Ben Taub Hospital

BACKGROUND: Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso. METHODS: We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room. RESULTS: Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group. CONCLUSIONS: For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.

BACKGROUND: Since the patient's skin is a major source of pathogens that cause surgical-site infection, optimization of preoperative skin antisepsis may decrease postoperative infections. We hypothesized that preoperative skin cleansing with chlorhexidine-alcohol is more protective against infection than is povidone-iodine. METHODS: We randomly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint. The primary outcome was any surgical-site infection within 30 days after surgery. Secondary outcomes included individual types of surgical-site infections. RESULTS: A total of 849 subjects (409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group) qualified for the intention-to-treat analysis. The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group (9.5% vs. 16.1%; P=0.004; relative risk, 0.59; 95% confidence interval, 0.41 to 0.85). Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections (4.2% vs. 8.6%, P=0.008) and deep incisional infections (1% vs. 3%, P=0.05) but not against organ-space infections (4.4% vs. 4.5%). Similar results were observed in the per-protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period. Adverse events were similar in the two study groups. CONCLUSIONS: Preoperative cleansing of the patient's skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery. (ClinicalTrials.gov number, NCT00290290.)

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

Introduction Abbreviations used in this article: AIDS, acquired immunodeficiency syndrome, ALT, alanine aminotransferase, CMV, cytomegalovirus, CSF, cerebrospinal fluid, HAART, highly active antiretroviral therapy, HBV, hepatitis B virus, HCV, hepatitis C virus, HIV, human immunodeficiency virus, IRIS, immune reconstitution inflammatory syndrome, MAC, Mycobacterium avium complex, MTB, Mycobacterium tuberculosis, PML, progressive multifocal leukoencephalopathy The discovery of effective therapy for human immunodeficiency virus (HIV) infection has improved the outlook for patients with the acquired immunodeficiency syndrome (AIDS) (75,88,115,121,134). Since the introduction of highly active antiretroviral therapy (HAART), there has been a decrease in the incidence of opportunistic infections among HIVinfected patients along with a corresponding reduction in the mortality rate (7,30,45,102,117). The basis for these improvements appears to be a result of partial recovery of the host’s immune system. Suppression of viral replication by antiretroviral therapy allows for the reappearance of immune effector cells, that in turn, provide vital protection against opportunistic pathogens (15,32,92,95,132). However beneficial HAART has been, experience during the past several years has disclosed the emergence, in a small proportion of cases, of a unique set of complications. Soon after treatment is begun, some patients experience clinical deterioration due to restoration of their capacity to mount an inflammatory immune response against both infectious and noninfectious antigens. This phenomenon which carries such labels as the immune reconstitution syndrome (IRS) and immune restoration disease (IRD), has been described for a wide variety of infectious pathogens (26,36,46). The manifestations of this syndrome are diverse and depend on the particular infectious agent involved. Given that an increased inflammatory response underlies its presentation, we propose the name immune reconstitution inflammatory syndrome (IRIS). Autoimmune diseases that occur following institution of HAART may also be considered as part of the same process. For the purpose of this review, IRIS is defined as a paradoxical deterioration in clinical status attributable to the recovery of the immune system during HAART. Recognition of this entity is crucial, for successful treatment relies on alleviation of the patient’s symptoms without compromising antiretroviral or antimicrobial therapy. In this article, we review the present understanding of the basic science underlying IRIS, with illustrative examples from our case series, and review the existing clinical literature. Patients and Methods Patient identification and chart review; case definition After IRIS had been discussed at several teaching conferences in the Texas Medical Center, members of the full-time faculty, Department of Medicine (Infectious Disease Section), Baylor College of Medicine, were asked to identify patients with clinical scenarios compatible with this syndrome. The medical records of these patients were then reviewed by 1 of the investigators. Patients were included if they fulfilled the following 4 criteria: The patient had a diagnosis of AIDS; Treatment with anti-HIV medicines (usually, but not necessarily including a protease inhibitor) had led to an increase in CD4+ T lymphocytes and a decrease in HIV-1 viral load if measured. [Some cases of IRIS preceded the widespread use of HIV-1 viral loads. All cases where viral loads are not mentioned occurred during this era.]; Symptoms consistent with an infectious/inflammatory (autoimmune) condition appeared while on antiretroviral therapy, and; These symptoms could not be explained by a newly acquired infection, by the expected clinical course of a previously recognized infectious agent, or by side effects of therapy. Literature review We performed a computer-based search (MEDLINE, National Library of Medicine, Bethesda, MD; years 1996–2001, AIDSLINE, and AIDS conferences). Key words used in the search were immune restoration disease, immune reconstitution, immunoreconstitution, immune restitution, HAART, paradoxical reaction, HIV, and AIDS. The citations in all identified articles were evaluated, and all titles not previously found via the computerized search that contained the key words were reviewed. In addition, multiple Internet search engines were used to identify conferences related to AIDS, and papers presented at these conferences were reviewed. Articles published from 1996 until April 2001 that described various opportunistic infections and syndromes were also reviewed to elicit reports consistent with this syndrome. Pathophysiology of Immune Reconstitution with HAART Most studies evaluating HAART have utilized the combination of 1 protease inhibitor or nonnucleoside reverse transcriptase inhibitor plus 2 nucleoside analogue