Improved Pain and Function with Triamcinolone Acetonide Extended-Release and Cryoneurolysis for Knee Osteoarthritis: Use of a New Real-World Registry.

INTRODUCTION: Knee osteoarthritis (OA) affects 19% of American adults over 45 years old and costs $27+ billion annually. A wide range of non-operative treatment options are available. This study compared six treatments: cryoneurolysis with deep genicular nerve block (Cryo-Deep/Both), cryoneurolysis with superficial nerve block (Cryo-Superficial), intra-articular hyaluronic acid (IA-HA) injections, non-steroidal anti-inflammatory drug injections (IA-NSAIDs), IA-corticosteroids (IA-CS) injections, or IA-triamcinolone extended release (IA-TA-ER) injections over 4 months for: 1) pain severity and analgesic use; and 2) physical function (from Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR)). METHODS: Patients who had unilateral knee OA and received non-operative intervention were enrolled in the Innovations in Genicular Outcomes (iGOR) registry, a novel, multi-center real-world registry, between September 2021 and February 2024. A total of 480 patients were enrolled. Both pain and functional outcomes were assessed at baseline, weekly, and monthly, which were analyzed by: overall trend, magnitude changes pre- to post-treatment, and distribution-based minimal clinically important difference score (MCID). Multivariate linear regressions with adjustments for seven confounding factors were used to compare follow-up outcomes among six treatment groups. RESULTS: Use of IA-TA-ER injections was associated with the lowest pain, greatest pain reduction, and highest prevalence of patients achieving MCID relative to other treatments (P < 0.001). Deep/Both-Cryo and IA-CS were associated with a higher prevalence of achieving MCID than IA-HA, IA-NSAIDs, and Cryo-Superficial (P ≤ 0.001). Use of IA-TA-ER was also associated with the greatest functional score, improvement from baseline, and highest prevalence of patients achieving MCID than other treatments (P ≤ 0.003). CONCLUSIONS: The IA-TA-ER appears to outperform other treatments in terms of pain relief and functional improvement for up to 4 months following treatment. In addition, outcomes in the novel cryoneurolysis and conventional IA-CS were similar to one another and better than those in IA-HA and IA-NSAIDs.

Cryoneurolysis Associated with Improved Pain, Function, and Sleep in Patients Following Total Knee Arthroplasty: Use of a New Real-World Registry.

INTRODUCTION: Total knee arthroplasty (TKA) is performed on approximately 790,000 patients annually in the United States and is projected to increase to 1.5 million by 2050. This study aimed at assessing the use of preoperative cryoneurolysis on patients undergoing TKA by analyzing: 1) pain severity; 2) opioid use; 3) functional status; and 4) sleep disturbance over 6 months following discharge. METHODS: Patients enrolled in the Innovations in Genicular Outcomes Registry (iGOR) between September 2021 and February 2024 were followed for 6 months. Our analyses included patients undergoing unilateral primary TKA with no pre-operative opioid prescription who either received, or did not receive, cryoneurolysis. Baseline patient demographics were collected before TKA and tabulated. Pain management was assessed via the Brief Pain Inventory-Short Form (BPI-SF) instrument for pain severity. Sleep disturbance was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. Each outcome measure was assessed prior to TKA, weekly, and at monthly follow-up. Data was analyzed by a generalized linear mixed-effect regression model to compare cryoneurolysis versus control patients, with a P < 0.05 as significant. RESULTS: There were 80 patients who were treated with preoperative cryoneurolysis, while 60 control patients did not have treatment. Patients receiving cryoneurolysis experienced significantly lower pain severity and sleep disturbance over the 6-month follow-up than control patients (P = 0.046). Cryoneurolysis was also associated with a trend toward greater functional improvement that did not reach statistical significance (P = 0.061). Further, patients who underwent cryoneurolysis were 72% less likely than controls to take opioids over six months following discharge (P <0.001). CONCLUSIONS: Pre-operative cryoneurolysis therapy in opioid-naïve patients undergoing TKA is associated with improved pain, decreased opioid use, and improved sleep disturbance for 6 months postoperatively. Cryoneurolysis, a non-opioid pain relief modality administered pre-operatively, demonstrated substantial benefits in patients who underwent TKA.

Neural and endocrine regulation of osmoregulatory organs in tick: Recent discoveries and implications.

