Current Modalities Research Articles

3D Cinematic rendering for evaluating femoral pseudoaneurysms in injection drug users.

The inguinal region, specifically the femoral vasculature, is a commonly used site of injection for intravenous drug users (IVDU). Repeated puncture of the vessel wall results in breakdown and subsequent arterial pseudoaneurysm- dilatations or outpouching of blood vessels, which, if left untreated, can result in fatal complications such as rupture with hemorrhage, sepsis, or even limb loss. The current modalities for arterial pseudoaneurysms include Doppler ultrasound and computed tomography (CT) angiography, both of which play important roles in management and surgical planning. However, 3D cinematic rendering (CR), a novel CT post-processing technique, offers timely, highly detailed photorealistic images that more clearly display the relation of anatomical structures, allowing for greater diagnostic confidence and precise surgical planning, particularly useful in the emergency setting. In this pictorial review, we demonstrate role of 3D CR in diagnosis and management of femoral pseudoaneurysms in IVDU through 9 illustrative cases.

Substratifying the risk of covert malignancy in significant rectal polyps: Outcomes from a specialist multidisciplinary team (MDT).

A treatment strategy for patients with a significant polyp or early colon cancer (SPECC) of the rectum presents a challenge due to the significant rate of covert malignancy and lack of standardized assessment. For this reason, NICE recommends multidisciplinary meetings to improve outcomes. The primary aim of the present study was to report the performance of our specialist early rectal cancer (SERC) multidisciplinary team (MDT) in correctly substratifying the risk of cancer and to discuss the limitations of staging investigations in those patients with "poor outcomes". This was a retrospective review of patients referred to our SERC MDT from 2014 to 2019. Lesions were assigned by the MDT to three pre-resection categories (low, intermediate, high) according to the risk of covert malignancy. Resection method and final histology were compared to the pre-resection categories. Of 350 SPECC lesions, 174 were assessed as low-risk, 108 intermediate-risk and 68 high-risk. The cancer incidence was 4.8%, 8.3% and 53%, respectively (15.5% overall). Eight lesions were categorized as low-risk but following piecemeal resection were found to be malignant. Five lesions, three of which were categorized as high-risk, were ultimately benign following conventional surgery. One pT1sm1 cancer, removed by anterior resection, may have been treated by local excision. A total of 83% of malignant polyps were triaged to an en bloc resection technique and surgical resection avoided for nearly all benign lesions. However, 12 patients from this cohort were deemed to have a poor outcome because of miscategorization. Further comparative research is needed to establish the optimum strategy for rectal SPECC lesion assessment. There is currently no consensus for staging significant polyps of the rectum. This paper reports the effectiveness of a specialist early rectal cancer MDT to correctly risk-stratify significant rectal polyps. It underscores the importance of accurate categorization for treatment decision-making, while acknowledging the limitations of current staging modalities.

A green and economic approach to synthesize magnetic Lagenaria siceraria biochar (γ-Fe2O3-LSB) for methylene blue removal from aqueous solution.

In the printing and textile industries, methylene blue (a cationic azo dye) is commonly used. MB is a well-known carcinogen, and another major issue is its high content in industrial discharge. There are numerous removal methodologies that have been employed to remove it from industrial discharge; however, these current modalities have one or more limitations. In this research, a novel magnetized biochar (γ-Fe2O3-LSB) was synthesized using Lagenaria siceraria peels which were further magnetized via the co-precipitation method. The synthesized γ-Fe2O3-LSB was characterized using FTIR, X-ray diffraction, Raman, SEM-EDX, BET, and vibrating sample magnetometry (VSM) for the analysis of magnetic properties. γ-Fe2O3-LSB showed a reversible type IV isotherm, which is a primary characteristic of mesoporous materials. γ-Fe2O3-LSB had a specific surface area (SBET = 135.30 m2/g) which is greater than that of LSB (SBET = 11.54 m2/g). γ-Fe2O3-LSB exhibits a saturation magnetization value (Ms) of 3.72emu/g which shows its superparamagnetic nature. The batch adsorption process was performed to analyze the adsorptive removal of MB dye using γ-Fe2O3-LSB. The adsorption efficiency of γ-Fe2O3-LSB for MB was analyzed by varying parameters like the initial concentration of adsorbate (MB), γ-Fe2O3-LSB dose, pH effect, contact time, and temperature. Adsorption isotherm, kinetic, and thermodynamics were also studied after optimizing the protocol. The non-linear Langmuir model fitted the best to explain the adsorption isotherm mechanism and resulting adsorption capacity ( =54.55mg/g). The thermodynamics study showed the spontaneous and endothermic nature, and pseudo-second-order rate kinetics was followed during the adsorption process. Regeneration study showed that γ-Fe2O3-LSB can be used up to four cycles. In laboratory setup, the cost of γ-Fe2O3-LSB synthesis comes out to be 162.75 INR/kg which is low as compared to commercially available adsorbents. The results obtained suggest that magnetic Lagenaria siceraria biochar, which is economical and efficient, can be used as a potential biochar material for industrial applications in the treatment of wastewater.