inhibitors. Following the initiation of such treatment, the levels of HIV RNA usually fall rapidly with a 90% decrease observed within 1–2 weeks (76,114). The viral load continues to decline for the first 8–12 weeks of therapy, often reaching levels ≤200 RNA copies/mL (112). An increase in immune effector cells appears coincident with the reduction in viral load. The initial expansion is seen in memory CD4+ T lymphocytes, as defined by CD45RO+. These cells have been activated previously by antigen exposure, and their increase can be detected within 1–2 weeks of starting therapy (7). Analysis of CD4+ cell turnover and lymphoid tissue suggests that redistribution rather than cell proliferation is responsible for the increase (19,75). Probable mechanisms include alterations in surface adhesion proteins as well as a decrease in apoptosis (5,87). The continuation of HAART leads to a proliferation in different subsets of CD4+ T lymphocytes. After 4–6 weeks, naive CD4+ cells, defined as CD45RA+, CD62L+, begin to increase (121). By definition, these cells have not been previously activated by antigen exposure. The numerical rise of naive CD4+ lymphocytes occurs in lymph nodes as well as in the blood, thus supporting the theory that the sustained increase in these cells reflects peripheral expansion as opposed to redistribution (57,105). The long-term rise in CD4+ lymphocytes is mainly accounted for by the persistent increase in these naive CD4+ cells (112). At the same time there is increased diversity of the T cell receptor repertoire along with a shift in cytokine production from a Th-2 to a Th-1 profile, with increases in interleukin (IL)-2 and interferon (IFN)-γ (64,77,81,99). The repopulation of these CD4+ cells is thought to depend on the amount of thymic tissue present, with patients who have higher baseline levels of thymic tissue having larger CD4+ cell increases following HAART (135). HIV infection appears to impair thymic function; studies using T-cell receptor rearrangement excision circles as markers of thymic output indicate that HAART generally brings about a rapid and sustained output of T cells from the thymus (40). HAART also affects CD8+ T lymphocytes, with increases in memory CD8+ cells seen in the first few weeks following the initiation of therapy (112). With prolonged treatment, these memory CD8+ cells decline and are gradually replaced by naive CD8+ T lymphocytes. CD8+ cells also show reduced activation markers along with broadened T-cell receptor profiles (58). The total CD8+ cell count remains steady during prolonged therapy, leading to a progressive increase in the CD4+/ CD8+ ratio (142). In addition to numerical increases in various arms of the immune system, HAART has been shown to result in functional improvements as well. Within 4 weeks of starting HAART, increases in delayed hypersensitivity and in vitro lymphocyte proliferative responses to common antigens such as Candida can be demonstrated (88). Responses continue to improve with increasing duration of therapy, as shown with assays using common antigens, as well as those from organisms that cause opportunistic infection (75,142). Komanduri et al (80) compared immune responses in patients with active cytomegalovirus (CMV) disease and those who had previously had CMV disease but had received HAART; the HAART-treated patients had significantly higher CMVspecific CD4+ cell responses than the non-HAART-treated CMV-infected patients. The enhancement in immune response appears to be especially marked toward widely prevalent organisms such as CMV or mycobacterium (87). Restoration of immune function occurs even when patients with advanced HIV disease are treated (100). The degree of HAARTinduced suppression of viral load and the increase in CD4+ cells, rather than their baseline values, best correlates with improvements in immune responses (90,138). Case Reports and Literature Review Mycobacterium avium complex Case 1: A 44-year-old with AIDS for 4 CD4+ cell count of on treatment with and for the past and Mycobacterium avium complex from and about a of then to antiretroviral and for therapy. to the with to and then and were for therapy without then due to of with and to therapy. weeks in 1 with and CD4+ cell count of the of the lymph nodes with all and A diagnosis of IRIS therapy and treatment for were the several weeks, symptoms Case A with AIDS, on treatment with seen in for and CD4+ cell count found to have of the and weeks this therapy and were to weeks of CD4+ cell count had and and of and lymph nodes were The diagnosis of IRIS HAART with and the several weeks symptoms and the to 1: Case of the and multiple lymph nodes in a with immune reconstitution inflammatory syndrome with Mycobacterium avium complex among the first infectious with the immune reconstitution inflammatory syndrome to its and infection is often a for a immune system In et al described patients who within weeks of on HAART. All of these patients had increases in memory CD4+ cells with a marked and of the nodes lymph with of and to an and response to HAART IRIS from the of infection in patients with AIDS The of which usually are not seen in AIDS, suggests that the clinical is due to a inflammatory In our Case is that the inflammatory response within the in of which in the patient’s 1: Immune reconstitution syndrome following highly active antiretroviral therapy, and present 1: Immune reconstitution syndrome following highly active antiretroviral therapy, and present immune response can in small and have all been described of these an inflammatory response if this inflammatory response can cause also long-term protection against the as shown in a of patients with infection who of disease without therapy for a immune response against by et al who described 4 patients who infection an of 4 weeks after starting HAART. all of the patients had been to antigens therapy, of the 4 a marked increase in the response to antigens at the time they presented et al that lymphocyte proliferative responses to antigens were in patients and patients with treated on HAART, but significantly in patients not HAART. patients thus with IRIS related to infection symptoms of IRIS within 1 of on HAART. In cases, there have been reports of IRIS as as Patients who infection in the of immune reconstitution to have a long-term even with of therapy Mycobacterium Case A not previously to have HIV infection, for and found to have to viral load HIV RNA and CD4+ cell count that contained Mycobacterium 4 rapidly this therapy, and were increased and infectious of the lymph of which and were