Subchondroplasty for Osteonecrosis of the Knee.

Subchondroplasty is a relatively new minimally invasive procedure that has been used to treat bone marrow edema associated with osteoarthritis. Subchondroplasty as treatment for early stage osteonecrosis of the knee has not been extensively studied. The authors hypothesized that subchondroplasty may be an effective treatment for relieving pain, improving function, and preventing collapse in osteonecrosis. In this study, a retrospective review of 11 cases of subchondroplasty of the distal femur was conducted. There were no surgical complications with the procedure, and patients reported statistically significant improvement in pain and function. The mean Knee injury and Osteoarthritis Outcome Score for Joint Replacement improved from 44.3±4.9 preoperatively to 65.73±17.2 postoperatively. The mean visual analog scale score for knee pain was 7.8±1.18 preoperatively and 3.7±1.57 postoperatively. There has been one case of recurrence of osteonecrosis and no cases of joint collapse since the procedures occurred between 2018 and 2021. Previously, subchondroplasty for the treatment of osteonecrosis of the talus as well as of the knee joint showed positive results. This study affirms that subchondroplasty may also be a useful treatment option for relieving pain, improving function, and preventing joint collapse in osteonecrosis of the knee. [Orthopedics. 2023;46(5):e287-e290.].

Synthetic cartilage implant hemiarthroplasty versus cheilectomy for the treatment of hallux rigidus.

Degenerative arthritis of the first metatarsophalangeal joint, hallux rigidus, is the most common type of arthritis of the foot, affecting nearly 2.5% of the population over the age of 50. Hallux rigidus can be treated surgically with either Cheilectomy or Synthetic cartilage implant (SCI) hemiarthroplasty. The purpose of this study is to compare outcomes from a single institution on the treatment of hallux rigidus using cheilectomy and SCI hemiarthroplasty. Between 2012 and 2020, 49 patients underwent either a SCI (Polyvinyl alcohol hydrogels) hemiarthroplasty or Cheilectomy for the treatment of hallux rigidus. Functional scores were assessed pre and postoperatively using the American Orthopedic Foot and Ankle scoring System (AOFAS) and the Foot and Ankle Outcome Score survey (FAOS). Plantar and Dorsal range of motion was also assessed pre and postoperatively. Outcomes, complications, and any reoperations were recorded for all patients. Mean pre-op AOFAS for Cheilectomy and SCI were 49.6 and 54.8, respectively, compared to 85.3 and 89.7, respectively, after surgery (p value < 0.05). Mean pre-op Dorsal range of motion (ROM) for Cheilectomy and SCI were 24.0 and 26.0 degrees, respectively, compared to 38.0 and 42.6 degrees, respectively, after surgery (p value < 0.05). SCI hemiarthroplasty patients had higher AOFAS and dorsal ROM at the latest follow up (p value < 0.05). Synthetic cartilage implant (SCI) hemiarthroplasty and cheilectomy both offer promising results and remain viable treatment options to decrease pain, improve function, and maintain motion for hallux rigidus. SCI hemiarthroplasty may offer superior range of motion and functional outcomes than cheilectomy for hallux rigidus. LEVEL OF CLINICAL EVIDENCE: 3.

Mini-Open Achilles Tendon Repair: Improving Outcomes While Decreasing Complications.

An acute rupture of the Achilles tendon is a traumatic injury that can cause considerable morbidity and reduced function. Nonoperative intervention may put patients at higher risk of rerupture, whereas surgical intervention carries risk of infection, wound complications, and iatrogenic nerve injury. The mini-open Achilles tendon repair technique has been popularized in helping decrease complications. The goal of this study was to examine and compare the functional outcomes and rate of complications in patients treated with a mini-open repair technique versus a traditional open repair for acute Achilles tendon ruptures. A retrospective review was performed of all patients with a complete Achilles tendon rupture that were treated by a single foot and ankle fellowship-trained surgeon. Functional outcome scores were assessed using the American Orthopaedic Foot and Ankle scoring system (AOFAS) and the Achilles Tendon Rupture Score (ATRS). Eighty-one patients with a complete Achilles tendon rupture underwent mini-open repair and 22 patients underwent traditional open repair surgery between 2013 and 2020. The mean follow-up was 38.40 months (range, 12-71). Mean preoperative AOFAS and ATRS improved in the mini-open group from 45.60 and 47.18 respectively, to 90.29 and 87.97 after surgery (p < .05). Mean preoperative AOFAS and ATRS scores for the traditional open repair (n = 22) cohort were 44.02 and 42.27, respectively. Postoperatively, the AOFAS and ATRS scores improved to 85.27 and 86.64 (P value < .05), respectively. There was no statistically significant difference in postoperative ATRS scores. However, the mini-open repair group showed a statistically higher postoperative AOFAS score (90.30) than the traditional open-repair group (85.27) (P value < .05). The overall complication rate for our study was 2.9% (2 mini-open repair and 1 traditional open repair). The complication rate in the mini-open repair group and traditional open repair cohort were 2.4% and 4.5%, respectively (P value > .05). One patient in the mini-open repair cohort (1.2%) reruptured his Achilles tendon 4 months postoperatively. A second patient in the mini-open repair group (1.2%) developed a superficial skin infection and suture irritation. One patient (4.5%) in the traditional open repair group developed a superficial skin infection. There were no sural nerve injuries in our series. The mini-open approach to repair a ruptured Achilles tendon is a viable treatment option to decrease the incidence rate of postoperative complications and rerupture rates while also producing a superior cosmetic result.Level of Evidence: 3 (retrospective cohort study N ≥ 30).

