Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.

Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.

Pre-injury neuro-psychiatric medication use, alone or in combination with cardiac medications, may affect outcomes in trauma patients.

BACKGROUND: Recent review of older (≥45-years-old) patients admitted to our trauma center showed that more than one-third were using neuro-psychiatric medications (NPMs) prior to their injury-related admission. Previously published data suggests that use of NPMs may increase patients' risk and severity of injury. We sought to examine the impact of pre-injury NPM use on older trauma patients' morbidity and mortality. MATERIALS AND METHODS: Retrospective record review included medication regimen characteristics and NPM use (antidepressants-AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day survival were examined. Comparisons included regimens involving NPMs, further focusing on their interactions with various cardiac medications (beta blocker - BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker - ACE/ARB; calcium channel blocker - CCB). RESULTS: 712 patient records were reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect of NPM monotherapy on hospital mortality. Patients taking ≥3 NPMs had significantly lower 90-day survival compared to patients taking ≤2 NPMs (81% for 3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac medication (CM) combinations were associated with increased mortality compared to monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs 4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). CONCLUSIONS: Large proportion of older trauma patients was using pre-injury NPMs. Several regimens involving NPMs and CMs were associated with increased in-hospital mortality. Additionally, use of ≥3 NPMs was associated with lower 90-day survival.

Disruption of murine cardiac allograft acceptance by latent cytomegalovirus.

Cytomegalovirus (CMV) reactivation is a well-described complication of solid organ transplantation. These studies were performed to (1) determine if cardiac allograft transplantation of latently infected recipients results in reactivation of CMV and (2) determine what impact CMV might have on development of graft acceptance/tolerance. BALB/c cardiac allografts were transplanted into C57BL/6 mice with/without latent murine CMV (MCMV). Recipients were treated with gallium nitrate induction and monitored for graft survival, viral immunity and donor reactive DTH responses. Latently infected allograft recipients had approximately 80% graft loss by 100 days after transplant, compared with approximately 8% graft loss in naïve recipients. PCR evaluation demonstrated that MCMV was transmitted to cardiac grafts in all latently infected recipients, and 4/8 allografts had active viral transcription compared to 0/6 isografts. Latently infected allograft recipients showed intragraft IFN-alpha expression consistent with MCMV reactivation, but MCMV did not appear to negatively influence regulatory gene expression. Infected allograft recipients had disruption of splenocyte DTH regulation, but recipient splenocytes remained unresponsive to donor antigen even after allograft losses. These data suggest that transplantation in an environment of latent CMV infection may reactivate virus, and that intragraft responses disrupt development of allograft acceptance.

Complications associated with pulmonary artery catheters: a comprehensive clinical review.

Care for the critically ill patient requires maintenance of adequate tissue perfusion/oxygenation. Continuous hemodynamic monitoring is frequently utilized to achieve these objectives. Pulmonary artery catheters (PAC) allow measurement of hemodynamic variables that cannot be measured reliably or continuously by less invasive means. Inherent to every medical intervention are risks associated with that intervention. This review categorizes complications associated with the PAC into four broad groups--complications of central venous access; complications related to PAC insertion and manipulation; complications associated with short- or long-term presence of the PAC in the cardiovascular system; and errors resulting from incorrect interpretation/use of PAC-derived data. We will discuss each of these four broad categories, followed by in-depth descriptions of the most common and most serious individual complications.

Neurogastroenterology of tegaserod (HTF 919) in the submucosal division of the guinea-pig and human enteric nervous system.

Actions of the 5-HT(4) serotonergic receptor partial agonist, tegaserod, were investigated on mucosal secretion in the guinea-pig and human small intestine and on electrophysiological behaviour of secretomotor neurons in the guinea-pig small intestinal submucosal plexus. Expression of 5-HT(4) receptor protein and immunohistochemical localization of the 5-HT(4) receptor in the submucosal plexus in relation to expression and localization of choline acetyltransferase and the vesicular acetylcholine (ACh) transporter were determined for the enteric nervous system of human and guinea-pig small intestine. Immunoreactivity for the 5-HT(4) receptor was expressed as ring-like fluorescence surrounding the perimeter of the neuronal cell bodies and co-localized with the vesicular ACh transporter. Exposure of mucosal/submucosal preparations to tegaserod in Ussing chambers evoked increases in mucosal secretion reflected by stimulation of short-circuit current. Stimulation of secretion had a relative high EC(50) of 28.1 +/- 1.3 mumol L(-1), was resistant to neural blockade and appeared to be a direct action on the secretory epithelium. Tegaserod acted at presynaptic 5-HT(4) receptors to facilitate the release of ACh at nicotinic synapses on secretomotor neurons in the submucosal plexus. The 5-HT(2B) receptor subtype was not involved in actions at nicotinic synapses or stimulation of secretion.

