Immune Cell Response during COVID-19 Infection and following SARS-CoV-2 Vaccination in Patients Admitted to Intensive Care Unit.

Background: Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods: In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result: The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (p=0.0018). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions: Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.

sCXCL16 as a prognostic biomarker for COVID-19 outcome.

As elevated levels of the soluble CXCL16 (sCXCL16) chemokine have been reported in severe coronavirus disease 2019 (COVID-19) patients, this study examined whether sCXCL16 concentration on the first day of hospitalization predicted death in COVID-19 patients. A total of 76 patients with COVID-19 were admitted to the Military Hospital of Tunis, Tunisia, between October 2020 and April 2021, and later classified as survivors or nonsurvivors based on their outcomes. At admission, the groups were matched by age, gender, comorbidities, and the percentage of patients with moderate conditions. On the first day of admission, serum's sCXCL16 concentrations were measured using a magnetic-bead assay. There was an eightfold increase in serum sCXCL16 levels in the nonsurvivors' group (3661.51 ± 2464.87 pg/mL vs. 454.3 ± 338.07 pg/mL, p < 0.0001). For the optimal cutoff value of sCXCL16 at 2095 pg/mL, we found a 94.6% sensitivity and a 97.4% specificity, with an area under curve of 0.981 (p = 5.03E-08; 95% confidence interval [95% CI]: 0.951-1.0114). Considering the risk of death at a concentration above the threshold, the unadjusted odds ratio was 36 (p < 0.0001). The adjusted odd ratio was estimated at 1.003 (p < 0.0001; 95% CI: 1.002-1.004). Finally, there was a significant difference between survival and nonsurvival groups in leukocyte numbers (p = 0.006), lymphocytes (p = 0.001), polymorphonuclear neutrophils (p = 0.001), and C-reactive protein levels (p = 0.007), except for monocytes (p = 0.881). Based on these results, sCXCL16 level could be used for detecting nonsurvival COVID-19 patients. Therefore, we recommend assessing this marker in hospitalized COVID-19 patients.

[Comparative study of patients hospitalized for SARS-CoV-2 infection in two consecutive waves in Tunisia]. / Étude comparative de patients hospitalisés pour une infection SARS-CoV-2 au cours de deux vagues consécutives en Tunisie.

Introduction: Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a global pandemic with a heavy medical and societal-economic toll. The health consequences were not similar during the successive waves that affected several countries. The aim of our study was to compare the sociodemographic, clinical and evolutionary features of COVID-19 patients hospitalized at the Military Hospital of Tunis (HMPIT) during the 2nd and 3rd waves that affected the country. Patients and methods: Observational prospective study involving 1,527 COVID-19 patients hospitalized at HMPIT over 11 months, divided into two periods: from July 2020 to December 2020 called the second wave (V2) and from January 2021 to May 2021 called the third wave (V3). We compared the epidemiological data, the clinical form and the evolution of the patients for each period. Results: The number of hospitalized patients was 636 during V2 compared to 891 during V3. Average age was 63.5 ± 15.3 years during V2 versus 65.8 ± 17.8 years during V3 (P = not significant [NS]). The percentage of young adults [18-40 years] was 6.5% during V2 compared to 6.7% during V3 (P = NS). The gender ratio (M/F) was 1.59 for V2 and 1.42 for V3 (P = NS). Comorbidities were present in 65% of V2 patients and 66.3% of V3 patients (P = NS), with hypertension being the most prevalent one in both groups (47.2% for V2 versus 44.9% for V3; P = NS), followed by overweight, dyslipidemia and diabetes (33% for V2 versus 39.3% for V3; P = 0.012). The median duration between symptoms onset and hospitalization was 7 days [5-10] during V2 versus 8.5 days during V3 [5-12] (P = 0.0004). The severe clinical form was present in 49% of patients admitted during V2 compared to 34.8% during V3 (P < 10-3). The critical form represented 18.6% of cases during V2 against 16.8% during V3 (P = NS). The average hospital length of stay in COVID units (outside of intensive care unit) was 8.4 ± 5.4 days during V2 and 9.8 ± 5.7 days during V3. The average length of stay was significantly longer for the intensive care unit (11.3 ± 3.4 days for V2 versus 13.8 ± 3.9 days for V3; P = 0.01). The case fatality rate was 24.5% during V2 and 20.7% during V3 (P = NS). Median age of death was 70.2 years [42-88] during V2 and 70.4 years [22-96] during V3 with 2 patients less than 40 years of age (1%) for the latter period. The gender ratio (M/F) of deceased patients was 3.21 for V2 and 1.5 for V3 (P = 0.001). The case fatality rate was higher in the intensive care unit (65.4% for V2 versus 69.7% for V3; P = NS). Causes of death were dominated by ARDS (acute respiratory distress syndrome) for both periods (55.1% for V2 versus 70.8% for V3; P = 0.002), followed by septic shock (12.8% for V2 versus 10.8% for V3; P = NS) and multi-organ failure (9.6% for V2 versus 7.0% for V3; P = NS). Conclusion: This study revealed a decrease in severe and critical clinical forms during the 3rd wave, as well as a decrease in the case fatality rate compared to the previous wave, due to improved management and vaccination. On the other hand, the percentage of ARDS was significantly higher during this wave probably related to the beginning of circulation in our country of the Delta variant causing more severe clinical cases.

