Nevin Manimala

Clin Rheumatol. 2023 Sep 7. doi: 10.1007/s10067-023-06761-y. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to investigate the plasma levels and cell surface expression of two checkpoint molecules, TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3) and PD-1 (programmed cell death protein 1), in pediatric patients with chronic non-bacterial osteomyelitis (CNO).

METHODS: Plasma samples of CNO patients were collected at diagnosis or during biologic agent treatment. Plasma levels of TIM-3 and PD-1 were measured using the sandwich enzyme-linked immunosorbent assay method, and the expression of the two immune checkpoint molecules on the cell surface was analyzed by isolating peripheral blood mononuclear cells by density gradient centrifugation technique.

RESULTS: Twenty-seven patients with CNO (14 boys, 51.9%) and six healthy controls (3 boys, 50%) were enrolled in the study. There were no age differences between CNO patients and healthy controls (median age 14.5 vs. 13.5 years, respectively, p=0.762). Of the CNO patients, 18 were included at the time of diagnosis while 9 were receiving biologic treatment at enrollment. The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls (p=0.011). However, no significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls (p=0.083 and p=0.245, respectively). There was also no statistically significant difference in plasma TIM-3 levels of the patient and control groups (p=0.981).

CONCLUSION: CNO is an autoinflammatory disease, and overall, our results suggest that T cell exhaustion may not be significant in CNO. Further research is needed to find out whether the immune checkpoints are mainly associated with autoimmunity but not autoinflammation. Key Points • The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls. • No significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls. • Our results suggest that T cell exhaustion may not be significant in CNO pathogenesis.

PMID:37676588 | DOI:10.1007/s10067-023-06761-y

Int Orthop. 2023 Sep 7. doi: 10.1007/s00264-023-05960-1. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to compare the clinical and radiographic outcomes and arthroscopic findings after high tibial osteotomy (HTO) between neutral and classic targeted coronal alignments in patients with medial meniscus posterior root tears (MMPRTs).

METHODS: Ninety-eight patients with MMPRT were prospectively enrolled in the final cohort and randomized into two groups. Fifty-two patients with the targeted alignment through the Fujisawa point (60-62.5% of the entire tibial plateau width measured from the medial side) during HTO were included in group A, whereas 46 patients with the targeted alignment through the point at 50-55% of the tibial plateau width were included in group B. The clinical and radiographic outcomes and second-look arthroscopic findings were statistically compared for comprehensive assessments.

RESULTS: After a mean follow-up of 37.1 months, we found no significant differences between the two groups regarding the final Lysholm (p = 0.205) and Hospital for Special Surgery scores (p = 0.084). However, we only observed significant differences between the two groups in terms of the final hip-knee-ankle angle, weight-bearing line ratio, and medial proximal tibial angle (p < 0.001). Second-look arthroscopy did not reveal a significant difference in meniscal healing rate (p = 0.786).

CONCLUSIONS: Performing HTO with the aim to achieve neutral alignment leads to similar clinical outcomes in patients with MMPRT compared to classic alignment. Although subsequent research is required, the current study provides clinical evidence for the safety and efficacy of the new targeted alignment during HTO, which may avoid long-term complications associated with overcorrection when using the traditional technique.

PMID:37676496 | DOI:10.1007/s00264-023-05960-1

J Gastroenterol. 2023 Sep 7. doi: 10.1007/s00535-023-02033-3. Online ahead of print.

ABSTRACT

BACKGROUND: This substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients.

METHODS: The Cancer-VTE Registry was an observational study that collected VTE data from patients with solid tumors across Japan. We measured baseline VTE prevalence, and at 1-year follow-up, the cumulative incidence of symptomatic and composite VTE (symptomatic VTE and incidental VTE requiring treatment), bleeding, cerebral infarction/transient ischemic attack (TIA)/systemic embolic event (SEE), and all-cause death.

RESULTS: Of 1006 pancreatic cancer patients, 86 (8.5%) had VTE at baseline, and seven (0.7%) had symptomatic VTE. Significant risk factors of baseline VTE were Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, body mass index (BMI) ≥ 25 kg/m², history of VTE, D-dimer > 1.2 µg/mL, and hemoglobin < 10 g/dL. At 1-year follow-up, the cumulative incidence of events was higher for pancreatic cancer vs other cancers. Pancreatic cancer patients with VTE vs those without VTE had significantly higher incidences of bleeding, cerebral infarction/TIA/SEE, and all-cause death. No significant risk factors for composite VTE were identified.

CONCLUSIONS: The cumulative incidence of composite VTE during cancer treatment was higher in pancreatic cancer than in other cancer types. Some risk factors for VTE prevalence at cancer diagnosis were identified. Although VTE prevalence at cancer diagnosis did not predict the subsequent 1-year incidence of composite VTE, it was a significant predictor of other events such as all-cause death in pancreatic cancer patients.

TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000024942.

PMID:37676492 | DOI:10.1007/s00535-023-02033-3

Eur J Pediatr. 2023 Sep 7. doi: 10.1007/s00431-023-05168-w. Online ahead of print.

ABSTRACT

Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020-2022) and sepsis (cohorts 2010-2014 and 2017-2018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (n = 87). Patients with MIS-C were older (10 vs. 4 years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (p < 0.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever > 48 hours (20 points), thrombocytopenia < 150 × 10³/µL (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS) > 10 (7 points). The cutoff > 25 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95. Conclusion: MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment. What is Known: • Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. • It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients. What is New: • Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis. • The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.

PMID:37676491 | DOI:10.1007/s00431-023-05168-w

Echocardiography. 2023 Sep 7. doi: 10.1111/echo.15676. Online ahead of print.

ABSTRACT

AIM: This study assessed RV dyssynchrony (irrespective to QRS duration) and RV systolic function in non-ischemic dilated cardiomyopathy (NIDCM) versus ischemic dilated cardiomyopathy (IDCM) patients by using different echo-Doppler modalities.

METHODS: Eighty-five cases (48 patients with DCM [whether ischemic or non-ischemic] and 37 age-matched healthy controls) were studied. Conventional echo-Doppler study, tissue Doppler (TDI), and speckle tracking (STE) were carried out to measure LV and RV systolic function. Time-to-peak negative longitudinal strain at the four RV sites were assessed by TDI derived strain and 2D speckle tracking.

RESULTS: Patients with DCM (whether ischemic or non-ischemic) had significantly lower fractional area change, RV tricuspid annular systolic velocity (p < .001 for both), tricuspid annular plane systolic excursion (p = .01), RV-GLS whether TDI or 2D derived (p < .001). Twenty-nine patients (60%) showed right intraventricular delay (RV4SD > 60 ms). The RV-dyssynchrony index was negatively correlated to %FAC (r = -.362, p = .01), RV Sm (r = -.312, p = .04), and 2D-RV GLS (r = -.305, p = .05). Insignificant higher RV-dysynchrony index was detected in NIDCM compared to IDCM group; however, the basal septal segment was significantly delayed in dilated group. More impaired RV systolic function was detected in ischemic group. 2D STE and TDI showed a significant correlation in the assessment of the right-intraventricular delay (p = .001).

CONCLUSION: Right-intraventricular dyssynchrony are detectable in patients with dilated cardiomyopathy (whether ischemic or non-ischemic) with a higher statistically insignificant value in non-ischemic group by using tissue Doppler imaging and 2D speckle tracking. More impairment of the RV systolic function was noticed in the ischemic group. Impaired RV systolic function was associated with right intraventricular delay.

PMID:37676474 | DOI:10.1111/echo.15676

CNS Drugs. 2023 Sep 7. doi: 10.1007/s40263-023-01037-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.

AIM: The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.

METHODS: The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.

RESULTS: Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.

CONCLUSIONS: The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.

TRIAL REGISTRATION: CRD42023388343.

PMID:37676473 | DOI:10.1007/s40263-023-01037-0

Environ Sci Pollut Res Int. 2023 Sep 7. doi: 10.1007/s11356-023-29683-3. Online ahead of print.

ABSTRACT

Hypertension is a key risk factor for cardiovascular disease (CVD). Thallium is a highly toxic metal that exists in all aspects of our lives and can cause damage to human health. The aim of this study was to identify the potential correlation between urinary thallium (U-Tl) and hypertension in American youth aged 8-17 years. The National Health and Nutritional Examination Survey (NHANES) database was mined for cross-sectional information on 2295 American children and adolescents aged 8-17 years. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure U-Tl levels, and the results were categorized into four quartiles (Q1-Q4). Logistic generalized linear models and unweighted restricted cubic spline (RCS) regression were used to investigate the relationship between U-Tl and hypertension. After adjusting for covariates, the odds ratios (ORs) at 95% confidence intervals (CIs) for hypertension prevalence in the 2nd, 3rd, and 4th quartiles were 0.43 (0.22-0.81), 0.54 (0.29-0.99), and 0.43 (0.22-0.81), when compared to the lowest quartile (P for trend = 0.024). RCS plot showed a negative linear correlation between log2-transformed U-Tl levels and hypertension (P for non-linearity = 0.869). Subgroup analysis based on sex indicated a statistically significant link between U-Tl and hypertension in male (P < 0.05). There is a negative linear relationship between U-Tl and hypertension in American children and adolescents aged 8-17 years with low thallium exposure. Due to the nature of cross-sectional studies, further studies are necessary to validate our conclusions and elucidate possible mechanisms.

PMID:37676453 | DOI:10.1007/s11356-023-29683-3

J Cancer Educ. 2023 Sep 7. doi: 10.1007/s13187-023-02367-9. Online ahead of print.

