Porin Loss Impacts the Host Inflammatory Response to Outer Membrane Vesicles of Klebsiella pneumoniae

Antibiotic-resistant strains of Klebsiella pneumoniae often exhibit porin loss. In this study, we investigated how porin loss impacted the composition of secreted outer membrane vesicles as well as their ability to trigger proinflammatory cytokine secretion by macrophages. We hypothesize that porin loss associated with antibiotic resistance will directly impact both the composition of outer membrane vesicles and their interactions with phagocytic cells. Using clonally related clinical isolates of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae with different patterns of porin expression, we demonstrated that altered expression of OmpK35 and OmpK36 results in broad alterations to the protein profile of secreted vesicles. Additionally, the level of OmpA incorporation was elevated in strains lacking a single porin. Porin loss significantly impacted macrophage inflammatory responses to purified vesicles. Outer membrane vesicles lacking both OmpK35 and OmpK36 elicited significantly lower levels of proinflammatory cytokine secretion than vesicles from strains expressing one or both porins. These data demonstrate that antibiotic resistance-associated porin loss has a broad and significant effect on both the composition of outer membrane vesicles and their interactions with phagocytic cells, which may impact bacterial survival and inflammatory reactions in the host.     

Metabolic Surgery for the Treatment of Type 2 Diabetes in Patients with BMI <35 kg/m<Superscript>2</Superscript>: An Integrative Review of Early Studies

Type 2 diabetes mellitus (T2DM) resolution in morbidly obese patients following metabolic surgery suggests the efficacy of T2DM surgery in non-morbidly obese patients (body mass index [BMI] <35 kg/m²). This literature review examined research articles in English over the last 30 years (1979–2009) that addressed surgical resolution of T2DM in patients with a mean BMI <35. Weighted and simple means (95% CI) were calculated to analyze study outcomes. Sixteen studies met inclusion criteria; 343 patients underwent one of eight procedures with 6–216 months follow-up. Patients lost a clinically meaningful, not excessive, amount of weight (from BMI 29.4 to 24.2; −5.1), moving from the overweight into the normal weight category. There were 85.3% patients who were off T2DM medications with fasting plasma glucose approaching normal (105.2 mg/dL, −93.3), and normal glycated hemoglobin, 6% (−2.7). In subgroup comparison, BMI reduction and T2DM resolution were greatest following malabsorptive/restrictive procedures, and in the preoperatively mildly obese (30.0–35.0) vs overweight (25.0–25.9) BMI ranges. Complications were few with low operative mortality (0.29%). Novel and/or known mechanisms of T2DM resolution may be engaged by surgery at a BMI threshold ≤30. The majority of low-BMI patients experienced resolution of laboratory and clinical manifestations of T2DM without inappropriate weight loss.     

Patterns of readmission and reoperation within 90 days after Roux-en-Y gastric bypass

BackgroundHealth insurance payors harbor concerns regarding the cost of bariatric procedures that are chiefly related to early readmissions and reoperations. We have attempted to identify the avoidable causes of readmission.MethodsWe retrospectively reviewed the indications for short-term (<90-d) emergency department (ED) visits, readmissions, and reoperations from August 2004 through May 2007 for patients undergoing primary Roux-en-Y gastric bypass (RYGB) for morbid obesity at a tertiary care teaching hospital. The electronic medical record of the primary hospital was reviewed, as well as the electronic medical records of 9 local hospitals serving the area, allowing the incorporation of data from 35 locoregional hospitals.ResultsA total of 1222 consecutive patients underwent RYGB, 1051 laparoscopically. Of these 1222 patients, 173 had 252 ED visits, readmissions, and/or reoperations; 147 (58%) visits were to the primary institution and 105 (42%) occurred at a local or regional hospital. No age difference was found between the patients who underwent ED visits, hospital readmissions, or reoperations and those who did not (mean age 43 yr for both groups, P > .05). Patients who were seen in the ED, readmitted to the hospital, or underwent reoperation had had a greater body mass index (50 kg/m² versus 48 kg/m², P = .001). On average, the readmissions occurred 27.3 days (range 2–88) postoperatively, and the mean hospital length of stay for readmitted patients was 3.3 days (range 1–16). Patients who presented for ED visits, readmission, or reoperations were more likely to have undergone open RYGB than laparoscopic RYGB (P = .002). The <90-day all-cause ED visit, readmission, and reoperation rate was 21% (n = 252). Considering all 1222 patients, the incidence of nausea, vomiting, and dehydration, abdominal pain, and wound issues was 5% (n = 65), 4% (n = 50), and 2% (n = 21), respectively. Considering only the 173 patients with ED visits, readmissions, or reoperations (n = 252), the admitting diagnosis was nausea, vomiting, and dehydration in 26%, abdominal pain in 20%, and wound issues in 8%. The unemployed, disabled, or retired were more likely to have been seen in the ED or readmitted compared with the employed, nondisabled, or not retired (P = .01).ConclusionA considerable number of patients are affected by nausea, vomiting, and dehydration, abdominal pain, and wound issues <90 days postoperatively. Socioeconomic and functional status might have an effect on the rate of ED visits and readmissions. By ensuring that the appropriate outpatient mechanisms for management of these problems are available, early ED visits and readmission rates should significantly decrease.     