Intravenous lidocaine for the treatment of acute pain in the emergency department.

OBJECTIVE: To evaluate intravenous lidocaine's safety and efficacy as an analgesic agent in the treatment of a variety of painful conditions presenting to the emergency department. METHODS: This case series identified seventeen patients who received lidocaine over a six month period and recorded demographic data, amount of lidocaine administered, the amount of opioid medication administered before and after lidocaine, pre- and post-lidocaine pain scores, and any qualitative descriptors of the patient's pain recorded in the record. Side effects and adverse events were also recorded. RESULTS: Of the seven patients who had a pre- and post-lidocaine pain score recorded, the mean reduction was 3 points on a 10 point scale. Patients who received lidocaine used less opioid medication. One patient received an improperly high dose of lidocaine and suffered a brief seizure and cardiac arrest, but was quickly resuscitated. CONCLUSION: This series suggests that lidocaine may be a useful adjunct in the treatment of acutely painful conditions in the emergency department.

Denervation and beta2-adrenoceptor-agonist administration on craniofacial bone density.

OBJECTIVE: Beta2-agonist medications are thought to have adverse effects on bone density. Surgical denervation and intramuscular beta2-agonist injections appear to have opposing effects on skeletal muscles. The present study has been designed to assess the effects of denervation of the masseter, intramuscular injection of a beta2-agonist and the combination of both procedures, on bone density in the craniofacial skeleton in rats. MATERIALS AND METHODS: Sprague-Dawley rats were prepared as four groups: 1. surgical sham + saline injection into the masseter (sham); 2. surgical denervation of the masseter (den.); 3. surgical denervation of the masseter + intramuscular formoterol injection into the affected muscle (den.+form.); 4. intramuscular formoterol injection into the masseter (form.). All specimens were submitted for CT examination and volumetric calculations of the mineralised bone tissue were performed. RESULTS: The sham and form. groups had a greater volume of mineralised bone in the zygoma on the experimental side compared with the control side. The maxilla on the experimental side had a higher volume of mineralised bone in the den.+form. and form. groups compared with the sham and den. groups. The control side of the maxilla had a higher volume of mineralised bone in the den.+form. and form. groups compared with the den. group only. CONCLUSION: Intramuscular administration of formoterol appears to induce a bilateral increase in bone mineral density in the maxilla and the zygoma, likely explained as a secondary effect of the well-described increase in muscle mass and strength associated with beta2-agonist administration.

The effects of denervation and formoterol administration on facial growth.

OBJECTIVE: To identify and demonstrate possible alterations of skeletal structures which might follow either unilateral surgical denervation of the masseter muscle, unilateral intramuscular injection of formoterol directly into the masseter muscle, or intramuscular formoterol injection after surgical denervation. MATERIALS AND METHODS: Male Sprague Dawley rats (N = 16; four weeks of age) were prepared as four groups: 1. surgical sham + saline injection into the masseter muscle (sham); 2. surgical denervation of the masseter muscle only (den.); 3. surgical denervation of the masseter muscle plus intramuscular formoterol injection into the affected muscle (den.+form.); 4. intramuscular formoterol injection into the masseter muscle only (form.). The specimens were submitted for CT examination, the skulls and hemimandibles were photographed and measurements of craniofacial bones were made. RESULTS: In this relatively small sample, comparisons between non-experimental and experimental sides revealed differences, both within the groups and for the same measurements between groups, with the den. and den.+form. groups showing the most change. Relative increases in the gonial angle shown in these groups occurred bilaterally, with the change on the experimental side always greater in magnitude than the change on the contralateral side. CONCLUSIONS: Surgical denervation of the masseter muscle leads to an alteration in the size and shape of the skeletal structures close to the zygoma and the mandible. The intramuscular injection of formoterol into denervated masseter muscle seems to limit this skeletal alteration after surgical denervation.

Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

BACKGROUND: Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons. RESULTS: We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12. CONCLUSIONS: Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.

Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine.

Thiamine (Vitamin B1) is an essential vitamin that must be obtained from the diet for proper neurological function. At higher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)-a phosphorylated derivative of thiamine-have antinociceptive effects in animals and humans, although how these compounds inhibit pain is unknown. Here, we found that Prostatic acid phosphatase (PAP, ACPP) can dephosphorylate BT in vitro, in dorsal root ganglia (DRG) neurons and in primary-afferent axon terminals in the dorsal spinal cord. The dephosphorylated product S-benzoylthiamine (S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes. This unique reaction mechanism reveals that BT only requires a phosphatase for conversion to thiamine. However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine-a compound that is not phosphorylated-were entirely dependent on PAP at the spinal level. Moreover, pharmacokinetic studies with wild-type and Pap(-/-) mice revealed that PAP is not required for the conversion of BT to thiamine in vivo. Taken together, our study highlights an obligatory role for PAP in the antinociceptive effects of thiamine and phosphorylated thiamine analogs, and suggests a novel phosphatase-independent function for PAP.

Industry self-regulation to improve student health: quantifying changes in beverage shipments to schools.

OBJECTIVES: We developed a data collection and monitoring system to independently evaluate the self-regulatory effort to reduce the number of beverage calories available to children during the regular and extended school day. We have described the data collection procedures used to verify data supplied by the beverage industry and quantified changes in school beverage shipments. METHODS: Using a proprietary industry data set collected in 2005 and semiannually in 2007 through 2010, we measured the total volume of beverage shipments to elementary, middle, and high schools to monitor intertemporal changes in beverage volumes, the composition of products delivered to schools, and portion sizes. We compared data with findings from existing research of the school beverage landscape and a separate data set based on contracts between schools and beverage bottling companies. RESULTS: Between 2004 and the 2009-2010 school year, the beverage industry reduced calories shipped to schools by 90%. On a total ounces basis, shipments of full-calorie soft drinks to schools decreased by 97%. CONCLUSIONS: Industry self-regulation, with the assistance of a transparent and independent monitoring process, can be a valuable tool in improving public health outcomes.

Orally active adenosine A(1) receptor agonists with antinociceptive effects in mice.

Adenosine A(1) receptor (A(1)AR) agonists have antinociceptive effects in multiple preclinical models of acute and chronic pain. Although numerous A(1)AR agonists have been developed, clinical applications of these agents have been hampered by their cardiovascular side effects. Herein we report a series of novel A(1)AR agonists, some of which are structurally related to adenosine 5'-monophosphate (5'-AMP), a naturally occurring nucleotide that itself activates A(1)AR. These novel compounds potently activate A(1)AR in several orthogonal in vitro assays and are subtype selective for A(1)AR over A(2A)AR, A(2B)AR, and A(3)AR. Among them, UNC32A (3a) is orally active and has dose-dependent antinociceptive effects in wild-type mice. The antinociceptive effects of 3a were completely abolished in A(1)AR knockout mice, revealing a strict dependence on A(1)AR for activity. The apparent lack of cardiovascular side effects when administered orally and high affinity (K(i) of 36 nM for the human A(1)AR) make this compound potentially suitable as a therapeutic.

Secretion and N-linked glycosylation are required for prostatic acid phosphatase catalytic and antinociceptive activity.

Secretory human prostatic acid phosphatase (hPAP) is glycosylated at three asparagine residues (N62, N188, N301) and has potent antinociceptive effects when administered to mice. Currently, it is unknown if these N-linked residues are required for hPAP protein stability and activity in vitro or in animal models of chronic pain. Here, we expressed wild-type hPAP and a series of Asn to Gln point mutations in the yeast Pichia pastoris X33 then analyzed protein levels and enzyme activity in cell lysates and in conditioned media. Pichia secreted wild-type recombinant (r)-hPAP into the media (6-7 mg protein/L). This protein was as active as native hPAP in biochemical assays and in mouse models of inflammatory pain and neuropathic pain. In contrast, the N62Q and N188Q single mutants and the N62Q, N188Q double mutant were expressed at lower levels and were less active than wild-type r-hPAP. The purified N62Q, N188Q double mutant protein was also 1.9 fold less active in vivo. The N301Q mutant was not expressed, suggesting a critical role for this residue in protein stability. To explicitly test the importance of secretion, a construct lacking the signal peptide of hPAP was expressed in Pichia and assayed. This "cellular" construct was not expressed at levels detectable by western blotting. Taken together, these data indicate that secretion and post-translational carbohydrate modifications are required for PAP protein stability and catalytic activity. Moreover, our findings indicate that recombinant hPAP can be produced in Pichia--a yeast strain that is used to generate biologics for therapeutic purposes.