Children with primary immunodeficiency (PID) and secondary antibody deficiency (SAD) often require immunoglobulin replacement therapy due to low plasma immunoglobulin G (IgG) levels and recurrent infections. Existing pharmacokinetic models for immunoglobulin in PID patients predominantly focus on adults, with limited attention to secondary antibody deficiencies and a lesser emphasis on paediatric populations. This study aims to investigate the pharmacokinetic properties of IgG in paediatric patients with PID and SAD. Population pharmacokinetic analysis for PID and SAD children treated with intravenous immunoglobulin at a tertiary paediatric centre was conducted using NONMEM® (7.5.1). Dosing simulations to achieve therapeutic levels of 6 and 8 gL-1 were performed. A population pharmacokinetic analysis of 64 patients (median age 4.08 years, range 0.06-16.8) was performed. A two-compartment model with first-order elimination, incorporating both additive and proportional residual error, adequately described the data. Interindividual variability was modelled on clearance, volume of distribution and baseline IgG levels, with allometric scaling to a 70-kg body weight applied a priori. The estimated clearance was 0.308 L-1 day-1 70 kg-1 (95% CI 0.23, 0.67), and the volume of distribution was 10.96 L-1 70 kg-1 (95% CI 5.97, 15.79). Patients with SAD exhibited a lower clearance rate of 54% compared with PID patients. Dosing simulations indicated that the recommended SAD dosing regimen maintained therapeutic IgG levels in the simulated population. However, only 44.8% to 51.9% of patients with PID achieved target IgG levels with the standard regimen. This study provides insights into immunoglobulin pharmacokinetics in paediatric PID and SAD patients, guiding optimised dosing strategies. Administering a loading dose would improve the probability of maintaining therapeutic IgG levels during the 4-week dosing interval.

Postoperative pain control after total knee arthroplasty (TKA) remains challenging. Intraoperative dexmedetomidine and ketamine are commonly used in multimodal analgesia to reduce pain and opioid requirements. This study aimed to compare their effects on opioid consumption, pain, hemodynamics and satisfaction. This prospective, randomized, double-blind study included 104 adults (≥ 18years) with ASA I-III status undergoing TKA under spinal anesthesia. After all patients had received spinal anesthesia, they were randomized into two equal groups (n = 52). Group D received dexmedetomidine (1µg/kg loading dose, then 0.5µg/kg/h); Group K received ketamine (0.1mg/kg/h without a loading dose). Sedation level was titrated to achieve a modified Observer's Assessment of Alertness/Sedation (OAA/S) score of 3-4. Postoperatively, a single-shot femoral nerve block was administered to all patients. Primary outcome was total opioid consumption in 24h. Secondary outcomes included Visual Analog Scale (VAS) scores, hemodynamic parameters, side effects and patient satisfaction. Tramadol use in 24h was similar (Group D: 175.29 ± 44.62mg; Group K: 155 ± 44.48mg; p = 0.44). VAS scores were comparable at all time points. Time to ambulation was longer in the ketamine group (Group D: 4.4 ± 1.4h; Group K: 5.3 ± 2.5h; p = 0.04). Group D showed significantly lower heart rate and blood pressure values at multiple time points (p < 0.001). Patient satisfaction was high in both groups and no hypotension or bradycardia occurred in any group. Although no significant differences were found between dexmedetomidine and ketamine, both agents provided comparable analgesia and opioid consumption, supporting their potential role as adjuvants in multimodal analgesia for patients undergoing TKA. ISRCTN11906298, retrospectively registered on 13.06.2025.

