Familial Chiari malformation: a systematic review and illustrative cases.

OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.

The effects of keratin-coated titanium on osteoblast function and bone regeneration.

INTRODUCTION: Wool derived keratin, due to its demonstrated ability to promote bone formation, has been suggested as a potential bioactive material for implant surfaces. The aim of this study was to assess the effects of keratin-coated titanium on osteoblast function in vitro and bone healing in vivo. Methods: Keratin-coated titanium surfaces were fabricated via solvent casting and molecular grafting. The effect of these surfaces on the attachment, osteogenic gene, and osteogenic protein expression of MG-63 osteoblast-like cells were quantified in vitro. The effect of these keratin-modified surfaces on bone healing over three weeks using an intraosseous calvaria defect was assessed in rodents. Results: Keratin coating did not affect MG-63 proliferation or viability, but enhanced osteopontin, osteocalcin and bone morphogenetic expression in vitro. Histological analysis of recovered calvaria specimens showed osseous defects covered with keratin-coated titanium had a higher percentage of new bone area two weeks after implantation compared to that in defects covered with titanium alone. Conclusions: The keratin-coated surfaces were biocompatible and stimulated osteogenic expression in adherent MG-63 osteoblasts. Furthermore, a pilot preclinical study in rodents suggested keratin may stimulate earlier intraosseous calvaria bone healing. .

Functional Outcome of Lower Limb Long Bone Trauma Management in Pregnant Mothers: A Prospective Study of 30 Cases From a Tertiary Care Centre in North India.

INTRODUCTION: The occurrence of orthopedic injuries during pregnancy carries considerable morbidity and mortality for both the mother and fetus. Successful care of lower limb fractures during pregnancy requires a multidisciplinary approach. Both operative and non-operative treatments must be taken into account by the treating orthopedic physician. There is limited literature available on the management of these lower limb fractures in pregnancy, and peri-operative management of this obstetric and orthopedic trauma is largely unclear. Trauma during pregnancy is a common cause of non-obstetrical maternal death, having a significant public health burden to both the mother and child. The aims and objectives of this study were to review the common causes of lower limb long bone trauma during pregnancy and their functional outcome in terms of morbidity and mortality. This study evaluates various operative and conservative methods of treatment to provide a comprehensive management approach to pregnant patients with lower limb trauma. MATERIALS AND METHODS: A prospective study on functional outcomes of 30 pregnant females who were admitted with lower limb long bone fractures from 2017 to 2021 was done. The patients were randomly selected intra-operatively for various procedures based on the surgeon's preference. All patients were followed for two years or till union occurred, and the radiographic union score for tibial (RUST) and modified radiographic union score for tibial (mRUST) fracture criteria were used to assess bony union clinico-radiologically.  Results: During this study, the mean age of patients was 27 years (range 19-38), having right-side (53.33%) predominance with road traffic accidents (n=22) and falls (n=6) as the most common causes of injury. Two cases of domestic violence were also reported. In our study, the maximum number of cases was 17-25 weeks of their gestation; 12 (40%) patients had tibial fractures, and 18 (60%) had femoral fractures. Six tibial fractures were handled conservatively, while all femoral fractures required surgical intervention. Out of 18 femoral fractures, which were treated surgically, dynamic compression plating was done in 15 (83.33%) patients, while interlock nailing was done in three patients. Six tibial fractures have been operated upon, two (66.66%) with dynamic compression plating and four (33.33%) with an interlocking nail. CONCLUSION: A multidisciplinary approach in terms of both operative and non-operative methods must be taken into account for treating pregnant mothers by the orthopedic physician while carefully weighing the benefits and risks of both procedures. Based on the pattern and displacement of the fracture, many prenatal fractures can be treated conservatively. Another alternative that is frequently safe is to postpone the surgical procedure until childbirth. The physiologic changes associated with pregnancy and any potential dangers to the fetus must be taken into account by the orthopedic surgeon when fractures necessitate surgical intervention. The surgeon is responsible for the patient's correct placement, the C-arm's use, the radiation dose, and the intra-operative fetal monitoring, as well as the danger brought on by anesthetics, antibiotics, analgesics, and anticoagulants.

Advances in the polymeric nanoparticulate delivery systems for RNA therapeutics.

