Combination Drug Therapy for the Management of Chronic Neuropathic Pain.

Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combination therapies showed promise to improve efficacy over monotherapy, clinical trial data on their efficacy in specific populations are lacking and increased risk for adverse effects should be carefully considered. Drug-drug co-crystallization has emerged as an innovative pharmacological approach which can combine two or more different active pharmaceutical ingredients in a single crystal, optimizing pharmacokinetic and physicochemical characteristics of the native molecules, thus potentially capitalizing on the synergistic efficacy between classes of drugs while simplifying adherence and minimizing the risk of side effects by reducing the doses. In this work, we review the current pharmacological options for the treatment of chronic NP, focusing on combination therapies and their ongoing developing programs and highlighting the potential of co-crystals as novel approaches to chronic NP management.

Stand-Alone Percutaneous Pedicle Screw Lumbar Fixation to Indirectly Decompress the Neural Elements in Spinal Stenosis: A Radiographic Assessment Case Series.

BACKGROUND: The ideal surgical treatment of lumbar canal stenosis remains controversial. Although decompressive open surgery has been widely used with good clinical outcome, minimally invasive indirect decompression techniques have been developed to avoid the complications associated with open approaches. The purpose of this study was to evaluate the radiologic outcome and safety of the indirect decompression achieved with stand-alone percutaneous pedicle screw fixation in the surgical treatment of lumbar degenerative pathologies. METHODS: Twenty-eight patients presenting with spinal degenerative diseases including concomitant central and/or lateral stenosis were treated with stand-alone percutaneous pedicle screw fixation. Radiographic measurements were made on axial and sagittal magnetic resonance (MR) images, performed before surgery and after a mean follow-up period of 25.2 months. Measurements included spinal canal and foraminal areas, and anteroposterior canal diameter. RESULTS: Percutaneous screw fixation was performed in 35 spinal levels. Measurements on the follow-up MR images showed statistically significant increase in the cross-sectional area of the spinal canal and the neural foramen, from a mean of 88.22 and 61.05 mm2 preoperatively to 141.52 and 92.18 mm2 at final follow-up, respectively. The sagittal central canal diameter increased from a mean of 4.9 to 9.1 mm at final follow-up. Visual analog scale (VAS) pain score and Oswestry Disability Index (ODI) both improved significantly after surgery (p < 0.0001). CONCLUSION: Stand-alone percutaneous pedicle screw fixation is a safe and effective technique for indirect decompression of the spinal canal and neural foramina in lumbar degenerative diseases. This minimally invasive technique may provide the necessary decompression in cases of common degenerative lumbar disorders with ligamentous stenosis.

Evaluation of Lumbar Adhesiolysis Using a Radiofrequency Catheter During Epiduroscopy in the Treatment of Failed Back Surgery Syndrome (FBSS).

Failed back surgery syndrome (FBSS) is a complication of spinal surgery that results in severe and disabling back/leg pain. Epiduroscopy is a percutaneous minimally invasive surgical technique used in the treatment of lumbar radicular pain that enables both direct visualization of epidural adhesions in patients with FBSS and the mechanical release of fibrotic scars in the epidural space. Although the use of a balloon catheter during epiduroscopy can usually remove adhesions between the dura and the vertebrae, in the thickest areas of fibrosis, the use of a catheter with a molecular quantum resonance radiofrequency generator may resect hard epidural fibrotic obstructions. The aim of this study was to evaluate the efficacy and safety of this radiofrequency catheter in the treatment of severe epidural fibrotic scars. Ninety-three patients with FBSS were enrolled in this study. In 49 cases, a thick area of fibrosis was visualized during epiduroscopy and the use of a balloon catheter could not remove the fibrotic scars. In all of these cases, we used a molecular quantum resonance radiofrequency catheter to remove dense fibrotic areas. Intraoperatively during epiduroscopy, we could directly visualize lysis of the fibrotic scars. Immediately after the procedure and at 1-month and 6-month follow-up, the patients reported significant pain reduction. Pain reduction and patient satisfaction were also reported at 12 months in all but 5 cases. This study found a clinically relevant reduction of pain at 1 and 6 months after epiduroscopy in patients with FBSS. The use of a radiofrequency catheter is safe and effective in resection of hard and thick epidural scars.

Delphi-Based Expert Consensus Statements for the Management of Percutaneous Radiofrequency Neurotomy in the Treatment of Lumbar Facet Joint Syndrome.

