Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).

About a rare association: Guillain-Barré Syndrome and polymyositis.

Guillain-Barré syndrome (GBS) and polymyositis (PM) are two rare autoimmune diseases, one of which affects the peripheral nervous system and other the muscle. We report the case of a young woman with no previous medical history who was hospitalized with an ascending paralysis associated with acute respiratory failure due to a GBS. The patient was treated with plasmapheresis with unfavorable outcome and permanent proximal muscular disability. The diagnosis of an associated PM was retained based on biological myolysis and the results of electromyography and muscular biopsy. To our knowledge, this association of GBS and PM has been reported only once in the literature. The search for syndromic associations in the presence of an autoimmune helps to avoid diagnostic errors.

Prognostic Value of Serum Cholinesterase Activity in Severe SARS-CoV-2-Infected Patients Requiring Intensive Care Unit Admission.

We evaluated the prognostic value of serum cholinesterase (SChE) levels in SARS-CoV-2-infected patients requiring intensive care unit (ICU) admission. This is a retrospective study of severe, critically ill, adult COVID-19 patients, all of whom had a confirmed SARS-CoV-2 infection and were admitted into the ICU of a university hospital. We included all patients admitted to our ICU and whose SChE levels were explored on ICU admission and during ICU stay. One hundred and thirty-seven patients were included. There were 100 male and 37 female patients. The mean of SChE activity on ICU admission was 5,656 ± 1,818 UI/L (range: 1926-11,192 IU/L). The SChE activity on ICU admission was significantly lower in nonsurvivors (P < 0.001). A significant association between the SChE activity on ICU admission and the need for invasive mechanical ventilation was found. We also found a significant correlation between the SChE activity and other biomarkers of sepsis (C-reactive protein, procalcitonin, and leukocytes) on ICU admission and during the ICU stay. A significant correlation among SChE nadir value activity recorded during ICU stay, the occurrence of nosocomial infection, and the outcome of studied patients was found. Our study shows that the low SChE activity value is associated with a severe outcome. It might be used as a biomarker to aid in prognostic risk stratification in SARS-CoV-2-infected patients. Further studies for external validation of our findings are needed on this subject.

Clinical characteristics and outcomes of critically ill COVID-19 patients in Sfax, Tunisia.

BACKGROUND: Africa, like the rest of the world, has been impacted by the coronavirus disease 2019 (COVID-19) pandemic. However, only a few studies covering this subject in Africa have been published. METHODS: We conducted a retrospective study of critically ill adult COVID-19 patients-all of whom had a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection- admitted to the intensive care unit (ICU) of Habib Bourguiba University Hospital (Sfax, Tunisia). RESULTS: A total of 96 patients were admitted into our ICU for respiratory distress due to COVID-19 infection. Mean age was 62.4±12.8 years and median age was 64 years. Mean arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) ratio was 105±60 and ≤300 in all cases but one. Oxygen support was required for all patients (100%) and invasive mechanical ventilation for 38 (40%). Prone positioning was applied in 67 patients (70%). Within the study period, 47 of the 96 patients died (49%). Multivariate analysis showed that the factors associated with poor outcome were the development of acute renal failure (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.75-25.9), the use of mechanical ventilation (OR, 5.8; 95% CI, 1.54-22.0), and serum cholinesterase (SChE) activity lower than 5,000 UI/L (OR, 5.0; 95% CI, 1.34-19). CONCLUSIONS: In this retrospective cohort study of critically ill patients admitted to the ICU in Sfax, Tunisia, for acute respiratory failure following COVID-19 infection, the mortality rate was high. The development of acute renal failure, the use of mechanical ventilation, and SChE activity lower than 5,000 UI/L were associated with a poor outcome.

Impact of prone position on outcomes of COVID-19 patients with spontaneous breathing.

