.

PMID:36403035 | DOI:10.1186/s12885-022-10275-2