Within weeks of initiation of HAART, CD4+ cell count had to and had an viral load. A diagnosis of IRIS and at with of persistent and therapy and HAART were a lymph with and with a of which with and Case A had from had a CD4+ cell count of a viral load of HIV RNA and on and presented with and A a inflammatory of the and A with Review of the with All were CD4+ cell count with a viral load HIV RNA treated with therapy with Case of the and in a with immune reconstitution syndrome with The that clinical deterioration may treatment for an infectious is not to HIV In the of HIV infection, the institution of therapy may cause increasing and that of the disease et al found that of patients for were to After 2 weeks of therapy of these patients a response to antigens. infection with leads to some degree of immune suppression that is with therapy. This underlies the use of as therapy for if a inflammatory response vital such as the system A inflammatory response be with the use of HAART and therapy in patients who are with HIV and The shift a Th-1 cytokine with increased levels of be expected to the immune response to the In such have been et al paradoxical clinical deterioration in of patients with infections after initiation of HAART. included prolonged of increasing increasing of and A review of cases in of patients including increasing and Since in patients is often the inflammatory response by HAART can cause the of the system in the of immune reconstitution is et al described the paradoxical of an in a patient who while therapy and HAART. A review of patients with both HIV and treated with HAART found an of paradoxical system All but 1 of the patients were with found on and the use of for Given the that can IRIS in the of MTB, some have to the of HAART until therapy has the load of organisms The time from initiation of HAART to the of IRIS in patients with is than in those with MAC, within as few as to as as have been used in reports with at when vital especially the system. Case A with HIV-1 infection presented with 1 of and contained cells and antigen and CD4+ cell count with viral load of HIV RNA treated with B and with response and on on HAART of and after initiation of HAART to have and contained with and lymphocytes. in the had increased to and with a antigen of A enhancement and All were and for IRIS with rapid of were the several weeks, and the patient with and contained with lymphocytes. antigen and all were with to show CD4+ cell count with a viral load of HIV RNA were with clinical The patient on and a prolonged with of Case especially the in a patient with and immune reconstitution inflammatory syndrome. A with HIV infection and CD4+ cell count with a viral load of HIV RNA treated with B and well. After of B on and After of HAART to have of and increasing of A a with and of the underlying for increasing After an search for a infectious with IRIS and on symptoms and to be in CD4+ cell count with a viral load of RNA weeks with and after Case of the in a with in the of the due to a from the immune reconstitution inflammatory of the system by in the of advanced HIV may elicit a inflammatory as by in the is coincident with immune system recovery to HAART, the inflammatory response may be HAART has been shown to increase by alterations in and production A when is the of HIV there is response to therapy, but antigen can in the for a prolonged of on the cases seen at our is that the of antigen without organisms can a immune response in the HAART-treated by Case of our series, infection with in in the of immune reconstitution have been cases of both and as well as with infection that occurred after the institution of HAART of these patients had been treated with as after of the cases to therapy, while the 2 therapy. The experience with IRIS is compared with the experience with IRIS with of the IRIS patients seen with in our had symptoms within 2 weeks of starting HAART. This is consistent with the time described by et al In to the patients who the patients who presented with had been treated an of that a in the immune reconstitution may have their Case A with prolonged and and assays for to HIV-1 were with a CD4+ cell count of consistent with CMV treated with weeks of with of the on and 4 weeks with in the with CD4+ cell count HAART and with of CMV disease to with IRIS and has not had of CMV disease CMV is a common of AIDS. usually occurs in patients with CD4+ cell than and is by a with inflammatory after the introduction of protease to a of disease in the of CMV infection The of the inflammatory response than that seen in CMV and the syndrome recovery that the could also be the to recovery The inflammatory response in this can proliferative and leading to The incidence of recovery has from to of this syndrome a a course has been of the there have been reports of using The of CMV infection has been in cases of IRIS CMV, which have from to show that patients with IRIS are to a to IRIS among some patients The side of the increased immune response against CMV is that can a disease which allows for the of therapy patients not all patients CD4+ T-cell responses those patients at for CMV long-term therapy. Case A with AIDS cell count of multiple of HAART. then on and load HIV RNA copies/mL and CD4+ cell count improved until weeks when presented with of the of the load HIV RNA copies/mL while CD4+ cell count on with but then and of the Treatment with and to a of in the same opportunistic infections in at a consistent rate of the degree of have demonstrated a and increase in in patients treated with HAART non-HAART-treated patients The of cases have by of therapy with the starting HAART and weeks CD8+ lymphocyte proportion at baseline and response in CD8+ cells at 1 have been with of Case A with for 4 years and HIV infection for 1 presented with persistent previously CD4+ cell count with a viral load of HIV RNA and and of After of HAART, CD4+ cell count and viral load of at to and also had lymph with in but in for which cause than and increased of and institution of of the immune system with HAART has been to result in the of both and Given the of the CD4+ T lymphocyte in the of the of CD4+ cells by infection with HIV be expected to improve the clinical course of HAART there were reports of patients with both to or even improve as their HIV The introduction of HAART has the patient after the addition of to HAART patients who had years previously after HAART; both well to therapy Most of the cases have gradually after several of HAART and have not The patient described is which has shown some in the treatment