Nevin Manimala

Bratisl Lek Listy. 2023;124(11):802-809. doi: 10.4149/BLL_2023_123.

ABSTRACT

RATIONALE: Acute pancreatitis (AP) is a serious acute abdominal disease. AP is often referred to as an unpredictable illness, which can take a mild to severe (fatal) course.

AIMS OF THE STUDY: 1) To identify clinical parameters that are significantly related to the clinical course of acute pancreatitis. 2) To compile a scoring system enabling the severity of AP to be predicted when the patient is first admitted to hospital.

METHODS: Analysis of available publications and clinical guidance, and retrospective analysis of data on patients hospitalised with AP at our clinic enable us to identify clinical details and laboratory results recorded at the time of patients’ admission to hospital that are related to the subsequent severity of the disease. For the purposes of statistical analysis, the sample of patients was divided into two groups: group A (mild AP, without local or organ complications), group B (moderately severe and severe AP with local and/or organ complications).

PATIENT GROUPS AND RESULTS: In total, between 01.01.2013 and 30.06.2022, 312 patients with acute pancreatitis were allocated to the retrospective-prospective study sample. 74 % (231/312) of these patients were allocated to group A and 26 % (81/312) were allocated to group B. Univariate analysis of the data collected on the patient sample identified 5 parameters that are statistically significantly associated with the severity of the clinical course of the disease. Presence of SIRS on admission (A vs B, Odds ratio 10.787, 95% CI 5.09-22.85, p < 0.0001), diabetes mellitus type 2 in case history (A vs B, Odds ratio 7.703, 95% CI 3.04-19.51, p 2 mmol/l (A vs B, Odds ratio 3.293, 95% CI 1.59-6.82, p = 0.0013).In order to develop a scoring system, each of these parameters was allocated a points value based on its Odds ratio (OR): presence of SIRS 3 points, hypocalcaemia 3 points, diabetes mellitus type 2 in case history 2 points, urea concentration > 8 mmol/l 1 point and lactate concentration > 2 mmol/l 1 point. The authors refer to their scoring system as The Acute Pancreatitis Admission Score (APAS). The accuracy of APAS was modelled for various cut off values. Across the whole sample, we ascertained that an APAS ≥ 4 points predicts moderately severe or severe AP with a sensitivity of 81 % (95% CI: 71 – 89 %) and specificity of 87 % (95 CI: 81 – 91 %). The positive predictive value (PPV) of APAS ≥ 4 is 0.68, while its negative predictive value (NPV) is 0.93 and accuracy 0.85 (95% CI 0.81 – 0.89).

CONCLUSION: In this study we identify significant simple clinical and laboratory parameters that are commonly tested as part of an initial examination when admitting a patient with AP to hospital. Having identified these parameters we are able to establish a simple scoring system that is able to predict the severity of the course of AP at the moment of hospitalisation (Tab. 5, Fig. 2, Ref. 27).

PMID:37874801 | DOI:10.4149/BLL_2023_123

PLoS One. 2023 Oct 24;18(10):e0286476. doi: 10.1371/journal.pone.0286476. eCollection 2023.

ABSTRACT

OBJECTIVE: HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally.

METHODS: This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran’s Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis.

RESULTS: Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7-42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2-46.4%) than female (36.5%, 95% CI: 26.9-50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%).

CONCLUSIONS: Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation.

PMID:37874794 | DOI:10.1371/journal.pone.0286476

Br J Dermatol. 2023 Oct 24:ljad410. doi: 10.1093/bjd/ljad410. Online ahead of print.

ABSTRACT

BACKGROUND: Co-existing long-term conditions (LTC) in psoriasis and their potential causal associations with the disease are not well-established.

OBJECTIVES: This study aims to determine distinct clusters of LTC in people with psoriasis and the potential bi-directional causal association between these LTC and psoriasis.

METHODS: Using latent class analysis, cross-sectional data of people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related co-morbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTC. Two-sample bidirectional Mendelian randomisation (MR) analysis assessed potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10-8).

RESULTS: Five co-morbidity clusters were identified in a population of 10,873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure (rg = 0.23, p = 8.8 × 10-8), depression (rg = 0.12, p = 2.7 × 10-5), coronary artery disease (CAD) (rg = 0.15, p = 2 × 10-4), and type 2 diabetes (rg = 0.19, p = 3 × 10-3). Genetic liability to CAD was associated with an increased risk of psoriasis (ORIVW = 1.159; 95%CI 1.055-1.274; p = 2 × 10-3). The MR-PRESSO (ORMR-PRESSO = 1.13; 95%CI 1.042-1.228; p = 6 × 10-3) and the MR-RAPS (ORMR-RAPS = 1.149; 95%CI 1.062-1.242; p = 5 × 10-4) approaches corroborate the IVW findings. The weighted median generated similar and consistent effect estimates but was not statistically significant (ORWM = 1.076; 95%CI 0.949-1.221; p = 0.251). Evidence for a suggestive increased risk was detected for CAD (ORIVW = 1.031; 95%CI 1.003-1.059; p = 0.032) and heart failure (ORIVW = 1.019; 95%CI 1.005-1.033; p = 9 × 10-3) in those with genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance.

