Four weeks after treatment, abdominal pain was significantly worse in the PIPAC group . The differential effect over time for abdominal pain differed significantly between both groups . PIPAC-OX resulted in significantly worse postoperative abdominal pain than primary tumor surgery. These results can be used for patient counseling and stress the need for adequate analgesia during and after PIPAC-OX. Further research is required to prevent or reduce abdominal pain after PIPAC-OX.Oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) is an emerging palliative treatment for patients with unresectable colorectal peritoneal metastases. Previously, our study group reported that patients experienced abdominal pain for several weeks after PIPAC-OX. However, it is unknown how this compares to abdominal pain after regular colorectal cancer surgery. To provide some perspective, this study compared the presence of abdominal pain after PIPAC-OX to the presence of abdominal pain after primary tumor surgery. Patient reported abdominal pain scores (EORTC QLQ-CR-29), from two prospective, Dutch cohorts were used in this study. Scores ranged from 0 to 100, a higher score represents more abdominal pain. Abdominal pain at baseline and at four weeks after treatment were compared between the two groups. Twenty patients who underwent PIPAC-OX and 322 patients who underwent primary tumor surgery were included in the analysis. At baseline, there were no differences in abdominal pain between both groups  Given the lack of prospective studies5, the CRC-PIPAC study was conducted to prospectively investigate the safety, feasibility, preliminary efficacy of repetitive PIPAC-OX monotherapy in twenty patients with unresectable CPM7. A secondary aim was to explore patient-reported outcomes (PROs) during trial treatment8. It was observed that several PROs were affected, but ultimately all PROs remained unaffected or recovered over time except one PRO, abdominal pain. While abdominal pain did not worsen cumulatively, it worsened significantly after each PIPAC procedure8. The presence of abdominal pain after treatment with PIPAC-OX was also reported by other researchers9.Oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) is a new palliative treatment option for patients with unresectable colorectal peritoneal metastases (CPM)abdominal pain in patients treated with PIPAC-OX for unresectable CPM to CRC patients undergoing PTS and the results of this study will provide more insight into the burden of PIPAC-OX.Given the novelty of PIPAC-OX, it is unknown how the presence of abdominal pain after PIPAC-OX compares to the occurrence of abdominal pain after other surgical interventions within colorectal cancer (CRC) treatment, such as primary tumor surgery (PTS). Therefore, the aim of this study was to compare the PRO 10. The CRC-PIPAC study was conducted in two Dutch hospitals and the PROCORE study was conducted in four Dutch hospitals. Both studies were approved by a central medical ethics committee  and institutional review boards of all participating study centers . Informed consent was obtained from all participating patients and the research was performed in accordance with the Declaration of Helsinki.This study compared prospectively collected PROs from patients who were enrolled in the CRC-PIPAC study (NCT03246321 [01-10-2017]) to patients who were enrolled in the PROCORE study (NL51119.060.14 [01-01-2016])2) under general anesthesia with a simultaneous bolus of intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2). Oxaliplatin was prepared in a total volume of 150 mL dextrose solution and injected through the nebulizer  in 5 min, after which the Ultravision generator  administered electrostatic precipitation to the aerosol. The electrostatic field and the capnoperitoneum were maintained for 25 min. PIPAC-OX procedures were repeated every six weeks, until disease progression, unacceptable toxicity, physicians decision-, or patient’s request to discontinue. All patients who underwent at least one PIPAC-OX were included and only results from the first PIPAC-OX were used in the comparative analyses.The CRC-PIPAC study was a single-arm phase 2 clinical trial that prospectively enrolled twenty patients with isolated unresectable CPM between October 2017 and September 2018. Patients underwent PIPAC-OX . All patients diagnosed with stage 2–4 colorectal cancer between 1 January 2016 and 31 December 2018 who underwent PTS were included in the comparative analyses.Post-operative management for patients of both groups was in accordance to early recovery after surgery (ERAS) guidelines, meaning that analgesia protocols prescribed opioids only if necessary and only short-term.12. Only one PRO was included in this study: abdominal pain (EORTC QLQ-CR29). PRO scores were calculated according to the corresponding manual13. Scores range from 0 to 100, a higher score represents more abdominal pain.Patients in the CRC-PIPAC study were asked to complete PRO questionnaires at baseline and at one and four weeks after PIPAC-OX. Patients in the PROCORE study were asked to complete PRO questionnaires at baseline and four weeks after PTS. In both studies, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) CR29 questionnaire was usedp < 0.01 to adjust for multiple testing. The Cohen’s D (CD) was calculated to determine the clinical relevance (i.e. > 0.500). IBM SPSS Statistics  was used for all analyses.Categorical baseline characteristics were presented as n (%) and compared with the Chi-square test. PRO scores of both groups were presented as mean with standard deviation. Differential effects in abdominal pain scores over time and scores at both time points (i.e. baseline and four weeks after surgery / first PIPAC procedure) were compared between PTS-patients and PIPAC-OX-patients using linear mixed modeling (LMM). For LMM maximum likelihood estimation and an unstructured covariance matrix were used. The covariance matrix consisted of a two-level structure where the two repeated time points (i.e. baseline and 4 weeks post-operative) represented the lower levels and individual patients represented the higher level. Parameters known to potentially affect pain  were included in the model as covariates and subsequently removed if they did not improve the model. Statistical significance was set at The study population comprised 342 patients: 322 underwent PTS and 20 underwent PIPAC-OX.The baseline characteristics are provided in Table Among those in the PTS group, 104 (33%) patients underwent a right hemicolectomy or resection of the transverse colon; 109 (34%) patients underwent a left hemicolectomy or resection of the sigmoid colon; 99 (31%) patients underwent a low anterior or abdominoperineal resection; and 6 (2%) patients underwent a subtotal colectomy.p = 0.688). From baseline to four weeks postoperative, abdominal pain did not worsen in the PTS group , but worsened significantly in the PIPAC-OX group . This differential effect was significantly different between both patient groups   that were tested significantly improved the model and were therefore omitted.abdominal pain of patients with colorectal peritoneal metastases treated with PIPAC-OX to patients with colorectal cancer treated with primary tumor surgery. At four weeks postoperative, patients treated with PIPAC-OX experienced significantly more abdominal pain than patients treated with PTS. This is a counterintuitive finding, since no visceral resections are performed during PIPAC-OX, whereas visceral resection are regularly performed during PTS.This study aimed to compare 14. However, the previously published CRC-PIPAC study showed an increase in abdominal pain one week after each procedure followed by a relative decrease in abdominal pain three weeks later, suggesting that the increase in abdominal pain is at least in part due to PIPAC-OX8. Given the repetitive intent of treatment with PIPAC-OX, these palliative patients are repetitively exposed to abdominal pain. This should be considered by both treating physicians and patients before starting treatment and it stresses the need for adequate analgesic protocols.One of the major proclaimed benefits of PIPAC-OX is the limited effect of this treatment on quality of life, which would be favorable in the palliative setting. However, the current study suggests that patients undergoing PIPAC-OX experience significantly more abdominal pain than patients undergoing PTS. Patients undergoing PIPAC-OX have a more advanced cancer stage than PTS patients, therefore PIPAC-OX patients are more at risk for oncological pain, especially since no resections are performed in this patient group15. The effect of PIPAC on abdominal pain may be drug dependent, as two studies reported a greater inflammatory response16 and a greater morphine demand17 after PIPAC-OX than after PIPAC with cisplatin/doxorubicin. Furthermore, although a dose-dependent effect of PIPAC-OX on abdominal pain was not reported in two dose-escalating studies in the palliative setting19, a third study investigating PIPAC-OX in the adjuvant setting  observed severe abdominal pain in the majority of patients treated with PIPAC-OX, who required either dose-reduction of intraperitoneal oxaliplatin or discontinuation of adjuvant PIPAC-OX9. However, the different setting of this third study  may explain the observed dose-dependent effect on abdominal pain, since patients in the palliative setting might be more willing to accept (severe) adverse events from a last-resort treatment.Other studies investigating PIPAC in a palliative setting have also suggested that treatment with PIPAC-OX is less well-tolerated than initially thought, as it may result in chemical peritonitis or even peritoneal sclerosis, leading to abdominal pain25, three did not provide PRO results on abdominal pain22. Of the other four, one reported a transitory increase in pain23 whereas the other three reported that pain remained stable during treatment with PIPAC26. However, these studies did not provide separate PRO results for PIPAC-OX in patients with CPM25 nor for PIPAC-OX monotherapy26, which impedes the interpretation of these