Cutaneous Manifestations in Patients with SARS- CoV-2 Infections

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifesta- tions of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reac- tion (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Sev- eral cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19

Cutaneous Manifestations in Patients with SARS- CoV-2 Infections

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifesta- tions of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reac- tion (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Sev- eral cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19

SARSCOV-2 PSYCHOSOMATIC EFFECTS AND FEAR OF STIGMA ON THE DISCHARGE DAY OF INFECTED INDIVIDUALS: SAPFO STUDY

Background: Although research has been mainly focused on effective treatment for SARS-COV-2 infection, psychosocial aspects of the infection it is vital to be taken into consideration. The aim of the present study is to evaluate the psychosomatic effects and the fear of stigma which patients may face after the end of treatment and discharge from hospital. Subjects and methods:This was a non-intervention perspective study conducted in the Department of Infectious Diseases of University General Hospital of Alexandroupolis (Greece). Patients on the discharge day completed questionnaires in which 5 topics were evaluated: pain/discomfort, anxiety/distress, fear/worries, stigma and tolerance of treatment. The questionnaires were derived from similar Quality of Life Tools. The total score of each patient was normalized as percentage. Results: Females and younger than 40 years old had more worries and fears on discharge day. Significant factors were days of hospitalization, days of fever and need of oxygen therapy. Patients who hospitalized more than 10 days, particularly in isolation negative pressure rooms, with persistent fever more than 7 days and need of oxygen therapy had more anxiety, worries for their clinical condition and fear of stigma. The majority of patients (80%) were expecting to face moderate to severe problems with family members, friends and colleagues underlying the dimensions of stigma. Conclusions: It is crucial to evaluate the psychosocial aspects of this infection and limit the stigma which patients may face returning to their daily routine. Further studies are needed with larger patient series and with the usage of psychometric instruments

Synchronous Presence of Nasopharyngeal Carcinoma and Marginal Zone (MALT-Type) B-Cell Lymphoma in the Pharynx

Synchronous malignancy of squamous cell carcinoma and malignant lymphoma in the head and neck region is extremely rare. Nasopharyngeal carcinoma is a nonlymphomatous, squamous cell carcinoma that occurs in the nasopharyngeal epithelium. Reported herein is a unique case of nasopharyngeal carcinoma occurring simultaneously with MALT-type lymphoma in an 83-year-old woman, who complained of deglutition dysfunction. Endoscopic examination of respective organs revealed a submucosal tumour on the posterior wall of pharynx. Biopsy of the hypopharynx was taken and sent for histological examination, which revealed two different neoplasms. Immunohistochemical and molecular analysis confirmed the diagnosis of nasopharyngeal carcinoma coexisting with a MALT-type lymphoma

Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review)

The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID‑19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID‑19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts

Culture and labour productivity: an empirical investigation

Culture is considered as one of the most powerful forces that shape human behaviour and thereby economic activity. This paper investigates the effects of culture on labour productivity and examines the cultural traits driving this relationship. Using panel data analysis, empirical evidence is provided covering a sample of 34 OECD countries over a wide period of three decades. Our empirical results suggest a significant positive relationship between the cultural background and labour productivity. The main channels of this positive impact are control and work ethic environment, while obedience has a negative impact on productivity. These findings are robust to a series of robustness checks, including alternative cultural measures, additional control variables, various country samples, and alternative specifications

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Backward Running: Acute Effects on Sprint Performance in Preadolescent Boys

The aim of this study was to examine the acute effect of backward running (BwR) during warm-up on a 20-m sprint of boys’ performance, compared to forward running (FwR). Fourteen recreationally active preadolescent boys (aged 12.5 ± 0.5 years) were examined in 3 protocols: warm-up (control condition), warm-up with 3 × 10 m additional BwR sprints and warm-up with 3 × 10 m additional FwR sprints. Participants were evaluated 4 minutes after each protocol on a 20-m sprint and intermediate distances, as well as the rate of perceived exertion (RPE). Sprint speed across 10-20 m was significantly higher for the BwR warm-up compared to the regular warm-up (p < 0.05) and a significantly higher RPE after the BwR and FwR protocols compared to the control condition was recorded (p < 0.05). No significant difference was detected across the distances 0–5, 5–10, 0–10 and 0–20 m. Although adding 3 × 10-m sprints of BwR or FwR after the warm-up did not enhance performance in a 20 m sprint of preadolescent boys, the positive effect of BwR across 10–20 m distance suggests that BwR could be an alternative means for enhancing performance for certain phases of a sprint for this age. However, preadolescent boys’ response to different sprint conditioning exercise stimuli and the optimization of rest time to maximize performance remain to be determined