CONCLUSIONS: Five distinct clusters of psoriasis co-morbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Co-existing LTC share with psoriasis common genetic and non-genetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted coronary artery disease is possibly associated with an increased risk of psoriasis, altering our prior knowledge.

PMID:37874776 | DOI:10.1093/bjd/ljad410

Anal Chem. 2023 Oct 24. doi: 10.1021/acs.analchem.3c04316. Online ahead of print.

ABSTRACT

Rapid antimicrobial susceptibility testing (AST) with the ability of bacterial identification is urgently needed for evidence-based antibiotic prescription. Herein, we propose an enzymatic AST (enzyAST) that employs β-d-glucuronidase as a biomarker to identify pathogens and profile phenotypic susceptibilities simultaneously. EnzyAST enables to offer binary AST results within 30 min, much faster than standard methods (>16 h). The general applicability of enzyAST was verified by testing the susceptibility of two Escherichia coli strains to three antibiotics with different action mechanisms. The pilot study also shows that the minimal inhibitory concentrations can be determined by enzyAST with the statistical analysis of enzymatic activity of the bacteria population exposed to varying antibiotic concentrations. With further development of multiple bacteria and sample treatment, enzyAST could be able to evaluate the susceptibility of pathogens in clinical samples directly to facilitate the evidence-based therapy.

PMID:37874622 | DOI:10.1021/acs.analchem.3c04316

JMIR Res Protoc. 2023 Oct 24;12:e51861. doi: 10.2196/51861.

ABSTRACT

BACKGROUND: Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally.

OBJECTIVE: This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine.

METHODS: We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated.

RESULTS: The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group.

CONCLUSIONS: This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51861.

PMID:37874614 | DOI:10.2196/51861

Lab Chip. 2023 Oct 24. doi: 10.1039/d3lc00499f. Online ahead of print.

ABSTRACT

Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.

PMID:37874569 | DOI:10.1039/d3lc00499f

Neuro Endocrinol Lett. 2023 Oct 23;44(7). Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effect of postnatal primary repair surgery time on short-term (first 30 days) prognosis in newborns with Meningomyelocele (MMC).

METHODS: The study was conducted in the neonatal intensive care unit at a tertiary training and research hospital. The records of 41 MMC neonates were retrospectively reviewed. Demographic and clinical characteristics, surgical time, hospitalization and antibiotic duration, complications and associated anomalies were recorded.

RESULTS: There were 18 newborns in the early surgery (≤3 days) group and 23 newborns in the late surgery (>3 days up to 30 days) group.. There was no difference between groups in terms of birth weight, gestational week, head circumference, sex and type of delivery (p > 0.05). The length of hospitalization (17.2 ± 8.2 days vs 24.8 ± 16.1 days, p > 0.05) and antibiotic duration (11.8 ± 7.6 days vs 13.8 ± 10.1 days, p > 0.05) did not have significant difference. The number of neonates reoperated in the first 30 days was similar in early surgery group and in late surgery group (5 (27.7%) vs 6 (26.1%), p > 0.05). The number of patients requiring ventriculoperitoneal shunt was 9 (50%) in the early surgery group and 13 (56.5%) in the late surgery group. Surgical complications such as minor-major wound dehiscence, cerebrospinal fluid leakage, local infection, meningitis and ventriculitis were not statistically different between the groups (9 (50%) vs 8 (34.8%), (p > 0.05).

CONCLUSION: Surgical complications were not statistically different between the early and late surgery group, although the presence of surgical complications may be effective in the short-term prognosis of MMC.

PMID:37874554

Neuro Endocrinol Lett. 2023 Oct 23;44(7). Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the magnetic resonance imaging (MRI) and computed tomography (CT) findings along with other surgical and pathologic features as prognosis predictors in pancreatic neuroendocrine tumors (PNETs).

METHODS: In this study, we retrospectively analyzed a clinical data pool of patients with pathologically confirmed PNETs. CT and MRI findings were evaluated as potential prediction parameters of tumor-nodes-metastases (TNM) stage and grade, using Fisher’s exact test. Univariate and multivariate logistic regression models were used to estimate the risk factors associated with tumor recurrence after surgery. The Kaplan-Meier method and Cox proportional hazards model were used for recurrence-free survival analysis.