Ticks can survive in harsh and fluctuating vegetated environments for long durations between blood feedings with highly developed osmoregulatory mechanisms. Like the unique life history of hematophagous ticks, osmoregulatory organs and their regulatory mechanisms are significantly different from those in the closely related insect taxa. Over the last ten years, research has uncovered several neuropeptidergic innervations of the primary osmoregulatory organ, the salivary glands: myoinhibitory peptide (MIP), SIFamide, and elevenin. These neuropeptides are thought to be modulators of dopamine's autocrine or paracrine actions controlling the salivary glands, including the activation of fluid transport into the lumen of salivary acini and the pumping and gating action of salivary acini for expelling fluids out into salivary ducts. These actions are through two different dopamine receptors, D1 receptor and invertebrate D1-like dopamine receptor, respectively. Interestingly, MIP and SIFamide are also involved in the control of another important excretory/osmoregulatory organ, the hindgut, where SIFamide is myostimulatory, with MIP having antagonistic effects. FGLamide related allatostatin is also found to have axonal projections located on the surface of the rectum. Investigations of the osmoregulatory mechanisms of these critical vector species will potentially lead to the development of a measure to control tick species.

Dermal secretion physiology and thermoregulation in the lone star tick, Amblyomma americanum.

Ticks are hematophagous ectoparasites that transmit a wide range of pathogens. The lone star tick, Amblyomma americanum, is one of the most widely distributed ticks in the Midwest and Eastern United States. Lone star ticks, as other three-host ixodid ticks, can survive in harsh environments for extended periods without a blood meal. Physiological mechanisms that allow them to survive during hot and dry seasons include thermal tolerance and water homeostasis. Dermal fluid secretions have been described in metastriate ticks including A. americanum. We hypothesized that tick dermal secretion in the unfed tick plays a role in thermoregulation, as described in other hematophagous arthropods during blood feeding. In this study, we found that physical contact with a heat probe at 45 °C or high environmental temperature at ∼50 °C can trigger dermal secretion in A. americanum and other metastriate ticks in the off-host period. We demonstrated that dermal secretion plays a role in evaporative cooling when ticks are exposed to high temperatures. We find that type II dermal glands, having paired two cells and forming large glandular structures, are the source of dermal secretion. The secretion was triggered by an injection of serotonin, and the serotonin-mediated secretion was suppressed by a pretreatment with ouabain, a Na/K-ATPase blocker, implying that the secretion is controlled by serotonin and the downstream Na/K-ATPase.

A Multimodal Pain Management Protocol Including Preoperative Cryoneurolysis for Total Knee Arthroplasty to Reduce Pain, Opioid Consumption, and Length of Stay.

BACKGROUND: A retrospective analysis was conducted to determine if cryoneurolysis of superficial genicular nerves combined with standard care decreased postoperative opioids and pain after total knee arthroplasty (TKA). METHODS: Data from patients who underwent TKA at a single center were analyzed. Patients who received standardized cryoneurolysis before TKA were compared with a historical control group including patients who underwent TKA without cryoneurolysis. Both groups received a similar perioperative multimodal pain management protocol. The primary outcome was opioid intake at various time points from hospital stay to 6 weeks after discharge. Additional outcomes included pain, length of stay, and range of motion. RESULTS: The analysis included 267 patients (cryoneurolysis group: n = 169; control group: n = 98). During the hospital stay, the cryoneurolysis group had 51% lower daily morphine milligram equivalents (MMEs) (47 vs 97 MMEs; ratio estimate, 0.49 [95% confidence interval (CI), 0.43-0.56]; P < .0001) and 22% lower mean pain score (ratio estimate, 0.78 [95% CI, 0.70-0.88]; P < .0001) vs the control group. The cryoneurolysis group received significantly fewer cumulative MMEs, including discharge prescriptions, than the control group at week 2 (855 vs 1312 MMEs; ratio estimate, 0.65 [95% CI, 0.59-0.73]; P < .0001) and week 6 (894 vs 1406 MMEs; ratio estimate, 0.64 [95% CI, 0.57-0.71]; P < .0001). The cryoneurolysis group had significant 44% reduction in overall length of stay (P < .0001) and greater flexion degree at discharge (P < .0001). CONCLUSIONS: Addition of preoperative cryoneurolysis to a multimodal pain management protocol reduced opioids and in-hospital pain and optimized outcomes during the 6-week recovery period after TKA.

Acute colonic pseudo-obstruction (Ogilvie syndrome) after arthroplasty in the lower extremity.

