Reduced Bacterial Burden of the Skin Surrounding the Shoulder Joint Following Topical Protocatechuic Acid Application: Results of a Pilot Study.

BACKGROUND: Reducing the rising health-care burden associated with shoulder surgical site infection (SSI) is of paramount importance. The purpose of this study was to investigate the antimicrobial efficacy of protocatechuic acid (PCA) as a topical reagent for surgical skin antisepsis surrounding the shoulder joint. METHODS: This was a 2-phase skin-disinfection trial involving the human shoulder. The shoulders of healthy volunteers were randomized to topical treatment with PCA (a 10% concentration of PCA in Phase I [11 subjects] and a 17% concentration in Phase II [12 subjects]), with a control of isopropyl alcohol (IPA) applied to the contralateral shoulder. Mechanical scraping was performed for skin harvest following reagent application, and samples were sent for aerobic and anaerobic culture. Sterilization rates and bacterial counts were determined for each treatment group, and the proportion of subjects with persistent Cutibacterium acnes colonization following topical application of PCA was determined using DNA sequencing analysis. RESULTS: The topical application of 10% PCA was associated with significantly higher aerobic and anaerobic sterilization rates (90.9% and 81.8%, respectively) compared with treatment with IPA (p = 0.0143 and p = 0.0253, respectively). The topical application of 17% PCA was associated with a significantly higher anaerobic sterilization rate (83.3%) and trended toward a significantly higher aerobic sterilization rate (91.7%) compared with treatment with IPA (p = 0.0143 and p = 0.083, respectively). C. acnes was identified in 18.2% and 0% of subjects following treatment with 10% and 17% PCA, respectively. CONCLUSIONS: The topical application of PCA was associated with a reduction in the bacterial burden of human shoulder skin and demonstrated dose-dependent antimicrobial activity against C. acnes in young, healthy subjects. Clinical studies in a shoulder surgical population are warranted to determine the potential for application in surgical skin antisepsis to reduce shoulder SSI. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Protocatechuic Acid as a Topical Antimicrobial for Surgical Skin Antisepsis: Preclinical Investigations.

BACKGROUND: There is a need for novel skin antiseptic agents to combat the health-care burdens associated with surgical site infection (SSI) and bacterial resistance. The purpose of this proof-of-principle pilot study was to investigate the potential of the phenolic compound protocatechuic acid (PCA) as a topical antimicrobial for surgical skin antisepsis. METHODS: The Kirby-Bauer method of disc diffusion was used to investigate the in vitro antimicrobial activity and comparative effectiveness of PCA and 7 related compounds against SSI pathogens. To explore the in vivo efficacy of topical PCA for providing deep, penetrating skin antisepsis, living Cutibacterium acnes was intradermally injected into the skin of female BALB/c mice. Mice were assigned to treatment with daily applications of topical PCA at 3 doses (78, 39, and 19.5 mM) or no treatment (n = 2 mice per group). After 96 hours, infected skin samples were harvested to compare mean C. acnes counts by treatment. RESULTS: Compared with other polyphenols, PCA demonstrated the broadest spectrum of antimicrobial activity against tested SSI pathogens, including drug-resistant organisms. At 96 hours following infection, the mean C. acnes burden in untreated mice was 6.65 log colony-forming units (CFUs) per gram of skin. Compared with the untreated group, daily topical application of 78 mM of PCA was associated with a significantly lower C. acnes CFU burden in mice skin (mean, 5.51 log CFUs per gram of skin; p = 0.0295). Both lower dosages of topical PCA failed to show an effect. CONCLUSIONS: PCA demonstrated laboratory efficacy against pathogens implicated in SSI, including drug-resistant organisms. In vivo, topical PCA demonstrated dose-dependent skin penetration and antimicrobial activity against mouse skin C. acnes loads. Human clinical studies exploring the antimicrobial efficacy of topical PCA for preoperative shoulder skin antisepsis are warranted. CLINICAL RELEVANCE: Topical PCA may have the potential to improve current shoulder SSI treatment and prevention protocols.

Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis.

