Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic.

Adenoviruses encode proteins that block responses to interferons, intrinsic cellular apoptosis, killing by CD8(+) cytotoxic T lymphocytes and killing by the death ligands TNF, Fas ligand and TRAIL. The viral proteins are believed to prolong acute and persistent adenovirus infections. The proteins may prove useful in protecting adenovirus gene therapy vectors and transplanted cells from the immune system.

The time is now - a call to action for gender equality in global health leadership.

Gender equality is considered paramount to the success of the Sustainable Development Goals and incorporated into global health programming and delivery, but there is great gender disparity within global health leadership and an absence of women at the highest levels of decision making. This perspective piece outlines the current gaps and challenges, highlighting the lack of data and unanswered questions regarding possible solutions, as well as the activity of Women in Global Health and efforts to directly address the inequity and lack of female leaders. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equality and catalyzing change.

The role of women's leadership and gender equity in leadership and health system strengthening.

Gender equity is imperative to the attainment of healthy lives and wellbeing of all, and promoting gender equity in leadership in the health sector is an important part of this endeavour. This empirical research examines gender and leadership in the health sector, pooling learning from three complementary data sources: literature review, quantitative analysis of gender and leadership positions in global health organisations and qualitative life histories with health workers in Cambodia, Kenya and Zimbabwe. The findings highlight gender biases in leadership in global health, with women underrepresented. Gender roles, relations, norms and expectations shape progression and leadership at multiple levels. Increasing women's leadership within global health is an opportunity to further health system resilience and system responsiveness. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equity.

A bedside ultrasound sign ruling out pneumothorax in the critically ill. Lung sliding.

STUDY OBJECTIVES: To describe and evaluate an ultrasound pattern useful in the diagnosis of pneumothorax. DESIGN: Ultrasound examination of "lung sliding," a respiratory movement visible when investigating the chest wall. SETTING: The medical ICU of a university-affiliated hospital. PATIENTS: The study group included 43 proved pneumothoraces, either by chest radiograph (n = 40) or by CT (n = 3). The control group included 68 hemithoraces in which the absence of pneumothorax was proved by CT. INTERVENTION: Analysis of anterior chest wall in supine patients. MEASUREMENTS AND RESULTS: Feasibility was 98.1%. Disappearance of "lung sliding" was observed in 100% of 41 analyzable cases of pneumothorax vs 8.8% of the hemithorax without pneumothorax (6 of 68). In this series, sensitivity was 95.3%, specificity 91.1%, and negative predictive value 100% (p < 0.001). CONCLUSIONS: Ultrasound was a sensitive test for detection of pneumothorax, although false-positive cases were noted. The principal value of this test was that it could immediately exclude anterior pneumothorax.

A lung ultrasound sign allowing bedside distinction between pulmonary edema and COPD: the comet-tail artifact.

OBJECTIVE: Acute cardiogenic pulmonary edema and exacerbation of chronic obstructive pulmonary disease (COPD) can have a similar clinical presentation, and X-ray examination does not always solve the problem of differential diagnosis. The potential of lung ultrasound to distinguish these two disorders was assessed. DESIGN: Prospective clinical study. SETTING: The medical ICU of a university-affiliated teaching hospital. PATIENTS: We investigated 66 consecutive dyspneic patients: 40 with pulmonary edema and 26 with COPD. In addition, 80 patients without clinical and radiologic respiratory disorders were studied. MEASUREMENTS: The sign studied was the comet-tail artifact arising from the lung wall interface, multiple and bilaterally disseminated to the anterolateral chest wall. RESULTS: The feasibility was 100%. The length of the examination was always under 1 min. The described pattern was present in all 40 patients with pulmonary edema. It was absent in 24 of 26 cases of COPD as well as in 79 of 80 patients without respiratory disorders. The sign studied had a sensitivity of 100% and a specificity of 92% in the diagnosis of pulmonary edema when compared with COPD. CONCLUSIONS: With a described pattern present in 100% of the cases of pulmonary edema and absent in 92% of the cases of COPD and in 98.75% of the normal lungs, ultrasound detection of the comet-tail artifact arising from the lung-wall interface may help distinguish pulmonary edema from COPD.

Intensive use of general ultrasound in the intensive care unit. Prospective study of 150 consecutive patients.

