Local Infiltration Research Articles

The preventive efficacy of lipid emulsion on the occurrence of local anesthetic systemic toxicity in patients receiving local infiltration analgesia for total joint arthroplasty

BackgroundMotor-sparing local infiltration analgesia (LIA) enhances recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, LIA can induce local anesthetic systemic toxicity (LAST), sometimes necessitating rescue lipid emulsion therapy. Our institute initiated a pilot study to pretreat patients with lipid emulsion (SMOFlipid®) to test its efficacy in mitigating LIA-induced LAST events.MethodsThis retrospective study enrolled 1,621 adult patients who received LIA with bupivacaine (2–3 mg/kg, maximum 300 mg) for unilateral primary THA or TKA under general anesthesia between January 2020 and April 2022. A total of 439 patients received lipid pretreatment, while 1,182 did not. Demographics, surgical and anesthesia profiles, along with LAST events affecting the neurological, cardiovascular, and respiratory systems, were compared after propensity score matching for age, sex, body mass index (BMI), and surgery type.ResultsThe incidence of severe LAST events requiring rescue lipid emulsion slightly decreased after lipid pretreatment (from 2.54 to 2.28 per 1000). Lipid pretreatment significantly reduced the incidence of bradycardia and new-onset arrhythmia (odds ratio: 0.13, adjusted p-value: 0.024) but increased postoperative opioid requirement (odds ratio: 1.71, adjusted p-value: 0.032) after Benjamini-Hochberg correction for multiplicity.ConclusionsThe efficacy of lipid pretreatment (SMOFlipid® 1.5 ml/kg, maximum 100 ml) in mitigating LIA-induced LAST remains controversial. While lipid pretreatment reduced the incidence of new-onset arrhythmia, it showed no clear benefits for neurologic and respiratory outcomes. Additionally, lipid pretreatment might hinder postoperative recovery by increasing the need for rescue opioid analgesia. Further prospective pharmacokinetic studies are required to assess plasma bupivacaine concentrations following LIA and lipid pretreatment, examine their relationship to LAST events, and establish the efficacy and safety of lipid pretreatment.

Effectiveness of Local Glucocorticoid Infiltration Versus Traditional Gauze Bandaging for the Treatment of Onychocryptosis: A Randomized Controlled Trial

Background/objectives: Local intralesional corticosteroid injections into the periungual fold are used to treat patients with onychocryptosis, but their short- or medium-term effects are unknown. The goal was to compare the efficacy of this treatment in stages IIa, IIb, and III of the condition with a common conservative method such as gauze bandaging. Methods: A two-arm randomized trial with 40 patients with stage IIa, IIb, and III onychocryptosis equally assigned into two treatment groups—control (spiculotomy and application of gauze bandaging) and experimental group (spiculotomy and infiltration of corticosteroid)—was performed. Anthropometric data, initial clinical status, pain, and inflammatory measures were collected before and at least one month after the intervention. Results: Pain reduction was higher in the experimental group (5.5 vs. 4.8 points) but with no significant differences (p = 0.306).Corticosteroids significantly reduced inflammation over gauze bandaging (1.9 vs. 1) with significant differences between them (p = 0.029). Conclusions: Corticosteroid infiltration was more effective than gauze bandaging application in reducing inflammation in patients with onychocryptosis, with similar effects on pain. These findings support the clinical importance of corticosteroid treatment for this condition, although a single infiltration may not be sufficient to prevent relapses.

Tubulointerstitial nephritis with IgM-positive plasma cells complicated by liver failure.

Tubulointerstitial nephritis (TIN) is characterized by inflammation of the renal interstitium with the infiltration of immune cells, mainly consisting of T cells. Recently, patients with TIN with the predominant infiltration of immunoglobulin M (IgM)-positive plasma cells were reported, coined IgMPC-TIN. Here we report the case of a 70-year-old woman diagnosed with Fanconi syndrome and renal tubular acidosis. Renal biopsy revealed IgMPC-TIN. Her renal dysfunction and clinical findings improved after corticosteroid therapy. However, the patient died of progressive liver failure and spontaneous bacterial peritonitis. In laboratory tests, viral hepatitis was excluded, and autoantibodies associated with liver diseases were negative. Generally, IgMPC-TIN is often complicated by primary biliary cholangitis (PBC), whereas her autopsy revealed the local infiltration of IgM-positive plasma cells, obliterative portal venopathy, and nodular regenerative hyperplasia in liver. This case is the first demonstration that IgMPC-TIN is also seen in liver disease with nodular regenerative hyperplasia, although IgMPC-TIN is more common in anti-M2 antibody-positive disease.

