Reporting Quality of Endoscopic Colorectal Cancer Screening Randomized Controlled Trials: Adherence to Recommendations and Interventions.

Background and Aims: In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) steering group published recommendations to standardize reporting quality in randomized controlled trials (RCTs). We aim to assess adherence to SPIRIT reporting guidelines in RCTs on endoscopic colorectal cancer (CRC) screening and participants' adherence to trial protocols. Methods: We searched databases for RCTs evaluating flexible sigmoidoscopy or colonoscopy for CRC screening published in English language through September 2023. Each eligible study was evaluated using the 8 core SPIRIT statement areas, totaling 51 points. Each item received 1 point if it met the criteria and 0 points if it did not. Adherence to SPIRIT items was calculated, and participant adherence to RCT protocols was assessed as the proportion of participants screened compared to those invited. Results: Five RCTs, including 4 on flexible sigmoidoscopy and 1 on colonoscopy, were analyzed. Adherence to SPIRIT guidance ranged from 82.4% to 92.2%. The most missed recommendation was item 2b (trial registrations), scored 0 across all studies. Additionally, item 32 (informed consent materials) scored 20%, and items 17a & b (blinding) scored 40% each. In total, 587,572 participants were randomized across the 5 RCTs. Of these, 37% (200,610) underwent CRC screening, with 69.8% (139,983/200,610) adhering to the protocol. The Nordic-European Initiative on Colorectal Cancer (NordICC) trial, employing a unique invitation method, had a lower adherence rate of 42%. Excluding this trial would raise the adherence rate to 74.3% (128,050/172,390). Conclusion: The published CRC screening trials have acceptable adherence to the SPIRIT reporting guidelines. However, reporting appended consent form materials and disclosing all WHO trial registration data can be improved.

A Complex Interplay of Tumor Microenvironment Could Enhance Cholangiocarcinoma Progression Even After Surgery: A Prospective Study.

Background: The current study was conducted to explore the impact of macrophages and programmed cell death protein 1 (PD-1) expression on tumor-infiltrating lymphocytes (TILs) on treatment outcomes and to define the interaction between these factors and the clinicopathologic features of advanced cholangiocarcinoma (CCA) patients. Methods: Twenty-five patients with metastatic CCA were recruited for the current study from El-Rajhi Hospital and the Clinical Oncology Department of Assiut University. Additionally, 19 healthy controls were included. Before the flow cytometric detection of immune cells, the diagnosis and staging of CCA were performed based on surgical intervention, imaging, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) determinations. This was followed by flow cytometric detection of CD4+, CD8+, CD4+PD-1+, CD8+PD-1+, and CD11b+CD68+ macrophages in the peripheral blood of both patients and controls. Results: The current results revealed higher levels of CD4+, CD8+, and CD11b+CD68+ macrophages in controls compared to patients. At the same time, PD-1 expression was significantly higher in patients compared to controls. CD4+ was correlated with improved progression-free survival (PFS), while CD8+PD-1 was associated with shorter PFS. In general, CD4+ and CD8+ levels progressively increased with improved response to treatments, differentiation, single organ site metastasis, and surgical interventions. On the contrary, PD-1 expression and macrophages progressively increased with worsening response, dedifferentiation, multiple organ sites, and surgical interventions. The median PFS was 12 months, and the mean ± standard error (SE) was 13.1 ± 1.3. Conclusions: CCA has a desmoplastic microenvironment with complex immunologic topography and tumor-reactive stroma. The immune landscape of the peripheral blood mononuclear cells (PBMCs) in CCA patients before treatment could reflect the state of systemic immune function and response to treatments. Our results revealed that T-lymphocytes correlated with better prognosis while macrophages and PD-1+ expression were associated with poor outcomes.

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers.

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1ß, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1ß, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal.

Health-related quality of life in adults with hematological cancer: a 2023 cross-sectional survey from Qatar.