Intestinal lymphangiectasia (IL) is a heterogeneous syndrome characterized by dilation and rupture of lymphatic vessels, with subsequent leakage of lymphatic contents such as proteins, lymphocytes, and chylomicrons into the intestinal lumen. IL may manifest primarily, due to structural abnormalities of the lymphatic vessels related to genetic factors, or secondarily, due to conditions that lead to obstruction of lymphatic flow. Yorkshire Terriers, Shar-Peis, Rottweilers, and Lundehunds appear to be the most frequently affected breeds, while the Soft-Coated Wheaten Terrier is known to present the hereditary form of the disease. Affected dogs commonly exhibit diarrhea, vomiting, anorexia, progressive weight loss, and may also develop cavitary effusions. The present report aims to describe the clinical and pathological aspects, as well as the diagnostic and therapeutic approach applied to a patient with intestinal lymphangiectasia. A 6-year-old female Dachshund was examined with a history of recurrent vomiting and diarrhea throughout the year. On physical examination, the patient presented with sarcopenia, a distended abdomen with abundant free fluid, abdominal pain, alopecic areas, and a dull coat. Complementary tests, including a complete blood count and serum biochemistry, revealed hypoproteinemia and hypertriglyceridemia. An upper gastrointestinal endoscopy with mucosal biopsy was performed and revealed markedly congested, granular mucosa with whitish speckles “snow flakes”. Histopathology indicated moderate lymphoplasmacytic erosive duodenitis with evidence of edema and moderate, multifocal lymphangiectasia. Initial therapy for the patient included prednisolone at a loading dose (3 mg/kg BID), later tapered to a minimal effective dose (0.25 mg/kg every 72 hours), along with vitamin supplementation and a low-fat diet. Based on the findings, it is concluded that obtaining a definitive diagnosis is essential for the appropriate formulation of a therapeutic protocol and, consequently, for achieving clinical improvement in affected patients.

Lichen planus pigmentosus (LPP) is a form of lichen planus. It typically presents with pigmented, persistent skin patches. The etiology of LPP remains unclear, and there is no standardized or consistently effective treatment. Investigation of dupilumab, a monoclonal antibody not previously reported in the literature for LPP, may provide a new treatment option for disease management. A 42-year-old woman presented with progressive, pruritic, violaceous to dark brown patches on the neck, chest, and upper back for the past year. A biopsy from the neck and arm confirmed epidermal atrophy and pigment incontinence consistent with LPP. Multiple therapies were tried, including topical tacrolimus, oral cyclosporine, oral isotretinoin, narrowband ultraviolet B phototherapy, and oral dapsone, but the patient did not improve. Thus, off-label dupilumab was initiated with a 600 mg loading dose followed by 300 mg every two weeks. After three months of dupilumab therapy, the patient achieved complete resolution of pruritus and lightening of pigmented lesions. No new lesions developed, and the treatment was well tolerated. This significant clinical response to dupilumab following failure of previous therapies suggests potential efficacy in refractory LPP. The rapid response to dupilumab indicates that the T-helper 2 (Th2) immune pathway, particularly interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, may contribute to LPP pathogenesis. This is the first case of LPP successfully treated with dupilumab, encouraging the need for further research to judge the drug's efficacy.

Retained hardware/prosthetic infections frequently require antimicrobial suppression therapy. Treatment options are often limited by resistance, allergies, and dosing frequencies. Dalbavancin (DAL) is a potentially attractive option for suppression of gram-positive infections given its potential for infrequent dosing. However, optimal DAL suppression dosing is unknown. An in silico pharmacokinetic/pharmacodynamic simulation was performed to assess the predicted dalbavancin concentration resulting from suppressive regimens. Serum levels were deemed adequate if the fAUC24/MIC was above the PK target of 27.1. Patients at a U.S. medical center receiving DAL as suppressive therapy were reviewed. PK simulation of DAL dosed 1,500 mg monthly resulted in free serum concentrations above the PK target. Because many clinicians opt to initiate these regimens with two doses given 1 week apart, the next modeled regimen included this load, before initiating 1,500 mg monthly. This initial load did not significantly alter total drug exposure. The final simulated regimen was 1,000 mg monthly. With this simulation, the lower 95% CI fAUC24/MIC fell just below the PK target for an isolate at the breakpoint. Nine patients who received dalbavancin 1,500 mg monthly as suppressive therapy were reviewed. All had retained hardware and received DAL for a median 591 days, with 7 patients still receiving treatment and no reported suppressive therapy failure. Monthly 1500 mg dalbavancin dosing for suppressive therapy is supported by this case series and PK simulation data. An initial weekly loading dose appears unnecessary. Reducing the monthly dose to 1000 mg may also be appropriate for certain patients, though clinical data is needed to support this practice.