Abstract 3104: Adenine Base Editing To Correct Pathogenic Variants Causing Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive disorder caused by pathogenic variants in ABCC6 , resulting in systemic depletion of the anti-mineralization compound pyrophosphate. Pyrophosphate depletion drives ectopic calcification of elastic fibers within the skin, retina, and vasculature. Arterial calcification can lead to intermittent claudication of peripheral arteries and coronary artery disease. There are currently no targeted therapies for PXE. Genome editing may be a promising therapeutic option because ABCC6 is predominantly expressed in the liver, a site that is amenable to current genome editing delivery modalities. We sought to assess whether adenine base editing could efficiently correct one of the most frequent ABCC6 variants in PXE patients, c.3490C>T (p.R1164X) in human hepatocytes and a humanized mouse model. We used prime editing to generate a homozygous R1164X human hepatoma cell line. Treatment of R1164X cells with mRNA encoding the adenine base editor ABE8.8 and a synthetic guide RNA (gRNA) resulted in efficient correction of the variant. OligoNucleotide Enrichment and sequencing (ONE-seq) was used to nominate candidate off-target sites, which were evaluated by targeted amplicon sequencing of edited R1164X cells. To mitigate off-target editing, we generated 21 hybrid gRNAs in which various RNA nucleotides in the protospacer were replaced by DNA nucleotides. All hybrid gRNAs maintained on-target editing, and interestingly, several hybrid gRNAs improved on-target editing compared to the standard gRNA. All hybrid gRNAs improved off-target editing, with multiple hybrid gRNAs eliminating off-target editing at multiple off-target sites. To assess in vivo correction of the R1164X variant, we generated a homozygous R1164X humanized mouse model which displays depletion of plasma pyrophosphate. Studies to correct the variant in the humanized mouse model by lipid nanoparticle delivery of the lead candidate hybrid gRNA are underway. Efficient correction of the R1164X variant in the liver by adenine base editing and restoration of pyrophosphate would represent one of the first examples of using genome editing to improve the multisystemic manifestations of a heritable connective tissue disorder.

Regulatory considerations in the design, development and quality of monoclonal antibodies and related products for the diagnosis and treatment of cancer.

Over 160 therapeutic and in vivo diagnostic monoclonal antibodies have been approved by the US FDA since the first monoclonal antibody, muromonab, was approved in 1986. Approximately 42% of these approvals were for the treatment or in vivo diagnosis of oncology indications, although some products are no longer marketed. This review will look at the history of monoclonal antibody development and approvals, discuss current antibody-based modalities, regulatory considerations for engineering approaches, critical quality attributes for different modalities, immunogenicity of mAbs across oncology products, and the future directions for development of therapeutic and diagnostic monoclonal antibody-based products.

Numerical study of hemodynamic flow in the aortic vessel of Williams syndrome patient with congenital heart disease

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

A Machine Learning Model to Predict the Histology of Retroperitoneal Lymph Node Dissection Specimens.

While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) benefits patients with teratoma or viable germ cell tumors (GCT), it becomes overtreatment if necrosis is detected in PC-RPLND specimens. Serum microRNA-371a-3p correctly predicts residual viable GCT with 100% sensitivity; however, prediction of residual teratoma in PC-RPLND specimens using current modalities remains difficult. Therefore, we developed a machine learning model using CT imaging and clinical variables to predict the presence of residual teratoma in PC-RPLND specimens. This study included 58 patients who underwent PC-RPLND between 2005 and 2019 at the University of Tsukuba Hospital. On CT imaging, 155 lymph nodes were identified as regions of interest (ROIs). The ResNet50 algorithm and/or Support Vector Machine (SVM) classification were applied and a nested, 3-fold cross-validation protocol was used to determine classifier accuracy. PC-RPLND specimen analysis revealed 35 patients with necrosis and 23 patients with residual teratoma, while histology of 155 total ROIs showed necrosis in 84 ROIs and teratoma in 71 ROIs. The ResNet50 algorithm, using CT imaging, achieved a diagnostic accuracy of 80.0%, corresponding to a sensitivity of 67.3%, a specificity of 90.5%, and an AUC of 0.84, whereas SVM classification using clinical variables achieved a diagnostic accuracy of 74.8%, corresponding to a sensitivity of 59.0%, a specificity of 88.1%, and an AUC of 0.84. Our machine learning models reliably distinguish between necrosis and residual teratoma in clinical PC-RPLND specimens.