BACKGROUND: In this study, we explored whether early application of the prone position (PP) can improve severe hypoxemia and respiratory failure in coronavirus disease 2019 (COVID-19) patients with spontaneous breathing. METHODS: This is a prospective observational study of severe, critically ill adult COVID-19 patients admitted to the intensive care unit. All vital parameters were recorded in real time for all patients. Moreover, the results of chest computed tomography (CT), when available, were analyzed. RESULTS: PP was applied in 21 patients who were breathing spontaneously. The application of PP was associated with a significant increase in oxygen saturation measured by pulse oximetry (SpO2) from 82%±12% to 96%±3% (P<0.001) 1 hour later. Moreover, PP was associated with a significant reduction in respiratory rate from 31±10 to 21±4 breaths/min (P<0.001). Furthermore, the number of patients who exhibited signs of respiratory distress after PP was reduced from 10 (47%) to 3 (14%) (P=0.04). Early PP application also led to a clear improvement on CT imaging. It was not, however, associated with a reduction in mortality rate or in the use of invasive mechanical ventilation (P>0.05 for both). CONCLUSIONS: Our study confirmed that the early application of PP can improve hypoxemia and tachypnea in COVID-19 patients with spontaneous breathing. Randomized controlled trials are needed to confirm the beneficial effects of PP in COVID-19 patients with spontaneous breathing.

Letrozole and zoledronic acid changed signalling pathways involved in the apoptosis of breast cancer cells.

OBJECTIVES: Oestrogen plays a key role in the development of breast malignancies. Therefore, aromatase inhibitors (e.g. letrozole [LTZ]) are widely used in the treatment of breast cancer. On the other hand, oestrogen is important to the integrity of bone mass. Research has shown that zoledronic acid (ZLA) may prevent osteoporosis. Therefore, the present research aims to investigate the effect of a combination of LTZ and ZLA in the treatment of breast cancer and in reducing osteoporosis in patients with breast cancer. METHODS: We used immunocytochemistry and Western immunoblotting techniques in this study. RESULTS: We observed that LTZ inhibited cellular growth of Michigan Cancer Foundation-7 (MCF-7) and T-47D at IC50 (70 ± 0.001) and (140 ± 0.004) nM, respectively, whereas ZLA inhibited cellular growth at IC50 (50 ± 0.005) µM and (150 ± 0.004) µM for MCF-7 and T-47D cell lines, respectively. Interestingly, the LTZ and ZLA combination down-regulated the protein expression of signal transducer and activator of transcription 3 (STAT3) and up-regulated BRCA1 protein expression in both cell lines. Moreover, a notable enhancement in the nuclear localisation of the BRCA1 protein was obtained after treatment of T-47D cells with LTZ for 24 h compared to the control cells. In contrast, there was a reduction in the nuclear localisation of STAT3 protein, which could be an attractive target for inhibition of breast cancer proliferation and progression. CONCLUSION: Our study has shown that a combination of LTZ and ZLA enhanced apoptosis and inhibited growth of both breast cancer cell lines. This combination can be used to maintain bone integrity in women with breast cancer.

Macrophage activation syndrome in a patient affected by Plasmodium falciparum Aeroport malaria.

Malaria is a worldwide problem. Infection with Plasmodium. falciparum that may cause a multi-organ-failure, especially if the diagnose wasn't at time. Macrophage activation syndrome is a clinical and biological syndrome caused by an excessive proliferation of T lymphocytes. Plasmodium falciparum infection was rarely reported as a cause of this syndrome reported in the literature. We report a case of severe airport malaria in a 62-year-old man complicated by Macrophage activation syndrome. The patient was treated with intravenous quinine for 7days, catecholamine, volume expansion, mechanical ventilation, sedation and dialysis. But the evolution was marked by a multi-organ failure leading to the death of the patient. The occurrence of airport malaria stresses the need for sensitization of clinicians for considering malaria in febrile individuals even when they have not traveled to an endemic area. Clinicians should be aware of Macrophage activation syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.

Rapid detection and clinical spectrum of the novel influenza H1N1 strain in a diabetic pediatric population.