Introduction. Functional liver tests are a relevant group of methods for liver function screening, that can be used in a laboratory setting as well as in clinical practice. This group includes, among others, the Quick – Pytel test, which is based on the enzymatic formation of hippuric acid from glycine and benzoate in the liver. This test is minimally invasive and comparatively ease to perform, yet as of now, there is no detailed protocol to carry it out in small laboratory animals. Aim. The objective of this work was to develop a protocol of the Quick – Pytel test to assess liver antitoxic function in small laboratory animals. Materials and methods. Loading doses of sodium benzoate and glycine at an equimolar ratio (504 mg/kg and 264 mg/kg, respectively) were administered intraperitoneally to white outbred male mice ( n = 10), after which urine samples were collected over 18 h in metabolic cages. Following sample preparation, the newly formed hippuric acid was titrated by 0.01 N potassium hydroxide in the presence of 1 % phenolphthalein. In 1 week, the mice were injected with carbon tetrachloride (1 mL/kg) to induce acute toxic hepatitis, and the test was repeated. Liver injury was confirmed morphologically with haematoxylin and eosin staining. Results and discussion. Following carbon tetrachloride administration, urinary concentrations of hippuric acid decreased significantly ( p &lt; 0.01) by over 50 % from baseline. Liver samples exhibited characteristic features of acute toxic hepatitis. С onclusion. We have developed a protocol of the Quick – Pytel test in mice and confirmed its applicability to assess liver antitoxic function under acute injury conditions. The method we describe is simple and straightforward, is relatively low-cost, and can be used in routine practice to assess liver function in small laboratory animals.

ABSTRACT Objective Most antiseizure medications (ASMs) are prescribed off label for neonates. Lacosamide's efficacy in infants and availability in intravenous formulation suggest potential utility for neonates. We evaluated the safety and efficacy of lacosamide for neonatal seizures. Methods This 10‐center, retrospective study of neonates with seizures and lacosamide treatment initiated by ≤ 48 weeks postmenstrual age collected clinical data from medical records and electroencephalogram recordings. Lacosamide efficacy was determined by changes in seizure burden with lacosamide treatment and seizure cessation by hospital discharge. Potential adverse events were reviewed. Results Among 62 eligible neonates, 33 had acute provoked seizures while 29 had neonatal‐onset epilepsy; there was no difference in seizure type or baseline seizure severity between groups. There were high rates of pretreatment status epilepticus (48%) and treatment‐resistant seizures, with 93% receiving ≥ 3 ASMs before lacosamide. Most received intravenous lacosamide, with a median loading dose of 5.0 mg/kg and median daily dose of 7.3 mg/kg. Seizure cessation occurred in 37% of neonates; 21% had no additional ASM administered after lacosamide. Seizure burden, measured in seizure minutes per hour, was lower at both 4 h and 7 days following lacosamide administration. In addition, there was a median reduction in seizure frequency of 30 seizures per day at 7 and 30 days posttreatment ( p &lt; .05). Lacosamide was continued at discharge in most neonates (72%). Seventy adverse events were reported in 35 (56%) neonates. Four transient events with possible or unknown relationship to lacosamide were likely multifactorial in origin; none were cardiac arrhythmias. Summary Despite high rates of treatment‐resistant seizures in this neonatal cohort, 37% experienced seizure cessation and most remained on lacosamide at hospital discharge. Most adverse events were not attributed to lacosamide. These results favor use of lacosamide and provide a rationale for future prospective studies.

