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1.
Cureus ; 14(12): e32900, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36699780

ABSTRACT

Background and aim Respiratory Rate-Oxygenation (ROX) and modified ROX (mROX) indexes have been proposed to detect early high-flow nasal cannula (HFNC) therapy failure. We evaluated the utility and relationship of ROX and mROX indexes in COVID-19 patients started on HFNC oxygen therapy. Methods This pilot study collected data from adult COVID-19 patients requiring HFNC oxygenation from 29 Jan - 29 Jun 2021. The patients were divided into two cohorts based on HFNC therapy success. ROX and mROX were compared using statistical diagnostic testing, including receiver operating characteristics and area under the curve (AUC) using online Epitools (https://epitools.ausvet.com.au/) and MedCalc software (MedCalc Software Ltd, Ostend, Belgium, https://www.medcalc.org/); p<0.05 was considered significant. Results Twenty-seven patients fulfilled the inclusion criteria; 48.15% of therapy failed. The cohort's mean ± standard deviation age was 53.93 ± 10.67 years; 74.1% were male. The accuracy of predicting failure for mean ROX versus mROX at baseline and six-hour values was 59.81 versus 70.68 and 67.42 versus 74.88, respectively (all p>0.05). The AUC for ROX and mROX at baseline and at six hours were statistically indifferent. Only an mROX of 4.05 (mean value) and 3.34 (Youden's J cut-off) had a sensitivity plus specificity at 156% and 163%, respectively. Conclusion Both ROX and mROX at baseline and six hours had fair-to-good accuracies and AUC; the differences were insignificant. Both ROX and mROX had better accuracies at six hours. However, only mROX < 4.05 at six hours fulfilled the sensitivity plus specificity criteria to be a clinically valuable screener.

2.
Arch Razi Inst ; 77(3): 1017-1026, 2022 06.
Article in English | MEDLINE | ID: mdl-36618287

ABSTRACT

Helicobacter pylori(H. pylori) which are known as Gram-negative bacteria tend to selectively colonize in the gastric epithelium. The infiltration of neutrophilic and mononuclear cells in the antrum and corpus mucosa is one of the consequences of acute and chronic gastritis colonization with H. pylori. This chronic active gastritis is the primary condition related to H. pylori colonization, and other H. pylori-associated disorders result from this chronic inflammatory process. The present study aimed to assess the relationship between H. pylori infection and extra-gastroduodenal manifestations, such as iron deficiency anemia, chronic spontaneous urticarial, diabetes mellitus, and celiac diseases with low ferritin levels. There were 235 subjects aged 3-75 years in the patient's group. The selected eligible patients were subjected to examination by non-invasive methods using stool antigen test and 14C-urea breath test (14C-UBT). The H. pylori antigen rapid test cassette (feces) was used for the qualitative detection of H. pylori antigens in human feces specimens. In the present study, 183 (71.8%) patients demonstrated positive results for H. pylori which had been detected by stool antigen test, out of whom 106 (57.9%) and 77 (42.1%) cases were female and male, respectively. The recorded data pointed out that the rates of Iron deficiency anemia, diabetes mellitus, and celiac diseases were 92(50.3%), 62 (33.9%), and 25 (13.7%), respectively. The findings of the present study revealed that H. pylori is more prevalent in females. Moreover, the diagnostic potential of the 14C UBT method was higher and more accurate than the stool antigen assay.


