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Background: Drug-induced lupus erythematosus (DILE) accounts for 10-15% of systemic lupus erythematosus (SLE) cases, with more than 100 pharmaceutical agents implicated in its development. Depending on the offending drug, clinical and serological manifestations present great variability and, thus, DILE may be overlooked in clinical practice. Valproic acid (VPA) – induced lupus erythematosus has not been analytically reported in the literature, rendering the recognition of such cases even more difficult. Objective: The aim of this study was to analyze VPA – induced lupus features and to discuss possible pathophysiological mechanisms. Materials and Methods: This literature review was conducted in PubMed and Embase databases in June 2021, in search of DILE cases induced by VPA. We found 164 manuscripts, out of which 140 articles regarding other adverse effects or drugs were discarded. Finally, 15 cases fulfilled the eligibility criteria to be included in this review. Results: Although SLE is more common in females, VPA-induced lupus presented a male predilection. Patients developed DILE within the first three months of treatment with VPA at a percentage of 50%, whereas four patients from one to five years after VPA initiation. DILE frequently presented with mild symptoms. In most patients, serositis manifested with polyarthritis, pleural effusion or pericarditis. Notably, one patient presented with Rowell's syndrome, a rare subtype of lupus erythematosus with erythema multiforme and speckled pattern of antinuclear antibodies (ANAs). Central nervous system, renal and skin involvement was scarcely observed. Cytopenia was noted in 7 patients. Immunological findings included positive ANAs in the vast majority of the patients (86.7%), positive anti-histone antibodies in five, positive anti-dsDNA antibodies in three and hypocomplementemia in two patients. Despite the prompt resolution of clinical symptoms after VPA discontinuation, serological abnormalities persisted up to 18 months. Apart from the discontinuation of VPA administration for the resolution of DILE, treatment included corticosteroids in 8 cases. Conclusion: Valproic acid has been implicated in several cases of DILE. Clinicians should be aware of this entity and recognize it promptly to ensure a favorable outcome. Possible pathophysiologic associations may be extrapolated, but a clearer understanding of this syndrome is to be gained by further studies.

Valproic acid is a carboxylic acid derivative commonly prescribed for several types of seizure disorders or for acute manic episodes in patients with bipolar disorder. Several cases of valproate-induced pleural effusion have been reported, although the precise pathophysiological mechanism remains unknown.To describe the presentation of pleural effusion associated with valproate use and to categorize published case reports according to clinical, immunological, and pleural effusion cell type.PubMed/MEDLINE and Embase databases were systematically searched from January 1970 until November 2020 using the following search terms: "valproic acid" OR "valproate" OR "pleural fluid" OR "exudative effusion" OR "transudative effusion" OR "valproic lung adverse events". These searches yielded 171 references of which 135 articles were considered irrelevant, leaving 36 potentially relevant references which were carefully scrutinized. Twenty-eight cases of valproate-induced pleural effusion were identified after excluding two articles reporting five patients with lung parenchymal adverse reactions to treatment with valproic acid; two articles reporting three patients in whom the pleural effusion could not be attributed to valproic acid alone; one case discussing valproate therapy and fungal pleural effusion; and one describing a patient who suffered from severe cardiac failure. There were also two cases, in an abstract form, with pericardial and pleural effusion, but without any further informative details, and, thus, they were also excluded from this survey.This was the most common type of valproate-induced pleural effusion reported in 17 out of 28 cases (60.7%), with concurrent peripheral eosinophilia in ten. Acute hypersensitivity reaction, inflammation of the pleural cavity induced by the drug, drug toxicity, and damage to mesothelial cells due to oxidants, comprise the possible pivotal mechanisms.This was reported in two cases, with concurrent pericardial effusion in one. Discontinuation of valproate led to resolution of the effusion, although the underlying pathophysiological mechanisms remain abstruse. Interestingly, a patient presented with recurrent pleural effusion characterized by transition from eosinophilic to lymphocytic predominance after readministration of valproate.Three out of 28 cases (10.7%) were characterized by neutrophilic transudative pleural effusion after long-term therapy with valproate, while concurrent pericardial effusion was also noted in two.Five patients receiving valproate therapy (17.9% out of the 28 cases) developed drug-induced lupus erythematosus with concurrent pleural effusion that was eosinophilic in three. All patients had positive antinuclear antibodies; anti-histone antibodies were positive in two.Valproate-induced pleural effusion is rare, but patients receiving treatment with valproic acid who develop respiratory symptoms should be examined for valproate-induced pleural effusion.

