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Ryan S D’Souza,1 Yeng F Her,1 Nasir Hussain,2 Jay Karri,3 Michael E Schatman,4 Aaron K Calodney,5 Christopher Lam,6 Thomas Buchheit,7 Brennan J Boettcher,8 George C Chang Chien,9 Scott G Pritzlaff,10 Christopher Centeno,11 Shane A Shapiro,12 Johana Klasova,1 Jay S Grider,13 Ryan Hubbard,14 Eliana Ege,15 Shelby Johnson,8 Max H Epstein,16 Eva Kubrova,8 Mohamed Ehab Ramadan,17 Alexandra Michelle Moreira,18 Swarnima Vardhan,19 Yashar Eshraghi,20 Saba Javed,21 Newaj M Abdullah,22 Paul J Christo,17 Sudhir Diwan,23 Leslie C Hassett,24 Dawood Sayed,6 Timothy R Deer25 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesiology, The Ohio State Wexner Medical Center, Columbus, OH, USA; 3Departments of Orthopedic Surgery and Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Anesthesiology, Perioperative Care, & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Precision Spine Care, Tyler, TX, USA; 6Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 7Department of Anesthesiology, Duke University, Durham, NC, USA; 8Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 9Department of Regenerative Medicine, GCC Institute, Torrance, CA, USA; 10Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 11Centeno-Schultz Clinic, Broomfield, CO, USA; 12Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, USA; 13Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, KY, USA; 14Department of Sports Medicine, Anderson Orthopedic Clinic, Arlington, VA, USA; 15Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 16Department of Physical Medicine & Rehabilitation, Harvard Medical School, Boston, MA, USA; 17Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA; 18Department of Physical Medicine & Rehabilitation, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 19Department of Internal Medicine, Yale New Haven Health – Bridgeport Hospital, Bridgeport, CT, USA; 20Department of Anesthesiology & Critical Care Medicine, Ochsner Health System, New Orleans, LA, USA; 21Department of Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 22Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 23Department of Pain Medicine, Advanced Spine on Park Avenue, New York City, NY, USA; 24Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA; 25Department of Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1-(507)-284-9696, Fax +1-(507)-266-7732, Email dsouza.ryan@mayo.eduPurpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of “disagree” or “abstain”, they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose–response associations, and comparative analysis between different injectable biologics.Keywords: regenerative medicine, injectable biologics, platelet-rich plasma, mesenchymal stem cell, bone marrow aspirate concentrate, pain medicine

Abstract Background Invasive cervical cancer is the commonest cause of cancer morbidity and mortality in South African women. This study provides information on adult women's sexual activity and cervical cancer risk in South Africa. Methods The data were derived from a case-control study of hormonal contraceptives and cervical cancer risk. Information on age of sexual debut and number of lifetime sexual partners was collected from 524 incident cases and 1541 hospital controls. Prevalence ratios and adjusted prevalence ratios were utilised to estimate risk in exposures considered common. Crude and adjusted relative risks were estimated where the outcome was uncommon, using multiple logistic regression analysis. Results The median age of sexual debut and number of sexual partners was 17 years and 2 respectively. Early sexual debut was associated with lower education, increased number of life time partners and alcohol use. Having a greater number of sexual partners was associated with younger sexual debut, being black, single, higher educational levels and alcohol use. The adjusted odds ratio for sexual debut < 16 years and ≥ 4 life-time sexual partners and cervical cancer risk were 1.6 (95% CI 1.2 – 2.2) and 1.7 (95% CI 1.2 – 2.2), respectively. Conclusion Lower socio-economic status, alcohol intake, and being single or black, appear to be determinants of increased sexual activity in South African women. Education had an ambiguous effect. As expected, cervical cancer risk is associated with increased sexual activity. Initiatives to encourage later commencement of sex, and limiting the number of sexual partners would have a favourable impact on risk of cancer of the cervix and other sexually transmitted infections