OBJECTIVE: To assess the impact of systematic ultrasound (US) examination in patients admitted to the ICU. DESIGN: An observational study of 150 consecutive patients. SETTING: A medical ICU of a University-affiliated hospital. PATIENTS: All consecutively admitted patients were examined, but patients discharged within < 48 h were excluded from the analysis. INTERVENTIONS: A systematic examination of the abdomen, pleural space, cervical and femoral vein, was performed at the bedside by the same investigator. MEASUREMENTS: Results of US examinations were compared to findings from CT-scan, surgery, endoscopic procedures, autopsy, or other diagnostic tests. The impact of U.S. findings on immediate patients management was evaluated. RESULTS: In 33 of 150 patients (22%), U.S. findings influenced the diagnosis, work up of the patients, and had a direct impact on the therapeutic plan. In 30/33 cases, confirmation of diagnosis was obtained by another diagnostic and/or therapeutic procedure. CONCLUSIONS: Routine US examination may alter therapeutic plans in up to 1/4 of critically ill patients admitted to the ICU. US examination should be liberally performed on such patients.

The "lung point": an ultrasound sign specific to pneumothorax.

OBJECTIVE: We studied an ultrasound sign, the fleeting appearance of a lung pattern (lung sliding or pathologic comet-tail artifacts) replacing a pneumothorax pattern (absent lung sliding plus exclusive horizontal lines) in a particular location of the chest wall. This sign was called the "lung point". DESIGN: Prospective study. SETTING: The medical ICU of a university-affiliated teaching hospital. PATIENTS: The "lung point" was sought in 66 consecutive cases of proven pneumothorax analyzable using ultrasound--including 8 radio-occult cases diagnosed by means of CT and in 233 consecutive hemithoraces studied by CT and free of pneumothorax-- including 17 cases where pneumothorax was suspected. RESULTS: The "lung point" was observed in 44 of 66 cases of pneumothorax (including 6 of 8 radio-occult cases) and in no case in the control group. The location of this sign roughly correlated with the radiological size of the pneumothorax. The "lung point" therefore had an overall sensitivity of 66 % (75 % in the case of radio-occult pneumothorax alone) and a specificity of 100%. CONCLUSION: The presence of a "lung point" allows positive diagnosis of pneumothorax at the bedside using ultrasound.

The "sinusogram", a real-time ultrasound sign of maxillary sinusitis.

OBJECTIVE: To describe a real-time ultrasound sign, the visualization of the cavity and the walls of the maxillary sinus ("sinusogram"), and to assess its correlation with total opacity of the sinus. DESIGN: Prospective clinical study. SETTING: The medical ICU of a university-affiliated hospital. PATIENTS: The significance of this sign was assessed in 50 critically ill supine patients (100 maxillary sinuses) who underwent paranasal CT. MEASUREMENTS AND RESULTS: The "sinusogram" was defined as complete when the internal, external and posterior walls were frankly visible, and incomplete in the case of partial visualization of the walls. The "sinusogram" was present in all 21 cases of total opacity, in 2 of 12 cases of air-fluid level, in 8 of 14 cases of mucosal thickening, in one giant polyp, and in none of 52 normal sinuses. The "sinusogram" was complete in 10 of 21 cases of total opacity. It was incomplete in 11 of 21 cases of total opacity and in all 8 cases of mucosal thickening with positive ultrasound. For the diagnosis of radiologic maxillary sinusitis (total opacity or air-fluid level within the maxillary cavity), the sensitivity was 67 % and the specificity 87 %. For the diagnosis of total opacity (versus absence of total opacity, which includes fluid level), the sensitivity was 100% and the specificity 86%. When the "sinusogram" was complete, the specificity was 100% for the diagnosis of total opacity. CONCLUSIONS: Ultrasound may be proposed in first-line diagnosis of radiologic maxillary sinusitis.

The comet-tail artifact: an ultrasound sign ruling out pneumothorax.

