Is there a difference in the analgesic response to intra-articular bupivacaine injection in people with knee osteoarthritis pain with or without central sensitisation? Protocol of a feasibility randomised controlled trial.

INTRODUCTION: Pain is the main symptom of osteoarthritis (OA) with approximately 50% of patients reporting moderate-to-severe pain. Total knee replacement (TKR) is the ultimate treatment option to alleviate pain in knee OA. Nevertheless, TKR does not provide complete relief for all as approximately 20% of patients experience chronic postoperative pain. Painful peripheral stimuli may alter the central nociceptive pathways leading to central sensitisation that can influence treatment response in patients with OA. Currently, there is no objective protocol for detecting whether a patient will respond to a given treatment. Therefore, there is a need for a better mechanistic understanding of individual factors affecting pain relief, consequently informing personalised treatment guidelines. The purpose of this research is to examine the feasibility of conducting a full-scale mechanistic clinical trial in painful knee OA investigating the analgesic response to intra-articular bupivacaine between those with or without evidence of central sensitisation. METHODS AND ANALYSIS: The Understanding Pain mechanisms in KNEE osteoarthritis (UP-KNEE) study is a feasibility, double-blinded, placebo-controlled randomised parallel study in participants with radiographically defined knee OA and with self-reported chronic knee pain. The study involves the following assessments: (1) a suite of psychometric questionnaires; (2) quantitative sensory testing; (3) magnetic resonance imaging (MRI) scan of the knee and brain; (4) a 6-minute walk test; and (5) an intra-articular injection of bupivacaine or placebo (sodium chloride 0.9%) into the index knee. Assessments will be repeated post intra-articular injection apart from the MRI scan of the knee. Our aim is to provide proof of concept and descriptive statistics to power a future mechanistic trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (HRA) (REC: 20/EM/0287). Results will be disseminated via peer-reviewed journals and scientific conferences. The results will also be shared with lay audiences through relevant channels, such as Pain Centre Versus Arthritis website and patient advocacy groups. TRIAL REGISTRATION NUMBER: NCT05561010.

Postoperative ulnar neuropathy: a systematic review of evidence with narrative synthesis.

BACKGROUND: Postoperative ulnar neuropathy (PUN) is an injury manifesting in the sensory or motor distribution of the ulnar nerve after anaesthesia or surgery. The condition frequently features in cases of alleged clinical negligence by anaesthetists. We performed a systematic review and applied narrative synthesis with the aim of summarising current understanding of the condition and deriving implications for practice and research. METHODS: Electronic databases were searched up to October 2022 for primary research, secondary research, or opinion pieces defining PUN and describing its incidence, predisposing factors, mechanism of injury, clinical presentation, diagnosis, management, and prevention. RESULTS: We included 83 articles in the thematic analysis. PUN occurs after approximately 1 in 14 733 anaesthetics. Men aged 50-75 yr with pre-existing ulnar neuropathy are at highest risk. Preventative measures, based on consensus and expert opinion, are summarised, and an algorithm of suspected PUN management is proposed, based upon the identified literature. CONCLUSIONS: Postoperative ulnar neuropathy is rare and the incidence is probably decreasing over time with general improvements in perioperative care. Recommendations to reduce the risk of postoperative ulnar neuropathy are based on low-quality evidence but include anatomically neutral arm positioning and padding intraoperatively. In selected high-risk patients, further documentation of repositioning, intermittent checks, and neurological examination in the recovery room can be helpful.

The effects of open wedge high tibial osteotomy for knee osteoarthritis on the patellofemoral joint. A systematic review.

BACKGROUND (INCLUDING AIMS OF THE STUDY): To investigate the impact medial opening wedge high tibial osteotomy (MOWHTO) has on the progression of patellofemoral (PF) OA, patella height, contact pressure within the PF joint and clinical outcomes. METHODS: A systematic review was conducted in January 2022 according to PRISMA guidelines. The ICRS cartilage grade of the PF joint at the initial MOWHTO surgery and at second look surgery was compared and relative risk of progression of PF OA was calculated. Evaluation of patella height was assessed by Caton-Deschamps index, Blackburne-Peel index or Insall-Salvati index pre and post MOWHTO. Cadaveric studies assessing contact pressures in the PF after MOWHTO were included. RESULTS: Forty-two studies comparing 2419 patients were included. The mean age was 53.1 years (16-84), 61.3% female. The risk of progression of PF OA was highest in the uniplanar and biplanar MOWHTO with proximal tubercle osteotomy groups (RR = 1.28-1.51) compared to biplanar MOHWTO with distal tubercle osteotomy (RR = 0.96-1.04). Patella height was not affected after biplanar MOWHTO with distal tubercle osteotomy (p < 0.001). Cadaveric studies demonstrate that PF contact pressures increase with more severe corrections (15°) but suggest biplanar MWOHTO and distal tubercle osteotomy induces lower contact pressures within the PF joint than other MOWHTO techniques. Significant over correction is associated with worse clinical outcomes and anterior knee pain. CONCLUSION: Biplanar MOWHTO and distal tubercle osteotomy has minimal effect on the contact pressures in the PF joint resulting in less severe progression of PF OA and has minimal impact on patella height.

