Surgical Management of Irreparable Rotator Cuff Tears: A Survey of Current Practice and Literature Review.

Introduction Irreparable rotator cuff tears (RCTs) are a complex challenge encountered by shoulder surgeons. Despite a range of repair strategies, the preferences and indications of these remain unclear. Our study aims to identify current practices, preference for graft choice and indications for capsular reconstruction amongst UK-based surgeons. Methods An online survey was sent to members of the British Elbow and Shoulder Society (BESS). Procedural preferences, operative frequency, indications/contra-indications for superior capsular reconstruction (SCR) and graft choice were ascertained. An independent t-test was used to determine statistical significance. Results One hundred and ten upper limb surgeons responded to the survey. Of this cohort, 90/110 (81.8%) would be able to perform a partial cuff repair, 89/110 (80.9%) could offer a reverse shoulder arthroplasty (RSA) and 82/110 (74.6%) could perform debridement only. Less commonly, 35/110 (31.8%) could offer an InspaceTM balloon device, 31/110 (28.2%) SCR and 16/110 (14.6%) a tendon transfer. None of the respondents had performed more than 10 InspaceTM balloons in the previous year. 72/105 (68.6%) had never performed a SCR and 86/105 (82%) had never performed a tendon transfer. Over 58/105 (55.2%) had performed >10 RSA in the previous year. The graft of choice for SCR was human dermal allograft 33/100 (33%) and this choice was most frequently guided by surgeon preference. Conclusion Our study demonstrates that various treatment options can be offered for the management of irreparable RCTs. The commonest procedure offered is a partial cuff repair followed by RSA. Newer, novel procedures such as InspaceTM balloon and tendon transfers are less commonly offered in UK-based practices and their indications for use are less well defined. Future high-powered, multi-centre studies are required to identify the role and outcomes of these procedures.

Management of type III acromioclavicular joint dislocation: A Delphi consensus survey by Shoulder & Elbow Society, India (SESI).

PURPOSE: The study aimed to report the results of the Delphi survey conducted by the Shoulder, Elbow Society India (SESI), to achieve consensus on ambiguous topics in managing type III acromioclavicular joint (ACJ) dislocations. METHODS: This study was based on responses from the Shoulder Elbow Society India (SESI) panel of peer-selected twenty senior surgeons practicing shoulder orthopedics. They participated in two rounds of the survey to obtain consensus on several topics pertaining to the management of type III ACJ dislocations. Consensus was achieved when at least 70 % of the panel members selected at least a 4-point on a 5-point Likert scale. RESULTS: Our Delphi survey reached a consensus on seven topics of ambiguity. An anteroposterior and axillary view of the shoulder without any traction or weight in hand is sufficient in the setting of a suspected type III ACJ dislocation. Magnetic resonance imaging (MRI) is not routinely indicated in type III ACJ dislocation. Either cross-arm adduction X-rays or clinical examination may be used to distinguish between ISAKOS (International Society of Arthroscopy, Knee surgery and Orthopaedics Sports medicine) IIIA and B classification of ACJ to identify stable and unstable injuries. Conservative treatment can be offered to patients who have stable injuries and who are not high-demand individuals in acute type III ACJ dislocations. In conservative management of type III ACJ dislocation, a two-week sling suffices. Jones strapping has no clear advantage over a shoulder sling. Coracoclavicular reconstruction with an autograft is an acceptable way to treat symptomatic, chronic grade III ACJ dislocation. CONCLUSION: The survey helped achieve consensus on several controversial issues related to type III ACJ dislocations. However, there remains ambiguity on the definition of chronicity of such dislocations, the necessity of bilateral Zanca views, and the duration of conservative trial before switching to a surgical line of management.

Artificial Intelligence for the Management of Breast Cancer: An Overview.