Exploring a repurposed candidate with dual hIDO1/hTDO2 inhibitory potential for anticancer efficacy identified through pharmacophore-based virtual screening and in vitro evaluation

Discovering effective anti-cancer agents poses a formidable challenge given the limited efficacy of current therapeutic modalities against various cancer types due to intrinsic resistance mechanisms. Cancer immunochemotherapy is an alternative strategy for breast cancer treatment and overcoming cancer resistance. Human Indoleamine 2,3-dioxygenase (hIDO1) and human Tryptophan 2,3-dioxygenase 2 (hTDO2) play pivotal roles in tryptophan metabolism, leading to the generation of kynurenine and other bioactive metabolites. This process facilitates the de novo synthesis of Nicotinamide Dinucleotide (NAD), promoting cancer resistance. This study identified a new dual hIDO1/hTDO2 inhibitor using a drug repurposing strategy of FDA-approved drugs. Herein, we delineate the development of a ligand-based pharmacophore model based on a training set of 12 compounds with reported hIDO1/hTDO2 inhibitory activity. We conducted a pharmacophore search followed by high-throughput virtual screening of 2568 FDA-approved drugs against both enzymes, resulting in ten hits, four of them with high potential of dual inhibitory activity. For further in silico and in vitro biological investigation, the anti-hypercholesterolemic drug Pitavastatin deemed the drug of choice in this study. Molecular dynamics (MD) simulations demonstrated that Pitavastatin forms stable complexes with both hIDO1 and hTDO2 receptors, providing a structural basis for its potential therapeutic efficacy. At nanomolar (nM) concentration, it exhibited remarkable in vitro enzyme inhibitory activity against both examined enzymes. Additionally, Pitavastatin demonstrated potent cytotoxic activity against BT-549, MCF-7, and HepG2 cell lines (IC50 = 16.82, 9.52, and 1.84 µM, respectively). Its anticancer activity was primarily due to the induction of G1/S phase arrest as discovered through cell cycle analysis of HepG2 cancer cells. Ultimately, treating HepG2 cancer cells with Pitavastatin affected significant activation of caspase-3 accompanied by down-regulation of cellular apoptotic biomarkers such as IDO, TDO, STAT3, P21, P27, IL-6, and AhR.

NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury

The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia–reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia–reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.Graphical

Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma.

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of immuno-oncology in various hematologic and solid malignancies offers new targets with tremendous therapeutic potential in UC. Historically, there were no predictive biomarkers to guide the clinical management and treatment of UC, and biomarker development was an unmet need. However, recent and ongoing clinical trials have identified several promising tumor biomarkers that have the potential to serve as predictive or prognostic tools in UC. This review provides a comprehensive summary of emerging biomarkers and molecular tumor targets including programmed death ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice.

A Perspective Review: Analyzing Collagen Alterations in Ovarian Cancer by High-Resolution Optical Microscopy.

High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer (OC), occurring in more than 80% of patients diagnosed with this malignancy. Histological and genetic analysis have confirmed the secretory epithelial of the fallopian tube (FT) as a major site of origin of HGSOC. Although there have been significant strides in our understanding of this disease, early stage detection and diagnosis are still rare. Current clinical imaging modalities lack the ability to detect early stage pathogenesis in the fallopian tubes and the ovaries. However, there are several microscopic imaging techniques used to analyze the structural modifications in the extracellular matrix (ECM) protein collagen in ex vivo FT and ovarian tissues that potentially can be modified to fit the clinical setting. In this perspective, we evaluate and compare the myriad of optical tools available to visualize these alterations and the invaluable insights these data provide on HGSOC initiation. We also discuss the clinical implications of these findings and how these data may help novel tools for early diagnosis of HGSOC.

Impact of Body Composition on Esophagogastric Junction Opening Measures: Discordant FLIP and Manometric Findings Are More Common With Increased Body Mass Index.

Increased intra-abdominal pressure in patients with elevated body mass index (BMI) may affect measurements of esophagogastric junction (EGJ) opening. Findings from adult patients who underwent both impedance planimetry with functional luminal imaging probe (FLIP) and high-resolution manometry (HRM) were compared by BMI. Among patients with no EGJ outflow obstruction on HRM, abnormal EGJ classifications on FLIP were more common among those with elevated than normal BMI (61.1% vs 31.6%, P = 0.037). Discordant results between FLIP and HRM on EGJ opening are more common in patients with elevated BMI. Body composition may impact EGJ function and measures on current testing modalities.