Background: Hematological cancers impose a complex burden on individuals, affecting their physical health and mental and emotional well-being. This study evaluated the health-related Quality of Life (HRQOL) and its determinants among adults with hematological cancers in Qatar in 2023. Methods: A cross-sectional study used a validated structured questionnaire conducted among adult patients diagnosed with hematological cancers. All adult patients who attended The National Centre for Cancer Care and Research (NCCCR) in Qatar during the Data collection period (January to March 2023) and agreed to participate were included in the study. Results: A total of 257 participants were enrolled in the study. The highest median (IQR) score of the HRQOL domain was observed in the functionating score of 90.6 (13.8), followed by the global health score of 83.3(25. 0). The median (IQR) of the symptoms burden score was 07.4(12.3). Gender significantly affects HRQOL, with males reporting better functioning and lower symptom burden than females. Employment status is positively associated with functioning scores. Regular exercise correlates with higher global health and functioning scores and lower symptom burden, while depressive symptoms are linked to poorer HRQOL outcomes. Patients experiencing cancer recurrence or active disease report lower global health and functioning scores and higher symptom burden. Treatment modalities such as chemotherapy and bone marrow transplant (BMT) timing also influence HRQOL, with recent treatment recipients showing lower global health and higher symptom burden scores. Depressive symptoms were the primary factor, lowering the global health score by 15.2%. Regarding the low functioning score predictors, female gender, depressive symptoms, and cancer recurrence emerged as significant predictors of the low functioning score. Furthermore, Regular exercise increased the functioning score by 03.4 units (p-value=0.018). Finally, Multiple linear regression analysis reinforced the significance of depressive symptoms, active disease status, and recurrence within the past five years as substantial predictors of higher symptom scores. Conclusions: The study emphasizes the profound impact of depressive symptoms on all aspects of Health-Related Quality of Life (HRQOL), mainly affecting global health. It highlights the positive role of regular exercise in enhancing global health, functioning, and symptom burden scores.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

A rare case of carpal boss lesion with an overlying ganglion cyst: case report and literature review.

Carpal boss is a bony protrusion on the dorsal aspect of wrist quadrangular joint. The exact cause and prevalence are not well understood. Most of the patients are asymptomatic, although some experience pain, bony prominence, restricted mobility, and joint instability in sever neglected cases. We are presenting a case of a 24-year-old male had chronic dorsal wrist pain with bony prominence appearance underwent surgical excision of a carpal boss lesion in concomitant with soft tissue ganglion cyst over the carpal boss after failed conservative management, resulting in significant symptom improvement and restored range of motion. Carpal boss lesion is a common condition that can be undiagnosed due to asymptomatic presentation or the presence of overlying soft tissue pathology as ganglion cyst. Although conservative treatment is helpful in some patients, most symptomatic carpal boss lesion patients eventually need surgical excision.

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy.

Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV-Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti-O-Ti bond is identified by observing a peak between 400 and 800 cm-1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 µg/mL and standard (Vitamin C) IC50 is 87.62 µg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.

Adenomas and Sessile Serrated Lesions in 45- to 49-Year-Old Individuals Undergoing Colonoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Colorectal cancer (CRC) screening is now recommended at the age of 45 years in the United States. However, information regarding the adenomas detection rate (ADR) and sessile serrated lesions (SSLs) in 45- to 49-year-old individuals is limited. In addition, the impact of lowering the screening age to 45 years on the ADR and the detection rate of SSLs is not well elucidated. This systematic review and meta-analysis aims to report the overall ADR and SSL detection rate in 45- to 49-year-old individuals undergoing colonoscopy. METHODS: We searched MEDLINE, EMBASE, SCOPUS, Web of Science, ClinicalTrials.gov , and the Cochrane database from inception through October 2022 to identify studies reporting on ADR and SSL detection rates in 45- to 49-year-old individuals undergoing colonoscopies for all indications. This approach acknowledges the possibility of including individuals undergoing diagnostic colonoscopies or those with increased risk factors for CRC. We also conducted a separate analysis examining ADR in average-risk individuals undergoing screening colonoscopy. The pooled rates with their corresponding 95% confidence intervals (CIs) were generated using the fixed-effects model. I2 was used to adjudicate heterogeneity. RESULTS: Sixteen studies met the inclusion criteria. All studies were retrospective except one; 3 had data from national/local registries. There were 41,709 adenomas detected across 150,436 colonoscopies. The pooled overall ADR was 23.1% (95% CI 19.7%-27.0%, I2 = 98.6%). The pooled ADR in individuals with average risk of CRC from 7 studies was 28.2% (95% CI 24.6%-32.0%, I2 = 96.5%). The pooled overall SSL detection rate from 6 studies was 6.3% (95% CI 3.8%-10.5%, I2 = 97%). The included studies were heterogeneous because of differences in the inclusion and exclusion criteria and patient population. DISCUSSION: In 45- to 49-year-old individuals undergoing a colonoscopy for any indication, the ADR and SSL detection rates were 23.1% and 6.3%, respectively. We conclude that these outcomes in 45- to 49-year-olds are comparable with individuals aged 50-54 years.

Obstructive Sleep Apnea Does Not Exclude Polycythemia Vera: A Case Report.