Is the phoenix sign phenomenon due to vasodilation? A double-blinded, randomized controlled trial comparing motor function recovery after diagnostic common fibular nerve block with lidocaine and papaverine

BackgroundFocal entrapment of the common fibular (peroneal) nerve (CFN) is the most common nerve entrapment in the lower extremity. Accurate diagnosis can be difficult due to co-existent pathology such as low back pathology. A 1% lidocaine block of CFN is often used to confirm the local entrapment pathology and demonstrate possibility of pain relief. A surprising, unexpected and temporary strengthening of CFN supplied ankle and foot muscles is occasionally produced, termed the Phoenix sign. Aetiology of this phenomenon has been puzzling, but restoration of neural circulation and nutrition via improved local blood flow has been postulated to be responsible.MethodsThis is a double-blinded, randomized, prospective controlled trial of 20 patients, comparing 2 vasodilating agents and their ability to produce the Phoenix effect. Ultrasound guided infiltration of 0.3 mL 1% lidocaine or papaverine HCl 10 mg/mL was executed adjacent to CFN. Motor strength pre- infiltration and 4 min post-infiltration were measured for anterior compartment muscles utilizing MRC manual motor testing reported on a 0–5 scale. The extensor hallucis longus (EHL) muscle proved to be the most significant.ResultsAverage motor strength of the EHL improved from 2.2 (+/-0.40) to 4.9 (+/-0.32).) in the lidocaine group. In the papaverine group, pre-infiltration EHL motor strength averaging 2.1 (+/-0.93) improved to 4.4 (+/- 1.01) post-infiltration. Papaverine and lidocaine produced similar statistically significant increases in muscle strength (p = < 0.05).ConclusionThere was no difference between small local infiltrations of lidocaine or papaverine in production of increased anterior compartment EHL motor strength. It is most likely that the Phoenix Effect is explained by temporary local improvements in the microcirculation of the CFN vasa nervorum.Trial RegistrationNCT06637046 10/10/2024 Retrospectively registered.

The spatial overlap between left atrial epicardial adipose tissue and fibrosis is not associated to clinical stage of atrial fibrillation

Left atrial (LA) epicardial adipose tissue (EAT) and wall fibrosis are both proven to contribute to the pathogenesis and progression of atrial fibrillation (AF). The theory of LA wall fibrosis induction by local EAT infiltration, paracrine secretions, and activation of the inflammatory process is strongly advocated, but the imaging evidence for anatomical proximity of the two tissue types and its association to AF stage is lacking. Accordingly, the aim of the study was to analyse the spatial overlap between LA EAT and adjacent wall fibrosis using 3D Dixon water-fat separated late gadolinium enhancement (LGE-Dixon) MRI and correlate the findings with the clinical AF stage. Forty-two AF patients (18 paroxysmal, 10 persistent, and 14 permanent) and nine non-AF patients were scanned. The permanent AF patients had greater LA volume and EAT than the paroxysmal group. The LA fibrosis area showed the same trend. The LA EAT-fibrosis overlap area was small and there was no significant difference between the three AF stages. There was no significant relationship between LA EAT- fibrosis overlap area and AF type. The findings shed light on the complex interplay between LA fibrosis and EAT during the progression from paroxysmal to permanent AF.