BackgroundDespite classification as the most common endemic mycosis in the United States, few data exist supporting the optimal care of patients with histoplasmosis, making diagnosis and treatment challenging. This study aimed to describe patients with histoplasmosis across a Michigan health system.MethodsA retrospective, multicenter cohort study of patients diagnosed with histoplasmosis between January 2020 and April 2023. The primary objective was to describe patients diagnosed with histoplasmosis, methods of diagnosis, and treatment they received. Patient outcomes, including mortality with treatment, and 6-month relapse of disease, were also evaluated.ResultsA total of 88 patients were included in the study, and most received care from an infectious diseases provider (86.4%). Tissue histopathology was the most common diagnostic method (59%). Treatment was initiated in 58 patients (66%); 17 (29.3) had disseminated disease. Five (8.6%) patients died within 6 months. Itraconazole was the agent most prescribed for definitive therapy (81%) followed by posaconazole (17%). Median treatment duration was 24 weeks. Adverse events occurred in more than one quarter of patients receiving triazoles. Loading doses were absent in 35% of itraconazole prescriptions; therapeutic drug monitoring was absent in 19.2%. No patients experienced a relapse of disease within 6 months of therapy completion.ConclusionsIn a cohort of patients with histoplasmosis from Michigan, variation in diagnostic testing and treatment was observed. Most patients were diagnosed by positive tissue histopathology and itraconazole was the most frequently prescribed antifungal followed by posaconazole. Opportunities for more sensitive diagnostic testing and improved antifungal dose optimization and monitoring were identified.

Achieving adequate sedation on extracorporeal membrane oxygenation (ECMO) is challenging due to altered pharmacokinetics. Limited data exists on phenobarbital in adult ECMO patients. The aim was to characterize the volume of distribution (Vd) and dosing. This single-center retrospective study examined adult ECMO patients who received intravenous phenobarbital and corresponding serum concentrations between January 1, 2017 and March 1, 2024. Phenobarbital levels for analysis were obtained 0.5-4 h after phenobarbital loading dose (LD) and up to 4 h prior to a maintenance dose; this time frame was adjusted to 0.5-1 h if on continuous venovenous hemofiltration (CVVH). Sixteen venovenous ECMO patients with 18 LD and 70 phenobarbital concentrations were evaluated. The median LD was 1225 mg (796.3-1437.8); 15 mg/kg (8.8-16.2) total body weight (TBW). The median total Vd was 67.7 L (46.8-80.8), 0.94 L/kg (0.72-1.22) ideal body weight (IBW), and 0.71 L/kg (0.67-0.82) TBW. Weight-based LD and concentration demonstrated a stronger correlation for TBW (r = 0.93, p < 0.001) versus IBW (r = 0.64, p = 0.003). Comparing BMI <30 and BMI ⩾30 kg/m2 patients there was a difference in total Vd (p = 0.02) and IBW-normalized Vd (p = 0.006), but no difference in TBW-normalized Vd (p = 0.31). The median maintenance dose was 2.4 mg/kg/day (1.7-2.7) TBW; CVVH patients required 11.7 mg/kg/day TBW. Phenobarbital concentration change was <3% after ECMO decannulation. In adult ECMO patients, phenobarbital's Vd normalized to TBW, was consistent with critically ill non-ECMO patients. Obesity affected Vd, CVVH influenced maintenance dosing, but ECMO decannulation did not impact phenobarbital concentrations.

IntroductionMyxedema coma is the most severe form of decompensated hypothyroidism and represents a rare but life-threatening endocrine emergency. Standard treatment involves IV levothyroxine; however, access to this formulation is limited in many low-resource settings. This study aimed to describe the clinical characteristics, management, and outcomes of patients with myxedema coma treated with high-dose oral levothyroxine in a tertiary referral center in Colombia.Materials and MethodsWe conducted an observational study of adult patients diagnosed with myxedema coma between January 2011 and December 2021 at Fundación Valle del Lili. Diagnosis was based on Popoveniuc criteria (>60 points) or presence of coma in the context of hypothyroidism. Data were collected from electronic medical records. All patients received oral levothyroxine, and clinical, laboratory, and outcome variables were analyzed.ResultsTwelve patients were included (median age 66 years; 50% female). The most common precipitating factor was acute infection (41.6%). All patients received an oral loading dose of levothyroxine (median 500 µg), followed by high-dose maintenance therapy. Normalization of free T4 was observed in all patients by the fourth day. The intensive care unit admission rate was 100%, with a median stay of 11 days. Vasopressor support was required in 58.3%, and in-hospital mortality was 25%.ConclusionHigh-dose oral levothyroxine was effective in achieving early biochemical recovery in patients with myxedema coma. In settings where IV formulations are unavailable, oral therapy represents a viable and potentially life-saving alternative.