Breast cancer is a severe global health problem, and early detection, accurate diagnosis, and personalized treatment is the key to improving patient outcomes. Artificial intelligence (AI) and machine learning (ML) have emerged as promising breast cancer research and clinical practice tools in recent years. Various projects are underway in early detection, diagnosis, prognosis, drug discovery, advanced image analysis, precision medicine, predictive modeling, and personalized treatment planning using artificial intelligence and machine learning. These projects use different algorithms, including convolutional neural networks (CNNs), support vector machines (SVMs), decision trees, and deep learning methods, to analyze and improve different types of data, such as clinical, genomic, and imaging data for breast cancer management. The success of these projects has the potential to transform breast cancer care, and continued research and development in this area is likely to lead to more accurate and personalized breast cancer diagnosis, treatment, and outcomes.

Surgical Correction of Post-traumatic Residual Deformity of the Mandible: A Case Report.

Mandibular fractures are the most common trauma cases that we often come across in our day-to-day practice of oral and maxillofacial surgery. Various factors can lead to deformities and make those cases more challenging, which includes a delay in surgical treatment, resulting in non-union or malunion of the fracture site causing occlusal disturbances and functional abnormalities in the temporomandibular joint.

Atrial Myxoma: An Unusual Etiology of Ischemic Stroke in an Adult Patient.

Atrial myxoma is the most frequent primary cardiac tumor; however, it is a rare, substantial cause of cardiogenic emboli causing a stroke, especially in young adults. A cardiac myxoma has no specific clinical presentation, ranging from constitutional symptoms to non-cardiac symptoms and emboli, which leads to a diagnostic challenge in the clinical process. We report a case of a left atrial myxoma in an adult female who presented with sudden onset of right-sided weakness, headache, and numbness. Imaging confirmed cardiogenic emboli from the cardiac myxoma, which was reflected in an ischemic stroke.

Restoration of the joint geometry after stemless shoulder arthroplasty.

Aim: This study aims to evaluate restoration of anatomy following Total Shoulder Arthroplasty (TSA) with the Mathys Affinis Short prosthesis. Background: Over the last decade stemless shoulder arthroplasty has increased in popularity. One of the reported advantages of the stemless designs is the ability to restore anatomy following surgery. However, very few studies have evaluated restoration of anatomy following stemless shoulder arthroplasty. Methods: The study included all patients who had undergone TSA using the Affinis Short (Mathys Ltd, Bettlach, Switzerland) prosthesis for primary osteoarthritis between 2010 and 2016. The mean follow up was 42.8 months (range 9.4 to 83.4 months). Pre and post-operative radiographs were assessed for Centre of Rotation (COR), Humeral Head Height (HHH), Humeral Head Diameter (HHD), Humeral Height (HH) and, Neck Shaft Angle (NSA) using the best fit circle method on PACS software. Measurements were scored and compared to assess the accuracy of the implant in restoring the native geometry, including the intraobserver variability. The same data was collected by another experienced observer to measure the interobserver variability. Results: The deviation of COR of the prosthesis from the anatomical centre was less than 3 mm in 58 cases (85%). Humeral head height and humeral head diameter showed a variation of less than 3 mm in 66 cases (97%) and 43 cases (63%) respectively. Humeral height followed a similar trend, with 62 cases (91.2%) showing a difference of less than 5 mm. The neck shaft angle showed a variation of more than 8 degrees in 38 cases (55%), and 29 cases (42.6%) had a postoperative angle of less than 130 degrees. Conclusion: Overall, stemless total shoulder arthroplasty with the Affinis Short prosthesis allows excellent restoration of anatomy confirmed by most of the measured radiographic parameters. The variability in neck shaft angle might be due to differing surgical techniques, with some surgeons preferring a slightly vertical neck cut to protect the rotator cuff insertion.

Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect.

Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36-3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Factors Affecting Quality of Life of Cancer Patients in North India.