RNA therapeutics have emerged as potential treatments for genetic disorders, infectious diseases, and cancer. RNA delivery to target cells for efficient therapeutic applications remains challenging due to instability and poor uptake. Polymeric nanoparticulate delivery systems offer stability, protection, and controlled release. These systems shield RNA from degradation, enabling efficient uptake and extended circulation. Various polymeric nanoparticle platforms have been explored, including lipid-based nanoparticles, polymeric micelles, dendrimers, and polymer-drug conjugates. This review outlines recent breakthroughs of recent advances, design principles, characterization techniques, and performance evaluation of these delivery systems. It highlights their potential in translating preclinical studies into clinical applications. Additionally, the review discusses the application of polymeric nanoparticles in ophthalmic drug delivery, particularly for medications that dissolve poorly in water, and the progress made in siRNA-based therapies for viral infections, autoimmune diseases, and cancers. SiRNA holds great promise for precision medicine and therapeutic intervention, with the ability to target specific genes and modulate disease-associated pathways. The versatility and potency of siRNA-based drugs offer a broader scope for therapeutic intervention compared to traditional biological drugs. As research in RNA therapeutics continues to advance, these technologies hold tremendous potential to revolutionize the treatment of various diseases and improve patient outcomes.

Computational and in vitro screening validates the repositioning potential of Coxibs as anti-fibrotic agents.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with a survival rate of <5 years. The TGF-ß plays a significant role in the progression and severity of IPF. The TGF-ß receptor type1 TGFBR1 antagonists inhibit the process of fibrosis and may have a role in the treatment of IPF. The main objective of the study was to identify promising drug candidates against IPF using In-silico and In-vitro evaluation methods. An in-silico screening was carried out of the marketed Coxibs to find their TGFBR1 inhibitory potential considering their structural resemblance with the JZO-a co-crystalized ligand of the crystal structure of the TGFBR1. The virtual screening yielded rofecoxib as a TGFBR1 ligand with a significant docking score. To further validate the outcome of molecular docking studies, MD simulation of 200 ns was carried out followed by the determination of conformational stability, binding free energy calculation using MMPBSA/MMGBSA, and Free Energy Landscape (FEL). The therapeutic efficacy of rofecoxib was compared with that of nintedanib (a therapeutic agent used in the treatment of IPF) at equimolar concentrations (5 µM). The model of TGF-ß1 (1 ng/ml)-induced EMT of A549 was used to determine the effect of rofecoxib on the EMT markers like cellular morphology, cytokine expressions, fibrosis associated protein, E-cadherin, and α-smooth muscle actin. In vitro results indicated that rofecoxib significantly suppresses the TGF-ß1-induced EMT of A549 cells and validates the possible preventive/protective role of rofecoxib in pulmonary fibrosis. In conclusion, rofecoxib may be considered for repositioning as an anti-fibrotic agent.Communicated by Ramaswamy H. Sarma.

Residue behavior and consumer risk assessment of spirotetramat and chlorpyrifos on cabbage heads and cropped soil.

A field experiment following good agricultural practices was laid out to study the dissipation of spirotetramat (90 g a.i. ha-1 and 180 g a.i. ha-1) and chlorpyrifos (400 g a.i. ha-1 and 800 g a.i. ha-1) on cabbage heads and soil. Samples were processed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for residue estimation of spirotetramat and chlorpyrifos, which were further detected using HPLC-PDA and GC-FPD respectively. The residues of spirotetramat on cabbage heads reached below detection limit (BDL) (< 0.05 mg kg-1) on 7th and 10th day and for chlorpyrifos, BDL (< 0.01 mg kg-1) was achieved on 10th and 15th day for X and 2X dose, respectively. On 20th day after second spray, residues in soil were found to be BDL for both the pesticides. Half-life of spirotetramat and chlorpyrifos was found to be 3 and 2 days, respectively while a safe pre-harvest interval (PHI) of 9 days for spirotetramat and 10 days for chlorpyrifos is suggested on cabbage. The dietary risk assessment studies for various age groups of Indian population, ascertained safety of treated cabbage heads for consumption, as current study revealed that hazard quotient (HQ) < 1 and theoretical maximum dietary intake (TMDI) < maximum permissible intake (MPI) for both the pesticides at respective PHI.

