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Chondrosarcoma is the third most common primary malignant bone tumor. The proximal humerus is the most common site. Since it is resistant to chemotherapy and radiotherapy, the mainstay of treatment is surgery. Due to the extensive involvement of long bones, it requires reconstruction with either a prosthetic implant or bone graft. We present a case of a 43-year-old female who presented with chondrosarcoma involving 15 cm of humerus. The patient was managed with the resection of 15 cm of humerus and reconstruction with the same resected bone after autoclaving. It was secured with long fixation resulting in arthrodesis of the glenohumeral joint. The patient was followed for one year and there was evidence of callus formation by ultrasound and computed tomography (CT) scan.
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Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-related challenges during treatment. Various nanotechnology-driven approaches have been adopted to mitigate the issues associated with conventional formulations. Among these, cubosomes have shown potential applications owing to their liquid crystalline structure, which aids in bioadhesion, retention, sustained release, and loading hydrophilic and hydrophobic moieties. The phase transition behavior of glyceryl monooleate, the concentration of stabilizers, and critical packing parameters are crucial parameters that affect the formation of cubosomes. Microfluidics-based approaches constitute a recent advance in technologies for generating stable cubosomes. This review covers the recent topical applications of cubosomes for treating skin (psoriasis, skin cancer, cutaneous candidiasis, acne, and alopecia) and eye (fungal keratitis, glaucoma, conjunctivitis, and uveitis) diseases. The article summarizes the manufacturing and biological challenges (skin and ocular barriers) that must be considered and encountered for successful clinical outcomes. The patented products are successful examples of technological advancements within cosmeceuticals that support various topical applications with cubosomes in the pharmaceutical field.
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Bioactive compounds derived from medicinal plants, such as alkaloids, tannins and flavonoids, possess significant medicinal properties. These compounds have a broad and versatile impact on human nutrition and physiology, contributing to the treatment and management of various diseases. The isolation, structure elucidation and inhibition studies of two novel flavonoids against specific microorganisms, from the leaves of Nyctanthus arbor-tristis are reported in this study. It has been observed for the first time that the presence of an acyl aliphatic moiety, along with the O- glycoside unit at C-7, and the hydroxyl group at C-5, C-4' position in apigenin significantly enhanced antimicrobial activity. Moreover, bioactivity was also investigated through 'Molinspiration' on various parameters followed by the 'rule of five'. This study can be used to highlight the need for the potential development of natural therapeutic products with fewer side effects.
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Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.
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Polietilenoglicóis , Polietilenoglicóis/química , Solubilidade , Carvedilol/química , Estabilidade de Medicamentos , Polímeros/química , Lactonas/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodosRESUMO
INTRODUCTION: Pneumorrachis is presence of air in the epidural space. It could be the result of trauma, barotrauma, iatrogenic or spontaneous. The pneumorrachis per se is an underdiagnosed entity as most of the patients are asymptomatic or have subclinical symptoms. The spontaneous occurrence of pneumorrachis has been reported in literature but giant spontaneous occurrence causing cauda equina syndrome has not been reported so far. CASE PRESENTATION: We report a case of 56-year-old male patient who came to our OPD on wheelchair with complains of difficulty in walking for 6 months with dribbling of urine for 2 months with on and off back pain. His perianal sensation was reduced with absent voluntary anal contraction. Imaging revealed giant air pockets in the spinal canal of L5-S1 extending upto L4-L5. It was managed surgically wherein laminectomy without fusion was done. The patient responded well to the treatment. DISCUSSION: There are many causes of pneumorrachis described in literature. Most of the cases of pneumorrachis are asymptomatic and incidentally diagnosed. With the improvement in radio-diagnostic modalities, the diagnosis of pneumorrachis can be easily established. When symptomatic, they can be managed conservatively. Those presenting with neurological deficit may require surgical intervention or other invasive intervention.