Subject(s)
Anemia, Iron-Deficiency , Gastritis , Helicobacter Infections , Helicobacter pylori , Helicobacter , Animals , Humans , Male , Female , Anemia, Iron-Deficiency/complications , Anemia, Iron-Deficiency/veterinary , Gastritis/complications , Gastritis/microbiology , Gastritis/veterinary , Breath Tests/methods , Helicobacter Infections/epidemiology , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/veterinary
3.
Toxicol Rep ; 10: 56-75, 2023.
Article in English | MEDLINE | ID: mdl-36583135

ABSTRACT

In recent years, small molecule inhibition of LDHA (Lactate Dehydrogenase A) has evolved as an appealing option for anticancer therapy. LDHA catalyzes the interconversion of pyruvate and lactate in the glycolysis pathway to play a crucial role in aerobic glycolysis. Therefore, in the current investigation LDHA was targeted with bioactive phytochemicals of an ethnomedicinally important plant species Oroxylum indicum (L.) Kurz. A total of 52 phytochemicals were screened against LDHA protein through molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) assay and molecular dynamics simulation to reveal three potential lead compounds such as Chrysin-7-O-glucuronide (-8.2 kcal/mol), Oroxindin (-8.1 kcal/mol) and Oroxin A (-8.0 kcal/mol). ADMET assay unveiled favorable pharmacokinetic, pharmacodynamic and toxicity properties for all the lead compounds. Molecular dynamics simulation exhibited significant conformational stability and compactness. MM/GBSA free binding energy calculations further corroborated the selection of top candidates where Oroxindin (-46.47 kcal/mol) was found to be better than Chrysin-7-O-glucuronide (-45.72 kcal/mol) and Oroxin A (-37.25 kcal/mol). Aldolase reductase and Xanthine dehydrogenase enzymes were found as potential drug targets and Esculin, the FDA approved drug was identified as structurally analogous to Oroxindin. These results could drive in establishing novel medications targeting LDHA to fight cancer.

4.
Arch Acad Emerg Med ; 10(1): e74, 2022.
Article in English | MEDLINE | ID: mdl-36381968

ABSTRACT

Porphyria is a challenging metabolic disease due to its heterogeneous presentation symptoms and its difficult diagnosis. Many affected individuals can complain of recurrent neuro-visceral attacks per year, some of which may be persistent and life-threatening, which is confusing if there is no established diagnosis. Although the motor manifestations, autonomic changes and seizure are highly suggestive, the diagnosis is often overlooked and needs confirmatory genetic testing. To the best of our knowledge, the acute intermittent porphyria (AIP) reported in this case, involving severe electrolyte disturbances and rapid severe weakness is a challenging neuro-metabolic case and is extremely rare worldwide. Here, we reported a case of AIP in a young girl who presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache which had started 10 days ago. It seems that the diagnosis of porphyria should be considered particularly in those patients with abdominal complaints associated with electrolyte disturbances, seizures, and severe progressive neuropathy.

5.
Knee Surg Sports Traumatol Arthrosc ; 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36166095

ABSTRACT

PURPOSE: Computer-assisted surgery (CAS) total knee arthroplasty (TKA) remains a controversial area of surgical practice. The aim of this study is to report the ten-year revision rates and patient-reported outcome measures (PROMS) of a single-blinded, prospective, randomised controlled trial comparing electromagnetically (EM) navigated and conventional TKA. METHODS: 199 patients were randomised to receive either EM navigated or conventional TKA where the aim of implantation was neutral mechanical alignment in all cases. Ten-year revision rates were collated and compared between the two intervention groups. Longitudinal PROMS data was collected prospectively at various time points up to 10 years post-operatively. RESULTS: Over the ten-year period, there were 23 deaths (22.8%) in the EM navigation cohort and 30 deaths (30.6%) in the conventional cohort. At 10 years post-operatively, there was no statistically significant difference in all cause revision between the EM navigation and conventional cohort (4.0 vs 6.1%, p = 0.429). When analysing causes of revision that might be influenced by utilising EM navigation, there was no statistically significant difference in revisions (3.0% EM navigated vs 4.1% conventional group, p = 0.591). Patients that received navigated TKAs had improved Oxford Knee Society, American Knee Society Score and range of motion at 3 months following surgery compared to conventional TKA (p = 0.002, p = 0.032, and p = 0.05, respectively). However, from 1 to 10 years post-operatively, both interventions had equivalent outcomes. CONCLUSION: There is no difference in revision rates or clinical outcomes comparing EM navigated versus conventional TKA at ten-year follow-up. The expected mortality rate makes it unlikely that a difference in revision rates will reach statistical significance in the future. In the setting of an experienced knee arthroplasty surgeon, it is difficult to justify the additional costs of CAS in TKA surgery. LEVEL OF EVIDENCE: I.