findings. In addition, a recent study reported increased pain levels after repetitive PIPAC treatment, as measured through patient reported outcomes27. While some of these studies report increased pain levels, they do not provide context to these increased pain levels. The results of the present study show that the severity of abdominal pain after PIPAC is higher than that after conventional surgery, thereby providing important insights into the pain burden caused by PIPAC-OX.While seven other studies also presented PROs during PIPAC with various drugs for various primary tumors among which PIPAC-OX for CPM28. However, the present finding simultaneously signifies the difference in abdominal pain, which was greater after PIPAC despite the PTS group more frequently undergoing open surgery.Although this is the first study to compare abdominal pain in patients with CPM who were treated with PIPAC-OX to patients with colorectal cancer who underwent PTS, there are some limitations to this study. First, the PROCORE study population resembles a population-based study, since all patients with colorectal cancer were allowed to participate. In contrast, the PIPAC-OX study population consists of a highly selected group of palliative patients who required to be in an adequate clinical condition to participate in a clinical trial, which might have affected baseline quality of life. Second, the timing of only two PRO measurements matched between the two studies (i.e. baseline and four weeks after surgery). If the timing of more PRO measurements had matched, this could have provided more insight in short-term (e.g. one week after surgery) and longer-term  differences in PROs between the two groups. Given the poor prognosis of patients in the PIPAC-OX group, long-term PRO measurements were not available in this group. While these limitations may hinder the generalizability of the results to some extent, they do provide important information on patient reported pain after PIPAC-OX treatment, even if it only concerns the short-term, non-repetitive treatment situation. A third limitation concerns the operation-technique. Due to the registration in the PROCORE study, no information could be obtained regarding operation technique (e.g. open vs. laparoscopic). It is to be expected that an open technique would result in more post-operative pain, as the surgical trauma is larger. This might have increased the reported abdominal pain scores in the PTS group and might have attenuated the differential effect found in this study. A comparative study between laparoscopic PTS and PIPAC might thus result in an even bigger difference in abdominal pain as in the Netherlands approximately 32% of patients with CRC underwent open surgery, while 68% underwent laparoscopic surgery in 2015Patients with colorectal peritoneal metastases who were treated with PIPAC-OX reported significantly more abdominal pain at four weeks postoperative than patients with colorectal cancer who underwent PTS. Although this effect might in part be caused by a more advanced tumor stage, it nevertheless indicates that physicians should not underestimate the longevity and severity of abdominal pain after PIPAC-OX. Physicians should counsel patients accordingly and should consider analgesic measures to reduce these symptoms, especially since PIPAC-OX is mainly applied in the palliative setting and is often repeated several times. Future studies should focus on the development of analgesic protocols aiming to reduce abdominal pain during treatment with PIPAC-OX.


Background: This study aimed to compare local periarticular infiltration (LIA) with ultra-sound guided regional anesthesia (USRA) with ropivacaine and dexmedetomidine as an additive agent in primary total knee arthroplasty (TKA). Methods: Fifty patients were randomized into two groups in a 1:1 ratio. Patients in the LIA group received local periarticular infiltration into the knee joint. The USRA group received two single-shot USRA blocks. Functional outcomes and satisfaction , including well-being, were analyzed preoperatively and at five days, six weeks, and one and two years postoperatively. Results: Functional outcomes did not significantly differ between the two groups at six weeks and one and two years after the implementation of TKA. A moderate correlation was observed in the LIA group regarding well-being and pain on day five. Six weeks postoperatively, the LIA group showed significantly superior well-being but worse pain scores. No differences between the groups in well-being and functional outcomes could be observed one and two years postoperatively. Conclusion: Patients treated with LIA had superior postoperative well-being in the early postoperative phase of up to six weeks. Furthermore, LIA patients had similar functionality compared to patients treated with USRA but experienced significantly more pain six weeks postoperatively. LIA leads to improved short-term well-being, which is potentially beneficial for faster knee recovery. We believe that LIA benefits fast-track knee recovery with respect to improved short-term well-being, higher practicability, and faster application. Postoperative pain management is still developing  but is cThe optimization of analgesia in TKA patients plays an important role in postoperative clinical outcomes, as there is a strong association between postoperative pain, early recovery, and functionality . PostopeIn recent years, there has been a shift toward using multimodal analgesic regimens to aim at multiple pain pathways while reducing opioid consumption. Among these, multimodal pain regimens utilizing local infiltration analgesia (LIA), also known as the local periarticular infiltration anesthesia technique, and peripheral nerve blocks (PNB) have emerged to handle surgical pain and enable early postoperative mobilization ,16,17.Among peripheral nerve blocks (PNBs), the femoral, sciatic, and obturator nerves are the most common targets for postoperative analgesia by ultrasound-guided regional anesthesia (USRA) in TKA . FurtherHowever, although the combination of FNB and SNB shows excellent results in pain reduction, it is associated with reduced mobility from muscle weakness, which can prevent a rapid recovery from occurring ,22. ThisThe use of perineural dexmedetomidine in combination with nerve blocks has emerged as a potentially promising approach to enhance the outcomes of regional anesthesia ,27,28. SConcerning regional anesthesia and analgesia, it has shown superiority over fentanyl in elective cesarean sections by increasing the time to first rescue analgesia and prolonging the duration of the sensory block . AdditioGiven these promising outcomes, dexmedetomidine has also been described as one of the most promising additive drugs in the field of regional anesthesia . HoweverAs LIA is a feasible alternative to USRA due to its ease of implementation and rapid placement in clinical practice, we examined these two concepts in TKA as part of this prospective randomized controlled study with a two-year follow-up. We focused on ambulation, postoperative well-being, and functional outcome scores after surgery.This study aimed to compare local periarticular infiltration (LIA) with ultrasound-guided regional anesthesia (USRA) with ropivacaine and dexmedetomidine as an additive agent in primary total knee arthroplasty (TKA).This randomized, controlled clinical trial (RCT) followed accepted ethical, scientific, and medical standards and was conducted in compliance with recognized international standards, including the principles of the Declaration of Helsinki. Informed consent was obtained from all the participants, and the study protocol was approved by the institutional Ethics Committee (32–239 ex 19/20) and registered with data safety authorities .The study’s cohort was based on a previous study  that exahttps://www.randomizer.at, accessed on 27 November 2020, certified according to ISO-9001:2015) generated the random allocation sequence before the surgery. Patients and physicians were aware of the group assignments. In the LIA group, patients were given local infiltration analgesia from the surgeon at the end of TKA. In the USRA group, patients received two ultrasound-guided peripheral nerve blocks from their anesthesiologist immediately before anesthesia induction in the operating theater. Postoperatively, the patients followed a standardized rehabilitation protocol, which consisted of full weight bearing with crutches immediately after surgery and continuous passive motion (CPM) on the first postoperative day. The study adhered to the applicable CONSORT guidelines ) for nonparametric data, and the Kolmogorov–Smirnov and Shapiro–Wilk tests were used for normal distribution testing. For univariate analyses of statistical significance, Fisher’s exact test or the Mann–Whitney test for nonparametric data were performed. Statistical significance was analyzed with a two-sided alpha of less than 5% as a significance level. Further analyses included rank correlation with Spearman’s ρ and logistic regression. Spearman correlations were performed to assess a possible correlation between the use of LIA and the items of the questionnaires (at rest and during exercise). For the logistic regression models for well-being, the covariates “type of anesthesia” , “type of administration of local anesthetics “(LIA [binary]), and “sex” (binary) were adjusted. The well-being Likert scores with a threshold of good (two lowest disturbance scores) and bad (two highest scores) were dichotomized in this logistic regression analysis. A priori power analysis  regarding the endpoints well-being and clinical outcome was performed with a difference of 10% set for clinical relevance and revealed a number of n = 25 per group as sufficient, with a p = 0.037). No significant differences were observed between the two groups in baseline characteristics and demographics  (p = 1.000).The analysis of the questionnaires revealed that ten patients in the LIA group reported well-being, while only three did so in the USRA group, six weeks postoperatively (= 0.024) . No signp = 0.011). Differences in KSKS pain