Temporal changes in hematologic markers after splenectomy, splenic embolization, and observation for trauma.

INTRODUCTION: The spleen is one of the most commonly injured abdominal solid organs during blunt trauma. Modern management of splenic trauma has evolved to include non-operative therapies, including observation and angioembolization to preclude splenectomy in most cases of blunt splenic injury. Despite the shift in management strategies, relatively little is known about the hematologic changes associated with these various modalities. The aim of this study was to determine if there are significant differences in hematologic characteristics over time based on the treatment modality employed following splenic trauma. We hypothesized that alterations seen in hematologic parameters would vary between observation (OBS), embolization (EMB), and splenectomy (SPL) in the setting of splenic injury. METHODS: An institutional review board-approved, retrospective study of routine hematologic indices examined data between March 2000 and December 2014 at three academic trauma centers. A convenience sample of patients with splenic trauma and admission lengths of stay >96 h was selected for inclusion, resulting in a representative sample of each sub-group (OBS, EMB, and SPL). Basic demographics and injury severity data (ISS) were abstracted. Platelet count, red blood cell (RBC) count and RBC indices, and white blood cell (WBC) count with differential were analyzed between the time of admission and a maximum of 1080 h (45 days) post-injury. Comparisons between OBS, EMB, and SPL groups were then performed using non-parametric statistical testing, with statistical significance set at p < 0.05. RESULTS: Data from 130 patients (40 SPL, 40 EMB, and 50 OBS) were analyzed. The median age was 40 years, with 67 % males. Median ISS was 21.5 (21 for SPL, 19 for EMB, and 22 for OBS, p = n/s) and median Glasgow Coma Scale (GCS) was 15. Median splenic injury grade varied by interventional modality (grade 4 for SPL, 3 for EMB, and 2 for OBS, p < 0.05). Inter-group comparisons demonstrated no significant differences in RBC counts. However, mean corpuscular volume (MCV) and RBC distribution width (RDW) were elevated in the SPL and EMB groups (p < 0.01). Similarly, EMB and SPL groups had higher platelet counts than the OBS group (p < 0.01). In aggregate, WBC counts were highest following SPL, followed by EMB and OBS (p < 0.01). Similar trends were noted in neutrophil and monocyte counts (p < 0.01), but not in lymphocyte counts (p = n/s). CONCLUSION: This study describes important trends and patterns among fundamental hematologic parameters following traumatic splenic injuries managed with SPL, EMB, or OBS. As expected, observed WBC counts were highest following SPL, then EMB, and finally OBS. No differences were noted in RBC count between the three groups, but RDW was significantly greater following SPL compared to EMB and OBS. We also found that MCV was highest following OBS, when compared to EMB or SPL. Finally, our data indicate that platelet counts are similarly elevated for both SPL and EMB, when compared to the OBS group. These results provide an important foundation for further research in this still relatively unexplored area.

The effect of oral and topical tetracycline on acne severity and on surface lipid composition.

Groups of 20 males of high-school age with moderate acne were treated with oral tetracycline (500 mg/day), topical tetracycline (0.5% solution applied twice daily), or placebo for 8 weeks. The two panels treated with tetracycline showed a significant and equivalent reduction in acne severity as assessed by visual grading. The surface lipids in the panel treated with oral tetracycline showed a small but not statistically significant decrease in free fatty acid content, but the subjects receiving topical tetracycline showed no reduction in free fatty acids. Further, neither treatment was associated with a change in mass of surface lipid nor did the mass or weight percent of any component of the surface lipids change with the decrease in acne severity. These results show that acne severity can be reduced with tetracycline (both oral and topical) without any concomitant quantitative change in surface lipids.

Reducing overtriage without compromising outcomes in trauma patients.