6.
Micromachines (Basel) ; 13(6)2022 Jun 18.
Article in English | MEDLINE | ID: mdl-35744576

ABSTRACT

This paper presents a numerical reduced-order modeling (ROM) approach for complex multi-layered arrays of piezoelectric micromachined ultrasonic transducers (PMUTs). The numerical modeling technique adopted to generate an array of PMUTs consisting of a considerable number of transducers allows for a large reduction in computational cost without reducing accuracy. The modeling idea is based on coupling shell elements applied to the PMUT structural layers with 3D-solid elements applied to the piezoelectric layer. A set of eigenfrequency and frequency domain analyses are presented considering a single ROM of a PMUT performing in different ambients and the performing central frequencies are obtained for every considered scenario. A unique arrangement of 228 PMUTs is presented and tested for its ability to transmit and receive acoustic waves. The operating frequency band of the array and the level of interference and cross-talk among different PMUTs in the near field are estimated. Finally, the results from a preliminary experimental test performed to analyze the acoustic abilities of an 8 × 8 array of PMUTs are presented. A corresponding numerical model is created and the obtained results matched the experimental data, leading to a validation of the modeling technique proposed in this work.

7.
Cureus ; 14(4): e24054, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35573526

ABSTRACT

Transcatheter aortic valve replacement (TAVR) is a technique that can be performed through multiple approaches, and the benefits of one approach over another are still being evaluated to make sure patients receive the best possible care. Our meta-analysis aims to compare clinical and procedural outcomes of the transaxillary (TAx) and transaortic (TAo) approaches to validate the more optimal procedure. The systematic literature search was done via PubMed/MEDLINE, Embase, and the Cochrane Central databases from inception to December 2021, to identify articles reporting data on both TAx TAVR and TAo TAVR. In addition, we checked ClinicalTrials.gov for more published or unpublished trials. Baseline patient characteristics, procedure results, and clinical results were extracted from the article and pooled for analysis. A quantitative meta-analysis was conducted using Review Manager (RevMan) version 5.3 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). The outcomes extracted included blood transfusion, conversion to sternotomy, tamponade, contrast amount, procedure time, bleeding incidents (minor, major, or life-threatening), length of stay (LOS), vascular complications (minor or major), acute kidney injury (AKI), paravalvular leak (PVL), permanent pacemaker (PPM) implantation, 30-day mortality, one-year mortality, 30-day stroke, and device success. The final analysis included 11 articles, consisting of 10 observational studies and a pivotal trial. Cumulative results revealed that the TAo approach had a significantly lower incidence of vascular complications (RR = 2.30; 95% CI = 1.22 to 4.35), and the need for implantation of a permanent pacemaker (RR = 1.82; 95% CI = 1.30 to 2.54) along with a lower amount of contrast (mean difference (MD) = 27.40; 95% CI = 3.73 to 51.08) needed to be used. The TAx group was associated with a significantly lower 30-day mortality (RR = 0.46; 95% CI = 0.31 to 0.69), AKI (RR = 0.47; 95% CI = 0.33 to 0.67), and length of hospital stay (MD = -1.95; 95% CI = -2.51 to -1.38). No significant difference was observed between the outcomes of 30-day stroke (RR = 1.38; 95% CI = 0.81 to 2.33), PVL (RR = 1.05; 95% CI = 0.50 to 2.18), tamponade (RR = 0.71; 95% CI = 0.12 to 4.03), conversion to sternotomy (RR = 0.51; 95% CI = 0.06 to 4.30), device success (RR = 0.97; 95% CI = 0.88 to 1.07), the incidence of bleeding (RR = 0.75; 95% CI = 0.51 to 1.10), and procedure time (MD = 4.44; 95% CI = -96.30 to 105.17). Both the procedures were associated with their benefits and risks. Although most of the outcomes favored TAx transcatheter aortic valve implantation (TAVI), it is too early to say if it would be better than TAo TAVI. To authenticate the findings concluded in this meta-analysis and further improve our understanding of the efficacy, safety, and risk profile between TAx and TAo approaches for TAVI, large sample randomized clinical trials are required on a wide scale.