Comparison of ultrasound-guided internal jugular vein and supraclavicular subclavian vein catheterization in critically ill patients: a prospective, randomized clinical trial.

BACKGROUND: The aim of this study was to compare the effectiveness and safety of ultrasound-guided out-of-plane internal jugular vein (OOP-IJV) and in-plane supraclavicular subclavian vein (IP-SSCV) catheterization in adult intensive care unit. METHODS: A total of 250 consecutive patients requiring central venous catheterization, were randomly assigned to undergo either ultrasound-guided OOP-IJV or IP-SSCV cannulation. All catheterizations were carried out by three physicians. The primary outcome was the first attempt success rate. Ultrasound scanning time, venous puncture time, insertion time, overall access time, number of puncture attempts, number of needle redirections, success rate, guidewire advancing difficulties, venous collapse and adverse events were also documented. RESULTS: The first attempt success rate was significantly higher in IP-SSCV group (83.2%) compared to OOP-IJV group (63.2%) (p = 0.001). The IP-SSCV group was associated with a longer ultrasound scanning time (16.54 ± 13.51 vs. 5.26 ± 4.05 s; p < 0.001) and a shorter insertion time (43.98 ± 26.77 vs. 53.12 ± 40.21 s; p = 0.038). In the IP-SCCV group, we recorded a fewer number of puncture attempts (1.16 ± 0.39 vs. 1.47 ± 0.71; p < 0.001), needle redirections (0.69 ± 0.58 vs. 1.17 ± 0.95; p < 0.001), difficulties in guidewire advancement (2.4% vs. 27.4%; p < 0.001), venous collapse (2.4%, vs. 18.4%; p < 0.001) and adverse events (8.8% vs. 13.6%; p = 0.22). CONCLUSIONS: The IP-SSCV approach is an effective and a safe alternative to the classic OOP-IJV catheterization in critical adult patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03879954. Registered March 19, 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03879954 .

Deciphering the balance of IL-6/IL-10 cytokines in severe to critical COVID-19 patients.