Abstract In a case-control study among 2064 South African women to investigate the risk of clinically invasive cancer of the cervix, we found a marked reduction in the risk of cervical cancer among women who gave a history of ever having undergone even a single Pap smear, and a statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received. HPV infections and their associated low-grade lesions commonly regress, indicating that most often there is an effective host immune response against HPV infection. We hypothesized that act of performing a Pap smear is associated with inflammatory responses at the site of trauma, the cervix, and that this inflammatory signalling may be an immunological factor initiating these productive anti-HPV responses. In the present study, a randomized controlled trial, we enrolled 80 healthy young women to investigate the impact of performing a Pap smear on cervical inflammation. Forty one women, in the intervention group, received a Pap smear at enrollment and cervicovaginal lavages (CVLs) were collected at baseline and 2 weeks later. Thirty nine women received no intervention at enrollment (control group) but CVLs were collected at enrolment and 2 weeks later. We assessed various markers of inflammation including IL-12 p70, TNF-α, IL-8, IL-6, IL-10, and IL-1β in CVL specimens. While CVL levels of IL-8, IL-1β and IL-6 remained unchanged following a Pap smear, markers of cell mediated immunity (IL-12 p70 and TNF-α) and T cell regulation (IL-10) were significantly elevated.

Abstract Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both major public health problems in South Africa. The aim of this study was to determine the risk of cervical pre-cancer and cancer among HIV positive women in South Africa. Methods Data were derived from a case-control study that examined the association between hormonal contraceptives and invasive cervical cancer. The study was conducted in the Western Cape (South Africa), from January 1998 to December 2001. There were 486 women with invasive cervical cancer, 103 control women with atypical squamous cells of undetermined significance (ASCUS), 53 with low-grade squamous intraepithelial lesions (LSIL), 50 with high-grade squamous intraepithelial lesions (HSIL) and 1159 with normal cytology. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression. Results The adjusted odds ratios associated with HIV infection were: 4.4 [95% CI (2.3 – 8.4) for ASCUS, 7.4 (3.5 – 15.7) for LSIL, 5.8 (2.4 – 13.6) for HSIL and 1.17 (0.75 – 1.85) for invasive cervical cancer. HIV positive women were nearly 5 times more likely to have high-risk human papillomavirus infection (HR-HPV) present compared to HIV negative women [OR 4.6 (95 % CI 2.8 – 7.5)]. Women infected with both HIV and high-risk HPV had a more than 40 fold higher risk of SIL than women infected with neither of these viruses. Conclusion HIV positive women were at an increased risk of cervical pre-cancer, but did not demonstrate an excess risk of invasive cervical cancer. An interaction between HIV and HR-HPV infection was demonstrated. Our findings underscore the importance of developing locally relevant screening and management guidelines for HIV positive women in South Africa.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face., Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups., Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP., Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The maximum possible earthquake related to gas production in Western Europe's largest gas field, Groningen, Netherlands, is an urgent practical question. Here we show how to distinguish between induced and triggered tectonic earthquakes. We estimate the maximum possible induced magnitude in the Groningen gas field to be around M w = 4. We extend the concept of the seismogenic index to gas-production, and calculate the worst-case probability of triggering a larger-magnitude tectonic earthquake in a continuum. The probability of a M w 5.5 earthquake at Groningen is significantly higher than at Pohang Geothermal System (South Korea), where a M w 5.5 earthquake was actually triggered. Due to a long history of production in Groningen, our model estimates that strong earthquakes (M w ≥ 4) must have occurred there several times, in disagreement with the observations. This indicates that the Groningen gas field is inherently stable and the physical conditions to trigger large tectonic earthquakes likely do not exist., (© 2024. The Author(s).)