Strengthening India's Response to HIV/AIDS Epidemic Through Strategic Planning, Innovative Financing, and Mathematical Modeling: Key Achievements over the Last 3 Decades.

Indian HIV/AIDS numbers during the 2000s did not reach the high proportion of estimations provided by the WHO and UNAIDS. The number of HIV infections was high around 2.4 million in the 2020s, but given the country's population of 1.38 billion, the general positivity rate remained very low compared with several countries. There were several reasons for a successful control of the epidemic in India, for example, setting-up of the National AIDS Control Programs, strategic priorities, surveillance and data management, mathematical modeling, and coordinating with the civil society and galvanizing public response. In this review article, we will provide a recollection of India's response and management of the HIV/AIDS epidemic, challenges, and successful model building, and future challenges that play important role in sustaining the epidemic at a lower level and plan for reducing the future transmissions.

Chronic postoperative pain after total knee arthroplasty: The potential contributions of synovitis, pain sensitization and pain catastrophizing-An explorative study.

BACKGROUND: A subset of osteoarthritis patients will experience chronic postoperative pain after total knee arthroplasty (TKA), but the source of pain is unclear. The aim of this exploratory study was to assess patients with and without postoperative pain after TKA using magnetic resonance imaging (MRI), quantitative sensory testing (QST), clinical assessment of pain and assessments of catastrophizing thoughts. METHODS: Forty-six patients completed the 6-month postoperative assessment. MRI findings were scored according to the MRI Osteoarthritis Knee Score recommendation for Hoffa synovitis, effusion size and bone marrow lesions. QST included assessment of pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM). Pain catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). Clinical pain assessment was conducted using a visual analogue scale (VAS, 0-10 cm), and groups of moderate-to-severe (VAS > 3) and none-to-mild postoperative pain (VAS ≤ 3) were identified. RESULTS: Patients with moderate-to-severe postoperative pain (N = 15) demonstrated higher grades of Hoffa synovitis (p < 0.001) and effusion size (p < 0.001), lower PPTs (p = 0.039), higher TSP (p = 0.001) and lower CPM (p = 0.014) when compared with patients with none-to-mild postoperative pain (N = 31). No significant difference was found in PCS scores between the two groups. Multiple linear regression models found synovitis (p = 0.036), effusion size (p = 0.003), TSP (p = 0.013) and PCS (p < 0.001) as independent parameters contributing to the postoperative pain intensity. CONCLUSION: These exploratory findings could indicate that chronic postoperative pain after TKA is a combination of joint-related synovitis and effusion, sensitization of central pain mechanisms and potentially pain catastrophizing thoughts, but larger studies are needed to confirm this. SIGNIFICANCE: The end-stage treatment of knee osteoarthritis is total knee arthroplasty. Some patients experience chronic postoperative pain after total knee arthroplasty, but the mechanism for chronic postoperative pain is widely unknown. The current study indicates that higher levels postoperative of synovitis and effusion, higher temporal summation of pain and higher pain catastrophizing scores could be associated with higher chronic postoperative pain.

Excellent outcomes with combined single stage Physica ZUK medial unicompartment knee replacement and anterior cruciate ligament reconstruction results in young, active patients with instability and osteoarthritis with a mean follow up of 5 years.

BACKGROUND (INCLUDING THE AIM OF THE STUDY): Young and more active patients with medial compartment osteoarthritis (OA) in conjunction with anterior cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study was to explore the outcomes of combined fixed bearing Physica ZUK medial unicompartmental knee replacement (UKR) (Lima Corporate, Udine Italy) with ACL reconstruction for patients presenting with isolated medial compartment OA and symptomatic ACL deficiency. METHODS: Patients who underwent simultaneous single stage ACL reconstruction and medial UKR between 2012 and 2020 by a single surgeon (GG) were included. Preoperative outcome measures including Lysholm, Tegner, Oxford Knee Score and VAS pain score were evaluated and were repeated postoperatively at the most recent follow up appointment. RESULTS: Twenty four patients underwent simultaneous combined ACL and ZUK Medial UKR with a mean follow up of 5.1 years. Significant improvements in Lysholm (p < 0.001), Tegner (p < 0.001), Oxford Knee Score (p < 0.001) and VAS pain scores (p < 0.001) were seen with this combined approach with all patients returning to sport. Two patients had a minor peri-operative complication, which was treated conservatively. There were no revision procedures, and no evidence of implant loosening, however one patient had deceased due to an unrelated illness. CONCLUSION: UKR combined with ACL reconstruction can be an effective treatment option for selected patients suffering from medial unicompartmental knee osteoarthritis and symptomatic ACL deficiency. This allowed active patients to return to sports, addressing both instability and OA pain in a specific patient population.