The severity of COVID-19 is largely determined by the inflammatory response, a "Cytokine storm," that involves both pro- and anti-inflammatory cytokines. In the current study we investigated the balance of pro- and anti-inflammatory status as represented by the levels of IL-6/IL-10 in severe to critical COVID-19 patients. 66 confirmed COVID-19 patients admitted to the ICU were categorized into groups according to the mortality and respiratory failure. Data were collected retrospectively in ICU, including a peripheral immune cells and infection-related biomarker CRP. The measurements of cytokine levels were performed by Immulite analyzer for IL-6 and ELISA sandwich for IL-10. In addition, longitudinal measurement of IL-6 was performed during 5 days post admission. Longitudinal assays showed that IL-6 was sustained at a medium level within 5 days post admission in severe cases who survived or not requiring mechanical ventilation, whereas it was sustained at high levels throughout the disease course in either deceased cases or who developed respiratory failure. The ratio of IL-6/lymphocytes was positively correlated with the risk of mortality, while IL-10/lymphocytes ratio could predict respiratory failure in ICU. IL-6/IL-10 profiling revealed that deceased patients have different magnitudes of both IL-6 and IL-10 cytokine release. Notably, excessive levels of IL-6 concomitant with high levels of IL-10 were more common in diseased COVID-19 patients. Taking into account the IL-6/IL-10 profiling may help clinicians to identify the right time of anti-inflammation treatment and select patients who will respond to anti-cytokine therapies and maintain an adequate inflammatory response for SARS-CoV-2 clearance.

COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. METHODS: We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. RESULTS: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). CONCLUSION: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

[Clinical and epidemiological features of COVID-19-related deaths in Tunisia before the emergence of VOCs (March 2020-February 2021)]. / Caractéristiques cliniques et épidémiologiques des décès COVID-19 en Tunisie avant l'émergence des VOCs (mars 2020-février 2021).

Introduction: the purpose of this study was to describe the clinical and epidemiological features of COVID-19-related deaths in Tunisia notified at the ONMNE (National Observatory of New and emerging Diseases) between 2nd March 2020 and 28th February 2021 and to compare COVID-19-related deaths recorded in Tunisia with the international data. Methods: we conducted a national prospective longitudinal descriptive study of data collected from the National Surveillance System of SARS-CoV-2 infection of the ONMNE, Ministry of Health. All COVID-19-related deaths that occurred in Tunisia between March 2020 and February 2021 were included in this study. Data were collected from hospitals, municipalities and regional health departments. Death notifications were collected from multiple data sources (triangulation): The Regional Directorate of Basic Health Care, the ShocRoom (Strategic Health Operations Center), public and private health facilities, the Crisis Unit of the Presidency of the Government, the Directorate for Hygiene and Environmental Protection, the Ministry of Local Affairs and the Environment, as part of the follow-up of confirmed cases by the ONMNE team, positive RT-PCR / TDR post mortem results. Results: during this study, 8051 deaths were recorded, corresponding to a proportional mortality of 10.4%. The median age was 73 years, with an interquartile range of 17 years. Sex-ratio (M/F) was 1.8. The crude death rate was 69.1/100 000 inhabitants and fatality rate was 3.5%. The analysis of the epidemic curve showed 2 peaks of deaths on 29th October 2020 and 22nd January 2021, with 70 and 86 deaths notified respectively. The spatial distribution of mortality showed that the southern Tunisian region had the highest mortality rate. Patients aged 65 and over were most affected (73.7% of cases) with a crude mortality rate of 570.9/100,000 inhabitants and a fatality rate of 13.7%. Conclusion: prevention strategy based on public health measures must be reinforced by the rapid deployment of anti-COVID-19 vaccination, especially for people at risk of death.

Outcomes of treatment of severe COVID-19 pneumonia with tocilizumab: a report of two cases from Tunisia.

The SARS CoV-2 pandemic is a global health threat with high morbidity and mortality (1 to 4%) rates. COVID-19 is correlated with important immune disorders, including a "cytokine storm". A new therapeutic approach using the immunomodulatory drug, Anti-IL6 (tocilizimub), has been proposed to regulate it. We report here the first Tunisian experience using tocilizimub in two severe cases of COVID-19 pneumonia. The diagnosis was confirmed by chest scan tomography. Biological parameters showed a high level of Interleukin-6 (IL-6) that increased significantly during hospitalization. The patients developed hypoxia, so they received intravenously 8 mg/kg body weight tocilizumab. There was a resultant decrease in the level of IL6, with clinically good evolution. Blocking the cytokine IL-6 axis is a promising therapy for patients developing COVID-19 pathology.

