Association of serum lipid profile and other systemic risk factors with retinal hard exudates in diabetic retinopathy.

PURPOSE: Diabetic macular edema is one of the leading causes of vision loss across the world. Hard exudates at the macula can lead to structural abnormalities in the retina leading to irreversible vision loss. Systemic dyslipidemia and other modifiable risk factors when identified and treated early may help prevent substantial vision loss. The purpose of this study was to study the association between serum lipid levels and other systemic risk factors like hemoglobin, HbA1c, and serum creatinine with hard exudates and macular edema in patients with diabetic retinopathy. METHODS: It is a prospective cross-sectional study conducted in a tertiary health care center in South India. 96 patients having diabetic retinopathy with hard exudates were included. Modified Airlie house classification was used to grade the hard exudates. Blood investigations including serum lipid profile, hemoglobin, HbA1c, and serum creatinine were carried out. Central subfield macular thickness was measured using optical coherence tomography. RESULTS: 96 patients of type II DM with diabetic retinopathy were divided into three groups of hard exudates. A statistically significant correlation was observed between the severity of hard exudates and total cholesterol (p = 0.00), triglycerides (p = 0.00), LDL (p = 0.00), and VLDL (p = 0.00). HbA1c levels showed a statistically significant correlation with the severity of hard exudates (p = 0.09), no significant correlation was noted between hard exudates and hemoglobin levels (p = 0.27) and with serum creatinine (p = 0.612). A statistically significant association between CSMT and hard exudates (p = 0.00) was noted. CONCLUSION: In our study, we concluded that the severity of hard exudates is significantly associated with increasing levels of serum total cholesterol, triglycerides, LDL, VLDL, and HbA1c levels in type II DM patients presenting with diabetic retinopathy. The increasing duration of diabetes is significantly associated with increasing severity of hard exudates. Central subfield macular thickness increases with increasing severity of hard exudates in diabetic retinopathy.

Therapeutic potentials and targeting strategies of quercetin on cancer cells: Challenges and future prospects.

BACKGROUND: Every cell in the human body is vital because it maintains equilibrium and carries out a variety of tasks, including growth and development. These activities are carried out by a set of instructions carried by many different genes and organized into DNA. It is well recognized that some lifestyle decisions, like using tobacco, alcohol, UV, or multiple sexual partners, might increase one's risk of developing cancer. The advantages of natural products for any health issue are well known, and researchers are making attempts to separate flavonoid-containing substances from plants. Various parts of plants contain a phenolic compound called flavonoid. Quercetin, which belongs to the class of compounds known as flavones with chromone skeletal structure, has anti-cancer activity. PURPOSE: The study was aimed at investigating the therapeutic action of the flavonoid quercetin on various cancer cells. METHODS: The phrases quercetin, anti-cancer, nanoparticles, and cell line were used to search the data using online resources such as PubMed, and Google Scholar. Several critical previous studies have been included. RESULTS: Quercetin inhibits various dysregulated signaling pathways that cause cancer cells to undergo apoptosis to exercise its anticancer effects. Numerous signaling pathways are impacted by quercetin, such as the Hedgehog system, Akt, NF-κB pathway, downregulated mutant p53, JAK/STAT, G1 phase arrest, Wnt/ß-Catenin, and MAPK. There are downsides to quercetin, like hydrophobicity, first-pass effect, instability in the gastrointestinal tract, etc., because of which it is not well-established in the pharmaceutical industry. The solution to these drawbacks in the future is using bio-nanomaterials like chitosan, PLGA, liposomes, and silk fibroin as carriers, which can enhance the target specificity of quercetin. The first section of this review covers the specifics of flavonoids and quercetin; the second section covers the anti-cancer activity of quercetin; and the third section explains the drawbacks and conjugation of quercetin with nanoparticles for drug delivery by overcoming quercetin's drawback. CONCLUSIONS: Overall, this review presented details about quercetin, which is a plant derivative with a promising molecular mechanism of action. They inhibit cancer by various mechanisms with little or no side effects. It is anticipated that plant-based materials will become increasingly relevant in the treatment of cancer.