INTRODUCTION: Cancer is the second leading reason of death in many countries, and its burden and prognosis are highly dependent on disease stage at diagnosis. Lack of perception of the population about cancer and its related risk factors usually sequel in defer/delayed presentation and increased treatment morbidity and decrease survival chances. Quality of life (QOL) is defined as Individual view of life, merits, intentions, standards and interests in the framework of culture. AIMS AND OBJECTIVES: To study the socio-demographic profile and factors affecting quality of life of cancer patients. MATERIAL AND METHOD: Using a cross-sectional study, between 1 January 2021 to 31 December 2021, 192 cancer confirmed patients at cancer registry centre at District civil hospital, Ambala cantt. were interviewed using a pre tested semi-structured questionnaire along with EORTC QLQ-C30 (version 3) questionnaire scale for QOL. The data was entered into an excel sheet and was analysed using IBM SPSS version 28. RESULTS: Out of 192 patients, 95 were male and 97 were female. Results shows that female (60.05±19.167) had better mean score of QL2 than male (58.68±18.906) with P value=0.619. Overweight (BMI25.0-29.9) had better mean QL2 score (65.50±18.147) than obese (BMI>30.0) mean QL2 score (61.67±14.803), normal weight (BMI 18.0-24.9) mean QL2 score (59.57±18.575) and underweight (BMI<18.0) mean QL2 score (49.46±19.595) with P value of 0.004. CONCLUSION: Present study found that QOL had significant association with BMI, type of cancer, history of smoking, lost income after cancer diagnosis and stage of cancer at the time of diagnosis. While gender, occupation, age group, religion, residence, marital status, type of family, income, tobacco alcohol and physical activity showed no significance association with QOL.

In-Silico Prediction of Novel Fused Quinazoline Based Topoisomerase Inhibitors as Anticancer Agents.

BACKGROUND: The prospective uses of tryptanthrin and its analogues in cancer chemotherapy are well known, and they are also predicated on their capacity to reverse drug resistance in cancer therapy. OBJECTIVE: The current project entails developing a novel hybrid analogue that includes modifying the tryptanthrin molecule at the C-6 carbonyl position and is expected to exhibit substantial anticancer action. METHODS: In the ATPase domain of human topoisomerase II, a series of 162 substituted Schiff base analogues of tryptanthrin were developed, and molecular docking experiments were done using Gold 5.1 software interfaced with Hermes 1.6.2. (PDB ID: 1ZXM). RESULTS: Most of the compounds were found to have Goldscore above 100 and formed interactions with the residues like ASN91, ALA92, ASN95, ARG98, ASN120, ILE125, ILE141, PHE142, SER149, THR215, and ILE217. Compound RK-149 had highest Goldscore of 132.59, forming an interaction with ASN91 but had a lesser Goldscore as compared to the standard drug etoposide and had a better score than tryptanthrin. CONCLUSION: The nitrogen in the imine bond of the proposed compounds is responsible for significant interactions, demonstrating their anticancer potential.

Evaluation of oxindole derivatives as a potential anticancer agent against breast carcinoma cells: In vitro, in silico, and molecular docking study.

In this study we have performed the in vitro anticancer activity of spiro oxindole derivatives against MCF-7 (human Adreno carcinoma) and MDA-MB-231 (triple negative breast cancer) cell lines to propose a possible role of these derivatives in the treatment of cancer. Compound 6, which has an N-benzyl substitution with a chloro group on the indolin-2-one scaffold, had the most potent activity against MCF-7 (3.55 ± 0.49 µM) and MDA-MB-231 (4.40 ± 0.468 µM) of all the synthesized molecules. A normal mouse embryonic fibroblast (NIH/3 T3) cell line was used to test the cellular toxicity of these derivatives. The results showed that none of the compounds were cytotoxic to normal cells. In addition, pharmacokinetic (ADME) and toxicity study profiles were predicted in silico. All the synthesized derivatives (1 to 7) demonstrated the necessary physicochemical properties for bioavailability. Finally, in vitro results of promising compound 6 were validated using molecular docking and dynamic simulation studies, which revealed their binding affinities and conformational stability in the binding cavity. Thus, these derivatives may serve as lead structures for a new generation of anticancer agents.

