Generation of a Convalescent Model of Virulent Francisella tularensis Infection for Assessment of Host Requirements for Survival of Tularemia

Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR+ cells, γδTCR+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4+ and CD8+ cells are the primary producers of IFN-γand that γδTCR+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Biliary and other gastrointestinal interventions.

Over the past several years, renewed interest in biliary endoprostheses has developed among interventional radiologists. The experimental, technical, and clinical progress that produced this enthusiasm is reviewed, with emphasis on recently published reports. The application of percutaneous enterostomy for gastric decompression or feeding has become widely practiced, and recent reports of percutaneous and endoscopic gastrostomy are compared, with emphasis on controversial points. The technique of percutaneous enterostomy has been adapted for jejunal and colonic application, and these technical modifications, as well as miscellaneous biliary and gastrointestinal interventions, comprise the remainder of the review

Obstructions of the hepatic duct confluence: internal drainage of bilateral lesions with a single catheter.

Strictures at the confluence of the right and left hepatic ducts are difficult to treat surgically, endoscopically, or percutaneously. Percutaneous decompression techniques previously described involved separate transhepatic catheterizations of the isolated right and left ducts. In the present study, modifications of existing self-retaining loop drainage catheters allowed bilateral internal biliary drainage of isolated right and left hepatic ductal systems with a single catheter in three patients. The technique can be used for primary palliation and for recurrent strictures after hepaticojejunostomy

Role of endoprostheses in the management of malignant biliary obstruction.

Therapeutic and palliative procedures for treating biliary obstruction can be surgical, percutaneous, or endoscopic. Incurable malignancies can be palliated by each of these three approaches. None of these has an advantage in terms of longevity over the others. Choosing the procedure which offers the best quality of life for the individual patient is complex. The virulence of the underlying tumor, the anatomic location within the biliary tree, and the availability of expertise in each of the alternative methods must be considered. For the group of patients whose conditions are palliated with transhepatic biliary drainage, the choice between chronic indwelling internal-external catheter versus endoprosthesis placement involves questions of utility, patient acceptance, and the geometry of the obstructed biliary tree. Each of these must be considered before deciding on the approach which offers the best compromise of the technical preferences of the physician, the psychological preferences of the patient, and the limitations imposed by the level and number of obstructions. Research by radiologists and gastroenterologists has resulted in improved endoprosthesis function. Current research aimed at improving stability and patency promises further improvements in endoprosthesis efficacy

Early removal of retained biliary stone without T-tube removal: case report.

Techniques for removal of retained common bile duct stones through mature tracts are safe and well established. When symptomatic, the stones may require removal prior to the 4-6 week period required for tract maturation. We report a case in which substituting a Teflon sheath for the standard polyethylene basket sheath allowed manipulation through the T-tube lumen and basketing of an impacted distal common bile duct stone, which had caused pancreatitis. This technique is simple and avoids the problem of loss of access to the biliary tree in the early postoperative period

Malignant jejunal strictures after Whipple procedure: stenting with large-bore tubes and use of combined transhepatic and peroral approach.

Malignant strictures of the afferent jejunal limbs are difficult to treat. Surgical revision and chronic external drainage, two commonly used palliative procedures, have significant associated morbidity. A combined transhepatic and peroral approach was used to stent malignant jejunal strictures in two patients, allowing antegrade internal drainage of biliary and pancreatic secretions. Excellent palliation was achieved, and there were no associated complications

CT of pyogenic spine infection.

A retrospective review of 19 patients with a diagnosis of pyogenic spine infection evaluated with spine CT was performed. In addition to displaying bone involvement, CT routinely depicted paraspinous and epidural involvement often not apparent on conventional radiographs or nuclear medicine studies. CT proved particularly useful in workup of patients with clinical evidence of infection associated with back pain and neurologic symptoms, evaluation of patients with fever and recurrent back pain following recent spine surgery, guiding diagnostic aspiration of suspected spinal regions for culture and sensitivity, pre-operative planning of debridement surgery

Percutaneous drainage techniques. Alternatives to surgical therapy.

Percutaneous drainage techniques are widely used to relieve biliary and urinary obstructions as well as to evacuate abdominal abscesses. These drainage techniques are less expensive, safer, and in many cases more effective than comparable surgical procedures. Proper follow-up care of catheters is essential, however, to achieve maximum effectiveness

Percutaneous extraction of gallstones in 20 patients.

Percutaneous cholecystolithotomy (PCL) was accomplished successfully without general anesthesia in 17 of 20 consecutive symptomatic patients from an outpatient gallstone center who were at risk for or had refused cholecystectomy. The other three patients underwent cholecystectomy because of a gallbladder collapse before admission, a tight stone-bearing phrygian cap, and a cannula slippage, respectively. A subhepatic approach was preferentially used after the fundus of the gallbladder was stabilized with a percutaneous anchor to prevent invagination and bile leakage. Retrograde slippage of the anchor into the tract in the first six patients was remedied by elongating the anchor from 2 to 3 cm. Calculi were removed in one session (11 patients) or two consecutive sessions (six patients). Morbidity included rehospitalization for stitch infection (n = 1) and dehydration (n = 1), cannula slippage (n = 1), broken guide wire (n = 1), vasovagal reaction (n = 1), and unextractable anchors (n = 3). Gallbladder endoscopy enabled identification of stones not visible at cholecystography. Hospitalization lasted 3-5 days; outpatient gallbladder drains were removed in 2-3 weeks in 10 patients and 4-6 weeks in seven (older) patients. No retained stones were seen at 6 months. The authors recommend PCL for patients at risk for surgery