To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye.
Case control study.
Seventy-five female subjects divided into 3 groups: ...group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD).
A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate.
Conjunctival expression of MMP9 and TG2.
MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS.
The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.
Quantitative indoor monitoring, in a low-invasive and accurate way, is still an unmet need in clinical practice. Indoor environments are more challenging than outdoor environments, and are where ...patients experience difficulty in performing activities of daily living (ADLs). In line with the recent trends of telemedicine, there is an ongoing positive impulse in moving medical assistance and management from hospitals to home settings. Different technologies have been proposed for indoor monitoring over the past decades, with different degrees of invasiveness, complexity, and capabilities in full-body monitoring. The major classes of devices proposed are inertial-based sensors (IMU), vision-based devices, and geomagnetic and radiofrequency (RF) based sensors. In recent years, among all available technologies, there has been an increasing interest in using RF-based technology because it can provide a more accurate and reliable method of tracking patients’ movements compared to other methods, such as camera-based systems or wearable sensors. Indeed, RF technology compared to the other two techniques has higher compliance, low energy consumption, does not need to be worn, is less susceptible to noise, is not affected by lighting or other physical obstacles, has a high temporal resolution without a limited angle of view, and fewer privacy issues. The aim of the present narrative review was to describe the potential applications of RF-based indoor monitoring techniques and highlight their differences compared to other monitoring technologies.
Gait features differ between Parkinson's disease (PD) and healthy subjects (HS). Kinematic alterations of gait include reduced gait speed, swing time, and stride length between PD patients and HS. ...Stride time and swing time variability are increased in PD patients with respect to HS. Additionally, dynamic parameters of asymmetry of gait are significantly different among the two groups. The aim of the present study is to evaluate which kind of gait analysis (dynamic or kinematic) is more informative to discriminate PD and HS gait features.
In the present study, we analyzed gait dynamic and kinematic features of 108 PD patients and 88 HS from four cohorts of two datasets.
Kinematic features showed statistically significant differences among PD patients and HS for gait speed and time Up and Go test and for selected kinematic dispersion indices (standard deviation and interquartile range of swing, stance, and double support time). Dynamic features did not show any statistically significant difference between PD patients and HS.
Despite kinematics features like acceleration being directly proportional to dynamic features like ground reaction force, the results of this study showed the so-called force/rhythm dichotomy since kinematic features were more informative than dynamic ones.
Background: Alterations in glenohumeral range of motion, including increased posterior shoulder tightness and glenohumeral internal rotation
deficit that exceeds the accompanying external rotation ...gain, are suggested contributors to throwing-related shoulder injuries
such as pathologic internal impingement. Yet these contributors have not been identified in throwers with internal impingement.
Hypothesis: Throwers with pathologic internal impingement will exhibit significantly increased posterior shoulder tightness and glenohumeral
internal rotation deficit without significantly increased external rotation gain.
Study Design: Case control study; Level of evidence, 3.
Methods: Eleven throwing athletes with pathologic internal impingement diagnosed using both clinical examination and a magnetic resonance
arthrogram were demographically matched with 11 control throwers who had no history of upper extremity injury. Passive glenohumeral
internal and external rotation were measured bilaterally with standard goniometry at 90° of humeral abduction and elbow flexion.
Bilateral differences in glenohumeral range of motion were used to calculate glenohumeral internal rotation deficit and external
rotation gain. Posterior shoulder tightness was quantified as the bilateral difference in passive shoulder horizontal adduction
with the scapula retracted and the shoulder at 90° of elevation. Comparisons were made between groups with dependent t tests ( P < .05).
Results: The throwing athletes with internal impingement demonstrated significantly greater glenohumeral internal rotation deficit
( P = .03) and posterior shoulder tightness ( P = .03) compared with the control subjects. No significant differences were observed in external rotation gain between groups
( P = .16).
Clinical Relevance: These findings could indicate that a tightening of the posterior elements of the shoulder (capsule, rotator cuff) may contribute
to impingement. The results suggest that management should include stretching to restore flexibility to the posterior shoulder.
Keywords:
throwing
glenohumeral internal rotation deficit (GIRD)
impingement
Reperfusion therapy administration timing in acute ischaemic stroke is the main determinant of patients' mortality and long-term disability. Indeed, the first hour from the stroke onset is defined ...the "golden hour", in which the treatment has the highest efficacy and lowest side effects. Delayed ambulance transport, inappropriate triage and difficulty in accessing CT scans lead to delayed onset to treatment time (OTT) in clinical practice. To date brain CT scan is needed to rule out intracranial haemorrhage, which is a major contraindication to thrombolytic therapy. The availability, dimension and portability make CT suitable mainly for intrahospital use, determining further delays in the therapies administration. This review aims at evaluating portable neurophysiology technologies developed with the scope of speeding up the diagnostic phase of acute stroke and, therefore, the initiation of intravenous thrombolysis. Medline databases were explored for studies concerning near infrared spectroscopy (NIRS), bioelectrical impedance spectroscopy (BIS) and Microwave imaging (MWI) as methods for stroke diagnosis. A total of 1368 articles were found, and 12 of these fit with our criteria and were included in the review. For each technology, the following parameters were evaluated: diagnostic accuracy, ability to differentiate ischaemic and haemorrhagic stroke, diagnosis time from stroke onset, portability and technology readiness level (TRL). All the described methods seem to be able to identify acute stroke even though the number of studies is very limited. Low cost and portability make them potentially usable during ambulance transport, possibly leading to a reduction of stroke OTT along with the related huge benefits in terms of patients outcome and health care costs. In addition, unlike standard imaging techniques, neurophysiological techniques could allow continuous monitoring of patients for timely intrahospital stroke diagnosis.