Synthetic and Medicinal Perspective of 1,2,4-Triazole as Anticancer Agents.

Cancer is still one of the leading causes of death worldwide. Many researchers are working to design and develop heterocyclic-based drugs with the potential to treat cancer at various stages. There is always an unmet need to discover new anticancer drugs to treat different types of cancer. Based on literature reports, it was evident that hybrid 1,2,4-triazoles exhibit a wide spectrum of biological potential (particularly potent anticancer activity), as compared to the corresponding monocyclic compounds. In this review, we summarized fused/hybrid 1,2,4-triazole and poly-functionalized 1,2,4-triazoles as anticancer agents. Triazole may be fused with other heterocyclic scaffolds like pyrimidine, pyridine, piperidine, quinoxaline, quinazoline, thiadiazine, indole, phthalazine etc. A clear explanation of the method of synthesis, structure-activity relationship, and in vitro results plus the inhibitory concentration of new molecules are focused on in this review article.

Acute myeloid leukemia presenting as unilateral central retinal vein occlusion.

Ocular manifestations of leukemia are often bilateral and involve all ocular structures with non-specific features like retinal hemorrhages, cotton wool spots and choroidal infiltrates. We report a rare, atypical initial presentation of acute myeloid leukemia with unilateral central retinal vein occlusion in a middle-aged male. This case will raise awareness among ophthalmologists to recognize and diagnose underlying systemic disease early and decrease systemic morbidity in consultation with a hematologist.

Synthesis and Clinical Development of Palbociclib: An Overview.

Breast cancer is the second most commonly identified cancer in women in the United States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness campaigns and active research in fields of diagnosis and targeted therapy. These factors have led to a better mechanistic understanding of the disease, detection at earlier stages, and a more personalized approach to treatment, ultimately causing a crucial increase in the survival rates after detection. However, with the advances in treatment, cases of patients developing primary resistance and acquired resistance are increasing. Most of the breast cancers which develop resistance to therapy are ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one-third of women treated with these drugs develop resistance to them, lowering their chances of survival. This has directed the search for newer drug therapies to target advanced breast cancer and resistance. One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from the FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer. This review is focused on the various aspects of "Palbociclib" including its synthesis, molecular modeling studies, and efficacy and safety profile with data obtained from various clinical trials.

Microtubule associated proteins as targets for anticancer drug development.

The dynamic equilibrium of tubulin-microtubule is an essential aspect of cell survivality. Modulation of this dynamics has become an important target for the cancer drug development. Tubulin exists in the alpha-beta dimer form which polymerizes to form microtubule and further depolymerizes back to tubulin dimer. The microtubule plays an essential role in mitosis and cell multiplication. Antitubulin drugs disturb the microtubule dynamics which is essentially required for DNA segregation and cell division during mitosis so killing the cancerous cells. Microtubule Associated Proteins (MAPs) interact with cellular cytoskeletal microtubules. MAPs bind to the either polymerized or depolymerized tubulin dimers within the cell and mostly causing stabilization of microtubules. Some of the tubulin binding drugs are in clinical use and others in clinical trial. MAPs inhibitors are also in clinical trial. Post-translational modification of lysine-40 either in histone or in alpha tubulin has an important role in gene expression and is balanced between histone deacetylases (HDACs) and histone acetyltransferases (HATs). HDAC inhibitors have the anticancer properties to form a drug for the treatment of cancer. They act by inducing cell cycle arrest and cell death. Some of the HDAC inhibitors are approved to be used as anticancer drug while others are under different phases of clinical trial. The present review updates on various MAPs, their role in cancer progression, MAPs inhibitors and their future prospects.

Midterm clinical and radiologic survivorship of a stemless total shoulder arthroplasty.

