Chronic Gastro-Duodenal Ulcerative Disease and the Death of Father Stephan Schätzl from Viechtwang (Austria).

Stephan Schätzl was the parish priest of Viechtwang, Upper Austria. He lived in the aftermath of the Peace of Augsburg in a period of schism between Roman Catholics and Lutherans. His portrait, depicted only 6 days before his demise in 1590, shows that he had extreme ante mortem cachexia. Documentary sources detailed his life and ill-health and it is proposed that he had chronic gastro-duodenal ulcerative disease which ultimately led his to death.

Factors associated with sepsis development in 606 Spanish adult patients with cellulitis.

BACKGROUND: Cellulitis, a frequent cause of admission of adult patients to medical wards, occasionally evolves to sepsis. In this study we analyze the factors related to sepsis development. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Sepsis was diagnosed according to the criteria of the 2016 International Sepsis Definitions Conference. Multiple logistic regression modelling was performed to determine the variables independently associated with sepsis development. RESULTS: Mean age was 63.4 years and 51.8% were men. Overall 65 (10.7%) patients developed sepsis, 7 (10.8%) of whom died, but only 4 (6.2%) due to cellulitis. Drawing of blood (P < 0.0001) or any (P < 0.0001) culture, and identification of the agent (P = 0.005) were more likely among patients with sepsis. These patients had also a longer duration of symptoms (P = 0.04), higher temperature (P = 0.03), more extensive cellulitis (P = 0.02), higher leukocyte (P < 0.0001) and neutrophil (P < 0.0001) counts, serum creatinine (P = 0.001), and CRP (P = 0.008) than patients without sepsis. Regarding therapy, patients with sepsis were more likely to undergo changes in the initial antimicrobial regimen (P < 0.0001), received more antimicrobials (P < 0.0001), received longer intravenous treatment (P = 0.03), and underwent surgery more commonly (P = 0.01) than patients without sepsis. Leukocyte counts (P = 0.002), serum creatinine (P = 0.003), drawing of blood cultures (P = 0.004), change of the initial antimicrobial regimen (P = 0.007) and length of cellulitis (P = 0.009) were independently associated with sepsis development in the multivariate analysis. CONCLUSIONS: Increased blood leukocytes and serum creatinine, blood culture drawn, modification of the initial antimicrobial regimen, and maximum length of cellulitis were associated with sepsis in these patients.

Decreasing rates of acute myocardial infarction in people living with HIV: a nationwide cohort study in Spain, 2004-2015.

OBJECTIVES: Contemporary data from country-wide cohorts are needed to reveal trends in the occurrence of acute myocardial infarction (AMI) in people living with HIV (PLWH). We analysed time trends in the standardized incidence rate (sIR) of AMI in PLWH in Spain from 2004 to 2015, and compared them with trends in the general population. METHODS: A longitudinal study in a nationwide contemporary multicentre HIV-infected cohort was carried out. Data on all incident AMI events were collected, and age- and sex-standardized IRs calculated. To analyse the IR of AMI in the general population, the national rates of hospital discharges for AMI per 100 000 inhabitants stratified for age and sex from 2004 to 2015 were obtained using the morbidity report data from the National Statistics Institute. A Poisson regression model was fitted to assess the effect of covariates of interest on AMI occurrence. RESULTS: The sIRs of AMI in 2004-2015 were 237.92 [95% confidence interval (CI) 225.95-249.90] and 66.75 (95% CI: 23.49-110.01) per 100 000 patient-years in male and female PLWH, respectively. There was a decrease in the sIR of AMI in male PLWH from 279.02 (95% CI: 265.46-292.59) per 100 000 person-years in 2004-2009 to 222.13 (95% CI: 210.83-233.42) per 100 000 person-years in 2010-2015. Compared with the general population, the sIR ratio was 1.41 (95% CI: 1.26-1.55) in 2004-2009, and 1.28 (95% CI: 1.15-1.43) in 2010-2014. AMI occurrence was associated with older age (P < 0.066 for each 10-year age stratum ≥ 35-years compared with the 25-34 year stratum), higher plasma HIV RNA (P < 0.001), lower CD4 count (P < 0.04 for CD4 strata > 350 cells/µL compared with the 0-100 cells/µL stratum), and the period 2004-2009 (P < 0.001). CONCLUSIONS: There has been a decreasing incidence of AMI in PLWH in Spain, associated with improving immune and virological status, but the incidence of AMI has remained higher than in the general population.

