Skin and Soft Tissue Infections in Patients with Solid Tumours

Background. Skin and soft tissue infections (SSTIs) in cancer patients represent a diagnostic challenge, as etiologic diagnosis is often missing, and clinical assessment of severity is difficult. Few studies have described (SSTIs) in patients with solid tumours (STs). Patients and Methods. Records of patients with ST and SSTI, cared for at the University Hospital of Heraklion, from 2002 to 2006 were retrospectively studied. Results. A total of 81 episodes of SSTIs, occurring in 71 patients with ST, have been evaluated. Their median age was 65 years (34–82). The most common underlying malignancy was breast cancer in 17 patients (24%). Most episodes (89%) occurred in nonneutropenics. Cellulitis/erysipelas was the most common clinical presentation (56; 69%). Bacterial cultures were possible in 29 (36%) patients. All patients received antimicrobial therapy, while in 17 episodes (21%) an incision and drainage was required. Treatment failure occurred in 20 episodes (25%). Five patients (7%) died due to sepsis. None was neutropenic. Severe sepsis on admission (=0.002) and prior blood transfusion (=0.043) were independent predictors of treatment failure. Conclusion. SSTIs can be life threatening among patients with ST. Early diagnosis and appropriate treatment are of the utmost importance, since sepsis was proven a significant factor of unfavourable outcome

Thyroid hormone alterations in critically and non-critically ill patients with SARS-CoV-2 infection

Objective: Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, w e studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients. Design: Cohort observational study. Methods: We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism. Results: A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of neg ative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare. Conclusions: NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other crit ically ill patients

Diagnostic and prognostic value of procalcitonin among febrile critically ill patients with prolonged ICU stay

<p>Abstract</p> <p>Background</p> <p>Procalcitonin (PCT) has been proposed as a diagnostic and prognostic sepsis marker, but has never been validated in febrile patients with prolonged ICU stay.</p> <p>Methods</p> <p>Patients were included in the study provided they were hospitalised in the ICU for > 10 days, were free of infection and presented a new episode of SIRS, with fever >38°C being obligatory. Fifty patients fulfilled the above criteria. PCT was measured daily during the ICU stay. The primary outcome was proven infection.</p> <p>Results</p> <p>Twenty-seven out of 50 patients were diagnosed with infection. Median PCT on the day of fever was 1.18 and 0.17 ng/ml for patients with and without proven infections (p < 0.001). The area under the curve for PCT was 0.85 (95% CI; 0.71-0.93), for CRP 0.65 (0.46-0.78) and for WBC 0.68 (0.49-0.81). A PCT level of 1 ng/mL yielded a negative predictive value of 72% for the presence of infection, while a PCT of 1.16 had a specificity of 100%. A two-fold increase of PCT between fever onset and the previous day was associated with proven infection (p 0.001) (OR = 8.55; 2.4-31.1), whereas a four-fold increase of PCT of any of the 6 preceding days was associated with a positive predictive value exceeding 69.65%. A PCT value less than 0.5 ng/ml on the third day after the advent of fever was associated with favorable survival (p 0.01).</p> <p>Conclusion</p> <p>The reported data support that serial serum PCT may be a valuable diagnostic and prognostic marker in febrile chronic critically ill patients.</p

In vivo study of cross-resistance of Candida parapsilosis to echinocandins in a mouse model