BACKGROUND: Dextrose injection is reported to improve knee osteoarthritis (KOA)-related clinical outcomes, but its effect on articular cartilage is unknown. A chondrogenic effect of dextrose injection has been proposed. OBJECTIVE: To assess biological and clinical effects of intra-articular hypertonic dextrose injections (prolotherapy) in painful KOA. DESIGN: Case series with blinded arthroscopic evaluation before and after treatment. SETTING: Physical medicine and day surgery practice. PARTICIPANTS: Symptomatic KOA for at least 6 months, arthroscopy-confirmed medial compartment exposed subchondral bone, and temporary pain relief with intra-articular lidocaine injection. INTERVENTION: Four to 6 monthly 10-mL intra-articular injections with 12.5% dextrose. MAIN OUTCOME MEASURES: Visual cartilage growth assessment of 9 standardized medial condyle zones in each of 6 participants by 3 arthroscopy readers masked to pre-/postinjection status (total 54 zones evaluated per reader); biopsy of a cartilage growth area posttreatment, evaluated using hematoxylin and eosin and Safranin-O stains, quantitative polarized light microscopy, and immunohistologic cartilage typing; self-reported knee specific quality of life using the Western Ontario McMaster University Osteoarthritis Index (WOMAC, 0-100 points). RESULTS: Six participants (1 female and 5 male) with median age of 71 years, WOMAC composite score of 57.5 points, and a 9-year pain duration received a median of 6 dextrose injections and follow-up arthroscopy at 7.75 months (range 4.5-9.5 months). In 19 of 54 zone comparisons, all 3 readers agreed that the posttreatment zone showed cartilage growth compared with the pretreatment zone. Biopsy specimens showed metabolically active cartilage with variable cellular organization, fiber parallelism, and cartilage typing patterns consistent with fibro- and hyaline-like cartilage. Compared with baseline status, the median WOMAC score improved 13 points (P = .013). Self-limited soreness after methylene blue instillation was noted. CONCLUSIONS: Positive clinical and chondrogenic effects were seen after prolotherapy with hypertonic dextrose injection in participants with symptomatic grade IV KOA, suggesting disease-modifying effects and the need for confirmation in controlled studies. Minimally invasive arthroscopy (single-compartment, single-portal) enabled collection of robust intra-articular data. LEVEL OF EVIDENCE: IV.

A Novel Quantitative Pain Assessment Instrument That Provides Means of Comparing Patient's Pain Magnitude With a Measurement of Their Pain Tolerance.

BACKGROUND: Traditional pain assessment instruments are subjective in nature. They are limited to subjective reporting of the presence and magnitude of pain. There is no means of validating their response or assessing their pain tolerance. The objective of this study was to determine the potential value of a novel addition to the traditional physical examination concerning a patient's pain and more importantly their pain tolerance. METHODS: Extensive preliminary data were collected on 359 consecutive private practice knee patients referable the subject's pain, including the magnitude, the most pain ever experienced, and their opinion of personal pain tolerance. The novel evaluation included physical testing of a series of small ball drops through a vertical tube from various fixed levels on the index finger and patella. The patient's response to this impact testing provided quantitative information, from which a comparison was made to their pain opinion and also to that of other patients with similar demographics. RESULTS: Nine percent of the patients rated their pain tolerance below the midpoint on the visual analog scale. Seventy-one percent thought they were above the midpoint on the scale in regards to pain tolerance. There were discrepancies in both directions between the subject's opinion on pain tolerance and their rating of their pain experience to the ball drop testing. Twenty-eight percent of the entire patient group rated themselves above 5 on tolerance, but experienced above the average discomfort compared to other subjects reporting on the finger impact testing. CONCLUSIONS: This report introduces a novel method for collecting data concerning pain that can be subjected to quantification. The database included quantitative measures providing the opportunity to confirm, validate or refute the patient's assertions concerning pain magnitude and tolerance. This method is best described as a patient pain profile. It has the potential to give both the patient and the physician quantified objective information rendering insight not otherwise available.

The Long-Term Clinical Outcomes Following Autogenous Bone Grafting for Large-Volume Defects of the Knee: 12- to 21-Year Follow-Up.

OBJECTIVE: We report the long-term clinical outcomes of patients who underwent autogenous bone grafting of large-volume osteochondral defects of the knee due to osteochondritis dessicans (OCD) and osteonecrosis (ON). This is the companion report to one previous published on the biological response. We hypothesized that these grafts would integrate with host bone and the articular surface would form fibrocartilage providing an enduring clinical benefit. DESIGN: Three groups (patients/knees) were studied: OCD without a fragment (n = 12/13), OCD with a partial fragment (n = 14/16), and ON (n = 25/26). Twenty-five of 52 patients were available for clinical follow-up between 12 and 21 years. Electronic medical records provided comparison clinical information. In addition, there were plain film radiographs, MRIs, plus repeat arthroscopy and biopsy on 14 patients. RESULTS: Autogenous bone grafts integrated with the host bone. MRI showed soft tissue covering all the grafts at long-term follow-up. Biopsy showed initial surface fibrocartilage that subsequently converted to fibrocartilage and hyaline cartilage at 20 years. OCD patients had better clinical outcomes than ON patients. No OCD patients were asymptomatic at anytime following surgery. Half of the ON patients came to total knee replacement within 10 years. CONCLUSIONS: Autogenous bone grafting provides an alternative biological matrix to fill large-volume defects in the knee as a singular solution integrating with host bone and providing an enduring articular cartilage surface. The procedure is best suited for those with OCD. The treatment for large-volume articular defects by this method remains salvage in nature and palliative in outcome.

The Biological Response following Autogenous Bone Grafting for Large-Volume Defects of the Knee: Index Surgery through 12 to 21 Years' Follow-up.

