Category: Nevin Manimala

J Pediatr Orthop. 2021 Apr 23. doi: 10.1097/BPO.0000000000001836. Online ahead of print.

ABSTRACT

PURPOSE: Recurrent instability following a lateral patellar dislocation is a common indication for surgical intervention. Several surgical procedures are described in the literature to address recurrent patellar instability. Medial patellofemoral ligament (MPFL) reconstruction utilizing the quadriceps turndown technique attempts to restore medial stability. Results of the quadriceps turndown technique have previously only been reported in adult populations. The purpose of this study was to assess the safety, efficacy, and patient-reported outcomes following a quadriceps turndown MPFL reconstruction in the pediatric and adolescent population.

METHODS: Records of all patients who underwent MPFL reconstruction using a quadriceps turndown technique between 2011 and 2018 were reviewed for demographics, risk factors, complications, mechanism of injury, and concomitant procedures. Return to activities of daily living (ADLs), return to presurgery level of sport, length of bracing, and recurrent instability were assessed with the administration of the Kujala Anterior Knee Pain Score. All analyses were completed using IBM SPSS Statistics 26.

RESULTS: Thirty-six knees [14 female (39%), 22 male (61%)] from 34 patients met inclusion/exclusion criteria. The average follow-up length was 35.9±15.2 months. The average age was 16.3±1.8 years at the time of surgery. The average time for resumption of ADLs was 8.1±6.0 weeks after surgery. Ninety-four percent of patients returned to preinjury level of sport at an average of 23.6±12.0 weeks after surgery. Mean Kujala Anterior Knee Pain Score was 90.7±10.3. Female patients (P<0.001) reported significantly lower Kujala scores. Three patients (8%) experienced recurrent instability during ADLs and an additional 4 (11%) reported subjective feelings of instability only during sport or elevated activity. One knee required a return to the operating room for irrigation and debridement due to infection.

CONCLUSION: This study demonstrates that the quadriceps turndown technique for MPFL reconstruction is a safe and effective procedure for the management of recurrent patellar instability in pediatric and adolescent patients.

LEVEL OF EVIDENCE: Level III-therapeutic.

PMID:33900221 | DOI:10.1097/BPO.0000000000001836

Clin Transl Allergy. 2021 Mar;11(1):e12012. doi: 10.1002/clt2.12012.

ABSTRACT

In the 1980s, a global number of 72 fatalities were reported in the UK and the USA following the application of subcutaneous immunotherapy (SCIT). This resulted in a significant limitation of SCIT use and in the search of other routes of administration, among which sublingual immunotherapy (SLIT) showed the best balance between efficacy and safety. Data from controlled studies suggest that tablets-related anaphylaxis is an uncommon event. However, in the Eudravigilance (European database of suspected adverse drug reactions from Europe) we found reports of life-threatening events or severe local reactions under SLIT increasing over the last few years. Therefore, all efforts to minimize the related risk have to be strongly encouraged.

PMID:33900053 | DOI:10.1002/clt2.12012

J Proteome Res. 2021 Apr 26. doi: 10.1021/acs.jproteome.0c00747. Online ahead of print.

ABSTRACT

Proteinaceous aggregates containing α-synuclein protein called Lewy bodies in the substantia nigra is a hallmark of Parkinson’s disease. The molecular mechanisms of Lewy body formation and associated neuronal loss remain largely unknown. To gain insights into proteins and pathways associated with Lewy body pathology, we performed quantitative profiling of the proteome. We analyzed substantia nigra tissue from 51 subjects arranged into three groups: cases with Lewy body pathology, Lewy body-negative controls with matching neuronal loss, and controls with no neuronal loss. Using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach, we characterized the proteome both in terms of protein abundances and peptide modifications. Statistical testing for differential abundance of the most abundant 2963 proteins, followed by pathway enrichment and Bayesian learning of the causal network structure, was performed to identify likely drivers of Lewy body formation and dopaminergic neuronal loss. The identified pathways include (1) Arp2/3 complex-mediated actin nucleation; (2) synaptic function; (3) poly(A) RNA binding; (4) basement membrane and endothelium; and (5) hydrogen peroxide metabolic process. According to the data, the endothelial/basement membrane pathway is tightly connected with both pathologies and likely to be one of the drivers of neuronal loss. The poly(A) RNA-binding proteins, including the ones relevant to other neurodegenerative disorders (e.g., TDP-43 and FUS), have a strong inverse correlation with Lewy bodies and may reflect an alternative mechanism of nigral neurodegeneration.