Factors predictive of relapse in adult bacterial osteomyelitis of long bones.

BACKGROUND: Osteomyelitis is a difficult-to-cure infection with a high relapse rate despite combined medical and surgical therapies. Some severity factors, duration of antimicrobial therapy and type of surgical procedure might influence osteomyelitis relapse. METHODS: 116 patients with osteomyelitis were followed for ≥1 year after hospital discharge. Demographic, microbiological and clinical data, eight severity factors and treatment (surgical and antibiotic) were analyzed. RESULTS: Mean age was 53 years and 74.1% were men. Tibia (62.1%) and S. aureus (58.5%) were the most commonly involved bone and bacteria, respectively. Mean follow-up was 67.1 months. Forty-six patients underwent bone debridement, 61 debridement plus flap coverage and 9 antimicrobial therapy only. Twenty-six patients (22.4%) relapsed, at a mean of 11.2 months since hospital discharge. Duration > 3 months (p = 0.025), number of severity factors (P = 0.02) and absence of surgery (P = 0.004) were associated with osteomyelitis relapse in the univariate analysis. In the Cox regression analysis, osteomyelitis duration > 3 months (P = 0.012), bone exposure (P = 0.0003) and type of surgery (P < 0.0001) were associated with relapse. Regarding the surgical modalities, bone debridement with muscle flap was associated with better osteomyelitis outcomes, as compared with no surgery (P < 0.0001) and debridement only (P = 0.004). CONCLUSIONS: Osteomyelitis extending for > 3 months, bone exposure and treatment other than surgical debridement with muscular flap are risk factors for osteomyelitis relapse.

Factors associated with long-term CD4 cell recovery in HIV-infected patients on successful antiretroviral therapy.

OBJECTIVES: The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. METHODS: Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. RESULTS: The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/µL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/µL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. CONCLUSIONS: In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.

Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.

OBJECTIVE: To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. METHODS: Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. RESULTS: Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. CONCLUSIONS: Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.

The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions.

Matrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P = 0.0001), MMP-3(-1612 5A/6A) SNP (P = 0.001), higher levels of TIMP-4 (P = 0.004) and MMP-8 (P = 0.006) and lower levels of MMP-1 (P = 0.03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Risk of clinically significant depression in HIV-infected patients: effect of antiretroviral drugs.

OBJECTIVES: We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. METHODS: CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. RESULTS: In total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01-15.15] and 7.06 (95% CI 5.45-9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28-0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94; 95% CI 1.21-3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2-4 and > 4 years of ART was 0.72 (95% CI 0.36-1.44), 0.10 (95% CI 0.04-0.25) and 0.05 (95% CI 0.01-0.17), respectively, compared with ART-naïve patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. CONCLUSIONS: The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens.

Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV coinfected patients.

The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV- hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68 were HCV-monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B coinfection, non-infective liver diseases or HAART adherence <75% were excluded. LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs (MMP -1,-2,-3,-8,-9,-10 and -13) and their tissue inhibitors (TIMP-1,-2 and -4) were measured by ELISA microarrays. Associations with LF were statistically analysed. Protease inhibitors, usually administered to patients with advanced LF were excluded from the analysis. Increased LF was significantly associated with d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001) and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P < 0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir (P = 0.02) and current CD4(+) T-cells (P < 0.0001), low gain of CD4(+) T-cells after HAART (P = 0.01) and higher MMP-2 (P = 0.02) and TIMP-2 serum levels (P = 0.02). By logistic regression the only variables significantly associated with increased LF were: use of ddI (OR 8.77, 95% CI: 2.36-32.26; P = 0.005), male gender (OR 7.75, 95% CI: 2.33-25.64, P = 0.0008), HCV viral load (in log) (OR 3.53, 95% CI: 2.16-5.77; P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09-1.34, P = 0.0003). We conclude that only higher HCV viral load, older age, male gender, and use of ddI associated independently with increased LF in our study.