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Síndrome da Cauda Equina , Masculino , Humanos , Pessoa de Meia-Idade , Síndrome da Cauda Equina/diagnóstico por imagem , Síndrome da Cauda Equina/etiologia , Laminectomia , Canal MedularRESUMO
INTRODUCTION: Spinal tuberculosis (TB) is the most common form of skeletal tuberculosis. Paradiscal continuous vertebral involvement at a single level is the most prevalent pattern among all forms of spinal TB. There is a wide range of reported incidences of multiple-level non-contiguous spinal TB in the literature. We would like to discuss on the utility of single whole spine screening T2-weighted (T2W) mid-sagittal magnetic resonance imaging (MRI) film in diagnosing multiple-level spinal TB and therapeutic benefits it can provide. METHODS: We have done a retrospective review of the collected data of patients in Vardhman Mahavir Medical College and Safdarjung Hospital from August 2017 to October 2021 to find the incidence of multiple-level spinal TB and possible factors attributed to this specific disease pattern. All the patients who had been diagnosed of spinal TB either microbiologically or histopathologically or by a good clinical response to anti-tubercular treatment (ATT) and had a whole spine screening MRI film, were included. Patients of spinal TB who did not have a whole spine screening MRI were excluded from the study. Multiple-level spinal TB was diagnosed when lesions were identified in vertebral levels other than a typical paradiscal lesion, and additional lesions were separated from the primary disease by at least one normal spinal segment. RESULTS: Among the patients, 242 met the inclusion criteria, and 76 showed multiple-level non-contiguous spinal TB on MRI, incidence being 31.4%. The rest of the 166 patients showed typical single-segment contiguous lesions. By doing multivariate analysis to determine the independent risk factors for multiple-level spinal TB, extremes of age (<20 years and >50 years) have been found to be a significant factor with p value of 0.0001. Though drug resistance was not found to be a significant risk factor (p value 0.051), the proportion of patients having multiple-level TB was far more in the drug-resistant group (13/76). CONCLUSIONS: Single sequence whole spine screening MRI film is an effective, economical, and time-saving tool to detect multiple-level spinal TB. Along with its diagnostic accuracy, it also provides therapeutic benefits like access to a more approachable site for biopsy.
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Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and extensively characterized. The in-vitro studies were performed using A-549 lung epithelial cancer cells. The in-vivo pharmaco-kinetic studies was performed on wistar rats. The aqueous solubility of venetoclax was increased upto 3.16 folds, as compared with pure venetoclax with entrapment efficiency (EE%) was determined 95.44 ± 0.3%. In-vitro cytotoxicity studies were carried on A-549 lung epithelial cancer cells, wherein BCL-2 receptors were highly over-expressed and IC 50 values for venetoclax and venetoclax- HP-ß-CD complex was calculated at 24 and 48 hrs in the order of 1.241 µg/ml, 0.68 µg/ml and 0.757719 µg/ml, 0.6125 µg/mL, respectively. The oral bioavailability was increased 4.03 times compared to the pure drug. The venetoclax-HP-ß-CD inclusion complexes showed the increased aqueous solubility with improved anticancer activities.Communicated by Ramaswamy H. Sarma.
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Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested â¼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs.
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Cardiotoxicidade , Humanos , Celecoxib/farmacologia , Administração Oral , Solubilidade , Liberação Controlada de Fármacos , EmulsõesRESUMO
Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid-polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core-shell nanoparticles, hollow core-shell nanoparticles, biomimetic lipid-polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core-shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core-shell-structured LPHNPs.
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A drug's aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70-90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques.
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OBJECTIVE: To quantify the reduction in wound size and change in wound quality following low-cost topical oxygen therapy (TOT) in patients with acute traumatic musculoskeletal wounds of the foot and ankle. METHOD: This prospective interventional study included patients with acute traumatic musculoskeletal wounds of the foot and ankle of <3 weeks' duration after they had undergone debridement and required subsequent wound coverage. A sterile C-Arm cover was used to cover the wound and 100% oxygen was administered at 1 atm, at a rate of 10l/min for 90 minutes on each of four consecutive days, through a suction catheter connected to an oxygen cylinder. The cycle was repeated after a three-day break. Wound surface area (by plotting on graph paper) and wound quality (by modified wound infection checklist score and swabs for culture and Gram staining) were assessed before and after TOT application. RESULTS: The study cohort included 20 patients ≥18 years of age. There was a statistically significant (p<0.001) reduction in mean wound surface area from 79.3cm2 at baseline to 69.6cm2 after two cycles of TOT. The mean modified wound infection checklist score was 13.6 and 0.8, respectively, before and after two cycles of TOT, suggesting statistically significant improvement (p=0.02) in wound quality. All patients showed no growth in their wound culture after TOT. CONCLUSION: TOT appears to be a promising and cost-effective alternative in the management of traumatic wounds. However, future studies with larger sample sizes and control groups for comparison are needed to establish the benefit of TOT in acute traumatic musculoskeletal wounds.