BACKGROUND: Acute colonic pseudo-obstruction, also known as Ogilvie syndrome, is an uncommon postoperative complication of total hip and total knee arthroplasty that is characterized by massive colonic dilatation and the potential for substantial morbidity and mortality. METHODS: We conducted a retrospective case-control study of 1170 total hip and knee arthroplasties performed by one surgeon from 1995 to 2002, and identified eighteen patients with Ogilvie syndrome. Radiographs and medical records were analyzed for risk factors and treatment effectiveness. RESULTS: Eleven (1.6%) of 708 patients who had a total hip arthroplasty and seven (1.5%) of 462 patients who had a total knee arthroplasty had Ogilvie syndrome develop postoperatively. Seventeen of these patients had preoperative conditions and/or had received medications identified as risk factors for Ogilvie syndrome. The use of patient-controlled analgesia was associated with an earlier development of symptoms. Colonic decompression was performed in seven patients and was associated with a significantly shorter hospital stay (p = 0.019). CONCLUSIONS: Acute colonic pseudo-obstruction was equally prevalent after total hip and total knee arthroplasties. Most patients who had Ogilvie syndrome had risk factors that could be identified preoperatively. Knowledge of these risk factors can enable the physician to anticipate which patients may have Ogilvie syndrome develop and, therefore, to be vigilant for its development and judicious in the use of patient-controlled analgesia. We also found that decompressive colonoscopy reduced the risk of perforation and decreased the length of hospitalization for the patients in whom Ogilvie syndrome developed.

Cost analysis of surgical site infections.

BACKGROUND: Patients with surgical site infections (SSIs) require a longer time in the hospital, more nursing care, additional dressings, and, possibly, readmission to the hospital and further surgery. The combined direct and indirect costs of treating SSIs may be extremely high. METHODS: Review of current practice and guidelines. RESULTS: The direct costs of SSI include a longer hospital stay, readmission, outpatient and emergency visits, further surgery, and prolonged antibiotic treatment. Other direct costs arise from radiologic procedures, laboratory tests, home health visits and other ancillary services, drugs, and professional fees. Indirect costs, which are difficult to quantify, include lost productivity of the patient and family and a temporary or permanent decline in functional or mental capacity. The cost of SSIs increases with the depth of the infection. That is, the costs associated with superficial incisional SSIs are relatively low, but increase with deep SSI, and especially when organ or space infection is present. The estimated costs of managing SSI differ widely, from less than dollar 400 per case for superficial SSI to more than dollar 30,000 per case for serious organ or space infections. CONCLUSIONS: The need to treat SSIs places a severe financial strain on health care resources. It is possible that treating high-risk surgical patients medically will prove to be more cost-effective than repeated operations.

Multiple functions of Na/K-ATPase in dopamine-induced salivation of the Blacklegged tick, Ixodes scapularis.

Control of salivary secretion in ticks involves autocrine dopamine activating two dopamine receptors: D1 and Invertebrate-specific D1-like dopamine receptors. In this study, we investigated Na/K-ATPase as an important component of the secretory process. Immunoreactivity for Na/K-ATPase revealed basal infolding of lamellate cells in type-I, abluminal interstitial (epithelial) cells in type-II, and labyrinth-like infolding structures opening towards the lumen in type-III acini. Ouabain (10 µmol l(-1)), a specific inhibitor of Na/K-ATPase, abolished dopamine-induced salivary secretion by suppressing fluid transport in type III acini. At 1 µmol l(-1), ouabain, the secreted saliva was hyperosmotic. This suggests that ouabain also inhibits an ion resorptive function of Na/K-ATPase in the type I acini. Dopamine/ouabain were not involved in activation of protein secretion, while dopamine-induced saliva contained constitutively basal level of protein. We hypothesize that the dopamine-dependent primary saliva formation, mediated by Na/K-ATPase in type III and type II acini, is followed by a dopamine-independent resorptive function of Na/K-ATPase in type I acini located in the proximal end of the salivary duct.

Relationship between product demand, tibial polyethylene insert shelf age, and total knee arthroplasty survival: retrospective review of total knees of one design.

Shelf aging of gamma-irradiated-in-air polyethylene tibial components has been associated with increased articular surface wear and an elevated risk for revision. Nine hundred fifty cruciate-retaining inserts of one design were implanted between 1987 and 1996 (shelf age, 1.0 +/- 1.2 years). Less frequently used inserts (smallest/largest sizes, thicker thicknesses, supplemental articular constraint) had longer shelf ages (means ranged from 1.2 to 2.6 years). Survival analysis showed that shelf age (P < .01) and gamma-sterilization in air (P = .01) elevated the risk for revision. Surgeons must remain attentive to identify the shelf-aged gamma-irradiated-in-air polyethylene tibial component while following designs from the era when this sterilization method was used. Recognition is expedited by understanding how shelf life is related to product demand and can be of aid when diagnosing the painful knee.