OBJECTIVE: Ultrasound artifacts arising from the lung-wall interface are either vertical (comet-tail artifacts) or horizontal. The significance of these artifacts for the diagnosis of pneumothorax was assessed. DESIGN: Prospective clinical study. SETTING: The medical ICU of a university-affiliated teaching hospital. PATIENTS: We compared 41 complete pneumothoraces with 146 hemithoraces in 73 critically ill patients in which computed tomography showed absence of pneumothorax. MEASUREMENTS: The anterior chest wall was investigated in supine patients using a portable device. The test was defined as positive for complete pneumothorax when only horizontal artifacts were visible, and negative when artifacts arising from the pleural line and spreading up to the edge of the screen (referred to as "comet-tail artifacts") were present. RESULTS: The feasibility was 98%. Ultrasound showed exclusive horizontal artifacts in all 41 analyzable cases of complete pneumothorax. In the pneumothorax-free group, "comet-tail artifacts" were present in 87 cases and exclusive horizontal artifacts in 56. Ultrasound as well as computed tomography showed anterior consolidation or anterior pleural effusion in three cases. Horizontal artifacts had a sensitivity and a negative predictive value of 100% and a specificity of 60% for the diagnosis of pneumothorax. Horizontal artifacts and absent lung sliding, when combined, had a sensitivity and a negative predictive value of 100% and a specificity of 96.5%. CONCLUSIONS: Ultrasound detection of the "comet-tail artifact" at the anterior chest wall allows complete pneumothorax to be discounted.

Feasibility and safety of ultrasound-aided thoracentesis in mechanically ventilated patients.

OBJECTIVE: Thoracentesis in a ventilated patient is rarely performed because of the risk of pneumothorax. We have evaluated the safety of this procedure when aided by ultrasound. DESIGN: Prospective study. SETTING: Medical intensive care unit, university-affiliated hospital. PATIENTS: 45 procedures were performed in 40 consecutive patients with ultrasound signs of pleural effusion, all mechanically ventilated. INTERVENTIONS: Pleural effusion was defined on ultrasound as a collection of fluid between parietal and visceral pleura leading to variations in interpleural distance during breathing. When the interpleural distance was >/= 15 mm and visible over three intercostal spaces, a needle (16 or 21 G) was inserted after ultrasound localization in a patient in either dorsal or lateral decubitus. RESULTS: No complication occurred in the 45 thoracenteses. Fluid was obtained in 44 of 45 procedures, thus confirming the diagnosis of pleural effusion. The procedure was immediate (less than 10 s) in 40 of 45 cases. It was easy (i. e., keeping the patient supine) in 22 of 45 procedures. In 44 cases where fluid was obtained, only 27 bedside radiographs revealed signs of effusion, whereas 17 showed absence of a visible effusion. Ultrasound thus appeared more efficient than bedside X-ray in detecting pleural effusion. CONCLUSIONS: If basic rules are followed, ultrasound localization makes thoracentesis a safe, easy and simple procedure in patients on mechanical ventilation.

The Internal jugular veins are asymmetric. Usefulness of ultrasound before catheterization.

OBJECTIVE: To demonstrate an asymmetry of the internal jugular veins, a finding which will have consequences for catheterization. DESIGN: Prospective study. SETTING: The medical ICU of a university-affiliated teaching hospital. PATIENTS: Eighty critically ill consecutive patients. INTERVENTION: Measurement of the cross-sectional area of the internal jugular veins. Search for an asymmetry, defined as an area at least twice that of the contralateral vein. RESULTS: An asymmetry was noted in 62.5% of the patients. The dominant vein was the right in only 68 % of these cases. In addition, 23% of the 160 jugular internal veins had an area of 0.4 cm2 or less. CONCLUSIONS: Using a simple technique, ultrasound identifies the dominant internal jugular vein, thus indicating the safer side before blind catheterization.

Urinary trypsinogen activation peptides (TAP) are not increased in mild ERCP-induced pancreatitis.

Acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) occurs in 3-18% of patients undergoing either diagnostic or therapeutic ERCP. We prospectively measured urinary trypsinogen activation peptides (TAP) by an automated anti-TAP enzyme-linked immunoassay among 107 patients 4 h after ERCP to determine whether this measurement helps in the early diagnosis of ERCP-induced pancreatitis. Pancreatitis was documented in 10 of 107 patients (9.3%). All episodes were graded as mild. Urinary TAP was not significantly increased. We conclude that measurement of urinary TAP 4 h after ERCP is not helpful in documenting mild ERCP-induced acute pancreatitis.

Chronic radiodermatitis following cardiac catheterization.