HYPOTHESIS: Changing category 1 criteria to include primarily physiologic and anatomic indicators of injury, eliminating mechanism of injury criteria, decreases the rate of overtriage without compromising outcomes. METHODS: Retrospective review of our American College of Surgeons-verified level I trauma registry from January 1, 1996, to December 31, 1998, comparing patients before and after trauma alert criteria changes. RESULTS: There was a significant decrease in category 1 alerts, representing a reduction in overtriage. There was a concomitant increase in injury severity and mortality in category 1 patients. There was no significant change in injury severity or mortality for category 2 patients. CONCLUSIONS: There was a significant reduction in overtriage of trauma patients demonstrated without an appreciable impact on patient outcome. Changing trauma response criteria to more physiologic and anatomic indicators allowed improved triage of trauma patients, which improves resource allocation.

Topical use of tetracycline in the treatment of acne: a double-blind study comparing topical and oral tetracycline therapy and placebo.

A group of 75 subjects with moderate or severe acne was divided by random selection into three treatment groups. One group was treated with a topically applied placebo liquid and with 500 mg of orally administered tetracycline hydrochloride daily; one group received orally administered lactose capsules and topically applied placebo liquid each day; and one group was treated with orally administered lactose capsules and with a topical preparation containing tetracycline hydrochloride and n-decylmethyl sulfoxide, an agent intended to enhance antibiotic penetration. At the conclusion of the 13-week study and at several points during the study, the conditions of the subjects receiving topically or orally administered tetracycline hydrochloride were significantly (P less than .05) more improved than the conditions of the subjects receiving lactose capsules and the topically applied placebo liquid. However, there was no significant difference between the effects of topically and orally administered tetracycline hydrochloride.

An acne grading method using photographic standards.

A grading system for following the clinical course of acne was devised in which overall severity of acne is evaluated on a zero to eight scale anchored to photographic standards that illustrate grades 0, 2, 4, 6, and 8. Experience with use of this system in large-scale clinical trials has shown it to be useful and reliable. Photographs taken at each visit create a permanent and regradable record of each subject's clinical status throughout the course of treatment.

Survival of critically ill surgical patients discharged to extended care facilities.

BACKGROUND: Rates of discharge of surgical ICU (SICU) patients to extended care facilities (ECF) increase as SICU length of stay (LOS) increases. Increased SICU LOS and APACHE II scores have been related to increased hospital mortality. This study evaluated factors influencing ECF survival after SICU patient discharge. STUDY DESIGN: We did a longitudinal followup study of patients admitted to our tertiary care SICU during a 2-year period who were eventually discharged to ECF Demographic data, SICU admission APACHE II score, and LOS data were obtained prospectively. Patient followup was obtained 2 years after discharge by telephone interviews with patients themselves or next of kin to ascertain current status or date of demise. RESULTS: Of 1,799 SICU patients admitted during the study period, 160 patients (9%) were discharged to an ECF Telephone followup was obtained from 150 patients (94%). Mean length of followup was 21 months after hospital discharge (range 7 to 34 months), mean patient age 64 years (range 16 to 96 years), mean SICU admission APACHE II score 13 (range 2 to 29), and mean SICU LOS 11 days (range 1 to 146 days). At followup, 45% of patients had died, 37% had been discharged home, and 18% still resided in an ECF or hospital. Elderly patients (above age 65) had significantly worse 1-year (p < 0.001) and 2-year (p < 0.001) ECF survival than nonelderly patients. Patients admitted to the SICU after otolaryngologic procedures also had significantly worse 1- and 2-year ECF survival than all other patients. Severity of illness as estimated by admission APACHE II scores or SICU LOS does not seem to influence survival. CONCLUSIONS: Outcomes of ECF discharge after SICU admission is poor, with nearly 50% 2-year mortality. ECF mortality seems significantly higher for the elderly, with patients undergoing otolaryngologic procedures being at highest risk. Severity of illness at the time of SICU admission and SICU LOS does not seem to influence ECF outcomes.

Occult herpes family viruses may increase mortality in critically ill surgical patients.