INTRODUCTION: A modified Delphi strategy was implemented for obtaining recommendations that could be useful in the management of percutaneous radiofrequency treatment of lumbar facet joint syndrome, as the literature on the argument was poor in quality. METHODS: An Italian research team conducted a comprehensive literature search, defined the investigation topics (diagnosis, treatment, and outcome evaluation), and developed an explorative semi-structured questionnaire. They also selected the members of the panel. After an online meeting with the participants, the board developed a structured questionnaire of 15 closed statements (round 1). A five-point Likert scale was used and the cut-off for consensus was established at a minimum of 70% of the number of respondents (level of agreement ≥ 4, agree or strongly agree). The statements without consensus were rephrased (round 2). RESULTS: Forty-one clinicians were included in the panel and responded in both rounds. After the first round, consensus (≥ 70%) was obtained in 9 out of 15 statements. In the second round, only one out of six statements reached the threshold. The lack of consensus was observed for statements concerning the use of imaging for a diagnosis [54%, median 4, interquartile range (IQR) 3-5], number of diagnostic blocks (37%, median 4, IQR 2-4), bilateral denervation (59%, median 4, IQR 2-4), technique and number of lesions (66%, median 4, IQR 3-5), and strategy after denervation failure (68%, median 4, IQR 3-4). CONCLUSION: Results of the Delphi investigations suggest that there is a need to define standardized protocols to address this clinical problem. This step is essential for designing high-quality studies and filling current gaps in scientific evidence.

Ultrasound-guided Percutaneous Laser Disc Decompression (PLDD) with Fluoroscopic Validation for the Treatment of Cervical Disc Herniation: Technical Note.

OBJECTIVE: Percutaneous laser disc decompression (PLDD) has been regarded as an effective alternative for the treatment of cervical soft disc herniations. Repeated X-Ray scanning is essential when performing this technique. DESIGN: Technical note. METHODS: We present a new method for the treatment of cervical disc herniation using ultrasound to guide the needle entry to the cervical disc, to avoid excess of radiation exposure during the surgical procedure. We evaluated the efficacy of this cervical approach. We retrospectively reviewed the clinical data of 14 cases who underwent a PLDD under ultrasound guidance for the treatment of contained cervical disc herniation using a 1,470 Nm diode laser. The lower cervical discs (C5-C6 and C6-C7) were the most affected sites, accounting for 78.6% of surgical discs. A significant NRS reduction between baseline and 1 month (P = .0002) and between baseline and 12 months (P = .0007) was observed. CONCLUSIONS: Our results support the conclusion that ultrasound guided PLDD with fluoroscopic validation is a minimally invasive technique for patients affected by herniated cervical discs, but proper choice of patients is critical. This approach should not be performed except after adequate training under close supervision of surgeons experienced in this procedure and in interventional US.

Radiation Exposure during Fluoroscopy-Guided Ozone Chemonucleolysis for Lumbar Disc Herniation.

Introduction: Radiation exposure is a frequent drawback of spinal surgery, even if X-ray guidance plays a pivotal role in improving the accuracy and safety of spinal procedures. Consequently, radiation protection is essential to reduce potential negative biological effects. The aim of this study was to evaluate patients' radiation exposure, the radiation dose emission during fluoroscopy-guided ozone chemonucleolysis (OCN), and the potential role of patient characteristics. Methods: The radiation dose emission reports were retrospectively evaluated in patients who underwent single-level OCN for lumbar disc herniation. A generalized linear model (GLM) with a gamma distribution and log link function was used to assess the association between radiation emission and patients' characteristics such as age, sex, BMI, level of disc herniation, disc height, and site of disc herniation. Results: Two hundred and forty OCN cases were analyzed. A safe and low level of radiation exposure was registered during OCN. The median fluoroscopy time for OCN was 26.3 (19.4−35.9) seconds, the median radiation emission dose was 19.3 (13.2−27.3) mGy, and he median kerma area product (KAP) was 0.46 (0.33−0.68) mGy ⋅ m2. The resulting KAP values were highly dependent on patient variables. In particular, sex, obesity, and residual disc height < 50% significantly increased the measured KAP, while levels of disc herniations other than L5-S1 reduced the KAP values. Conclusions: The radiation exposure during OCN is low and quite similar to a simple discography. However, patient characteristics are significantly related to radiation exposure and should be carefully evaluated before planning OCN.

The modified NUTRIC score (mNUTRIC) is associated with increased 28-day mortality in critically ill COVID-19 patients: Internal validation of a prediction model.