Single-center experience with the On-X prosthetic heart valve between 1996 and 2005

BACKGROUND AND AIM OF THE STUDY: Herein are presented long-term results for the On-X mechanical heart valve. All On-X heart valve recipients since the first implantation worldwide at the University of Bochum in September 1996 were followed retrospectively; the present authors' single-center experience over a period of almost 10 years is reported. METHODS: A total of 428 patients (255 males, 173 females; mean age 62.7 years) underwent either aortic valve replacement (AVR; n = 264) or mitral valve replacement (MVR; n = 164) using the On-X prosthesis. Preoperatively, 329 patients (76.8%) were in NYHA class III or IV. Approximately 5% of AVR and 23% of MVR patients had undergone previous cardiac surgery. Concomitant surgery was performed in 189 patients (44.2%). The mean follow up was 3.9 years, and cumulative follow up 1,625 patient-years (pt-yr); the overall follow up rate was 98.7%. RESULTS: Early mortality (< or = 30 days) was 3.7% after AVR and 14.0% after MVR, with valve-related mortality rates of 0.4% and 1.2%, respectively. At autopsy (n = 12) all implants were intact. Freedom from valve-related death at nine years was 85.0 +/- 3.9% after AVR and 87.6 +/- 3.2% after MVR. The overall survival rate was 67.9 +/- 4.3% after AVR and 52.7 +/- 8.1% after MVR. The linearized rate of thromboembolism for AVR and MVR was 1.49%/pt-yr and 1.61%/pt-yr; of thrombosis 0%/pt-yr and 0.35%/pt-yr; of hemorrhage 0.93%/pt-yr and 1.43%/pt-yr; of endocarditis 0.37%/pt-yr and 0.17%/pt-yr; of non-structural failure 0.18%/pt-yr and 1.43%/pt-yr; and of reoperation 0.28%/pt-yr and 0.53%/pt-yr. There were no cases of structural valve failure. CONCLUSION: After almost one decade of clinical experience in a single center, the On-X heart valve continues to be reliable and effective.     

Improvements in motor and non-motor symptoms in parkinson patients under ropinirole therapy

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.     

Feeling Bad in More Ways than One: Comorbidity Patterns of Medically Unexplained and Psychiatric Conditions

BACKGROUND: Considerable overlap in symptoms and disease comorbidity has been noted among medically unexplained and psychiatric conditions seen in the primary care setting, such as chronic fatigue syndrome, low back pain, irritable bowel syndrome, chronic tension headache, fibromyalgia, temporomandibular joint disorder, major depression, panic attacks, and posttraumatic stress disorder. OBJECTIVE: To examine interrelationships among these 9 conditions. DESIGN: Using data from a cross-sectional survey, we described associations and used latent class analysis to investigate complex interrelationships. PARTICIPANTS: 3,982 twins from the University of Washington Twin Registry. MEASUREMENTS: Twins self-reported a doctor's diagnosis of the conditions. RESULTS: Comorbidity among these 9 conditions far exceeded chance expectations; 31 of 36 associations were significant. Latent class analysis yielded a 4-class solution. Class I (2% prevalence) had high frequencies of each of the 9 conditions. Class II (8% prevalence) had high proportions of multiple psychiatric diagnoses. Class III (17% prevalence) participants reported high proportions of depression, low back pain, and headache. Participants in class IV (73% prevalence) were generally healthy. Class I participants had the poorest markers of health status. CONCLUSIONS: These results support theories suggesting that medically unexplained conditions share a common etiology. Understanding patterns of comorbidity can help clinicians care for challenging patients.     

Anti-ganglioside antibodies alter presynaptic release and calcium influx

Acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti-ganglioside mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody-mediated muscle weakness in AMAN.     

Adipokine response in diabetics and nondiabetics following the Roux-en-Y gastric bypass: a preliminary study

INTRODUCTION: The adipocyte influences eating behavior and metabolism via cytokine secretion. We report our findings of adipokine secretion in a cohort of diabetic and nondiabetic morbidly obese patients before and after Roux-en-Y gastric bypass (RYGB). METHODS: Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: five were diabetic and nine were female. Nonfasting plasma levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha were determined preoperatively and 6 mo postoperatively. C-reactive protein (CRP) was followed as a marker of the metabolic syndrome. RESULTS: The patient age was 42 +/- 11 y, and the preoperative BMI was 50 +/- 6 kg/m(2). The 6 mo BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In nondiabetic patients, there were significant increases compared with preoperative levels for adiponectin, resistin, and tumor necrosis factor-alpha; leptin was significantly decreased while CRP was unchanged. CRP and leptin levels were both significantly lower (P < 0.05), while all other protein levels were unchanged in diabetic patients. CONCLUSIONS: At 6 mo postoperation, RYGB significantly altered most adipokine levels for nondiabetic patients. Only CRP and leptin were changed in diabetic patients. All patients lost a significant amount of weight over 6 mo, suggesting a different metabolic effect between nondiabetic and diabetic patients after RYGB.