BACKGROUND: Fluoroscopy and cineradiography used during coronary angiography expose patients to some of the highest doses of ionizing radiation in diagnostic radiology. The possibility of radiation-induced damage has been discussed by several authors in the past. However, to the best of our knowledge, chronic radiation dermatitis caused by exposure to x-rays during cardiac catheterization has not been described. OBSERVATIONS: We describe 4 patients in whom chronic radiodermatitis developed following multiple cardiac catheterizations and coronary angioplasties. The cumulative radiation doses to which these patients were exposed were retrospectively calculated to be a mean of 24.6 Gy per patient, with a range of 11.4 to 34.9 Gy. CONCLUSIONS: Chronic radiodermatitis is a threat in patients undergoing multiple cardiac catheterizations and angioplasties. In susceptible patients, radiation doses as small as 11.4 Gy, which can sometimes be emitted during 1 or 2 procedures, are potentially harmful. Awareness and protective measures against this long-term side effect of cardiac catheterization should be encouraged.

Mucin-secreting tumors of the pancreas.

Mucinous pancreatic neoplasms present diagnostic and therapeutic challenges. These tumors behave in an indolent nature, with frequent overlap of symptoms and radiographic appearance with other forms of pancreatic cysts, pseudocysts, and malignancy. Some authors propose that all mucin-producing tumors of the pancreas are variants of the same basic entity and have subclassified them on the basis of their predominant location within the pancreas. These disorders must be considered in the evaluation of chronic abdominal pain, particularly in the presence of a cystic pancreatic lesion or when associated with idiopathic chronic or acute recurrent pancreatitis. The clinicopathologic features of IMHN overlap to a great extent with classic mucinous cystic neoplasms but are different significantly enough to be distinct clinical entities. These tumors originate from the pancreatic duct epithelium, produce mucin, demonstrate a papillary growth pattern, and are considered premalignant or frankly malignant at the time of diagnosis. Both lesions biologically are much less aggressive than that of pancreatic ductal adenocarcinoma and appear to infiltrate peripancreatic tissue and to metastasize to lymph nodes or other adjacent structures late in the course of disease. Nevertheless, IMHNs are located primarily in the head of the pancreas, commonly affect elderly men, and present clinically with obstructive pancreatitis, often leading to pancreatic insufficiency, whereas mucinous cystic neoplasms are more likely to develop in the pancreatic body or tail, predominate in young women, and present with symptoms referable to tumor compression of adjacent structures. The location of the lesion is the primary differentiating feature because the lining epithelium of the two tumor types is indistinguishable pathologically. In mucinous cystic tumors, the mucus is secreted and retained within the cyst lumen because of the absence of communication between the cyst and the main pancreatic duct. In contrast, mucus produced in MDE flows into the main pancreatic duct, resulting in obstructive pancreatitis and, ultimately, dilatation of the pancreatic duct. Intraductal mucus provides an important clue to the diagnosis of intraductal pancreatic neoplasms and, whenever present, should prompt an aggressive diagnostic evaluation. Both lesions are managed by resectional surgery because the opportunity for cure is high in the absence of metastatic disease.

Endoscopic palliation for unresectable pancreatic carcinoma.

Endoscopic stenting has revolutionized the palliation of malignant biliary obstruction. Individuals with biliary obstruction due to pancreatic malignancy are best managed by a team approach comprising individuals with expertise in oncology, surgery, endoscopy, and radiology. The clinical value of alleviating jaundice and associated symptoms of anorexia, pruritus, and malaise cannot be overestimated. These quality-of-life factors deserve more attention in future studies to define subgroups of patients most likely to derive benefit from the array of treatment options. Further technical improvements are required to solve the most important clinical problem of late stent occlusion. New developments such as expandable metallic stents and refinements in existing equipment and techniques have already resulted in measurable gains and hold great promise for future expansion of their use in malignant gastric outlet obstruction secondary to tumor infiltration of the duodenum. Corresponding advances are being made in the fields of percutaneous transhepatic intervention and hepatobiliary surgery such that further prospective randomized trials are necessary to define optimal therapy.

Knuckle pads--a forgotten skin condition: report of a case and review of the literature.