Milk miRNA expression in buffaloes as a potential biomarker for mastitis.

BACKGROUND: Buffaloes have the highest potential for production due to a promising gene pool that is being enhanced and upgraded. Mastitis is a significant health impediment that greatly diminishes milk yield and quality, affecting rural farmers' livelihoods. The traditional gold standard used for diagnosing mastitis or subclinical mastitis is CMT, but it has the drawback of false positive or negative results. Subclinical mastitis, if not treated promptly, can lead to mammary tumors. To address the gap in early diagnosis of subclinical mastitis in CMT-negative milk of buffaloes, we performed a retrospective analysis and evaluated the milk miRNA expression profiles as potential biomarkers. RESULTS: Thirty buffalo milk samples based on clinical signs and CMT were divided into normal, subclinical, and clinical mastitis. SCC evaluation showed significant differences between the groups. The data analysis demonstrated that the elevation of miR-146a and miR-383 differed substantially between normal, subclinical, and clinical mastitis milk of buffaloes with 100% sensitivity and specificity. The relationship of SCC with miR-146a and miR-383 in normal/healthy and subclinical mastitis was positively correlated. CONCLUSION: The overexpression of miR-146a and miR-383 is associated with inflammation. It can be a valuable prognostic and most sensitive biomarker for early mastitis detection in buffaloes with SCC below 2 lakhs and CMT-ve, enhancing the accuracy of subclinical mastitis diagnosis.

The Utilization of Preoperative Steroids Safely Decreases the Risk of Postoperative Delirium in Geriatric Patients After Hip Fracture Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: Postoperative delirium is an acute neurocognitive complication that can have adverse effects on outcomes of geriatric patients after undergoing hip fracture surgery. The objective of this study was to examine the efficacy of preoperative steroids in preventing postoperative delirium after hip fracture surgery. DATA SOURCES: A systematic review and meta-analysis was performed using PubMed, SPORTDiscus, CINAHL, MEDLINE, and Web of Science from database inception until September 28, 2023. STUDY SELECTION: Inclusion criteria were randomized controlled trials of patients who underwent surgical intervention for hip fracture, were examined for postoperative delirium, and used preoperative steroids. DATA EXTRACTION: Data included the risk of postoperative delirium, postoperative all-cause infection, and postoperative hyperglycemia. Articles were graded via the Cochrane Collaboration's tool. DATA SYNTHESIS: Statistical analysis included a random-effects binary model with relative risk, 95% confidence intervals along with a defined "number needed to treat" threshold (number needed to treat). RESULTS: Four randomized controlled trials were included from 128 articles initially retrieved. Patients (n = 416; average age: 82.2 ± 2.2 years) underwent surgical intervention for hip fracture after receiving either preoperative steroids (n = 209) or control interventions (n = 207). There was a statistically significant decrease in the incidence of postoperative delirium among patients who received preoperative steroids (12.9%; 27 cases) as compared with patients who received control interventions (26.7%; 55 cases) after hip fracture surgery ( P < 0.001; RR: 0.84). The absolute risk difference was 13.8%, and the number needed to treat was 7.2 patients. There was no statistically significant difference in the risk of postoperative all-cause infection among patients who received preoperative steroids as compared with patients who received normal saline as placebo after hip fracture surgery ( P = 0.850; RR: 0.96). CONCLUSIONS: The utilization of preoperative steroids seems to decrease the risk of postoperative delirium after hip fracture surgery in elderly adults. Furthermore, this decreased risk of postoperative delirium was not associated with a significant increase in postoperative infection, indicating possible safety of preoperative steroid administration. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Associations between e-cigarette use and sleep health among adults in the United States, NHANES 2015-2018.

