Purpose
Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves’ hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD.
To evaluate ...whether ‘Block and Replace’ (B + R) and ‘Titration’ (T) regimes are equivalent in terms of frequency of euthyroidism and Graves’ Orbitopathy (GO) during ATD therapy.
Methods
A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution’s policy.
Results
Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27–0.85) lower in the B + R group at all time points (
p
= 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (
p
< 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (
p
= 0.096). GO was mild in 13% and moderate-to-severe in 2%.
Conclusion
The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.
To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis.
Data forms and questionnaires ...from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed.
Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points.
In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.
PurposeIn daily clinical practice, it is not rare to observe a relevant discordance between patient’s global assessment (PGA) and physician’s global assessment (PhGA), because of different illness ...perceptions.The purpose was to evaluate the presence of PGA/PhGA discrepancy in patients with SLE who were in clinical remission and to evaluate how this discrepancy affects PROs. In addition, to explore whether this discordance could be influenced by the presence of additional elements affecting patients’ quality of life, such as sleep disturbances and psycho-emotional factors.MethodsOur study included adult SLE patients consecutively followed in a single Lupus Clinic from March to July 2021 fulfilling at minimum the definition of clinical remission of treatment according to the definition of Zen et al.1 (cSLEDAI=0, corticosteroids ≤5mg/die, stable dosage of DMARD). Medical records including demographic data, clinical characteristics and outcomes measures were collected. Pain assessment, PGA and PhGA were rated on a visual analogue scale (0–100 mm) on the same day of the clinical evaluation. To analyse the discrepancy between PGA and PhGA, the PGA-PhGA variable was calculated, considering as discordant a difference ≥25 mm as previously proposed.2 All the subjects completed the following questionnaires: Health Assessment Questionnaire (HAQ), SF36 Health Survey, State-Trait Anxiety Inventory (STAI-Y1/Y2), Self-rating Depression Scale (SDS Zung) and Insomnia Severity Index (ISI). Statistical analysis was performed to compare concordant and discordant groups.ResultsThe study included 106 patients, (93 women, 13 men) with a median age of 48 (41–58) and a median SLE duration 227 months (124–330). At the last evaluation median SLEDAI was 0 (0–2) and median SLICC was 1 (0–1). According to Zen definitions of remission, 51 patients (48%) and 20 (19%) also fulfilled the criteria of clinical remission of corticosteroids and complete remission respectively. Nevertheless, in 24 patients (22,7%) PGA-PhGA≥25. Patients in the discordant group were older and less frequently achieved the definition of clinical remission of corticosteroids (see table1) than concordant. No differences were found in gender, SLE duration, serology, disease activity or damage and other treatment. Data about differences in PROs between two groups are reported in the Table 1: discordant patients had a worse performance in all the PROs included in the study. At multivariate analysis SF-36 Physical Component Summary (PCS) resulted associated with PGA-PhGA≥25 (p=<0,0001).Abstract S04.1 Table 1Data are expressed as absolute number and percentage or median and interquartile range (IQR) and compared using Mann-Whiteney test or Chi Squared testConclusionsIn our study we found that, even in patients considered in remission, in more than 20% of patients there is a considerable discordance between the global disease assessment reported by patients and their physicians. Patients that had a higher PGA also presented worse score at PROs. Our data seems to confirm that potential causes for discordance could be more related to the presence of non-inflammatory processes, depression, or anxiety than clinical manifestations or damage related to SLE.ReferencesZen et al. Ann. Rheum. Dis. 2015;74:2117–2122Neville C, et al. J Rheumatol 2000;27:675–9
Epoxide hydrolases are ubiquitous in nature and are utilized to catalyze the cofactor-independent hydrolysis of epoxides to their corresponding diols. These enzymes have tremendous potential and have ...been applied in the synthesis of bulk and fine chemical industry and utilized as chiral building blocks. Herein, we report a green, facile, and economical method for immobilization of epoxide hydrolase based on biomimetic mineralization. The organic-inorganic hybrid nanoflowers have received tremendous attention due to their higher catalytic activity and stability. The nanoflowers were synthesized, with the organic component being enzyme epoxide hydrolase and the inorganic component being Ca2+ ions. A unique hierarchical flower-like spherical structure with hundreds of spiked petals was observed. The synthesized nanoflowers were applied for styrene oxide hydrolysis, producing 1-phenyl-1,2-ethanediol. Further, the factors influencing the morphology, catalytic activity, and stability studies were performed to study the activity recovery of the synthesized organic-inorganic hybrid epoxide hydrolase nanoflowers. The findings will have interesting applications.
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•A facile and green method for immobilization of enzymes.•The organic-inorganic hybrid nanoflowers synthesized using epoxide hydrolase, CaCl2.•A hierarchical structure with flower-like morphology observed.•Synthesized nanoflowers applied for hydrolysis of styrene oxide.
Temporary COVID-19 hotels have been established in Italy to assist the homeless people that test positive for SARS-CoV-2 and require isolation. This observational study aimed to investigate the ...characteristics of the subjects who were isolated at the Casa tra Noi COVID-19 hotel in Rome between October 2020 and May 2021 and to estimate the duration of SARS-CoV-2 positivity according to their main socio-demographic, behavioural and clinical features.