AIM: The aim of this study was to evaluate the clinical and radiologic outcomes of stemless total shoulder arthroplasty (TSA) in patients with glenohumeral arthritis. PATIENTS AND METHODS: This is a retrospective case series of all patients who underwent a TSA with Affinis Short prosthesis during the period 2010-2017. Seventy-two TSAs were performed within our unit, in 62 patients (45 females and 17 males), with 10 patients having bilateral TSAs with this prosthesis. The mean follow-up was 3.9 years (2-8.7 years). Patients were evaluated clinically with the Oxford Shoulder Score, range of movement assessment, and a numerical patient satisfaction score. Follow-up radiographs were evaluated by 2 reviewers assessing for lucency and assigned a Lazarus grade. RESULTS: Six patients were lost to follow-up prior to their 2-year review. At last follow-up, the mean forward elevation was 157° (80°-180°), abduction was 150° (60°-180°), and external rotation was 39° (20°-60°). The mode internal rotation was to the lumbar spine, with 95% of patients achieving internal rotation to L5 or higher. The mean Oxford Shoulder Score was 45 (18-48). The mean patient satisfaction score was 4.93/5. No humeral lucencies were observed. Sixty-four percent (n=47) of the glenoids were Lazarus grade 0, showing no evidence of radiolucency. The remaining patients were Lazarus grade 1-3, although none were progressive and all patients were asymptomatic. No patients were revised for aseptic loosening. Four patients underwent revision: 1 for infection, 1 for heterotrophic ossification and stiffness, and 2 for rotator cuff failure. CONCLUSION: Midterm follow-up results indicate good clinical and radiologic survivorship for this stemless TSA. Our findings suggest good patient function and satisfaction, and no patients have required revision for aseptic loosening. Further follow-up is required to determine long-term survivorship.

Synthetic and medicinal perspective of quinolines as antiviral agents.

In current scenario, various heterocycles have come up exhibiting crucial role in various medicinal agents which are valuable for mankind. Out of diverse range of heterocycle, quinoline scaffold have been proved to play an important role in broad range of biological activities. Several drug molecules bearing a quinoline molecule with useful anticancer, antibacterial activities etc have been marketed such as chloroquine, saquinavir etc. Owing to their broad spectrum biological role, various synthetic strategies such as Skraup reaction, Combes reaction etc. has been developed by the researchers all over the world. But still the synthetic methods are associated with various limitations as formation of side products, use of expensive metal catalysts. Thus, several efforts to develop an efficient and cost effective synthetic protocol are still carried out till date. Moreover, quinoline scaffold displays remarkable antiviral activity. Therefore, in this review we have made an attempt to describe recent synthetic protocols developed by various research groups along with giving a complete explanation about the role of quinoline derivatives as antiviral agent. Quinoline derivatives were found potent against various strains of viruses like zika virus, enterovirus, herpes virus, human immunodeficiency virus, ebola virus, hepatitis C virus, SARS virus and MERS virus etc.

Synthetic and Medicinal Perspective of Fused-Thiazoles as Anticancer Agents.

BACKGROUND: Cancer is second leading disease after cardiovascular disease. Presently, Chemotherapy, Radiotherapy and use of chemicals are some treatments available these days. Thiazole and its hybrid compounds extensively used scaffolds in drug designing and development of novel anticancer agents due to their wide pharmacological profiles. Fused thiazole scaffold containing drugs are available in market as a promising group of anticancer agents. METHODS: The detailed study has been done using different database that focused on potent thiazole hybrid compounds with anticancer activity. The literature included in this review is focused on novel fused thiazole derivatives exhibiting anticancer potency in last decade. RESULTS: Literature suggested that thiazoles and its fused and linked congener serve excellent pharmacological profile as an anticancer agent. Various synthetic strategies for fused thiazole are also summarized in this article. Novel thiazole and its fused congener showed anticancer activity against various cancer cell lines. INTERPRETATION: Thiazole is a promising scaffold reported in literature with broad range of biological activities. This article covers the thiazole compounds fused with other carbocyclic/heterocycle including benzene, imidazole, pyridine, pyrimidine, quinoline, phenothiazine, thiopyrano, steroids, pyrrole etc. with anticancer activity from last decades. Several inhibitors for breast cancer, colon cancer, melanoma cancer, ovarian cancer, tubulin cancer etc. were reported in this review. Thus, this review will definitely aid to develop a lead for the new selective anticancer agents in future.