Objectives. C. parapsilosis is one of the most common causes of invasive candidiasis. The echinocandins, including caspofungin (CAS) , micafungin (MICA) and anidulafungin (ANF), possess broad spectrum fungicidal activity and are currently considered the treatment of choice for many forms of invasive candidiasis. Importantly, these agents retain their activity against azole-resistant Candida spp. Nonthelless, the echinocandins demonstrate reduced in vitro activity against C. parapsilosis, whereas clinical failure due to CAS-resistant (CAS-R) C. parapsilosis isolates have been recently reported in patients receiving CAS, causing breakthrough infections to echinocandins. Overall, this recent shift in the epidemiology of Candida infections raises concerns about the optimal regiment for empirical treatment of invasive candidasis.However, the clinical implications of the differencial activity of echinocandins against C. parapsilosis remain currently unknown, as comparative in vivo studies are completely lacking. Furthermore, because the echnocandins possess significant immunomodulatory properties that are mediated via beta-glucan unmasking, it is plausible that differences in the in vitro activity of echinocandins against Candida spp. may also result in significant quantitative and qualititive changes in antifungal host immune response in vivo. The purpose of the present study was to establish a clinically relevant mouse model of invasive C. parapsilosis infection in immunocompetent mice, and to compare the in vivo activity of ANF and CAS in experimental candidemia caused by C. parapsilosis isolates that are sensitive in vitro to ANF but are resistant to CAS. The degree of the in vivo cross-resistance among echinocandins and the fitness loss associated with caspofungin (CAS) non-susceptibility of C. parapsilosis are not well studied. Overall, we anticipate that the results of our in vivo studies in murine model of invasive candidiasis should provide important information on the optimal management of infections caused by this emerging Candida spp.Materials and Methods. Female BALB/c mice were infected with three different ANF-susceptible isolates of C. parapsilosis with different degrees of non-susceptibility to CAS via injection of blastospores dissolved in 200 μL of phosphate-buffered saline into the lateral tail veins. Initial experiments were performed to define the optimal C. parapsilosis inoculum (LD50) for studying antifungal activity (inoculum range 10^5-10^7 blastospores). It will be established a mouse model of invasive candidiasis for evaluation of survival, assessment of fungal burden in organs and measurement of weight loss.The efficacy of respective echinocandin regimens (CAS, ANF) against 3 C. parapsilosis isolates was analyzed. Starting 6 hours after infection with each of C. parapsilosis isolate, intraperitoneal administration of each echinocandin (CAS, ANF), in two doses (1 mg/kg and 10 mg/kg) corresponding to that used for treatment of invasive candidiasis in humans, or DMSO (control group) was administered once daily for 7 days or until the death of the animal. Fungal burden was measured in kidney, spleen and liver in selected mice (n=6) euthanized on day 2 after infection. In addition, measurement of weight loss of infected mice, an established marker of disease severity, distributed to the evaluation of comparative efficacy of echinocandins against invasive candidiasis of C. parapsilosis. To further evaluate differences in fungal burden of the organs in mice infected with CAS-S, CAS-I or CAS-R C. parapsilosis isolates, histopathological examination of the kidneys was performed in selected mice (n=3) euthanized on day 2 