There is a lack of information regarding the combination therapy of phenobarbital (PB) and benzodiazepine (BZD) for the symptomatic management of patients in or at risk of severe alcohol withdrawal syndrome (AWS). The objective of this study was to assess the safety and efficacy of a PB loading dose in addition to symptom-triggered BZD treatment for patients in or at risk of severe AWS. Between January 2024 and May 2025, patients treated for AWS were screened for inclusion. Criteria for inclusion were age of at least 18 years old, a Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score of 4 or higher, and a record of receiving treatment for AWS. Patients were excluded from the study if they were directly admitted to the intensive care unit (ICU) or psychiatric service, transferred to the ICU within 12 hours of admission, or with a length of stay less than 24 hours. The primary endpoint was the difference in cumulative BZD requirements. Secondary endpoints included the need for adjunct therapies, incidence of adverse events, and escalation of care. The final analysis included 75 patients in the BZD group and 63 patients in the PB group. There was a statistically significant decrease in the cumulative BZD utilization in the PB loading group. Patients who exclusively received BZD therapy for AWS used an average of 148 mg of diazepam equivalents versus 112 mg in the PB group (P = 0.002). The PB group was also associated with a statistically significant reduction in the incidence of hypotension, respiratory depression, and the need for adjunct therapies. The addition of a weight-based PB loading dose showed a significant reduction in BZD utilization for patients in or at risk of severe AWS and was associated with fewer adverse events. Application of this information may aid in enhancing treatment for patients in or at risk of severe AWS.

Various sedation methods are used during endoscopic retrograde cholangiopancreatography (ERCP) procedures, which are increasingly performed in elderly patients. Our study aimed to compare the effects of propofol anesthesia with a propofol-dexmedetomidine combination on cognitive function in elderly patients undergoing ERCP. This prospective observational study included 184 inpatients aged 65 years and older who received either propofol or a propofol-dexmedetomidine combination for sedation during ERCP. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) at three time points: before the procedure and at 2 and 24 h after the procedure. The degree of frailty in patients was assessed via a frailty questionnaire. In the propofol (P) group, the propofol loading dose was 0.2–0.5 mg/kg, with a maintenance infusion dose of 0.5-4 mg/kg/h. In the propofol + dexmedetomidine (P + D) group, in addition to propofol infusion at the same doses, a loading dose of 0.5 µg/kg dexmedetomidine was administered over 10 min, followed by an infusion at a dose of 0.2–0.7 µg/kg/h. There was no statistically significant difference between the P and P + D groups in terms of the MMSE score before the procedure (p > 0.05). However, in the P + D group, a significant improvement in the MMSE score was observed at both 2 h (z = 2.943, p = 0.003) and 24 h (z = 2.816, p = 0.005) after the procedure. The increase in MMSE scores was significantly greater in the P + D group, particularly among pre-frail patients. Our study demonstrated that dexmedetomidine yielded more favorable results in terms of cognitive function than propofol following ERCP in geriatric patients. NCT06719960. Retrospectively registered.