OBJECTIVES: H1N1 infection in diabetic patients is of special concern and serious interest since the virus can place individuals, especially children, at great possible risk of subsequently developing type 1 diabetes. This work aims to describe the demographic characteristics, clinical features, and severity of illness of children with type 1 diabetes mellitus (DM), compare the incidence of pandemic H1N1 virus in children with that of the general pediatric population with influenza-like symptoms, and identify the complications of H1N1 virus infection associated with glycemic control. METHODS: The present study included 45 children and adolescents with type 1 diabetes, who were subject to clinical and laboratory investigations. Another 30 healthy adolescents and children with a mean age of 10.43 ± 4.38 years were included as a control group. H1N1 reverse-transcriptase quantitative PCR (RT-Q PCR) was tested for H1N1 virus detection. RESULTS: Diabetic patients positive for (H1N1) showed significantly higher random blood sugar (RBS) levels than diabetic patients negative for (H1N1). Moreover, the H1N1-positive patients had significantly higher hemoglobin (Hb) g/dL, platelet counts, total leukocyte counts (TLCs), and CRP levels. Newly diagnosed patients who were tested positive for (H1N1) and diabetic ketoacidosis (DKA) had significantly higher RBS levels and TLCs than patients who were presented with hyperglycemia. CONCLUSION: RT-PCR is a rapid and specific method for influenza A (H1N1) virus diagnosis. In addition, early administration of oseltamivir no later than 48 hours after the infection is highly recommended in either diabetic or DKA patients suspected of having H1N1.

Clinical characteristics and prognosis of traumatic head injury following road traffic accidents admitted in ICU "analysis of 694 cases".

BACKGROUND: The aim of the present study is to analyze the clinical and epidemiological characteristics of Traumatic Brain Injury (TBI) following Road Traffic Accidents (RTAs). Moreover, we aim to evaluate the outcome of the TBI victims referred to our medico-surgical Intensive Care Unit (ICU), and to define predictive factors associated with poor prognosis. METHODS: A retrospective study over a 4-year period (2009 to 2012) of 694 patients with head injuries, incurred during road traffic accidents, admitted to the Intensive Care Unit (ICU) of a university hospital (Sfax-Tunisia). Basic demographic, clinical, biological, and radiological data were recorded on admission and during the ICU stay. RESULTS: There were 592 males (85.3%), and 102 female patients. The mean age was at 31.8 ± 17.8 years (range 1-91). The mechanism of the accident was detailed in 666 patients (96%). The majority of the victims were motorcycle riders and/or passengers (40.5%), followed by pedestrians (29.1%). Extra-cranial pathology was present in 452 patients (65%). A total of 677 patients (97.6%) required intubation, mechanical ventilation, and sedation. Mean ICU stay was 16 ± 17.4 days. A total of 187 patients (26.9%) died during their hospital stay. The GOS performed within a mean delay of 6 months after hospital discharge was as follows: 198 deaths (28.5%), 13 vegetative state (1.9%), and 349 (50.3%) good recovery and/or moderate disability. A multivariate analysis showed that the factors which correlated with a poor prognosis (mortality and severe disability) were: age > 38 years, Glasgow coma scale score < 8, subdural hematoma, and development of secondary systemic insults (respiratory, circulatory, and metabolic). CONCLUSION: In Tunisia, traumatic brain injury due to RTAs is a frequent cause of ICU admission, especially among young adults, and is associated with high mortality and morbidity rates. The majority of the victims were motorcycle riders and/or passengers and pedestrians. The factors associated with a poor outcome were: age > 38 years, Glasgow Coma Scale score < 8, subdural hematoma, and development of secondary systemic insults (respiratory, circulatory, and metabolic). As a consequence, prevention is highly warranted.

Acute renal failure and pregnancy: a seventeen-year experience of a Tunisian intensive care unit.

PURPOSE: To describe the epidemiologic features of acute renal failure related to pregnancy (PRARF) and to evaluate its prognostic impact. METHODS: Retrospective study conducted in a Tunisian intensive care unit over a period of 17 years (1995-2011). Women were included if they were more than 20 weeks pregnant and were admitted to the ICU during pregnancy or immediately (<7 d) post partum. PRARF was defined by a serum creatinine level >0.8 mg/dL and was classified as mild (0.9 to 1.4 mg/dL), moderate (1.5 to 2.9 mg/dL) or severe (>3 mg/dL). RESULTS: Five hundred and fifty patients were included. Mean age was 31 ± 6 years. Mean SOFA score was 4 ± 3. PRARF was diagnosed in 313 patients (56.9%). ARF was mild in 215 cases (39.1%), moderate in 65 cases (11.8%) and severe in 33 cases (6%). Main causes leading to this complication were preeclampsia (66.5%) and acute hemorrhage (27.8%). Only two patients (0.4%) developed chronic renal failure and needed long-term dialysis. Patients who developed this complication had higher SOFA score (4.7 ± 3.5 vs. 3.2 ± 2.1; p < 0.001). Thirty-three patients (6%) died in the ICU. The rate of ICU mortality was significantly higher in patients with PRARF (9.3 vs. 1.7%; p < 0.001). CONCLUSIONS: PRARF is associated with higher mortality. Thus, appropriate monitoring of pregnancies is needed in order to prevent its onset by an early and prompt management of the underlying risk factors.