8.
Trans R Soc Trop Med Hyg ; 116(12): 1123-1128, 2022 Dec 02.
Article in English | MEDLINE | ID: mdl-35474480

ABSTRACT

BACKGROUND: Lactating mothers are susceptible to anaemia. Little published data are available on lactational anaemia in Africa, including Sudan. This study was conducted to assess the prevalence of and associated factors for anaemia among lactating mothers in eastern Sudan. METHODS: A cross-sectional study was conducted and sociodemographic and clinical characteristics were gathered through a questionnaire. RESULTS: A total of 650 lactating mothers were included in the analysis. Their median age and parity were 28.0 y (interquartile range [IQR] 23.7‒32.0) and 3.0 (IQR 2.0‒4.0), respectively. Haemoglobin (Hb) levels ranged from 7.0 to 15.0 g/dL (median 11.2 [IQR 10.4‒12.0]). Of the 650 lactating mothers, 442 (68.0%) had anaemia (Hb <12.0 g/dL). In multivariate analysis, lactating mothers with education less than the secondary level (adjusted odds ratio [AOR] 1.58 [95% confidence interval {CI} 1.05 to 2.37]) and lactating mothers who underwent caesarean delivery (AOR 1.74 [95% CI 1.17 to 2.58]) had a higher probability of being anaemic. Employment was associated to a lower frequency of anaemia (AOR 0.39 [95% CI 0.20 to 0.79]). CONCLUSIONS: This study showed a high prevalence of anaemia among lactating mothers. Public health intervention activities designed towards education would be helpful to reduce anaemia.


Subject(s)
Anemia , Mothers , Pregnancy , Female , Humans , Prevalence , Cross-Sectional Studies , Lactation , Sudan/epidemiology , Risk Factors , Anemia/epidemiology
9.
Genome Integr ; 13: 1, 2022.
Article in English | MEDLINE | ID: mdl-35444787

ABSTRACT

Radiotherapy is one of the most important options for treating breast cancer in humans. The development of biomarkers to monitor radiosensitivity is scarce. The aim of this study is to investigate the γH2AX levels in the human blood samples 0.5 h after radiotherapy compared to the levels before radiotherapy in breast cancer patients in relation to their respective body mass index (BMI). Blood plasma samples were collected from a total of 20 breast cancer patients before and after radiotherapy to measure γH2AX levels with an antibody against γH2AX based on enzyme-linked immunosorbent assay technique. The median BMI of the patients was 30 kg/m2. γH2AX was differentially expressed in breast cancer patients before radiotherapy. γH2AX levels significantly increased in 14 patients after radiotherapy (P = 0.006), whereas γH2AX levels decreased in three patients after radiotherapy, and three patients were excluded. There was no correlation between γH2AX values after radiotherapy and BMI (P = 0.5, r = 0.1). Our results suggest that γH2AX can be used by ELISA technique to measure γH2AX in the blood plasma of breast cancer patients undergoing radiotherapy and can be considered a biomarker of radiosensitivity.

