Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial.

BACKGROUND: Regenerative medicine interventions are applied to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous/allogenic biologics and it continues to expand. The anti-inflammatory, immunomodulatory, and regenerative properties of bone marrow mesenchymal stem cells (BM-MSCs), and investigation into their therapeutic efficacy and safety in patients with severe chronic low back pain, have not been demonstrated in controlled studies. Multiple pain generators have been hypothesized to be responsible in severe spinal degeneration and it is difficult to identify a single pain generator; consequently, resulting in inadequate therapeutic results. OBJECTIVES: The study was undertaken to evaluate the effectiveness of autologous bone marrow MSCs in the treatment of chronic low back pain due to severe lumbar spinal degeneration with involvement of multiple structures. STUDY DESIGN: Prospective, open-label, nonrandomized, parallel-controlled, 2-arm exploratory study. SETTING: A private, specialized, interventional pain management and regenerative medicine clinic. METHODS: The treatment group patients received a one-time bone marrow concentrate injection into spinal structures (i.e., discs, facets, spinal nerves, and sacroiliac joints), along with conventional treatment, whereas, the control group received conventional treatment with nonsteroid anti-inflammatory drugs, over-the-counter drugs, structured exercise programs, physical therapy, spinal injections and opioids, etc., as indicated. OUTCOMES ASSESSMENT: Outcomes were assessed utilizing multiple instruments, including the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS-11), EuroQOL 5-Dimensional Questionnaire (EQ-5D-3L), Global Mental Health (GMH), and Global Physical Health (GPH). Multiple outcomes were assessed with primary outcomes being minimal clinically important differences (MCID) in ODI scores between the groups and/or a 2-point reduction in pain scores. In the study group, total nucleated cells, colony forming units-fibroblast, CD34-positive  cell numbers and platelets were also recorded, along with post-procedure magnetic resonance imaging changes. Outcomes were assessed at 1, 3, 6, and 12 months. RESULTS: Significant improvement was achieved in functional status measured by ODI, pain relief measured by NRS-11, and other parameters measured by EQ-5D-3L, GMH, and GPH, in the study group relative to the control group at all time periods. The results showed significant improvements at 12-month follow-up with 67% of the patients in the study group achieving MCID utilizing ODI when compared to 8% in the control group. Greater than 2-point pain reduction was seen in 74% of the patients at 3 months, 66% of the patients at 6 months, and 56% of the patients at 12 months. Both MCID and pain relief of 2 points were significantly different compared to the control group. Opioid use decreased in the investigational group, whereas, there was a slight increase in the control group. Age, gender, opioid use, and body mass index did not affect the outcomes in the stem cell group. LIMITATIONS: Single center, nonrandomized study. CONCLUSIONS: The first available controlled study utilizing BM-MSCs in severe degenerative spinal disease with interventions into multiple structures simultaneously, including disc, facet joints, nerve roots, and sacroiliac joint based on symptomatology, showed promising results.

Spondylodiscitis due to Cutibacterium acnes following lumbosacral intradiscal biologic therapy: a case report.

A 40-year-old woman with a history of chronic low back pain underwent a fluoroscopically guided intradiscal platelet-rich plasma injection (PRP) at the L5-S1 level. She subsequently developed progressive low back pain, night sweats and decreased ability to ambulate. Laboratory work-up revealed elevated acute phase reactants and imaging revealed L5-S1 intervertebral disc and vertebral end-plate abnormalities highly suggestive of spondylodiscitis. Computed tomography-guided aspiration and biopsy cultures grew Cutibacterium acnes and the patient was subsequently treated with intravenous antibiotics without surgical management. To the best of our knowledge, this is the first published case of lumbar spondylodiscitis following an intradiscal PRP injection, and brings to the forefront several clinically relevant issues including the antimicrobial effects of PRP, the role of C. acnes in spine infections and the ideal treatment protocol for intradiscal biologics in order to minimize morbidity and optimize functional outcomes.

Fluoroscopically guided caudal epidural steroid injections for axial low back pain associated with central disc protrusions: a prospective outcome study.