IP3R1 dysregulation via mir-200c-3p/SSFA2 axis contributes to taxol resistance in head and neck cancer

Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Although current modalities offer a wide variety of therapy choices, head and neck carcinoma has poor prognosis due to its diagnosis at later stages and development of resistance to current therapeutic tools. In the current study, we aimed at exploring the roles of miR-200c-3p during head and neck carcinogenesis and acquisition of taxol resistance. We analyzed miR-200c-3p levels in HNC clinical samples and cell lines using quantitative real-time polymerase chain reaction and evaluated the effects of differential miR-200c-3p expression on cancer-related cellular phenotypes using in-vitro tools. We identified and characterized a direct target of miR-200c-3p using in-silico tools, luciferase and various in-vitro assays. We investigated potential involvement of miR-200c-3p/SSFA2 axis in taxol resistance in-vitro. We found miR-200c-3p expression as significantly downregulated in both HNC tissues and cells compared to corresponding controls. Ectopic miR-200c-3p expression in HNC cells significantly inhibited cancer-related phenotypes such as viability, clonogenicity, migration, and invasion. We, then, identified SSFA2 as a direct target of miR-200c-3p and demonstrated that overexpression of SSFA2 induced malignant phenotypes in HNC cells. Furthermore, we found reduced miR-200c-3p expression in parallel with overexpression of SSFA2 in taxol resistant HNC cells compared to parental sensitive cells. Both involved in intracellular cytoskeleton remodeling, we found that SSFA2 works collaboratively with IP3R1 to modulate resistance to taxol in HNC cells. When considered collectively, our results showed that miR-200c-3p acts as a tumor suppressor microRNA and targets SSFA2/IP3R1 axis to sensitize HNC cells to taxol.

Immunopathogenesis and Therapeutic Insights into Cicatricial Pemphigoid: A Comprehensive Review

Cicatricial Pemphigoid (CP), also known as mucous membrane pemphigoid, is a rare autoimmune blistering disorder characterized by subepithelial blistering and scarring of mucous membranes. The hallmark of CP is the formation of autoantibodies against structural proteins within the basement membrane zone, leading to an array of clinical manifestations affecting oral, ocular, and other mucosal surfaces. This review aims to elucidate the complex immunopathogenic mechanisms underlying CP, exploring the role of autoantigens such as BP180 and BP230, as well as the involvement of inflammatory mediators and immune cells. Additionally, the article provides a comprehensive overview of current diagnostic modalities and therapeutic approaches, ranging from systemic corticosteroids to novel immunomodulatory agents and biological therapies. The challenges in managing CP, including potential side effects of immunosuppressive treatments, are discussed alongside emerging strategies to enhance treatment efficacy and minimize adverse effects. A deeper understanding of the molecular pathways involved in CP pathogenesis is crucial for the development of targeted therapies, fostering improved patient outcomes and quality of life

Management of Pulmonary Hypertension in the Context of Heart Failure with Preserved Ejection Fraction.

To review the current evidence and modalities for treating pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). In recent years, several therapies have been developed that improve morbidity in HFpEF, though these studies have not specifically studied patients with PF-HFpEF. Multiple trials of therapies specifically targeting the pulmonary vasculature such as phosphodiesterase (PDE) inhibitors, prostacyclin analogs, endothelin receptor antagonists (ERA), and soluble guanylate cyclase stimulators have also been conducted. However, these therapies demonstrated lack of consistency in improving hemodynamics or functional outcomes in PH-HFpEF. There is limited evidence to support the use of pulmonary vasculature-targeting therapies in PH-HFpEF. The mainstay of therapy remains the treatment of the underlying HFpEF condition. There is emerging evidence that newer HF therapies such as sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors are associated with improved hemodynamics and quality of life of patients with PH-HFpEF. There is also a growing realization that more robust phenotyping PH and right ventricular (RV) function may hold promise for therapeutic strategies for patients with PH-HFpEF.