10.
Bone Joint J ; 104-B(4): 504-509, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35360946

ABSTRACT

AIMS: The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases. METHODS: This retrospective cohort study using a prospectively collected database involved 56 patients who underwent acetabular reconstruction for periacetabular bone metastases or haematological malignancy using a single APC between January 2009 and 2020. The mean follow-up was 20 months (1 to 143). The primary outcome measure was implant survival. Postoperative radiographs were analyzed for loosening and failure. Patient and implant survival were assessed using a competing risk analysis. Secondary parameters included primary malignancy, oncological treatment, surgical factors, length of stay in hospital, and postoperative complications. RESULTS: A total of 33 patients (59%) died during the study period at a mean of 15 months postoperatively (1 to 63). No patient had radiological evidence of loosening or failure. Acetabular component survival was 100%. Three patients (5.4%) had further surgery; one (1.8%) underwent revision of the femoral component for dislocation, one required debridement with implant retention for periprosthetic joint infection, and one required closed reduction for dislocation. Using death as a competing risk, at 100 months, the probability of revision was 0.036 and the risk of death was 0.84. CONCLUSION: With appropriate patient selection, the antiprotrusio cage offers good implant survival, with a reasonable perioperative complication rate in this high-risk group of patients when managing metastatic disease or haematological malignancy around the acetabulum. Cite this article: Bone Joint J 2022;104-B(4):504-509.


Subject(s)
Arthroplasty, Replacement, Hip , Bone Neoplasms , Acetabulum/pathology , Acetabulum/surgery , Arthroplasty, Replacement, Hip/adverse effects , Bone Neoplasms/pathology , Humans , Postoperative Complications/etiology , Retrospective Studies
11.
Ann Hum Genet ; 86(4): 181-194, 2022 07.
Article in English | MEDLINE | ID: mdl-35118659

ABSTRACT

BACKGROUND: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes. METHOD: We applied exome sequencing to identify potential variants causing syndromic intellectual disability in six Sudanese patients from four unrelated families. Data sharing through the Varsome portal corroborated the diagnosis of one of these patients and a Tunisian patient investigated through exome sequencing. Sanger sequencing validated the identified variants and their segregation with the phenotypes in the five studied families. RESULT: We identified three pathogenic/likely pathogenic variants in CCDC82, ADAT3, and HUWE1 and variants of uncertain significance in HERC2 and ATP2B3. The patients with the CCDC82 variants had microcephaly and spasticity, two signs absent in the two previously reported families with CCDC82-related intellectual disability. CONCLUSION: In conclusion, we report new patients with pathogenic mutations in the genes CCDC82, ADAT3, and HUWE1. We also highlight the possibility of extending the CCDC82-linked phenotype to include spastic paraplegia and microcephaly.


Subject(s)
Adenosine Deaminase , Intellectual Disability , RNA-Binding Proteins , Tumor Suppressor Proteins , Ubiquitin-Protein Ligases , Adenosine Deaminase/genetics , Exome , Humans , Intellectual Disability/diagnosis , Microcephaly/genetics , Mutation , Paraplegia/genetics , Pedigree , Phenotype , RNA-Binding Proteins/genetics , Sudan , Tumor Suppressor Proteins/genetics , Tunisia , Ubiquitin-Protein Ligases/genetics
12.
Molecules ; 27(1)2022 Jan 04.
Article in English | MEDLINE | ID: mdl-35011528

ABSTRACT

In this study, ultrasound-assisted extraction conditions were optimized to maximize the yields of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol from S. alexandrina (aerial parts). The three UAE factors, extraction temperature (S1), extraction time (S2), and liquid to solid ratio (S3), were optimized using response surface methodology (RSM). A Box-Behnken design was used for experimental design and phytoconstituent analysis was performed using high-performance liquid chromatography-UV. The optimal extraction conditions were found to be a 64.2 °C extraction temperature, 52.1 min extraction time, and 25.2 mL/g liquid to solid ratio. The experimental values of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol (2.237, 12.792, 2.457, 0.261, and 1.529%, respectively) agreed with those predicted (2.152, 12.031, 2.331, 0.214, and 1.411%, respectively) by RSM models, thus demonstrating the appropriateness of the model used and the accomplishment of RSM in optimizing the extraction conditions. Excellent antioxidant properties were exhibited by S. alexandrina methanol extract obtained using the optimized extraction conditions with a DPPH assay (IC50 = 59.7 ± 1.93, µg/mL) and ABTS method (47.2 ± 1.40, µg/mL) compared to standard ascorbic acid.