Avelumab in the Treatment of Advanced Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Avelumab, a programmed death ligand-1 inhibitor, has shown success in providing durable responses for difficult-to-treat Merkel cell carcinomas (MCCs). OBJECTIVE: Evaluate the efficacy and safety of avelumab in the treatment of advanced MCC. METHODS: Studies reporting the use of avelumab as a monotherapy or in combination with other agents in the treatment of stage III or IV (advanced) MCC were included. The primary outcomes were overall response rate, overall survival (OS), and treatment-related adverse events. RESULTS: A total of 48 studies were included, involving 1,565 patients with advanced MCC. Most patients were male (1,051, 67.3%) with stage IV MCC (517, 97.0%). The overall response rate was 46.1% (partial response-25.4% and complete response-20.7%) after a mean follow-up period of 9.5 months. Kaplan-Meier survival curves for the pooled stage III and IV group demonstrated OS rates of 58% at 1 year, 47% at 2 years, and 28% at 5 years after completion of treatment with avelumab (median OS: 23.1 months). The most common treatment-related adverse events consisted of constitutional (44%), gastrointestinal (19%), and dermatologic (12%) symptoms. CONCLUSION: Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.

Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation.

PURPOSE: This research endeavor was undertaken to elucidate the impact of an innovative ascorbate formulation on the regeneration process of full-thickness excision wounds in a rat model exposed to whole-body gamma irradiation, replicating conditions akin to combat or radiation emergency scenarios. MATERIALS AND METHODS: We established a comprehensive rat model by optimizing whole body γ-radiation doses (5-9 Gy) and full-thickness excision wound sizes (1-3 cm2) to mimic radiation combined injury (RCI). The developed RCI model was used to explore the healing potential of ascorbate formulation. The study includes various treatment groups (i.e., sham control, radiation alone, wound alone, radiation + wound, and radiation + wound + formulation). The ascorbate formulation was applied twice daily, with a 12-hour gap between each application, starting 1 hour after the initiation of the wound. The healing potential of the formulation in the RCI context was evaluated over 14 days through hematological, molecular, and histological parameters. RESULTS: The combination of a 5 Gy radiation dose and a 1 cm2 wound was identified as the optimal setting to develop the RCI model for subsequent studies. The formulation was used topically immediately following RCI, and then twice daily until complete healing. Treatment with the ascorbate formulation yielded noteworthy outcomes and led to a substantial reduction (p < .05) in the wound area, accelerated epithelialization periods, and an increased wound contraction rate. The formulation's localized healing response improved organ weights, normalized blood parameters, and enhanced hematopoietic and immune systems. A gene expression study revealed the treatment up-regulated TGF-ß and FGF, and down-regulated PDGF-α, TNF-α, IL-1ß, IL-6, MIP-1α, and MCP-1 (p < .05). Histopathological assessments supported the formulation's effectiveness in restoring cellular architecture and promoting tissue regeneration. CONCLUSION: Topical application of the ascorbate formulation in RCI resulted in a significant improvement in delayed wound healing, leading to accelerated wound closure by mitigating the expression of inflammatory responses.

A retrospective study on the prognostic factors and success, survival, and failure outcomes of treated endodontic-periodontal lesions.

OBJECTIVES: The objective of this retrospective study was to determine possible prognostic factors of endodontic-periodontal lesions and to compare success, survival, and failure outcomes of treated endodontic-periodontal lesions across different treatment modalities, demographic variables, and anatomical tooth variations. MATERIALS AND METHODS: Data was collected from patient records in the patient management system (Salud, Titanium Solutions) from the Griffith University Dental Clinic between January 2008 and December 2021. The search strategy used the terms "endodontic periodontal lesion," "periodontal endodontic lesion," "endo perio lesion," "perio endo lesion," and "EPL." The 88 cases which met inclusion and exclusion criteria were analyzed. RESULTS: The overall success rate was 46.6%, with 21.6% of teeth surviving and 31.8% of teeth failing. Bone loss extending to the apical third (OR = 0.3, 95% CI [0.104, 0.866]), and probing depths of 5-7 mm (OR = 0.147, 95% CI [0.034, 0.633]) and 8-10 mm (OR = 0.126, 95% CI [0.029, 0.542]) were associated with a statistically significant lower odds of success (p < .05). A history of no periodontal disease (OR = 7.705, 95% CI [1.603, 37.037]) was associated with a statistically significant higher odds of success (p < .05). CONCLUSION: Practitioners should be aware of bone loss to the apical third, deep probing depths, and a history of periodontal disease as possible prognostic factors that can affect the success rate when treating endodontic-periodontal lesions. Further research with more stringent control over operator factors should be done to investigate these variables.

CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.

The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [68 Ga]Ga-AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 (KD : 19.1 ± 0.99 × 10-9 m) by surface plasmon resonance. Further, [68 Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [68 Ga]Ga-AJ206 detects CD38 expression in cell line-derived xenografts, patient-derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68 Ga]Ga-AJ206-PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all-trans retinoic acid (ATRA) therapy. In conclusion, [68 Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68 Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.

Current paradigms in employing self-assembled structures: Drug delivery implications with improved therapeutic potential.

Recent efforts have focused on developing improved drug delivery systems with enhanced therapeutic efficacy and minimal side effects. Micelles, self-assembled from amphiphilic block copolymers in aqueous solutions, have gained considerable attention for drug delivery. However, there is a need to further enhance their efficiency. These micelles offer benefits like biodegradability, biocompatibility, sustained drug release, and improved patient compliance. Yet, researchers must address stability issues and reduce toxicity. Nanoscale self-assembled structures have shown promise as efficient drug carriers, offering an alternative to conventional methods. Fine-tuning at the monomeric and molecular levels, along with structural modifications, is crucial for optimal drug release profiles. Various strategies, such as entrapping hydrophobic drugs and using polyethylene oxide diblock copolymer micelles to resist protein adsorption and cellular adhesion, protect the hydrophobic core from degradation. The polyethylene oxide corona also provides stealth properties, prolonging blood circulation for extended drug administration. Amphiphilic copolymers are attractive for drug delivery due to their adjustable properties, allowing control over micelle size and morphology. Emerging tools promise complex and multifunctional platforms. This article summarizes about the challenges as far as the use of micelles is concerned, including optimizing performance, rigorous pre-clinical and clinical research, and suggests further improvement for drug delivery efficacy.

Developing, validating, and comparing an analytical method to simultaneously detect z-drugs in urine samples using the QuEChERS approach with both liquid chromatography and gas chromatography-tandem mass spectrometry.

Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC-MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1-200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC-MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC-MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.

Development of the EldenCare application: Empowering physicians and clinical pharmacists towards enhancing elderly care.

The growing healthcare burden on the elderly population, combined with an increase in prescription drug use, necessitates the development of novel solutions for improving elderly care. EldenCare connects doctors, clinical pharmacists, and elderly patients. EldenCare was developed by a multidisciplinary team comprising geriatricians, clinical pharmacists, and software engineers. The software offers various features tailored to the needs of each user group, revolutionizing medication management and patient care. For geriatricians, EldenCare provides efficient means of recording patient information, scheduling appointments, and documenting follow-up. Clinical pharmacists can take advantage of the software's advanced features, including identifying medication risks, facilitating dose adjustments, identifying potentially inappropriate medications, and tracking adverse drug reactions. Elderly patients benefit from features such as medication alerts, appointment management, medication lists and an adverse drug reaction diary. The study is divided into five distinct phases: requirements phase, design phase, coding & unit testing phase-frontend, coding & unit testing phase-database/cloud, testing phase. The expected benefits of the EldenCare software include increased medication safety, improved communication between healthcare providers and patients, and improved healthcare outcomes for older adults. EldenCare aims to revolutionise medication management and promote a patient-centered healthcare system by empowering clinical pharmacists and engaging older adults in their care-using technology.

Residue estimation and dietary risk assessment of fenvalerate, novaluron, and profenofos in bell pepper grown under protected and open field conditions.

Residue studies were conducted in bell pepper crops (green and yellow bell pepper) to ensure the safe use of fenvalerate, profenofos, and novaluron (under open field and protected conditions) in randomized block design (RBD) following three applications at a 10-day interval over two consecutive years, 2021 and 2022. A robust analytical method was developed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS) for the determination of pesticide residues in bell pepper samples. The half-lives for fenvalerate were 2.47-2.87 and 2.50-3.03 days on bell pepper under open field conditions, whereas the corresponding values for bell pepper under protected conditions were 3.84-4.58 and 4.17-4.71 days, during 2021 and 2022, respectively. Profenofos displayed half-lives of 2.03-2.65 and 2.15-2.77 days in open field conditions and 3.05-3.89 and 3.16-3.78 days in protected conditions during 2021 and 2022, respectively. Similarly, novaluron had half-lives of 2.87-3.49 and 3.24-3.75 days under protected conditions in 2021 and 2022, respectively. The maximum residue limits (MRLs) were calculated to be 0.6 mg/kg for fenvalerate, while for profenofos it was 0.7 mg/kg on bell pepper under open field conditions at double doses, at the proposed pre-harvest interval (PHI) of 3 days. Likewise, for bell peppers grown under protected conditions, MRLs at the PHI of 3 days were determined to be 0.8 mg/kg for fenvalerate, 0.3 mg/kg for novaluron, and 1.5 mg/kg for profenofos. A dietary risk assessment study indicated that the percentage of acute hazard index (% aHI) was significantly lower than 100, and hazard quotient (HQ) values were below 1, signifying no acute or chronic risk to consumers. These findings underscore the safety of consuming bell peppers treated with fenvalerate, profenofos, and novaluron under the protected and open field conditions.