RESULTS: The predictors of higher TNM stages were tumor diameter, tumor boundary, distant metastases, and lymphadenopathy on CT scan. From MRI images, tumor diameter, T2-weighted image, tumor enhancement, and pancreatic duct dilatation showed statistically significant differences among TNM stages. Univariate analysis showed that American Joint Committee on Cancer (AJCC) TNM stage, World Health Organization (WHO) tumor grade, sex, smoking, and drinking were associated with tumor recurrence and disease-free survival (DFS); while tumor and metastasis also affected DFS. Multivariate survival analysis confirmed that AJCC TNM was an independent predictor after adjusting other covariates. Peripancreatic invasion and lymph node metastases as well as blurred boundary detected by CT or MRI may be independent risk factors for TNM stage and clinical outcome of PNETs.

CONCLUSION: TNM stage is a valuable predictor of prognosis in PNETs. Information from CT and MRI imaging can be used to determine the TNM stage, and to estimate the tumor prognosis, guide the follow-up, and avoid ineffective treatments.

PMID:37874552

Eur J Clin Invest. 2023 Oct 24:e14114. doi: 10.1111/eci.14114. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatic heart disease remains the most common cardiovascular disease in children and young adults. The outcome of interventional versus medical therapy on the long term is not fully elucidated yet. This study provides contemporary data on the clinical profile, treatment and follow up of patients with rheumatic mitral stenosis (MS) in Tanzania.

METHODS: Patients’ medical information, investigations and treatment data were recorded in this prospective cohort study. They were followed up for 6-24 months to determine the long-term outcome. Interventional therapy was defined as a combination of surgery and percutaneous balloon mitral valvuloplasty. Kaplan-Meier curves and Cox proportional hazards model were used in analyses. p-Value < 0.05 was considered statistically significant.

RESULTS: We enrolled 290 consecutive patients. Interventions were done in half of the patients. Median follow up was 23.5 months. Mortality was higher in the medical than interventional treatment (10.4% vs. 4%, log-rank p = 0.001). Median age was 36 years, females (68.3%) and low income (55.5%). Multivalvular disease was found in 116 (40%) patients, atrial fibrillation (31.4%), stroke/transient ischaemic attack (18.9%) and heart failure class III-IV (44.1%). Median (IQR) duration of disease was 3 (4) years, secondary prophylaxis (27.7%) and oral anticoagulants use (62.3%). In multivariable analysis, the risk of death among patients on medical was 3.07 times higher than those on interventional treatment (crude HR 3.07, 95% CI 1.43-6.56, p = 0.004), 2.44 times higher among patients with arrhythmias versus without arrhythmias (crude HR 2.44, 95% CI 1.19-4.49, p = 0.015) and 2.13 times higher among patients with multivalvular than single valve disease (crude HR 2.13, 95% CI 1.09-4.16, p = 0.026).

CONCLUSIONS: Intervention is carrying low mortality compared to medical treatment. Arrhythmias and multivalvular disease are associated with a high mortality. Rheumatic MS is more prevalent in young people, females and individuals with low income. There is a late hospital presentation and a low use of both secondary prophylactic antibiotics and anticoagulants.

PMID:37874538 | DOI:10.1111/eci.14114

Odontology. 2023 Oct 24. doi: 10.1007/s10266-023-00851-8. Online ahead of print.

ABSTRACT

To evaluate the osteogenic potential of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on human stem cells from the apical papilla (SCAP) we isolated, characterized, and then cultured in an osteogenic medium cells with PRF and/or LLLT (660 nm, 6 J/m2-irradiation). Osteogenic differentiation was assessed by bone nodule formation and expression of bone morphogenetic proteins (BMP-2 and BMP-4), whereas the molecular mechanisms were achieved by qRT-PCR and RNA-seq analysis. Statistical analysis was performed by ANOVA and Tukey’s post hoc tests (p < 0.05* and p < 0.01**). Although PRF and LLLT increased bone nodule formation after 7 days and peaked at 21 days, the combination of PRF + LLLT led to the uppermost nodule formation. This was supported by increased levels of BMP-2 and -4 osteogenic proteins (p < 0.005). Furthermore, the PRF + LLLT relative expression of specific genes involved in osteogenesis, such as osteocalcin, was 2.4- (p = 0.03) and 28.3- (p = 0.001) fold higher compared to the PRF and LLLT groups, and osteopontin was 22.9- and 1.23-fold higher, respectively (p < 0.05), after 7 days of interaction. The transcriptomic profile revealed that the combination of PRF + LLLT induces MSX1, TGFB1, and SMAD1 expression, after 21 days of osteogenic differentiation conditions exposition. More studies are required to understand the complete cellular and molecular mechanisms of PRF plus LLLT on stem cells. Overall, we demonstrated for the first time that the combination of PRF and LLLT would be an excellent therapeutic tool that can be employed for dental, oral, and craniofacial repair and other tissue engineering applications.

PMID:37874511 | DOI:10.1007/s10266-023-00851-8