Intensive care admission for Coronavirus OC43 respiratory tract infections.

BACKGROUND: Coronavirus OC43 infection causes severe pneumonia in patients presenting with comorbidities, but clinical signs alone do not allow for viral identification. OBJECTIVES: To analyze acute manifestations of Coronavirus OC43 infections and outcomes of patients admitted to an intensive care unit (ICU). PATIENTS AND METHODS: Retrospective and monocentric study performed during a Coronavirus OC43 outbreak. We used multiplex PCR to detect an OC43 outbreak in Reunion Island during the 2016 Southern Hemisphere's winter: seven admissions to the ICU. RESULTS: Mean age of patients was 71 [67;76] years, SAPS II was 42 [28;53], pneumonia severity index 159 [139;182] vs 73 [40.5;107] for patients in medical wards, and 43% required mechanical ventilation. Comorbidities were diabetes mellitus (87%), chronic respiratory failure (57%), and chronic renal failure (29%). One patient died from Haemophilus influenzae co-infection. CONCLUSION: As for MERS Co-V infections, underlying comorbidities impacted the clinical outcomes of OC43 infections.

Cutaneous infection and bactaeremia caused by Erwinia billingiae: a case report.

Cellulitis and erysipelas are common skin infections usually caused by Staphylococcus aureus and streptococci. Gram-negative rods are rarely implicated. We report here a case of dermohypodermitis and bactaeremia caused by Erwinia billingiae, a Gram-negative bacteria usually pathogenic and epiphytic to pome fruit tree.

Pattern and consequences of cardiologic medications management for patients with elevated troponin I upon admission into an intensive care unit not linked to type 1 acute myocardial infarction: A prospective observational cohort study.

OBJECTIVES: No recommendations are currently available to help the clinician with the pharmacological management of intensive care unit (ICU) patients with elevated cardiac troponin (cTn) not linked to type 1 AMI. The aim of this study was to evaluate the pattern of cardiologic medications for patients with elevated cTnI in ICU not link to type 1 AMI and their effects on in-hospital mortality. MATERIAL AND METHODS: A prospective observational cohort study conducted in two ICU units. Patients with increased plasma concentration of cTnI at admission not linked to type 1 AMI were consecutively included. RESULTS: One hundred and ninety of the 835 patients admitted (23%) had an increased plasma concentration of cTnI not related to type 1 AMI. Antiplatelet therapy (AT) and statin were prescribed in 56 (29.5%) and 50 (26.3%) of patients, respectively. Others cardiologic medications were prescribed in less than 5% of all cases and were considered as contraindicated in more than 50% of cases. Antiplatelet therapy was the only cardiologic treatment associated with reduction of in-hospital mortality following uni- and multivariate analysis. The death rate was 23% and 40% in these patients treated with and without AT, respectively (aOR=0.39 [95% CI: 0.15-0.97]). CONCLUSIONS: Statin and AT were frequently prescribed to patients with a cTnI elevation not linked to type 1 AMI. This study suggests that AT in patients with an increased plasma concentration of cTnI, not related to type 1 AMI in ICU, could reduce in-hospital mortality.

A study to evaluate the first dose of gentamicin needed to achieve a peak plasma concentration of 30 mg/l in patients hospitalized for severe sepsis.

Previous studies have shown that the high dose of gentamicin (8 mg/kg) rarely achieves the desired peak plasma concentration (Cmax) of ≥30 mg/l in patients with severe sepsis or septic shock. The aim of this study was to determine the first dose of gentamicin needed to achieve a Cmax ≥ 30 mg/l. We conducted a prospective observational cohort study in one intensive care unit. All consecutive patients hospitalized for severe sepsis or septic shock and treated with a first dose of gentamicin >6 mg/kg were evaluated. During the study period, 15 of the 57 patients (26.3 %) treated with gentamicin had a Cmax ≥ 30 mg/l. The median dose of gentamicin administered was 8.9 [7.8-9.9] mg/kg. Independent factors in the multivariate analysis associated with a Cmax ≥ 30 mg/l were higher body mass index (per kg/m(2) increment) (OR: 1.173, 95%CI: 1.015-1.356, P = 0.03) and higher first dose of gentamicin (per mg/kg increment) (OR: 2.343, 95%CI: 1.346-4.08, P = 0.003). The optimal first dose to achieve a Cmax ≥ 30 mg/l was 11 mg/kg, with a specificity and a sensitivity of 100 % and 53.3 % respectively. These results suggest that a first dose of gentamicin >11 mg/kg is needed to achieve a Cmax ≥ 30 mg/l in most patients.