PMID:33900085 | DOI:10.1021/acs.jproteome.0c00747

Glob Health Action. 2021 Jan 1;14(1):1904628. doi: 10.1080/16549716.2021.1904628.

ABSTRACT

Background: Dental diseases are chronic, lifelong and preventable yet affect over half the world’s population. Personal oral hygiene practices and socio-economic factors contribute to oral health outcomes affecting oral health quality of life. Integrating basic oral care within community level health systems increases accessibility and availability of oral health resources.Objective: National Oral Health Survey of Rwanda (NOHSR) data were investigated for associations of socio-demographic characteristics, personal oral hygiene practices, oral health outcomes, and oral health quality of life indicators.Methods: Data were analyzed and descriptive statistics calculated. Multivariable logistic regression models were developed to assess associations between untreated caries, calculus, and pain with various independent variables (demographics and personal oral hygiene practices). Additional logistic regression models examined associations between quality of life indicators and the aforementioned independent variables as well as untreated caries and pain.Results: Those who did not use a toothbrush (62.7%), or toothpaste (70.0%), and cleaned their teeth less than once per day (55.3%) had a higher prevalence of untreated caries. Approximately one-third of those in rural areas cleaned their teeth once per day or more compared to two-thirds of those in urban areas (35.4% vs. 71.2%). Those cleaning their teeth less than once daily were estimated to have 56.0% higher odds of caries than those who cleaned their teeth once a day or more (OR = 1.56, [95% CI 1.25-1.95]). Those with secondary education or higher and those with skilled jobs demonstrated more frequent teeth cleaning and higher toothbrush and toothpaste use. Quality-of-life indicators varied significantly with untreated caries and pain.Conclusion: Socio-economic, individual, and workforce characteristics are important considerations when assessing oral health outcomes. This study investigated social demographic disparities in relation to oral health related behaviors and outcomes. This information can help guide oral health care programming in Rwanda.

PMID:33900155 | DOI:10.1080/16549716.2021.1904628

Clin Exp Pharmacol Physiol. 2021 Apr 26. doi: 10.1111/1440-1681.13508. Online ahead of print.

ABSTRACT

Epilepsy is a chronic widely prevalent neurologic disorder, affecting brain functions with broad spectrum of deleterious consequences. High-mobility group box1 (HMGB1) is a nuclear non-histone protein that targets vital cell receptor of toll like receptor 4 (TLR4) and advanced glycation end products (RAGE). HMGB1 mediated TLR4/RAGE cascade has been scored as a key culprit in neuro-inflammatory signaling that critically evokes development of impaired cognition and epilepsy. The current study aimed to investigate the neuroprotective effect of pentoxifylline (PTX) on pentylenetetrazol (PTZ)-Kindling rats by its anti-inflammatory/antioxidant capacity besides its impact on memory and cognition were investigated, too. PTZ was intraperitoneally injected 35 mg/kg, every (48) hours, for 14 doses, to evoke kindling model. Phenytoin (30 mg/kg, i.p.) and PTX (60 mg/kg, i.p.) or their combination were given once daily for 27 days. PTX treatment showed a statistically significant effect on behavioral, histopathological and neurochemical analysis. PTX protected the PTZ kindling rats from epileptic seizures and improved memory and cognitive impairment through Morris water maze (MWM) test. Furthermore, PTX reversed PTZ hippocampal neuronal loss by decreasing protein expression of amyloid-β peptide (Aβ), Tau and β site-amyloid precursor protein-cleavage enzyme 1 (BACE1), associated with a marked reduction in expression of inflammatory mediators such as HMGB1, TL4, and RAGE proteins. Furthermore, PTX inhibited hippocampal apoptotic caspase 1 protein, total reactive oxygen species (TROS) along with upregulated erythroid 2-related factor 2 (Nrf2) content. In conclusion, PTX or its combination with phenytoin represent a promising drug to inhibit the epilepsy progression via targeting HMGB1/TLR4/RAGE signaling pathway.