after infection and treated, as described above. Results. Increasing CAS resistance was associated with reduced virulence of C. parapsilosis isolates (mortality rates CAS-S 100% vs CAS-I 11.1% vs CAS-R 0% P = 0.001). The CAS-S isolate was more virulent in comparison to the other two isolates, while there was a trend towards reduced mortality following infection with CAS-R isolate when compared to the CAS-I isolate. High doses of either echinocandin were active against infection with CAS-I isolate when assessed by fungal burden reduction and weight gain. However, no reduction in fungal burden in mice infected with the CAS-R isolate following treatment with either echinocandin in both doses. Nevetherless, mice infected with the CAS-R isolate had reduced disease severity following echinocandin treatment, suggesting that echinocandins have activity in vivo, even against echinocandin-resistant strains. In animals infected with the CAS-S strain, high and low dose doses of CAS or low dose of ANF treatment resulted in lower organ fungal burdens versus controls. Weight loss was less in mice infected by the CAS-S C. parapsilosis following high dose CAS or ANF treatment, while all mice of the control group lost substantial weight and died on day 5 after infection. Conclusions. A reproducible model of C. parapsilosis IC in immunocompetent mice was established that mimics the pathobiology of hematogenous infection in humans and allows comparisons of antifungal drug activity based on differences in fungal burden and weight loss of infected mice. It is suggested that echinocandins are effective antifungal agents against C. parapsilosis infections and concurrently, they possess significant immunomodulatory properties. There is no straightforward in vitro/in vivo correlation of echinocandin activity against C. parapsilosis displaying non-susceptibility to CAS. A complex interplay of residual echinocandin activity, decreased virulence and/or fitness of isolates with altered cell wall, and possible immunomodulatory effects, can be encountered in vivo during infection with CAS-non-susceptible C. parapsilosis isolates.Εισαγωγή. Η Candida parapsilosis αποτελεί ένα συχνό αίτιο διηθητικής καντιντίασης (ΔΚ). Οι εχινοκανδίνες (κασποφουγκίνη-CAS, μικαφουγκίνη-MIC και ανιντουλαφουγκίνη -ANF), έχουν ευρέως φάσματος μυκητοκτόνο δράση και αποτελούν θεραπεία εκλογής για την ΔΚ. Ωστόσο, παρουσιάζουν μειωμένη in vitro δραστηριότητα κατά της C. parapsilosis που προκαλεί “breakthrough” λοιμώξεις σε ασθενείς υπό θεραπεία με τα φάρμακα αυτά, ενώ, πρόσφατα, έχουν αναφερθεί και περιπτώσεις κλινικής αποτυχίας, οφειλόμενες σε ανθεκτικά στην CAS στελέχη. Η αλλαγή στην επιδημιολογία των καντιντιάσεων προβληματίζει σχετικά με την εμπειρική θεραπεία της ΔΚ.Ο βαθμός διασταυρούμενης αντοχής της C. parapsilosis στις εχινοκανδίνες in vivo δεν είναι ακόμα γνωστός και καλά κατανοητός. Επιπλέον, οι εχινοκανδίνες έχουν σημαντικές ανοσοτροποποιητικές ιδιότητες, μέσω «αποκάλυψης» της β-γλυκάνης, του κύριου ανοσοδιεγερτικού μορίου του κυτταρικού τοιχώματος του μύκητα. Παρά την επισήμανση του ανοσοτροποποιητικού μηχανισμού των εχινοκανδινών, μεγάλο τμήμα της κλινικής δράσης τους κατά της C. parapsilosis παραμένει άγνωστο, καθώς συγκριτικές in vivo μελέτες είναι λίγες. Ο σκοπός της μελέτης είναι να καθιερωθεί πειραματικό μοντέλο ΔΚ σε ανοσοεπαρκή ποντίκια, που μιμείται ανάλογες συνθήκες στον άνθρωπο, και να συγκριθεί η in vivo αποτελεσματικότητα της ANF και CAS κατά διαφορετικών στελεχών C. parapsilosis που είναι ευαίσθητα in vitro στην ανιντουλαφουγκίνη, ενώ παρουσιάζουν διαφορετικού βαθμού αντοχή in vitro στην CAS. Προσδοκούμε ότι τα αποτελέσματα της μελέτης θα δώσουν σημαντικές πληροφορίες για την καλύτερη διαχείριση των λοιμώξεων από C. parapsilosis.