PURPOSE: To determine if axial low back pain (LBP) associated with central disc protrusions can be improved by caudal epidural steroid injections (ESIs). METHODS: Adults with chronic (> 3 months) moderate-to-severe axial LBP with L4-5 and/or L5-S1 central disc protrusions were enrolled in this prospective study. Participants underwent caudal ESIs under standard-of-care practice. The numerical rating scale (NRS) pain score, modified North American Spine Society satisfaction, and Roland Morris Disability Questionnaire (RMDQ) were collected at one week, one month, three months, six months, and one year post-injection. Pre-injection magnetic resonance images were assessed by a musculoskeletal radiologist. RESULTS: Sixty-eight participants (42 males, 26 females) were analyzed. There were statistically significant improvements in all outcome measures at all follow-up time points, with the exception of NRS best pain at six months. Clinically significant improvements in outcomes were observed at various time points: at three months and one year for current pain; at one week, one month, three months, six months, and one year for worst pain; and at one month and one year for RMDQ. The proportion of satisfied participants ranged from 57 to 69% throughout the study. No adverse events were observed. CONCLUSIONS: This study demonstrated significant improvements in pain and function following caudal ESIs in a cohort of axial LBP with associated central disc protrusions. Further studies, including the use of randomized controlled trials, are needed to determine the ideal subset of candidates for this treatment and to explore additional applications that caudal ESIs may have for chronic LBP.

The electrodiagnostic natural history of parsonage-turner syndrome.

INTRODUCTION: Recovery from Parsonage-Turner syndrome (PTS) is generally favorable, although recovery times have been shown to vary, in part because there are no universally accepted outcome measures. In this study, we describe the electrodiagnostic natural history of this condition based on objective electrodiagnostic testing, and propose that complete electrodiagnostic recovery can be seen as early as 1 year. METHODS: Twenty-six subjects with 29 affected nerves confirmed as PTS were followed every 3 months for electrodiagnostic testing, or until full reinnervation was confirmed. RESULTS: Twenty-three cases (79.3%) demonstrated electrodiagnostic evidence of initial recovery at a mean of 5.8 months. Nine cases (31%) showed complete electrodiagnostic recovery at a mean of 1 year. When excluding cases with <1 year of follow-up, 52.9% achieved complete electrodiagnostic recovery. CONCLUSIONS: In contrast to previous reports, full electrodiagnostic recovery of PTS was demonstrated at a mean of 1 year in > 50% of patients with longer term follow-up. Muscle Nerve 56: 737-743, 2017.

Platelet-Rich Plasma Injections With Needle Tenotomy for Gluteus Medius Tendinopathy: A Registry Study With Prospective Follow-up.

BACKGROUND: Gluteal tendinopathy is a prevalent condition that can be associated with significant pain and disability. To date, no studies have prospectively assessed the efficacy of intratendinous platelet-rich plasma (PRP) injections as a minimally invasive treatment for gluteus medius tendinopathy. PURPOSE: To prospectively assess the efficacy of intratendinous PRP injections as treatment for chronic recalcitrant gluteus medius tendinopathy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: During the study period between July 2011 and November 2015, data were collected from the Hospital for Special Surgery Center for Hip Preservation Outcomes Registry on participants who underwent ultrasound-guided intratendinous PRP injections for recalcitrant gluteus medius tendinosis and/or partial tears of the tendon associated with moderate to severe lateral hip pain for longer than 3 months. All participants were assessed pre- and postinjection with 4 outcome measures: modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living subscale (HOS-ADL), Hip Outcome Score-Sport-Specific subscale (HOS-Sport), and the International Hip Outcome Tool-33 (iHOT-33). Demographic data, including age, sex, height, weight, body mass index, and smoking status, were also collected. RESULTS: A total of 21 patients were included in the study, with a mean follow-up of 19.7 months (range, 12.1-32.3 months). The mean improvements from preinjection to postinjection follow-up were 56.73 to 74.17 for mHHS, 68.93 to 84.14 for HOS-ADL, 45.54 to 66.72 for HOS-Sport, and 34.06 to 66.33 for iHOT-33. All mean outcome measure improvements were clinically and statistically significant (P < .001). Length of follow-up was positively correlated with improvements in HOS-ADL (P = .021) and HOS-Sport (P = .004) scores. No adverse events were observed during or after the procedure. CONCLUSION: In this registry study with prospective follow-up, we found ultrasound-guided intratendinous PRP injections to be a safe and effective treatment option for chronic recalcitrant gluteus medius tendinopathy due to moderate to severe tendinosis and/or partial tendon tears. Well-powered randomized controlled studies are warranted to confirm our findings and further define the ideal candidates for this treatment.

Regenerative Treatments for Spinal Conditions.

A literature review of clinical and translational studies was performed to provide an overview of current concepts on regenerative treatments for spinal conditions, including platelet rich plasma and stem cell treatments to treat low back pain.

Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: an update.