of to In addition to the patient described had of coincident with immune recovery due to HAART. In cases, HAART is in the of et al a case where the initiation of HAART in a patient with by of the to of the by a The that an increased immune response to human in and a previously disease Case A with HIV therapy with and CD4+ cell count presented with the of and and at a of increased in the consistent with of the CD4+ cell count of the with of in addition to the 1 described have disease following the institution of HAART et al and et al were to receptor in these of demonstrated the of the institution of HAART and the that of the T-cell repertoire during HAART be for the proliferation of T These cells from the mechanisms of immune leading to Case A with AIDS, a CD4+ cell count of and a viral load of HIV RNA on and CD4+ cell count after starting HAART presented with and progressive CD4+ cell count with a viral load of HIV RNA with a an with infection to and have recognized the effects of an inflammatory response in the treatment of in advanced studies have shown the beneficial effects of in the course of therapy, by the immune response to organisms The of HAART has the incidence of and there is that patients CD4+ cell rise can against the have been few reports of the CD4+ cell count as occurred in our patient (100). of the case described the of The seen in cases of of a of organisms and in the with a cell inflammatory there have been cases of a response to in all but 1 of these patients were some of antiretroviral therapy, the that an increased immune response responsible in those cases C and B hepatitis C virus and HIV have of there is a patient who are with from HAART affects levels and the immune response to has not been may cause from of hepatitis is HAART a rise in RNA and alanine after 2 weeks of therapy, of an increase in CD8+ T lymphocytes In cases, RNA levels to baseline within patients who were HAART hepatitis and after of by et al described a patient with infection who had marked after HAART. marked and inflammatory with an increase in CD8+ T lymphocytes that the patient’s immune of such as an there for a such as In after of HAART in a patient with infection and after initiation of HAART in patients with HIV and hepatitis B virus In the of HAART, patients have higher levels of of and levels of compared with patients with This suggests that the immune suppression by HIV allows for increased replication and by the immune system. HAART the immune response to is with 1 an incidence of as defined by among treated patients. this due to or an on viral is not et al described an patient who had symptoms of hepatitis after initiation of HAART. At the time that HAART for of that had been and of and had In cases, in levels have occurred in with clinical hepatitis following initiation of HAART of therapy led to the of a variety of hepatitis B with of and of the The diagnosis of IRIS in patients with or is patients can be expected to have increases in in the first few weeks after starting HAART. this the and HIV or the immune system and is for these patients to be of this that HAART is not patients to be observed there is a for both and may be to the multifocal leukoencephalopathy The of progressive multifocal leukoencephalopathy in advanced HIV disease has been with a time in The use of HAART, while not the of in all has been shown to increase significantly in patients with of an increased immune response to the virus, the With HAART, levels of virus in the decrease and levels of to virus increase an inflammatory has in several patients treated with HAART, with of these patients a inflammatory of these has with of In marked to the course of PML, all the patients described who in the of immune reconstitution have had or at of their Treatment The of the reports of IRIS therapy. At this the is to IRIS as a for this can to and for the use of The experience with in the has been in the treatment of tuberculosis, and These organisms have a for the system, which has for In the case of CMV disease, have been used in both and with treatment to decrease CMV antigen has also been have been used in the treatment of IRIS infection, especially in the of with appears in IRIS, increased is a as is in the of have been the of treatment, and have been used when in the cases the addition of to these in the of disease has in clinical in a the effects of are a found with use in advanced HIV infection The use of than has been cases of to which could be used by or in with The use of such as is We clinical and in patients who paradoxical clinical deterioration while highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) The patients had to antiretroviral therapy as defined by increased CD4+ T cell lymphocyte and in HIV viral loads. In of the deterioration attributable to a response to an infectious agent to be present starting HAART. of the patients against that had not been recognized starting HAART, that these organisms were the institution of therapy. of these patients had disease of the 2 had symptoms to cytomegalovirus, 1 had in with infection, and 1 had an in response to infections with were responsible for symptoms in 2 1 patient to while had progressive a disease with human the 2 1 had of a disease in which CD4+ T lymphocytes a in while the an which may have been related to the production of T lymphocytes during immune We propose that a capacity of the to mount an inflammatory response against persistent antigens or led to the of symptoms in these we this of the immune reconstitution inflammatory syndrome (IRIS). We found reports of an cases of We the on the basic science of immune reconstitution with HAART, along with immune responses that occur following HAART. The of cases occurred in with Mycobacterium avium complex Mycobacterium cytomegalovirus or diseases included and progressive multifocal disease, and For some such as and the clinical manifestations were to the same disease in the of HAART. such as Mycobacterium avium complex cytomegalovirus and inflammatory PML, were unique to patients with immune reports that there may be some from treatment with if the inflammatory response vital or has The of HAART has improved the of with in the of these patients to be of the for this therapy to cause a paradoxical decline in clinical the search for infectious be and the of to be evaluated, is to that improved immune can be the In IRIS, the to the and symptoms of immune reconstitution has to be with the to the patient on effective anti-HIV therapy. With increasing of patients with IRIS, may be to clinical to the to