Performance of Sepsis-3 Definitions in a Middle Income Country Intensive Care Unit.

BACKGROUND: Since they were first published in 2016, Sepsis-3 definitions have not been universally accepted. Rather, they have become a source of controversy because the clinical and laboratory parameters used had been derived mainly from patients hospitalized in Intensive Care Units (ICU) in the United States. PURPOSE: The aim of this study was to evaluate the performance of the Sepsis-3 definitions for the prediction of ICU-mortality in a Tunisian ICU population as compared to the 2003 Consensus Definitions (Sepsis-2 definitions). METHOD: The study, conducted in an 18-bed medical-surgical ICU at the Military Hospital of Tunis (Tunisia), was retrospective in nature. From January 2012 to January 2016, all patients admitted to the ICU for sepsis, severe sepsis, or septic shock as defined according to the 2003 Consensus Definitions (Sepsis-2 consensus) were eligible for this study. The new Sepsis-3 definition was then used to classify the included patients. The primary area of interest was ICU mortality, defined as death before ICU discharge. RESULTS: A total of 1080 patients were included during the recruitment period. When Sepsis-2 definitions were used, there was a difference in mortality only between septic shock and sepsis patients. Sepsis-3 definitions show that mortality increased from 16 % among no-dysfunction-infected patients to 30 % among patients with qSOFA ≥ 2 and 44% and 46% for sepsis or septic shock patients, respectively. CONCLUSIONS: Sepsis-3 definitions were better than sepsis-2 definitions at stratifying mortality among septic patients admitted to an ICU of a middle-income country (Tunisia).

Immediate Psychological Responses, Stress Factors, and Coping Behaviors in Military Health-Care Professionals During the COVID-19 Pandemic in Tunisia.

Objective: The COVID-19 epidemic began in Tunisia in March 2020; health-care workers (HCWs) were suddenly confronted with a particularly stressful situation. The aim of this study was to assess the psychological responses of HCWs during the epidemic, determine the stressors and identify ways to cope. Methods: This cross-sectional study used an online questionnaire that included 62 questions. ANOVAs and t-tests were used to compare the responses between professional groups, age groups, and genders. Results: Questionnaires were completed by 368 HCWs. HCWs believed they had a social and professional obligation to continue working long hours (95.3%). They were anxious regarding their safety (93.7%) and the safety of their families (97.8%). Youthful age (p = 0.044) and female gender (ps <0.046) were identified as stressors. The availability of personal protective equipment (PPE; 99.7%) and good communication between colleagues (98.1%) and managers (91.6%) were important protective factors. Family and friend support (95.9%), following strict protective measures (99.4%), knowing more about COVID-19 (94.8%), adopting a positive attitude (89.6%), and engaging in leisure activities (96.1%) helped in dealing with this epidemic. Conclusion: This study highlights the importance of providing HCWs with infection control guidelines and adequate PPE. Communication and support within the team and maintaining family support help in coping with this stressful situation.

Isolation and characterization of lytic phage TUN1 specific for Klebsiella pneumoniae K64 clinical isolates from Tunisia.