were non-significant thereafter. Furthermore, there were no significant differences in the other clinical outcome scores after TKA with dexmedetomidine LIA or combined FNB and SNB in the short (day 5 and week 6) or long term (one and two years), as reported in Functional outcome scores differed only in KSKS pain on day 5, with higher pain scores in the LIA group (p = 0.011). Differences in KSKS pain were non-significant thereafter. Furthermore, there were no significant differences in the other clinical outcome scores after TKA with dexmedetomidine LIA or combined FNB and SNB in the short- (day 5 and week 6), long-term (one and two years), which is reported in Functional outcome scores differed only in KSKS pain on day 5, with higher pain scores in the LIA group (p < 0.01) were correlated moderately. When the well-being of patients was placed in a logistic regression model adjusted for LIA, sex, and type of anesthesia , only the performance of LIA remained significant (p = 0.231), allodynia (p = 0.191), and hyperalgesia (p = 0.280) six weeks and one and two years after surgery showed no significant differences between groups.Regarding the observed correlations between LIA and the questionnaires, only well-being and KSKS pain five days after surgery  with ultrasound-guided regional anesthesia (USRA) with ropivacaine and dexmedetomidine as an additive agent in primary total knee arthroplasty (TKA).The most important finding of our investigation was that patients reported significantly higher rates of well-being when LIA was performed than USRA, despite higher postoperative opioid requirements during the first 24 postoperative hours . AlthougThis could mean that the sensory/motor block caused by USRA has a greater influence on early well-being than more intense pain and a greater need for opioids, as observed in our LIA group. We interpret this in light of the patients’ expectations, which certainly include postoperative pain more often than temporary motor paralysis for up to two days postoperatively, leading to the aforementioned results. This circumstance can probably be best explained by the brief and simplified definition of well-being, “… the state of feeling healthy and happy”, which can only be assessed subjectively .It is known that general physical well-being affects satisfaction in patients following TKA . FurtherKampitak et al.  assessedRegarding postoperative short-term functionality, our findings align with previous studies that evaluated patients who underwent TKA with regional anesthesia or LIA, showing no significant differences up to one year after surgery ,58. Fan A recent study compared the additional implementation of dexmedetomidine with ropivacaine in LIA and USRA  and revealed a superior opioid-sparing effect in both groups, with USRA being superior to LIA when compared directly . As withFor patient satisfaction, FNB combined with LIA was determined as the best option . StudiesThe results of LIA and various types of USRA in terms of functional outcomes, postoperative pain, length of hospital stay, satisfaction, and opioid consumption are still controversial in the current literature ,57,62,65This RCT observed that USRA and LIA influence patient well-being and early postoperative pain differently but show similar functional outcomes. We emphasize that the decision regarding whether to perform LIA or USRA should be sought individually, primarily depending on the medical indications, patient expectations, and perceptions, including the careful evaluation of individual risk factors and benefits for each patient, as well as the goals of the rehabilitation process after surgery. Our results suggest that determining the postoperative analgesic method of choice in TKA patients should also rely on whether analgesia (USRA) or motor function (LIA) is the priority, especially in the early postoperative period, to improve patient outcomes.We wish to underline that the discrepancy between spinal and general anesthesia, with more LIA patients having undergone spinal anesthesia, was a confounder within the data. Moreover, this study did not compare outcomes during the first four postoperative days, which would likely have provided additional valuable information for the comparison between the two groups, as the effects of the agents used typically disappeared after the first or second postoperative day. The observed differences among both groups (LIA vs. USRA) were based on the study’s small sample size, and the results should therefore be interpreted with caution. Based on the study’s limitations, we cannot suggest one method over the other as both approaches have advantages and disadvantages when it comes to well-being and pain in the early postoperative period.Patients treated with LIA had superior postoperative well-being in the early postoperative phase of up to 6 weeks and had similar functionality in comparison to patients treated with USRA but experienced significantly more pain. LIA leads to improved short-term well-being, which is potentially beneficial for faster knee recovery, including the motivation for rehabilitation and physical therapy. Additionally, LIA has advantages in its practicability, as it is easier and faster to perform than USRA.


To evaluate the effectiveness of dry needling (DN) and instrumental myofascial release (IMR) therapies in the cervico-cranio-mandibular system through pain, bite force, and distribution of occlusal contacts in patients with muscular temporomandibular disorders. p<0.05). Thirty patients were divided into treatment groups: DN (n=15) and IMR (n=15). Therapeutic efficacy regarding pain perception and tolerance of masticatory, facial, and cervical muscles, bite force, and distribution of occlusal contacts were analyzed in this observational longitudinal clinical study pre/post-intervention and pre/post one month of therapeutic intervention. The data were tabulated and statistically analyzed , right masseter, and left trapezius muscles. There was a statistically significant effect of the intervention on the mentalis, supraorbital, and infraorbital (right and left) muscles. There was a statistically significant effect of the interaction on the upper masseter (right and left), anterior temporal (left), suboccipital, sternocleidomastoid, and mentalis (left) muscles. There was an increase in post-intervention molar bite force in the groups, with a statistical effect on time versus intervention in the right and left regions. Contact of occlusal forces at the maxilla/mandible interface showed a difference between the mean times on teeth 26–36 after versus 1 month after the intervention. The two therapeutic techniques are viable for the treatment of muscular temporomandibular disorders; however, IMR proved to be more effective immediately after the intervention and after one month. Key words:Temporomandibular disorders, pain, masticatory muscles, facial muscles, cervical muscles, dry needling, instrumental myofascial release. The temporomandibular joint is considered a complex anatomical structure when observing biomechanics. It has a pair of interdependent condyles, in which harmonic work is needed between the sides to carry out the movements, and any modification will exceed the physiological tolerance of these structures .Among the functional alterations that compromise the temporomandibular joint, temporomandibular disorder (TMD) stands out. It encompasses a series of clinical problems involving the masticatory muscles, temporomandibular joint, and associated structures, and is characterized by the presence of pain, joint sounds, and irregular or limited mandibular function . It is dTemporomandibular dysfunction can involve the entire stomatognathic system, which is an important system of the human body that allows the processing and transport of food from the oral cavity to the internal part of the body in a safe way, as well as assisting in the processes of phonation, breathing, and swallowing .This musculoskeletal chronic pathological clinical condition is associated with myofascial pain, which also involves the function of the head and neck and becomes a syndrome with the presence of myofascial trigger points in the involved muscles, mainly the masticatory muscles . It is cFunctional evaluation methods are also fundamental for the analysis of the muscles of the cervico-cranio-mandibular system, as they allow the study of the muscular system after the application of therapeutic techniques. These provide important results on morphology and levels of functional activity and contribute to patient recovery .Therefore, this study aimed to evaluate the effectiveness of DN and IMR therapies in the cervico-cranio-mandibular system through pain, bite force, and distribution of occlusal contacts in patients with muscular TMD. The null hypothesis was that the two interventions do not improve the pain symptoms and the performance of the cervico-cranio-mandibular system in patients with muscular TMD.This observational longitudinal clinical study was approved by the ethics committee (process # 23555119.3.0000.5419). All the participants provided written informed consent.