247 Virtual community and partner-engaged panels - We can do them, but should we?

OBJECTIVES/GOALS: We describe the transition of ShAred Resource Panels (ShARPs) within the Center for Community Health (CCH) at Northwestern University’s Clinical and Translational Sciences (NUCATS) Institute to virtual sessions and explore ongoing practices. METHODS/STUDY POPULATION: Restrictions placed during the COVID-19 pandemic led to changes in community-engaged health equity research, such as the transition of community and partner-engaged panels from in-person to virtual. ShARPs have occurred since December 2015. The model includes research team members, community members, community co-facilitator, and CCH staff. These custom panels bring together 8-10 community members familiar with a research topic or community of focus, offering feedback on adaptations that can improve research relevance and feasibility. Until the COVID-19 pandemic, all ShARPs were conducted in person. From March 2020 to January 2023, panels occurred virtually. From 2023, the option of virtual or in-person ShARPs has been available. Count data and informal interview data were reviewed. RESULTS/ANTICIPATED RESULTS: The number of ShARPs peaked in 2019 and has remained stable. The first virtual ShARP occurred on April 22, 2020, and all subsequent sessions have been virtual. As of October 2023, 6 ShARPs have occurred, with no research teams pursuing an in-person session despite its availability. Participants described virtual ShARPs as convenient and accessible. Academic teams cited concern about low community member participation should they opt for an in-person session. DISCUSSION/SIGNIFICANCE: It is feasible to conduct ShARPs virtually and is the current preferred modality. Whether virtual ShARPs enhance, neutralize, or detract from the effectiveness of the session is unknown and guides our future work. More research is needed, including discussion, and learning from our CTSA colleagues.

Multimodality Imaging of Benign and Malignant Diseases of the Nipple-Areolar Complex.

The nipple-areolar complex (NAC), a unique anatomic structure of the breast, encompasses the terminal intramammary ducts and skin appendages. Several benign and malignant diseases can arise within the NAC. As several conditions have overlapping symptoms and imaging findings, understanding the distinctive nipple anatomy, as well as the clinical and imaging features of each NAC disease process, is essential. A multimodality imaging approach is optimal in the presence or absence of clinical symptoms. The authors review the ductal anatomy and anomalies, including congenital abnormalities and nipple retraction. They then discuss the causes of nipple discharge and highlight best practices for the imaging workup of pathologic nipple discharge, a common condition that can pose a diagnostic challenge and may be the presenting symptom of breast cancer. The imaging modalities used to evaluate and differentiate benign conditions (eg, dermatologic conditions, epidermal inclusion cyst, mammary ductal ectasia, periductal mastitis, and nonpuerperal abscess), benign tumors (eg, papilloma, nipple adenoma, and syringomatous tumor of the nipple), and malignant conditions (eg, breast cancer and Paget disease of the breast) are reviewed. Breast MRI is the current preferred imaging modality used to evaluate for NAC involvement by breast cancer and select suitable candidates for nipple-sparing mastectomy. Different biopsy techniques (US -guided biopsy and stereotactic biopsy) for sampling NAC masses and calcifications are described. This multimodality imaging approach ensures an accurate diagnosis, enabling optimal clinical management and patient outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention.

Lymphedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. Despite early hypotheses identifying lymphedema as a disease of mechanical lymphatic disruption alone, the progressive inflammatory nature underlying this condition is now well-established. In this review, we provide an overview of the various inflammatory mechanisms that characterize lymphedema development and progression. These mechanisms contribute to the acute and chronic phases of lymphedema, which manifest clinically as inflammation, fibrosis, and adiposity. Furthermore, we highlight the interplay between current therapeutic modalities and the underlying inflammatory microenvironment, as well as opportunities for future therapeutic development.

Effectiveness of transdermal diclofenac patch versus intramuscular diclofenac injection in management of pain among patients with rib fracture in a tertiary care hospital

Most common injuries in trauma are rib fractures which leads to increase rick of mortality and morbidity. In India alone, there is are about 10 million cases per year for incidence of rib fractures more commonly due to vehicle accidents whereas 6% are of global accidents in India, itself. The current modality of treatment is with NSAID’s for relief of pain in rib fractures. A prospective study of 203 patients with rib fractures found a prevalence of chronic pain 22% and disability of 53%. Thereby, adequate pain management is crucial for improving the recovery and quality of life. The preferred route of administration of analgesics is either oral or intramuscular. This study entails in determining the effectiveness of transdermal Diclofenac patch versus intramuscular administration of Diclofenac.

Pilonidal sinus: an overview of historical and current management modalities.

Pilonidal disease is a common condition that commonly affects the younger adult population and is often seen in both the general practice and the hospital setting. Multiple treatment methods have gained and lost popularity over the last several decades, but more recent intervention principles show promising results. This article details the different methods of managing acute and chronic pilonidal disease ranging from treatments in the primary care setting to those in hospital theatres, with special attention to newer modalities of minimally invasive interventions. As a chronic illness that often affects those of working age, pilonidal disease can confer significant morbidity especially, but not limited to, a substantial amount of time off work. Treatment of chronic disease in particular, has evolved from midline techniques to off-midline techniques, with more recent developments offering promising solutions to reduce acute flare ups and hasten recovery time.