ABSTRACT
BACKGROUND: Frailty is a multidimensional state of increased vulnerability. Frail patients are at increased risk for poor surgical outcomes. Prior research demonstrates that rehabilitation strategies deployed after surgery improve outcomes by building strength. OBJECTIVES: Examine the feasibility and impact of a novel, multi-faceted prehabilitation intervention for frail patients before surgery. DESIGN: Single arm clinical trial. SETTING: Veterans Affairs hospital. PARTICIPANTS: Patients preparing for major abdominal, urological, thoracic, or cardiac surgery with frailty identified as a Risk Analysis Index≥30. INTERVENTION: Prehabilitation started in a supervised setting to establish safety and then transitioned to home-based exercise with weekly telephone coaching by exercise physiologists. Prehabilitation included (a)strength and coordination training; (b)respiratory muscle training (IMT); (c)aerobic conditioning; and (d)nutritional coaching and supplementation. Prehabilitation length was tailored to the 4-6 week time lag typically preceding each participant's normally scheduled surgery. MEASUREMENTS: Functional performance and patient surveys were assessed at baseline, every other week during prehabilitation, and then 30 and 90 days after surgery. Within-person changes were estimated using linear mixed models. RESULTS: 43 patients completed baseline assessments; 36(84%) completed a median 5(range 3-10) weeks of prehabilitation before surgery; 32(74%) were retained through 90-day follow-up. Baseline function was relatively low. Exercise logs show participants completed 94% of supervised exercise, 78% of prescribed IMT and 74% of home-based exercise. Between baseline and day of surgery, timed-up-and-go decreased 2.3 seconds, gait speed increased 0.1 meters/second, six-minute walk test increased 41.7 meters, and the time to complete 5 chair rises decreased 1.6 seconds(all P≤0.007). Maximum and mean inspiratory and expiratory pressures increased 4.5, 7.3, 14.1 and 13.5 centimeters of water, respectively(all P≤0.041). CONCLUSIONS: Prehabilitation is feasible before major surgery and achieves clinically meaningful improvements in functional performance that may impact postoperative outcomes and recovery. These data support rationale for a larger trial powered to detect differences in postoperative outcomes.
Subject(s)
Exercise Therapy , Frailty , Humans , Exercise Therapy/methods , Physical Functional Performance , Postoperative Complications , Preoperative Care/methods , Preoperative ExerciseSubject(s)
Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/therapy , Adrenal Cortex Hormones/administration & dosage , Adult , Antidepressive Agents/administration & dosage , Behavior Therapy/methods , Clinical Trials as Topic , Combined Modality Therapy , Evidence-Based Medicine , Fatigue Syndrome, Chronic/classification , Female , Humans , Male , Prognosis , Severity of Illness IndexABSTRACT
The surface-exposed antigens of Borrelia burgdorferi represent important targets for the development of a protective immune response. We have identified a proteinase K-accessible, 66-kDa protein from B. burgdorferi and have demonstrated that at least a portion of this protein is surface exposed. The 66-kDa protein was purified by sequential extraction of spirochetes with butanol and Triton X-114 followed by preparative gel electrophoresis. Polyclonal antibodies developed against the purified 66-kDa protein were Borrelia spp. specific, whereas a monoclonal antibody, Route 66, displayed a genospecies-specific pattern of recognition for the 66-kDa protein. N-terminal amino acid sequence was obtained from an internal fragment, a truncated version, and the full-length form of the 66-kDa protein. A search of protein and gene databases for homologous sequences yielded a match with the predicted amino acid sequence from a segment of B. burgdorferi chromosomal DNA (P. A. Rosa, D. Hogan, and T. G. Schwan, J. Clin. Microbiol. 29:524-532, 1991). The construction of primers based on this DNA sequence and the N-terminal amino acid sequence allowed the amplification and cloning of the 66-kDa-protein gene. The identity of the cloned gene was verified by the recognition of the expressed gene product by Route 66. Pulsed-field gel electrophoresis and Southern blot analysis were performed to confirm the chromosomal location of the 66-kDa-protein gene. This study describes the identification and cloning of the first chromosomally encoded, surface-exposed protein from B. burgdoferi.