Orthobiologic therapies show significant promise to improve outcomes for patients with musculoskeletal pathology. There are considerable research efforts to develop strategies that seek to modulate the biological environment to promote tissue regeneration and healing and/or provide symptomatic relief. However, the regulatory pathways overseeing the clinical translation of these therapies are complex, with considerable worldwide variation. The introduction of novel biologic treatments into clinical practice raises several ethical dilemmas. In this review, we describe the process for seeking approval for biologic therapies in the United States, Europe, and Japan. We highlight a number of ethical issues raised by the clinical translation of these treatments, including the design of clinical trials, monitoring outcomes, biobanking, "off-label" use, engagement with the public, marketing of unproven therapies, and scientific integrity., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the Orthoregeneration Network. J.C. has received education payments from Arthrex and Smith & Nephew; consulting fees from DePuy, Linvatec, and Smith & Nephew; speaking fees from Linvatec; and hospitality payments from Medical Device Business Services, Medwest, and Stryker. N.S.P. has received research support from Zimmer Biomet Holdings and RegenLab. R.M.F. has received grant support from Arthrex, education payments from Arthrex and Smith & Nephew, nonconsulting fees from Arthrex, and hospitality payments from Joint Restoration Foundation. J.H. has received education payments from Gemini Mountain. B.M. has received speaking fees from Arthrex and consulting fees from Arthrex, Biomarin Pharmaceutical, DePuy, and Exactech. J.L.D. has received grant support from Terumo BCT; consulting fees from Arthrex, Bioventus, DePuy, RTI Surgical, and Zimmer; and nonconsulting fees from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Background: The application of orthobiologics at the time of arthroscopic rotator cuff repair (RCR) has received an increasing amount of clinical interest despite a relative scarcity of human clinical studies on their efficacy., Purpose: To utilize a national administrative database to determine the association of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) applied at the time of RCR with revision surgery rates., Study Design: Cohort study; Level of evidence, 3., Methods: The Mariner data set from the PearlDiver patient records repository was utilized to identify patients undergoing RCR using Current Procedural Terminology (CPT) code 29827. Patients receiving BMAC or PRP at the time of RCR were then identified using CPT coding. For comparison purposes, a matched cohort was created consisting of patients who underwent RCR without biologic augmentation in a 5:1 fashion for each biologic separately. Cases were matched according to age, sex, tobacco use, biceps tenodesis, distal clavicle excision, and subacromial decompression. All groups were then queried for revision RCR or conversion to reverse shoulder arthroplasty. Revision rates were compared utilizing a multivariate binomial logistic regression analysis. Adjusted odds ratios (ORs) and 95% CIs were calculated., Results: A total of 760 patients who underwent biologic augmentation during RCR were identified, including 646 patients in the PRP group and 114 patients in the BMAC group. They were compared with 3800 matched controls without documented biologic application at the time of surgery. Compared with matched controls, patients who received BMAC at the time of surgery experienced a significantly lower incidence of revision surgery at 2 years (OR, 0.36; 95% CI, 0.15-0.82; P = .015). There was no significant difference in revision rates between PRP and matched controls (OR, 0.87; 95% CI, 0.62-1.23; P = .183)., Conclusion: The application of BMAC at the time of RCR was associated with a significant decrease in the incidence of revision surgery. There was no apparent effect of PRP on the incidence of revision surgery after primary RCR. Higher-level clinical studies considering surgical factors are needed to more clearly define the role of biologic adjuvants in RCR., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: B.S.S. has received education payments from Arthrex, consulting fees from Exactech, and honoraria from Encore Medical. B.C.W. has received education payments, consulting fees, and speaking fees from Arthrex and hospitality payments from Integra LifeSciences. C.C. has received nonconsulting fees from Arthrex. P.C. has received education payments from Active Medical, consulting fees from DePuy/Medical Device Business Services, and nonconsulting fees from Arthrex. J.C. has received research support from Arthrex, education payments from Arthrex and Smith & Nephew, and hospitality payments from Medical Device Business Services and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Despite patient demand for stem cell therapies (SCTs) for musculoskeletal conditions, there remains limited research on why patients seek SCTs or their sources of information. We employ three questions into a consult intake form: (1) Why are you interested in stem cell treatment for your condition? (2) How did you find out about stem cell treatment for your condition? (3) Have you contacted a stem cell clinic? Responses analyzed, using a qualitative content analysis approach to identify themes reveal many patients seek SCTs to treat pain or delay surgery which may align with some current clinical evidence while other patients express motivations as expected outcomes (e.g., SCTs are better than standard of care or can regenerate tissue) which are not supported by current medical evidence. These differences suggests that patient-centered counseling may help patients by addressing misconceptions and increasing health literacy about expected outcomes of SCTs for treating musculoskeletal conditions., (© 2022. The Author(s).)