Υλικά και Μέθοδοι. Θηλυκά ανοσοεπαρκή BALB/c ποντίκια μολύνθηκαν ενδοφλεβίως με τρία διαφορετικά στελέχη C. parapsilosis, ευαίσθητα στην ANF και διαφορετικού βαθμού αντοχή στην CAS. Αφού βρέθηκε η ιδανική ποσότητα των ενέσιμων βλαστοσπορίων του μύκητα, καθιερώθηκε το μοντέλο ΔΚ με εκτίμηση της επιβίωσης, ανάλυση του μυκητικού φορτίου στα όργανα των ζώων και καθημερινή μέτρηση της απώλειας βάρους. Καθορίσθηκε η δράση της CAS και ANF έναντι των 3 χρησιμοποιούμενων στελεχών C. parapsilosis ευαίσθητων στην ANF και διαφορετικού βαθμού αντοχής στην CAS. Τα ζώα χωρίστηκαν σε ομάδες κι έλαβαν ενδοπεριτοναϊκά CAS, ANF σε 2 δόσεις (1mg/Kg/ημέρα και 10mg/Kg/ημέρα) ή φυσιολογικό ορό (τα ζώα μάρτυρες). Για να επιβεβαιωθεί η ΔΚ και να εκτιμηθεί η δραστηριότητα της CAS σε σύγκριση με αυτήν της ANF, καταγράφηκε το μυκητικό φορτίο σε ήπαρ, σπλήνα και νεφρούς ποντικών που θανατώθηκαν μετά την μόλυνση. Παράλληλα, καταγράφηκε η απώλεια βάρους των ζώων, που θεωρείται δείκτης νοσηρότητας και έτσι, εκτιμήθηκε η συγκριτική δραστηριότητα των εχινοκανδινών κατά της ΔΚ από C. parapsilosis. Μόλις η in vivo δραστηριότητα της ANF και της CAS έχει πλήρως διασαφηνιστεί, θα επιβεβαιωθούν τα αποτελέσματα σχετικά με την δράση της CAS με αυτή της ANF στα 3 στελέχη C. parapsilosis, μέσω της ιστοπαθολογικής ανάλυσης του μυκητικού φορτίου στα όργανα-στόχους.Αποτελέσματα. Τα αρχικά πειράματα έδειξαν ότι το στέλεχος C. parapsilosis που είναι ανθεκτικό στην CAS παρουσιάζει μία τάση για εξασθενημένη επιθετικότητα στο συγκεκριμένο μοντέλο ΔΚ. Αντίθετα, το στέλεχος που είναι ευαίσθητο στην CAS είναι πιο επιθετικό, προκαλώντας τον θάνατο των ποντικών κατά την μόλυνση με την ίδια ποσότητα βλαστοσπορίων/ποντίκι (ποσοστό θνητότητας: CAS-S 100% vs CAS-I 11.1% vs CAS-R 0%, P = 0.001). Στα ποντίκια που μολύνθηκαν με την ενδιάμεσης αντοχής στην CAS C. parapsilosis, και οι δύο εχινικανδίνες ανέδειξαν παρόμοια και σημαντική δραστηριότητα, όπως αποδείχτηκε από την κάθαρση του μυκητικού φορτίου στα όργανα των ζώων και τη μείωση της βαρύτητας της νόσου, βάσει της απώλειας βάρους. Στα ποντίκια που μολύνθηκαν με το στέλεχος C. parapsilosis που είναι ανθεκτικό στην CAS, δεν υπήρχε καμία σημαντική διαφορά ανάμεσα στις ομάδες θεραπείας, όσον αφορά την δράση των εχινοκανδινών έναντι του στελέχους αυτού. Ωστόσο, τα ποντίκια που έλαβαν θεραπεία με οποιαδήποτε εχινοκανδίνη και ιδιαίτερα στις υψηλές δόσεις, είχαν πιο γρήγορη ανάκαμψη και μειωμένη βαρύτητα λοίμωξης, σε σύγκριση με τα ποντίκια-μάρτυρες.Στα ποντίκια που μολύνθηκαν με στέλεχος ευαίσθητο στην CAS, παρατηρήθηκε μείωση στο μυκητικό φορτίο σε όλα τα όργανα μετά από την χορήγηση CAS ή χαμηλής δόσης ANF. Η απώλεια βάρους ήταν μικρότερη στα ποντίκια που έλαβαν θεραπεία, ενώ όλα τα ποντίκια που δεν έλαβαν καμία θεραπεία έχασαν σημαντικό βάρος και πέθαναν μετά την μόλυνση με το συγκεκριμένο στέλεχος C. parapsilosis.Συμπεράσματα. Καθιερώθηκε ένα μοντέλο υποξείας ΔΚ από C. parapsilosis σε ανοσοεπαρκή ποντίκια, που μιμείται την παθοβιολογία των ανθρώπων και επιτρέπει την σύγκριση της δράσης των εχινοκανδινών έναντι των διαφορετικών στελεχών C. parapsilosis.Προέκυψαν σημαντικές ενδείξεις ότι εκτός από την αντιμυκητική τους δράση, οι εχινοκανδίνες κατέχουν και ανοσοτροποποιητικές ιδιότητες. Διεπιστώθη ότι δεν υπάρχει συσχέτιση της in vitro/in vivo δραστηριότητας των εχινοκανδινών έναντι διαφορετικών στελεχών C. parapsilosis και προτείνεται ότι ένα σύμπλεγμα αλληλεπίδρασης ανοσοτροποποιητικών ιδιοτήτων και της απώλειας «fitness» του μύκητα, καθώς και της γνωστής φαρμακολογικής δράσης των εχινοκανδινών μπορεί να προκύψει in vivo σε ασθενείς με ΔΚ από στελέχη C. parapsilosis μη ευαίσθητα στην CAS