Study of clinicopathological and immunohistochemical variables with prognostic and predictive value in cancer of unknown primary (CUP) and development of a prognostic algorithm

Background: CUP represents a heterogeneous population of patients with systemicmalignancy, variable outcomes and managed on the basis of ‘‘one size fits all’’therapeutic concepts.Identification of clinical, pathologic and laboratory parameters with prognostic utilitycould contribute to estimation of death hazard and tailoring of therapy. Also insightsinto the molecular biology of CUP are urgently needed.Patients and Methods: Our study is divided in two parts. In the first part, clinical,pathologic and laboratory data from 311 patients with CUP diagnosed in a singleuniversity centre from 1988 to 2011 were examined for prognostic significance inunivariate, multivariate and Classification and Regression Tree (CART) analyses. Weanalysed all published CUP prognostic algorithms in PubMed and EmBase from 1985to date in order to describe defining characteristics.We also retrospectively examined in the second part the immunohistochemical (IHC) expression of PTEN, phospho-AKT, Cyclin D1, p21, phospho-RPS6, Notch1, 2,3, Jagged1, cMET, and pMAPK biomolecules in 100 CUP tumors using tissuemicroarrays. From the percentage of staining tumour cells and the literature, we selectedcut-offs to classify the expression of each biomolecule, aiming to study their correlationto clinicopathologic characteristics and prognostic utility for patient outcome.Results: In the 311 patients which were examined for the development of a prognosticalgorithm, most patients harboured poorly differentiated adenocarcinoma or carcinoma(85%) in visceral sites (62%) and were managed with combination chemotherapy.Median overall survival for all patients was 8 months (95% CI 6.7–9.1). Multivariateanalysis established that only leucocytosis (HR 0.37, p = 0.001, cut off <10,000/mm3 leucocytes), clinicopathologic CUP subgroup (HR 2.44, p = 0.001 for the visceralsubgroup) and performance status (HR 0.58, p = 0.002 for PS 0–1) retained independent prognostic significance. These three parameters were used for developinga prognostic algorithm (Ioannina Score for CUP Outpatient Oncologic Prognostication,I-SCOOP) which produced a dynamic 5-tier point score and classified patients in low,intermediate and high risk groups with median survival times of 36, 11–14 and 5–8months respectively.The immunoistochemical analysis of the 100 CUP patients showed thatPTEN, pAKT, pRPS6, Notch3, and pMAPK were frequent expressed. At univariateanalysis, high IHC expression of pAKT and pRPS6 displayed statistically significantassociation with worse survival. Prognosis was worse upon concurrent high IHCexpression of pMAPK and pAKT {median overall survival = 8 months [95%confidence interval (CI) 5.3-10.7] versus 17 months [95% CI 13.1-20.9]}. Inmultivariate analysis, high p21 was associated with better survival (risk ratio [RR] =0.34 [95% CI 0.16-0.73], P = 0.005). High expression of pAKT (RR = 2.39 [95% CI1.23-4.66], P = 0.01) or pRPS6 (RR = 2.76 [95% CI 1.31-5.84], P = 0.008) wasassociated with worse survival. A linear correlation of Notch3 and cMET expression was found (p = 0.001), while pMAPK emerged as the major adverse prognostic factor(median overall survival OS 9 vs. 17 months, p = 0.016), carrying also a significantlypositive predictive value (p = 0.02). Our study indicated a favorable prognostic impactof cMET expression in CUP, both