BACKGROUND: Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control. OBJECTIVE: To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections. DESIGN: Multicenter, randomized clinical trial. SETTING: Five university-based medical centers. PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters. INTERVENTION: 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls. MEASUREMENTS: Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections. RESULTS: The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs. CONCLUSIONS: Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.

Medical Writings: Book Notes18 January 2000Tropical Infectious Diseases: Principles, Pathogens, and PracticeA. Clinton White Jr., MD, Robert L. Atmar, MD, and Stephen B. Greenberg, MDA. Clinton White Jr., MDBaylor College of Medicine and Ben Taub General Hospital, Houston, Texas. (White, Atmar, Greenberg)Search for more papers by this author, Robert L. Atmar, MDBaylor College of Medicine and Ben Taub General Hospital, Houston, Texas. (White, Atmar, Greenberg)Search for more papers by this author, and Stephen B. Greenberg, MDBaylor College of Medicine and Ben Taub General Hospital, Houston, Texas. (White, Atmar, Greenberg)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-2-200001180-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 2 volumes. Guerrant RL, Walker DH, Weller PF, eds. 1644 pages. Philadelphia: Churchill Livingstone; 1999. $295.00. ISBN 0443079080. Order phone 800-543-1918.Field of medicine: Infectious diseases and tropical medicine.Format: Two hardcover books.Audience: Specialists in infectious disease and tropical medicine; generalists who treat immigrants and travelers from developing countries; and practitioners in tropical countries.Purpose: To provide a comprehensive scholarly textbook on tropical infectious diseases.Content: The first section of the book discusses general considerations and noninfectious conditions. The second section covers individual bacterial, rickettsial, fungal, parasitic, and viral pathogens. Chapters on pathogens that are common worldwide (such as ... Author, Article, and Disclosure InformationAffiliations: Baylor College of Medicine and Ben Taub General Hospital, Houston, Texas. (White, Atmar, Greenberg) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited by1,2,3-triazenes and 1,2,3-triazoles as antileishmanial, antitrypanosomal, and antiplasmodial agentsA Bibliometric Analysis of Global Scientific Research on Scrub Typhus 18 January 2000Volume 132, Issue 2Page: 168KeywordsHospital medicineInfectious diseasesPneumococcusSoftware toolsStaphylococcusStreptococcusToxinsTropical diseasesTuberculosisViral pathogens ePublished: 15 August 2000 Issue Published: 18 January 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