Evaluation of the possible influence of hepatitis C virus and liver fibrosis on HIV type 1 immunological and virological outcomes.

OBJECTIVES: The aim of the study was to evaluate the possible effect of hepatitis C virus (HCV) coinfection on the viroimmunological outcomes of HIV-1 infection. METHODS: A cross-sectional study of 805 patients with active HCV infection receiving or not receiving antiretroviral therapy (ART) was carried out. RESULTS: A number of parameters were significantly associated with undetectable HIV-1 viral load in univariate analyses, such as age, toxic habits, CD4 cell count, liver test results, HCV viral load and ART. However, only current ART (P<0.0001), CD4 cell count (P<0.0001), age (P=0.004) and current injecting drug use (P=0.02) were independently associated with undetectable viral load in multivariate analysis. None of the many HCV- and liver fibrosis-related parameters analysed showed a significant association with HIV-1 viral load or CD4 cell count in multivariate analyses, with the exception of the annual fibrosis progression index which almost reached statistical significance in the subgroup of ART-untreated patients (P=0.06) and was inversely predictive of CD4 cell count in the whole group (P=0.007). However, its relative weight was modest, as it only explained 0.8% of the total variability in CD4 cell count. CONCLUSIONS: HCV-related parameters did not significantly affect virological and immunological outcomes of HIV-1 infection in ART-treated and untreated patients. In contrast, liver fibrosis, as measured using the annual fibrosis progression index, was inversely associated with CD4 cell count, although its weight was relatively small. Therefore, HCV- and liver fibrosis-related factors do not seem appreciably to influence these outcomes from a practical viewpoint in ART-naïve patients, nor impair CD4 and HIV-1 viral load responses to ART.

The IL-1ß (+3953 T/C) gene polymorphism associates to symptomatic lumbar disc herniation.

PURPOSE: To determine whether polymorphisms (SNPs) in the genes encoding cytokines and nitric oxide synthase (NOS) might play some role in lumbar disc herniation (LDH). PATIENTS AND METHODS: Case-control study in which 179 patients were retrospectively reviewed. The case group was made of 50 patients with symptomatic LDH diagnosed by MRI while the control group was made of 129 individuals undergoing routine hip or knee arthroplasty with a lifetime lack of low back pain. SNPs in the cytokine genes of IL-1 [IL-1α (-889 C/T), IL-1ß (+3953 T/C)], TNF-α (-308 G/A and -238 G/A) and NOS genes [eNOS (r 27 bp, intron 4 and -786 T/C) and iNOS (22 G/A)]. RESULTS: The CC genotype and C allele of the IL-1ß (+3953 T/C) SNP were significantly more frequent among LDH patients compared to controls. On the other hand, eNOS (-768 T/C) and iNOS (22 G/A) SNPs were significantly more common in the control group. CONCLUSIONS: Carriers of the CC genotype of the IL-1ß (+3953 T/C) SNP were more frequent among LDH patients suggesting some potential role of the IL-1ß SNP on LDH pathogenesis. The eNOS (-786 T/C) and iNOS (22 G/A) SNPs were more frequent among the control subjects, suggesting their possible protective role against LDH. Genotyping these SNPs could be useful to identify persons with an increased lifetime risk of disc herniation in whom measures to avoid LDH could be implemented.

Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions.