-SampleThe a priori sample calculation performed using the G* Power 3.1.9.2 software  considered the level of α = 0.05, test power of 0.95, and an effect size of 1.56 for the main result of the pain threshold on palpation of the study by Blasco-Bonora and Martín- Pintado-Zugasti  and IMR . There was a pairing between the participants by sex, age, weight, and height .Information regarding personal data, medical and dental history, presence of systemic diseases, parafunctional habits, and possible signs and symptoms of TMD was obtained. Therapeutic efficacy regarding pain perception and tolerance of masticatory, facial, and cervical muscles, bite force, and distribution of occlusal contacts were analyzed pre/post-intervention and pre/post one month of therapeutic intervention. The treatment was applied on two occasions separated by one month.Exclusion criteria were as follows: absence of cognitive system integrity; having a poorly adapted fixed prosthesis, a removable prosthesis, or a complete prosthesis; presence of periodontal disease  or restorations at risk of fractures; physical or mental indisposition present at the time of the examination; a clinical history of systemic diseases that require chronic medication, such as neurological and psychiatric disorders, as well as users of medications that could interfere with muscle activity; absence of all teeth; orthodontic treatment; speech therapy; physiotherapy or otolaryngology (previous or current).Inclusion criteria were as follows: age between 18 and 60 years, presence of TMD of muscular origin (Diagnostic Criteria for Temporomandibular Disorders - RDC/TMD), presence of pain and trigger points in the masseter muscles for more than three months with a score greater than three on the visual analog pain scale.Participants were confirmed with muscle TMD by digital palpation. To be included in the research, they demonstrated one or more muscle diagnoses for TMD, thus being classified in one or more of the subgroups of diagnoses of Axis I of the RDC/TMD: myofascial pain without limitation of mouth opening and myofascial pain with limitation of mouth opening .The DN technique was performed by needling the myofascial trigger points using short needles with a caliber and length of 0.20x13mm. The disposable and individual needles were placed in a plastic guide tube. The technical procedure consisted of inserting and deepening the needle by approximately 1 cm, and subsequently, the slow movements of insertion and partial removal of the needle in the region began. At each withdrawal, the insertion angle was modified in a circular manner, covering the entire region of the myofascial trigger points .The IMR technique was performed with a modified instrument called Gancho QuiuTech , which is composed of two stainless steel rods with active tips responsible for instrumentation, and an aluminum cable in which the rods were joined with the function handle developed within the anatomical and technical concepts, providing a dynamic instrumentation technique. The instrument was applied for approximately 20 s in a direction parallel to the muscle fibers treated with the instrument at an angle of 45°. The instrument was immediately manipulated into the muscles in a direction perpendicular to the muscle fibers with the instrument at a 45° angle for an additional 20 s, resulting in a total treatment time of approximately 40 s .-Pain intensity analysisThe visual analog scale (VAS) was used to indicate the intensities of pain before and immediately after performing the therapies. The scale consisted of a horizontal or vertical line of 100 millimeters (mm) or 10 centimeters (cm) with the ends marked as “no pain” and “maximum pain.” The patient registered a point on the line or between the extremes, and the researcher took measurements. Each VAS was completed on a separate piece of paper to avoid bias from the previous records. The patient was marked with a vertical line cutting the scale, where he believed his pain was located at the time of the examination.-Maximum molar bite force analysisThe maximum molar bite force was recorded using a digital dynamometer , with a capacity of up to 980,665 Newtons, adapted for oral conditions. This equipment was provided by two rods that contained Teflon disks at the ends on which the bite force was applied .At the time of bite force analysis, the patients remained seated in a position corresponding to the meato-orbital plane, parallel to the ground, and relaxed with the palms of the hands resting on the thighs. The bite struts were disinfected with alcohol and protected using disposable latex fingers  to avoid cross-contamination.The patients received instructions and performed tests by squeezing the rods of the equipment in the region of the first permanent molars on both sides before the records were obtained to ensure the reliability of the procedure. The patients were then asked to bite the rods with maximum effort to collect the maximum force. Six measurements were performed, with a 2-min interval between them, with alternating sides; that is, there were three measurements on the right side and three on the left side with alternating measurements per side. The highest strength measurements obtained on each side were adopted.-Evaluation of force distribution and occlusal analysisThe evaluation of the occlusal force distribution was performed using the Occlusense digital equipment  with a sensor that transmitted data via a Wi-Fi connection to the iPad application. The Occlusense tag could record up to 0.056 frames/s. The outer surfaces of the sensor were coated with an articulated red paint that marked the teeth simultaneously with the same time as the digital recording of the data.Occlusense has 256 strength levels with a four-color-coded scheme (green/yellow/orange/red). This color gradient demonstrated the distribution of the masticatory force in the evaluated area and the difference in pressure between the pressure points through the height of the pixels. Pixel color and height indicate the differences in contact with adjacent contacts. This equipment made it possible to dynamically record the relative strength of the arches and the distribution of dental contacts over time .To perform the procedure, the patients were instructed to remain seated in a chair without head support, with their feet flat on the floor. The sensor was positioned between the dental arches and was adjusted to the oral cavity. The patients were instructed to press the sensor on maximum dental intercuspation and apply the maximum force for six seconds, which was constant from the beginning to the end of the procedure. Two recordings were performed with an interval between the resting muscles. The system provides a graph with continuous recording. After performing the examination, the occlusal force distribution between the left and right sides and occlusal force distribution on teeth 16, 26, 36, and 46 were recorded. The occlusal analysis was performed using the OccluSense-iPad-App.-Pressure pain threshold analysisPressure pain threshold was measured in Kgf/cm2 using an algometer . The points chosen to measure the pressure pain threshold were the masseter, temporal, suboccipital, sternocleidomastoid, trapezius, supraorbital, infraorbital, and mentalis muscles.The patient was guided by the examiner in relation to pressure in order to advise him to activate the device when the increasing stimulus exerted on his face ceased to be a pressure and became painful. The patient was instructed not to endure the pain but to register the moment when the pain started.Prior to muscle assessment, a measurement was performed on each patient’s wrist to familiarize them with the methodology . The pre-Statistical analysisRepeated-measures analysis of variance (ANOVA) was performed to calculate the main effects of time (pre- versus post- versus pre-1 month versus post-1 month), group (GDN versus GLMI), and interaction (time versus intervention). Sphericity was tested using the Mauchly test, and homogeneity of variance was tested using Levene’s test. If sphericity was violated, the Greenhouse-Geisser correction was used. In the case of a significant effect of time and intervention, multiple comparison tests were used. Cohen’s coefficient was used to estimate the effect size (η2), interpreted as small (η2 = 0.2), medium (η2 = 0.5), or large (η2 = 0.8). A significance level of 5% was considered statistically significant. All analyses were performed using the Statistical Package for Social Sciences .p=0.018). A statistical effect of time was observed for the upper, middle, and lower right masseter; middle left masseter; anterior, middle, and posterior right and left temporal; right and left suboccipital; right and left sternocleidomastoid; left trapezius; and right and left mental muscles. There was a statistical effect of the intervention on the right and left supraorbital, right and left infraorbital, and right and left mental muscles. There was a statistical effect of the interaction between the right and upper left masseter, anterior left temporal, left suboccipital, left sternocleidomastoid, and left mental muscles.In this study, patients were divided into two groups: GDN and GIMR, which were evaluated pre- and immediately after the first and second interventions. The interval between the two interventions was one month. There was a positive effect on most of the evaluated parameters; therefore, the null hypothesis was rejected.The pain VAS results showed a reduction in the mean post-intervention pain values for both groups with the effect of time and interaction (time versus intervention) for the head and neck region. The reduction in the mean pain values for the GDN group was gradual until the last assessment. For GIMR, although the reduction in the mean values after the intervention was greater , after one month of treatment, the mean value increased and decreased after the second intervention.The positive effects of both treatments are in line with the literature; however, there is still no consensus on the number of interventions . In an aFrom a mechanical standpoint, drilling or massaging the trigger point can disrupt dysfunctional endplates, reduce the overlap between actin and myosin filaments, and decrease acetylcholine levels. Decreased acetylcholine levels may lead to increased muscle blood flow and oxygenation, consequently reducing sarcomere contracture .Regarding the neurophysiological effect, both techniques can reduce peripheral and central sensitization, removing the source of peripheral nociception, modulating spinal dorsal horn activity, and activating the central pain inhibitory pathways . Areas wThe results of the maximum molar bite force showed an increase in the mean values after the intervention in both groups, with a statistical effect of time and interaction (time versus intervention) in the region of the right and left molars. An increase in molar bite force indicates that both techniques are effective in treating myofascial pain. However, in the GDN group, after one month of treatment, the mean values decreased, increasing only after the second