Preoperative Neuropathic Pain-like Symptoms and Central Pain Mechanisms in Knee Osteoarthritis Predicts Poor Outcome 6 Months After Total Knee Replacement Surgery.

Preoperative pain characteristics in patients with osteoarthritis may explain persistent pain after total knee replacement. Fifty patients awaiting total knee replacement and 22 asymptomatic controls were recruited to evaluate the degree of neuropathic pain symptoms and pain sensitization. Patients with OA were pain phenotyped into 2 groups based on the PainDETECT questionnaire: high PainDETECT group (scores ≥19) indicating neuropathic pain-like symptoms and low PainDETECT group (scores <19) indicating nociceptive or mixed pain. Cuff algometry assessing pain detection thresholds and pain tolerance thresholds was conducted on the lower legs. Temporal summation of pain was assessed using 10 sequential cuff stimulations and a von Frey stimulator. Conditioning pain modulation was assessed by cuff pain conditioning on 1 leg and parallel assessment of pain detection thresholds on the contralateral leg. Pressure pain thresholds were recorded by pressure handheld algometry local and distant to the knee. Knee pain intensity (visual analogue scale) and pain assessments were collected before and 6 months after total knee replacement. Thirty percent of patients demonstrated neuropathic pain-like symptoms (high PainDETECT group). Facilitated temporal summation of pain and reduced pressure pain thresholds distant to the knee were found in the high PainDETECT group compared with the low PainDETECT group and healthy controls (P < .001). Patients with OA with high PainDETECT scores had higher postoperative visual analogue scale pain scores than the low PainDETECT patients (P < .0001) and facilitated temporal summation of pain (P = .022) compared with healthy control subjects. Perspective: This study has found that preoperative PainDETECT scores independently predict postoperative pain. Patients with knee OA with neuropathic pain-like symptoms identified using the PainDETECT questionnaire are most at risk of developing chronic postoperative pain after TKR surgery.

Neuropathic pain-like symptoms and pre-surgery radiographic severity contribute to patient satisfaction 4.8 years post-total joint replacement.

AIM: To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement (TJR) in people who had undergone knee or hip replacement for osteoarthritis. METHODS: Participants (n = 1151) were recruited from Nottinghamshire post-total hip or knee replacement. Questionnaire assessment included medication use, the pain-DETECT questionnaire (PDQ) to assess neuropathic pain-like symptoms (NP) and TJR satisfaction measured on average 4.8 years post-TJR. Individual factors were tested for an association with post-TJR satisfaction, before incorporating all factors into a full model. Data reduction was carried out using LASSO and receiver operator characteristic (ROC) curve analysis was used to quantify the contribution of variables to post-TJR satisfaction. RESULTS: After data reduction, the best fitting model for post-TJR satisfaction included various measures of pain, history of revision surgery, smoking, pre-surgical X-ray severity, WOMAC function scores and various comorbidities. ROC analysis of this model gave AUC = 0.83 (95%CI: 0.80-0.85). PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes: AUC = 0.79 (0.75-0.82). Pre-surgical radiographic severity was associated with higher post-TJR satisfaction: ORsatisfied = 2.06 (95%CI: 1.15-3.69), P = 0.015. CONCLUSION: These results highlight the importance of pre-surgical radiographic severity, post-TJR function, analgesic medication use and NP in terms of post-TJR satisfaction. The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.

Resection and Resolution of Bone Marrow Lesions Associated with an Improvement of Pain after Total Knee Replacement: A Novel Case Study Using a 3-Tesla Metal Artefact Reduction MRI Sequence.

We present our case report using a novel metal artefact reduction magnetic resonance imaging (MRI) sequence to observe resolution of subchondral bone marrow lesions (BMLs), which are strongly associated with pain, in a patient after total knee replacement surgery. Large BMLs were seen preoperatively on the 3-Tesla MRI scans in a patient with severe end stage OA awaiting total knee replacement surgery. Twelve months after surgery, using a novel metal artefact reduction MRI sequence, we were able to visualize the bone-prosthesis interface and found complete resection and resolution of these BMLs. This is the first reported study in the UK to use this metal artefact reduction MRI sequence at 3-Tesla showing that resection and resolution of BMLs in this patient were associated with an improvement of pain and function after total knee replacement surgery. In this case it was associated with a clinically significant improvement of pain and function after surgery. Failure to eradicate these lesions may be a cause of persistent postoperative pain that is seen in up to 20% of patients following TKR surgery.