Predictive Factors for Submandibular Gland Involvement in Oral Cavity Squamous Cell Carcinoma-a Prospective Study from a Tertiary Cancer Center.

The oncological necessity of submandibular gland removal during neck dissection for oral cavity squamous cell carcinoma surgery has remained controversial. This study was aimed to determine the rate of SMG involvement and assess the feasibility of submandibular gland (SMG) preservation. We present a prospective study conducted at a tertiary cancer center from June 2017 to May 2019. All patients of oral squamous cell carcinoma who underwent primary surgery with neck dissection were included and analyzed for incidence and predictive factors for incidence of level IB nodal and SMG involvement as per CAP guidelines. A total of 60 patients were inducted in the study, wherein 63 neck dissections were performed including bilateral dissection in three cases. There was involvement of SMG in 6 patients with two cases each in floor of mouth cancer, gingivo-buccal, and alveolar lesions. The SMG was involved by direct contiguous spread from the primary lesion in two cases, extra-capsular extension from level IB lymph nodes in one and by both mode of spread in three glands. Perineural invasion was seen in 83.33% (n = 5) patients with SMG involvement (p- < 0.001), while 66.67% (4/6) patients had lympho vascular invasion (p-0.006) and all the cases with SMG involvement had extra-capsular extension (p < 0.001), suggesting PNI, LVI, and ECE as the strongest predictors of SMG involvement. This study demonstrates that oral cavity squamous cell carcinoma has low potential to metastasize to the SMG; however, high-risk factors include primary tumor site in floor of mouth or tongue, heavy level IB nodal burden, presence of LVI, PNI, and ECE. In the absence of these high-risk factors, SMG preservation with complete nodal clearance in level IB is a promising technique for reducing future complications.

Operative versus non-operative treatment of humeral shaft fractures: A systematic review.

BACKGROUND: Humeral shaft fractures are common but debate still occurs as to whether these are best managed operatively or non-operatively. We sought to undertake a systematic review and meta-analysis of randomised and non-randomised studies to clarify the optimal treatment. METHODS: We performed a search for all randomised and non-randomised comparative studies on humeral shaft fracture. We included only those with an operative and non-operative cohort in adult patients. We undertook a meta-analysis of the following outcome measures: nonunion, malunion, delayed union, iatrogenic nerve injury and infection. Non-operative management was with a functional brace. RESULTS: Non-operative management resulted in a significantly higher nonunion rate of 17.6% compared to 6.3% with fixation. Operative management had a significantly higher iatrogenic nerve injury rate of 3.4% and infection rate of 3.7%. All nonunions within the included studies went on to union after plate fixation. There was no significant difference in delayed union or patient reported outcome measures. There was a significantly increased risk of malunion with non-operative treatment however this did not correlate with the outcome. DISCUSSION: Our findings suggest that in the majority of cases, humeral shaft fractures can be managed with non-operative treatment, and any subsequent nonunion should be treated with plate fixation.

A multi-institutional real world data study from India of 3453 non-metastatic breast cancer patients undergoing upfront surgery.

The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25-94.98), 96.17% (95.2-97.15) and 91.83% (90.36-93.31), respectively, and the corresponding DFS were 88.1% (86.96-89.31), 92.0% (90.64-93.39) and 83.93% (82.03-85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12-97.1), 92.74% (90.73-94.8) and 90.62% (88.17-93.15), respectively, and the corresponding DFS were 91.59% (90.19-93.02), 85.46% (82.79-88.22) and 81.29% (78.11-84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.