intervention. In contrast, the mean values of maximal molar bite force in the GIMR group increased continuously and gradually. This difference proves that the results of IMR are long-lasting.The results of this study revealed a difference between the mean values of teeth 26–36 immediately after the first and second interventions. This result was expected since the absence of a statistical difference between the right and left hemiarch indicated that the patients had a balanced occlusion .The ability to perceive pain in nociceptors showed an effect of time in all the evaluations for the right masseter and only for the middle left masseter. The interaction effect occurred for the right and upper left masseter, indicating that the mean pain tolerance values were higher for the GDN group in the relationship between time and intervention. The increase registered by the right and left masseter muscles was gradual and continuous in the GIMR group. In contrast, in the GDN group, this result was obtained only for the right inferior masseter muscle. For the other evaluations of the right and left masseters , there was a decrease in pain tolerance immediately after the intervention, with a tendency towards an increase in mean values after one month, when compared to the initial values.An increase in the tolerance of pain perception in these muscles is desirable, as pain in the masseter muscles is one of the greatest complaints in patients with TMD with the presence of myofascial trigger points . As for One of the post-needle-induced pain hypotheses is neuromuscular damage caused by consecutive needle insertions in the muscle, as well as by the hemorrhagic and inflammatory reactions triggered by the needle. A study supported this hypothesis of neuromuscular damage when it identified the lesion caused by the application of DN in the gastrocnemius muscle through magnetic resonance imaging .While the masseter is the most powerful mandibular elevator muscle, the temporalis is considered the mandibular repositioning muscle. The anterior bundles of the temporalis contract during maximum mouth opening. The posterior bundles contract during mandibular retraction and cause contralateral displacement. Thus, the temporal bone is fundamental not only in determining muscle tone in the postural position of the mandible but also in chewing movements .In this study, the effect of time was observed in all the evaluations of the temporal muscles. Continuous gradual increases in the mean values were recorded for the right and middle left temporal regions in both the groups and for the anterior and posterior left temporal regions only in the GIMR group. In the other analyses, there was a decrease in pain tolerance immediately after the intervention, with an increase in the mean values after one month, when compared to the initial values.These results were similar to those for the masseter muscles, the reasons for which have been discussed earlier. The success of IMR and DN in reducing pain in the temporal and masseter muscles in patients with TMD has been reported in other studies .Regarding the suboccipital muscle, which plays an important role in muscle posture, as it stabilizes the atlanto-occipital joint during head movements, helping to extend, laterally flex, and rotate the neck, an effect of time was observed on this musculature. The interaction effect for the left suboccipital muscle indicated that the mean pain tolerance values were higher for the GDN group in the relationship between time and intervention. Gradual and continuous increases were recorded in the right and left suboccipital regions in the GLMI group, and the left suboccipital regions in the GDN group. For the right suboccipital region in the GDN group, there was a decrease in pain tolerance immediately after the intervention, as already discussed. These results are in agreement with the literature .The sternocleidomastoid muscle is another important cervical muscle that has multiple functions, such as unilateral and bilateral contraction of the cervical region of the spine, which influences the masseter muscle. This study demonstrated that there was an effect of time on the right sternocleidomastoid muscle and an interaction for the left sternocleidomastoid muscle. Given the importance of this muscle, the results are promising as they demonstrate a positive impact of both techniques. These findings corroborate those of other studies that have used these techniques to treat patients with headaches or other disorders .The trapezius muscle is considered the dominant stabilizer of the scapula that contributes not only to the normal mechanics of the scapula but also to the entire shoulder region. Altered activation, poor control, and reduced strength of different parts of the trapezius have been associated with pain and reduced function. Data from this study showed that time had an effect on the left trapezius muscle. The positive impact of both techniques on this muscle is in agreement with the literature .The orbicularis oculi muscle is considered the sphincter of the eyelids and is involved in facial expressions, eye protection, and reflexes. Electrical stimulation of the supraorbital branch of the trigeminal nerve on one side results in ipsilateral short latency and bilateral long-latency orbicularis muscle contraction . In contIn contrast, the mentalis muscle is responsible for lifting the lower lip and assisting in facial expression, providing vertical support for the lower lip . It was This study had some limitations. Two interventions, one month apart, were not sufficient to eliminate pain. Future research should analyze the impact of treatment with a greater number of interventions and whether these results extend to other populations and clinical situations.This study suggests that DN and IMR techniques are viable therapeutic techniques for patients with muscular TMD; however, IMR proved to be more efficient both in the immediate post-intervention evaluation and after one month, as evidenced by the reduction of chronic pain and better performance of the cervico-cranio-mandibular system.


To verify the rates of heat effectiveness generated by Carbon Nanotubes (CNT) in the resolution of dizziness in individuals diagnosed with Cervical Dizziness (CD).Randomized clinical trial was performed and samples from volunteers diagnosed with CD, divided into a Study Group (SG) and Control Group (CG). Patches containing CNT with thermotherapeutic effect were used in SG and inert patches in the CG. Treatment was performed over 30 days and measures of pain, dizziness and asymmetry of cervical muscle tension were evaluated over 60 days.Pain, dizziness and asymmetry of cervical muscle tension were reduced in the SG. The variables analyzed in this study did not change in the CG.Our results show that the therapeutic effect of heat was effective in the treatment of patients diagnosed with CD. We could also observe a clear interrelationship between pain and dizziness symptoms with the asymmetry of cervical muscle tension.1B. Cervical origin accounts for 7.5% of dizziness etiologies; it impacts quality of life and is a growing concern within the realm of community health.By definition, CD is a clinical syndrome characterized by the presence of cephalic signs and symptoms originating in the cervical segment.Advancements in understanding the mechanisms involved in CD have facilitated the development of potential therapies. The use of manual therapy with positive outcomes in treatment has been described.This investigation had as its primary objective to analyze the role of CNT in relieving cervical pain and dizziness and to provide a new method to treat these disorders. In addition, the secondary objective was to evaluate how muscle tension asymmetry is associated with cervical pain and dizziness in patients diagnosed with CD.This is a randomized, double-blind clinical trial. The research team consisted of two physicians, a coordinator, an executor, and a physiotherapist. Participant randomization into Study Group (SG) and Control Group (CG) was performed based on a randomization list by the coordinating physician. The executing physician, physiotherapist, and participants were blinded to treatment allocation, which involved the application of patches with active CNT or placebo. Placebo patches, inert in nature, were employed in the study and prepared to be visually indistinguishable in appearance, form, and packaging. Envelopes containing the patches for application were coded to conceal their identity from participants, the physiotherapist, and the executing physician. Furthermore, the subtle thermal alteration ensures that both the SG and the CG do not perceive any difference in the adhesive applied to their skin. The coordinating physician monitored the integrity of blinding throughout the study, ensuring the objectivity and reliability of results. This approach was fundamental, aiming to minimize potential bias in the study and thereby ensuring the validity of the obtained outcomes.The patients were previously submitted to anamnesis, complete otoneurological examination, serological and electrophysiological tests, diagnostic imaging, and psychological evaluation. The diagnosis was based on dizziness characterized as imbalance, instability, or vertigo, necessarily related to the onset of cervical pain. No other vestibular diseases were identified, including vestibular migraine. All participants underwent cervical X-ray and computed tomography, or magnetic resonance imaging of the cervical spine were used when available.The inclusion criteria were diagnosis of CD, normal otoneurological examination findings, signing the informed consent form, no cervical radiological changes other than those attributable to ageing. The exclusion criteria were active vestibular disease; traumatic neck injury; neurological, rheumatic, or orthopaedic diseases not attributable to ageing  and/or those for which surgery is indicated; somatoform diseases; or cognitive limitations.Data from a preliminary pilot study provided the basic scenario for calculating the experiment’s sample size. A comparison of two