The triad of hypothermia, acidosis, and coagulopathy in critically injured patients is a vicious cycle that, if uninterrupted, is rapidly fatal. During the past 7.5 years, 200 patients were treated with unorthodox techniques to abruptly terminate the laparotomy and break the cycle. One hundred seventy patients (85%) suffered penetrating injuries and 30 (15%) were victims of blunt trauma. The mean Revised Trauma Score, Injury Severity Score, and Trauma Index Severity Score age combination index predicted survival were 5.06%, 33.2%, and 57%, respectively. Resuscitative thoracotomies were performed in 60 (30%) patients. After major sources of hemorrhage were controlled, the following clinical and laboratory mean values were observed: red cell transfusions--22 units, core temperature--32.1 C, and pH--7.09. Techniques to abbreviate the operation included the ligation of enteric injuries in 34 patients, retained vascular clamps in 13, temporary intravascular shunts in four, packing of diffusely bleeding surfaces in 171, and the use of multiple towel clips to close only the skin of the abdominal wall in 178. Patients then were transported to the surgical intensive care unit for vigorous correction of metabolic derangements and coagulopathies. Ninety-eight patients (49%) survived to undergo planned reoperation (mean delay 48.1 hours), and 66 of 98 (67%) survived to leave the hospital. With the exception of intravascular shunts, there were survivors who were treated by each of the unorthodox techniques. Of 102 patients who died before reoperation 68 (67%) did so within 2 hours of the initial procedure. Logistic regression showed that red cell transfusion rate and pH may be helpful in determining when to consider abbreviated laparotomy. The authors conclude that patients with hypothermia, acidosis, and coagulopathy are at high risk for imminent death, and that prompt termination of laparotomy with the use of the above techniques is a rational approach to an apparently hopeless situation.

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.