BACKGROUND: Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. OBJECTIVE: The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. METHODS: SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. RESULTS: A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/µL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were -13 mg/dL (-7%; P<0.0001), -19 mg/dL (-13%; P<0.0001) and -7 mg/dL (-6%; P=0.021), respectively. CONCLUSIONS: In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

Association of HIV transmission categories with sociodemographic, viroimmunological and clinical parameters of HIV-infected patients.

To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0.0001) and viral load (P=0.02). There were differences in the groups regarding the CD4 response (P=0.01), but not the virological response (P=0.4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0.01), viral load at 12 months (P=0.0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0.001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0.003) and men who have sex with men (MSM) groups (P=0.02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

Hydroxy-chloroquine to treat COVID-19 - infected patients: Some lessons from medical anthropology and history of medicine.

It is certainly too early to take stock of Professor Raoult's intuitions, and moreover, that is not the aim of this short article. Nevertheless, experience has shown that in times of unprecedented health crises, prescriptions often turn out to be adventurous, especially when it comes to a new virus. The collective imagination around a remedy often takes the place of a guarantee or, on the contrary, a safeguard. Here, the authors question the implementation of hydroxy-chloroquine treatment in the context of the COVID-19 pandemic. How was his prescription discussed in this context of crisis? What lesson can we learn from medical anthropology and the history of medicine, by witnessing other epidemics and atypical or unconventional substances or behaviors of practitioners?

Il est certainement trop tôt pour faire le point sur les intuitions du professeur Raoult, et ce n'est d'ailleurs pas le but de ce court article. Néanmoins, l'expérience a montré qu'en période de crise sanitaire sans précédent, les prescriptions se révèlent souvent aventureuses, surtout lorsqu'il s'agit d'un nouveau virus. L'imagination collective autour d'un remède se substitue souvent à une garantie ou, au contraire, à une sauvegarde. Ici, les auteurs s'interrogent sur la mise en œuvre du traitement à l'hydroxy-chloroquine dans le contexte de la pandémie de la COVID-19. Comment sa prescription a-t-elle été discutée dans ce contexte de crise ? Quelle leçon pouvons-nous tirer de l'anthropologie médicale et de l'histoire de la médecine, en étant témoins d'autres épidémies et de substances ou comportements atypiques ou non conventionnels des praticiens ?

Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments.

BACKGROUND: The treatment of multidrug-resistant Acinetobacter baumannii meningitis is a serious therapeutic problem due to the limited penetration of antibiotics into the CSF. We describe the clinical features and the outcome of a group of patients with nosocomial neurosurgical meningitis treated with different therapeutic options. METHODS: All patients with nosocomial post-surgical meningitis due to A. baumannii diagnosed between 1990 and 2004 were retrospectively reviewed. RESULTS: During the period of study, 51 cases of this nosocomial infection were identified. Twenty-seven patients were treated with intravenous (iv) monotherapy: carbapenems (21 cases), ampicillin/sulbactam (4 cases) and other antibiotics (2 cases). Four patients were treated with iv combination therapy. Nineteen patients were treated with iv and intrathecal regimens: colistin by both routes (8 cases), carbapenems plus iv and intrathecal (4 cases) or only intrathecal (5 cases) aminoglycosides, and others (2 cases). Seventeen patients died due to the infection. One patient died without treatment. The mean (SD) duration of therapy was 17.4 (8.3) days (range 3-44). Although no patients treated with colistin died, we did not observe statistically significant differences in the mortality among the groups with different treatments. CONCLUSIONS: Nosocomial Acinetobacter meningitis has a high mortality. Combined therapy with iv and intrathecal colistin is a useful and safe option in the treatment of nosocomial Acinetobacter meningitis.

Incidence of anaemia and impact on sustained virological response in HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin.