means was performed, considering a standard deviation of 1.7, in a superiority test with a significance level of 5% and a power of 80%. A sample size of 16 patients per group was obtained. After patient recruitment commenced, a preliminary analysis was conducted, resulting in a statistically significant difference. The study was concluded with 20 patients: 15 in the SG and five in the CG.The groups received ten patches each. They were placed in the posterior cervical region: two in the suboccipital region, two around the fifth and sixth vertebrae, two in the transition region between the neck and shoulder, and the others in the region of greatest pain reported by the patient. The same physical therapist performed all assessments.All patients followed the same steps and procedures, except for the type of intervention, whether active or placebo patches. The complete protocol lasted 60 days. During the intervention period, the patches were initially applied and subsequently replaced on day 15. Particularly, on day 30, the patches were removed, and patients remained patch-free for the ensuing 30 days to discern post-treatment effects. This strategic approach was guided by the findings of a prior study, which indicated a reduction in effectiveness of the patches after two weeks of continuous use.Day 1 — the volunteers answered the Visual Analogue Scale (VAS) questionnaires. Subsequently, the physiotherapist accessed the cervical region. Muscle and/or joint tender points were identified. Muscle tension was measured in the posterior region of the neck using a Neutone® device in its upper, middle, and lower portions. Each region was measured three consecutive times and the weighted mean was calculated. The patches were placed, and patients were instructed to remain with the patches for the entire time and replace them if they fell out and not to use pain medication.Day 15 — first return. Participants were questioned about neck pain and dizziness preceding period using the VAS. Muscle tension was measured. Side effects or medication use were recorded. Patches were replaced with new ones.Day 30 — procedures performed in the previous appointment were repeated and the data were registered. The patches were removed.Day 60 — in the fourth and final evaluation, one month after the intervention, VAS was administered, and the measurement of muscle tension was performed.Of the 20 selected patients, only one patient in the SG reported localized pruritus as a side effect. Due to the mild nature of the reported complaint, there was no interruption of treatment until the completion of the research.t-test. Imaging tests were compared with the Fisher’s test.Study variables showed a normal distribution and were compared at baseline using the Student’s Muscle tension measurements related to pain and dizziness over time were evaluated by a mixed linear model. The model factors included patient, time, and treatment. The patient was considered a random factor. Therapy and time were fixed effects. The model also evaluated the treatment-time interaction. There were repeated measurements for each patient. The Restricted Maximum Likelihood method was used for adjustments. Significance levels of multiple comparisons were corrected using the Tukey-Kramer procedure.α = 0.05) and a Confidence Interval of 95%.The study considered a significance level of 5%  participants were women (90%). The groups had no different study variables at baseline .Table 1Ep < 0.0001), which did not occur in the CG (p = 0.1060), as shown in There is a difference in the indices obtained by the VAS for pain between 0 and 15, 30 and 60 days in the SG (p < 0.0001), and not occurred in the CG (p = 0.3395)  .Figure 2p = 0.0165) between 0 and 30 days, which did not occur in the CG, as shown in There was a statistically significant difference in muscle tension asymmetry over time in the SG  in the CG can be attributed to the placebo effect itself, as the perception of pain increased again in later assessments. The decrease in pain perception demonstrates the effect of heat on the reduction of muscular tension, leading to diminished local contraction, vertebral tension, and pain. According to Mense, the contracted muscle presents ischemia and decreased pH, which sensitizes the nociceptors that trigger pain.Dizziness significantly improved in the SG between baseline and the following assessments. The same did not occur in the CG, which mimicked the results found for pain and showed no improvement. These observations show the association of pain and dizziness found in our study, corroborating previous studies.19As described for pain, muscle tension asymmetry was more intense in the SG, although not significantly. After treatment with local heat, asymmetry was significantly reduced in the SG at 15 and 30 days, increasing again on day 60 — one month from treatment ending. These findings demonstrate the heat's action, reducing the tension and asymmetry of the trapezius muscle during the intervention period with Helical® patches. Our results corroborate previous studies reporting the effectiveness of heat in reducing muscle and fascia tensionImaging tests showed similar degenerative cervical changes in both groups. Some authors attribute dizziness to the higher concentration of Ruffini’s corpuscle mechanoreceptors in the degenerated cervical discs of patients with CD.Based on our results, patients with CD show a clear interrelationship between pain, dizziness, and muscle tension asymmetry. Throughout the study, the improvement or worsening of one of these variables was always directly associated with the improvement or worsening of the others. As for treatment, thermotherapy was effective in controlling symptoms (pain and dizziness) up to one month after the end of the intervention. These results present a significant impact on clinical practice and point towards a promising direction for future research. The efficacy of nanotechnology in relieving pain and dizziness in patients diagnosed with CD has been established. The identification of asymmetry in muscle tension as a closely related factor to dizziness and pain clarifies some fundamental aspects for diagnosis. Due to its innocuous, practical, and straightforward application, nanotechnology emerges as an interesting approach for addressing cervical-origin dizziness.The main limitations of the study lie in the selection of only 20 subjects with non-equitable distribution: 15 in the SG and five in the CG, as well as the short follow-up period, defined within 60 days. Nevertheless, rigorous selection criteria were employed, and these early and preliminary findings are promising. The benefits derived from this innovative treatment approach towards CD provide groundwork for more comprehensive investigations in the future.Dizziness is related to pain and asymmetry of muscular tension in the neck region. Heat from the CNT was effective in reducing dizziness in patients with CD.FAPESP ‒ Fundação de Amparo à Pesquisa do Estado de São Paulo ‒ Project 2016/20176-4.The authors declare no conflicts of interest.


Introduction: Knee osteoarthritis (KOA) is a degenerative joint disease that progresses over time due to articular cartilage loss. Orthopedic surgeons use plain radiography (X-ray) with an anteroposterior (AP) standing (weight-bearing) view, which is currently considered the gold standard modality, to diagnose KOA. They base this diagnosis on the clinical history and physical examination of the knee joint. However, many previous studies have reported a weak correlation between knee-joint structural abnormalities on X-rays and described pain. Therefore, our study aimed to assess the incompatibility between patients’ pain-severity complaints and radiographic findings on standing AP view. No similar study has been recently published in the Middle East.Methods: 158 participants were selected for the study from King Abdulaziz University Hospital, Jeddah, between March 2022 and August 2022. We graded the patients’ AP knee radiographs using the Kellgren-Lawrence (KL) grading scale and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, by which we made phone calls to assess pain severity on a 0-10 pain subscale.p < 0.05). Comparing KL scores on X-ray on a 0-10 pain subscale, we found a significant association between mild pain and severe radiological findings on X-ray and vice versa. In addition, the comparison between KL scores on X-ray and WOMAC questions describing difficulty in sitting showed a significant association between moderate difficulty in sitting and severe radiological findings and vice versa.Results: We found a significant association between the 0-10 pain subscale and WOMAC questions describing difficulty in sitting (Conclusion: Our results indicated that there was a significant relationship between mild pain and severe radiological findings on X-rays and vice versa. Additionally, there was a significant relationship, based on the KL score and the WOMAC item that assessed sitting difficulty, between moderate sitting difficulty and severe radiological findings and vice versa. This may suggest that central and peripheral sensitization could be one factor in the causes of pain.  