PMID:33899956 | DOI:10.1111/1440-1681.13508

Water Environ Res. 2021 Apr 26. doi: 10.1002/wer.1576. Online ahead of print.

ABSTRACT

In the present study, the spatial-temporal variations of iron, lead, copper, cadmium, mercury, nickel, and zinc accumulations in the water of Şehriban Stream (northern Turkey) were investigated. Water Quality Index (WQI), Heavy Metal Evaluation Index (HEI), Pearson Correlation Index (PCI), and Factor Analysis (FA) were used in analyzing the water quality. Sampling was performed in 12 stations on monthly basis between February 2019 and January 2020 (a hydrological year). The data showed that the Şehriban Stream had significantly high water quality characteristics and the investigated toxicants were not found as dangerous for health. Although there was a slight decrease in the water quality from upstream to downstream, the stream was found to have 1^st class water quality in general. As a result of WQI and HEI, although it was determined that the water quality decreased slightly in autumn, the stream was found to be “A Grade – Excellent (<50)” and “Low Contamination (<10)”, respectively. As a result of PCI, strong positive correlations were found between almost all the toxicants investigated here (p <0.01). As a result of FA, 2 factors ( “Agriculture – Forestry” and “Rock Structure”) explained 86% of the total variance.

PMID:33899977 | DOI:10.1002/wer.1576

Colorectal Dis. 2021 Apr 26. doi: 10.1111/codi.15690. Online ahead of print.

ABSTRACT

AIM: The aim was to investigate the influence of distal resection margin and extent of mesorectal excision on long-term oncological outcomes.

DESIGN: Consecutive patients with upper and middle third rectal cancer from June 2006 to February 2016 were reviewed. Patients were divided into four groups depending on the distal margin considered as a surrogate marker of the extension of mesorectal excision (Q1: ≤ 10mm, Q2: 11-20mm, Q3: 21-30mm, Q4: ≥ 31mm).

MAIN OUTCOME MEASURES: Local recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS) were estimated. Cox regression models were used to investigate the influence of surgical and clinicopathological variables on prognosis by adjusting for confounding factors.

RESULTS: 211 patients with mid (125) and upper (86) rectal cancer underwent wide mesorectal excision. The median follow-up was 48.64 months (IQR: 28-63). 17.5% patients developed recurrence. The 5-year LRFS, DFS and OS for all patients were 93.20 %, 83.89% and 80.1%, respectively with no statistical significant differences among groups (DFS, p= 0.487; LRFS, p= 0.601; OS, p=0.468). At the multivariable analysis the recurrences and survival were associated with the quality of the mesorectum (LRFS, HR: 10.629 CI 95% 2.324-48.610; p=0.002; DFS, HR: 2.789 CI 95% 1.314-5.922; p:0.008).

CONCLUSION: A wide anatomical resection with partial mesorectal excision and shorter distal resection margin does not jeopardize the oncological outcomes.

PMID:33900002 | DOI:10.1111/codi.15690

Clin Exp Immunol. 2021 Apr 26. doi: 10.1111/cei.13608. Online ahead of print.

ABSTRACT

Renal cell carcinoma (RCC) comprises of clear cell (ccRCC) and non-clear cell (nccRCC) tumors. Despite definitive surgical resection in localized disease, recurrence often occurs. A commercial method based on a multiplex PCR assay exclusively targets rearranged T-cell receptor (TCR) genes to generate high-throughput sequencing-based data, thus allowing to characterize the immune repertoire within tumors. Here we performed a retrospective analysis on archived tumor samples from patients with recurring vs non-recurring T3 ccRCC and on samples from early nccRCC vs ccRCC. Following genomic DNA extraction and multiplex PCR, the fraction of T cells within tumors, the number of unique receptors (‘richness’) and their relative abundances (‘clonality’) were calculated. Statistical significance and correlations were calculated using Student’s T test and Spearman rho, respectively. Average fraction and clonality of T cells in tumors from non-recurring patients was 2.5-fold and 4.3-fold higher than in recurring patients (p=0.025 and p=0.043, respectively). A significant positive correlation was found between T cell fraction and clonality (Spearman rho=0.78, p=0.008). The average fraction of T cells in ccRCC tumors was 2.8-fold higher than in nccRCC tumors (p=0.015). Clonality and estimated richness were similar between ccRCC and nccRCC tumors. In summary, Recurrence of ccRCC is associated with a lower fraction and clonality of T cells within tumors. nccRCC tumors are more ‘deserted’ than ccRCC, but similar in their ability to generate a clonal T cell repertoire. Our work suggests associations between the characteristics of T cell infiltrate, histology and tumor recurrence.

PMID:33899933 | DOI:10.1111/cei.13608

Med J Aust. 2021 Apr 26. doi: 10.5694/mja2.51043. Online ahead of print.

ABSTRACT

OBJECTIVES: To estimate initial levels of symptoms of depression and anxiety, and their changes during the early months of the COVID-19 pandemic in Australia; to identify trajectories of symptoms of depression and anxiety; to identify factors associated with these trajectories.

DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study; seven fortnightly online surveys of a representative sample of 1296 Australian adults from the beginning of COVID-19-related restrictions in late March 2020 to mid-June 2020.

MAIN OUTCOME MEASURES: Symptoms of depression and anxiety, measured with the Patient Health Questionnaire (PHQ-9) depression and Generalised Anxiety Disorder (GAD-7) scales; trajectories of symptom change.

RESULTS: Younger age, being female, greater COVID-19-related work and social impairment, COVID-19-related financial distress, having a neurological or mental illness diagnosis, and recent adversity were each significantly associated with higher baseline depression and anxiety scores. Growth mixture models identified three latent trajectories for depression symptoms (low throughout the study, 81% of participants; moderate throughout the study, 10%; initially severe then declining, 9%) and four for anxiety symptoms (low throughout the study, 77%; initially moderate then increasing, 10%; initially moderate then declining, 5%; initially mild then increasing before again declining, 8%). Factors statistically associated with not having a low symptom trajectory included mental disorder diagnoses, COVID-19-related financial distress and social and work impairment, and bushfire exposure.

CONCLUSION: Our longitudinal data enabled identification of distinct symptom trajectories during the first three months of the COVID-19 pandemic in Australia. Early intervention to ensure that vulnerable people are clinically and socially supported during a pandemic should be a priority.

PMID:33899939 | DOI:10.5694/mja2.51043

JPEN J Parenter Enteral Nutr. 2021 Apr 26. doi: 10.1002/jpen.2125. Online ahead of print.

ABSTRACT

BACKGROUND: Uncertainty remains about the best route and timing of medical nutrition therapy in the acute phase of critical illness. Early combined enteral (EN) and parenteral nutrition (PN) may represent an attractive option to achieve recommended energy and protein goals in select patient groups. This meta-analysis aims to update and summarize the current evidence.

METHODS: This systematic review and meta-analysis includes randomized controlled trials (RCTs) targeting the effect of EN alone vs. a combination of EN with PN in the acute phase of adult critically ill patients. Assessed outcomes include mortality, ICU and hospital-length of stay (LOS), ventilation days, infectious complications, and physical recovery, as well as quality of life outcomes.

RESULTS: 12 RCTs with 5543 patients were included. Treatment with a combination of EN with PN led to increased delivery of macronutrients. No statistically significant effect of a combination of EN with PN vs. EN alone on any of the parameters were observed: mortality (Risk Ratio 1.0, 95% confidence intervals [CI], 0.79 to 1.28 p = 0.99), hospital LOS (mean difference -1.44, CI -5.59 to 2.71, p = 0.50), ICU LOS and ventilation days. Trends toward improved physical outcomes were observed in two of four trials.

CONCLUSION: A combination of EN with PN improved nutrition intake in the acute phase of critically ill adults and was not inferior regarding the patient´s outcomes. Large, adequately designed trials in select patient groups are needed to answer the question if this nutritional strategy has a clinically relevant treatment effect. This article is protected by copyright. All rights reserved.

PMID:33899951 | DOI:10.1002/jpen.2125