ABSTRACT

Geriatric cancer patients and their caregivers have unique needs that make it difficult for their healthcare providers (HCPs) to effectively communicate with them. As ineffective communication can lead to negative health outcomes, it is important that oncology HCPs receive specialized training on communication with older adult patients and their caregivers. We conducted a small pilot study examining audio recordings of clinical encounters between HCPs and older adult cancer patients/caregivers and questionnaires completed by the patients and their caregivers before and after the HCPs participated in a geriatric communication skills training program. Eleven HCPs completed the 6-h Geriatric Comskil Training. Two clinic consultations with unique geriatric patients (n = 44) and their caregivers (n = 29) were recorded before and after training and coded for HCPs’ use of communication skills. Patients and caregivers also completed surveys measuring their satisfaction with HCP communication and perceived empathy. Analysis of the audio recordings revealed that HCPs did not increase their use of communication skills after training. Although our sample was too small to detect statistical significance, measures of effect size showed trending improvements in patients’ and caregivers’ perceptions of HCPs’ empathy and satisfaction with their communication after training. Our findings build on previous studies evaluating the feasibility and effectiveness of the Geriatric Comskil Training in real world setting and indicate that the training may have improved HCPs’ communication with older adult patients and their caregivers even if their use of their observable communication skills did not change.

PMID:37676422 | DOI:10.1007/s13187-023-02367-9

Int J Implant Dent. 2023 Sep 7;9(1):27. doi: 10.1186/s40729-023-00493-z.

ABSTRACT

PURPOSE: To investigate the influence of teeth and dental restorations on the facial skeleton’s gray value distributions in cone-beam computed tomography (CBCT).

METHODS: Gray value selection for the upper and lower jaw segmentation was performed in 40 patients. In total, CBCT data of 20 maxillae and 20 mandibles, ten partial edentulous and ten fully edentulous in each jaw, respectively, were evaluated using two different gray value selection procedures: manual lower threshold selection and automated lower threshold selection. Two sample t tests, linear regression models, linear mixed models, and Pearson’s correlation coefficients were computed to evaluate the influence of teeth, dental restorations, and threshold selection procedures on gray value distributions.

RESULTS: Manual threshold selection resulted in significantly different gray values in the fully and partially edentulous mandible. (p = 0.015, difference 123). In automated threshold selection, only tendencies to different gray values in fully edentulous compared to partially edentulous jaws were observed (difference: 58-75). Significantly different gray values were evaluated for threshold selection approaches, independent of the dental situation of the analyzed jaw. No significant correlation between the number of teeth and gray values was assessed, but a trend towards higher gray values in patients with more teeth was noted.

CONCLUSIONS: Standard gray values derived from CT imaging do not apply for threshold-based bone segmentation in CBCT. Teeth influence gray values and segmentation results. Inaccurate bone segmentation may result in ill-fitting surgical guides produced on CBCT data and misinterpreting bone density, which is crucial for selecting surgical protocols. Created with BioRender.com.

PMID:37676412 | DOI:10.1186/s40729-023-00493-z

J Med Radiat Sci. 2023 Sep 7. doi: 10.1002/jmrs.724. Online ahead of print.

ABSTRACT

INTRODUCTION: Bolus track and test bolus are the most commonly used contrast timing protocols to undertake computed tomography pulmonary angiography (CTPA). The aim of this study was to compare test bolus and bolus track contrast enhancement protocols in terms of enhancement of the pulmonary vessels and aorta, radiation dose and suboptimal scan rate to determine the optimal technique for CTPA.

METHODS: A total of 200 CTPA examinations (100 using each protocol) performed between January and February 2021 were assessed retrospectively. All scans were performed on a 2×128 Dual Source Siemens Drive Scanner. CT attenuation was measured in Hounsfield Units (HU), with measurements taken from the main pulmonary trunk, right pulmonary artery and left pulmonary artery, ascending and descending aorta. The mean effective dose was calculated from the dose-length product (DLP). The suboptimal scan rate was calculated as the percentage of examinations below 210HU.

RESULTS: The average HU of the pulmonary arteries was 358 HU ± SD 129.2 in the test bolus group and increased to 394 HU ± SD 133.9 in the bolus track group with a P value of ≤0.05. The average HU of the aorta was 235 HU ± SD 82.8 in the test bolus group and increased to 319 HU ± SD 91.8 in the bolus track group with a P value of <0.001. Although not statistically significant, the mean effective dose was reduced by 4.2% for the bolus track protocol (2.4 mSv vs. 2.5 mSv, P > 0.05). Fewer suboptimal scans were performed with the bolus track protocol (5 scans <210HU Bolus Track vs. 9 scans <210HU Test Bolus).

CONCLUSION: The bolus track protocol results in increased enhancement of the pulmonary arteries and aorta, with the added benefits of a lower suboptimal scan rate and lower effective dose.

PMID:37675768 | DOI:10.1002/jmrs.724