Gallstone-Associated Histopathological Changes in Liver: A Prospective Observational Study.

AIM AND OBJECTIVES: To assess the effect of gallstone disease on liver parenchyma and the prevalence and extent of liver pathology in cholelithiasis in our population at the Department of General Surgery, Indira Gandhi Institute of Medical Science (IGIMS), Patna. MATERIAL AND METHODS: The present prospective observational study was conducted on 100 either-sex patients scheduled for open or laparoscopic cholecystectomy. In all the patients, laboratory and radiological investigations were performed. An undamaged portion of the liver edge around the gallbladder fossa was selected and held by atraumatic forceps. Using sharp scissors, around 1 cm of the liver edge was taken out and sent for histopathological examination. RESULTS: The mean age of the patients was 39.28 ± 13.73 years. The majority of patients were females (69%). Pain was the predominant clinical feature in 51% of the patients, followed by vomiting (21%), nausea (18%), and indigestion (10%). In 36% of cases, the liver histology was abnormal, including steatosis, fibrosis, cholestasis, portal tract infiltration, and lobular parenchymal infiltration. A significant association was found between the duration of symptoms and abnormal histology findings (P<0.0001). CONCLUSION: Gallstone disease is associated with notable alterations in liver histology, and these changes tend to be more prevalent in individuals with a prolonged duration of symptoms.

A Path of Novelty from Nanoparticles to Nanobots: Theragnostic Approach for Targeting Cancer Therapy.

Pharmaceutical development of cancer therapeutics is a dynamic area of research. Even after decades of intensive work, cancer continues to be a dreadful disease with an ever-increasing global incidence. The progress of nanotechnology in cancer research has overcome inherent limitations in conventional cancer chemotherapy and fulfilled the need for target-specific drug carriers. Nanotechnology uses the altered patho-physiological microenvironment of malignant cells and offers various advantages like improved solubility, reduced toxicity, prolonged drug circulation with controlled release, circumventing multidrug resistance, and enhanced biodistribution. Early cancer detection has a crucial role in selecting the best drug regime, thus, diagnosis and therapeutics go hand in hand. Furthermore, nanobots are an amazing possibility and promising innovation with numerous significant applications, particularly in fighting cancer and cleaning out blood vessels. Nanobots are tiny robots, ranging in size from 1 to 100 nm. Moreover, the nanobots would work similarly to white blood cells, watching the bloodstream and searching for indications of distress. This review articulates the evolution of various organic and inorganic nanoparticles and nanobots used as therapeutics, along with their pros and cons. It also highlights the shift in diagnostics from conventional methods to more advanced techniques. This rapidly growing domain is providing more space for engineering desired nanoparticles that can show miraculous results in therapeutic and diagnostic trials.

Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

Primary hepatic functional neuroendocrine tumor in an elderly female: Case report.

Key Clinical Message: Primary hepatic neuroendocrine tumor, an exceptionally rare subtype, poses a diagnostic challenge. Oncological resections should be considered, even in elderly patients after following protocolized pre-operative optimizations. Abstract: Neuroendocrine tumors (NETs) are rare tumors that primarily develop in the gastrointestinal and respiratory tracts. While the liver is commonly affected by NET metastases, primary hepatic neuroendocrine tumors (PHNETs) are an exceptionally rare subtype. The characteristic slow growth and nonfunctional nature of PHNETs pose challenges in their diagnosis. Furthermore, PHNETs often exhibit a lack of unique radiological characteristics that differentiate them from other liver tumors, leading to frequent misdiagnosis as hepatocellular carcinoma. We performed left hepatectomy for PHNET in an elderly lady with prolonged stormy postoperative course. This case report of a PHNET highlights the importance of histopathology and immunohistochemistry in the diagnosis and emphasizes that oncological resection, if feasible, is the preferred treatment even in the elderly population.

Role of 18F-FDG PET/CT in Guiding Surgical Management of Clinically Node Negative Neck (cN0) in Carcinoma Oral Cavity.

Conventional staging paradigm with clinical examination or imaging invariably leads to underestimation of occult metastatic neck disease in oral cavity carcinoma. The advantage of 18F-FDG PET/CT is in its ability to identify lymph nodes without morphological changes yet harboring occult metastases. We present findings of our study to evaluate diagnostic accuracy of 18F-FDG PET/CT, in detecting occult cervical lymph node metastasis in carcinoma oral cavity. In a single institution prospective study, 51 consecutive patients with histologically proven (cT1/T2) oral cavity carcinoma and clinically node negative neck (cNo), underwent 18F-FDG PET/CT before elective neck dissection of 58 neck sides. 18F-FDG PET/CT findings were compared with histopathology of dissected nodes, to calculate diagnostic accuracy. 18F-FDG PET/CT correctly characterized the occult lymph node metastasis status (true positive + true negative) in 51 of 58 neck sides, yielding diagnostic accuracy of 87.93%. Sensitivity of 18F-FDG PET/CT was 90% and specificity was 87.5%. While a positive 18F-FDG PET/CT accurately predicted the disease in only 60% (positive predictive value), a negative 18F-FDG PET/CT reasonably ruled out occult metastases in 97.67% (negative predictive value). If a decision regarding the need for neck dissection had been based solely on 18F-FDG PET/CT, the number of neck dissections would have been reduced by 74.13%. Based on diagnostic accuracy and high negative predictive value, incorporating 18F-FDG PET/CT in preoperative staging paradigm of cT1/T2 carcinoma oral cavity will guide in selection of patients in which cN0 neck can be safely observed.

Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders.

BACKGROUND: Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood-brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. AIM: The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain-Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed. MAIN BODY: There have been reports that the SARS-CoV-2 virus can cross the blood-brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain. CONCLUSIONS: SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics.

To compare neoadjuvant concurrent chemo-radiotherapy followed by surgery and neoadjuvant chemotherapy followed by surgery in carcinoma esophagus patients: A single institutional study in the Indian population.

Objective: This single institutional study compared neoadjuvant concurrent chemo-radiotherapy (NACCRT) and neoadjuvant chemotherapy (NACT) followed by surgery in locally advanced middle and lower-1/3 carcinoma esophagus patients in terms of toxicity, clinical response, operative complications, disease downstaging, resection rates, pathological response, recurrence, and survival. Methods: This randomized prospective comparative study comprised 40 consecutive patients divided equally between two study arms NACCRT (n = 20; 41.4 Gy radiation dose; carboplatin area under the curve (AUC) 2/paclitaxel 50 mg/m2; 5 cycles) and NACT (n = 20; carboplatin AUC 5/paclitaxel 175 mg/m2; 2 cycles) from March 2014 to December 2016. Follow-up was done for 4 years. Chi-square test, Fischer's-exact test were used for comparative analysis and Kaplan-Meier analysis for survival. Results: Statistically significant esophagitis in NACCRT and peripheral-neuropathy in NACT was observed (P < 0.001). NACCRT recorded more postoperative complications, higher complete resection (R0) rates, and pathologically complete response (pCR). Tumor downstaging was significant in both study groups (n < 0.001). Four-year median disease-free survival (DFS) and overall survival (OS) were 28.50 months and 38 months in NACCRT versus 28 months and 35.5 months in NACT, respectively. In both NACCRT and NACT, pCR cases showed improved median DFS and OS compared to pathological partial response (pPR) (n < 0.001). Conclusion: This study demonstrated significant activity and tolerable toxicity of taxane-based therapy in NACCRT and NACT. Both groups recorded no survival benefit over each other, although pCR cases resulted in statistically significant survival advantage compared to clinical partial response. NACCRT resulted in lesser toxicity, numerically higher R0-resection, pCRs, median DFS, and OS compared to NACT.

Comparison of Extended Total Extraperitoneal (E-TEP) Repair and Trans-Abdominal Pre-Peritoneal (TAPP) Mesh Repair in Inguinal Hernia Repair.

BACKGROUND AND AIM: To find the superiority of extended total extraperitoneal (E-TEP) repair and trans-abdominal pre-peritoneal (TAPP) mesh repair in inguinal hernia repair. MATERIAL AND METHODS: A total of 30 patients with a unilateral or bilateral inguinal hernia (IH), and recurrent IH, following open repair were studied. Out of 30 patients, laparoscopic TAPP or E-TEP mesh repair was performed in an equal number of inguinal hernia patients. The patient's demographic parameters, duration of surgery, postoperative hospital stay, and complications were compared. RESULTS:  In the E-TEP group, 33.33% of patients had left inguinal hernia (LIH), 60% of patients were diagnosed with right inguinal hernia (RIH) and 6.67% of patients had right inguinal and right direct hernia (RDH). In the TAPP group, 33.33% of patients had LIH and 53.33% of patients were suffering from RIH. Moreover, 6.67% of patients were diagnosed with a left inguinal direct hernia, and a similar proportion of patients had a right inguinal direct hernia. The mean duration of surgery was found to be significantly higher in the TAPP group (P<0.0000). The mean postoperative hospital stay was 2.07±0.59 and 2.80±1.32 days in E-TEP and TAPP groups, respectively (P=0.044). CONCLUSION: In the present study, E-TEP mesh repair is a superior technique in the management of inguinal hernia as compared with TAPP repair.

Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer's Disease.

The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.

Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders.

A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3ß) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease. Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.

Outcomes of Rubber Band Ligation in Haemorrhoids Among Outdoor Patients.