OBJECTIVE: To examine the associations between e-cigarette use or dual (e-cigarette and combustible cigarette) use and short sleep duration and trouble sleeping among U.S. adults. METHODS: We used 2015-2018 data from the National Health and Nutrition Examination Survey (NHANES) (n = 11,659). E-cigarette use and dual use were categorized as current, former, and never use. Short sleep duration was defined as sleep duration ≤6 h. Trouble sleeping was self-reported. Weighted logistic regression analyses were performed. RESULTS: Among those with current e-cigarette use, 53.9 % were with current dual use and 23.8 % were with former dual use. Compared to never e-cigarette use, current e-cigarette use was associated with significantly higher odds of trouble sleeping (OR = 2.16, 95 % CI: 1.49-3.13), adjusting for potential confounders. Significant associations were also observed for former e-cigarette use versus never use with trouble sleeping (OR = 1.54, 95 % CI: 1.15-2.07) after full adjustment. Current cigarette use was associated with both short sleep duration (OR = 1.65, 95 % CI: 1.28-2.14) and trouble sleeping (OR = 1.36, 95 % CI: 1.03-1.79) after full adjustment. Additionally, the fully adjusted ORs for short sleep duration and trouble sleeping were 1.64 (95 % CI: 1.06-2.54) and 2.14 (95 % CI: 1.34-3.42) among those with current dual use, and 1.46 (95 % CI: 1.17-1.81) and 2.11 (95 % CI: 1.66-2.67) among those with former dual use, compared to those without dual use. CONCLUSIONS: Current cigarette use or dual use is associated with significantly higher odds of short sleep duration and trouble sleeping. Moreover, former e-cigarette use or dual use is associated with increased odds of trouble sleeping.

Rates and risk factors for anastomotic leak following blunt trauma-associated bucket handle intestinal injuries: a multicenter study.

Objectives: The risk factors for anastomotic leak (AL) after resection and primary anastomosis for traumatic bucket handle injury (BHI) have not been previously defined. This multicenter study was conducted to address this knowledge gap. Methods: This is a multicenter retrospective study on small intestine and colonic BHIs from blunt trauma between 2010 and 2021. Baseline patient characteristics, risk factors, presence of shock and transfusion, operative details, and clinical outcomes were compared using R. Results: Data on 395 subjects were submitted by 12 trauma centers, of whom 33 (8.1%) patients developed AL. Baseline details were similar, except for a higher proportion of patients in the AL group who had medical comorbidities such as diabetes, hypertension, and obesity (60.6% vs. 37.3%, p=0.015). AL had higher rates of surgical site infections (13.4% vs. 5.3%, p=0.004) and organ space infections (65.2% vs. 11.7%, p<0.001), along with higher readmission and reoperation rates (48.4% vs. 9.1%, p<0.001, and 39.4% vs. 11.6%, p<0.001, respectively). There was no difference in intensive care unit length of stay or mortality (p>0.05). More patients with AL were discharged with an ostomy (69.7% vs. 7.3%, p<0.001), and the mean duration until ostomy reversal was 5.85±3 months (range 2-12.4 months). The risk of AL significantly increased when the initial operation was a damage control procedure, after adjusting for age, sex, injury severity, presence of one or more comorbidities, shock, transfusion of >6 units of packed red blood cells, and site of injury (adjusted RR=2.32 (1.13, 5.17)), none of which were independent risk factors in themselves. Conclusion: Damage control surgery performed as the initial operation appears to double the risk of AL after intestinal BHI, even after controlling for other markers of injury severity. Level of evidence: III.

Posterolateral tibial plateau bone bruises in anterior cruciate ligament (ACL) injuries and its association with lateral meniscal injuries.

INTRODUCTION: This study examined the prevalence of posterolateral tibial bone bruising in isolated anterior cruciate ligament (ACL) injuries, prevalence of meniscal injuries in ACL injuries, as well as the association between posterolateral tibial bone bruising and lateral meniscal tears among those with ACL injury undergoing Primary ACL Reconstruction. MATERIALS AND METHODS: Retrospective data on 130 patients who underwent primary ACL reconstructions was analysed. Their preoperative magnetic resonance images (MRI) were reviewed for the presence of posterolateral tibial bone bruise. The presence of meniscal injuries was recorded based on the arthroscopic findings from the operative records. RESULTS: 95 patients were recruited into the study. The prevalence of posterolateral bone bruise in this study was 41%. There was a statistically significant difference when comparing the prevalence of bone bruising to the time of injury to MRI (p<0.001). The prevalence of an injury to at least one meniscus at the time of ACLR surgery was 83.2%. The prevalence of lateral meniscus injuries in patients with bone bruise was found to be 53.9%. The crude odds ratio of a patient having a lateral meniscal tear in the presence of bone bruising was 1.56 (0.68, 3.54). This figure was even higher when it was adjusted for time to MRI and was 2.06 (0.77, 5.46). CONCLUSION: Prevalence of posterolateral tibial bone bruising in our study was 41%, and the prevalence of meniscal injury to either meniscus at the point of surgery was 83.2%, out of which the lateral meniscus tears were identified during ACLR surgery in 47.3% of the patients. We found there was no association between posterolateral tibial bone bruising to sex, age and mode of injury, but was sensitive to the interval between time of injury and MRI. The overall prevalence of lateral meniscal tears was higher in patients with posterolateral bone bruising but was not statistically significant with a P value of 0.31; however, the Crude odd ratio was 1.56 (0.68, 3.54) and was higher when adjusted to time of injury to MRI 2.06 (0.77, 5.46). We suggest for MRI to be done as soon as possible after injury in regard to bone bruising identification. We should be vigilant to look for lateral meniscal tears and anticipate for its repair in ACL injuries, especially so when we identify posterolateral tibial bruising on the preoperative MRI.

A rare presentation of idiopathic small bowel diaphragm disease - A case report.

INTRODUCTION: Diaphragm disease, typically associated with long-term non-steroidal anti-inflammatory drug (NSAID) use, manifests as diaphragm-like small bowel strictures, often resulting in bowel obstruction. CASE DESCRIPTION: A 75-year-old male presented with features of recurrent subacute intestinal obstruction, later diagnosed with multiple small bowel strictures via CT imaging. Surgical intervention, including resection and anastomosis, was performed to alleviate the obstruction. Histopathological examination of the resected specimen confirmed diaphragm disease, challenging its traditional association with NSAID use. DISCUSSION: Diaphragm disease, characterized by mucosal and submucosal diaphragm-like strictures, is typically attributed to NSAID usage. However, this case underscores the possibility of diaphragm disease in the absence of NSAID exposure. Pathological findings supported the presence of diaphragm-like strictures, despite the patient's denial of NSAID use. CONCLUSION: This case emphasizes the importance of considering diaphragm disease as a differential diagnosis in patients with intermittent bowel obstruction, even in the absence of NSAID history.

Cs-131 prostate brachytherapy boost and effect of hydrogel rectal spacer on long-term patient-reported rectal bleeding and bowel quality of life.

PURPOSE: This study evaluates long-term patient-reported bowel quality of life (QOL), rectal bleeding, and bleeding bother in patients with prostate cancer treated with external beam radiation therapy (EBRT) and Cesium-131 LDR brachytherapy (LDR-BT) boost with and without hydrogel rectal spacer. METHODS AND MATERIALS: This is a retrospective analysis of prostate cancer patients treated between 2007 and 2022 with 45 Gy EBRT followed by 85 Gy Cs-131 LDR-BT boost with or without hydrogel rectal spacer. Expanded Prostate Cancer Index Composite (EPIC) QOL questionnaires pre-treatment and at each follow-up were collected. Patient-reported rectal bleeding occurring more than "rarely" and bother from rectal bleeding occurring more than a "very small problem" were deemed clinically significant. Fisher's exact test was used to test the association of rectal spacer use and the incidence of clinically significant rectal bleeding and bleeding bother. Paired samples t-test was used to analyze mean bowel scores at each time point. RESULTS: Three hundred and forty-one patients were included in the analysis. The rectal spacer was used in 108 patients. Overall median follow-up was 48 months (IQR, 24-72), with a median follow-up of 24 months (IQR, 12-37.5) for the hydrogel group and 60 months (IQR, 36-84) for the non-hydrogel group. EPIC questionnaire response rates at median follow-up were 33% and 37% for the hydrogel and non-hydrogel groups, respectively. A clinically significant decrease in mean bowel domain scores was seen in the bowel bother domain at 6 and 12 months for patients who did not receive a rectal spacer. At the last follow-up of 60 months, the prevalence of clinically significant rectal bleeding and bleeding bother were 2.2% and 2.2%, respectively. The cumulative incidence of clinically significant long-term rectal bleeding was 2.8% and 18.9% in the hydrogel group and non-hydrogel group, respectively (Fisher's exact test, p < 0.0001). The cumulative incidence of clinically significant long-term bowel bother was 4.6% and 19.7% in the hydrogel group and non-hydrogel group, respectively (Fisher's exact test, p < 0.001). CONCLUSIONS: Use of hydrogel rectal spacer with EBRT and Cs-131 LDR-BT boost was significantly associated with a lower incidence of patient-reported rectal bleeding and bother from rectal bleeding, and better long-term bowel QOL. Cumulative incidence was 2.8% (hydrogel group) versus 18.9% (non-hydrogel group) and 4.6% (hydrogel group) versus 19.7% (non-hydrogel group) for clinically significant long-term rectal bleeding and long-term bleeding bother, respectively.

Phases of the hard-plate lattice gas on a three-dimensional cubic lattice.

We study the phase diagram of a lattice gas of 2×2×1 hard plates on the three-dimensional cubic lattice. Each plate covers an elementary plaquette of the cubic lattice, with the constraint that a site can belong to utmost one plate. We focus on the isotropic system, with equal fugacities for the three orientations of plates. We show, using grand canonical Monte Carlo simulations, that the system undergoes two phase transitions when the density of plates is increased: the first from a disordered fluid phase to a layered phase, and the second from the layered phase to a sublattice-ordered phase. In the layered phase, the system breaks up into disjoint slabs of thickness two along one spontaneously chosen Cartesian direction, corresponding to a twofold (Z_{2}) symmetry breaking of translation symmetry along the layering direction. Plates with normals perpendicular to this layering direction are preferentially contained entirely within these slabs, while plates straddling two adjacent slabs have a lower density, thus breaking the symmetry between the three types of plates. We show that the slabs exhibit two-dimensional power-law columnar order even in the presence of a nonzero density of vacancies. In contrast, interslab correlations of the two-dimensional columnar order parameter decay exponentially with the separation between the slabs. In the sublattice-ordered phase, there is twofold symmetry breaking of lattice translation symmetry along all three Cartesian directions. We present numerical evidence that the disordered to layered transition is continuous and consistent with universality class of the three-dimensional O(3) model with cubic anisotropy, while the layered to sublattice transition is first-order in nature.

Spontaneous layering and power-law order in the three-dimensional fully packed hard-plate lattice gas.

We obtain the phase diagram of fully packed hard plates on the cubic lattice. Each plate covers an elementary plaquette of the cubic lattice and occupies its four vertices, with each vertex of the cubic lattice occupied by exactly one such plate. We consider the general case with fugacities s_{µ} for "µ plates," whose normal is the µ direction (µ=x,y,z). At and close to the isotropic point, we find, consistent with previous work, a phase with long-range sublattice order. When two of the fugacities s_{µ_{1}} and s_{µ_{2}} are comparable, and the third fugacity s_{µ_{3}} is much smaller, we find a spontaneously layered phase. In this phase, the system breaks up into disjoint slabs of width two stacked along the µ_{3} axis. µ_{1} and µ_{2} plates are preferentially contained entirely within these slabs, while plates straddling two successive slabs have a lower density. This corresponds to a twofold breaking of translation symmetry along the µ_{3} axis. In the opposite limit, with µ_{3}≫µ_{1}∼µ_{2}, we find a phase with long-range columnar order, corresponding to simultaneous twofold symmetry breaking of lattice translation symmetry in directions µ_{1} and µ_{2}. The spontaneously layered phases display critical behavior, with power-law decay of correlations in the µ_{1} and µ_{2} directions when the slabs are stacked in the µ_{3} direction, and represent examples of "floating phases" discussed earlier in the context of coupled Luttinger liquids and quasi-two-dimensional classical systems. We ascribe this remarkable behavior to the constrained motion of defects in this phase, and we sketch a coarse-grained effective field theoretical understanding of the stability of power-law order in this unusual three-dimensional floating phase.

Human papillomavirus-driven repression of NRF2 signalling confers chemo-radio sensitivity and predicts prognosis in head and neck squamous cell carcinoma.

PURPOSE: To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV+ve) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV-ve) HNSCC and develop molecular markers for selection of HPV+ve HNSCC patients for treatment de-escalation trials. METHODS: NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV+ve HNSCC and HPV-ve HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy. RESULTS: Prospective analysis revealed a marked reduction in expression of NRF2, and its downstream genes in HPV+ve tumors compared to HPV-ve tumors. A retrospective analysis by IHC revealed significantly lower NQO1 in p16high tumors compared to p16low tumors and the NQO1 expression correlated negatively with p16 and positively with p53. Analysis of the TCGA database confirmed low constitutive NRF2 activity in HPV+ve HNSCC compared to HPV-ve HNSCC and revealed that HPV+ve HNSCC patients with 'low NQO1' expression showed better overall survival compared to HPV+ve HNSCC patients with 'high NQO1' expression. Ectopic expression of HPV-E6/E7 plasmid in various cancer cells repressed constitutive NRF2 activity, reduced total GSH, increased ROS levels, and sensitized the cancer cells to cisplatin and ionizing radiation. CONCLUSION: Low constitutive NRF2 activity contributes to better prognosis of HPV+ve HNSCC patients. Co-expression of p16high, NQO1low, and p53low could serve as a predictive biomarker for the selection of HPV + ve HNSCC patients for de-escalation trials.

Tranexamic acid in burn surgery: A systematic review and meta-analysis.

Burn injury causes a coagulopathy that is poorly understood. After severe burns, significant fluid losses are managed by aggressive resuscitation that can lead to hemodilution. These injuries are managed by early excision and grafting, which can cause significant bleeding and further decrease blood cell concentration. Tranexamic acid (TXA) is an anti-fibrinolytic that has been shown to reduce surgical blood losses; however, its use in burn surgery is not well established. We performed a systematic review and meta-analysis to investigate the influence TXA may have on burn surgery outcomes. Eight papers were included, with outcomes considered in a random-effects model meta-analysis. Overall, when compared to the control group, TXA significantly reduced total volume blood loss (mean difference (MD) = -192.44; 95% confidence interval (CI) = -297.73 to - 87.14; P = 0.0003), the ratio of blood loss to burn injury total body surface area (TBSA) (MD = -7.31; 95% CI = -10.77 to -3.84; P 0.0001), blood loss per unit area treated (MD = -0.59; 95% CI = -0.97 to -0.20; P = 0.003), and the number of patients receiving a transfusion intraoperatively (risk difference (RD) = -0.16; 95% CI = -0.32 to - 0.01; P = 0.04). Additionally, there were no noticeable differences in venous thromboembolism (VTE) events (RD = 0.00; 95% CI = -0.03 to 0.03; P = 0.98) and mortality (RD = 0.00; 95% CI = -0.03 to 0.04; P = 0.86). In conclusion, TXA can potentially be a pharmacologic intervention that reduces blood losses and transfusions in burn surgery without increasing the risk of VTE events or mortality.

Comparative study of risk assessment for noncommunicable diseases among out patients visiting urban and rural health centers in Belagavi, Karnataka.

Purpose/Background: Hence, this comparative study of risk assessment was carried out among out patients visiting urban and rural health centers. This study aimed to find out and compare the risk factors for NCDs among out-patients visiting urban and rural health centers. Methods: This cross-sectional study was carried out in Urban health centre Rukmini Nagar and Rural health centre Vantamuri. Using convenient universal sampling, 200 out-patients from urban area and 200 from rural area were selected. The data were entered into MS-EXCEL and analyzed using SPSS software. Results: In urban area, males were more common (53.7%), whereas females were more common in rural areas (53.8%). Maximum study participants were laborers in urban area (24.5%), whereas home makers were common in rural area (40.5%). Most people in urban areas (11.5%) were indulged in smoking, whereas only 5% smoked in rural area. Participants in urban area had higher waist circumference (20.5%) than those in rural area (17.5%). Physical inactivity was more in rural area (68%), as compared to urban area (47%). 29.5% of participants were found to be at risk for NCDs in urban area, whereas 30% of those were found to be at risk in rural area. Conclusions: Awareness regarding ill effects of risk factors: smoking, alcohol consumption, physical inactivity, and obesity should be created among the community through health education and behavioral change communication to prevent its progression as a disease in future.

Chemotherapeutic Activity of Pitavastatin in Vincristine Resistant B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (ALL) is derived from an accumulation of malignant, immature B cells in the bone marrow and blood. Relapse due, in part, to the emergence of tumor cells that are resistant to front line standard chemotherapy is associated with poor patient outcomes. This challenge highlights the need for new treatment strategies to eliminate residual chemoresistant tumor cells. Based on the use of pitavastatin in acute myeloid leukemia (AML), we evaluated its efficacy in an REH ALL cell line derived to be resistant to vincristine. We found that pitavastatin inhibited the proliferation of both parental and vincristine-resistant REH tumor cells at an IC50 of 449 nM and 217 nM, respectively. Mitochondrial bioenergetic assays demonstrated that neither vincristine resistance nor pitavastatin treatment affected cellular oxidative phosphorylation, beta-oxidation, or glycolytic metabolism in ALL cells. In a co-culture model of ALL cells with bone marrow stromal cells, pitavastatin significantly decreased cell viability more robustly in the vincristine-resistant ALL cells compared with their parental controls. Subsequently, NSG mice were used to develop an in vivo model of B-cell ALL using both parental and vincristine-resistant ALL cells. Pitavastatin (10 mg/kg i.p.) significantly reduced the number of human CD45+ REH ALL cells in the bone marrow of mice after 4 weeks of treatment. Mechanistic studies showed that pitavastatin treatment in the vincristine-resistant cells led to apoptosis, with increased levels of cleaved PARP and protein-signaling changes for AMP-activated protein kinase/FoxO3a/Puma. Our data suggest the possible repurposing of pitavastatin as a chemotherapeutic agent in a model of vincristine-resistant B-cell ALL.

Subjective and Objective Outcome Assessment in Patients with Sinonasal Disease After Microdebrider Assisted Endoscopic Sinus Surgery.

Microdebrider is a modern powered instrument which is electrically driven with a shaver and a suction. The present study aims to assess the subjective and objective outcome in patients with sinonasal disease after microdebrider assisted endoscopic sinus surgery. A prospective observational study was carried out among 40 patients with symptoms suggestive of sinonasal diseases willing to undergo microdebrider assisted sinus surgery at our tertiary care hospital from January 2019 to December 2019. All the patients underwent microdebrider assisted endoscopic sinus surgery (ESS). Patients were subjectively evaluated using the Lund and Mackay staging system using visual analogue score and objectively using nasal endoscopy by the Lund and Kennedy scoring system preoperatively and post operatively after 6 weeks. 40 patients were included in the study. A mean age of 37 years were noted. All patients showed significant statistical improvement in Lund Mackay scoring system by visual analogue scoring and Lund Kennedy endoscopic scoring postoperatively. Thus, microdebrider offers a better therapeutic approach for patients with sinonasal diseases when compared to endoscopic surgery with the conventional instruments. The advantage of using microdebrider in ESS remains to be proper removal of the pathology, good surgical field and better postoperative outcome.