Background Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW P P P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (P = 0.01)]. Conclusions Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Lane-Hamilton syndrome (LHS) presents a medical emergency, with 14% mortality due to Idiopathic Pulmonary Hemosiderosis (IPH) in acute phase. Despite the clinical severity of this entity, there has been no published review in the international literature, resulting in lack of awareness and delayed diagnosis.A rigorous search of international databases yielded a total of 80 LHS cases from January 1971 to August 2020. We analyzed 44 children (8.56 ± 4.72 years, 21 boys) and 36 adults (33.61 ± 13.41 years, 12 men) to present the clinical manifestations, radiological and immunological pattern, therapeutic approaches and outcome of LHS. We also elaborated on clinical and laboratory findings' associations to propose diagnostic indexes and clarified differences based on age distribution.Celiac disease (CD) and IPH diagnosis was made concurrently in 46 patients, whereas in 21 patients, the diagnosis of LHS was delayed for 2.5y (3 months-11 years). Hemoptysis (

This meta-analysis explored the safety and effectiveness of mucolytics as an add-on treatment for chronic obstructive pulmonary disease (COPD) exacerbations. Based on a pre-registered protocol and following Cochrane methods, we systematically searched for relevant randomised or quasi-randomised controlled trials (RCTs). We used the Risk of Bias v2 tool for appraising the studies and performed random-effect meta-analyses when appropriate. We assessed certainty of evidence using GRADE. This meta-analysis included 24 RCTs involving 2192 patients with COPD exacerbations, entailing at least some concerns of methodological bias. We demonstrated with moderate certainty that mucolytics increase the rate of treatment success (relative risk 1.37, 95% CI 1.08–1.73, n=383), while they also exert benefits on overall symptom scores (standardised mean difference 0.86, 95% CI 0.63–1.09, n=316), presence of cough at follow-up (relative risk 1.93, 95% CI 1.15–3.23) and ease of expectoration (relative risk 2.94, 95% CI 1.68–5.12). Furthermore, low or very low certainty evidence suggests mucolytics may also reduce future risk of exacerbations and improve health-related quality of life, but do not impact on breathlessness, length of hospital stay, indication for higher level of care or serious adverse events. Overall, mucolytics could be considered for COPD exacerbation management. These findings should be validated in further, rigorous RCTs.