Introduction: Direct to consumer stem cell and regenerative interventions (SCRIs) for various medical conditions have increased in popularity due to unmet medical needs and the promise of SCRIs to meet those needs. These interventions may have varying levels of safety and efficacy data and many lack sufficient scientific data to be marketed. The direct to consumer SCRI industry has received significant attention due to potential physical, economic, and emotional harms to patients. Patients may seek the counsel of their primary care providers when considering stem cell therapy for their condition., Methods: Here we describe strategies primary care providers can utilize when counseling patients., Results: Although we recommend constructing these discussions around individual patients' needs, one can utilize a general approach consisting of 4 parts. First, providers should recognize what information the patient is seeking and what is their understanding of stem cell and regenerative medicine. Next, providers should convey evidence-based information at the level of patients understanding so that they are aware of the risks, benefits, and descriptions of possible procedures. Throughout the conversations, attempts should be made to guide patients to a trusted resource that can provide additional information. Finally, providers should make an effort to address misinformation in a way that is nonjudgmental and patient-centered to make the patient feel safe and comfortable., Conclusion: Effectively communicating risk information by primary care providers to patients is important given the harms reported from direct-to-consumer SCRIs. Correcting misinformation remains a priority when discussing SCRI's. Providers should strive to offer patients with additional resources such as the opportunity for consultation with a specialist or a consultation service dedicated to informing patients about regenerative medicine.

Seismicity associated with subsurface operations is a major societal concern. It is therefore critical to improve predictions of the induced seismic hazard. Current statistical approaches account for the physics of pore pressure increase only. Here, we present a novel mathematical model that generalises adopted statistics for use in arbitrary injection/production protocols and applies to arbitrary physical processes. In our model, seismicity is driven by a normalised integral over the spatial reservoir volume of induced variations in frictional Coulomb stress, which-combined with the seismogenic index-provides a dimensionless proxy of the induced seismic hazard. Our model incorporates the classical pressure diffusion based and poroelastic seismogenic index models as special cases. Applying our approach to modeling geothermal systems, we find that seismicity rates are sensitive to imposed fluid-pressure rates, temperature variations, and tectonic conditions. We further demonstrate that a controlled injection protocol can decrease the induced seismic risk and that thermo-poroelastic stress transfer results in a larger spatial seismic footprint and in higher-magnitude events than does direct pore pressure impact for the same amount of injected volume and hydraulic energy. Our results, validated against field observations, showcase the relevance of the novel approach to forecast seismic hazards induced by subsurface activities., (© 2021. The Author(s).)

Objective: To explore the experiences, approaches, and challenges of physicians consulting patients about experimental stem cell and regenerative medicine interventions (SCRIs)., Participants and Methods: From August 21, 2018, through July 30, 2019, semistructured interviews of 25 specialists in cardiology, ophthalmology, orthopedics, pulmonology, and neurology were conducted and qualitatively analyzed using modified grounded theory., Results: All specialists used informational approaches to counsel patients, especially orthopedists. Informational approaches included explaining stem cell science, sharing risks, and providing principles. Several specialists also used relational counseling approaches including emphasizing that physicians want what is best for patients, acknowledging suffering, reassuring continued care, empathizing with patients and families, and underscoring that patients have the final decision. Many specialists reported being comfortable with the conversation, although some were less comfortable and several noted challenges in the consultation including wanting to support a patient's decision but worrying about harms from unproven SCRIs, navigating family pressure, and addressing stem cell hype and unrealistic expectations. Specialists also desired that additional resources be available for them and patients., Conclusion: Physicians relied more heavily on providing patients with information about SCRIs than using relational counseling approaches. Efforts should be directed at helping physicians address the informational and relational needs of patients, including providing tools and resources that inform physicians about the unproven SCRI industry, building skills in empathic communication, and the creation and dissemination of evidence-based resources to offer patients., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