Ribavirin (RBV) exposure is important for maximizing the response to chronic hepatitis C virus (HCV) therapy. However, RBV-associated haemolytic anaemia may force dose reductions or even treatment discontinuation. The use of zidovudine might further increases the risk of anaemia in HCV/HIV-coinfected patients. The predictors of anaemia were examined in PRESCO, a large trial conducted in HIV/HCV-coinfected patients treated with pegylated interferon alpha-2a 180 mug/week plus RBV 1000-1200 mg/day. Measurements included maximal decrease in haemoglobin (Hb) throughout treatment, drops in Hb to <10 (moderate) or to <8.5 g/dL (severe), and premature RBV discontinuation because of anaemia. Finally, the impact of anaemia on sustained virological response (SVR) was assessed. Moderate or severe anaemia occurred, respectively, in 51 (13%) and 13 (3.3%) of 389 patients included in the study. Lower baseline Hb [RR: 0.14 (95% CI 0.07-0.27); P < 0.0001] and greater Hb drops during the first 4 weeks of therapy [RR: 4.74 (95% CI 2.95-7.60); P < 0.0001] were independent predictors of moderate anaemia at any time point in the multivariate analysis. Mean drops in Hb from baseline to week 4 were significantly greater in patients receiving zidovudine compared with other drugs (-3.09 vs-2.3 g/dL; P < 0.001). Lower baseline Hb [RR: 0.33 (95% CI 0.11-0.95); P = 0.04] and maximal Hb drops during treatment [RR: 2.48 (95% CI 1.33-4.59); P = 0.004] predicted treatment discontinuation because of anaemia. However, maximal Hb drops, development of moderate-severe anaemia and RBV dose reductions were comparable among patients who achieved SVR and those who did not. Lower baseline Hb predicts maximal drops in Hb and development of anaemia in HIV/HCV-coinfected patients treated with pegylated interferon plus RBV. The use of zidovudine is associated with greater Hb declines at week 4. However, severe anaemia is relatively infrequent and seems not to have much impact on SVR. Given the availability of alternative antiretroviral drugs, it is advised to avoid zidovudine while receiving anti-HCV treatment.

Bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of 344 episodes.

OBJECTIVE: Osteomyelitis is a difficult-to-cure infection, with high relapse rate despite adequate therapy. Large published osteomyelitis series in adults are rare. METHODS: A total of 344 adult osteomyelitis patients were studied and followed > 12 months after hospital discharge. Demographic, microbiological, clinical, therapeutic and outcome data were analyzed. RESULTS: Mean age was 52.5 ± 18.3 years and 233 (67.7%) were male. Main osteomyelitis types were post-surgical (31.1%), post-traumatic (26.2%) and hematogenous (23%). Tibia (24.1%) and femur (21.8%), and methicillin-susceptible S. aureus (29.6%) were the most commonly involved bone and bacteria, respectively. Median follow-up was 12.0 (IQR 0-48) months. Inflammatory markers were increased in 73.6%. Overall, patients were treated by IV and oral routes with one (IV: 44.5%, oral: 26.7%), two (IV: 30.1%, oral: 21.8%) or ≥ 2 (IV: 15.2%, oral: 6.1%) antibiotics. Median duration on IV/oral antimicrobials was 28.0 (IQR 24-28) and 19.5 (IQR 4-56) days, respectively. Anti-staphylococcal ß-lactams cloxacillin/cefazolin (19.2%) and ciprofloxacin (5.5%) were the most frequently used IV and orally, respectively. Overall 234 (68.0%) underwent surgery, 113 (32.8%) debridement, 97 (27.4%) debridement + muscle flap and 24 (7%) amputation. At the end of follow-up 208 patients (60.6%) did not have relapsed. Operated patients had significantly less relapses (p<0.0001). A total of 23 (6.7%) died, 11 (3.2%) by infectious complications and 48 (14%) were lost in the follow-up. CONCLUSIONS: Osteomyelitis is due to different causes complicating its therapy. Risk factors or causal microorganism could influence its treatment and outcome. Aggressive surgery along with adequate antimicrobial therapy are mandatory for cure.