OBJECTIVE: This report focuses on the biological events occurring at various intervals following autogenous bone grafting of large-volume defects of the knee joint's femoral condyle secondary to osteochondritis dissecans (OCD) or osteonecrosis (ON). It was hypothesized that the autogenous bone graft would integrate and the portion exposed to the articular surface would form fibrocartilage, which would endure for years. METHODS: Between September 29, 1987 and August 8, 1994, there were 51 patients treated with autogenous bone grafting for large-volume osteochondral defects. Twenty-five of the 51 patients were available for long-term follow-up up to 21 years. Patient follow-up was accomplished by clinical opportunity and intentional research. Videotapes were available on all index surgeries for review and comparison. All had preoperative and postoperative plain film radiographs. Long-term follow-up included MRI up to 21 years. Second-look arthroscopy and biopsy were obtained on 14 patients between 8 weeks and 20 years. RESULTS: Radiological assessment showed the autogenous bone grafts integrated with the host bone. The grafts retained the physical geometry of the original placement. MRI showed soft tissue covering the grafts in all cases at long-term follow-up. Interval biopsy showed the surface covered with fibrous tissue at 8 weeks and subsequently converted to fibrocartilage with hyaline cartilage at 20 years. CONCLUSION: Autogenous bone grafting provides a matrix for large osteochondral defects that integrates with the host bone and results in a surface repair of fibrocartilage and hyaline cartilage that can endure for up to 20 years.

The pathology of the end-stage osteoarthritic lesion of the knee: potential role in cartilage repair.

The purpose was to explore whether there were any pathological characteristics of the end-stage osteoarthritic sclerotic lesion that have potential to participate in cartilage repair. Specimens harvested following total knee surgery were examined for gross pathology including staining with Safranin O. Multiple small sections of the lesion were placed in tissue culture for 6 weeks. Gross examination and photographic documentation was made at 3 and 6 weeks. At 6 weeks the specimens from culture were subject to histological examination. The pathology of the end-stage osteoarthritic lesion showed sclerotic bone, dead osteons, hypervascularity and scattered cartilaginous aggregates. Additional observations showed multiple pitting on the sclerotic surface, which histologically was related to three events; fragmentation of dead bone, ruptured blood vessels, and eroded aggregates. There were no pathological or biological changes in the specimens following the time in tissue culture. The in-depth pathological evaluation showed the end-stage osteoarthritic lesion to have certain features with potential to facilitate cartilage repair. The cartilaginous aggregates may be a participant in cartilage repair following surgery. The cartilaginous aggregates remained unchanged in the tissue culture absent the normal synovial joint chemical and physical environment and therefore further testing with a different experimental model would be necessary to establish these aggregates as a source of cartilage regeneration. The multiple small depressions in this lesion may have potential to be a "home" for therapeutics.

Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: histomorphometric study of PRG4 distribution in osteoarthritic cartilage.

The objective of this study was to identify and characterize cartilaginous deposits aggregates in the subchondral bone in areas of the human osteoarthritic knee with exposed bone. A specific aim was to determine the distribution of the joint lubrication molecule, lubricin/superficial zone protein [referred to by its gene, proteoglycan4 (PRG4)], in these cartilaginous deposits and in osteoarthritic cartilage. This work was carried out in the context of assessing the potential contribution of these chondrocyte aggregates for joint resurfacing in certain cartilage repair procedures. The discarded bone cuts of femoral condyles and tibial plateaus were collected from 11 patients with advanced osteoarthritis (OA) of the knee during total knee arthroplasty; 9 women and 2 men with a mean age of 68 years. Sections of paraffin-embedded tissue were stained with Safranin-O, and with antibodies to type II collagen, alpha-smooth muscle actin (SMA), and PRG4. Chondrocyte aggregates were found in the subchondral bone of regions of exposed bone in sections from five individuals. The average diameter of cartilaginous aggregates was 152 microm, and the average depth of the aggregates below the surface was about 475 microm. Most aggregates were fibrocartilaginous and stained positive for type II collagen. Of interest was the finding that the cartilaginous deposits and osteoarthritic cartilage contained PRG4. Only a small percentage of chondrocytes stained positive for SMA. Cartilaginous deposits containing chondrocyte aggregates exist in subchondral bone in regions of exposed bone in some patients with advanced OA of the knee. These cells may be able to contribute to the resurfacing of the joint in certain cartilage repair procedures.

An introduction to mountain search and rescue.

Alpine search and rescue teams must perform each incident response safely. To do so requires experience, organizational skills, technical training, and ability. In addition, teams should interface with emergency medical control advisors who are familiar with local terrain, mountain rescue operations, and the evacuation techniques employed. To facilitate safety and organization, each mission can be divided into four linked stages: location, reach, stabilize, and evacuate.

Taking medicine back: Dx and Rx for orthopedic surgeons.

The present day practice of medicine is cause of considerable malaise for physicians. This article will invoke the ancient proverb, "Physician Treat Thyself". In other words this article addresses the problems from a diagnostic and therapeutic perspective, working toward a permanent cure. The history of medical practice groups, in-office surgery, and ancillary services is reviewed. The co-morbidity of health maintenance organizations, Evaluation and Management requirements, and cost shifting are mentioned. Finally a list of symptoms and the appropriate therapeutic measures are administered to control costs, increase income, and re-establish some form of authority in the practice of medicine.