Severe scorpion envenomation among children: does hydrocortisone improve outcome? A case-control study.

BACKGROUND: To analyse the efficacy and safety of systemic infusion of hydrocortisone hemisuccinate in children admitted to the intensive care unit with severe scorpion envenomation, we assessed the impact on mortality and length of hospital stay. METHOD: We conducted a pair-wise, case-control study with 1:1 matching, reviewing records over a 13-year period (1990-2002) for the intensive care unit (ICU) of the Habib Bourguiba University Hospital, Sfax, Tunisia. A total of 184 children were included in the study (92 cases and 92 controls); cases received hydrocortisone hemisuccinate during hospitalization and controls received no steroids. Patients were matched according to age (±2 years), severity factors at admission (pulmonary edema and grades of severity of scorpion envenomation) and scorpion antivenom administration. RESULTS: Cases and controls did not differ significantly in age (4.9 ± 5.5 years vs 6.2 ± 3.8 years; p > 0.05), mean temperature on admission (37.2 ± 1.2 vs 37.2 ± 1.06; p = 0.99) or presence of systemic inflammatory response syndrome (SIRS) (77 vs 70; p = 0.198). The proportion of patients with pulmonary edema was similar in the two groups (77 vs 71; p > 0.05), and in each group 46 patients (50%) received scorpion antivenom (p > 0.05). The use of mechanical ventilation, ICU length of stay and ICU mortality was not significantly different between the studied groups. CONCLUSION: We detected no significant difference between patients receiving steroids and steroid-free patients in terms of mortality and ICU length of stay. The hydrocortisone hemisuccinate regimen described here had a limited effect in critically ill envenomated children and, therefore, we suggest that it should not be recommended.

Efficacy of corticosteroid therapy in severe decompensation of chronic obstructive pulmonary disease requiring mechanical ventilation.

The purpose of this study was to analyze the efficacy of corticosteroids in severe acute decompensation of chronic obstructive pulmonary disease requiring mechanical ventilation and intensive care unit (ICU) admission. Pairwise retrospective case-control study with 1:1 matching. Patients were defined as cases when they received corticosteroids and as controls when they did not received any steroids. Patients were matched according to age, severity factors at admission represented by the PaO2/FiO2 ratio, and simplified acute physiology score. Thirty-four patients were included. There were 17 patients in the case group and 17 patients in the control group. There were 27 men (80%) and 7 women (20%). The mean age (±SD) was 70 ± 9 years with a range of 40-85 years. Thirty-two patients (94 %) were older than 60 years. The comparison between the 2 groups showed that they had the same epidemiological, clinical, and biological findings on ICU admission. Homodynamic parameters were also not significantly different between the 2 groups. Moreover, there is the same proportion of invasive mechanical ventilation use in 2 groups. Concomitant drugs used were also not significantly different between the 2 groups. Finally, the comparison of outcome between the steroid and steroid-free groups showed that mortality rate was not significantly different (64% vs. 58%, P = 0.72). However, systemic corticosteroid therapy was associated with a significant increase in a reduction in the duration of mechanical ventilation (P = 0.004) and a trend toward a shorter length of ICU stay (P = 0.053). Although the authors detected no significant difference in mortality rate at the time of discharge between steroid and streroid-free patients, this study confirms that systemic corticosteroid therapy in patients with chronic obstructive pulmonary disease exacerbations requiring mechanical ventilation is associated with a significant reduction in the duration of mechanical ventilation. Other studies are needed on this subject.