Dexmedetomidine was widely used in anesthesia management during cardiac surgery. The purpose was to evaluate the safety and efficacy of intraoperative dexmedetomidine in the treatment of postoperative depression in adult patients undergoing cardiac surgery. A randomized trial was conducted to enroll patients undergoing elective cardiac surgery between April and August 2024. Patients aged 18-85 with an American Society of Anesthesiologists classification of I-IV were randomized in a 1:1 ratio to receive intraoperative dexmedetomidine (following a 10 min 0.6μg/kg loading dose, 0.4μg/kg/h maintenance infusion) or placebo (normal saline). The primary outcome was the positive screening rate for depression assessed by the Patient Health Questionnaire-9 (PHQ-9) scale at postoperative 7days. Secondary outcomes encompassed the incidence of delirium, anxiety, sleep disturbance, pain, and quality of life. All participants, care providers, and investigators remained blinded to treatment allocation throughout the study. Analyses were done by intention-to-treat populations. A total of 313 patients provided informed consent, of whom 200 were randomized (100 assigned to dexmedetomidine and 100 assigned to placebo). Dexmedetomidine demonstrated favorable tolerability and safety profiles. The incidence of depression at postoperative 7days was significantly lower in the dexmedetomidine group than in the placebo group [11.0% vs 31.0%; adjusted relative risk (aRR): 0.29; 95% CI: 0.08-0.48; P < 0.001]. The incidence of delirium (5.0% vs 19.0%; aRR: 0.17; 95% CI: 0.06-0.54; P =0.001), anxiety (8.0% vs 21.0%; aRR: 0.22; P =0.005), sleep disturbance (32.0% vs 42.0%; aRR: 0.67; P =0.022), and pain during movement (31.0% vs 59.0%; aRR: 0.38; P =0.001) at postoperative 7days was also significantly lower in the dexmedetomidine group than in the placebo group. The EQ-5D-5L score of the dexmedetomidine group was significantly higher than that of the placebo group at postoperative 7days. However, there were no significant differences in depression, anxiety, sleep disturbance, pain incidence, and quality of life scores between the two groups at postoperative 30days. Intraoperative dexmedetomidine significantly reduced the incidence of depression, delirium, anxiety, sleep disturbance, and pain and improved quality of life in adult cardiac surgery patients at postoperative 7days. But dexmedetomidine did not reduce depression, anxiety, pain and sleep disturbance in patients undergoing cardiac surgery at postoperative 30days.

Amlitelimab (SAR445229, KY1005), a nondepleting anti-OX40 ligand monoclonal antibody, reduced lesions and pruritus in phase2a and 2b trials in adults with moderate-to-severe atopic dermatitis (AD). Here, efficacy and durability of amlitelimab across body regions were evaluated, given that unmet needs remain for treatment of head and neck AD. STREAM-AD phase2b trial data were used in this post hoc analysis. Patients were randomized 1:1:1:1:1 to receive amlitelimab subcutaneously (250mg with 500-mg loading dose, 250mg, 125mg, or 62.5mg) or placebo every 4weeks from weeks0 to 24 (part1). In part2, clinical responders (patients achieving Investigator Global Assessment 0/1 and/or ≥ 75% reduction in Eczema Area and Severity Index [EASI-75] at week24) were re-randomized 3:1 to withdraw from amlitelimab or continue their pre-week24 amlitelimab dose through week52. EASI subscores and signs were evaluated for head and neck, trunk, lower extremities, and upper extremities. Part1 included 390 randomized patients; 190 continued to part2. In part1, all EASI body region subscores were reduced with all amlitelimab doses at week24 (P ≤ 0.01). Additionally, the four EASI signs-erythema, edema, excoriation, and lichenification-were reduced with amlitelimab vs. placebo. Greater proportions of patients achieved EASI-75 per body region with all amlitelimab doses, compared to placebo (P ≤ 0.05). At week52, clinical responders maintained improvements in each body region achieved in part1, regardless of treatment continuation or withdrawal. Improvements in AD signs and severity were observed with amlitelimab across all body regions. Notably, clinical responses were sustained following treatment withdrawal, supporting the potential for extended dosing intervals and durable off-treatment efficacy. Amlitelimab may be a treatment option for hard-to-treat head and neck AD that disproportionately impairs quality of life. ClinicalTrials.gov Identifier NCT05131477.