in univariate (median OS 15 vs. 9 months, p = 0.05)and in multivariate analysis (Relative Risk RR for death 0.48, p = 0.025). cMET andNotch3 expression were found to be statistically more frequent in squamous carcinomas(positive in 90 % of cases), associated with a unique metastatic IHC pattern (cMEThighin soft tissue/lymph node metastases, p\0.001, Notch3-high in visceral,peritoneal/pleural and soft tissue/lymph node metastases, p\0.001).Conclusions: We developed a simple and easy to use CUP prognostic algorithm basedon readily available clinicopathologic and laboratory variables. A major limitation ofmost studies on CUP prognostic scores is the inability to proceed to prospective orretrospective validation of the algorithm in an independent CUP patient population.However, intrinsic statistical validation generated promising, though not definite, hints that our model is stable and independent of random population and data fluctuationsOur preliminary data pinpoint the MAPK and cMET axes as crucial in definingcancer progression and outcome in CUP patients and, if prospectively validated inindependent series, could identify these biomolecules as promising therapeutic targets.Εισαγωγή. Το ΚΑΠΕ αποτελεί ετερογενή κλινική οντότητα, για την οποία αφενός δενείναι δυνατή η ανίχνευση της πρωτοπαθούς εστίας ακόμη και μετά από πλήρηδιαγνωστική προσέγγιση αφετέρου η θεραπευτική του προσέγγιση είναι σχεδόνομοιόμορφη. Για το λόγο αυτό η ταυτοποίηση κλινικών, παθολογικών ή/καιεργαστηριακών παραμέτρων με προγνωστική αξία θα μπορούσε να συνεισφέρει στηνσυσχέτιση της νόσου με τον κίνδυνο θανάτου, αλλά και στην εξατομίκευση τηςθεραπείας ενώ η αποσαφήνιση της βιολογικής συμπεριφοράς αποτελεί επιτακτικήανάγκη για την βελτίωση της θεραπευτικής αντιμετώπισης και κατά συνέπεια τηςπαράτασης της 12μηνης ολικής επιβίωσης.Ο στόχος δηλαδή αυτής της διδακτορικής διατριβής ήταν διπλός. Αρχικά ηδημιουργία προγνωστικού αλγόριθμου ικανού να κατηγοριοποιήσει τους ασθενείς μεΚΑΠΕ και να βοηθήσει στην εξατομίκευση της θεραπευτικής προσέγγισης και σεδεύτερο βαθμό, υποθέτοντας ότι αυτός ο τύπος κακοήθειας μπορεί να κατέχει ιδιαίτεραβιολογικά χαρακτηριστικά προσπαθήσαμε να ανιχνεύσουμε την πιθανή προγνωστικήή/και προβλεπτική αξία βιομορίων που συμμετέχουν στην μετάδοση σήματος μέσω των μονοπατιών ΡΤΕΝ/ΑΚΤ, cΜΕΤ, ΝΟΤCΗ και ΜΑΡΚ, με την χρήση τηςανοσοϊστοχημικής τους έκφρασης.Ασθενείς και Μέθοδοι. Έγινε αναδρομική έρευνα των κλινικών αρχείων τηςΟγκολογικής Κλινικής του Πανεπιστημίου Ιωαννίνων ασθενών με ΚΑΠΕ πουδιεγνώσθησαν από το 1988 ως το 2011 με επικαιροποίηση των δεδομένων έκβασης καιεισαγωγή σε ηλεκτρονικό αρχείο. Καταφέραμε την συλλογή δεδομένων από 311ασθενείς. Τα δεδομένα υποβλήθηκαν σε στατιστική ανάλυση, με τη χρήση τουμοντέλου Cox αναλογικού κινδύνου για μονοπαραγοντική και πολυπαραγοντικήανάλυση, καθώς και τη χρήση της στατιστικής μεθόδου των δέντρων ταξινόμησης καιπαλινδρόμησης (Classification and Regression Tree -CART).Ακολούθησε η συλλογή δεδομένων, από 100 δείγματα ασθενών με ΚΑΠΕ καιεξετάσαμε την ανοσοϊστοχημική έκφραση των p21, CyclinD1, pAKT, pRPS6, PTEN,cMET, Jagged1, NOTCH 1-3 και pMAPK βιομορίων. Χρησιμοποιήσαμε την τεχνικήτων ιστικών μικροσυστοιχιών σκοπεύοντας να καθορίσουμε την έκφραση αυτών των βιομορίων με κλινικο-παθολογοανατομικά χαρακτηριστικά καθώς και με τηνπρογνωστική σημασία που αυτή έχει στην έκβαση των ασθενών.