BACKGROUND: Effects of cytomegalovirus (CMV) or herpes simplex virus (HSV) infection on surgical intensive care unit (SICU) patients' hospital outcome are unknown. METHODS: Between July 1, 1994, and September 1, 1995, general SICU patients with persistent sepsis and no bacterial or fungal source identifiable had viral cultures obtained. Patients with positive broncho-alveolar lavage, blood, skin, or sputum cultures for CMV or HSV were studied. RESULTS: Twenty eligible patients had positive viral cultures during the study period, and 85% of these patients developed subsequent bacterial and/or fungal infections. Mortality was significantly higher following viral infection than in chronic SICU patients (65% vs 35%, P <0.006). Patients with thrombocytopenia complicating their viral infection had significantly higher mortality than those without thrombocytopenia (92% vs 25%, P <0.004). CONCLUSIONS: At least 14% of critically ill surgical patients have occult infection or reactivation of herpes family viruses. These viruses have known immunosuppressive effects, which may predispose chronic SICU patients to subsequent bacterial and fungal infection, and subsequent organ system failure and death.

Increased acute and chronic mitotic activity in rat laryngeal muscles after botulinum toxin injection.

OBJECTIVES: To characterize the acute and chronic cellular effects of botulinum toxin (BT) injection into rat laryngeal muscles. A complete characterization of these effects is important because patients with focal dystonias of the head and neck are commonly treated with BT injection. Further, potential muscular changes in the larynx must be carefully delineated owing to the critical phonatory and airway protective functions of these muscles. STUDY DESIGN: The acute and chronic cellular effects of BT injection were studied using 5'-bromo 2'-deoxyuridine (BrdU) following single and repeated BT injection into rat laryngeal muscles. BrdU is incorporated into mitotically active nuclei such that changes in cell proliferative behavior following BT injection can be monitored. RESULTS: Increased mitotic activity was detected in the tissue samples studied following BT injection. Differences in the times of the peak distribution of BrdU-labeled cells in each laryngeal muscle were observed. This may be related to the diffusion effects of BT. Prolonged muscle fiber changes, including splitting, were also observed as the result of repeated BT injection. CONCLUSIONS: The results of this study suggest that BT may induce a proliferative response in muscle tissue.

Endoscopic management of stomal stenosis after Roux-en-Y gastric bypass.

BACKGROUND: In the United States, Roux-en-Y gastric bypass has evolved into the procedure of choice for clinically severe obesity. Stomal stenosis resulting in gastric outlet obstruction is a recognized complication. Endoscopic balloon dilation is often used to treat this condition. To evaluate the safety and efficacy of endoscopic management of stomal stenosis we evaluated our treatment methods and outcomes. METHODS: The records of all patients undergoing Roux-en-Y gastric bypass from 1 July 2000 to 30 June 2002 were studied. Stenosis was defined as signs and symptoms of obstruction with inability to cannulate the gastrojejunostomy using an 8.5-mm diagnostic endoscope. Charts were reviewed and demographic data, operative course, symptoms, and outcomes were recorded. RESULTS: A total of 562 patients underwent Roux-en-Y gastric bypass for obesity during the study period. Of these, 38 patients underwent endoscopic balloon dilation for stomal stenosis, for a stenosis rate of 6.8%. The average time from surgery to initial dilation was 7.7 weeks (range 3 to 24). The average number of dilations required was 2.1 (range one to six). The mean initial balloon size was 13 mm and the mean final balloon size was 16 mm. Two patients failed endoscopic dilation and proceeded to surgery, including one patient who developed pneumomediastinum and pneumothorax after dilation. All patients were relieved of their gastric outlet obstruction. The success rate for endoscopic balloon dilation was 95% with a 3% complication rate. CONCLUSIONS: In our experience, the rate of gastrojejunostomy stenosis following Roux-en-Y gastric bypass is 6.8%. Endoscopic balloon dilation is a safe and effective therapy for stomal stenosis with a high success rate. It should be considered an appropriate intervention with a low risk for reoperation.

Pharmacokinetics of iodine-125 CC49 monoclonal antibody in patients with colon cancer.