PURPOSE: The aim of this article is to provide an overview of clinical and translational research on intradiscal platelet-rich plasma (PRP) as a minimally invasive treatment for discogenic low back pain. METHODS: A literature review of in vitro, in vivo, and clinical studies was performed. RESULTS: There is strong in vitro evidence that supports the use of intradiscal PRP for discogenic low back pain. There are also promising findings in select preclinical animal studies. A clinical study of 29 participants who underwent intradiscal PRP injections for discogenic low back pain found statistically and clinically significant improvements in pain and function through two years of follow-up. CONCLUSIONS: Intradiscal PRP is a safe and a possibly effective treatment for discogenic low back pain. Future studies are warranted to determine the best candidates for this treatment, what the optimal injectate is and what relationships exist between patient-reported outcomes and radiological findings.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

OBJECTIVE: To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. DESIGN: Prospective, double-blind, randomized controlled study. SETTING: Outpatient physiatric spine practice. PARTICIPANTS: Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. METHODS: Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. MAIN OUTCOME MEASURES: Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. RESULTS: Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. CONCLUSION: Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP injectate.

Long-term results of rectal cancer surgery with a systematical operative approach.

BACKGROUND: Variabilities of both oncologic and functional outcomes are major problems after rectal cancer treatment. Standardized techniques might produce more consistent surgical quality. This study reports outcomes during a 20-year period resulting from a systematically applied surgical approach. METHODS: Between 1990 and 2010, 368 rectal cancer patients, treated with total mesorectal excision conducted in a standardized, stepwise approach, were prospectively entered into a database. Influence of time period, surgeon, tumor and anastomotic height, and resection type was evaluated with multivariable regression analyses adjusting for age, disease stage, diversion, and (neo)adjuvant treatment. Function outcome questionnaires were sent to 50 patients at least 5 years after surgery. RESULTS: Five-year overall survival was 76.4 %. Local and distant recurrence rates were 5.2 % and 22.1 %. Anastomotic leakage occurred in 5.4 % of patients treated with low anterior resection (n = 259). Time period, surgeon, tumor and anastomotic height, diversion, and abdominoperineal resection were not independent risk factors for any of these outcome measures. Both preoperative and postoperative radiotherapy were independently associated with increased risk of metastases (P = 0.035, hazard ratio (HR) = 3.04; and P = 0.029, HR = 3.59). Function questionnaires were completed by 38 of 50 patients (76 %). One of 13 nonirradiated patients reported mild fecal incontinence compared with 20 of 25 irradiated patients reporting mostly moderate-severe incontinence (P < 0.001). CONCLUSIONS: Systematically applied surgical dissection results consistently in excellent oncologic outcomes with enhanced function outcomes. The findings suggest that in the presence of highly disciplined surgery, radiotherapy might make a smaller contribution to oncologic outcome, while leading to serious adverse effects.

Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study.

Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.

Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer?

BACKGROUND: Oncotype DX is a 21-gene assay that calculates a risk of distant recurrence in women with estrogen-receptor-positive, lymph node-negative breast cancer. The purpose of this study was to determine whether the results of Oncotype DX influence the decision to administer chemotherapy. METHODS: A retrospective study was performed on 85 consecutive patients with estrogen-receptor-positive, lymph node-negative breast cancer who had an Oncotype DX recurrence score (RS) obtained. Tumor size, tumor grade, and treatment were then compared within each risk category. Statistical analysis was performed using STATA software. RESULTS: Tumors that were high grade and Her-2/neu positive more frequently had a high RS. Treatment was changed as a result of Oncotype DX in 44% of patients. CONCLUSIONS: Oncotype DX RS is significantly related to tumor grade and Her2/neu status. In this study, the treatment of 44% of patients was altered as a consequence of Oncotype DX RS.

Do additional shaved margins at the time of lumpectomy eliminate the need for re-excision?

BACKGROUND: Most women diagnosed with breast cancer undergo breast-conservation surgery. Re-excision rates for positive margins have been reported to be greater than 50%. The purpose of our study was to determine if removing additional shaved margins from the lumpectomy cavity at the time of lumpectomy reduces re-excisions. METHODS: A retrospective study was performed on 125 women who had undergone lumpectomy with additional shaved margins taken from the lumpectomy cavity. Pathology reports were reviewed for tumor size and histology, lumpectomy and additional margin status, and specimen and margin volume. RESULTS: If additional margins were not taken, 66% would have required re-excision. Because of taking additional shaved margins, re-excision was eliminated in 48%. CONCLUSION: Excising additional shaved margins at the original surgery reduced reoperations by 48%. There is a balance between removing additional margins and desirable cosmesis after breast-conservation surgery. The decision to take extra margins should be based on the surgeon's judgment.