A retrospective study of the safety and efficacy of peritoneal dialysis catheter placement under combined local infiltration anesthesia and monitored anesthesia care

ObjectiveGiven the lack of global consensus on anesthesia selection for peritoneal dialysis catheter (PDC) placement via open surgery, this study investigates the safety and efficacy of combining local infiltration anesthesia (LIA) with monitored anesthesia care (MAC) in patients with end-stage renal disease (ESRD).MethodsThis retrospective analysis of ESRD patients who underwent open surgical placement of PDC in the Department of Nephrology, the First Affiliated Hospital of the Army Medical University from 1 August 2020 to 31 May 2022. Patients were categorized into two groups based on anesthesia method: LIA group and LIA + MA group. MA was defined as preoperative sedation (0.2–0.7 µg/kg/h) with dexmedetomidine injection (Huidrican trade name, DEX), and intraoperative analgesia with dexrazoxane injection (Garonin trade name, DEZ) as appropriate according to the patients’ pain scores. We compared the general clinical data of the two groups of patients, the changes in blood pressure and heart rate during the whole operation, the intraoperative and postoperative pain, the total duration of the operation and the immediate postoperative complications.ResultsThe study included 123 patients (59 in the LIA + MAC group and 64 in the LIA group). The LIA + MA group exhibited lower pain scores measured by Visual Analogue Scale(VAS) during surgery (skin incision, subcutaneous adipose tissue dissection, anterior fascia, muscle traction, posterior fascia, peritoneum, and catheterization) compared to the LIA group(p<0.05). In terms of surgical incisions, to intraoperative pain scores (VRS), the LIA + MA group showed higher score level I and lower score level II compared to the LIA group (p = 0.002, 0.004, respectively). The LIA + MA group experienced lower postoperative resting pain (NRS) and VAS than the LIA group (p = 0.001,0.003, respectively). The surgical duration for the LIA + MA group was shorter than that of the LIA group (p<0.001). Preoperative systolic and diastolic blood pressures (SBP and DBP) were higher in the LIA + MA group compared to the LIA group (p<0.001,<0.001, respectively). Postoperative heart rate and DBP were lower in the LIA + MA group (p<0.001, 0.004, respectively). The LIA + MA group exhibited greater changes in heart rate, SBP, and DBP during and after surgery compared to the LIA group (p = 0.009, <0.001,<0.001, respectively). In terms of immediate postoperative complications, the proportion of patients requiring analgesics within 24 h post-surgery was significantly lower in the LIA + MA group (p = 0.031).ConclusionOpen surgery for PDC placement under LIA + MAC is both safe and effective.

Localized Pneumocystis jirovecii pneumonia in a malnourished, non-HIV-infected man in the absence of any established or diagnosed immunosuppressive condition: a case report

BackgroundPneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings.Case presentationA 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung.ConclusionsPJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions.

Case report: Comparative treatment course of generalized lichen nitidus: effectiveness of topical steroids versus maxacalcitol

Lichen nitidus is a chronic skin disease characterized by scattered shiny papules and is common among relatively young individuals. We report a persistent rash covering the body of a 6-year-old boy, unresponsive to prior treatments like moisturizers and topical steroids. Clinical examination revealed small yellow papules predominantly distributed on the trunk, around the eyes, and clustered around the elbow and knee fossa. Histopathological analysis showed a localized infiltrate of lymphocytes and basal epithelial cells, along with giant cells. The overlining rete ridges extended to surround the inflammatory cells, resembling a claw clutching a ball image. Topical treatment with alclometasone dipropionate ointment was more effective compared to maxacalcitol. Remarkably, after about 3 months of treatment, the rash had completely disappeared. We summarized treatments of lichen nitidus in Japan. Maxacalcitol had never been tried. In this report, we demonstrated the effectiveness of the steroid ointment compared to maxacalcitol through the clinical course.

A Novel Chimeric Oncolytic Virus Mediates a Multifaceted Cellular Immune Response in a Syngeneic B16 Melanoma Model

Background/Objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored. Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8+ T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings. Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8+ T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.

Is pericapsular nerve group block superior to other regional analgesia techniques following total hip arthroplasty? a systematic review and network meta-analysis