[Disseminated histoplasmosis caused by Histoplasma capsulatum in a renal transplant patient: first case report in the Reunion Island]. / Premier cas d'histoplasmose disséminée a Histoplasma capsulatum a la Réunion, chez une transplantée rénale.

The purpose of this report is to describe the first case of indigenous disseminated histoplasmosis caused by Histoplasma capsulatum in a patient on immunosuppression 22 months after renal transplantation in the Reunion Island. Involvement was predominantly pulmonary and outcome was rapidly fatal. Diagnosis based on isolation of characteristic intramacrophagic Histoplasma capsulatum yeast cells from bronchoalveolar fluid was delayed since indigenous cases of this opportunistic infection were unprecedented. In addition to demonstrating the difficulty of achieving diagnosis in places located outside endemic areas without modern facilities, this case underlines the potentially the poor prognosis of disseminated histoplasmosis. This disease should be included in differential diagnosis in the Reunion Island where many patients undergo immunosuppresion and receive organs shipped in from outside locations.

Laparoscopic approach for idiopathic segmental infarction of the greater omentum.

Idiopathic segmental infarction of the greater omentum is an uncommon condition that should be considered in the differential diagnosis of right-side abdominal pain. The case presented concerns a 40-year old woman admitted with right flank pain. Computed tomography scan of the abdomen showed the characteristic features of greater omentum infarction. Given worsening symptoms under conservative treatment, the patient underwent a laparoscopy with resection of the necrotic portion of the greater omentum. Segmental infarction of the greater omentum is usually treated conservatively. Nevertheless, surgical intervention may be necessary in order to establish definitive diagnosis and treatment. In this respect, laparoscopic approach offers substantial advantages for the patients while permitting definitive diagnosis and treatment.

Endovascular isolated hepatic perfusion under pneumoperitoneum.

AIMS: Isolated hepatic perfusion (IHP) allows loco-regional administration of high drug doses for cancer treatment. Minimally invasive endovascular occlusion techniques can be used for IHP, but control of leakage remains a major drawback. We hypothesized that the increased intraabdominal pressure generated by a CO(2)-pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by mechanical compression of the capillary beds connecting the liver to the systemic circulation. METHODS: IHP was performed on adult pigs through laparotomy using a fenestrated double balloon-catheter placed into the retrohepatic vena cava to collect the hepatic outflow which was reinfused into the hepatic artery through an extracorporeal circulation system. Each pig underwent IHP during four consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20 mmHg pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase IV). The leakage rate from the liver to the systemic circulation was continuously monitored using a nuclear medicine technique. The systemic arterial pressure, the IHP inflow and outflow pressures and the flow rate were recorded. RESULTS: Leakage from the hepatic extracorporeal circulation to the systemic circulation occurred in all animals during Phase I. Under PP (Phases II and III), two leakage profiles were observed: (1) a major increase of the leakage rate in two animals with a high differential pressure (>50 mmHg) between the IHP inflow and the systemic pressures; (2) no change or a decrease of the leakage rate in the other three animals who had a low or negative differential pressure (<30 mmHg). Leakage was undetectable in all animals after exsufflation of the PP (Phase IV). CONCLUSIONS: IHP under PP is feasible. Leakage is not reduced during PP. A high gradient between the IHP inflow and the systemic pressure increases systemic leakage during PP. Upon release of the PP, the leakage is most likely redirected towards the volume depleted low resistance portal territory.

[Agauria salicifolia intoxication]. / Intoxication par bois de gale (Agauria salicifolia).

INTRODUCTION: Several plants of the Ericaceae family produce grayanotoxins, which can poison humans. The best-known of these intoxications involves the eating of "mad honey" contaminated by rhododendron nectar grayanotoxins. The authors report a case of poisoning due to ingestion of Agauria salicifolia, an Ericaceae species endemic in the Mascarene Islands. CASE: A 28-year-old woman mistakenly ingested a herbal tea made with leaves of this plant. Symptoms were characteristic of grayanotoxin intoxication, with vomiting, arterial hypotension and bradycardia. The patient was managed in an intensive care unit and recovered within a few hours after symptomatic treatment of the low blood pressure and the severe digestive disorders. CONCLUSION: This case underlines that ingestion of some plants can be toxic.