BACKGROUND: Multidrug-resistant Klebsiella pneumoniae spp. (kp) are emerging agents of severe infections of the respiratory, urinary tract and wounds that can progress to fatal septicemia. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy. RESULTS: In this study, we report capsule (K)-typing of 163 carbapenem-resistant Kp (CRKP) isolated 2014-2018 at the Military Hospital of Instruction of Tunis (MHT), Tunisia, by partial amplification and sequencing of the Kp wzi gene. The most prevalent K-type overall was K64 with 50.3% followed by K17 and K27 (22.7 and 11.0%, respectively). K64 Kp strains were most common and associated with increased case/fatality rates, especially at the intensive care unit (ICU). Using a K64 Kp strain we isolated and characterized a lytic Kp phage, vB_KpP_TUN1 (phage TUN1), from wastewater samples of the ICU at the MHT. TUN1 belongs to the Autographiviridae family and specifically digests K64 Kp capsules most probably via a depolymerase encoded by gp47. Furthermore, we successfully assembled phage TUN1 in a non-replicative host (E. coli) raising the possibility of in vitro assembly in the absence of live bacterial hosts. We propose that phage TUN1 is a promising candidate to be used as an adjuvant or an alternative to antibiotic therapy in CRKP infections, facilitating regulatory approval of phage therapy. CONCLUSIONS: K64, K17 and K27 are the most common wzi capsule types in this geographical location in Northern Africa. The lytic phage TUN1 efficiently lyses K64 Kp strains associated with increased case/fatality rates at body temperature. Together with its ability to be rescued in a non-replicative host these features enhance the utility of this phage as an antibacterial agent.

[Disseminated intravascular coagulation: role of the International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring system]. / La coagulation intravasculaire disséminée: intérêt du score de la société internationale sur la thrombose et l´hémostase.

Disseminated intravascular coagulation (DIC) is a life-threatening event during resuscitation. The International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring system enables early diagnosis of DIC. We here report three clinical cases of DIC characterized by several etiologies: prostatic adenocarcinoma, septic shock and retroplacental hematoma. The tests of hemostasis needed to calculate international society on thrombosis and haemostasis (ISTH) score (platelet count, prothrombin ratio, values of fibrinogen and D-dimer levels) were performed regularly. Additional, complementary tests (soluble complexes test, euglobulin lysis test, antithrombin level dosing, activated protein C and factor V dosing) were also performed. ISTH score enables early diagnosis of DIC.

Impact of high fidelity simulation on perceptions and professional skills in obstetrics.

BACKGROUND: In our country, the introduction of simulation as a teaching tool for obstetric emergencies is very recent. Several studies are being developed to evaluate its benefit in the continuing education of health professionals. OBJECTIVE: To evaluate the impact of a continuing medical education program based on High fidelity simulation drills (HFS) on professional skills in obstetrics. METHODS: 91 Learners were able to benefit from HFS continuing education program. Mean job tenure was 7.94 years [1-40]. RESULTS: We were able to highlight a positive impact of level 1 with satisfaction rates of more than 90%. 92% of participants said they left with tools applicable in the function framework. Midwives and emergency physicians were the most satisfied. The general evaluation before the beginning of the training had revealed an average score of 7.12/20 [2/20-13/20]. The variance of scores initially obtained was significantly related to the profession of the learner (p <0.0001, R = 0.61). We found significant improvement in post-training scores (p = 0.0001) and a mean difference of +1.46 [-6, +8.66]. These results highlight a level 2 impact of HFS training on learners' knowledge.

Postoperative analgesia after wound infiltration with Dexmedetomidine and Ropivacaine versus Ropivacaine alone for lumbar discectomies: a randomized-controlled trial.

INTRODUCTION: Current LA may provide solid analgesic effect however, their analgesic advantages might be limited by their short life. Several reviews highlight the potential role of ?2-adrenergic receptors agonists like dexmedetomidine (DEX) for postoperative pain control. AIM: Compare the analgesic efficacy of the sole LA: ropivacaine (R) with the combination of both: ropivacaine and DEX (RD) for wound infiltration (WI) in lumbar discectomies. METHODS: Prospective, randomized, double-blind, controlled study in nature. Adult patients undergoing elective lumbar discectomies were randomly allocated into two groups: group (R) received 2mg/kg with ropivacaine: 4.75 mg/ml in WI, group RD received the same dose of ropivacaine as the first group adding 0.5 ug/kg of DEX. Visual analog scale (VAS) at 0, 2, 6, 12, 18, and 24 hours (h); time to first rescue analgesia, total post-operative opiate dose was assessed during the first 24 h postoperatively. RESULTS: VAS values at all time intervals were significantly lower (p< 10-3) in the RD group as compared with the R group. The median time to first rescue analgesia was significantly shorter in the R group 8h [7-12] than RD group 21 h [18-24]. The median (interquartile range) opioid use was 3 [3-6] morphine mg equivalents in the R group and 0 [0-2] morphine mg equivalents in the RD group. The first time to mobilization was significantly shorter in RD group (22±03 h) than R group (27±06 h).

Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomized Controlled Pilot Study.

INTRODUCTION: Mitochondrial dysfunction and consequent cellular energetic failure play a key role in the development of sepsis-related organs failure. Evidence suggests that the pleiotropic effects of levosimendan may positively affect cellular metabolism during septic shock. OBJECTIVES: To investigate changes in the concentration of glucose, lactate, pyruvate, and glycerol in the extracellular fluid of the skeletal muscle following levosimendan administration in patients with septic shock. METHODS: The study was designed as a prospective, double-blind, controlled, clinical pilot trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mm Hg, 20 septic shock patients were randomized to receive either levosimendan 0.2 µg/kg/min (n = 10), or dobutamine 5 µg/kg/min as active comparator (n = 10). Interstitial tissue concentrations of lactate, pyruvate, glucose, and glycerol were obtained by using muscle microdialysis. All measurements, including data from right heart catheterization, were obtained at baseline and every 6 h for the following 72 h after randomization.The trial is registered with Clinicaltrials.gov, number NCT02963454. RESULTS: Compared with dobutamine, levosimendan increased interstitial tissue pyruvate concentration (153.3 ±â€Š73 and 187. 2 ±â€Š13.5 vs. 210.7 ±â€Š76.2 and 161 ±â€Š64.6; P < 0.05), and lactate clearance (55 vs. 10). Lactate/pyruvate ratio was lower in the levosimendan group at the end of study period (37. 7 ±â€Š18.9 and 29.3 ±â€Š12.7 vs. 10.9 ±â€Š4.5 and 31.4 ±â€Š13. 2; P < 0.05). CONCLUSION: Although we investigated a small number of patients, our preliminary results suggest that levosimendan may improve cellular metabolic alterations in patients with septic shock.

Exertional heat stroke: about 4 cases.

Exertional heat stroke is defined as hyperthermia associated with neurological signs related to intense physical activity performed in a hot environment. This is a medical emergency and life-threatening. In this study, we investigated four cases of exertional heat stroke hospitalized at the military hospital in Tunis (Tunisia) to describe the clinical, therapeutic and preventive characteristics and factors favoring this disease. Four young soldiers, 23 to 44 years older, have developed Exertional heat stroke after Intense and prolonged exercise. Exercises were performed in May and June, in high ambient temperature, high humidity and lack of wind. Three soldiers were in battle dress, a backpack and their weapon. Our four subjects had overweight, were not sufficiently trained and were highly motivated. Insufficient hydration and a diet rich in carbohydrates were noted. Upon hospitalization, patients were febrile and had neurological disorders, neuromuscular disorders, rhabdomyolysis and hemoconcentration. The medical care consisted of a rehydration and oxygen.

Successful treatment of a Carbapenem-resistant Klebsiella pneumoniae carrying bla OXA-48 , bla VIM-2 , bla CMY-2 and bla SHV- with high dose combination of imipenem and amikacin.

