Should we be concerned when COVID-19-positive patients take opioids to control their pain? Insights from a pharmacological point of view.

OBJECTIVE: The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches. MATERIALS AND METHODS: Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language. RESULTS: Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters. CONCLUSIONS: Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder.

Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. METHODS: Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers.

Visceral leishmaniasis and anti-TNF-alpha therapy: case report and review of the literature.

OBJECTIVES: Visceral leishmaniasis (VL) is an extremely rare example of opportunistic infection in patients treated with TNF-alpha antagonists and only a few cases have been described. In this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing VL under biologic therapy are described. METHODS: Case report and review of the published cases of VL in patients under biologic treatment. RESULTS: We retrieved six patients, including ours, all of whom presented anarchic fever and pancytopenia. In 5 cases, splenomegaly was detected. The same number of patients came from endemic areas for VL. In the majority of the cases a bone marrow examination was not diagnostic, requiring the performance of a second one and/or the execution of other diagnostic tests. One fatal outcome was observed. CONCLUSION: Even if VL represents a sporadic complication of biologic treatments, its presence should always be suspected in patients developing a triad of signs and symptoms constituted by fluctuant fever, pancytopenia and splenomegaly, especially if coming from endemic areas. In these cases an extensive diagnostic work-up must be warranted. Atypical and confusing features may resemble autoimmune diseases at presentation and during the course of the illness.

Linezolid as rescue drug: a clinical case of soft tissue infection caused by a Staphylococcus aureus strain resistant in vivo to teicoplanin.

The authors report and discuss a patient admitted to intensive care unit (ICU) for acute respiratory failure due to upper airway obstruction caused by face and neck soft tissue infection. An oxacillin-resistant Staphyloccoccus aureus was isolated from necrotic skin lesions and from skin biopsy. The strain was susceptible in vitro to teicoplanin, but it showed resistance in vivo, despite appropriate dosage. After 6 days of full dose therapy, since the clinical course worsened, teicoplanin was interrupted and linezolid was started. In 48 hours signs of infection regressed, and the patient was discharged from the ICU after 10 days of linezolid treatment. Linezolid resulted as a rescue drug for a life-threatening infection.

Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with progression in human neuroblastoma.

In human tumors changes in angiogenesis and expression of extracellular matrix-degrading enzymes occur simultaneously during invasion and metastasis. Tissues from 20 biopsies of human neuroblastoma (NB) were investigated immunohistochemically by using an antibody against factor VIII to determine their microvessel number, and by in situ hybridisation to determine the expression of mRNA of the matrix metalloproteinase-2 (MMP-2) and MMP-9. The extent of angiogenesis and the expression of the MMP-2 and MMP-9 mRNA were upregulated in advancing stages. These in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with NB tumor progression.

Curariform peripheral block of muscular tone selectively increases precentral N30 somatosensory evoked potentials component. A pharmacological study carried out on healthy subjects and parkinsonian syndromes.

In the present study we investigated whether the precentral component (N30) of short somatosensory evoked potentials (SEPs) to median nerve stimulation may be modified by peripheral neuromuscular blocking agent in patients affected by rigidity. We, therefore, recorded SEPs in nine Parkinson's disease (PD) patients and in seven psychotic patients affected by neuroleptic malignant syndrome (NMS), all showing severe rigidity. Each patient group was studied before and after the placebo, and before and after an atracurium besilate bolus of 0.05 mg/kg, in a single recording session. At the time of the test the PD patients had not taken any antiparkinsonian therapy for at least 48 h. The same recordings were also taken on nine neurologically normal subjects undergoing surgical procedures. Atracurium administration produced a remarkable amplitude increase of the major precentral component (N30) of SEPs. An atracurium-induced N30 amplitude increase was observed in both PD patients (from 2.41 to 4.07 microV) and NMS psychotic patients (from 2.03 to 3.97 microV), whereas there was a minor N30 amplitude increase in healthy subjects (from 3.53 to 4. 10 microV). The N30 latency was unaffected. Amplitude and latency of the major parietal SEPs component (N20) was unchanged in the three groups studied. Our results lead to the conclusion that a neuromuscular blocking agent is capable of increasing the N30 amplitude in patients affected by severe rigidity, exclusively reducing their muscular tone without interfering with the central dopaminergic system. Thus, a "peripheral gating" of sensory input to the supplementary motor area due to rigidity may play a relevant role in producing the N30 amplitude decrease described in patients affected by degenerative or pharmacologically induced parkinsonism. The reduction of rigidity could be the mechanism by which dopamine may increase the precentral N30 amplitude in parkinsonian syndromes.

[Perioperative pain and stress: a comparison between video laparoscopic cholecystectomy and "open" cholecystectomy]. / Dolore e stress perioperatori: confronto tra videolaparocolecistectomia e colecistectomia "open".

Pain and endocrine-metabolic response to surgical stress, during surgery and in the early postoperative period, was compared in two groups of patients affected by gallstones and randomly assigned to Laparoscopic Cholecystectomy or Open Cholecystectomy. Pain was assessed by the VAS method also taking into account the need of analgesic administration in the postoperative period. The so called "stress hormones" (Prolactin (PRL), Cortisol (CORT), Human Growth Hormone (HGH)) and glycaemia were monitored during surgery and in the first postoperative 24 hours. The minimal invasive technique of laparoscopic cholecystectomy accounted for a very limited analgesic administration. In the intraoperative period laparoscopic cholecystectomy plasma hormone levels overlapped the open cholecystectomy ones, while in the postoperative period a constant increase in PRL and CORT levels was registered in the open cholecystectomy group demonstrating a prolonged stressful condition. The end results of this study show that laparoscopic cholecystectomy has major advantages than open cholecystectomy in the treatment of gallstones as far as pain and endocrine-metabolic response are concerned.