BACKGROUND: Out of all anorectal diseases, haemorrhoids are the most common benign disease. Haemorrhoids can be treated by various treatment modalities like medical, surgical, and instrumental. Instrumental treatment comprises rubber band ligation, sclerotherapy, and infrared and laser therapy. Out of these modalities, the rubber band ligation technique is the least invasive with a reduced rate of complications and without the need for hospitalization. Hence, the current study was conducted to evaluate the outcomes with respect to the effectiveness of rubber band ligation in grade II and III internal haemorrhoids along with the magnitude and pattern of post-procedural complications. METHODS: This is a prospective observational study, conducted on a sample of 100 patients who presented to our outdoor patient's department and were diagnosed with haemorrhoids, either grade II or III. All enrolled study patients having haemorrhoids were banded with rubber band by Barron Ligator (Precise, Canada) with local anaesthetic agent xylocaine jelly in a single session. All patients were followed on the 10th day, 1st month, and 6th month after the procedure to assess symptomatic improvement. The endpoint of this study is to know the effectiveness of rubber band ligation in different clinical parameters such as post-ligation pain or discomfort, the requirement of analgesic, any complication, and time off work. RESULTS: Out of 100 patients 17 patients had grade II and 83 patients had grade III haemorrhoids. Among them, 89% were symptomatically relieved after rubber band ligation whereas the rest 11% of patients had residual symptoms. CONCLUSION: Thus, we conclude that rubber band ligation for grade II and III haemorrhoids is simple, safer, easy-to-perform daycare procedure with lesser requirements of analgesics and without any need for anaesthesia.

Novel Technique of Laparoscopic e-TEP (Extended View Totally Extraperitoneal Repair) for Umbilical Hernia at a Tertiary Care Centre of Eastern India: a Case Series.

Introduction:The field of abdominal wall hernias has undergone many innovations. Ventral hernias have conventionally been treated by open on-lay mesh hernioplasty, open retromuscular mesh hernioplasty (Rives-Stoppa procedure) and laparoscopic intraperitoneal mesh hernioplasty. Objective: To develop an alternative strategy where a mesh is placed in retromuscular space by minimal access technique of the laparoscopic extended view totally extraperitoneal approach (e-TEP). Methodology: This was an interventional and prospective study on series of 25 cases of either sex with age ≥18 years and ≤65 years presenting with umbilical hernia with abdominal wall defect. Laparoscopic e-TEP (extended view totally extraperitoneal repair) for umbilical hernia was performed and patients were usually discharged within 48.72 hours of the procedure. Follow-up surveillance for complications and recurrence of hernia was performed in an outpatient clinic the sixth week after surgery and by telephonic conversation every sixth months. Demographic profile, medical history, preoperative (comorbidities), perioperative and postoperative (during hospital stay) clinical profile of each patient was documented. Results:Among our study participants there was a female preponderance, with a male to female ratio of 0.47:1. Patients' ages ranged from 27 to 61 years, with a mean (SD) of 41.7 (11.4) years. Average defect size was 4.2 cm². One hernia involved divarication of recti muscles. A polypropylene mesh of size 15 x 15 cm was placed. The mean operative times were 94 minutes, ranging from 60 to 120 minutes. The average hospital stay was three days. The mean follow-up period was 12.6 months. Two patients developed seroma at umbilicus with discharge from suture site which resolved in two weeks with regular dressing. Prolonged ileus was noted in two patients, which resolved spontaneously by the fourth day. None of the patients developed surgical site infection, skin necrosis, wound dehiscence, bowel obstruction, urinary complications, or deep vein thrombosis. Also, none of the patients required conversion to open surgery. Conclusion:The current study generates evidence in support of this technique to be adapted in centers with advanced laparoscopic skills.

In pursuit of next-generation therapeutics: Antimicrobial peptides against superbugs, their sources, mechanism of action, nanotechnology-based delivery, and clinical applications.

Antimicrobial peptides (AMPs) attracted attention as potential source of novel antimicrobials. Multi-drug resistant (MDR) infections have emerged as a global threat to public health in recent years. Furthermore, due to rapid emergence of new diseases, there is pressing need for development of efficient antimicrobials. AMPs are essential part of the innate immunity in most living organisms, acting as the primary line of defense against foreign invasions. AMPs kill a wide range of microorganisms by primarily targeting cell membranes or intracellular components through a variety of ways. AMPs can be broadly categorized based on their physico-chemical properties, structure, function, target and source of origin. The synthetic analogues produced either with suitable chemical modifications or with the use of suitable delivery systems are projected to eliminate the constraints of toxicity and poor stability commonly linked with natural AMPs. The concept of peptidomimetics is gaining ground around the world nowadays. Among the delivery systems, nanoparticles are emerging as potential delivery tools for AMPs, amplifying their utility against a variety of pathogens. In the present review, the broad classification of various AMPs, their mechanism of action (MOA), challenges associated with AMPs, current applications, and novel strategies to overcome the limitations have been discussed.

Blood-brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders.

The integrity of the blood-brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.