Knee osteoarthritis (KOA) is a degenerative joint disease that progresses over time owing to articular cartilage loss. Typically, KOA has two types: primary osteoarthritis (OA), without apparent underlying causes, and secondary OA, resulting from either abnormal articular cartilage, such as rheumatoid arthritis or from abnormal force to the knee joint (in cases of trauma) . During Many previous studies have reported a weak correlation between structural knee joint abnormalities on X-rays and reported pain . FurtherAnother prospective study in Hong Kong in 2014 was conducted on 193 patients with primary KOA. The study aimed to determine whether there was a link between ultrasonographic findings and pain score and whether these findings showed a better association with pain level than conventional X-rays. The findings revealed that both imaging modalities had a significant relationship with pain aspects; neither was superior to the other but rather complementary . AnotherMoreover, in Turkey in 2012, a cross-sectional study was conducted on 114 patients with KOA to explore the relationship between pain, disability, and radiographic findings. The results revealed that the KL grading scale was positively and significantly associated with age and disease duration. However, the difference in pain severity, disability, or stiffness according to the KL grading scale was not statistically significant. Therefore, the study found no correlation between function and radiographic features . A prospTherefore, in this study, we aimed to assess the relationship between the severity of KOA pain among Saudi patients and radiographic findings at King Abdulaziz University Hospital (KAUH) during the previous six months, between March 2022 and August 2022. In addition, we aimed to assess the incompatibility between patients’ pain-severity complaints and radiographic findings on standing AP view, aiming to update the old data from previous studies -9. To daWe conducted this cross-sectional study at KAUH, Jeddah, Saudi Arabia, between March 2022 and August 2022. The participants in our study were patients with KOA who had undergone a standing anteroposterior (AP) view X-ray of the knee. Saudi adults of all ages who had data of standing AP view radiographs of the knee through the orthopedic department were included in our study. However, we excluded patients who were surgically treated with total/hemi knee replacement (arthroplasty). The estimated required sample size was 248 participants with a 95% confidence level and a margin of error of 5%. We performed our calculations using the Raosoft sample size calculator. All patient identifiers were removed for data collection, database storage, and statistical analysis. The patients’ records were assigned numbers using a numbering reference sheet and referred to during communication and study interactions using that reference number. Individual participants’ information cannot be identified in any publications or presentations resulting from this study. Only aggregated data were provided and analyzed. Data were stored in a secure computer system in the principal investigator’s office, accessible only by the researchers during the study. We recruited the participants through the hospital’s information system. We evaluated the participants’ pain severity by means of structured phone interviews because the pain severity scoring system is not united in the hospital’s information system. The KL score, which describes joint changes in severity on AP standing X-ray, has five stages starting from 0 to 4, which means no osteoarthritic changes, mild, moderate, and severe, respectively. Demographic data  were recorded electronically on organized Microsoft Excel sheets . During the phone call, we asked structured questions of the participants, which assessed pain severity using a scale of 0 to 10, and we asked four extracted questions from the WOMAC pain subscale. We entered and analyzed the data using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. We compared three groups  using a one-way ANOVA test and used an independent t-test to compare two independent variables . Ethical approval was provided by the Research Ethics Committee at King Abdulaziz University, Faculty of Medicine, with the registration number HA-02-J-008.Our study aimed to evaluate the relationship between KOA pain severity and radiographic findings and to assess the incompatibility between severity complaints and radiographic findings on standing AP view among Saudi patients at KAUH.Two hundred nineteen patients, all of whom were Saudi, visited our clinic and were diagnosed with KOA; their data were considered for our analysis. However, only 153 of the patients were willing to participate in our study. The ages of the patients with KOA ranged from 30 to 84 years, with a mean of 59.2. The majority of the patients were female: 128 (83.7%); 25 were male (16.3%). All patients had already been diagnosed with KOA and had been given a standing AP view X-ray of the knee in the previous six months. We reviewed and scored the radiographic findings using the KL score, showing that 27 (17.6%) of the patients had mild changes, 54 (35.3%) had moderate changes, and 72 (47.1%) had severe changes. This indicated that most of the patients were categorized as having KOA pain ranging from moderate to severe. Furthermore, we asked the patients about their pain severity using the WOMAC pain subscale and 0-10 pain scale, where 0 = no pain, 1 and 2 = very weak pain, 3 and 4 = weak pain, 5 = moderate pain, 6 and 7 = strong pain, 8 and 9 = very strong pain, and 10 = intense pain. Our analysis showed that the majority of the patients reported intense pain, 120 (78.4%), whereas a few of them reported very weak to moderate pain, 31 (20.3%). In addition, only two (1.3%) patients had no pain at all. When the patients responded to the WOMAC, 58 (37.9%) had experienced extreme pain at night while in bed, 28 (18.3%) had severe pain, 17 (11.1%) had moderate pain, six (3.9 %) had mild pain, and 44 (28.8%) had none.Regarding standing difficulty, 72 (47.1%) patients reported extreme difficulty, 32 (20.9%) had severe difficulty, 23 (15%) had moderate difficulty, 15 (9.8%) had mild difficulty, and 11 (7.2%) had none. Furthermore, 43 (28.1%) patients reported extreme difficulty in sitting, 33 (21.6%) severe, 35 (22.9%) moderate, 19 (12.4%) mild, and 23 (15%) none. Asked about the difficulty in rising from sitting, 77 (50.3%) patients reported extreme difficulty, 30 (19.6%) reported severe difficulty, 26 (17%) reported moderate difficulty, nine (5.6%) reported mild difficulty, and 11 (7.2%) reported none. We compared the KL score on X-ray to the 0-10 pain subscale and WOMAC subscore. We concluded, based on the results of the p-values, that there was a significant difference between the 0-10 pain subscale and the third WOMAC question, which was about the degree of difficulty in sitting (p <0.05) . While comparing KL scores on X-ray to the 0-10 pain subscale, there was a significant association between mild pain and severe radiological findings on X-ray and vice versa Table . FurtherComparing gender with pain severity, our data showed significant differences (p < 0.05) in the 0-10 pain subscale and WOMAC questions 1, 2, and 4. Forty-four (34.4%) female patients experienced intense pain, while only two (1.6%) had no pain, and the other two (1.6%) had very weak pain. In contrast, eight (32%) male patients reported strong pain, while none were pain-free (0%). In the WOMAC question that assessed pain severity at night while in bed and asked if pain disturbed sleep, 56 (43.8%) female patients reported pain during sleep, while five (3.9%) had mild pain. Sixteen (64%) male patients had no pain during sleep, and one (4%) patient had mild pain. In the WOMAC question that assessed difficulty in standing, 64 (50%) female patients experienced extreme pain, whereas only nine (7%) had no pain. In contrast, eight of the male patients (32%) had extreme pain, and two (8%) had no pain. In the WOMAC question, which assessed difficulty in rising from sitting, 69 (53.9%) female patients exhibited extreme pain, whereas only six (4.7%) had mild pain. Similarly, most of the male patients (32%) had extreme pain, while only three (12%) had mild pain; the other three (12%) patients had no pain.In this cross-sectional study, we evaluated whether there was a relationship between KOA pain severity and radiographic findings and assessed the incompatibility between patient severity complaints and radiographic findings on standing AP view among Saudi patients at KAUH. Our results demonstrated a significant association between mild pain and severe radiological findings on radiography and vice versa in comparison with the KL score on X-ray to the 0-10 pain subscale. In addition, the comparison between KL scores on X-ray and the WOMAC question that assessed difficulty in sitting showed a significant association between moderate difficulty in sitting and severe radiological findings, and vice versa.KOA is a common disease with a high prevalence worldwide , especiaA previously published cross-sectional study illustrated that the majority of participants were female patients . SimilarAnother published article showed that 32% of patients had mild KOA, 33% had moderate KOA, and 23% had severe KOA on X-ray . HoweverA longitudinal cohort study was conducted to measure KOA pain severity and analyze the radiographic findings with duration and severity separately . It founA study conducted in Turkey could not establish an association between WOMAC scores and the KL grading scale . In thisIn our study, we had a limited number of blinded readers for X-rays, which decreased the possibility of bias and had more accuracy in reading and scoring. In addition to online surveillance, we collected our data using archival data, in addition to questions via phone. However, our study has some limitations. First, the sample size was small and from a single center. Therefore, our results cannot be generalized to the whole population. Furthermore, we did not assess obesity or other comorbidities that could play a role in the physical functional status of patients with KOA . Our results showed multiple significant values, which we interpreted as revealing that the patients with mild knee pain showed severe radiological findings on X-ray and vice versa, and also that patients with moderate knee pain showed severe radiological findings on X-ray and vice versa. Therefore, we recommend that orthopedic surgeons identify the risk factors for KOA and develop a screening program in coordination with radiologists for early detection and management to improve the functional status in patients and prevent the transition from mild to severe stages of KOA. Additionally, to fully understand the relationship between radiological damage and functional status in patients with KOA, we recommend further studies with larger samples and further assessment of risk factors that could have an impact on KOA development, such as obesity, vitamin D deficiency, race, dietary factors, and occupation.