A damaging Mw5.5 earthquake occurred at Pohang, South Korea, in 2017, after stimulating an enhanced geothermal system by borehole fluid injections. The earthquake was likely triggered by these operations. Current approaches for predicting maximum induced earthquake magnitude ([Formula: see text]) consider the volume of the injected fluid as the main controlling factor. However, these approaches are unsuccessful in predicting earthquakes, such as the Pohang one. Here we analyse the case histories of induced earthquakes, and find that [Formula: see text] scales with the logarithm of the elapsed time from the beginning of the fluid injection to the earthquake occurrence. This is also the case for the Pohang Earthquake. Its significant probability was predictable. These results validate an alternative to predicting [Formula: see text]. It is to monitor the exceedance probability of an assumed [Formula: see text] in real time by monitoring the seismogenic index, a quantity that characterizes the intensity of the fluid-induced seismicity per unit injected volume., (© 2021. The Author(s).)

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA., Competing Interests: One or more of the authors has declared a potential conflict of interest or source of funding: see supplemental material for details. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Here the authors report a case of complications occured after injection of a site enhancement oil in the upper extremity for cosmetic muscles' volume enhancement and a literature review on the topic. The medical and sports communities should be aware of the secondary effects of site enhancement oils use, which could bring to severe complications.

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.

Objective: Bone marrow aspiration and concentration (BMAC) is becoming a more common regenerative therapy for musculoskeletal pathology. In our current pilot study, we studied patients with mild-to-moderate bilateral knee osteoarthritis, compared pain at 12-month follow-up between BMAC-injected and saline-injected knees, and examined cartilage appearance measured by magnetic resonance imaging (MRI) T2 quantitative mapping., Design: Twenty-five patients with mild-to-moderate bilateral osteoarthritic knee pain were randomized to receive BMAC into one knee and saline placebo into the other. Bone marrow was aspirated from the iliac crests, concentrated in an automated centrifuge, combined with platelet-poor plasma for knee injection, and compared with saline injection into the contralateral knee. Primary outcome measures were T2 MRI cartilage mapping at 6-month and Visual Analog Scale and Osteoarthritis Research Society International Intermittent and Constant Osteoarthritis Pain scores and radiographs at 12-month follow-up., Results: Constant, intermittent, and overall knee pain remained significantly decreased from baseline at 12-month follow-up (all P ⩽ 0.01), with no apparent difference between BMAC- and saline-treated knees (all P ⩾ 0.54). A similar significant increase from baseline to 12-month follow-up regarding quality of life was observed for both BMAC- and saline-treated knees (all P ⩽ 0.04). T2 quantitative MRI mapping showed no significant changes as a result of treatment., Conclusions: BMAC is safe to perform and relieves pain from knee arthritis but showed no superiority to saline injection at 12-month follow-up. MRI cartilage sequences failed to show regenerative benefit with single BMAC injection. The mechanisms of action that led to pain relief remain unclear and warrant further studies.

The recent surge of seismicity in Oklahoma and Kansas is related to fluid disposal. Evidences suggest that critical parameters are the injection volume as well as injection depth but dominant physical processes and a corresponding model to describe the physics are still not clear. We analyse the spatio-temporal distribution of induced earthquakes in the basement and find visible signatures of pore pressure diffusion and poroelastic coupling, features which strongly resemble seismicity induced by the filling of artificial lakes, so-called reservoir-induced seismicity. We developed a first-principle model of underground reservoir-induced seismicity. The physics of the model are based upon the combined mechanisms of fluid mass added to the pore-space of the injection layer and acting as a normal stress on the basement surface, pore-fluid pressure diffusion in the basement as well as poroelastic coupling contributing to the pore-fluid pressure and stress. Furthermore, we demonstrate that underground reservoir-induced seismicity occurs preferably in normal faulting and strike-slip settings, the latter being prevalent in Oklahoma. Our model explains observed injection volume and depth dependence of the seismicity and should be considered as a basis for future hazard prediction and prevention as well as for planning possible disposal sites.