Η κατάθλιψη είναι μια διαταραχή που αφορά περισσότερους από 300 εκατομμύρια ανθρώπους παγκοσμίως. Είναι γνωστό ότι η μείζονα κατάθλιψη αυξάνει τον κίνδυνο για καρδιαγγειακή νόσο, και πολλοί μηχανισμοί έχουν προταθεί προκειμένου να ερμηνευθεί αυτή η συσχέτιση, όπως η ενεργοποίηση του συμπαθητικού συστήματος, διαταραχές στην ανοσολογική απόκριση, νευροενδοκρινικές αλλαγές. Όλο και περισσότερα δεδομένα υποστηρίζουν πως η κατάθλιψη σχετίζεται με ενδοθηλιακή δυσλειτουργία και αυξημένη αρτηριακή σκληρία, που μπορούν να οδηγήσουν σε ανάπτυξη αρτηριακής υπέρτασης και αυξημένο καρδιαγγειακό κίνδυνο. Ωστόσο η επίδραση που μπορεί να έχει η αντικαταθλιπτική θεραπεία στη λειτουργία του ενδοθηλίου δεν έχει διασαφηνιστεί. Σκοπός της παρούσας διατριβής είναι να εκτιμήσει την επίδραση της αντικαταθλιπτικής αγωγής στην ενδοθηλιακή λειτουργία και την αρτηριακή σκληρία ασθενών με μείζονα κατάθλιψη. Αρχικά επιλέχθηκαν 69 ασθενείς που πληρούσαν τα κριτήρια διάγνωσης μείζονος κατάθλιψης με ψυχωσικά στοιχεία, κατά DSM-IV-TR με ένδειξη αγωγής με σιταλοπράμη και ρισπεριδόνη. Έγινε εκτίμηση της αγγειακής τους λειτουργίας στο εργαστήριο και 1:1 αντιστοίχιση με ομάδα ελέγχου χωρίς κατάθλιψη. Σαρανταεννέα από αυτούς δέχτηκαν να συνεχίσουν στο προοπτικό σκέλος της μελέτης και κλήθηκαν, κατά την κρίση του θεράποντος ψυχιάτρου, να λάβουν συνδυασμό σιταλοπράμης με ρισπεριδόνη, σε προσαρμοσμένες δόσεις, για διάρκεια 6 μηνών. Τριανταεπτά ασθενείς ολοκλήρωσαν τη θεραπεία, ενώ 12 δε συμμορφώθηκαν ή αρνήθηκαν τη θεραπεία, εντούτοις συμφώνησαν με την 6μηνη παρακολούθηση. Αυτή η ομάδα χρησιμοποιήθηκε στην ανάλυση ως ομάδα ελέγχου. Η εκτίμηση της αγγειακής λειτουργίας έγινε στην αρχική επίσκεψη και στην επανεκτίμηση, με τον υπολογισμό της εξαρτώμενης από τη ροή αγγειοδιαστολής (Flow Mediated Dilatation, FMD), τη μέτρηση της ταχύτητας του σφυγμικού κύματος (Pulse Wave Velocity, PWV) καρωτιδο-μηριαία, και την εκτίμηση των ανακλώμενων κυμάτων, της κεντρικής (αορτικής) πίεσης και του δείκτη επαύξησης της αρτηριακής πίεσης (Augmentation Index, AI). Κατά την επανεκτίμηση στους 6 μήνες αξιολογήθηκε η ανταπόκριση της καταθλιπτικής συμπτωματολογίας των ασθενών στη θεραπεία (n=37, βελτίωση σε 24 και μη βελτίωση σε 13 ασθενείς). Από τη σύγκριση των 69 καταθλιπτικών ασθενών που είχαν αρχικά εισαχθεί με τον πληθυσμό ελέγχου, παρατηρήθηκε ότι οι ασθενείς με μείζονα κατάθλιψη παρουσίαζαν χειρότερη ενδοθηλιακή λειτουργία σε σχέση με την ομάδα ελέγχου χωρίς κατάθλιψη, που είχαν αντιστοιχισθεί για τους κλασικούς παράγοντες καρδιαγγειακού κινδύνου. Επίσης η αρτηριακή πίεση περιφερικά και στην αορτή, οι τιμές των FMD, PWV και AI, βελτιώθηκαν σημαντικά (p

Major depression is associated with endothelial dysfunction and arterial stiffening, which may mediate development of hypertension and increased cardiovascular risk. The effect of response to antidepressant treatment on these vascular parameters has not been elucidated.We aimed to assess the net effect of antidepressant therapy on endothelial function and arterial stiffness in patients with psychotic depression.Thirty-seven patients with major psychotic depression, according to DSM-IV-TR, were treated with titrated citalopram 20-60 mg and risperidone 0.5-1 mg and were followed for 6 months. Twelve additional patients who denied treatment, or were non-compliant, were also followed for the same time period. Vascular function was assessed by flow-mediated dilatation (FMD), carotid-femoral pulse wave velocity (PWV) and augmentation index (AI), at baseline and at the end of follow-up.Aortic and peripheral blood pressure (BP), PWV, FMD and AI (p 0.05 for all) were significantly improved in the group that received treatment. Overall, only responders to treatment (n = 24) presented significant improvements in all hemodynamic and vascular parameters (p 0.05 for all), irrespectively of traditional cardiovascular risk factors (TRFs), vasoactive medication and BP lowering. In a secondary analysis, patients with psychotic depression presented worse endothelial function as compared to controls matched for TRFs.Non-randomized study.Patients who respond to therapy for major psychotic depression present sustained improvement in vascular function. Given that depressed patients are considered to be at high cardiovascular risk and are often non-compliant with treatment, further research to assess cardiovascular benefits of vigilant monitoring of antidepressant therapy is warranted.