Hepatitis A outbreak associated with kava drinking.

Hepatitis A is caused by the hepatitis A virus (HAV), with transmission occurring through the faecal-oral route. In May 2013, a case of hepatitis A infection was reported to a Western Australian regional public health unit, with infection acquired in Fiji. Following this, 2 further cases were linked to the index case by kava drinking and 1 further case was a household contact of a secondary case. This outbreak highlights that the preparation of kava drink and/or the use of a common drinking vessel could be a vehicle for the transmission of HAV.

Synthesis, growth and vibrational spectroscopic study of a novel coumarinoylthiazole.

An efficient route was developed for the synthesis of novel 3-(2-morpholinyl-4-phenylthiazol-5-oyl)coumarin (MPTC). FT-IR spectrum of MPTC was recorded and analyzed. The crystal structure data are also described. The vibrational wavenumbers were computed theoretically using the Gaussian03 package of programs using HF/6-31G(d) and B3LYP/6-31G(d) levels of theory. The data obtained from vibrational wave number calculations are used to assign vibrational bands observed in the infrared spectra of MPTC. The first hyperpolarizability, infrared absorption band intensities and intensities of raman active bands are reported. The calculated first hyperpolarizability is comparable with the values reported for compounds of similar structure. The structural parameters of MPTC obtained from XRD studies are in agreement with the calculated values. The unit cell parameters of crystals of MPTC are: a=8.6017(10)Å, b=9.9735(5)Å, c=13.3870(13)Å, α=111.123(6)°, ß=90.102(9)°, γ=110.246(6)°, and Z=2,1.397 Mg/m(3).

An uncommon endocrine cause of pyrexia of unknown origin.

We report a previously healthy 43 yr old male who presented with prolonged fever, weight loss and neck pain for 3 weeks. Even after extensive work up for the possible causes of pyrexia, the cause remained elusive. In view of persistent tachycardia and neck pain, possibility of subacute thyroiditis was suspected. Thyroid function test (TFT) revealed thyrotoxicosis, which on further evaluation was found to be secondary to DeQuervains thyroiditis. He was treated with NSAIDs, beta-blockers and steroids. He improved rapidly but went on to develop hypothyroidism on follow-up and required levothyroxine replacement.

Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer.

Mucins are a large family of glycoproteins expressed by many epithelial cells and their malignant counterparts. Much interest has been focused on expression of its members in breast cancer because of their potential role as prognostic indicators and their involvement in cancer therapy. We have examined 1447 cases of invasive breast carcinoma with a long-term follow-up, using tissue microarray (TMA) technology and immunohistochemistry to evaluate the expression profiles of several mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and to assess their prognostic value. We detected MUC1 expression in 91% of tumours. MUC1 overexpression was associated with a lower grade, smaller tumour size, a higher oestrogen receptor (ER)-positive phenotype and absence of both regional recurrence and distance metastasis. The subcellular localization but not the level of expression had a prognostic value in predicting outcome. The aberrant cytoplasmic and membranous localization of MUC1 was associated with poor outcome compared with apical localization, which is the normal physiological site of expression. MUC2 expression was noticed in only 8.3% of all cases and was restricted to the cytoplasm of the tumour cells. An inverse trend was identified between MUC2 expression and lymph node stage and vascular invasion status. On excluding cases of mucinous carcinoma from the analysis, the inverse association with vascular invasion was still defined and in addition an inverse association with ER status emerged. MUC3 expression was detected in 91% of cases and its expression was associated with increased local recurrence, and lymph node stage. The membranous expression of MUC3 was found to be a potentially poor prognostic feature, with higher grade and poorer Nottingham Prognostic Index (NPI), and negative ER expression. MUC4, MUC5AC and MUC6 were expressed in 95, 37 and 20% of cases, respectively. Apart from an association between MUC4 expression and tumour grade and between MUC6 and ER-negative tumours, no other associations with any clinicopathological variables were found. Apart from the higher expression of MUC2 and MUC6 in mucinous carcinomas, no association was found between the expression of different mucins and tumour type. No association between the level of expression of any of the studied mucins and patient outcomes has been identified. In conclusion, most breast carcinomas express MUC1, MUC3 and MUC4. Among the various mucins expressed in breast cancer, MUC1 and MUC3 are potential prognostic indicators, MUC1 having the strongest relationship with patient outcome.