BackgroundA systematic review and network meta-analysis (NMA) to compare the safety and efficacy of pericapsular nerve group block (PENGB) with other regional analgesia techniques in patients undergoing total hip arthroplasty (THA).MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant research from inception to May, 2024. Randomized controlled trials (RCTs) comparing PENGB with other regional analgesia techniques in patients undergoing THA were included. The primary outcome was resting pain scores at 6 h after surgery. The NMA was made by using Stata 15.1 software. Potential risk of bias was assessed by using CINeMA. Sensitivity and subgroup analyses were performed on the primary outcome.ResultsA total of 11 RCTs including 766 patients were eligible for inclusion. For postoperative resting and movement pain scores within 24 h analysis, PENGB + periarticular local anesthetic infiltration (PLAI) was found to be significantly more effective than other treatments and its Surface under the cumulative ranking curve (SUCRA) was the lowest. Moreover, PENGB + PLAI was ranked the best in reducing opioid consumption within 24 h and the length of hospital stay. PENGB was found to have significantly lower incidence of quadriceps motor block and postoperative nausea and vomiting (PONV).ConclusionsPENGB is more likely to reduce the incidence of quadriceps motor block and PONV in patients undergoing THA, but PENGB + PLAI is superior to other regional analgesia techniques (PLAI, PENGB, fascia iliaca compartment block, and quadratus lumborum block) in improving postoperative pain and shortening the length of hospital stay.Trial registration numberCRD42024538421.

Transcutaneous Immunization of 1D Rod-Like Tobacco-Mosaic-Virus-Based Peptide Vaccine via Tip-Loaded Dissolving Microneedles.

Peptide vaccines induce specific neutralizing antibodies and are effective in disease prevention and treatment. However, peptide antigens have a low immunogenicity and are unstable, requiring efficient vaccine carriers to enhance their immunogenicity. Here, we develop a tobacco mosaic virus (TMV)-based peptide vaccine for transdermal immunization using a tip-loaded dissolving microneedle (MN) patch. TMV is decorated with the model peptide antigen PEP3. The prepared TMV-PEP3 promotes dendritic cell maturation and induces dendritic cells to overexpress MHC II, costimulatory factors, and pro-inflammatory factors. By encapsulation of TMV-PEP3 in the tips of a trehalose MN, TMV-PEP3 can be delivered by MN and significantly promote local immune cell infiltration. In vivo studies show that both subcutaneous injection and MN administration of TMV-PEP3 increase the production of anti-PEP3 IgG antibodies and the harvested serum can induce complement-dependent cytotoxicity. This work provides a promising strategy for constructing efficient and health-care-friendly peptide vaccines.

A comparative study to access the impact of TAP block with wound infiltration in laparoscopic cholecystectomy

Background: The transversus abdominis plane (TAP) block and local anesthetic wound infiltration have been used to relieve pain after laparoscopic cholecystectomy. This study investigated whether the subcostal transversus abdominis block was superior to traditional port-site infiltration of local anesthetic in reducing post-operative pain, opioid consumption, and time for recovery. Aim and Objectives: To investigated whether the subcostal transversus abdominis block is superior to traditional port-site infiltration of local anesthetic in reducing post-operative pain, opioid consumption, and time for recovery. Materials and Methods: All patients were randomly assigned to two equal groups (n=30) using computer-generated randomization. Patients in Group 1 (TAP group) received a TAP block by administration of 10 mL of 0.5% bupivacaine on each side just before completion of surgery, and patients in Group 2 (local wound infiltration [LWI] group) received 10 mL of 0.5% bupivacaine as a local infiltrate at the local site just before completion of surgery. The pain was measured using a Visual Analog Scale (VAS) at intervals of 30 min to 24 h after the procedure. Results: The mean VAS score was significantly lower in group 1 as compared to group 2 at 2 h and 4 h. Whereas the VAS score was not significantly different post-operative 30 min, 6 h, 12 h, and 24 h. The mean first rescue analgesia was significantly more in Group 1 than in Group 2 (P&lt;0.001). Conclusion: The TAP block patients had significant VAS scores at 2 and 4 h postoperatively compared to the LWI patients. The TAP group had a significantly longer median time to first emergency analgesia compared to the LWI group, with a higher proportion of patients requiring only one dose of emergency analgesia.