Αποτελέσματα. Η επεξεργασία των δεδομένων των 311 ασθενών με ΚΑΠΕ ανέδειξεότι οι περισσότεροι ασθενείς παρουσίασαν χαμηλής διαφοροποίησης αδενοκαρκίνωμαή αδιαφοροποίητο καρκίνωμα (85%), κυρίως με σπλαχνικές μεταστάσεις(62%), είχανκαλή φυσική κατάσταση (55%) και έλαβαν χημειοθεραπεία με βάση τηνπλατίνα(68%). Η μέση επιβίωση όλων των ασθενών ήταν 8 μήνες (95% CI 6.7–9.1).Στη μονοπαραγοντική ανάλυση αρκετοί παράμετροι συσχετίστηκαν με την έκβαση τωνπεριστατικών. Η πολυπαραγοντική ανάλυση ανέδειξε ως ανεξάρτητους προγνωστικούςπαράγοντες την καλή φυσική κατάσταση (HR 0.58, p = 0.002 για PS 0–1), την κλινικο-παθολογοανατομική υποομάδα (HR 2.44, p = 0.001 για την υποομάδα της σπλαχνικήςνόσου) και την λευκοκυττάρωσης (HR 0.37, p = 0.001, cut off <10,000/mm3λευκοκύτταρα). Αυτοί οι τρεις παράμετροι χρησιμοποιήθηκαν για την δημιουργία τουπρογνωστικού αλγόριθμου (Ioannina Score for CUP Outpatient OncologicPrognostication, I-SCOOP), ο οποίος κατάφερε τον διαχωρισμό των ασθενών σε 3 ομάδες, την ευνοϊκής, την ενδιάμεσης και την πτωχής πρόγνωσης. Οι ομάδες αυτέςπαρουσίασαν μέση επιβίωση 36, 11-15 και 5-8 μήνες αντίστοιχα. Ο αλγόριθμοςυποβλήθηκε σε αξιολόγηση επιβεβαιώνοντας την στατιστική του δυναμική.Τα 100 δείγματα που υποβλήθηκαν σε ανοσοϊστοχημική ανάλυση ανέδειξαντα pAKT, Notch3 και pMAPK ως τα βιομόρια με τη μεγαλύτερη έκφραση. Το pAKT[RR = 2.39 (95% CI 1.23–4.66),p = 0.01] και pRPS6 [RR = 2.76 (95% CI 1.31–5.84), p = 0.008] εκφραζόμενο φαίνεται να προσδίδει στον ασθενή πτωχή πρόγνωση.Βρέθηκε μία γραμμική σχέση της έκφρασης μεταξύ του Notch3 και του cMET (p =0.001) ενώ η αυξημένη έκφραση του pMAPK συνδέθηκε με πτωχή έκβαση (μέσηολική επιβίωση 9 έναντι 17 μηνών, p = 0.016) καθώς και θετική προβλεπτική αξία (p =0.02). Η πρόγνωση ήταν ακόμη χειρότερη όταν υπήρξε η συνδυασμένη έκφραση τωνpMAPK και pAKT [μέση ολική επιβίωση 8 μηνών (95% CI 5.3–10.7) έναντι 17 μηνών(95% CI 13.1–20.9]. Η μελέτη αυτή ανέδειξε επιπλέον θετική προγνωστική σημασίαπου έχει η έκφραση του cMET με (μέση ολική επιβίωση 15 έναντι 9 μηνών, p = 0.05)τόσο στη μονοπαραγοντική όσο και στην πολυπαραγοντική ανάλυση (κίνδυνοςθανάτου RR 0.48, p = 0.025). Και η αυξημένη έκφραση του p21 σχετίστηκε μεκαλύτερη επιβίωση. [RR = 0.34 (95% CI 0.16–0.73),p= 0.005]. Τα cMET και Notch3εκφράζονται πιο συχνά στα πλακώδη καρκινώματα καθώς και σε ΚΑΠΕ με μονήρη μετάσταση (η έκφραση του cMET είναι αυξημένη όταν υπάρχει λεμφαδενική ήμαλακών μορίων μεταστατική νόσος, p=0.001, και του Notch3 στη σπλαχνική νόσο καιστη λεμφαδενική ή μαλακών μορίων μεταστατική νόσος, p=0.001).Συμπεράσματα. Αναπτύξαμε έναν απλό και εύκολο στη χρήση προγνωστικόαλγόριθμο βασιζόμενο σε κλινικο-ιστολογικές και εργαστηριακές μεταβλητές πουεπιτρέπει την καταλληλότερη πρόγνωση αλλά και την εξατομίκευση της θεραπευτικήςπροσέγγισης.Η έκφραση των p21 και cMET φαίνεται να σχετίζεται με ευνοϊκότερηπρόγνωση, σε αντίθεση με την αυξημένη έκφραση των pMAPK, pAKT τα οποίασχετίστηκαν με πτωχή πρόγνωση. Το ίδιο επιβεβαιώθηκε και από τον συνδυασμό τους.Η μελέτη μας προσπάθησε να καθορίσει τον ρόλο των βιομορίων που συμμετέχουνστην λειτουργία των ΡΤΕΝ/ΑΚΤ, ΜΑΡΚ, Notch και ΜΕΤ μονοπατιών. Πρόκειται γιακυτταρικά μονοπάτια μετάδοσης σήματος η λειτουργία των οποίων καθορίζει τηνέναρξη και την ανάπτυξη της καρκινικής διαδικασίας. Ο προγνωστικός αλγόριθμος I-SCOOP και η συσχέτιση της έκφρασης τωνυπό μελέτη βιομορίων θα μπορούσε μετά ίσως και από αξιολόγησης τους σεμεγαλύτερο και ανεξάρτητο πληθυσμό να συμβάλλει περαιτέρω στην θεραπευτικήστρατηγική και αντιμετώπιση αυτών των ασθενών. Η χρήση τεχνικών μοριακήςβιολογίας θα μπορούσε να συμπληρώσει την προγνωστική αξία αυτού του αλγόριθμου