We describe a case of 58-year-old man with septic shock due to Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bloodstream infections (BSI) who was successfully treated with a high dose association of amikacin and imipenem combined with continuous venovenous hemodiafiltration (CVVHDF). A Klebsiella pneumoniae (Kp) was isolated from the catheter culture and from two blood samples, drawn from the catheter before removal and from a peripheral vein. The Kp was intermediate to Amikacin (MIC = 16 µg/ml) and was resistant to all other antibiotics including Imipenem (MIC = 4 µg/ml), Colistin (MIC = 16 µg/ml) and Tigecycline (MIC = 4 µg/ml) according to the Clinical and Laboratory Standards Institute (CLSI) published in 2011. PCR amplification and sequencing verified the presence of blaOXA-48, blaVIM-2, blaCMY-2 and blaSHV-1 genes. Amikacin was given at a dose of 30 mg/kg (2.5 g) in a 30 min infusion and the dose of imipenem was increased to 1 g every 6 h despite patient's altered renal function (Creatinine Clearance = 25 ml/min). To avoid amikacin nephrotoxicity and to allow the use of high doses of imipenem, continuous venovenous hemodiafiltration (CVVHDF) (blood flow, 200 ml/h; dialysate, 1000 ml/h; ultrafiltrate, 2000 ml/h) was initiated 1 h after the start of the amikacin infusion and continued thereafter. The patient improved hemodynamically and norepinephrine was stopped five days after antibiotherapy adaptation.

Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study.

A prospective, observational, feasibility study was carried out on four patients with end-stage renal failure undergoing bicarbonate hemodialysis to study the feasibility of an on-line hemodiafiltration technique using a citrate dialysate with pre-dilutional infusion of citrate as a technique for regional citrate anticoagulation. All patients had contraindication to systemic heparin anticoagulation. The dialysis technique consisted of an on-line hemodiafiltration with a citrate dialysate without calcium using a Fresenius 4008S dialysis machine and Fresenius Polysulfone F60 dialyzers. The infusion solution was procured directly from the dialysate and was infused into the arterial line. To avoid the risk of hypocalcemia, calcium gluconate was infused to the venous return line. The study was carried out in two stages. During the first stage, the citrate infusion rate was 80 mL/min and the calcium infusion rate was 9 mmol/h. At the second stage, the rates were 100 mL/min and 11 mmol/h, respectively. The primary endpoint of this study was the incidence of thrombosis in the extracorporeal blood circuit and/or the dialyzer. A total of 78 sessions were conducted. All the sessions were well tolerated clinically and there were no major incidents in any of the four patients. At the first stage of the study, there were five incidences of small clots in the venous blood chamber, an incidence of extracorporeal blood circuit thrombosis of 12.5%. At the second stage of the study, no cases of extracorporeal blood circuit or dialyzer thrombosis were noted. Hemodiafiltration with on-line citrate dialysate infusion to the arterial line is safe and allows an effective regional anticoagulation of the extracorporeal blood circuit without the need for systemic anticoagulation.

Effect of Ondansetron on the Occurrence of Hypotension and on Neonatal Parameters during Spinal Anesthesia for Elective Caesarean Section: A Prospective, Randomized, Controlled, Double-Blind Study.

To prevent hypotension during spinal anesthesia for caesarean section, we assessed IV ondansetron of invasive maternal hemodynamic and fetal gazometric parameters.

Nosocomial dissemination of plasmids carrying blaTEM-24, blaDHA-1, aac(6')-Ib-cr, and qnrA6 in Providencia spp. strains isolated from a Tunisian hospital.

The aim of this study is to report the emergence of IncA/C conjugative plasmids harboring blaTEM-24, blaDHA-1, qnrA6, and aac(6')-Ib-cr genes among Providencia spp. isolates recovered in 2008 in Tunisia. The double-disk synergy test confirmed the phenotype extended-spectrum ß-lactamase (ESBL) in 2 Providencia stuartii and 5 Providencia rettgeri. These ESBLs were coresistant to cefoxitin, chloramphenicol, ofloxacin, and sulfonamides but remained susceptible to imipenem. Three ß-lactamases TEM-2, TEM-24, and DHA-1 were detected. blaTEM-24, blaDHA-1, aac(6')-Ib-cr, and qnrA6 genes were successfully transferred to Escherichia coli strain HB101, and they were found located on the conjugatifs IncA/C plasmids. Genetic relatedness showed similar and different patterns among P. stuartii and P. rettgeri strains, respectively.