Assessment of intercostal nerve block analgesia and local anesthetic infiltration for thoracoscopic pulmonary bullae resection: a comparative study

ObjectiveThe purpose of this study was to compare the analgesic effects of intercostal nerve block (ICNB) and local anesthetic infiltration (LAI) on postoperative pain and recovery following thoracoscopic resection of pulmonary bullae.MethodsA total of 160 patients undergoing thoracoscopic pulmonary bullae resection were randomly assigned to receive either ICNB (n = 80) or LAI (n = 80). An experienced anesthesiologist administered ultrasound guided ICNB at the T4 and T7 levels with 5 mL of 0.375% ropivacaine hydrochloride for the ICNB group. Instead, the LAI group received 10 mL of the same concentration of ropivacaine hydrochloride at the same concentration used for ICNB for infiltration anesthesia at the incision sites. Out of the initial cohort, 146 patients completed the study (ICNB group, n = 71; LAI group, n = 75). The collected data included preoperative clinical characteristics, visual analog scale (VAS) scores for pain at various time points post-surgery (6, 12, 24, 48, and 72 h). Additionally, the Quality of Recovery-15 (QoR-15) questionnaire was administered 24 h after surgery, and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI).ResultsNo significant differences were found in drainage volume, use of additional analgesics, duration of chest tube placement, or hospital stay between the two groups. However, the ICNB group had significantly lower VAS scores and QoR-15 scores 24 h postoperatively (p < 0.05), indicating better pain management and recovery. The ICNB group also reported better sleep quality, as reflected by lower PSQI scores.ConclusionICNB provides superior analgesia compared to LAI after thoracoscopic resection of pulmonary bullae, significantly improving postoperative recovery.

Effect of adding sodium bicarbonate 8.4% to local anesthesia on pain during upper canine infiltration

Background: Alkalization of local anesthetics may have an impact on alleviating the injection pain by buffering these solutions with sodium bicarbonate. The present study aimed to evaluate the pain during local anesthetic buccal infiltration for the maxillary canines after adding sodium bicarbonate 8.4% during local anesthesia. Materials and Methods: A buffered 2% lidocaine with 1:80,000 epinephrine and sodium bicarbonate 8.4% was used for one site, and an unbuffered 2% lidocaine with 1:80,000 epinephrine was used for the other site at the same appointment. Two groups of volunteers (15 male and 15 female) participated. Each participant received 0.6 mL of the anesthetic solution. Injection discomfort was assessed using a visual analog scale. Results: 73% and 93% of patients in group 1 experienced pain in sites A and B, respectively, during the injection, whereas 80% and 100% of patients in group 2 experienced pain in sites A and B, respectively, during the injection. Both groups showed a significant difference in pain scores between the two injected sites (P ˂ 0.01). Conclusion: Upper canine infiltration anesthesia with buffered lidocaine and epinephrine with sodium bicarbonate has less pain during injection than when unbuffered lidocaine with epinephrine is used.

BMAL1 Deficiency Provokes Dry Mouth and Eyes by Down-regulating ITPR2/3

Secretory glands, responsible for tears and saliva production, play essential roles in maintaining ocular and oral well-being. Disruptions in gland secretion can arise from various factors, including rhythm disturbances associated with sleep disorders. However, the underlying mechanisms governing these disruptions remain largely unexplored. We demonstrate that BMAL1, a core component of the circadian system, plays a critical role in regulating secretory gland secretion. Loss of BMAL1 induces vacuolation and atrophy phenotypes in acinar cells, subsequently leading to cell apoptosis and gland hypofunction, but does not cause Sjogren's syndrome, which is characterized by localized inflammatory cell infiltration. Mechanically, BMAL1 directly modulates the transcription of ITPR2 and ITPR3, thereby altering the secretion of Lactoferrin and Lysozyme. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats effectively alleviated the symptoms of lacrimal and parotid glands secretory dysfunction and significantly reduced dry mouth and dry eye conditions in rhythm-disordered rats. These findings highlight the essential role of BMAL1 in regulating salivary and lacrimal gland secretion and suggest a novel therapeutic approach for treating dry mouth and dry eyes associated with rhythm disorders.

