Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in various indications. They act as inhibitors of β-(1,3)-glucan synthesis in the fungal cell wall and have a favorable pharmacological profile. They have a broad spectrum of activity against all Candida species. Higher MIC's have been observed against C. parapsilosis and C. guilliermondii. Data from clinical trials for invasive Candida infections/candidaemia suggest that the clinical outcome of patients treated with either drug may be very similar. A comparison has been done between caspofungin and micafungin but for anidulafungin a comparative trial with another echinocandin is still lacking. All three drugs are highly effective if not superior to treatment with either fluconazole or Amphotericin B, particularly in well-defined clinical settings such as invasive Candida infections, Candida oesophagitis and candidaemia. Differences between the three echinocandins with regard to the route of metabolism, requirement for a loading dose, dose adjustment in patients with moderate to severe hepatic disease and different dosing schedules for different types of Candida infections have to be considered. Relevant drug-drug interactions of Caspofungin and Micafungin are minimal. Anidulafungin has no significant drug interactions at all. However, echinocandins are available only for intravenous use. All three agents have an excellent safety profile.

ObjectiveTo improve the quality of organs from brain-dead donors by assessing the influence of alternative strategies on the early behavior of kidneys after transplantation into unmodified hosts. Summary Background DataKidneys transplanted from living donors perform consistently better than those from cadaver sources. The authors have recently shown that donor brain death produces inflammatory changes in peripheral organs within hours, amplifies coincident ischemia-reperfusion injury, and accelerates acute and chronic rejection. Normalization of the graft by donor hormone treatment has hitherto been unsuccessful. MethodsA standardized rat model of brain death was used. Experimental groups included recipients of allogeneic grafts from living and brain-dead donors (F3443 LEW). Donors were treated immediately after induction of brain death either with intravenous steroids, which block inflammatory cytokine release, or a soluble P-selectin glycoprotein ligand (sPSGL), which blocks initial selectin-mediated cellular adhesion. Kidney grafts were examined serially up to 10 days by morphology, immmunohistology, and reverse transcriptase-polymerase chain reaction. ResultsOverall survival of ummodified recipients of kidneys from brain-dead donors was significantly reduced versus living donors. Animals with organs from brain-dead donors that had received steroids or sPSGL survived significantly longer than those from untreated brain-dead donors. The intensity of ischemia-reperfusion injury and of acute rejection was reduced. Cellular infiltration and transcription of mRNA of representative proinflammatory mediators were diminished. ConclusionsTreatment of organ donors at the time of brain death markedly improves organ quality after kidney transplantation, upgrading it to that from a living donor.The catastrophic central injury of brain death (BD) has been shown to perturb significantly the function and structure of somatic organs in situ by rapid upregulation of inflammatory mediators and other acute phase proteins.

NCT01544686 (Clinicaltrials.gov).

Early diagnosis of CNS aspergillosis requires a high degree of clinical suspicion, because there are no typical clinical symptoms or CSF findings. Clinical features are usually dramatic and tend to progress rapidly. Changes in mental status, hemiparesis and seizures are most common, but other nonspecific neurological features may occur and should always be an indication for neuroradiological examination in high-risk patients, in order to allow early initiation of antifungal therapy. Low density lesions with little or no mass effect and minimal or no contrast enhancement on CT scans that are usually more numerous on MRI and show intermediate signal intensity within high-signal areas on T2-weighted images, may suggest CNS aspergillosis. Cerebral lesions in CNS aspergillosis are often located not only in the cerebral hemispheres but also in the basal ganglia, thalami, corpus callosum and perforator artery territories. There is frequently a lack of contrast enhancement or perifocal oedema, due to the immunosuppressed status of the patient. A definite diagnosis requires brain tissue for histopathological analysis. However, neurosurgery is often not feasible, so that any of the neuroradiological findings mentioned above should raise the suspicion of CNS aspergillosis in immunocompromised patients and lead to early initiation of antifungal therapy. In the past, amphotericin B-based therapy was the treatment of choice for CNS aspergillosis, but this treatment produced negligible effects. Recently, voriconazole has been reported to be more effective than amphotericin B in the treatment of invasive aspergillosis. Response rates of about 35% have been achieved with voriconazole in patients with CNS aspergillosis. Combination therapy with antifungal agents, such as voriconazole plus caspofungin or liposomal amphotericin B, is being investigated in vitro and in animal models, and optimistic results have been observed. A combined medical and neurosurgical treatment should be considered in all patients with this disease.

Purpose The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009–2019). Results 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.