Abstract Methods of scoring osseous defects and joint space narrowing in the hands and wrists of patients with definite or classical rheumatoid arthritis were devised. The usefulness of the scores was tested in a group of 90 patients who had one or more sets of X‐ray films of the hands and wrists 36 months or more after onset of illness. Correlations were found between the extent of radiographic abnormalities or the rate of progression of radiographic changes and the age at onset, hand and wrist deformities, preceding physical signs of inflammation in the joints of the hands and wrists, hand function as measured by fist formation, the early appearance of subcutaneous nodules, and the titer of anti‐IgG. Among black patients the extent of elevation of γ‐globulins was associated with roentgenographic changes. The correlations between the scores of radiologic abnormalities and the clinical and laboratory manifestations of rheumatoid arthritis establish the value of the described methods of assessing the roentgenographic changes and indicate the usefulness of these methods in evaluating the effect of therapy in this disease.

Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists, intensivists, nurses and other health care providers have to cooperate to provide optimal benefit. However, many treatment decisions are opinion-based and few are evidenced-based. This consensus paper provides guidance to practicing physicians and nurses to manage acute heart failure in the pre-hospital and hospital setting. Criteria of hospitalization and of discharge are described. Gaps in knowledge and perspectives in the management of acute heart failure are also detailed. This consensus paper on acute heart failure might help enable contiguous practice.

Large epidemiologic analyses of cardiovascular injuries have been limited to studies of military campaigns compiled from many surgeons working in many hospitals with variable protocols. A detailed civilian vascular trauma registry provides a unique opportunity for an epidemiologic evolutionary profile. During the last 30 years in a single civilian trauma center directed by a consistent evaluation and treatment philosophy, 4459 patients were treated for 5760 cardiovascular injuries. Eighty-six per cent of the patients were male, and the average age was 30.0 years. Penetrating trauma was the etiology in more than 90% (GSW,51.5%; SW,31.1%; SGW,6.8%). All other injuries were iatrogenic or secondary to blunt trauma. Truncal injuries (including the neck) accounted for 66% of all injuries treated, while lower extremity injuries (including the groin) accounted for only 19%. Injuries to the abdominal vasculature accounted for 33.7% of the injuries. One thousand fifty-seven patients had 2 or more concurrent vascular injuries, and 32 patients had 4 or more separate vascular injuries. The 27 patients-per-year average of the early 1960s has risen to a current average of 213 patients per year. Economic and population factors influenced wounding agents and injury patterns during the evaluation period. This extensive civilian series presents epidemiologic profiles that are distinctly different from military reports and serves as a guide for current trauma center and health planners.

Antimicrobial control programs are widely used to decrease drug expenditures, but effects on antimicrobial resistance and outcomes for patients are unknown. When a requirement for prior authorization for selected parenteral antimicrobial agents was initiated at our urban, county teaching hospital, total parenteral antimicrobial expenditures decreased by 32%. Susceptibilities to all beta-lactam and quinolone antibiotics increased, with dramatic increased susceptibilities in isolates recovered in intensive care units, increased susceptibilities in isolates recovered in other inpatient sites, and little change in susceptibilities in isolates recovered in outpatient sites despite no change in infection control practices. For patients with bacteremia due to gram-negative organisms, overall survival did not change with restrictions. No differences occurred in the median time from initial positive blood culture to receipt of an appropriate antibiotic or in the median time from positive blood culture to discharge from the hospital. Thus, requiring preapproval for selected parenteral agents can decrease antimicrobial expenditures and improve susceptibilities to antibiotics without compromising patient outcomes or length of hospital stay.

We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations. Cells were counted in endobronchial biopsies of (1) patients with COPD intubated for exacerbations (E-COPD; n = 15), (2) those with COPD in a stable phase of their disease (S-COPD; n = 7), and (3) nonsmoker surgical control subjects intubated for a nonrespiratory surgical procedure (n = 15). In comparison with the nonrespiratory surgical procedure and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1, and CXCR2 were each upregulated in the E-COPD group (p < 0.01); compared with the S-COPD group, by 97-, 6-, 6-, 3-, and 7-fold, respectively (p < 0.01). In E-COPD, there was a significant positive association between the number of neutrophils and CXCR2 mRNA-positive cells (r = 0.79; p < 0.01) but not between the number of neutrophils and CXCR1 mRNA-positive cells. At the time of sampling of the mucosa, there was no association between neutrophil number and either the length of intubation or viral infection. Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations.

