Strongyloides stercoralis hyperinfection syndrome due to the acceleration of the autoinfective cycle of the nematode is a life-threatening form of the infection occurring in immunocompromised hosts. Intestinal ileus, which is commonly encountered in this form, may reduce the bioavailability and thus the efficacy of oral anthelminthic drugs used in the treatment of the S. stercoralis hyperinfection syndrome. We report the efficacy and safety of subcutaneous administration of ivermectin in a patient infected with human T cell lymphotropic virus type I with S. stercoralis hyperinfection syndrome who was unresponsive to an oral combination of ivermectin and albendazole.

HIV-1 is dependent on the host cell for providing the metabolic resources for completion of its viral replication cycle. Thus, HIV-1 replicates efficiently only in activated CD4 + T cells. Barriers preventing HIV-1 replication in resting CD4 + T cells include a block that limits reverse transcription and also the lack of activity of several inducible transcription factors, such as NF-κB and NFAT. Because FOXO1 is a master regulator of T cell functions, we studied the effect of its inhibition on T cell/HIV-1 interactions. By using AS1842856, a FOXO1 pharmacologic inhibitor, we observe that FOXO1 inhibition induces a metabolic activation of T cells with a G0/G1 transition in the absence of any stimulatory signal. One parallel outcome of this change is the inhibition of the activity of the HIV restriction factor SAMHD1 and the activation of the NFAT pathway. FOXO1 inhibition by AS1842856 makes resting T cells permissive to HIV-1 infection. In addition, we found that FOXO1 inhibition by either AS1842856 treatment or upon FOXO1 knockdown induces the reactivation of HIV-1 latent proviruses in T cells. We conclude that FOXO1 has a central role in the HIV-1/T cell interaction and that inhibiting FOXO1 with drugs such as AS1842856 may be a new therapeutic shock-and-kill strategy to eliminate the HIV-1 reservoir in human T cells.

In an open prospective study, adrenaline administration in ten patients with eleven episodes of septic shock was studied. Appropriate supportive therapy (antibiotics, laparotomies, parenteral alimentation, ventilation) was given as needed. Haemoglobin was kept at or above 12 g%, pulmonary capillary wedge pressure kept at approximately 15 mmHg, and cardiac index at greater than 4.5 IIminlm 2. Only when systemic vascular resistance (SVR) dropped below 600 dyn. s. cm-5 was adrenaline given to raise the latter to no higher than 800 dyn. s. cm-5 and the adrenaline was titrated to this end point. Adrenaline was used at doses up to 0.47 Jiglkglmin for up to nineteen days. There was no reliable dose response curve for adrenaline: each septic insult needed different dosages. However, if high enough doses were given, SVR eventually increased. There was no deterioration in cardiac index nor further increase in pulse rate and no renal damage was demonstrated. Only one patient died in septic shock. Two others died from causes not directly related to sepsis and another two while still in hospital, but again not septic. Five patients were eventually discharged from hospital. Adrenaline can thus be used as a vasoconstrictor in septic shock without adverse effects, but initial doses have to be high and the effects measured and titrated carefully. Used this way, adrenaline provides time for the eradication of sepsis.

Background Information regarding coronavirus disease 2019 (COVID-19) in haemodialysis (HD) patients is limited and early studies suggest a poor outcome. We aimed to identify clinical and biological markers associated with severe forms of COVID-19 in HD patients. Methods We conducted a prospective, observational and multicentric study. Sixty-two consecutive adult HD patients with confirmed COVID-19 from four dialysis facilities in Paris, France, from 19 March to 19 May 2020 were included. Blood tests were performed before diagnosis and at Days 7 and 14 after diagnosis. Severe forms of COVID-19 were defined as requiring oxygen therapy, admission in an intensive care unit or death. Cox regression models were used to compute adjusted hazard ratios (aHRs). Kaplan–Meier curves and log-rank tests were used for survival analysis. Results Twenty-eight patients (45%) displayed severe forms of COVID-19. Compared with non-severe forms, these patients had more fever (93% versus 56%, P < 0.01), cough (71% versus 38%, P = 0.02) and dyspnoea (43% versus 6%, P < 0.01) at diagnosis. At Day 7 post-diagnosis, neutrophil counts, neutrophil:lymphocyte (N:L) ratio, C-reactive protein, ferritin, fibrinogen and lactate dehydrogenase levels were significantly higher in severe COVID-19 patients. Multivariate analysis revealed an N:L ratio >3.7 was the major marker associated with severe forms, with an aHR of 4.28 (95% confidence interval 1.52–12.0; P = 0.006). After a median follow-up time of 48 days (range 27–61), six patients with severe forms died (10%). Conclusions HD patients are at increased risk of severe forms of COVID-19. An elevated N:L ratio at Day 7 was highly associated with the severe forms. Assessing the N:L ratio could inform clinicians for early treatment decisions.

rHU-EP free patients seem to restore the EPO-hepcidin axis that is critical for erythropoiesis. A specific combination of clinical and biological parameters may help to detect future rHU-EPO free patients. This article is protected by copyright. All rights reserved.

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Summary The utility of zero‐time kidney biopsies (KB) in deciding to accept expanded criteria donor (ECD) kidneys remains controversial. However, zero‐time histology is one of the main causes for discarding kidneys in the United States. In a single‐centre study, we examined the utility and impact on outcome of the use of frozen section zero‐time KB among ECD. Ninety‐two zero‐time KB were analysed for accept/discard decision between 2005 and 2015 among ECD. 53% of kidneys were rejected after zero‐time KB analysis; there was no difference in individual clinical and biological data between accepted/rejected groups. However, histology of rejected kidneys showed more sclerotic glomeruli (20% vs. 8%; P < 0.001), increased interstitial fibrosis (1.25 ± 0.12 vs. 0.47 ± 0.09; P < 0.0001), more arteriosclerosis (2.14 ± 0.17 vs. 1.71 ± 0.11; P = 0.0032) and arteriolar hyalinosis (2.15 ± 0.12 vs. 1.55 ± 0.11; P = 0.0006). Using propensity score matching, we generated a group of 42 kidney allograft recipients who received a transplant matched for donor zero‐time histology and clinical characteristics with donors whose kidneys were rejected. Interestingly, their 1‐ and 5‐year graft survival and function were similar to the global cohort of ECD recipients. In conclusion, when performed, zero‐time KB was a decisive element for kidney discard decision. However, adverse zero‐time histology was not associated with poorer graft survival and kidney function among ECD.