Introduction: Polycythemia vera (PV) is one of the myeloproliferative neoplasms (MPN) diagnosed by World Health Organization (WHO) criteria 2016, which requires the presence of 3 major criteria: high hemoglobin/hematocrit, bone marrow findings, and Janus Kinase 2 (JAK2) mutation or two major and one minor criteria, including erythropoietin (EPO) level. However, in clinical practice, difficulties in diagnosis can arise as it may be masked by secondary causes for erythrocytosis such as smoking or obstructive sleep apnea (OSA). Case Presentation: Here, we report a 55-year-old gentleman, morbidly obese with OSA on home continuous positive airway pressure (CPAP) machine, who was incidentally found to have polycythemia. Further evaluation confirmed the diagnosis of PV. Conclusion: PV can be masked by the assumption of secondary polycythemia based on history. This underscores the importance of screening such cohort through JAK2 and EPO testing to avoid missing PV.

The prevalence of anxiety and depression in bronchiectasis patients and their association with disease severity: a cross-sectional study.

Bronchiectasis is a chronic lung disease characterized by recurrent respiratory symptoms. Several studies demonstrated that psychological comorbidities are common in patients with bronchiectasis. The aim of this study is to investigate the prevalence of anxiety and depression in bronchiectasis patients and assess their association with disease severity. In this cross-sectional study, we included patients diagnosed with bronchiectasis. The study was conducted using an interviewer-administered questionnaire via phone calls and data collected from the electronic medical records at JUH. The questionnaire included patients' demographics and disease characteristics. Anxiety and depression were assessed using GAD7 and PHQ9 respectively. Bronchiectasis disease severity was assessed using BSI and FACED score. The total number of included patients was 133. Moreover, 53.4% of the participants were females while the rest were males (46.6%). PHQ9 demonstrated that 65.4% of the patients had depression. Regarding anxiety, GAD7 scale showed that 54.1% of the patients had anxiety. Pearson correlation showed that bronchiectasis severity index was significantly associated only with PHQ9 depression scores (r = 0.212, P value = 0.014). The prevalence of depression and anxiety is high among patients with bronchiectasis. We believe that patients affected with bronchiectasis should be screened for depression to improve their quality of life.

Efficacy and Safety of Cold Snare Endoscopic Mucosal Resection (CS-EMR) for Nonampullary Duodenal Polyps: Systematic Review and Meta-Analysis.

INTRODUCTION: There is an increasing interest in cold snare endoscopic mucosal resection (CS-EMR), and studies have shown its safety and efficacy for colonic polyps. This meta-analysis aims to assess the safety and efficacy of CS-EMR for the removal of duodenal adenomas. METHODS: We conducted a comprehensive literature search of several databases, from inception through February 2023, for studies that addressed outcomes of CS-EMR for nonampullary duodenal adenomas. We used the random-effects model for the statistical analysis. The weighted pooled rates were used to summarize the technical success, polyp recurrence, bleeding, and perforation events. Cochran Q test and I2 statistics adjudicated heterogeneity. RESULTS: Six studies were included in the analysis. In all, 178 duodenal polyps were resected using CS-EMR. The pooled rates were 95.8% (95% CI 89.1-98.5%, I2=21.5%) for technical success and 21.2% (95% CI 8.5-43.6%, I2=78%) for polyp recurrence. With regards to CS-EMR safety, the pooled rates were 4.2% (95% CI 1.6-10.5%, I2=12%) for immediate bleeding, 3.4% (95% CI 1.5-7.6%, I2=0%) for delayed bleeding, 2.8% (95% CI 1.1-6.7%, I2=0%) for perforation, and 2% (95% CL 0.5-7.5%, I2=0%) for post-polypectomy syndrome. Rates were not significantly different for large adenomas. Three studies reported data on CS-EMR and conventional EMR. Compared with conventional EMR, CS-EMR had lower odds of delayed bleeding, OR 0.11 (CI 0.02-0.62, P value 0.012, I2=0%). CONCLUSION: Our findings suggest that CS-EMR is a safe and effective strategy for the resection of nonampullary duodenal adenomas, with an acceptable recurrence rate. Data from larger randomized controlled studies are needed to validate our findings.

Toe Gangrene as the First Presenting Symptom of Essential Thrombocythemia: A Case Report.

Essential thrombocythemia is a myeloproliferative neoplasm. Thrombosis and bleeding complications are common with myeloproliferative neoplasms, particularly essential thrombocythemia and polycythemia vera. Here, we report the case of a 52-year-old female who presented initially with painful toe swelling and discoloration. Initial imaging showed a small abscess. An incision and drainage, and debridement of toe dry gangrene were performed twice in two months with no improvement in her complaint and worsening discoloration, ending in a toe amputation. Two years later, the patient was referred to a hematology clinic for a high platelet count. On review of her medical records, the patient had the same numbers during the initial presentation. The patient's condition was diagnosed retrogradely by a hematologist as essential thrombocythemia. This case sheds light on myeloproliferative neoplasm as a differential diagnosis in patients with atypical thrombosis. Thinking in such a way could have diagnosed our patient two years earlier.