BackgroundCervical dilation during ambulatory hysteroscopy often triggers somatic responses that challenge patient comfort and procedure smoothness. While esketamine’s unique analgesic profile could address this, its effective dose within a dexmedetomidine-remifentanil monitored anesthesia care (MAC) protocol is undefined.MethodsIn this prospective, double-blind, dose-finding study, 30 women received a standardized MAC protocol (dexmedetomidine 0.6 μg∙kg−1 loading dose followed by 0.4 μg∙kg−1∙h−1, with remifentanil 5 μg∙kg−1∙h−1). Esketamine was administered via Dixon’s up-and-down sequential design (initial dose 0.3 mg∙kg−1; increments/decrements 0.02 mg∙kg−1) before cervical dilation. Positive response is defined as the absence of purposeful movement. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using probit regression.Results30 patients completed the study. The ED50 of esketamine was 0.36 mg∙kg−1 (95% CI 0.35–0.37) and the ED95 was 0.39 mg∙kg−1 (95% CI 0.37–0.42). Hemodynamic stability was maintained (mean arterial pressure change ≤15% from baseline) with no respiratory depression. Adverse events were self-limiting dizziness (66.7%) and nausea (6.7%). Recovery was swift, with a time to meet post-anesthesia care unit (PACU) discharge criteria of 17.93±3.30 min, and patient satisfaction was high (median score 9/10, IQR 8–10).ConclusionUnder dexmedetomidine-remifentanil MAC, esketamine 0.39 mg∙kg−1 (ED95) effectively suppresses the cervical dilation response, promotes hemodynamic and respiratory stability, and facilitates a rapid, enhanced recovery after surgery (ERAS)-compliant recovery. This dose-finding study provides a practical and effective anesthetic combination for clinical implementation in ambulatory hysteroscopy.Clinical Trial RegistrationClinicalTrials.gov (identifier: NCT07034963). Principal Investigator: Lijuan Yan.

ABSTRACTPaliperidone, a second‐generation antipsychotic commonly used to treat schizophrenia and schizoaffective disorder, has been rarely associated with inducing catatonia, a severe neuropsychiatric syndrome characterized by motor disturbances and altered mental status. We present two cases demonstrating variable onset of paliperidone‐induced catatonia: a 20‐year‐old male with acute symptoms following intramuscular loading doses and a 24‐year‐old female with a delayed presentation. Both cases highlight the clinical challenge of timely recognition, which is critical to prevent serious complications such as dehydration and respiratory failure. Assessment using the Bush‐Francis Catatonia Rating Scale (BFCRS) guided treatment with benzodiazepines and antipsychotic adjustments, resulting in significant symptom improvement. This case series underscores the need for heightened awareness of this rare adverse effect to facilitate early diagnosis and optimize outcomes in patients receiving paliperidone.

Tranexamic acid (TXA) stabilizes clot formation by inhibiting fibrin degradation and improves postoperative outcomes. However, rare adverse events (e.g., thrombosis, seizures) warrant dose-risk evaluation. This study examines how perioperative blood loss and transfusion practices affect TXA concentrations during paediatric scoliosis surgery. Forty-three patients undergoing scoliosis surgery with TXA were retrospectively analysed. The study assessed the impact of packed red blood cell (PRBC) transfusion on plasma TXA levels and whether maintaining concentrations ≥10μg/mL correlated with intraoperative blood loss. TXA levels were measured using UHPLC-MS/MS. Median TXA concentration 30 min after the loading dose was 37.8μg/mL (IQR: 31.4-39.6μg/mL), decreasing to 10.6μg/mL (IQR: 9.7-13.5μg/mL) after transfusion. At surgery end, the mean concentration was 12.9 ± 2.5μg/mL. Thirty-one patients maintained TXA levels ≥10μg/mL, associated with ~80% inhibition of tissue plasminogen activator. Of six patients below this threshold, five had received transfusions. A significant correlation was found between higher intraoperative blood loss and lower TXA levels, consistent with a dilutional effect. In contrast, among patients with TXA ≥ 10μg/mL, correlation with blood loss was weak (Spearman's ρ = -0.11, p = 0.54). Findings suggest homologous PRBC transfusion reduces plasma TXA through volume expansion. Sustaining TXA concentrations >10μg/mL is essential for antifibrinolytic efficacy and haemostatic outcomes. The dilutional impact of PRBC transfusion underscores the need for intraoperative dose adjustment. Optimizing TXA dosing requires understanding pharmacokinetics and patient variability.