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Pé Diabético , Infecção dos Ferimentos , Humanos , Cicatrização , Pé Diabético/terapia , Tornozelo , Estudos Prospectivos , OxigênioRESUMO
STUDY DESIGN: A retrospective case-control study. OBJECTIVE: Only a few studies have studied the incidence of new-onset SI joint pain following lumbar spine fusion surgery. We aimed to explore the association between new-onset SI joint pain following Transforaminal Lumbar Interbody Fusion (TLIF) for degenerative spine disorders and changes in spinopelvic parameters. METHODS: A retrospective review of hospital records and imaging database of a tertiary care institute was done for patients who underwent TLIF from October 2018 to October 2019. The 354 patients who satisfied the eligibility criteria were divided into 2 groups(Group A, new-onset SI joint pain group, n = 34 and Group B, normal controls, n = 320). Symptomatic relief (>70% reduction in the VAS [Visual Analogue Scale] score) after 15 minutes of SI joint injection was considered diagnostic of SI joint pain. Clinical and radiological spinopelvic parameters were compared between the 2 groups. RESULTS: Patients with postoperative SI joint pain (Group A) had significantly less preoperative and postoperative lumbar lordosis (p < 0.001) compared to the other group. Most of the patients in Group A had a cephalad migration of the apex postoperatively (30/34 patients) whereas majority of patients in group B had either predominant caudal migration (44/320 patients) or no migration of the lumbar apex (272/320 patients). CONCLUSIONS: The preoperative and postoperative lumbar lordosis are significantly less and the postoperative pelvic tilt is significantly high in patients with new-onset SI joint pain compared to the control group. The cephalad migration of the lumbar apex is significantly associated with new-onset SI joint pain.
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BACKGROUND: Compensatory changes in cervical sagittal alignment after C1-C2 arthrodesis have been reported in a few studies. No studies have explored the differences in these compensatory changes between traumatic and non-traumatic pathologies. Conflicting reports exist on the correlation between cervical sagittal parameters and neck pain or function. METHODOLOGY: Medical records of 81 consecutive patients [Jan 2010-Dec 2018] who underwent Harms arthrodesis were retrospectively reviewed. 53 patients were included in the final analysis. Radiological parameters [C0-C1, C1-C2, C2-C7 angles and T1 slope] and clinical parameters [VAS (Visual analogue scale) and NDI (Neck disability index)] were compared between the two groups, Group A (traumatic) and Group B (non-traumatic). RESULTS: The 53 patients [Group A (n = 24,) and Group B (n = 29)] had a mean age of 49.98 ± 21.82 years (42 males, 11 females). Mean follow up duration was 48.9 months. Δ C1-C2 angle is significantly correlated with ΔC2-C7 angle (Group A, p = 0.004; Group B, p = 0.015) but not with ΔC0-C1 angle (Group A, p = 0.315; Group B, p = 0.938). Though significant improvement in the clinical parameters (VAS/NDI) has been noted in both groups, Group A showed a greater improvement in VAS scores [Group A, (p < 0.001); Group B, (p < 0.023)]. CONCLUSIONS: The sub-axial sagittal profile was strongly correlated with the ΔC1-C2 angle in both groups. Group B showed greater changes in sagittal parameters after Harms fixation and Group A showed greater improvement in long-term functional outcomes. The final functional outcomes were not related to the initial or final radiological sagittal profile in both groups.
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Artrodese , Vértebras Cervicais , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , PescoçoRESUMO
Spinal adhesive arachnoiditis is a rare occurrence with a diverse etiology. The clinical picture is not universal, and varying degrees of neurodeficit have been mentioned. Spontaneous spinal cord herniation or idiopathic spinal cord herniation occurs due to displacement of the cord through a dural or arachnoid defect. We report a case of a 29-year-old male paraplegic patient with a nontraumatic spinal cord injury (SCI) following surgery for an intradural extramedullary lesion at T10-T11 level who developed loss of truncal balance after two years of the index surgery. After a thorough clinical examination and MRI as well as other investigations, the patient was diagnosed as having spontaneous-onset delayed spinal arachnoiditis with dorsal cord herniation through the laminectomy window with effacement of neural tissue and ascending edema up to T6 level. A new-onset weakness or the development of an ascending loss of sensory level with a loss of truncal balance should alarm the therapist about some new pathology happening at the cord level in patients with SCI. In this regard, spinal adhesive arachnoiditis with or without cord herniation should always be suspected in a paraplegic patient with delayed-onset deterioration of neurology. Differential diagnoses like arachnoid web and arachnoid cysts should also be kept in mind.