Stormwater retention performance of tree integrated infiltration trenches designed for suburban streetscapes

The volume of stormwater generated by streetscapes in cities is a primary driver of urban stream degradation. Large infiltration trenches can be integrated into streetscapes to potentially retain large volumes of runoff and increase growth rates of nearby trees. To test this, a field study was conducted where three structural soil infiltration trenches receiving runoff (12 m long, 0.6 m wide and 0.6 deep) were installed alongside a carpark in Melbourne, Australia, with sizing determined by space constraints in a typical streetscape. The three structural soil trenches had raised outflow drainage, which created internal water storage for runoff received from a carpark. To separate the effects on tree growth of i) the presence of structural soil from ii) passive irrigation into the structural soil, three structural soil trenches (6 m long, 0.6 m wide and 0.6 deep) not receiving runoff and without outflow drainage were also installed. Runoff capture, exfiltration, outflow and tree growth was monitored over 19 months. Only one system performed close to the design intent and retained 18 % of runoff, due to slow soil exfiltration rates (<0.1 mm h−1). Compacted soil generated pervious-area runoff that filled the structural soil trenches not receiving impervious-area runoff from the carpark. Tree growth near these structural soil trenches was poor (59 % relative growth) compared with trees receiving runoff from the carpark (112 % relative growth), due to a lack of drainage, emphasising the need for drainage of stormwater systems in heavy textured soils to promote tree growth. This study highlights that options for creating storage for stormwater in streetscapes have the potential to meet local runoff infiltration targets. However, meeting local runoff volume reduction targets will require alternative ways to reduce surface runoff.

Deltamethrin exposure caused renal inflammation and renal fibrosis via upregulating endoplasmic reticulum stress-mediated TXNDC5 level in mice

Deltamethrin (DLM) is a type II pyrethroid insecticide that is extensively applied to agriculture, veterinary medicine and livestock pest control. Excessive accumulation of DLM in the body can lead to nephrotoxicity, but the precise toxic mechanism remains obscure. Therefore, we established in vivo models of DLM-exposed mice for 30 days and in vitro models of DLM-exposed renal tubular epithelial cells of mice. The results revealed adverse effects on renal function in mice exposed to excessive DLM, manifested as endoplasmic reticulum (ER) swelling, local inflammatory infiltration in renal tissue and increased collagen fibers, suggesting renal inflammation and fibrosis, etc. Subsequently, in vivo experiments, we found that DLM exposure increased expression levels of endoplasmic reticulum stress (ERS)-related factors, significantly upregulated the expression of TXNDC5, and enhanced the colocalization of GRP78 with TXNDC5. Notably, DLM exposure also strengthened the co-localization of TXNDC5 with NF-κB p65 and TGF-β1, upregulated the expression levels of TLR4/MYD88/NF-κB and TGF-β/SMAD2/3 pathways, alongside inflammation and fibrosis-related factors, these changes exhibited a dose-dependent effect. Meanwhile, in vitro experiments, the results of ERS, inflammation, and fibrosis-related factor expression levels were consistent with those observed in vivo. In conclusion, our results demonstrated that TXNDC5 might played a certain role in DLM-induced nephrotoxicity. Specifically, DLM exposure could trigger ERS, increase TXNDC5 expression, and promote TLR4/MYD88/NF-κB and TGF-β/Smad2/3 pathways, leading to renal inflammation and fibrosis in mice. These discoveries not only deepen our understanding of DLM toxicity but also provide valuable avenues for exploring mitigation strategies and therapeutic interventions.

Clinical Trial Study Protocol: A Prospective Blinded, Randomized, Controlled Clinical Trial Protocol to Assess the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block on Postoperative Analgesia and Recovery Quality in Laparoscopic Donor Hepatectomy.

Liver transplantation is considered an effective treatment for end-stage liver disease. Laparoscopic donor hepatectomy (LDH) has become a new standard procedure. And it is important to minimize the pain of the donor. Good postoperative analgesia can reduce the occurrence of postoperative complications and promote the early recovery of the donor. Ultrasound-guided transversus abdominis plane (TAP) block can provide effective analgesia for liver donors and reduce postoperative opioid consumption. This study aims to use ultrasound-guided TAP block for LDH to improve postoperative analgesia for donors while reducing opioid consumption and improving patient rehabilitation quality. This study is a prospective blinded, randomized, controlled clinical trial with a concealed allocation of patients (living liver donors) scheduled to receive laparoscopic partial hepatectomy 1:1 to receive local infiltration anesthesia or TAP block. This study will recruit a total of 80 patients. The primary outcome is the dosage of opioids within 24hours after surgery. This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. This trial study protocol was approved on 8 May 2023. The trial will start recruiting patients after being registered on the Chinese Clinical Trial Registry. ChiCTR2300071694.