Encapsulation of packaging cell line results in successful retroviral-mediated transfer of a suicide gene in vivo in an experimental model of glioblastoma.

AIMS: Retroviral-mediated gene therapy has been proposed as a primary or adjuvant treatment for advanced cancer, because retroviruses selectively infect dividing cells. Efficacy of retroviral-mediated gene transfer, however, is limited in vivo. Although packaging cell lines can produce viral vectors continuously, such allo- or xenogeneic cells are normally rejected when used in vivo. Encapsulation using microporous membranes can protect the packaging cells from rejection. In this study, we used an encapsulated murine packaging cell line to test the effects of in situ delivery of a retrovirus bearing the herpes simplex virus thymidine kinase suicide gene in a rat model of orthotopic glioblastoma. MATERIALS AND METHODS: To test gene transfer in vitro, encapsulated murine psi2-VIK packaging cells were co-cultured with baby hamster kidney (BHK) cells, and the percentage of transfected BHK cells was determined. For in vivo experiments, orthotopic C6 glioblastomas were established in Wistar rats. Capsules containing psi2-VIK cells were stereotaxically implanted into these tumours and the animals were treated with ganciclovir (GCV). Tumours were harvested 14 days after initiation of GCV therapy for morphometric analysis. RESULTS: Encapsulation of psi2-VIK cells increased transfection rates of BHK target cells significantly in vitro compared to psi2-VIK conditioned medium (3 x 10(6) vs 2.3 x 10(4) cells; P<0.001). In vivo treatment with encapsulated packaging cells resulted in 3% to 5% of C6 tumour cells transduced and 45% of tumour volume replaced by necrosis after GCV (P<0.01 compared to controls). CONCLUSION: In this experimental model of glioblastoma, encapsulation of a xenogeneic packaging cell line increased half-life and transduction efficacy of retrovirus-mediated gene transfer and caused significant tumour necrosis.

Isolated liver perfusion for non-resectable liver tumours: a review.

Many treatments have been proposed for non-resectable primary or secondary hepatic cancer but the results have generally been disappointing. Isolated Hepatic Perfusion (IHP) was first attempted four decades ago but it gained acceptance only recently, after spectacular tumour responses were obtained by isolated limb perfusion with melphalan and tumour necrosis factor (TNF) for melanomas and sarcomas. Surgical isolation of the liver is a technically demanding operation that allows the safe administration of high doses of chemotherapeutics and TNF. Percutaneous techniques using balloon occlusion catheters are simpler but result in higher leakage rates from the perfusion circuit into the systemic circulation. Several phase I-II trials indicate that IHP can yield high tumour response rates, even when there is resistance to systemic chemotherapy. However, no significant advantage in overall survival has been demonstrated so far. IHP offers unique pharmacokinetic advantages for locoregional chemotherapy and biotherapy. It might also allow gene therapy with limited systemic exposure and toxicity. At present, IHP nevertheless remains an experimental treatment modality which should therefore be used in controlled trials only.

Postoperative pulmonary dysfunction after bilateral inguinal hernia repair: a prospective randomized study comparing the Stoppa procedure with laparoscopic total extraperitoneal repair (TEPP).

The infraumbilical incision required for open repair of bilateral inguinal hernia with a giant prosthesis is associated with postoperative pain and respiratory impairment. The aim of this study was to evaluate the postoperative respiratory dysfunction after bilateral hernia surgery. Thirty-nine patients were randomized into two groups: open repair according to the Stoppa technique and laparoscopic extraperitoneal repair (TEPP). Respiratory function tests were performed before and 24 hours after surgery. The two groups were well matched for age, American Society of Anesthesiologists (ASA) risk score, type of hernia, and preoperative lung function. The postoperative forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume in 1 second (FEV 1.0) were significantly altered in both groups. The PEF dropped 15% in both groups. The FVC dropped 22% after Stoppa versus 25% after laparoscopy (P = 0.7). The FEV 1.0 dropped 21% after Stoppa versus 9% after laparoscopy (P = 0.12). We conclude that laparoscopic preperitoneal and open bilateral hernia repair are followed by similar ventilatory dysfunction, although a trend toward better postoperative FEV 1.0 was noted after laparoscopy. This might play a role in selected patients with severe pulmonary limitations. Overall, the limited drop in pulmonary function following bilateral hernia repair under general anesthesia may serve to explain the low pulmonary morbidity that follows these procedures.