Abstract Background Vitamin D deficiency can cause secondary hyperparathyroidism (SHPT) which results in bone loss, particularly at cortical sites such as neck of femur, distal radius and humerus. Hip fracture patients have a higher prevalence of frailty and are at greater risk for vitamin D deficiency (25(OH)D&amp;lt; 30 nmol/l) or insufficiency (25(OH)D 30-49.9 nmol/l). Vitamin D replete status is also important in preventing hypocalcaemia in patients receiving zoledronate. We aimed to determine the prevalence of low vitamin D status and SHPT in acute hip fractures patients at our hospital. Methods Data on demographics, vitamin D status and PTH levels were recorded on acute hip fracture patients (aged &amp;gt;65 years) over a 12 month period from April 2023. A serum PTH level above 65 pg/ml in the presence of normal or low serum calcium was considered to represent SHPT. We explored for prevalence of vitamin D deficiency/insufficiency and predictors of SHPT in regression analysis. Results 149 patients were reviewed, mean age 82.5 years, 76.2% female. 22.8 % were vitamin D deficient and 16.1% had vitamin D insufficiency. Overall, 38.9% had serum 25(OH)D below 50 nmol/l. SHPT occurred in 22.9% and was predicted by low vitamin D status (&amp;lt;50 nmol/l, P=0.011) but not by age or gender. Conclusion Roughly 25% with hip fractures had vitamin D deficiency and about 40% suboptimal levels. Importantly, one in four also had SHPT. Vitamin D levels should be &amp;gt;50 nmol/l prior to zoledronic acid therapy. However, vitamin D results during the acute admission are often not available. In such cases, a consensus opinion has suggested 100,000 – 250,000 IU over 1-7 days. We suggest that if PTH results (that are more readily available) confirm SHPT, then large loading doses of vitamin D before zoledronic acid is advisable.

BackgroundPolymyxin B remains a key treatment option for infections caused by MDR Gram-negative bacilli, particularly in critically ill patients. However, its optimal dosing strategy recommendation remains uncertain, especially in those undergoing renal replacement therapy.ObjectivesTo compare the clinical and microbiological outcomes of low, usual and high-dose polymyxin B in a real-world ICU population.MethodsThis 5 year retrospective cohort study included critically ill adult patients with Gram-negative sepsis who received polymyxin B. Patients were categorized into low-, usual- and high-dose groups based on loading and total daily maintenance dose. Pairwise propensity score matching was performed to adjust for baseline differences. The primary outcome was 28 day all-cause mortality. Secondary outcomes included microbiological clearance, ventilator-free days, ICU-free days and vasopressor-free days. Subgroup and sensitivity analyses were conducted, including within patients requiring dialysis. All the statistical analysis was performed using R software.ResultsA total of 674 patients were included. After matching, usual-dose polymyxin B was associated with significantly higher 28 day mortality compared to the low-dose group (HR: 1.47 [1.11–1.95]; P=0.007). Vasopressor, ventilator and ICU-free days were also significantly higher in the low-dose group. No significant survival advantage was observed with high-dose regimens. Among dialysis-dependent patients (n=254), mortality did not differ significantly across dosing groups, though microbiological clearance was better with low dosing. Sensitivity and subgroup analysis also supported the robustness of the results.ConclusionsLow-dose polymyxin B was found to be non-inferior to the conventional dose in terms of clinical outcomes, without compromising microbiological efficacy. Supplemental dose offered no added benefit in patients undergoing dialysis. These findings support the use of individualized, lower dosing strategies, particularly in patients with renal impairment. Prospective trials are needed to define the optimal dosing threshold balancing efficacy and safety.

Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen−/PH−, Drusen+/PH−, Drusen−/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan–Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH− group had a higher retreatment rate and required more injections than the Drusen−/PH+ and Drusen+/PH+ groups. The Drusen+/PH− group was older than the Drusen−/PH+ and Drusen−/PH− groups. The Drusen−/PH+ group had a thicker choroid than the Drusen+/PH− group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH− group and the thicker choroid of the Drusen−/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies.