Untoward

Therapy-induced senescence (TIS) is a primary response to chemotherapy, contributing to untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role of the complement system in the immune response to cancer, the role of complement in mediating the immune response against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast adenocarcinoma (MCF7) and pancreatic carcinoma (Panc-1) cell lines to sublethal doses of either etoposide or doxorubicin to trigger TIS...

BACKGROUND AND AIMS: Hypercholesterolemia (HC) has previously been shown to augment the restenotic response in animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC, are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model...

BACKGROUND: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is typically incurable, and palliative treatment is the only option for most patients, resulting in a poor prognosis and reduced quality of life. Carbon ion radiotherapy (CIRT) has emerged as a promising modality for treating LRRC. This report presents a case of LRRC with sacral involvement that was managed via multidisciplinary therapy incorporating CIRT. CASE PRESENTATION: A 55-year-old male was diagnosed with an anastomotic recurrence of rectal cancer 15 months after undergoing anterior resection...

Most antirheumatic drugs with high toxicity exhibit a narrow therapeutic window due to their nonspecific distribution in the body, leading to undesirable side effects and reduced patient compliance. To in response to these challenges, prodrug-based nanoparticulate drug delivery systems (PNDDS), which combines prodrug strategy and nanotechnology into a single system, resulting their many advantages, including stability for prodrug structure, the higher drug loading capacity of the system, improving the target activity and bioavailability, and reducing their untoward effects...

BACKGROUND: Levodopa is used to treat hyperkinetic movements in children with dopa-responsive dystonia. However, levodopa may also be helpful in treating other forms of dystonia when used beyond a brief trial period. METHODS: We performed a retrospective review of all children referred to our institution for evaluation of generalized dystonia and subsequently treated with carbidopa-levodopa. Motor function was assessed using video recordings and examination notes, quantified with the Burke-Fahn-Marsden Dystonia Rating Scale...

Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a significant proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in regulation of energy balance, we examined the signaling properties of one such mutant MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice...

INTRODUCTION: Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment. CONTENT: Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system...

BACKGROUND: The global burden of chronic hepatitis B remains high and the best possible treatment remains long-term viral suppression expecting cure. METHODS: Total 154 patients of chronic hepatitis B (48 HBeAg positive, e + ve) treated with oral entecavir (0.5 mg/1 mg per day) were recruited from June 2007 and followed prospectively until December 2022 for persistent HBV DNA negativity, HBeAg and HBsAg loss/seroconversion and other liver and drug-related events in real-life settings...

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is a B-cell-mediated autoimmune encephalitis with wide non-specific symptoms like acute-onset psychiatric or neurological ones mimicking various other conditions. A careful history and appropriate workup, including cerebrospinal fluid analysis for anti-NMDAR antibodies, imaging, and electroencephalogram, should be conducted, considering all differential diagnoses that can mimic its presentation. Combination therapy with high-dose steroids, plasma exchange, or immunoglobulin therapy has been shown to be more efficacious...

Cholangiocarcinoma (CCA) is a biliary epithelial cancer conferring a grim prognosis. Metastatic recurrence of CCA is often discovered because of symptoms stemming from the site of metastasis. It is rarely reported that colonic obstruction serves as the presenting symptom of disease recurrence. We report the unusual discovery of malignant colonic obstruction because of metastatic CCA. Our report highlights the benefit of minimally invasive colonic stenting for palliation yielding immediate relief of pain while avoiding untoward sequelae from high-risk surgical intervention...

Immune-related adverse events (irAEs) represent an increasingly concerning challenge in the assessment of biopharmaceutical products. In contrast to historically rare allergic reactions associated with small chemical drugs, contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs, because of their complex structure and comprehensive mechanisms of action. While the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies (ADAs), the pathogenesis of irAEs in advanced biologics, such as cell and gene therapy, remains to be further delineated...

Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs...

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up...

At our institution, we occasionally see pregnant patients in the later stages of pregnancy who present with severe pulmonary arterial hypertension caused by congenital heart disease. The physiological changes in pregnancy may worsen the cardiovascular status leading to heart failure which is associated with a high incidence of morbidity and mortality. A scheduled caesarean section in such patients ensures delivery in a controlled environment, avoiding prolonged labour, which is detrimental. Perioperative complications that may worsen pulmonary arterial hypertension should be prevented...

STUDY DESIGN: Retrospective observational study. OBJECTIVE: The purpose of this publication is to address the absence of literature detailing respiratory management in patients with syndromic craniosynostosis and obstructive sleep apnea during the immediate postoperative interval following LeFort III advancement with placement of distraction hardware but prior to sufficient midface advancement. METHODS: After IRB approval, the investigators retrospectively selected candidates for inclusion in this case series...

BACKGROUND: Abnormal morphological variations of nasolacrimal canal (NLC) and its lack of understanding contributes to acquired injuries during craniomaxillofacial surgical procedures which leads untoward postoperative complications like nasolacrimal obstruction (NLO) and epiphora. PURPOSE: The purpose of this study was to determine dimensional and volumetric morphological variations of nasolacrimal canal in various facial skeletal relationships which aid in performing a precise and safe surgery...

We describe a potential cause of eye injury, its concerns and ways to prevent it. The first author underwent a left cataract operation and was prescribed eye drops postoperatively. While applying one of the eye drops, he felt an object hitting the lower eyelid. A serrated plastic piece had fallen off the bottle. Had it fallen on the operated site, it might have caused serious untoward complications. Nurses, carers and patients need to be educated to remove the serrated piece from the bottle before applying eye drops...

BACKGROUND: Central nervous system dysfunction has been postulated to cause debilitating symptoms in patients with myalgic encephalomyelitis (ME) (originally called "chronic fatigue syndrome"). Repetitive transcranial magnetic stimulation (rTMS) is a newly developed neuromodulatory procedure and has been suggested to facilitate the cortical neural activity. METHODS: This study enrolled 30 patients with ME (7 men and 23 women) with a mean age of 39 ± 12 years, who received rTMS treatment of both the left dorsolateral prefrontal cortex and the left primary motor area in the brain...

OBJECTIVE: Oral anticoagulant drugs, such as warfarin, are widely used for preventing and treating vascular and thromboembolic disease in patients with chronic atrial fibrillation, venous thrombosis, and coronary heart disease. As oral anticoagulant therapy has such a narrow therapeutic range, complications in administering these drugs can prove to have a detrimental effect on patients such as life-threatening bleeding might occur. It is therefore necessary to have an adequate knowledge about its actions and its interactions with other dietary factors or any other medication involved...

The clinical relevance of head and neck (H&N) tumors is related to the potential disfiguration of anatomical structures (by the tumor or surgical intervention), defining patients' individual features and emotional expression, loss or restraint of vital structures functions, and untoward socio-economic sequelae. This study is aimed to improve clinical outcomes of cryosurgery in patients with H&N basal cell skin cancer by refining the indications for cryosurgical treatment. In this study, cryosurgery was used in 234 patients with different stages of cutaneous basal cell carcinoma (BCC) of the head, including 101 patients with T1 tumors, 86-with T2, 5-T3, and 42 patients with tumors relapsing after failure of preceding various treatment modalities...