BACKGROUND: High prevalence of malnutrition was found in critically ill COVID-19 patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score is frequently used for nutritional risk assessment in intensive care unit (ICU) COVID-19 patients. The aim of this study was to investigate the role of mNUTRIC score to predict 28-day mortality in critically ill COVID-19 patients admitted to ICU. METHODS: A cohort of consecutive COVID-19 critically ill patients admitted to ICU was retrospectively evaluated and the nutritional risk was assessed with the use of mNUTRIC score. A multivariable Cox regression model to predict 28-day mortality was therefore developed including the mNUTRIC as a covariate. Internal validation was performed using the bootstrap resampling technique to reduce possible bias in the estimated risks. The performance of the prediction model was assessed via calibration and discrimination. RESULTS: A total of 98 critically ill COVID-19 patients with a median age of 66 years (56-73 IQR), 81 (82.7%) males were included in this study. A high nutritional risk (mNUTRIC ≥5 points) was observed in 41.8% of our critically ill COVID-19 patients while a low nutritional risk (mNUTRIC <5 points) was observed in 58.2%. Forty-five patients (45.9%) died within 28 days after ICU admission. In multivariable model after internal validation, mNUTRIC ≥5 (optimism adjusted HR 2.38, 95% CI 1.08-5.25, p = 0.02) and high-sensitivity C-reactive protein values (CRP) (optimism adjusted HR 1.02, 95% CI 1.01-1.07, p = 0.005) were independent predictors of 28-day mortality. CONCLUSIONS: A high prevalence of malnutrition as revealed by mNUTRIC was found in our critically ill COVID-19 patients once admitted in ICU. After adjustment for covariables, mNUTRIC ≥5 and CRP levels were independently associated with 28-day mortality in critically ill COVID-19 patients. The final model revealed good discrimination and calibration. Nutritional risk assessment is essential for the management of critically ill COVID-19 patients as well as for outcome prediction.

Prediction of 28-day mortality in critically ill patients with COVID-19: Development and internal validation of a clinical prediction model.

BACKGROUND: COVID-19 pandemic has rapidly required a high demand of hospitalization and an increased number of intensive care units (ICUs) admission. Therefore, it became mandatory to develop prognostic models to evaluate critical COVID-19 patients. MATERIALS AND METHODS: We retrospectively evaluate a cohort of consecutive COVID-19 critically ill patients admitted to ICU with a confirmed diagnosis of SARS-CoV-2 pneumonia. A multivariable Cox regression model including demographic, clinical and laboratory findings was developed to assess the predictive value of these variables. Internal validation was performed using the bootstrap resampling technique. The model's discriminatory ability was assessed with Harrell's C-statistic and the goodness-of-fit was evaluated with calibration plot. RESULTS: 242 patients were included [median age, 64 years (56-71 IQR), 196 (81%) males]. Hypertension was the most common comorbidity (46.7%), followed by diabetes (15.3%) and heart disease (14.5%). Eighty-five patients (35.1%) died within 28 days after ICU admission and the median time from ICU admission to death was 11 days (IQR 6-18). In multivariable model after internal validation, age, obesity, procaltitonin, SOFA score and PaO2/FiO2 resulted as independent predictors of 28-day mortality. The C-statistic of the model showed a very good discriminatory capacity (0.82). CONCLUSIONS: We present the results of a multivariable prediction model for mortality of critically ill COVID-19 patients admitted to ICU. After adjustment for other factors, age, obesity, procalcitonin, SOFA and PaO2/FiO2 were independently associated with 28-day mortality in critically ill COVID-19 patients. The calibration plot revealed good agreements between the observed and expected probability of death.

Practical Advices for Treating Chronic Pain in the Time of COVID-19: A Narrative Review Focusing on Interventional Techniques.

BACKGROUND: Since the management of chronic pain has become even more challenging secondary to the occurrence of SARS-CoV-2 outbreaks, we developed an exhaustive narrative review of the scientific literature, providing practical advices regarding the management of chronic pain in patients with suspected, presumed, or confirmed SARS-CoV-2 infection. We focused particularly on interventional procedures, where physicians are in closer contact with patients. METHODS: Narrative Review of the most relevant articles published between June and December of 2020 that focused on the treatment of chronic pain in COVID-19 patients. RESULTS: Careful triage of patients is mandatory in order to avoid overcrowding of hospital spaces. Telemedicine could represent a promising tool to replace in-person visits and as a screening tool prior to admitting patients to hospitals. Opioid medications can affect the immune response, and therefore, care should be taken prior to initiating new treatments and increasing dosages. Epidural steroids should be avoided or limited to the lowest effective dose. Non urgent interventional procedures such as spinal cord stimulation and intrathecal pumps should be postponed. The use of personal protective equipment and disinfectants represent an important component of the strategy to prevent viral spread to operators and cross-infection between patients due to the SARS-CoV-2 outbreaks.

Factors Predicting Successful Outcome for Ozone Chemonucleolysis in Lumbar Disk Herniation.

OBJECTIVES: The aim of this study was to retrospectively investigate factors predicting a successful outcome after ozone chemonucleolysis (OCN) in patients with radicular pain and poor response to conservative treatments. METHODS: Univariable and multivariable logistic regression analysis was used to identify the predictors of good outcome after OCN. Good outcome was defined as 33% Oswestry Disability Index (ODI) reduction (model 1) or 13-point ODI improvement (model 2) at 1 month after OCN. RESULTS: Two hundred seventy-three patients were analyzed. A significant pain reduction (pre-operative Numerical Rating Scale [NRS] 6.7 ± 1.5, postoperative NRS 2.6 ± 2.2, P < 0.0001) and ODI improvement (pre-operative ODI 39 ± 13.7, postoperative ODI 21.4 ± 13.8, P < 0.0001) was obtained 1 month after OCN. Pain duration (< 1 year), type of disk herniation based on Michigan State University classification (MSU), stages of disk degeneration revealed by discogram and absence of foraminal stenosis (bony or ligament flavum hypertrophy) appeared as predictors of successful outcome. Age, gender, previous spine surgery, level site of disk herniation, presence of uncontained lumbar disk herniation, and vertebral Modic changes were not statistically associated with the outcome. Both the models showed a good accuracy (model 1, area under the curve [AUC] = 0.84 ± 0.027, 95% confidence interval [CI] = 0.79 to 0.89; model 2, AUC = 0.86 ± 0.024, 95% CI = 0.81 to 0.91). CONCLUSIONS: OCN is an effective treatment for radicular pain due to disk herniation. Pain duration (< 1 year), MSU disk herniation type (1A, 1B, 1C, 2A, and 2B), disk degeneration grade 2, and absence of foraminal stenosis are all associated with the successful outcome and should be carefully evaluated before OCN.

Genicular Nerve Pulsed Dose Radiofrequency (PDRF) Compared to Intra-Articular and Genicular Nerve PDRF in Knee Osteoarthritis Pain: A Propensity Score-Matched Analysis.

BACKGROUND: Chronic knee osteoarthritic (OA) pain is a common and debilitating complaint in elderly patients. Despite numerous pharmaceutical options, the majority of patients still experience long-term pain. Genicular nerve (GN) radiofrequency has become increasingly popular as a treatment for knee pain. This retrospective study aimed to evaluate the effects of pulse dose radiofrequency (PDRF) in patients with chronic knee OA pain. PATIENTS AND METHODS: Propensity score matching analysis was performed in a retrospective cohort of 78 patients with moderate-severe knee OA pain unresponsive to conservative treatment who underwent PDRF GN or intra-articular (IA) and PDRF GN. Pain relief was measured using the numeric rating scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Patient Global Impression of Change (PGIC) at 3 and 6 months post-intervention. RESULTS: A significant reduction in NRS scores was reported at 3 (p<0.001) and 6 months (p<0.001) after PDRF in both groups. NRS was lower in PDRF IA + GN than PDRF GN (p<0.0001). WOMAC pain was significantly reduced at 3 months in PDRF IA + GN group (baseline: 10.12±3.14, 3 months: 6.25±2.44, p=0.0001). WOMAC stiffness and function were improved only at 3 months in PDRF IA + GN compared to baseline (p=0.007 and p=0.006, respectively). A longer period of pain relief was reported after PDRF IA + GN (6.75±2.42 months) compared to PDRF GN (4.31±2.85 months, p<0.001) in association with higher PGIC scores. CONCLUSION: This is the first study that compared two different PDRF techniques. PDRF GN and PDRF IA + GN were both effective in reducing pain at 3 and 6 months follow-up. However, only PDRF IA + GN was able to improve WOMAC scores at 3 months after the treatment with a longer period of efficacy compared to PDRF GN alone.

Quantitative Sensory Testing (QST) Estimation of Regional Cutaneous Thermal Sensitivity During Waking State, Neutral Hypnosis, and Temperature Specific Suggestions.

This study aimed to determine the effects of neutral hypnosis and hypnotic temperature suggestions in thermal and pain thresholds compared to resting state. Sixteen healthy medium or high hypnotizable volunteers were enrolled. Hypnotizability was assessed with the Hypnotic Induction Profile (HIP); QST was checked in resting state, in neutral hypnosis, after suggestions of heat and cold, and after deinduction. A significant increase in heat threshold was recorded during hypnosis with both cold and heat suggestions compared to neutral hypnosis. HIP induction score showed a linear correlation with changes of temperature thresholds after heat and cold suggestions. Thermal suggestions may result in a significant increase of heat perception thresholds with respect to neutral hypnosis. HIP score is related to thermal threshold changes. QST is a valuable and manageable tool to measure temperature threshold change during hypnosis.