Cold snare endoscopic mucosal resection for colon polyps: a systematic review and meta-analysis.

BACKGROUND: Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. METHODS: We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. RESULTS: 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, I2  = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, I2  = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, I2  = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, I2  = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, I2  = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, I2  = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, I2  = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, I2  = 0 %), respectively. CONCLUSION: CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.

Potential anticancer and antioxidant lauric acid-based hydrazone synthesis and computational study toward the electronic properties.

The modification of natural products is one of the key areas of synthetic organic chemistry for obtaining valuable chemical building blocks that have medicinal significance. In this study, lauric acid-based hydrazones, namely (E)-N'-(2-nitrobenzylidene)dodecanehydrazide (NBDH), (E)-N'-(naphthalen-1-ylmethylene)dodecanehydrazide (NMDH), and (E)-N'-(4-fluorobenzylidene)dodecanehydrazide (FBDH), were synthesized and characterized using spectroscopic techniques. The newly synthesized lauric acid-based hydrazones were screened for their anticancer and antioxidant potential. The antioxidants showed their activity by inhibiting the oxidative chain reactions that produce reactive oxygen species. The antioxidant activity showed that NBDH exhibited the maximum DPPH inhibitory activity when compared with that of NMDH and FBDH, whereas the anticancer activity showed that FBDH exhibited maximum percent viability when compared to that of NBDH and NMDH. The reactivity and biological needs of the synthesized compounds NBDH, NMDH, and FBDH were met by performing geometrical, FT-IR vibrational, UV-visible, global reactivity parameters (GRP), MEP, FMO, NBO, ELF, LOL, and nonlinear optical (NLO) analysis at the DFT/B3LYP/6-311+G(d,p) level. NBO analysis confirmed the existence of extended conjugation and intramolecular charge transfer among NBDH, NMDH, and FBDH, which have the lowest gap in π → π*, which are in line with the FMO results where successful charge transfer occurred from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). GRP analysis confirmed the potential of NBDH, NMDH, and FBDH for biological, electronic, and NLO applications. It is clear from the comparative analysis of the urea molecule that NBDH, NMDH, and FBDH all comprise fine NLO properties.

Relation Between Baseline CXCR1 Expression And Neoadjuvant Chemotherapy Response In Breast Cancer Patients.

Objectives: To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. RESULTS: Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response. CONCLUSIONS: There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

Dissuasive cigarettes as a tobacco control measure: a scoping review.

OBJECTIVE: The aim was to identify and review the research literature on dissuasive cigarettes, including key concepts, types, sources of evidence and research gaps. DATA SOURCES: PubMed, Scopus and Web of Science databases were searched up to January 2023 with no language or date restrictions. All study designs were included. Reference lists of the identified studies were manually searched. Studies on tobacco products other than cigarettes or on external cigarette packaging alone were excluded. STUDY SELECTION: Two reviewers screened titles and abstracts independently using eligibility criteria. The full text of the selected articles was subsequently screened independently by two reviewers to confirm eligibility. DATA EXTRACTION: Two reviewers independently extracted data from all studies using data abstraction forms. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SYNTHESIS: We identified 24 original studies, 3 review articles and 4 commentary articles. Research on dissuasive cigarettes was reported from Australia, New Zealand, Europe and North America. We presented results in four themes: the concept of dissuasive cigarettes; approaches and types; potential benefits, barriers and concerns; and current research gaps. CONCLUSIONS: Dissuasive cigarettes represent a promising strategy that could be used in tobacco control. Parallel implementation with plain packaging would be feasible and synergistic.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

A practical guide to managing cardiopulmonary toxicities of tyrosine kinase inhibitors in chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) but their use was associated with a range of serious cardiopulmonary toxicities including vascular adverse events, QT prolongation, heart failure, pleural effusion, and pulmonary arterial hypertension. Dedicated clinical management guidelines for TKI-induced toxicities are not available. This review aims to discuss TKI-associated cardiopulmonary toxicities and proposes a practical guide for their management.

Fibrolamellar hepatocellular carcinoma: An epidemiologic and 5-year cancer survival assessment based off SEER data.

The fibrolamellar variant of hepatocellular carcinoma makes up a small percentage of liver tumors. Despite being a subset, it has been noted in the literature to have variations in terms of its epidemiology and intervention recommendations. Using the Surveillance, Epidemiology, and End Results database, 339 cases from 1988 to 2016 were studied. Favorable prognostic epidemiological factors included male sex, younger ages, and white race. Those who underwent any lymph node resection (combined with liver resection) did better than those without lymph node resection; chemotherapy proved beneficial for those where surgery was contraindicated. To our knowledge, this report is the largest conglomerate dataset analyzing prognostic profiles and treatment strategies for fibrolamellar hepatocellular carcinoma.