Subject(s)
Antioxidants/pharmacology , Chemical Fractionation/methods , Plant Components, Aerial/chemistry , Senna Extract/pharmacology , Senna Plant/chemistry , Sonication , Ultrasonic Waves , Algorithms , Antioxidants/chemistry , Antioxidants/isolation & purification , Dose-Response Relationship, Drug , Models, Theoretical , Molecular Structure , Phytochemicals , Senna Extract/chemistry , Senna Extract/isolation & purification
14.
Eur J Orthop Surg Traumatol ; 32(8): 1591-1599, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34628535

ABSTRACT

INTRODUCTION: Limb-sparing surgery with negative margins is possible in most soft tissue sarcoma (STS) resections and focuses on maximising function and minimising morbidity. Various risk factors for surgical site infections (SSIs) have been reported in the literature specific to sarcoma surgery. The aim of this study is to determine whether systemic inflammatory response prognostic scoring systems can predict post-operative SSI in patients undergoing potentially curative resection of STS. METHODS: Patients who had a planned curative resection of a primary STS at a single centre between January 2010 and December 2019 with a minimum follow-up of 6 months were included. Data were extracted on patient and tumour characteristics, and pre-operative blood results were used to calculate inflammatory prognostic scores based on published thresholds and correlated with risk of developing SSI or debridement procedures. RESULTS: A total of 187 cases were included. There were 60 SSIs. On univariate analysis, there was a statistically significant increased risk of SSI in patients who are diabetic, increasing specimen diameter, American Society of Anaesthesiology (ASA) grade 3, use of endoprosthetic replacement, blood loss greater than 1 L, and junctional tumour location. Modified Glasgow prognostic score, C-reactive protein/albumin ratio and neutrophil-platelet score (NPS) were statistically associated with the risk of SSI. On multivariate analysis, ASA grade 3, junctional tumour location and NPS were independently associated with the risk of developing a SSI. CONCLUSION: This study supports the routine use of simple inflammation-based prognostic scores in identifying patients at increased risk of developing infectious complications in patients undergoing potentially curative resection of STS.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Surgical Wound Infection/diagnosis , Surgical Wound Infection/etiology , Prognosis , C-Reactive Protein , Sarcoma/surgery , Sarcoma/pathology , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology , Risk Factors , Retrospective Studies
15.
Int J Clin Pract ; 75(12): e14892, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34541736

ABSTRACT

OBJECTIVE: The aim of this study was to determine the prevalence and associated factors for diabetic foot (DF) amongst patients with diabetes Mellites (DM) in Nahr an Nil State (River Nile State), Sudan. METHODS: We conducted a cross-sectional study between May and August 2018. DM patients were examined for DF, and clinical data were collected through a questionnaire. RESULTS: A total of 2048 DM patients were enrolled in the study. Their median (interquartile range) age was 58 (15) years. Over half (54.2%) of the patients were female. The median (interquartile range) of the duration of diabetes was 5 (6) years. In this sample, 70.1% of the patients had type 2 DM and 47.6% had hypertension as well. Of all enrolled patients, 21.2% had normal weight, 1.2% were underweight, 37.2% were overweight and 40.4% were obese. Two hundred and sixty (12.7%) patients had DF. Multivariate regression analyses showed that age [adjusted odds ratio (AOR) = 1.21; 95% confidence interval (CI): 1.18-1.24] and duration of DM (AOR = 1.09; 95% CI: 1.05-1.14) were positively associated with DF. Moreover, type 2 DM (AOR = 1.77; 95% CI: 1.17-2.68), family history of DM (AOR = 1.5; 95% CI: 1.07-2.09), hypertension (AOR = 2.93; 95% CI: 2.07-4.16) and obesity (AOR = 2.86; 95% CI: 1.70-4.81) were associated with DF. There was no significant association between DF and gender or overweight status. CONCLUSION: This study found a high prevalence of DF. Older age, type 2 DM, duration of DM, family history of DM and hypertension are associated with DF.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Aged , Cross-Sectional Studies , Diabetic Foot/epidemiology , Female , Humans , Middle Aged , Prevalence , Risk Factors , Sudan/epidemiology
16.
Phys Rev X ; 10(1)2020.
Article in English | MEDLINE | ID: mdl-34540355