Reduced acute phase response after laparoscopic total extraperitoneal bilateral hernia repair compared to open repair with the Stoppa procedure.

BACKGROUND: Although laparoscopic hernia repair has been shown to be associated with less postoperative pain and an earlier recovery, there is still controversy about its role in hernia surgery. In general, laparoscopy produces less trauma to tissues than open surgery. This has been reflected by the reduced acute phase inflammatory response observed after laparoscopic surgery compared to open surgery in various settings, such as cholecystectomy or hysterectomy. The aim of this study was to evaluate the acute phase response after bilateral hernia repair by comparing the open Stoppa procedure with the laparoscopic totally extraperitoneal prosthetic repair (TEPP). METHODS: Patients were randomly allocated to either technique after written informed consent was obtained. Measurements were made of complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a) preoperatively and 4, 24, and 48 h postoperatively. VAS pain scores, consumption of analgesics, and delay before resumption of normal activities were also recorded. All the procedures were performed under general anesthesia by or in the presence of the same surgeon. RESULTS: Thirty-nine patients were included: 19 underwent the Stoppa procedure and 20 had a laparoscopic repair. The two groups were well matched for age, sex, ASA score, and preoperative values. The operation took longer (p <0.001) in the group undergoing TEPP. Patients resumed their normal activities earlier (p <0.05) after laparoscopy. In the open group, there was a larger decrease of the lymphocyte count after 4 (p <0.01) and 24 h (p = 0.04); an increased elevation of ESR after 48 h (p = 0.02); a larger increase of IL-6 after 4 (p = 0.05), 24 (p = 0.003), and 48 h (p <0.001); and a larger increase in CRP after 24 (p = 0.05) and 48 h (p = 0.01). There was no morbidity. There was no difference in postoperative IL-1b, TNF-a, total white blood cell count, polymorphonuclear count, VAS for pain, or need for analgesics between the two groups, except on the operative day. CONCLUSIONS: The acute phase inflammatory response in clearly more active after the open Stoppa procedure than after TEPP, indicating that the former is associated with increased tissue trauma. This may play a role in the earlier recovery seen after the TEPP procedure.

T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.

We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated T cells, is known to amplify T cell-mediated immunity. In this study, we compared the effect of a systemically delivered agonistic anti-4-1BB monoclonal antibody (anti-4-1BB mAb) with intra-tumoral adenoviral-mediated gene transfer of the 4-1BB ligand (ADV/4-1BBL) to liver metastases in a syngeneic animal model of breast cancer. Both treatments induced a dramatic regression of pre-established tumor. When combined with intra-tumoral delivery of the IL-12 gene, both anti-4-1BB mAb and ADV/4-1BBL were synergistic and led to survival rates of 87% and 78%, respectively. The anti-tumor immunity is mainly mediated by CD4+ T cells in IL-12 plus 4-1BB ligand-treated animals, and CD8+ T cells in IL-12 plus anti-4-1BB mAb-treated animals. However, only long-term survivors after treatment with IL-12 and 4-1BBL genes have showed significantly potent, systemic, and tumor-specific T cell-mediated immunity.

[Gene therapy and cancer]. / Thérapie génique et cancer.

Gene therapy by definition aims at modifying the genetic program of a cell towards a therapeutic or prophylactic goal. Several gene therapy strategies for cancer are currently under evaluation: 1) "suicide" gene therapy where an inactive prodrug is converted into a cytotoxic drug; 2) modification of the function of oncogenes and tumor suppressor genes; 3) modification of the host immune response towards the tumor; 4) disruption of the tumor neovascularisation; 5) lysis of tumor cells with replication-competent viruses. Recent results of phase I and II clinical studies have brought great hopes. However, the inefficiency of current gene vectors in infecting targeted cells and their inability to selectively access diseased cells distributed systemically are two major limitations that have to be overcome for further successful clinical applications.