Recognizing and Managing Pancreaticopleural Fistulas in Children

Background: Pancreaticopleural fistula, an abnormal communication between the pancreas and the pleural cavity, is a rare complication of pancreatic disease in children and is mainly associated with acute pancreatitis, chronic pancreatitis, trauma or iatrogenicinjury. The present review presents the current available data concerning the pathogenesis, clinical features, diagnosis and management of this unusual but difficult clinical problem among children, in order to shed light on its pathologic manifestation and raise clinical suspicion. Methods: The review of the literature was performed through a PubMed search of pediatric original articles and case reports, using the key words “pancreaticopleural fistula”, “pancreatitis”, “pleural effusion”, “pseudocyst” and “children”. The literature search revealed 47 cases of pediatric patients with pancreaticopleural fistula. Results: Diagnosis is based on the patient’s medical history, physical examination and imaging, while the cornerstone of diagnosis is the presence of high pleural effusion amylase levels. The management of this disorder includes conservative, endoscopic and surgical treatment options. If treated promptly and properly, this clinical entity could have a lower rate of complications. Conclusions: The incidence of pancreaticopleural fistula in children may be underestimated in the literature, due to a reduced degree of clinical suspicion. A more heightened awareness of this entity is needed to improve the quality of life in children that suffer from this condition, as early diagnosis is essential for effective treatment and improved outcome

Serious complications of COVID-19 vaccines: A mini-review.

Τhe most promising approach of fighting COVID-19 and restraining the course of this pandemic is indisputably the universal vaccination of the population with safe and effective vaccines. However, besides the common and usually mild side effects of the authorized vaccines, some rare, major adverse reactions are increasingly being reported worldwide during the post marketing surveillance phase of vaccines&apos; circulation, such as anaphylaxis, vaccine-induced thrombotic thrombocytopenia, myopericarditis and Guillain-Barré syndrome. Despite rare cases with complications from COVID-19 vaccines, the net benefit-risk ratio shows a clearly favorable balance towards COVID-19 vaccination for all age and sex groups. Vaccine adverse events should be identified early and monitored closely. As many aspects of these adverse effects remain still obscure for the medical community and the relevant stakeholders, it is also highly important to be promptly reported. Nonetheless, these complications should not constitute a reason to change the vaccine policy and further studies are needed to alleviate concerns and reluctance to COVID-19 vaccinations

Primary Duodenal Melanoma: Challenges in Diagnosis and Management of a Rare Entity

Primary melanoma of the duodenum is an extremely rare, aggressive and life-threatening malignant neoplasm. Published data regarding the effectiveness of current treatment strategies is limited, and our knowledge relies mostly on sporadic case reports. The diagnosis of primary duodenal melanoma is challenging and is based on the patient’s medical history and findings from physical examination and radiological and endoscopic imaging as well as proper and careful pathological examinations of the tumor. Despite the many advances in cancer treatment, the prognosis for patients with this type of melanoma remains extremely poor. Delayed diagnosis at advanced disease stage, the general aggressive behavior of this neoplasm, the technical difficulty in achieving complete surgical resection, along with the rich vascular and lymphatic drainage of the intestinal mucosa, all have a negative impact on patients’ outcome. In the present review, we aimed to collect and summarize the currently available data in the literature regarding the pathogenesis, clinical features, diagnosis, management and long-term outcomes of this rare, malignant tumor, in order to expand knowledge of its biological behavior and investigate optimal therapeutic options for these patients. Additionally, we present our experience of a case involving a 73-year-old female with primary duodenal melanoma, who was successfully treated with complete surgical resection

Medullary thyroid carcinoma in children: current state of the art and future perspectives

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results