A 12-year-old boy presented with knuckle pads, palmar keratoderma, and hand eczema. Since Morginson's description of knuckle pads associated with other dermatoses almost forty years ago, little attention has been given to this disorder. We describe a case and review some of the clinical aspects of this disorder.

Infection of bone marrow macrophages by equine infectious anemia virus.

OBJECTIVE: To characterize infection of bone marrow-derived macrophages (BMDM) with equine infectious anemia virus (EIAV) by determining virus production, effects on viability, and induction of cytokines. SAMPLE POPULATION: BMDM obtained from bone marrow of 6 clinically normal adult horses. PROCEDURE: BMDM were infected with EIAV at a multiplicity of infection of 8. Cell viability, percentage of cells with detectable viral protein, reverse transcriptase activity, and concentrations of infective virus (focus-forming units/ml), interleukin 6, and tumor necrosis factor-alpha were measured in culture supernatant samples obtained at various days after infection. RESULTS: Cell viability was decreased on day 4 and was maximally decreased on day 8. The number of cells with detectable viral protein and supernatant reverse transcriptase activity increased significantly on day 4 and increased until day 6. Virus concentration (focus-forming units per milliliter) peaked on day 4 after infection and was constant thereafter. Infection with EIAV caused significant induction of interleukin 6 production by BMDM. The maximal difference was seen on day 4 after infection. Control and infected BMDM produced only negligible amounts of tumor necrosis factor-alpha. CONCLUSIONS: BMDM are useful, as a cell population, to study the effects of infection with EIAV, including cell death and induction of interleukin 6 but not tumor necrosis factor-alpha production.

[Esophageal squamous cell papilloma. Report of 3 cases. Diagnostic aspects]. / Papiloma de células escamosas do esôfago. Apresentação de 3 casos. Aspectos diagnósticos.

UNLABELLED: Dysphagia is not always present in patients with esophageal squamous cell papilloma, and it can be an incidental finding during gastrointestinal endoscopy of an asymptomatic patient. PURPOSE: Three cases of squamous cell papilloma of the esophagus and aspects regarding diagnosis and association with human papillomavirus are presented. CASUISTIC: Two cases are male and one female what is consistent with a higher incidence showed in the literature in males. The three patients were submitted to upper gastrointestinal endoscopy: in one case the tumor was unusually large and in all patients it was located in the mid and lower esophagus. Chromoscopy was performed in one case and the lesion was not stained. We were unable to identify human papillomavirus using DNA-hybridization techniques. Our results are similar to those reported in the review of the literature. RESULTS: There is no other case published in the Brazilian literature and this is the first report on the use of chromoscopy. CONCLUSION: We were not able to show an association between esophageal squamous papilloma and human papillomavirus.

FALLS-protocol: lung ultrasound in hemodynamic assessment of shock.

The assessment of acute circulatory failure is a challenge in absence of solid gold standard. It is suggested that artifacts generated by lung ultrasound can be of help. The FALLS-protocol (Fluid Administration Limited by Lung Sonography) follows Weil's classification of shocks. Firstly, it searches for pericardial fluid, then right heart enlargment, lastly abolished lung sliding. In this setting, the diagnoses of pericardial tamponade, pulmonary embolism and tension pneumothorax, i.e. obstructive shock, can be schematically ruled out. Moreover, the search of diffuse lung rockets (i.e. multiple B-lines, a comet-tail artifact) is performed. Its absence excludes pulmonary edema, that in clinical practice is left cardiogenic shock (most cases). At this step, the patient (defined FALLS-responder) receives fluid therapy. He/she has usually a normal sonographic lung surface, an A-profile. Any clinical improvement suggests hypovolemic shock. The absence of improvement generates continuation of fluid therapy, eventually yielding fluid overload. This condition results in the change from A-profile to B-profile. Lung ultrasound has the advantage to demonstrate this interstitial syndrome at an early and infraclinical stage (FALLS-endpoint). The change from horizontal A-lines to vertical B-lines can be considered as a direct marker of volemia in this use. By elimination, this change indicates schematically distributive shock, while in current practice septic shock. The major limitation is the B-profile on admission generated by an initial lung disorder. FALLS-protocol, which can be associated with no drawback with traditional hemodynamic tools, uses a simple machine (without Doppler) and a suitable microconvex probe allowing for heart, lung and vein assessment.