A. Clinton White, Jr.; Neurocysticercosis: A Major Cause of Neurological Disease Worldwide, Clinical Infectious Diseases, Volume 24, Issue 2, 1 February 1997, P

Balance disorders in elderly patients are associated with an increased risk of falls but are often difficult to diagnose because of comorbid chronic medical problems. We performed a cross-sectional study to determine the prevalence of unrecognized benign paroxysmal positional vertigo (BPPV) and associated lifestyle sequelae in a public, inner-city geriatric population. Dizziness was found in 61% of patients, whereas balance disorders were found in 77% of patients. Nine percent were found to have unrecognized BPPV. Multivariate analysis demonstrated that the presence of a spinning sensation and the absence of a lightheadedness sensation predicted the presence of unrecognized BPPV. Patients with unrecognized BPPV were more likely to have reduced activities of daily living scores, to have sustained a fall in the previous 3 months, and to have depression. These data indicate that unrecognized BPPV is common within the elderly population and has associated morbidity. Further prospective studies are warranted.

The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis in adult male cynomolgus monkeys (Macaca fascicularis). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment in the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean intimal area measurement, based on all arterial sections, served as a coronary index for each animal. Results indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed in stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (i.e., unstable) subordinates. A similar pattern was observed in the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen in the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences in total serum cholesterol or high density lipoprotein cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an individual behavioral characteristic) is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (i.e., under behavioral challenge).

This study of human immunodeficiency virus (HIV)-infected patients coinfected with Cryptococcus neoformans found that 30% of patients who initiated highly active antiretroviral therapy developed immune reconstitution inflammatory syndrome (IRIS). Patients with C. neoformans-related IRIS had higher cerebrospinal fluid opening pressures, glucose levels, and white blood cell counts, compared with patients with typical HIV-associated C. neoformans meningitis.

More than 30 neurodegenerative diseases including Alzheimer disease (AD), frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are characterized by the accumulation of an aggregated form of the microtubule-binding protein tau in neurites and as intracellular lesions called neurofibrillary tangles. Diseases with abnormal tau as part of the pathology are collectively known as the tauopathies. Methylthioninium chloride, also known as methylene blue (MB), has been shown to reduce tau levels in vitro and in vivo and several different mechanisms of action have been proposed. Herein we demonstrate that autophagy is a novel mechanism by which MB can reduce tau levels. Incubation with nanomolar concentrations of MB was sufficient to significantly reduce levels of tau both in organotypic brain slice cultures from a mouse model of FTD, and in cell models. Concomitantly, MB treatment altered the levels of LC3-II, cathepsin D, BECN1, and p62 suggesting that it was a potent inducer of autophagy. Further analysis of the signaling pathways induced by MB suggested a mode of action similar to rapamycin. Results were recapitulated in a transgenic mouse model of tauopathy administered MB orally at three different doses for two weeks. These data support the use of this drug as a therapeutic agent in neurodegenerative diseases.

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).

Presently available techniques for control of hepatic hemorrhage in patients with extensive parenchymal injuries include direct suture, topical hemostatic agents, hepatotomy or resectional debridement with selective vascular ligation, lobectomy, and selective hepatic artery ligation. In many trauma centers the placement of intra-abdominal packing for hepatic tamponade has been an infrequently used technique in recent years. From 1 July 1978 to 1 September 1980, ten patients with continued hepatic parenchymal oozing following all attempts at surgical control of extensive injuries were treated by the insertion of intra-abdominal packing around the liver as a last desperate maneuver. Packing was removed at relaparotomy in four patients and through abdominal drain sites in five patients. Nine of ten patients survived, and there were no instances of rebleeding following removal of the packing. Four patients developed postoperative perihepatic collections and two of the four patients underwent reoperation for drainage. Based on the recent experience at the Ben Taub General Hospital, intra-abdominal packing for control of exsanguinating hepatic hemorrhage appears to be a lifesaving maneuver in highly selected patients in whom coagulopathies, hypothermia, and acidosis make further surgical efforts likely to increase hemorrhage.