Introduction: Drug-induced diffuse alveolar hemorrhage (DAH) has been associated with the administration of various medications, among which levonorgestrel (LN) has not been reported until now. Case Presentation: This case study describes a 42-year-old woman who presented with hemoptysis, hypoxemia, and radiological depiction of ground glass opacities, 3 days after she had received emergency contraceptive medication containing levonorgestrel. Emergent bronchoscopy was performed, and BAL was diagnostic of diffuse alveolar hemorrhage (DAH). A thorough diagnostic approach was followed, in order to detect the underlying pathological condition that induced DAH. The absence of other identifiable pathological conditions in this patient raised suspicion of LN’s potential causative role. Conclusion: DAH has not been reported as an adverse effect of LN until now. However, LN has been found to exert immunomodulatory effects and to present potential for manifestations of vasculitis as well as severe hypersensitivity reactions. These mechanisms may have been implicated in the development of DAH in our patient, who presented no other pathological conditions.

Introduction: Among the reported cases of valproic acid - induced pleural effusion, recurrence of pleural fluid accumulation has scarcely been presented in the literature. Case presentation: This case study reports a 51-year-old man under treatment with valproic acid, who presented with recurrent pleural effusion characterized by transition from eosinophilic to lymphocytic predominance. The recurrence of the effusion upon re-administration of the drug, along with its resolution upon discontinuation of treatment with valproic acid, is strongly indicative of a causative association. Conclusion: This is the first reported case of recurrent valproic acid - induced pleural effusion presenting with transition from eosinophilic to lymphocytic predominance. We aim to highlight the importance of taking into consideration the causative role of valproic acid in inducing pleural effusion, even when the pleural fluid demonstrates alteration in the predominant cell type.

An extensive four-year research program has been carried out to explore and acquire knowledge about the fundamental agricultural practices and processes affecting the mobility and bioavailability of pesticides in soils under semi-arid Mediterranean conditions. Pesticide leaching was studied under field conditions at five different depths using suction cups. Monitoring of metolachlor, alachlor, atrazine, deethylatrazine (DEA), deisopropylatrazine (DIA), and bromide ions in soil water, as well as dye patterns made apparent the significant role of preferential flow to the mobility of the studied compounds. Irrespective to their adsorption capacities and degradation rates, atrazine, metolachlor and bromide ions were simultaneously detected to 160 cm depth. Following 40 mm irrigation, just after their application, both alachlor and atrazine were leached to 160 cm depth within 18 h, giving maximum concentrations of 211 and 199 μg L −1 , respectively. Metolachlor was also detected in all depth when its application was followed by a rainfall event (50 mm) two weeks after its application. The greatest concentrations of atrazine, alachlor and metolachlor in soil water were 1795, 1166 and 845 μg L −1 , respectively. The greatest concentrations of atrazine’s degradation products (both DEA and DIA) appeared later in the season compared to the parent compound. Metolachlor exhibited the greatest persistence with concentrations up to 10 μg L −1 appearing in soil water 18 months after its application. Brilliant blue application followed by 40 mm irrigation clearly depict multi-branching network of preferential flow paths allowing the fast flow of the dye down to 150 cm within 24 h. This network was created by soil cracks caused by shrinking of dry soils, earthworms and plant roots. Chromatographic flow of the stained soil solution was evident only in the upper 10–15 cm of soil.