Comparison Between Effectiveness of Topical Mometasone Furoate Nasal Spray Versus Topical Fluticasone Furoate Nasal Spray in the Treatment of Chronic Rhinosinusitis: A One Year Hospital Based Study.

To compare the effectiveness between topical mometasone furoate nasal spray versus topical fluticasone furoate nasal spray in the treatment of chronic rhinosinusitis. Randomized control trial was conducted involving 70 patients. One group received topical mometasone furoate nasal spray and the other group received fluticasone furoate nasal spray for 3 weeks. All patients were prescribed oral ciprofloxacin for 3 weeks and were subjectively evaluated using the Lund and Mackay staging system and objectively using nasal endoscopy by the Lund and Kennedy scoring system. There was no inter group significance but all patients improved significantly after the administration of either of the steroid sprays. Following administration of steroid nasal sprays, there was clinically significant improvement in the symptoms and signs of chronic rhinosinusitis, but there was no statistical significance between the two study groups. Thus, steroid nasal sprays significantly improve the symptoms and resolution of signs of chronic rhinosinusitis. The choice of drug still remains uncertain to the clinician. However, long term studies with more sample size is needed to arrive at sound conclusions.

Substance Use Disorders in the Elderly.

The population of elderly in the United States with substance use disorders (SUDs) is growing appreciably. SUDs among the elderly are often associated with poor outcomes and are frequently underdiagnosed. The current diagnostic criteria are less sensitive in identifying SUDs among the elderly. Routine screening with validated screening tools may improve the diagnosis of SUDs among the elderly. There is a dearth of data from controlled studies on SUDs among the elderly and the use of pharmacologic agents for treatment, although data indicate that older adults with SUDs respond well to treatments that are specifically designed for this age group.

Higher Expression of Annexin A2 in Metastatic Bladder Urothelial Carcinoma Promotes Migration and Invasion.

In this study, we aim to evaluate the significance of AnxA2 in BLCA and establish its metastatic role in bladder cancer cells. Analysis of TCGA data showed that AnxA2 mRNA expression was significantly higher in BLCA tumors than in normal bladder tissues. High mRNA expression of AnxA2 in BLCA was significantly associated with high pathological grades and stages, non-papillary tumor histology, and poor overall survival (OS), progression-free survival (PFS), and diseases specific survival (DSS). Similarly, we found that AnxA2 expression was higher in bladder cancer cells derived from high-grade metastatic carcinoma than in cells derived from low-grade urothelial carcinoma. AnxA2 expression significantly mobilized to the surface of highly metastatic bladder cancer cells compared to cells derived from low-grade tumors and associated with high plasmin generation and AnxA2 secretion. In addition, the downregulation of AnxA2 cells significantly inhibited the proliferation, migration, and invasion in bladder cancer along with the reduction in proangiogenic factors and cytokines such as PDGF-BB, ANGPT1, ANGPT2, Tie-2, bFGF, GRO, IL-6, IL-8, and MMP-9. These findings suggest that AnxA2 could be a promising biomarker and therapeutic target for high-grade BLCA.

Diagnostic dilemma in hyperechoic breast masses.

Hyperechoic breast lesions are relatively uncommon, constituting only 0.6-6% of all breast masses and 0.6% of all biopsied lesions. The majority of these lesions are benign. There are rare malignancies that can present as hyperechoic masses and careful ultrasonographic assessment must be employed to avoid misdiagnosis.[1] We discuss the case of a 67-year-old female patient with a strong family history of breast and ovarian cancer, who presented with one such rare breast cancer in a hyperechoic mass.