KEY MESSAGES
First hour from the stroke onset is defined the "golden hour", in which the treatment has the highest efficacy and lowest side effects.
The delay for stroke onset to brain imaging time is one of the major reasons why only a minority of patients with acute ischaemic stroke are eligible to reperfusion therapies.
Neurophysiology techniques (NIRS, BIS and MWI) could have a potential high impact in reducing the time to treatment in stroke patients.
Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke ...diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature for potential biomarkers that may aid in early diagnosis, differentiation between ischemic and hemorrhagic stroke, and prediction of hemorrhagic transformation in ischemic stroke. After a thorough analysis, four promising biomarkers were identified: Antithrombin III (ATIII), fibrinogen, and ischemia-modified albumin (IMA) for diagnostic purposes; glial fibrillary acidic protein (GFAP), micro RNA 124-3p, and a panel of 11 metabolites for distinguishing between ischemic and hemorrhagic stroke; and matrix metalloproteinase-9 (MMP-9), s100b, and interleukin 33 for predicting hemorrhagic transformation. We propose a biomarker panel integrating these markers, each reflecting different pathophysiological stages of stroke, that could significantly improve stroke patients' early detection and treatment. Despite promising results, further research and validation are needed to demonstrate the clinical utility of this proposed panel for routine stroke treatment.
Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, ...resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3–0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.
The increasing use of ionizing radiation in healthcare is causing growing alarm about radiation protection of patients and the doses they receive during procedures. Radiation dose assessment for ...patients in radiodiagnostic procedures is the subject of interest in view of the recent Italian D.Lgs 31 July 2020, n. 101 (Decreto Legislativo 31 luglio 2020, n. 101) and one of its most important focuses is the prescription to provide patient exposure information as an integral part of the examination report. Dose monitoring systems are therefore essential for the collection of the dosimetric data. In order to analyse potential and critical issues of these software, different systems, adopted at the Antonio Cardarelli Hospital in Naples, were employed. Data extracted from the DoseWatch software (GE Healthcare) and Gray Detector (EL.CO. S.r.l. Healthcare Solutions, Italy) and relating to several protocols adopted for computed tomography (CT), were retrospectively analysed for the purpose of identifying critical issues in the data acquisition and recording phase, comparing with Italian nationwide diagnostic reference levels (DRLs), as provided for in regulatory provisions for radiation safety. Multiphase examinations were also included in this study. Once the distributions of volumetric CT Dose Index (CTDIvol) and dose-length product (DLP) were determined for each acquisition phase and total DLP (DLPtot) for each examination, the 25th, 50th and 75th percentiles were calculated for each distribution and then compared with the relevant Italian nationwide DRLs. In addition, to improve protocol optimization and dose reduction the magnitude of the CT acquisition settings chosen in each procedure was evaluated. In conclusion, these systems allow accurate analysis of radiation dose according to equipment and protocol over time. For the application of optimization measures, a constant use of the dose tracking software is required, which can be translated into actions on scan parameters and prospective data analysis.
Background
Primary mediastinal germ cell tumors (GCTs) are rare in children and still represent a challenge for both adult and pediatric oncologists because of their worse outcome compared to their ...gonadal counterpart.
Procedure
Prospectively collected data concerning patients enrolled in the Italian Association of Pediatric Haematology and Oncology study on malignant GCTs (AIEOP TCGM 2004) protocol for the treatment of GCTs were analyzed. Patients with malignant mediastinal primary GCTs were included in this study. Data regarding patients with newly diagnosed mediastinal teratoma were also collected.
Results
From 2005 to 2013, 20 children diagnosed with mediastinal GCTs were registered in AIEOP TCGM 2004 protocol. With a median follow‐up of 89 months (range 35–123), the overall survival (OS) and event free survival (EFS) rates were 100% for teratoma and 90% for malignant GCTs.
Conclusions
We confirm the favorable outcome of children affected by mediastinal teratoma and malignant GCTs. For malignant tumors, further studies on the clinical characteristics and genetic signatures on tumor samples might be necessary to better understand differences observed in high‐risk patients and to assist the development of more effective treatment for this subgroup.
Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ...ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.
PDF