Fermented formulation of Silybum marianum seeds: Optimization, heavy metal analysis, and hepatoprotective assessment.

BACKGROUND: Fermented formulations are extensively used in Ayurveda due to several benefits like improved palatability, bioavailability, pharmacological potential, and shelf life. These formulations can also quench the heavy metals from the plant material and thus reduce the toxicity. Seeds of Silybum marianum (L.) Gaertn. are widely used for the management of many liver diseases. STUDY DESIGN AND METHODS: In the present study, we developed a novel fermented formulation of S. marianum seeds and evaluated parameters like safety (heavy metal analysis) and effectiveness (hepatoprotective). As the developed formulation's validation is crucial, the critical process variables (time, pH, and sugar concentration) are optimized for alcohol and silybin content using the Box-Behnken design (BBD). RESULTS: The response surface methodology coupled with BBD predicted the optimized conditions (fermentation time (28 days), pH 5.6, and sugar concentration (22.04%)) for the development of a fermented formulation of the selected herb. Moreover, the alcohol content (6.5 ± 0.9%) and silybin concentration (26.1 ± 2.1%) were confirmed in optimized formulation by GC-MS and HPTLC analysis. The optimized formulation was also analyzed for heavy metals (Pb, As, Hg, and Cd); their concentration is significantly less than the decoction of herbs. Further, the comparative evaluation of the developed formulation with the marketed formulation also confirmed that the fermented formulation's silybin concentration and percentage release were significantly enhanced. In addition, the developed fermented formulation's percentage recovery of HepG2 cell lines after treatment with CCl4 was significantly improved compared with the marketed formulation. CONCLUSION: It can be summarized that the developed fermented formulation improves safety and effectiveness compared to other market formulations. Finally, it can be concluded that the developed fermented formulation could be further explored as a better alternative for developing Silybum marianum preparation.

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR > 60 mL/min/1.73 m2-a cross-sectional study.

BACKGROUND: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m2 (chronic kidney disease (CKD) stage 2). We compared agreement and accuracy of the Pierce U25 (ages 2-25), Pottel (ages 2-100), and CKD-EPI (ages 18-100) formulae to GFR measurements. METHODS: Post hoc analysis of the three eGFRs compared to 367 99m technetium-diethylene-triamine penta-acetic acid (99Tc DTPA) GFR measurements (240 patients) using 3 sampling points and Brockner/Mørtensen correction (body surface area calculation based on ideal weight) on simultaneous serum creatinine and cystatin C measurements. RESULTS: Overall, the U25 formula performed well with a Spearman r of 0.8102 (95% confidence interval 0.7706 to 0.8435, p < 0.0001) while diagnostic accuracy was low in patients with normal mGFR. The U25 formula reclassified 29.5% of patients with normal mGFR as CKD stage 2; whereas the average of the modified Schwartz formula based on serum creatinine and the Filler formula based on cystatin C, only over-diagnosed CKD stage 2 in 8.5%, 24.5% within 10% and 62.7% within 30%. We therefore combined both. The average Schwartz/Filler eGFR had 36.5% of results within 10%, 84.7% within 30%, and normal mGFR accuracy was 26.8%, 63.9% for 10% and 30%, respectively, outperforming the CKD-EPI and Pottel formulae. CONCLUSIONS: The Pierce U25 formula results correlated well with mGFR < 75 mL/min/1.73 m2. Over the entire GFR range, accuracy was better for patients with a higher mGFR, when averaging the combined Schwartz/Filler formulae. More work is needed to prospectively confirm our findings in other centers.