ABSTRACT

Fluorescence time traces are used to report on dynamical properties of molecules. The basic unit of information in these traces is the arrival time of individual photons, which carry instantaneous information from the molecule, from which they are emitted, to the detector on timescales as fast as microseconds. Thus, it is theoretically possible to monitor molecular dynamics at such timescales from traces containing only a sufficient number of photon arrivals. In practice, however, traces are stochastic and in order to deduce dynamical information through traditional means-such as fluorescence correlation spectroscopy (FCS) and related techniques-they are collected and temporally autocorrelated over several minutes. So far, it has been impossible to analyze dynamical properties of molecules on timescales approaching data acquisition without collecting long traces under the strong assumption of stationarity of the process under observation or assumptions required for the analytic derivation of a correlation function. To avoid these assumptions, we would otherwise need to estimate the instantaneous number of molecules emitting photons and their positions within the confocal volume. As the number of molecules in a typical experiment is unknown, this problem demands that we abandon the conventional analysis paradigm. Here, we exploit Bayesian nonparametrics that allow us to obtain, in a principled fashion, estimates of the same quantities as FCS but from the direct analysis of traces of photon arrivals that are significantly smaller in size, or total duration, than those required by FCS.

17.
Bone Joint J ; 104-B(1): 168-176, 2022 01.
Article in English | MEDLINE | ID: mdl-34969280

ABSTRACT

AIMS: The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. METHODS: This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. RESULTS: We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. CONCLUSION: This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168-176.


Subject(s)
Sarcoma/blood , Sarcoma/surgery , Adult , Aged , Biomarkers, Tumor/analysis , Blood Cell Count , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Sarcoma/mortality , Sarcoma/pathology , Serum Albumin/analysis , Survival Analysis
18.
Eur J Orthop Surg Traumatol ; 32(6): 1127-1136, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34357474

ABSTRACT

INTRODUCTION: The optimum choice of bearing surfaces in total hip replacement (THR) in the younger and active patient remains controversial. The aim of this study was to report the 10 year clinical outcomes, and a median of 15 year implant survival and incidence of complications in a series of Alumina ceramic-on-ceramic THRs utilising an uncemented shell and cemented stem. METHODS: From January 2004 to December 2007, 175 consecutive patients (195 hips) underwent primary THR. The acetabular components was Trident Peripheral Self Locking (Stryker Orthopaedics) with a third-generation ceramic head and liner (Alumina ceramic, Stryker Orthopaedics). The stem utilised was an Exeter V-40 (Stryker Orthopaedics). Data were collated on demographics, surgical factors, clinical outcomes, radiographic outcomes and revision. RESULTS: 23 patients (27 THRs) died during the follow-up period at a median of 7.8 (3.8 to 9.0) years post-operatively due to causes unrelated to the THR. Median age at time of surgery was 55 (interquartile range 48-60) years. Median follow-up for surviving patients was 15.2 years. Survivorship for all-cause revision was 97.2%. Increasing patient age at time of surgery was associated with a higher OHS at 10 years (p = 0.022). 32 mm head diameter had an improved OHS at 3 months (p = 0.014) and 10 years (p = 0.030). Posterior surgical approach had a statistically significant better OHS at 3 months (p = 0.015) and 1 year (p < 0.001), but the effect was not significant at 10 years (p = 0.440). CONCLUSION: The findings of this study support excellent long-term outcomes and survivorship of Alumina ceramic-on-ceramic bearing in a hybrid THR in a younger population. Surgical factors leading to a more favourable outcome were the use of a 32 mm femoral head and a posterior approach. Increasing age at surgery demonstrated the most sustained improvement in 10 year clinical outcomes.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Aluminum Oxide , Arthroplasty, Replacement, Hip/adverse effects , Ceramics , Follow-Up Studies , Humans , Middle Aged , Prosthesis Design , Prosthesis Failure , Reoperation , Treatment Outcome
19.
Pediatr Res ; 91(5): 1049-1056, 2022 04.
Article in English | MEDLINE | ID: mdl-34230621

ABSTRACT

There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5-64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0-7.3 kPa: 45.0-54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. IMPACT: There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5-7 kPa was inferred following systematic review.


Subject(s)
Hypocapnia , Infant, Premature, Diseases , Carbon Dioxide , Humans , Hypercapnia , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/etiology , Respiration, Artificial/adverse effects
20.
Bone Joint J ; 103-B(5): 872-880, 2021 May.
Article in English | MEDLINE | ID: mdl-33934654

ABSTRACT

AIMS: Uncemented metal acetabular components show good osseointegration, but material stiffness causes stress shielding and retroacetabular bone loss. Cemented monoblock polyethylene components load more physiologically; however, the cement bone interface can suffer fibrous encapsulation and loosening. It was hypothesized that an uncemented titanium-sintered monoblock polyethylene component may offer the optimum combination of osseointegration and anatomical loading. METHODS: A total of 38 patients were prospectively enrolled and received an uncemented monoblock polyethylene acetabular (pressfit) component. This single cohort was then retrospectively compared with previously reported randomized cohorts of cemented monoblock (cemented) and trabecular metal (trabecular) acetabular implants. The primary outcome measure was periprosthetic bone density using dual-energy x-ray absorptiometry over two years. Secondary outcomes included radiological and clinical analysis. RESULTS: Although there were differences in the number of males and females in each group, no significant sex bias was noted (p = 0.080). Furthermore, there was no significant difference in age (p = 0.910) or baseline lumbar bone mineral density (BMD) (p = 0.998) found between any of the groups (pressfit, cemented, or trabecular). The pressfit implant initially behaved like the trabecular component with an immediate fall in BMD in the inferior and medial regions, with preserved BMD laterally, suggesting lateral rim loading. However, the pressfit component subsequently showed a reversal in BMD medially with recovery back towards baseline, and a continued rise in lateral BMD. This would suggest that the pressfit component begins to reload the medial bone over time, more akin to the cemented component. Analysis of postoperative radiographs revealed no pressfit component subsidence or movement up to two years postoperatively (100% interobserver reliability). Medial defects seen immediately postoperatively in five cases had completely resolved by two years in four patients. CONCLUSION: Initially, the uncemented monoblock component behaved similarly to the rigid trabecular metal component with lateral rim loading; however, over two years this changed to more closely resemble the loading pattern of a cemented polyethylene component with increasing medial pelvic loading. This indicates that the uncemented monoblock acetabular component may result in optimized fixation and preservation of retroacetabular bone stock. Cite this article: Bone Joint J 2021;103-B(5):872-880.


Subject(s)
Absorptiometry, Photon , Arthroplasty, Replacement, Hip/methods , Bone Density , Hip Prosthesis , Aged , Aged, 80 and over , Biomechanical Phenomena , Cementation , Female , Humans , Male , Materials Testing , Middle Aged , Osseointegration , Polyethylene , Prospective Studies , Prosthesis Failure , Retrospective Studies , Surface Properties , Titanium
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