ObjectivesA multimodal approach to pain management, including potential interventional techniques, is suggested to achieve adequate pain control. This study discusses the techniques and medications employed to manage pain in pediatric oncology patients.MethodologyThis study included 90 patients under 18 years of age who underwent pain management in the algology clinic between 2002 and 2020. From the algology follow-up records, the following data were recorded: demographic information, follow-up time, cancer diagnosis and stage, cause and location of pain, systems involved, duration and intensity of pain, analgesic and adjuvant drugs prescribed, routes and duration of drug administration, complications, interventional procedures if performed, “pain intensity” scores prior to and following treatment, and daily and total analgesic consumption of the patients.Resultsn = 73). At admission, 72.3% (n = 65) had severe pain for at least a month. It was determined that 90% (n = 81) of the patients were using opioids and 28.9% (n = 26) were using dual opioids. The mean tramadol dose was 129.0±97.9 mg/day (12-380 mg/day), and the mean morphine dose was 14.8±11.3 mg/day (1-52 mg/day). The mean transdermal fentanyl dose was 33.2±21.6 µgr/h (12-75 µgr/h). Adjuvant therapy was administered in 25.6% (n = 24) of the patients. Epidural catheterization was performed on 6.6% (n = 6) of the patients. The mean initial pain scores were 5.2±1.7, which decreased to 1.5±0.7 with a significant difference (p < 0.001). In the study, 93% (n = 84) of the patients had no pain management complications noted.The mean age was 11.4±4.1 years (min-max: 2-17). Leukemia and lymphoma were the most frequently diagnosed (30%). Of the 31 features identified in the staging, 27 (87.1%) were stage 4 at admission. The causes of pain in children were neoplasms in 81.2% (ConclusionsThe pain level that pediatric cancer patients endure critically influences their and their family’s quality of life. The fact that opioid-related adverse effects associated with pediatric pain management occur far less frequently than previously thought may help prevent opiophobia. Effective and safe analgesia can be provided with multimodal analgesia to manage pediatric cancer pain. Around 400,000 children are diagnosed with cancer annually. The World Health Organization (WHO) has started the CureAll framework study for children with pediatric cancer who are considered undertreated. One of the most vital activities of this organization is pain management , as onlyPain in pediatric cancer may be caused directly by the tumoral tissue, or it may develop due to the paraneoplastic effects of the tumor and the compression of the surrounding healthy tissue . MoreoveMultimodal analgesia is a pain management approach that combines medicines with multiple mechanisms of action and advantageous adverse-effect profiles. Pain management that spares opioids can be effectively achieved by combining multimodal analgesia with regional anesthesia .At Mersin University Algology Clinic , researchers have followed pediatric oncological patients for 20 years. Based on the WHO step therapy, pain palliation is provided using multimodal analgesia. This study aims to share the details of the methods and drugs used at this clinic in the pain management of pediatric oncological patients.Ethics committeeApproval for the study was obtained from the Mersin University Clinical Research Ethics Committee .Study designPatients under 18 years of age diagnosed with cancer and treated for pain in the gastroenterology clinic between 2002 and 2020 were included in this study. Patients over 18 years of age and those missing algology clinic follow-up data were excluded from the study. We evaluated 93 patients and excluded three patients who met the exclusion criteria. The demographic data, follow-up period, diagnosis and stage of cancer, cause and location of pain, systems involved, duration and intensity of pain, analgesic and adjuvant drugs prescribed, routes and duration of drug administration, complications, interventional procedures if performed, “pain intensity” scores before and after treatment, and daily and total analgesic consumption by patients were documented from algology hard copy follow-up records.Principles of pain managementPediatric oncological outpatients who are admitted to or present to our clinic are evaluated by an algologist with physical examination, laboratory values, and imaging methods. According to the definition of cause and severity of pain, the choice of treatment and method is determined on the basis of the WHO’s analgesic ladder principle. The WHO's analgesic ladder is used to organize analgesia treatment for pediatric cancer patients:WHO step 1: Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) for mild painWHO step 2: Weak opioids, paracetamol, and NSAIDs for mild-to-moderate painWHO step 3: Potent opioids, paracetamol, and NSAIDs for severe painWe prefer to use codeine and tramadol as weak opioids, and morphine, fentanyl, and oxycodone as potent opioids. Tramadol and the WHO step 2 were not used under the age of 12 after 2018, when the Ministry of Health of our country restricted its use in children. Adjuvant medications might be added for specific pain subtypes  were used when indicated. Bupivacaine or morphine was administered when necessary.Follow-upAt least twice a day, bedside visits were conducted to patients who were inpatients. Patients are followed until their pain levels drop to an acceptable level. Outpatients are called for control on the next day and third day when a new medication is started. Medication adjustments and controls are made every 10 days.Pain measurementDifferent evaluation methods were adopted because the recognition and compliance of children at different ages are distinct. The Revised Faces Pain Scale, visual analog scale (VAS), and numerical rating scale (NRS) are used as pain severity scales according to pediatric age groups in diagnosis and follow-ups at our clinic. In addition, the revised faces pain scale is included in the follow-up charts for pain monitoring in all pediatric services. The scores of the scales used are between 0 and 10. The degree of pain was scored as “0,” representing no pain, and “10,” representing the most severe pain.For our study, the results of the scales were defined as the “pain score.” Pain in the form of tingling, burning, and stabbing was evaluated as “neuropathic pain.”Statistical analysisThe data for the statistical analysis were entered using SPSS Version 24  application. The E-PICOS calculator was also used to do calculations in accordance with the MedicReS Good Biostatistical Practice recommendations. For categorical data, descriptive statistics were used, and percentages were used to explain frequency calculations. The chi-square method was used to evaluate categorical variables. A p-value of 0.05 was used to determine statistical significance.Of the 90 children, 45.6% (n = 41) were female, and the mean age was 11.4±4.1 (range: 2-17 years). The mean weight was 37.9±17.5 kg (range: 10-86 kg), and 76.7% (n = 69) of the patients were hospitalized pediatric patients. At admission, stage 4 cancer was present in 27 (87.1%) of the 31 individuals for whom staging was available.Leukemia and lymphoma were the most frequently diagnosed malignancies in children, occurring at a rate of 30% (n = 27) Figure .The causes of pain in children were neoplasms in 81.2% (n = 73), surgeries in 8.9% (n = 8), radiation in 4.4% (n = 4), and inflammation in 2.2% (n = 2). The localizations of pain at the first examination of the children are shown in Table The examination of the duration and severity of pain at admission revealed that 27.8% (n = 25) of the patients had mild to moderate pain, 45.6% (n = 41) had severe pain that kept going for less than a month, 10.0% had severe pain that persisted for one to three months, and 16.7% (n = 15) had severe pain that went on for longer than three months.While the mean initial pain scores of the children were 5.2±1.7 (min-max: 2-9), it decreased to 1.5±0.7 (min-max 1-4) with a significant difference (p<0.001). It was determined that seven (7.8%) of 36 children used a combination of paracetamol and ibuprofen. Detailed use of non-opioid analgesics is shown in Table Of the 90 patients, 81 (90%) used opioids and 26 (28.9%) used dual opioids. Nine (10%) patients had not received opioid treatment. Three (3.3%) patients with a starting pain score of 3 had taken paracetamol. The patient who required the most time-consuming care had an intracranial tumor treated with a fentanyl patch for 22 months. Pethidine was applied by the pediatric surgeon for postoperative analgesia. The opioids used are detailed in Table When we listed the diagnoses of individuals using adjuvant drugs  for neuropathic pain , it was found that nine had sarcoma, three had neuroblastoma, three had bone tumor, and two had leukemia-lymphoma. The frequency of adjuvant drug use is given in Table Epidural catheterization was performed in six children. Initial pain scores of those six patients were as follows: 8 in two patients, 7 in three patients, and 4 in one patient. Of the six children, four had musculoskeletal cancer, one had a gastrointestinal tumor, and one had a genitourinary system tumor. All of them had abdominal, perianal, and lower extremity pain.Complications of pain management were nausea-vomiting in 4.4% (n = 4) and itching in 2.2% (n = 2). Complications were not recorded in 93.3% (n = 84) of children. Among children, cancer or its complications caused deaths of 30% (n = 27) of them.The study results demonstrate that multimodal analgesia is a practical treatment for pediatric cancer-related pain. A patient was admitted with stage 4 and severe pain in the study population. With the potent opioids and interventional procedures, analgesia can be provided safely with close follow-up. Effective analgesia was provided compared to baseline treatment and end mean pain scores for all patients .The most common childhood cancers are listed in the literature. Among these cancers, leukemia is responsible for 30%, brain tumors for 25%, lymphoma for 15%, neuroblastoma for 8%, intra-abdominal sarcoma for 15%, retinoblastoma for 3%, and liver tumors for 15% . Except Non-opioid drugs are commonly used to treat mild-to-moderate cancer pain and are recommended in the WHO cancer pain treatment ladder, alone or in combination with opioids . ParacetMild opioids are often preferred for palliation of cancer pain. WHO’s analgesic ladder was used as a protocol in the pediatric cancer pain trial, which included 224 patients. The authors revealed that tramadol was the most frequently used weak opioid . TramadoOpioids, such as morphine, fentanyl, and oxycodone, remain the gold standard of pharmacology for children in severe pain . MoreoveCancer-related neuropathic pain is common and can be disease-related or related to the acute or chronic effects of cancer treatment . AccordiAccording to the WHO guidelines, steroids should be used to treat cancer pain in adults and adolescents experiencing visceral, neuropathic, or metastatic bone pain . NotablyA multimodal approach to pain management is suggested to achieve adequate pain control, including potential interventional techniques . In MehlOpioid side effects might occur in approximately 14% of pediatric cancer patients. Opioid side effects, such as constipation, sedation, pruritis, and nausea, are often unavoidable . It has LimitationsThe key limitation of our study was its retrospective design. Although our clinic has a process for treating children with cancer, each patient is assessed individually before a treatment choice is determined. This is the study's standardization limitation. The single-center nature of our study was our limitation in terms of the number of patients. Another one of our limitations was the variation in age groups, oncological diagnoses, and pain management in our patient sample. Due to our large age range, one of our limitations was that the pain assessment scores we used varied. Instead of reporting the doses we used for breakthrough pain, we had to show the total opioid consumption. The current study includes approximately 20 years of patient data. An additional limitation of the study is the limited number of pain interventions administered within this timeframe. Interventional pain management has come a long way in this process.The pain intensity experienced by pediatric cancer patients significantly affects their and their family’s quality of life. In this study, participants were not referred to the pain clinic until they reached stage 4 cancer. Opiophobia may be prevented partly because opioid-related side effects linked to pediatric pain management occur considerably less frequently than previously believed. Studies examining the multidisciplinary approach to pain management must be conducted, as effective pain management is crucial to improving quality of life.