Can gabapentinoids decrease perioperative opioid requirements in orthopaedic trauma patients? A single-centre retrospective analysis.

INTRODUCTION: Perioperative pain control in patients with orthopaedic trauma/extremity fractures has gained a lot of attraction from the scientific community in the last two decades. In addition to multimodal analgesia, the use of non-opioid drugs like gabapentinoids for pain relief is gradually finding its place in several orthopaedic subspecialties like spinal surgery, arthroplasty, and arthroscopic procedures. We envisage investigating the effectiveness of gabapentin in perioperative pain control in patients with extremity fractures undergoing surgical fixation. METHODOLOGY: This was a retrospective comparative study conducted between January 2020 and January 2022. Patients with isolated fractures of the extremity involving long bones who were treated at our trauma centre, during the study period were divided into two groups based on the analgesics they received. Patients who received gabapentin and paracetamol were placed in group GP and those who received only paracetamol were assigned group NGP. Gabapentin was given in a single dose of 300 mg 4 h before surgery. Postoperatively, they were given 300 mg 12 hourly for 2 days. All patients in our trauma centre are usually managed with parenteral paracetamol administration pre and postoperatively. VAS score was calculated postoperatively at 2, 6, 12, 24 and 48 h. Patients requiring additional analgesics for pain relief were administered intravenous tramadol or a buprenorphine patch was applied. Patients in both groups were compared in terms of pain control, the additional requirement of opioid analgesics, and any adverse event related to medications. RESULTS: One hundred and nineteen patients were enrolled in the study. Out of 65 patients in the NGP group (non-gabapentin group), 74% of patients received additional opioid analgesics apart from paracetamol. Out of the 54 patients in the GP group (gabapentin group), only 41% required additional opioid analgesia for pain control. There was a significant difference in opioid consumption between the two groups (p < 0.01). VAS scores were not significantly different between the two groups at 2, 4, 6, 12, 24 and 48 h. Gender and fracture morphology did not affect opioid intake in the GP group. However, in the non-gabapentin group, there was a significant difference in opioid requirement in patients with intraarticular fractures (p < 0.01). CONCLUSION: Analgesic requirements vary from patient to patient depending on the injury's severity and surgery duration. However, there are no strict guidelines for pain relief in limb trauma surgeries which often leads to overuse and opioid-related complications or underuse and chronic pain. Gabapentinoids can supplement the analgesic effect of paracetamol in trauma patients during the perioperative period, decreasing the need for opioids.

Primary congenital glaucoma: An iridotrabeculodysgenesis?

PURPOSE: To analyze primary congenital glaucoma (PCG) anterior chamber and angle anomalies over 360° as possible biomarkers of severity and prognosis. METHODS: A cross-sectional observational study was conducted analyzing anterior segment anomalies of PCG patients over 4 years of age who underwent trabeculectomy combined with trabeculotomy and age-matched controls using anterior segment optical coherence tomography (ASOCT), CASIA-2. Anterior iridotrabecular adhesions or anterior iris insertion was identified and quantified from the scleral spur using the iridotrabecular contact (ITC) index parameter as a surrogate. RESULTS: There was a variable but significantly increased anterior iridotrabecular adhesion on ITC index, ITC area, corneal volume, anterior chamber volume, iris volume, anterior chamber depth, and small/absent trabecular meshwork in PCG eyes compared to control eyes. In PCG eyes, anterior iridotrabecular adhesion had a positive correlation with pre-operative central corneal thickness (CCT) (r = 0.53, P = 0.02), review iris thickness (r = 0.4, P = 0.04), and ITC area (r = 0.85, P < 0.001). Review iris thickness had a negative correlation with pre-operative vertical cup-disc ratio (r = -0.51, P = 0.008). Iris hypoplasia with fewer or absent folds, collarette, pupillary ruff, and pupillary ruff to collarette distance was significantly different from controls. CONCLUSION: ASOCT in PCG eyes has shown that they have variable anterior iridotrabecular tissue adhesions, anomalous tissue/membranes in the angle, and iris hypoplasia correlating with pre-operative cup-disc ratio. These features could be used as gonioscopic and clinical biomarkers to assess the severity and prognosis of the disease. The presence of abnormal iris morphology and iridotrabecular tissue anomalies in PCG suggests that it is more than just isolated trabeculodysgenesis and is probably best considered as part of the anterior segment dysgenesis spectrum.