The Addition of a Non-Steroidal Anti-Inflammatory Drug (NSAID) in Local Infiltration Analgesia During Total Knee Arthroplasty Increases the Risk of Acute Kidney Injury in Patients Who Have Renal Impairment: A Propensity-Matched Retrospective Cohort Study

BackgroundLocal infiltration analgesia (LIA) is a crucial component of pain management during total knee arthroplasty (TKA). Various formulations of the LIA drug cocktail have been described, with non-steroidal anti-inflammatory drugs (NSAIDs) commonly included. Although NSAIDs are highly effective in improving postoperative pain, they are associated with adverse renal, gastrointestinal, and cardiovascular effects. This study aimed to investigate whether the addition of an NSAID in LIA affects the incidence of acute kidney injury (AKI) in TKA patients, especially those who have pre-existing renal impairment. The secondary aim was to determine overall AKI incidence. MethodsA retrospective cohort study was conducted on elective, primary TKA patients in a single tertiary institution between January 2020 and April 2024. Data was obtained from a prospectively collected institutional knee arthroplasty registry. Patients were administered LIA intraoperatively, with or without an NSAID (30 mg of ketorolac). The study population was divided into two subpopulations, patients who did or did not have chronic kidney disease (CKD), and analyzed separately. Propensity matching was performed on the CKD group, correcting for age, sex, BMI, ASA score, and presence of diabetes mellitus/hypertension. The outcome of interest was the incidence of AKI. A t-test or Chi-square test was used, where appropriate, to determine the statistical significance of the results. ResultsIn patients who had CKD (n = 114), the presence of ketorolac in LIA was associated with a higher AKI incidence (12.7 versus 2.0%, P = 0.041). In patients who did not have CKD (n = 870), the presence of ketorolac in LIA was not associated with a higher AKI incidence (2.0 versus 1.9%, P = 1.0). Overall AKI incidence was 2.6%. ConclusionIn patients who have CKD, orthopaedic surgeons should be highly cautious of administering ketorolac in LIA during TKA, as it is associated with a higher risk of AKI. Patients who have normal renal function can be safely given ketorolac in LIA without an elevated risk of AKI. Further studies are needed to examine AKI incidence when other NSAIDs are used in LIA.

High-Dose Compound Betamethasone Used in Local Infiltration Analgesia Does Not Increase Reinfection Rates Following Periprosthetic Joint Infection Treatment

BackgroundThe administration of cocktails that contain glucocorticoids for local infiltration analgesia (LIA) is highly advocated and has been shown to be effective in managing pain in total joint arthroplasty (TJA). However, it remains ambiguous whether this protocol maintains its safety and efficacy in the treatment of periprosthetic joint infection (PJI), a devastating complication of TJA. MethodsA comprehensive retrospective study was carried out on 299 single-stage revision cases for PJI spanning the years 2010 to 2021. Of these, 127 received LIAs containing high-dose compound betamethasone (CB) were termed the CB group, and the other 172 were termed the non-CB group. The rates of reinfection and other postoperative complications, along with postoperative visual analog scale (VAS) scores, and opioid consumption were compared. ResultsDuring minimum 2-year follow-up, there was no significant difference in the reinfection rate between the non-CB and CB groups (9.3 versus 8.7%; P = 0.85), consistent within the subsets of hip (8.4 versus 4.5%; P = 0.51) and knee (10.4 versus 13.3%; P = 0.60) PJIs individually. The administration of high-dose CB was neither an independent risk factor for reinfection (P > 0.05; 95% CI [confidence interval] including 1) nor was it associated with the occurrence of reinfection (P > 0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the CB group (P < 0.05). In the initial 48-hour postoperative period, the CB group exhibited lower mean scores in both resting and movement VAS evaluations (P < 0.05). Notably, the movement VAS scores of the CB group remained lower even at 72 hours post-surgery for knee PJIs (P < 0.001). Furthermore, within the first 72 hours post-surgery, the necessity for additional opioid analgesics in the CB group was significantly reduced compared to the non-CB group (P < 0.05). ConclusionA LIA with a high-dose compound betamethasone reduces postoperative pain, opioid consumption, and the incidence of PONV following a single-stage revision without affecting reinfection and other complication rates.