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Functionalization of polymers is an attractive approach to introduce specific molecular forces that can enhance drug-polymer interaction to achieve higher drug loading when used as drug delivery systems. The novel amphiphilic block copolymer of methoxy poly(ethylene glycol) and poly(jasmine lactone) i.e., mPEG-b-PJL, derived from renewable jasmine lactone provides free allyl groups on the backbone thus, allowing flexible and facile post-synthesis functionalization. In this study, mPEG-b-PJL and its carboxyl functionalized polymer mPEG-b-PJL-COOH were utilised to explore the effect of ionic interactions on the drug-polymer behaviour. Various drugs with different pK a values were employed to prepare drug-loaded polymeric micelles (PMs) of mPEG-b-PJL, mPEG-b-PJL-COOH and Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) via a nanoprecipitation method. Electrostatic interactions between the COOH pendant on mPEG-b-PJL-COOH and the basic drugs were shown to influence the entrapment efficiency. Additionally, molecular dynamics (MD) simulations were employed to understand the polymer-drug interactions at the molecular level and how polymer functionalization influenced these interactions. The release kinetics of the anti-cancer drug sunitinib from mPEG-b-PJL and mPEG-b-PJL-COOH was assessed, and it demonstrated a sustainable drug release pattern, which depended on both pH and temperature. Furthermore, the cytotoxicity of sunitinib-loaded micelles on cancer cells was evaluated. The drug-loaded micelles exhibited dose-dependent toxicity. Also, haemolysis capacity of these polymers was investigated. In summary, polymer functionalization seems a promising approach to overcome challenges that hinder the application of polymer-based drug delivery systems such as low drug loading degree.
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STUDY DESIGN: Cross-sectional study. PURPOSE: This study aimed to understand the sagittal spinopelvic parameters, segmental lumbar parameters, and lumbar apex location in asymptomatic adults and analyze their correlations with each other. OVERVIEW OF LITERATURE: Roussouly and his colleagues reported that pelvic incidence (PI) influences the lower arc of lumbar lordosis, whereas Pesenti and his colleagues reported that PI influences only the proximal part of lordosis and not the distal part. Both studies have their shortcomings. METHODS: One hundred asymptomatic adult volunteers (mean age, 29.1±7.9 years; 69 males, 31 females) who satisfied the selection criteria were enrolled in this study. Standing antero-posterior and lateral whole spine and pelvis X-rays were performed, and the radiographic parameters were analyzed. We introduced a "segmentation line" bisecting the apical vertebra/disk to divide the upper arc of lumbar lordosis (ULL) and lower arc of lumbar lordosis (LLL). RESULTS: The mean PI was 48.02°, ULL 29.12°, LLL 16.02°, total lumbar lordosis (TLL) 45.14°, lumbar tilt angle 4.73°, and location of the apex of lumbar lordosis (LLA) 4.11°. The location of the lumbar apex moved higher as the PI increased. The PI was strongly positively correlated with the LLL (r =0.582, p <0.001) and TLL (r =0.579, p <0.001) but not with the ULL (r =0.196, p =0.05). The LLA was strongly positively correlated with the ULL (r =0.349, p <0.001), negatively with the LLL (r =-0.63, p <0.001), and not correlated with the TLL (r =-0.177, p =0.078). CONCLUSIONS: The PI influences the location of the lumbar apex, the LLL, and the TLL but not the ULL. The location of the lumbar apex significantly influences the segmental lordosis but not the TLL.
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McCune-Albright syndrome (MAS) is a complex endocrinopathy with polyostotic fibrous dysplasia and café-au-lait spots. Pathological femoral shaft fracture along with MAS is not a common occurrence. Bisphosphonates can be used for the management of pathological fractures. A seven-year-old male child presented with pathological femoral shaft fracture with MAS (café-au-lait macules and hyperthyroidism). The patient was managed conservatively with closed reduction along with hip spica and oral alendronate. Fracture consolidation occurred within six to eight weeks with improvement in bone pains. Oral alendronate can be used as an adjuvant to conservative therapy for pathological fracture in MAS in children.
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Introduction To analyze the change in Visual Analog Scale (VAS), QuickDASH score, and the range of motion at the shoulder joint following a single injection of platelet-rich plasma (PRP) in shoulder impingement syndrome. Methods Twenty patients (21 shoulders) of either sex above the age of 18 years with a clinical diagnosis of shoulder impingement having a positive shoulder impingement test (positive Hawkins-Kennedy impingement test and/or positive Neer's impingement sign), ultrasonographic confirmation of shoulder impingement, and a failure to respond to standard non-operative methods for a minimum period of four weeks were included in this prospective interventional study. PRP was injected at the proposed site. At three months after the injection, the changes in the VAS, QuickDASH score, and the range of motion at the shoulder joint were analyzed. Results There were significant changes in the VAS, QuickDASH score, and range of motion at the shoulder joint following a single injection of PRP. Conclusions Platelet-rich plasma (PRP) injection results in a significant decrease in pain and improvement in the range of motion and an overall excellent functional outcome in shoulder impingement syndrome. However, future studies with a bigger sample size and longer follow-up are needed.