Socio-demographic data, clinical history, and anamnestic data of guests were collected by the clinicians reviewing the medical documentation and face-to-face interviewing. Nasopharyngeal swabs were performed every 7 days and the presence of SARS-CoV-2 was assessed by RT-PCR. Median duration of SARS-CoV-2 positivity according to socio-demographic, behavioral factors and clinical condition was calculated.
The 196 guests (161 males, 82.1%) had a median age of 41 years (IQR: 30-53), and were mostly African (87, 44.4%). Only asymptomatic/paucisymptomatic infections were observed. Almost half of the individuals (84, 42.9%) were affected by at least one co-morbidity, the frequency of which was higher among women (57.1% vs. 39.8%, p=0.06). The date of the negative SARS-CoV-2 molecular test was known for 144 guests (73.5%). Among these, the median duration of positivity was 21 days (IQR: 14-26) and did not significantly vary with age, country of origin, smoking status, alcohol or drug abuse. Among the co-morbidities, only infectious diseases significantly modified the duration of positivity, which increased from 21 to 34 days (p=0.013).
Hotel guests were frequently affected by physical/mental co-morbidities. Duration of SARS-CoV-2 positivity was significantly prolonged only in individuals affected by an infectious disease.
Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved ...in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on- and off-exposure periods (4.7 ± 0.9 and 4.5 ± 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.
Vitamin D is the precursor of a hormone (1,25-dihydroxyvitamin D3), which has many biological effects in the skin. The immune modulator properties of vitamin D are mediated in part through effects on ...regulatory T cells (T-reg). Currently, in psoriasis, the relationship between vitamin D and T-reg has not well elucidated. We assess whether vitamin D status is correlated with circulating T-reg in patients affected by psoriasis and if there is a correlation with the severity of the disease evaluated with Psoriasis Area Severity Index (PASI) score.
For each patient we have analyzed, PASI-score, serum levels vitamin D and regulatory T cell percentages. Spearmen's coefficient was used between serum vitamin D levels and the predictors. Subsequently, the independent predictive factors were assessed by Multiple Regression.
A total of 26 patients were included in our analysis. Using no parametric Spearman's Coefficient test between serum levels of vitamin D and the single variables, we found an association with T-reg population (p < 0.001) and with PASI-score (p = 0.04).
While vitamin D treatment induces a cytokine profile known to favor the differentiation of T cells with suppressive activity, at the same time, several studies showed how vitamin D can prime for tolerogenic dendritic cells able to favor the differentiation of Treg from T naïve cells. Low levels of vitamin-D may decrease the number of circulatory T-reg, disrupting the immunological homeostasis in psoriatic patients and encouraging the inflammatory activity.
Purpose: To describe our experience in performing biopsy of post-septal orbital masses with core needle under computerized tomography guidance (CT-CNB). Methods: The medical records of all patients ...who underwent this procedure were reviewed. The procedure was performed under local anesthesia on a day case basis under a peribulbar block. A planning non-contrast computerized tomography (CT) scan of the orbits was performed to localise the mass. A 6-cm 18-G Temno Evolution® semi-automated biopsy needle was inserted through the skin into the orbit. Prior to further advancement of the needle, a low-dose CT limited to the previously determined plane was performed to confirm its position. The needle was then advanced, and the cutting needle was deployed to obtain the biopsy. Results: Five patients who underwent CT-CNB were identified. The CNB was successful in 4 patients and revealed a metastatic prostate adenocarcinoma, diffuse large B-cell lymphoma, a metastatic neuroendocrine tumour, and orbital inflammatory disease. The biopsy failed in the fifth patient when the needle failed to penetrate the tumour despite good localisation on CT. He was eventually diagnosed with fibrous meningioma of the greater wing of sphenoid on open biopsy. None of the patients had any complications other than peri-ocular bruising which was present in all of them. Conclusion: CT-CNB of mass lesions located in the lateral aspect of the orbit can be an alternative to open biopsy in selected cases. It avoids major surgery and allows the use of radiotherapy, if required, without any delay.
Analyses of human phosphoproteome based on primary structure of the aminoacids surrounding the phosphor Ser/Thr suggest that a significant proportion of phosphosites is generated by a restricted ...number of acidophilic kinases, among which protein kinase CK2 plays a prominent role. Recently, new acidophilic kinases belonging to the Polo like kinase family have been characterized, with special reference to PLK1, PLK2, and PLK3 kinases. While some progress has been made in deciphering the PLK1-dependent phosphoproteome, very little is known about the targets of PLK2 and PLK3 kinases. In this report by using an in vitro approach, consisting of cell lysate phosphorylation, phosphoprotein separation by 2D gel electrophoresis and mass spectrometry, we describe the identification of new potential substrates of PLK2 and PLK3 kinases. We have identified and validated as in vitro PLK2 and PLK3 substrates HSP90, GRP-94, β-tubulin, calumenin, and 14-3-3 epsilon. The phosphosites generated by PLK3 in these proteins have been identified by mass spectrometry analysis to get new insights about PLKs specificity determinants. These latter have been further corroborated by an in silico analysis of the PLKs substrate binding region.
► PLK2 and PLK3 recognize the same specific determinants. ► HSP90, GRP-94, β-tubulin, calumenin, and 14-3-3ε are PLK2 /3 in vitro substrates. ► PLK2/3 specific determinants are significantly different from those of PLK1 and CK2.
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