Adipose-derived therapies have increased in popularity for treatment of painful orthopaedic conditions, such as osteoarthritis. We report the passage of fat into a Baker's cyst after injection of micro-fragmented adipose tissue in a patient with bilateral knee arthritis. Following fat grafting, the patient required drainage of fatty fluid from within the Baker's cyst on multiple occasions. Approximately 3 months postprocedure, she began to notice an improvement in her knee pain with no further recurrence of pain or swelling from her Baker's cyst., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: We review relevant anatomy of the iliac crest, and describe an interventional technique to maximize harvesting of desired progenitor cells with ultrasound to guide safe trochar placement., Materials & Methods: We validated the technique on both sides of the pelvis in four human cadavers., Results: Using ultrasound guidance, 32 BMA needles were placed in a safe zone along various portions of the iliac crest., Conclusion: Ultrasound guidance can improve accuracy of bone marrow aspirations form the iliac crest. Mastery of this procedure will facilitate cell harvest and aid in patient safety when procuring mesenchymal stem cells from a bone marrow source.

The main objective of this pictorial essay is to illustrate the sonographic appearance of the postoperative carpal tunnel and median nerve. Carpal tunnel surgical treatment failures have been shown to occur in up to 19% of a large series requiring re-exploration. Surgical management options for recurrent carpal tunnel syndrome (CTS) include revision release, neurolysis, vein wrapping, and fat grafting procedures. While several descriptions of median nerve entrapment in CTS exist in the ultrasound literature, little is written regarding its postoperative appearance. We report the sonographic changes in the appearance of the median nerve and postoperative carpal tunnel.

Membrane vesicles isolated from Azotobacter vinelandii strain O by lysis of spheroplasts in potassium of sodium phosphate buffer develop a transmembrane electric potential during respiration. The magnitude of this potential was determined by three independent methods: (i) fluorescence of 3,3'-dipropylthiodicarbocyanine and 3,3'-dihexyloxacarbocyanine; (ii) uptake of 86Rb+ in the presence of valinomycin; and (iii) uptake of [3H]triphenylmethyl phosphonium. In method (i), the relative fluorescence of these cyanine dyes in the presence of intact cells or derived vesicles is quenched during oxication of electron donors. A linear relationship between this quenching and a potassium diffusion potential was employed to calibrate the probe response. In method (ii), the steady-state concentration ratio of rubidium across the vesicle membrane during oxidation of L-malate was converted to potential by the Nernst equation. In method (iii), the steady-state concentration ratio of this lipophilic cation was likewise converted to a potential. With the exception of 3,3'-dihexyloxacarbocyanine fluorescence, these methods gave good agreement for the potential developed during L-malate oxidation by membrane vesicles. A value of 75 to 80 mV (inside negative) was obtained for vesicles prepared in potassium phosphate, and 104 mV (inside negative) was obtained for vesicles prepared in sodium phosphate. Electrogenic expulsion of hydrogen ion was observed during L-malate oxidation, and the amount of proton exodus was greater in potassium rather than the sodium-containing vesicles. This indicates the presence of a sodium-proton antiport mechanism. In addition, D-glucose uptake was observed during development of a potassium diffusion potential that was artificially imposed across the vesicle membrane. These observations suggest the presence of a glucose-proton symport mechanism in accordance with the principles of Mitchell.

Antibody responses of two doses of a bivalent influenza vaccine containing A/Victoria/75 (A/Vic/75) and A/New Jersey/76 (A/NJ/76) viral antigens were studied in 22 children receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL), 16 children no longer receiving therapy for ALL, and 50 sibling controls. Before immunization, the three groups showed no difference in titer of antibody to either antigen. After the first immunization, children off therapy showed significantly higher titers to A/NJ/76 than did either sibling controls of children receiving therapy (P less than 0.01). After the second immunization, children off therapy showed significantly higher antibody titers to both antigens than did children receiving therapy or controls (P less than 0.01 for both A/NJ/76 and A/Vic/75). Antibody titers of children receiving therapy were not significantly different from those of controls. A year later, there were no significant differences in antibody titers among the groups. Thus, children with ALL who are receiving chemotherapy respond normally to two doses of influenza vaccine, whereas children off therapy manifest abnormally high titers of antibody to both influenza virus antigens.