UNLABELLED: Radioimmunoguided Surgery techniques which use radiolabeled tumor specific markers and an intraoperative detector in an attempt to improve therapy and survival in patients with cancer have been under development for over fifteen years. Monoclonal antibody (MAb) CC49 is a second-generation murine IgG1 which has improved localization properties over its predecessor, MAb B72.3, and has been studied in a number of patients. In order to determine the pharmacokinetics of iodine-125 (125I) CC49 MAb, size-exclusion, high-performance liquid chromatography (HPLC) was used to assess radioactive components in serum and urine following administration of the drug to colon cancer patients. METHODS: Five patients received an intravenous infusion of 10 mg of MAb CC49 labeled with 2 mCi 125I. Following infusion, serum and urine specimens were collected from patients at predetermined time intervals prior to surgery. HPLC analysis of these specimens was completed to determine the radioactive species in each sample. RESULTS: Serum and urine specimens showed that serum levels of CC49 decrease exponentially and become unmeasurable by day 14 (half-life 1.89 days, +/- 0.19), with a steady, low-level of free 125I measurable in postinjection serum until day 21 after infusion. There was no evidence of MAb fragmentation or antibody:antigen (Ab:Ag) complex formation in serum, and no evidence of whole MAb, F(ab')2, or Fab fragment excretion in urine. Preinjection sera with MAb added in vitro also failed to demonstrate Ab:Ag complex formation. Analysis of urine showed low level excretion of free 125I which peaked by day 1 and declined exponentially through day 21, with a very low molecular weight (< 1 kDa) MAb fragment excreted in urine between 1 and 21 days. CONCLUSION: Radioiodinated 125I CC49 MAb remains in serum of cancer patients approximately 14 days, and tissue radioactivity beyond this time may reflect tissue sequestered MAb and/or free 125I and not "bloo pool" radioactivity. CC49 MAb appears to be deiodinated in small but significant quantities before it is metabolized, and clearance of radioactivity is mainly in free 125I form in urine. Measurable quantities of a < 1 Kda MAb fragment in urine and not serum may suggest a renal mechanism of MAb metabolism, but may also represent a metabolic end product of MAb metabolism with a very short serum half-life (T1/2) which accumulates in urine.

Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx.

This study examined muscle fiber-type alterations after single or multiple botulinum toxin (BT) injections to better understand possible morphologic changes induced by therapeutic BT injections in patients with spasmodic dysphonia. Muscle fiber staining was accomplished in rat intrinsic laryngeal muscles with antibodies to specific myosin heavy chains. Results indicated that the typical baseline distributions of type II muscle fibers (ie, types IIa, IIb, IIx, and IIL) were altered by BT injection, while no change was observed in type I fibers. Embryonic fibers were observed only along the needle insertion site at 7 days post BT injection. Although inferences from these animal data to human neuromuscular function must be made with caution, our findings provide insight into the possible cellular and molecular changes characterizing BT-injected muscles.

Aortobronchial fistula after expandable metal stent insertion for pediatric bronchomalacia.

Indications for using expandable metal stents (EMS) for airway disease have expanded considerably during the past decade. Complications have been infrequent but can be potentially life threatening. There are four reported instances of vascular bronchial fistula after Gianturco EMS insertion for managing airway disease in adults. The authors report a case of an aortobronchial fistula in a pediatric patient after Palmaz EMS insertion for treatment of bronchomalacia. A 14-year-old boy with severe scoliosis underwent left mainstem bronchus insertion of two Palmaz stents in tandem for correction of complete bronchial obstruction caused by vascular compression. Three weeks later fatal hemoptysis from an aortobronchial fistula developed. Elective EMS insertion for treatment of airway obstruction secondary to compression by vascular structures should be approached with caution. EMS placement should be reserved for situations in which there is no other reasonable surgical alternative.

Ultrasonography incorrectly diagnoses gallbladder polyps.

To determine the accuracy of ultrasound-diagnosed polypoid lesions of the gallbladder in their institution, the authors reviewed the records of 41 patients with polypoid lesions of the gallbladder who underwent cholecystectomy, and collected data concerning age, sex, symptoms, and histopathologic diagnosis. Histopathologic evaluation confirmed polyps in only two patients (4.9%) categorized as having polypoid lesions of the gallbladder. Most specimens from patients with ultrasonography reports suggesting small polyps manifested cholesterolosis (17 of 41) or cholelithiasis (15 of 41). No specimen harbored malignancy. Mean patient age was 47.4 years, and the most common symptoms were pain (85%), nausea (44%), vomiting (29%), and abnormal liver function test results (14%). The accuracy of sonography for diagnosing polypoid lesions of the gallbladder was poor. Many of the small polyps seen on sonography most likely represented a stone embedded in the gallbladder wall or other abnormality. Because of the likelihood of cholelithiasis, the authors recommend that patients with biliary symptoms and ultrasonography findings suggesting polypoid lesions of the gallbladder undergo cholecystectomy.